Distribution of the tract of Lissauer and the dorsal root fibers in the primate spinal cord. The tract of Lissauer receives small caliber dorsal root fibers in addition to axons arising from dorsal horn neurons. The termination of Lissauer's tract and dorsal root fibers was examined in the C7 segment of the rhesus monkey spinal cord. The distribution of normal dorsal root afferents was mapped by labelling the C7 dorsal root ganglion with tritiated amino acids, and then compared with the degeneration of C7 dorsal root fibers following an intradural dorsal rhizotomy. To focus on the distribution of the small afferents, the degeneration following a Lissauer tractotomy was compared with the degeneration following dorsal rhizotomy and following selected lesions involving the large afferents. The survival times following the lesions and rhizotomies were varied to facilitate identification of groups of fibers and terminals which might degenerate at different rates. Both large and small diameter dorsal root afferents were found to exhibit the same rostro-caudal topography within the dorsal horn. The C7 root axons and terminals distribute throughout the mid-C7 dorsal horn grey. Proceeding rostrally through C6, the majority of the C7 root fibers ending in laminae I-IV shift to a lateral position. Proceeding caudally through C8, the C7 root fibers shift medially. Few of the small diameter C7 afferents entering via Lissauer's tract extend above C6 or below C8. Large diameter C7 afferents, arising as dorsal column collaterals, can extend several segments above and below C7. Autoradiography revealed label in all dorsal horn laminae, the heaviest always occurring in the substantia gelatinosa. After one day, label was absent over dorsal column and Lissauer's tract axons, suggesting that the label was mainly associated with fine axonal branches or possibly terminals. After six to ten days many axons were labelled and could be traced into the dorsal and ventral horn. Degeneration from the rhizotomies and lesions, as demonstrated with Fink-Heimer and Nauta methods, depended on the survival time. No degeneration products were present before three days. The large afferents begin to degenerate within the dorsal horn after three to four days and mainly terminate in laminae IV-VI; by 12 days they can also be traced into the intermediate and ventral grey. The small afferents, which include those serving pain and temperature sensibility, arise from the tract of Lissauer and distribute to laminae I, II and III. The tract of Lissauer consists of two populations, each containing small afferents. One population degenerates at three to five days and distributes mainly to laminae II and III (substantia gelatinosa); the other degenerates around 12 days and distributes mainly to lamina I and the outer zone of II. It is suggested that the exclusive termination of the small afferents to laminae I, II and III may be correlated with certain unique histochemical properties (e.g., high substance P and high opiate receptor binding levels) of these same dorsal horn areas...


Effects of ejaculation on levels of testosterone, cortisol, and luteinizing hormone in peripheral plasma of rhesus monkeys. Plasma levels of testosterone (T), luteinizing hormone (LH), and cortisol were measured in 10 adult male rhesus monkeys before and shortly after coitus. Mean levels of T and LH did not increase significantly after coitus or in control (no ejaculation) tests, but cortisol levels did in both cases. In 10 different males, no significant change was found in the plasma levels of T after electroejaculation; but in control tests (electric current withheld), the mean level of T was significantly lower at 80 and 140 min, but not at 50 min, after the test. According to present evidence, the effect of ejaculation on T levels differs in primate and nonprimate species. The effects on T levels produced by living with sexually receptive female rhesus monkeys may differ from those produced by intimate but brief contact with them.


Medial preoptic area and onset of maternal behavior in the rat. The present series of experiments examined whether the medial preoptic area (MPOA) is involved in the onset of maternal behavior in the rat. Previously, the MPOA had been shown to be important in the maintenance of maternal behavior in the lactating rat. The first experiment investigated whether estradiol benzoate (EB) acts on the MPOA to facilitate the onset of maternal behavior in the 16-day pregnant, hysterectomized, and ovariectomized female rat. Such rats when given EB implants in the MPOA had significantly shorter latencies for the onset of maternal behavior than had females implanted with cholesterol in the MPOA or with EB in the ventromedial hypothalamus, in mammillary bodies, or under the skin. A second experiment showed that estrogen-induced prolactin release was not involved in this facilitation. A third experiment indicated that MPOA lesions disrupt the onset of maternal behavior that is induced by pup stimulation in virgin females. It was concluded that the MPOA is involved not only in the maintenance of maternal behavior but in the hormonally mediated onset of maternal behavior and the onset of maternal behavior induced in virgin females by pup stimulation.


Hormonal control of mammogenesis and onset of lactation in cows--a review. Estrogen stimulates development of mammary ducts, and progesterone and estrogen stimulate proliferation of secretory tissues. In vivo, sequential addition of insulin (step 1), glucocorticoid (step 2), and prolcatin (step 3) leads to biosynthesis of casein and lactose. In cows, mammogenesis continues until termination of pregnancy and overlaps onset of lactation. Progesterone probably inhibits differentiation of secretory cells at step 2 or step 3. Sensitivity of individual cells to progestational inhibition may decrease variably which may be interdependent upon relative increases in estrogen, prolactin, corticoids, and growth hormone to cause asynchronies among them at calving. Since prolactin in plasma is not correlated with progesterone or the estrogens, factors other than feed-back effects of ovarian steroids may be responsible for its sustained increase periparturiently. Also, elevated prolactin periparturiently may be unrelated to subsequent rates of lactation because its "basal" concentrations may meet requirements when inhibiting effects of progesterone are removed. This concept is attractive because mammary cells neither are synchronized highly for biosynthesis nor secrete normal milk for several days after calving. At the latter time, concentrations in plasma are low for progesterone and estrogen, similar to 3 days before calving for glucocoiticoids and prolactin, and increasing for insulin. Evidence of lactation under unusual circumstances was discussed.


Lactose synthase activity of galactosyltransferase from human parotid saliva. Galactosyltransferase is human parotid saliva catalyzed the transfer of galactose from uridine 5'-diphospho (UDP)-galactose to D-glucose in the presence of exogenous alpha-lactalbumin. Some albumins other than alpha-lactalbumin did not have an effect on the appearance of lactosesynthesizing activity.


Cromolyn sodium nasal solution in the prophylactic treatment of pollen-induced seasonal allergic rhinitis. A large-scale multicenter investigation was undertaken in 3 cities with comparable pollen seasons and atmospheric pollen concentrations in order to obtain more definite information about the safety and efficacy of cromolyn sodium in the treatment of pollen-induced seasonal rhinitis. The 9-wk double-blind study was conducted in 104 patiets in Pittsburgh, Pa., Cleveland, Ohio, and Louisville, Ky., during the 1975 ragweed season. It indicated that a nebulized 4% aqueous solution of cromolyn sodium is effective in reducing sneezing, rhinorrhea, nasal congestion, and ocular irritation in ragweed hay fever patients. The efficacy of the drug was notable despite the fact that patients used an average of 52 mg instead of the recommended 62.4 mg daily. Cromolyn sodium did not appear to have a significant effect on transseasonal antiragweed IgE (IgEAR) levels. Patients acceptance of the cromolyn nasal solution was good, and there were no significant adverse reactions. The side effects, which were distributed equally between the drug and placebo groups, were mild and of limited duration.


Economics, management, and public health nutrition. Research has shown that including a nutritional functional area in comprehensive health care delivery can reduce the total cost per registrant. The savings occur when nutritionists substitute for more costly medical personnel in a team-care setting. Further research has demonstrated that the cost of nutritional care is related to the performance of nutritional staff, i.e., productivity, which may be improved as much as 25 to 70% through simple managerial techniques. The implications for nutritional planning and operations are discussed. Nevertheless, the greatest potential for improving nutritional health rests with the patient himself. Thus, the future orientation in public health nutrition must be directed toward the problems of shifting the major part of the responsibility from the provider to the patient, with accompanying competence in self-care and health maintenance. A promising approach to the idea of greater patient responsibility and autonomy is the so-called Vinland Center concept. Originally developed in Norway, a center incorporating the principles is now being planned in Minnesota and is expected to begin operation in 1979. Funds for the planning effort were given to the U.S. as a Bicentennial gift from Norway. The concept is explained.


Total parenteral nutrition. A brief review. The ideal solution for total parenteral nutrition (TPN) should contain nutrients equivalent to those of a well balanced, oral diet. With that goal in mind, available solutions usually provide adult patients with approximately 3,000 ml. solution daily, which supply about 12 gm. nitrogen and 2,400 kcal, with vitamins and minerals added as required. (Infants require relatively greater amounts of fluids and calories per kilogram.) The most critical concern in TPN is that of fluid and electrolyte balance, which varies with the patient. In this paper, the composition of four commercial TPN solutions is tabulated, as are recommendations for trace elements and vitamins which should be included.


Tourniquet ischemia: ultrastructural and histochemical observations of ischemic human muscle and of monkey muscle and nerve. Biopsies of muscle from ten patients and of muscle and nerve from three monkeys were obtained during periods of continuous ischemia and studied by light and electron microscopy and by histochemical means. Between the third and fourth hours of ischemia, swelling of the mitochondria was noted in monkey muscle. One week later the appearance was normal. In the monkey nerves degenerated myelin was seen one week later but appeared to be normal at 2 weeks. If after 3 hours the tourniquet was deflated for 30 minutes and then reapplied for 2 additional hours, no changes were found. Succinic dehyrogenase analysis was used to identify swelling of the mitochondria. No mitochondrial changes were seen in human muscle made ischemic by a tourniquet for 2 hours.


Increased visualization of microtubules by an improved fixation procedure. We have found that when a buffer utilized for in vitro polymerization of microtubules, i.e., 1 mM guanosine triphosphate, 1 mM MgSO4, 2 mM ethylene glycol bis(beta-aminoethyl ether)-N, N'-tetraacetic acid 100 mM piperazine-N,N'-bis(2-ethanesulfonic acid), pH 6.9 polymerization mix, was used in the glutaraldehyde prefixation regimen instead of classical fixative buffers, i.e., isotonic cacodylate or phosphate buffer, the following features were observed in thin-sections of the cytoplasm of interphase HeLa cells: (a) a greater than 2-fold increase in total microtubule contour length, (b) a 2-fold increase in a number of microtubules greater than or equal to 1 mu long, (c) an enhanced association of microtubules with cytoplasmic organelles, and (d) an increased clustering of 100 A filaments located in a perinuclear region of the cell. Furthermore, we found that after we incubated purified chick brain microtubules on a Sephadex G-25 column pre-equilibrated with polymerization mix, cacodylate or phosphate buffer at 37 degrees C, and then eluted the microtubules at 37 degrees C, the exposure to cacodylate or phosphate buffer caused extensive depolymerization, but exposure to polymerization mix buffer allowed reisolation of highly polymerized microtubules. Our results imply that prefixation with cacodylate or phosphate buffered glutaraldenyde destabilizes microtubules leading to the decreased visualization of microtubules.


Characterization of two species of Fc fragments obtained from rat IgG2a by prolonged papain digestion. Prolonged papain digestion of rat IgG2a produced two molecular species of Fc fragments, termed Fc(I) and Fc(II). Studies by gel filtration chromatography and polyacrylamide gel electrophoresis in SDS/urea indicated that the two subunit polypeptide chains in each Fc preparation were associated by non-covalent bonds only. By analytical ultracentrifugation Fc(I) was found to have a m.w. of 47,100 and a sedimentation coefficient of 4.08S. Fc(II) had a m.w. of 39,800 and a sedimentation coefficient of 3.83S. The m.w. for the subunit chains of Fc(I) and Fc(II) were 25,300 and 20,300, respectively, as determined by analytical ultracentrifugation under dissociating conditions. Calculation of the frictional coefficient ratios indicated that both Fc fragments possessed compact globular structures. The difference in size between these two Fc fragments probably was due to a loss of some carboxy-terminal residues in Fc(II). Both Fc fragments possessed nearly identical amino-terminal amino acid sequences. Papain cleavage occurred primarily between residues 233/234 and 234/235. The carbohydrate compositions of the two species of Fc fragments were similar. It was concluded that under acid and reducing conditions papain cleavage of rat IgG2a occurred to the carboxy-terminal side of the hinge region. Prolonged papain digestion led to secondary attack in the carboxy-terminal end of the CGAMMA3 domain at an unidentified site, or sites, producing a stable second species of Fc fragments.


Species specificity in the isoelectric spectra of immunoglobulin light chains. Light chains isolated from normal immunoglobulin give rise to a finite number of discrete bands when analyzed by isoelectric focusing in polyacrylamide gel. The positions and relative intensities of the bands were identical in light chains isolated from different individuals of a species, but clear differences were evident when light chains of several mammalian species were compared.


Bullous pemphigoid antigen: isolation from normal human skin. A protein moiety from epidermal PBS-soluble products was isolated by gel filtration (Bio-Gel A-1.5m) and ion exchange chromatography (DEAE-cellulose). This protein (A-1-Epid) was not retarded by DEAE-cellulose in Tris-HCl buffer, 15mM, pH 8.1. By IEP against an antiserum to epidermal antigens, it showed a single cathodal arc. On disc electrophoresis, at low pH (4.3) a single band was apparent. On SDS gels this protein demonstrated two bands, one with a molecular weight of 20,000, and the second with a molecular weight of 9,200. This purified antigen was able to block the staining of the basement membrane zone produced by bullous pemphigoid antibodies on monkey esophagus and normal human skin with the use of indirect immunofluorescence. This study also demonstrates that bullous pemphigoid antigen (A-1-Epid) and a second epidermal protein (A-2-Epid) are present in the PBS-soluble products of human esophageal mucosa, saliva, and urine. These antigens appear to be unrelated with the blood group substances or secretor status of the donors.


Complement activation by measles virus cytotoxic antibodies: alternative pathway C activation by hemagglutination-inhibition antibodies but classical activation by hemolysin antibodies. Antibodies against measles virus hemagglutinating (HA particles and hemolysin were shown to activate C differently. HA antibodies of rabbit or human origin activated C via the alternative pathway in cytotoxicity against chronically measles-infected cells. This cytotoxicity was expressed in C-4 deficient guinea-pig C or in rabbit C in the presence of 3 mM EGTA (ethylene-glycol-tetraacetic-acid) but not in 3 mM EDTA (ethylene-diamine-tetraacetic-acid). In contrast, human hemolysin antibodies activated C only via the classical way. F (ab')2 fragments from rabbit or human anti-HA IgG antibodies were as efficient in C activation via the alternative pathways as intact IgG antibodies with a corresponding hemagglutination-inhibition titer.


Histaminase release from human eosinophils. Phagocytosis of opsonized zymosan by human eosinophils results in a dose-dependent noncytotoxic release of histaminase as well as arylsulfatase and beta-glucuronidase. The calcium ionophore A23187 also stimulates release of eosinophil histaminase at concentrations of ionophore which barely release arylsulfatase and beta-glucuronidase. Zymosan-induced histaminase release from eosinophils but not from neutrophils was abolished or markedly reduced in the presence of cytochalasin B, suggesting a difference in the mechanisms of histaminase release from the two granulocyte cell types.


Immunologic reactivity of purified human urinary kallikrein (urokallikrein) with antiserum directed against human pancreas. Donkey antiserum to normal human pancreas absorbed with lyophilized human plasma recognized human urokallikrein in concentrated crude urine or after an approximately 500-fold purification. The urokallikrein antigen was associated with kinin-generating and alpha-N-p-tosyl-L-arginine methyl ester (TAMe) cleaving activity on isoelectric focusing, with the isoelectric point being 3.8 to 4.4. Both kiningenerating and esterolytic activity were removed from the purified urokallikrein by an immunoadsorbent prepared by coupling the IgG fraction of the absorbed donkey antiserum to Sepharose 6B. The failure of anti-plasma kallikrein to react in immunodiffusion with purified urokallikrein indicates that urinary kallikrein is distinct from plasma kallikrein although antigenically related to glandular kallikreins.


Templates for antiserum application in immunoelectrophoresis and two-dimensional electroimmunodiffusion. Two forms of template are described for use with flat-cast agarose gels to simplify and improve immunoelectrophoresis and two-dimensional electroimmunodiffusion tests.


Procedure for the isolation of mouse anti H-2 antibodies from complex alloantisera. B6AF1-anti-B10.D2 ascites fluid was incubated with donor strain red blood cells to absorb the anti-H-2 antibodies. The antibody-coated RBC were then lysed, and from the ghosts the antibodies were eluted. This anti-H-2 preparation was further purified by affinity chromatography, using an immobilized anti IgG2 antiserum. Thus a pure anti-H-2 IgG2 was obtained for in vitro and in vivo testing.


Immuno-ultracentrifugation: a combination of density gradient centrifugation and immunodiffusion. By incorporating acrylamide in a sucrose gradient and photopolymerizing the tubes at the end of the run, direct immunochemical and other analysis can be performed on the separated material in situ without recovering fractions from the centrifuge tube. Immunodiffusion performed on the sliced gel can be employed to locate antibody activity in the gel slice or determine the distribution of antigens in a sucrose gradient


Bactericidal antibody in genital infection due to Neisseria gonorrhoeae. An assay of bactericidial antibody has been developed to study the host response to infection with Neisseria gonorrhoeae. This test for antibody was performed on the sera of women who were exposed to N. gonorrhoeae but who did not become infected, of patients with various types of genital infection with N. gonorrhoeae, and of a small number of individuals with no history of gonorrhea. Antibody was found in the sera of less than 31% of men and women with uncomplicated gonococcal infection. Prolonged mucosal infection with the gonococcus (greater than 33 days) correlated with the presence of bactericidal antibody. Bactericidal antibody was not detected in 95% of the specimens of acute-phase serum obtained from women with gonococcal pelvic inflammatory disease. The convalescent-phase sera of 70% of women with clinically severe pelvic inflammatory disease showed a rise in titer of bactericidal antibody to the infecting strain of N. gonorrhoeae, whereas only 11% of the convalescent-phase sera of women with mild or moderately severe disease showed a similar rise.


Reovirus-like agent in acute epidemic gastroenteritis in Japanese infants: fecal shedding and serologic response. The reovirus-like agent, sometimes referred to as duovirus or rotavirus, was visualized by electron microscopy in stool extracts from Japanese infants and young children with acute epidemic gastroenteritis. The virus particles measured 70 nm in diameter and had double-shelled capsids. One hundred ten (89%) of 124 patients with the gastroenteritis had such virus particles in stools obtained during the acute phase. The virus particles were excreted in the stools usually during the first eight days of illness. Agglutination of virus particles by antibody present in convalescent-phase sera was demonstrated by immune electron microscopy. Complement-fixing antibody was detected as early as day 3 of illness, and antibody titers peaked during the second and third weeks of the disease. The antibody appearing in the acute and early convalescent phases was sensitive to 2-mercaptoethanol. Antibody resistant to 2-mercaptoethanol was produced approximately 10 days after the onset of the symptoms. The serologic evidence suggests that a primary infection with the reovirus-like agent was responsible for the clinical attack of acute gastroenteritis.


Immunity in plague: protection of the vervet (Cercopithecus aethips) against pneumonic plague by the oral administration of live attenuated Yersinia pestis. Protection against pneumonic plague by the oral administration of a live, attenuated Yersinia pestis vaccine, EV76 (Paris) F, was evaluated in the vervet (Cercopithecus aethips). Six animals were vaccinated with a dose of 1.175 X 10(9) colony-forming units (cfu); all tolerated the dose and developed antibodies to Fraction I of Y. pestis. Three immunized animals were challenged with an inhaled dose of 3.2 X 10(6) cfu (160 LD50 [50% lethal dose]) of virulent Y. pestis strain 195/P and two survived; the other three received a challenge dose of 4.9 X 10(6) cfu (245 LD50) and one survived. The three surviving monkeys had high titers of antibody to Fraction I. At necropsy of the animals that succumbed to the challenge infection, almost complete consolidation of the lungs was apparent, and sizable effusions were present in the thoracic cavities. Indeed, the striking pathology indicated the severest form of pneumonic plague. Since it can be assumed that the animal surviving challenge with the larger inoculum would have survived the smaller dose, we conclude that the immunization procedure protected half of the vervets that were exposed to challenge.


Cryoglobulinemia in a patient with Sjögren's syndrome, and factors of cryoprecipitation. The IgGK cryoglobulin in a patient with Sjögren's syndrome showed deviations from normal IgG involvine its amino acid composition as well as its carbohydrate components. The heavy chains showed abnormal numbers of arginine, threonine, valine and isoleucine residues, and there was an impressive reduction of fucose and hexose components. The carbohydrate deficits appear to be the reason for the incomplete solubility of the isolated IgGK(Ru) at 37 degrees C. with completion at 52 degrees C.


Indirect immunofluorescent detection of antibodies against thermophilic actinomycetes in patients with hypersensitivity pneumonitis. With slide culture preparations of Micropolyspora faeni, Thermoactinomyces candidus, and Thermoactinomyces vulgaris used as antigens, 59 sera from patients with hypersensitivity pneumonitis and 23 sera from normal controls were studied for the presence of specific antibodies by indirect immunofluorescence and immunodiffusion methods. Of the 82 sera, 31 showed precipitins to M. faeni, five to T. candidus, and four to T. vulgaris. A group of 19 sera positive to Aspergillus antigens showed questionable reactions to thermophilic actinomycetes. The 23 sera from normal individuals were negative for specific antibodies when tested by immunodiffusion. In indirect immunofluorescence studies, we found that IgG antibodies in high titers are present only in the precipitin-positive sera whereas other antibody classes either are negative or failed to show consistent differences in titers of the positive, questionable, and control groups. The titer of IgG antibodies varied from 0 to 1:20 in the normal control group, 0 to 1:40 to 1:640 in the precipitin-positive group.


Quantitative relationships of the fourth complement component in human cerebrospinal fluid. A technique for the measurement of cerebrospinal fluid C4 concentration in unconcentrated specimens has been developed with the methods of electroimmunodiffusion and immunofixation. The method has proved to be reproducible and requires only microliter volumes of undiluted cerebrospinal fluid (CSF). The mean value for CSF C4 concentrations in 16 neurologically normal individuals was 325 +/- 32 mug/100 ml. A positive correlation between CSF C4 concentration and the concentration of CSF albumin and total protein was observed. The positive correlation between the concentrations of CSF C4 and albumin was, however, more clearly defined than the relationship of CSF C4 to total CSF protein.


[Evaluation of the diagnostic value of clinical chemical tests (author's transl)]. Little attention has been paid before to the diagnostic efficiency of clinical chemical tests. In view of the ever increasing number of clinical chemical analyses and the critical development of expenses in medical health care, an evaluation of this aspect of clinical chemical analyses seems to be urgently required. Various new methods, that might be used, are reviewed. Qualitative and quantiative tests, and the so-called multiple analysis are discussed as examples of clinical chemical methods. The necessary mathematical treatments (use of the Bayes theorem, information theory, likelihood ratio method, and others) are illustrated with the aid of worked examples. A new cost-effectiveness analysis of clinical chemical data is suggested.


A new marker for neuraminidase-treated human serum glycoproteins from the haemolymph of Tridacna maxima (Röding). Highly purified human serum glycoproteins were treated with neuraminidase. The exposed subterminal carbohydrate structures reacted strongly with an anti-galactan precipitin from the haemolymph of Tridacna maxima which detects terminal, non-reducing beta-D-galactoside residues. This invertebrate precipitin, Tridacnin, may be used as a marker for nearly two thirds of all asialo serum glycoproteins; A number of different cross-reactions with various other polysaccharides and galactans subdivides those neuraminidase-treated glycoproteins into several subgroups, indicating that the uncovered carbohydrate structures are not always completely identical. In this way, together with the cross-reacting precipitins from plant and invertebrate origin. Tridacnin may be a useful tool for elucidating and establishing the structure of the carbohydrate part of serum glycoproteins.


Developmental effects of exposing Drosophila embryos to ether vapour. Drosophila embryos at precise developmental stages were exposed to ether vapour. The defects in the resulting embryos and adults were observed. Ether disrupted embroygenesis in specific ways, causing defects primarily at the anterior of the embryo and disorganizing the arrangement of the segments. Adults showed deficiencies and duplications of many imaginal disc and histoblast derivatives. Phenocopies of the bithorax mutation which transforms metathorax to mesothorax were observed. They were first induced at the syncytial blastoderm stage, had their peak of production at the cellular blastoderm, and were no longer observed after the anterior and posterior midgut were partially invaginated. It was observed that not only are the halter/wing transformations confined to the anterior compartment, but also leg 3 to leg 2 transformations only occurred in the anterior leg compartment.


Calcium-activated conductance in skate electroreceptors: voltage clamp experiments. Voltage clamp experiments allow further characterization of the calcium-dependent repolarizing process in skate electroreceptor epithelium. Four current components are described: a prolonged capacity current, a leakage current, an early active current which flows inward across the lumenal membranes of the receptor cells, and a late current which flows outward. The leakage and capacity currents are linear and may be substracted from the total current, giving net active currents. The early active current is carried by calcium and does not undergo inactivation for at least several seconds. When large stimuli exceed the reversal potential for the early calcium current, the late current is suppressed. Reduction of the ionized calcium concentration in the lumen lowers the reversal potential for the early current and the suppression potential for the late current by the same amount. We conclude that the late current is initiated by a calcium influx into the cytoplasm. During pulses of moderate duration, activation of the late current does not begin until a fixed amount of calcium has entered the receptor cells. The required amount of calcium is reduced if a recent calcium influx has occurred. We suggest that the calcium-activated outward current is mediated by a distinct macromolecule that is insensitive to voltage. Such macromolecules are likely to have an important role in the regulation of electrical activity in excitable cells.


Characteristics of a short incubation model of scrapie in the golden hamster. Repeated passage of the "Chandler" strain of scrapie in female golden hamsters using the intracerebral route of inoculation reduces the minimum incubation period to 60 days, about half of the minimum incubation period so far found in any of the mouse models of scrapie. The infectivity titres in brain in the clinical stage of the disease are considerably higher (greater than 8-0 -log10 LD50 i.c. units/0-05 g) than those found in mouse scrapie. The biological characteristics of this model of hamster scrapie are reported, including the effects on incubation period of route of inoculation, dose of agent, sex of hamster, ambient temperature (hibernation) and splenectomy. Some general and specific applications of this experimental model of scrapie are discussed.


Intracellular calcium and extra-retinal photoreception of Aplysia Giant neurons. The early or "instantaneous" current-voltage relationship for the light-activated potassium current in Aplysia giant neurons was linear during the first second of illumination. However, the light current was greatly reduced or abolished by prolonged hyperpolarization. It was also greatly reduced by the injection of calcium EGTA buffers having calcium activities of 5.6 X 10(-8) M and simulated by injecting buffers with calcium activities of 2.8-5.6 X 10(-7) M. Removal of calcium from the extracellular fluid had no effect. Both the light- and calcium-activated outward potassium currents were reduced by tetraethylammonium (TEA) ions. The light current was not affected by substituting rubidium for potassium nor by substituting either lithium or Tris for sodium. The calcium-activated potassium current persisted when the neuron was cooled to 5 degrees C. However, the light response could no longer be elicited. Light hyperpolarizes Aplysia neurons probably by increasing intracellular calcium activity two-to six-fold which activates a membrane potassium conductance. Calcium levels appear to be restored within the cell and are energy dependent. The light-activated release of calcium is inhibited by cooling. The body wall of Aplysia transmits enough visible or 500 nm light to hyperpolarize some Aplysia giant neurons under ambient conditons. These neurons may be involved in the extraretinal light entrainment that occurs in Aplysia.


Lipochondria and the light response of Aplysia giant neurons,. The ultrastructure, absorbance, and elemental content of lipochondria present in the cytoplasm of Aplysia giant neurons have been investigated before and after 30-1,200 sec doses of white light at intensities which produce saturated light responses. The effects of exposure to the calcium ionophore A-23187 and to EGTA were also examined. The lipochondria of nonilluminated neurons are membrane-bound, and contain lipids, protein, Na, K, Mg Ca, Si, Cl, Br, P, and a pigment which is probably beta-carotene. The cytoplasm appeared to have little pigment. When neurons were illuminated for 20 min, 60-70% of the lipochondria showed marked ultrastructural alterations, the most notable being the appearance of membranous material. Earlier changes which occur after 30 sec of illumination include the appearance of paracrystalline arrays and mottling. Less than 10% of lipochondria in nonilluminated neurons have a similar appearance. These effects were greatly enhanced in illuminated neurons exposed to the calcium ionophore or EGTA. In nonilluminated neurons, the ionophore also produced ultrastructural changes. In frozen specimens, the calcium content of the most electron dense lipochondria of illuminated neurons was reduced. Other elements which were counted were also reduced. The lipochondria are the main intracellular site of photopigment. They may also act as an intracellular source for calcium which, as the accompanying paper indicated, may mediate phototransduction in Aplysia neurons.


Morphological characteristics of the acetylcholinesterase-containing neurons in the CNS of DFP-treated monkeys. The distribution of acetylcholinesterase (AChE, EC3.1.1.7) within extrapyramidal and related structures was studied in 4 monkeys following the i.m. administration of bis-(1-methylethyl) phosphorofluoridate (di-isopropylfluorophosphate: DFP). In 1 animal, sacrificed 4 hr after the injection of 0.43 mg/kg C, AChE is virtually absent in all structures. In the other 3 animals, which received 0.20 mg/kg DFP 10, 12 and 18 hr prior to sacrifice, AChE activity is greatly reduced in the neuropil of those structures which normally show intense AChE activity in pharmacologically unmanipulated monkeys. As a consequence of the lower background AChE activity in the latter 3 DFP-treated monkeys, the perikarya and processes of several groups of neurons can be readily identified. The perikarya and processes of two types of neurons of the neostriatum, representing a small percentage of all neurons in this structure, are intensely stained. They apparently correspond to the chromatic giant aspiny neurons and the achromatic medium-size "spidery aspiny" neurons. Most perikarya and processes of the neurons of the medial and lateral divisions of the pallidum, as well as the morphologically similar neurons of the pars reticulata of the substantia nigra, display light to moderate AChE activity. The pars compacta of the substantia nigra contains a small number of intensely stained elongated and triangular neurons and numerous moderately stained ovoid neurons whose processes are very lightly reactive. The cell bodies of the neurons of the subthalamic nucleus and associated groups of neurons (nucleus ansae peduncularis) are moderately stained whereas the perikarya and processes of the subnucleus compactus of the pedunculopontine tegmental nucleus are intensely and moderately stained, respectively. Numerous large and multipolar neurons associated with the lenticular nucleus (intralamellar groups) or the pallidum (peripallidal groups) including the nucleus ansae lenticularis have somata and processes which show an intense AChE activity. Certain of the latter groups of neurons, partially interspersed with the neurons of the substantia innominata, correspond in part to the nucleus basalis of Meynert. The present data are compatible with the idea that the large AChE neurons of the neostriatum may be the source of the acetylcholinesterasic striatopallidal and strionigral fibers. The similarity between the neurons of the pallidum and those of the pars reticulata of the substantia nigra suggests that the latter structure may represent a caudal extension of pallidal tissue. Therefore, the nigrothalamic projection, which has been claimed to originate in the pars reticulata of the substantia nigra, would correspond to pallidothalamic projections.


The effect of alpha adrenergic blockade on spinal cord autoregulation in the monkey. Spinal cord blood flow (SCBF) was measured over a wide range of artificially varied mean systemic arterial blood pressures (MAP) in a group of monkeys with alpha adrenergic receptors blocked by the intravenous administration of phenoxybenzamine (Dibenzyline). The SCBF was found to vary linearly with changes in MAP. Autoregulation appeared to have been abolished. These data are cited as evidence for a dominant role of the sympathetic nervous system in control of the spinal circulation.


The value of preplacement medical examinations for nonhazardous light duty work. A prospective study on 6,125 job applicants for light duty telephone company work is presented, which indicates that a preplacement medical evaluation is not predictive of risks relating to work attendance or job performance in nonhazardous assignments. Results show that between groups of employees, who were medically classified at the time of hire into categories with or without employment risk factors, there was no significant difference relative to sickness, accident or other absence, or to work performance during the first twelve months after hire. A work force loss of 25% is seen during the first year after hire without significant difference between groups for either numbers of employees lost or reason for loss. A cost-benefit analysis based on this study is presented, which demonstrates that the preplacement medical evaluation for light duty assignments is not cost effective. In addition, further unnecessary costs are incurred when job applicants are medically evaluated but not hired, which is shown to occur here for 27.5% of healthy applicants.


Occupational habituation to aliphatic nitrates and the withdrawal hazards of coronary disease and hypertension. The symptoms of acute aliphatic nitrate toxicity are the same whether the exposure was to excess clinical medication or to percutaneous absorption during manufacture or packaging. In industrial exposures there is good evidence of chronic toxicity, with hazards of (a) increased risk of coronary pain and sudden death after withdrawal, and (b) increased risk of sustained hypertension in predisposed persons. On this basis we must suspect that certain types of therapy with aliphatic nitrate drugs might aggravate the course of coronary heart disease or hypertension. Should not these drugs be removed from the market until their long-term safety has been proved? Industrial experience with these chemicals has been incompletely reported, and more data are needed.


Focal epithelial hyperplasia in a group of south africans: Its clinical and microscopic features. Thirty-seven cases of focal epithelial hyperplasia were discovered among pupils of reform schools and none among pupils of ordinary schools. This difference in occurrence was significant (P less than 0.01). Lesions were either discrete papules or clusters of papules; and the lining mucosa was the most affected part. Eighteen cases were examined microscopically revealing the typical features of the condition. The fact that these lesions occurred in a select group of pupils all of whom are classified as Cape Coloured points to either a selective distribution of the disease or a spread of the disease among people living in communal circumstances. This pattern of distribution coupled with the clinical and histological features would fit a disease of viral origin which is also communicable.


Focal epithelial hyperplasia in a group of South Africans: Its ultrastructural features. Electron microscopic observation of samples of tissues from lesions diagnosed as focal epithelial hyperplasia revealed the presence of viral particles in six (possibly seven) of 13 cases examined. Viral particles were intranuclear and varied from sparsely scattered to densely packed. A crystalline arrangement was present in one case. The chromatin of affected cells was typically condensed into clumps and thick bands, and the nuclear membrane was usually absent in pronounced cases. The nuclei of the basal and prickle cells were frequently indented and the chromatin peripherally condensed. Numbers of lysosomal-like organelles were observed in many of these cells. The ballooning epithelial cells with their mitosis-like aberrations observed with light microscopy consisted of a rim of tonofilaments and organelles and a homogeneous granular center interspersed with dense areas. It is suggested that the nuclear characteristics and numerous lysosomes observed in basal and prickle cells are cellular changes induced by the viral infection and that the mitosis-like aberrations represent a bizarre and arrested form of mitosis.


Intra-uterine healing of fetal rat oral mucosal, skin and cartilage wounds. Orofacial wounds, including rupture of the palate, were surgically created in utero on 19 1/2 day Sprague Dawley rat fetuses. Six hours prior to sacrifice 0.1 mgm/100 gm maternal body weight of colchicine was injected subcutaneously. Five fetuses in each group of operated and unoperated controls were sacrificed at 0, 24, 48 and 72 h postoperatively. Serial histological sections in the frontal plane were stained with hemotoxylin and eosin and modified Mallory's. Rapid and complete epithelialization of oral and skin wounds was observed within the 72 h period. There was a complete lack of inflammatory response, scab formation and involvement of nasal epithelium in healing. Nasal cartilage wounds rapidly rounded off and the perichondrium reformed without evidence of callus formation. These findings are discussed in regard to the etiology of some congenital defects and the prospects of fetal surgical correction of orofacial deformity.


Pigmented cells in adenolymphoma (Warthin's tumor). A study of a series of adenolymphomas showed the presence of pigmented cells in the lymphoid stroma in 85% of the cases. The pigmented cells contained light brown cytoplasmic pigment and manifested sudanophila, acid-fastness, silver reduction capacity, PAS positivity and yellow autofluorescence in ultraviolet light. The morphology, histochemical reactions and autofluorescence suggest that the pigmented cells are macrophages containing ceroid derived from breakdown of damaged organelles of the epithelial tumor cells. It is possible that these cells play a role in the elimination of undigestable pigment material present in the cystic spaces of the tumor.


The histological effects of composite resin materials on the pulps of monkey teeth. Pulpal response of three bis glycol methacrylate composite resins, Smile, Simulate and Experimental Composite no. 2 were tested on primary and permanent monkey teeth using zinc oxide eugenol (ZOE) and silicate as controls. All materials were placed in Class V cavity preparations in Rhesus monkey teeth and evaluated at 3 days and 5 and 8 weeks. The materials were randomly placed in anterior and posterior teeth utilizing 75 primary and 75 permanent teeth. Following perfusion the teeth were prepared by routine histological procedures. The 3 day response of the composite resins was moderate, characterized by disruption of the odontoblasts, vacuolization and mild inflammatory response underlying the cavity. At 5 weeks the formation of reparative dentin and a decrease in the inflammatory response was similar for all resins observed. At 8 weeks a slight increase in reparative dentin and continued decrease in inflammation was noted when compared to the 5 weeks responses. At all time intervals ZOE produced the least pulpal response while silicate produced the most severe response.


Changes in the fine structure of the human dental pulp subsequent to carious exposure. Sections of human pulp tissue taken from the region of a carious exposure in four young patients each having a clinical history of spontaneous dental pain were examined with the electron microscope. All the tissues examined exhibited a generalized edema, and an infiltration with lymphocytes, plasma cells, polymorphonuclear leukocytes and macrophages. Varying degree of lysis of pulp and inflammatory cells were evident. The unmyelinated nerve axons of the pulp appeared to be least affected. Extracellular lysosomes were present in many of the necrotic areas. Edematous vacuoles were noted in two of the pulp specimens. In some of the sections these vacuoles appeared to be responsible for a physical distortion of adjacent unmyelinated nerve axons. It was postulated that such distortion may be a contributing factor to the pain of pulpitis. In another of the pulp specimens, micro-organisms were found intracellularly and extracellularly. Intracellularly they were present within the cytoplasm of polymorphonuclear leukocytes and macrophages and exhibited evidence of lysis. Only two morphological forms, a gram positive rod, and a gram positive coccus were identified.


Experimental allergic sialoadenitis. X. Chronic destructive parotitis induced in immunized rats by daily intraductal challenges with antigen. The right parotid duct of rats was instilled five to eight times with bovine serum albumin at daily intervals. Acute parotitis developed in non-sensitized animals, while chronic destructive sialoadenitis ensued in preimmunized rats. The morphological changes were reminiscent of those found in the salivary glands of patients with Sjögren's syndrome.


Conjugated hyperbilirubinemia in infancy associated with parenteral alimentation. Liver biopsy was performed to exclude anatomic obstruction of the biliary tract in five prematurely born infants who had developed conjugated hyperbilirubinemia during intravenous alimentation with a protein hydrolysate. Each was being treated after having undergone a segmental intestinal resection for necrotizing enterocolitis. Bacterial and viral infections, metabolic disorders, and isoimmune hemolytic disease were excluded as possible causes of jaundice. Light microscopic and ultrastructural analysis disclosed cholestasis and hepatocellular injury without significant inflammatory reaction. Jaundice abated following permanent discontinuation of parenteral alimentation. The jaundice and cholestasis are interpreted to be hepatotoxic effects because of (1) their temporal relationship to the treatment and (2) the presence of hepatocellular damage.


Impaired assimilation of nasojejunal feeds in healthy low-birth-weight newborn infants. We compared nasojejunal with nasogastric tube feeding in 18 healthy low-birth-weight infants from eight to 15 days of age. NJ-fed infants had significantly more stools and excreted significantly more fat and potassium in their stools. Growth and weight gain did not differ between the groups during the study period. Future use of NJ feeding in LBW infants should take into account the possibility of malabsorption associated with this technique.


Platelet dysfunction in the neonate with essential fatty acid deficiency. Platelet aggregation in response to ADP was studied in five EFA-deficient sick premature newborn infants who were receiving fat-free parenteral nutrition. EFA deficiency was diagnosed by analysis of plasma lipid fatty acid values. The deficient infants had impaired platelet aggregation when compared to other low-birth-weight infants fed orally who served as control subjects (maximum 18.1% versus 43.4% at 2.5 muM ADP; 34.5% versus 52.2% at 5.0 muM ADP). In addition, the platelets from EFA-deficient infants demonstrated clearly evident disaggregation. On recovery from their deficient state, the low-birth-weight infants had platelet functions similar to those of apparently healthy premature infants. Clinical hemorrhage occurred in four of the EFA-deficient infants. Thus a deficiency of arachidonic acid, the precursor of thromboxane A2, is correlated with an impairment of the aggregation of platelets, a phenomenon mediated by thromboxane A2. This correlation provides the basis for a hypothesis that the observed EFA deficiency is causally related to the platelet dysfunction.


Reservoirs of pseudomonas in an intensive care unit for newborn infants: mechanisms of control. Potential reservoirs of pseudomonas within a neonatal ICU were evaluated. Colonization of infants by the same pseudomonas pyocin types could be classified as a cluster colonization (occurring over three to ten days), or serial colonization (occurring over longer times). Hands of personnel, sink surfaces, and solutions used to rinse nasopharyngeal catheters were identified as the principle reservoirs. Utilization of a liquid iodophor agent for hand washing and of acetic acid for rinsing suction catheters was associated with a significant reduction in the histologic evidence of sepsis and of pneumonia observed among autopsied infants.


Development of bilirubin transport and metabolism in the newborn rhesus monkey. Hepatic transport and metabolism of bilirubin have been examined in term, premature, and postmature newborn Macaca mulatta (rhesus) monkeys with and without prior phenobarbital treatment of pregnant mother and neonate. In untreated neonates a biphasic pattern of physiologic unconjugated hyperbilirubinemia has been observed. Phase I was characterized by a rapid increase in serum bilirubin concentration to 4.5 mg/dl by 19 hours and an equally rapid decline to 1.0 mg/dl by 48 hours of age. Phase II was characterized by a stable elevation at 1.0 mg/dl (four times greater than in the adult) from 48 to 96 hourse of age, followed by a decline to normal adult concentrations thereafter. An identical pattern was observed in 29 normal, term human neonates, but the duration of each phase was approximately three times as long as that in the monkey. Phase I hyperbilirubinemia appears to result from a sixfold increase in bilirubin load presented to the liver in the neonatal period, combined with marked deficieny in hepatic bilirubin conjugation, the rate-limiting step during Phase I. Hepatic uptake of bilirubin is not rate limiting during Phase I but may contribute to Phase II hyperbilirubinemia. An increased bilirubin load persists throughout the first 19 days of life in the monkey. Phase I physiologic jaundice in the monkey neonate was completely eliminated by prenatal maternal and neonatal administration of phenobarbital. A threefold enhancement of hepatic conjugation of bilirubin (glucuronyl transferase activity) during Phase I entirely accounted for the prevention of hyperbilirubinemia. The bilirubin load was unaffected by administration of phenobarbital. Whereas in control neonates the bilirubin load slightly exceeded hepatic bilirubin conjugating capacity and resulted in retention of bilirubin, in phenobarbital-treated neonates, hepatic conjugating capacity slightly exceeded that required for the bilirubin load. Administration of phenobarbital failed to alter Phase II hyperbilirubinemia and did not enhance either maximal hepatic uptake or excretion of bilirubin. Hepatic glucuronly transferase activity was increased threefold during Phase II and during the remainder of the neonatal period. Premature birth retarded maturation of hepatic glucuronyl transferase activity. In one phenobarbital-treated premature monkey neonate, there was no apparent response to treatment. Accelerated maturation of bilirubin uptake, conjugation, and excretion of bilirubin was observed in one postmature monkey neonate.


Keratinizing potential of sulcular epithelium. It has been shown that the connective tissue base determines the epithelial surface characteristics. Although there is no apparent difference between the connective tissues underlying the subcular and the surface gingival epithelium, the sulcular epithelium is not keratinized as is the gingival surface. The influence of the sulcular environment in determination of keratinization was explored in three adult Rhesus monkeys. Twenty-four intrasulcular mucoperiosteal flaps were elevated beyond the buccal mucogingival border, were turned inside out and sutured to leave the sulcular epithelium exposed on the surface. Short term speciments (1 hour to 7 days) were obtained from one monkey which received H3 thymidine 1 hour prior to sacrifice. Biopsies were obtained from the other two monkeys covering intervals of 1 week to 2 months. The findings indicate that the sulcular epithelium has potential for keratinization. The contact to the tooth appears to determine the lack of keratinization of the sulcular epithelium.


Vaginal drug absorption in rhesus monkeys I: development of methodology. Earlier reports from these laboratories described a procedure for determining vaginal drug absorption in the rabbit based upon a perfusion system, and data on the vaginal absorption of the straight-chain aliphatic alcohols and carboxylic acids were given. These studies have been extended to the rhesus monkey. Rib-cage-type cells were designed for intravaginal insertion through the vulval orifice and to fit the specific dimensions of the monkey vagina. The general design of the cell was similar to that used in the rabbit vaginal absorption studies. The persusion system was checked by using 3H-polyethylene glycol 4000, and no significant leaks from the cell were found. The absorption of the alcohols followed first-order kinetics. The computed apparent permeability coefficients for the alcohols were of comparable magnitude to those previously reported for the rabbit vaginal membrane.


Effects of long-term exposure to environmental levels of polychlorinated biphenyls on pharmacokinetics of pentobarbital in rats. The pharmacokinetics of pentobarbital, 30mg/kg iv, were studied in untreated rats and rats pretreated with 1,5, and 25 ppm of polychlorinated biphenyls in food for up to 140 days. Environmental contaminants may contribute to variations in metabolic rates of drugs by causing enzyme induction. The objective of this work was to quantitate the effects of environmental levels of the contaminant and enzyme inducer, a polychlorinated biphenyl, on the pharmacokinetics of pentobarbital, a drug whose primary elimination route is liver metabolism. The pharmacokinetics of pentobarbital in rats could be fit to a biexponential equation of the type Cp = Ae-alpha t+ Be-beta t. After 35 days of pretreatment, only the 25-ppm-treated rats showed any significant acceleration of pentobarbital elimination. At the 70- and 140-day samplings, both the 5- and 25-ppm pretreatments showed significant acceleration of pentobarbital elimination. There were no significant effects on A, alpha, B, and Vd for any pretreatment. The beta-values for the 25-ppm-pretreated rats reached a constant value from the 35-day pretreatment period onward. A calculation of total body clearance suggested that pentobarbital elimination in those rats had approached portal blood flow rate-limited metabolism.


Rapid determination of nitroglycerin volatility using thermogravimetric analysis. The effect of selected tablet components on the volatility of nitroglycerin from compressed sublingual tablets was studied by thermogravimetric analysis. The results, confirmed by chemical analyses, showed that nitroglycerin volatility is significantly reduced by the use of povidone USP and microcrystalline cellulose NF in tablet formulations. In general, the stabilizing effect of these materials was dependent on the presence and the concentration of each other. These studies demonstrated the utility of thermogravimetric analysis as a rapid and reliable means of screening nitroglycerin formulations for stability purposes.


Chemistry and pharmacology of homologs of 6-acetyl-and 3,6-diacetylmorphine. 3,6-Diformyl- and 3,6-dipropanoylmorphine and 6-formyl- and 6-propanoylmorphine were prepared to obtain longer acting, heroin-like compounds. The 6-acylated compounds were more potent than heroin subcutaneously and were orally effective, and their duration of action was at least two to three times greater than that of heroin in monkey species.


Calcium absorption in diphosphonate-treated rats: effect of parathyroid function, dietary calcium and phosphorus. 1. The role of parathyroid hormone (PTH) and 1, 25-dihydroxy-cholecalciferol (1,25-(OH)2D3) in modulation of intestinal Ca absorption was studied in rats, using disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP), which is known to reduce 1,25-(OH)2D3 formation. 2. EHDP decreased intestinal Ca absorption. This effect could be abolished by small amounts of 1,25-(OH)2D3, whereas even large doses of PTH were ineffective. EHDP also decreased Ca absorption in thyroparathyroidectomized (TPTX) rats. Therefore the effect of EHDP on 1,25-(OH)2D3 production is unlikely to be mediated through PTH. 3. The correction by PTH of the decreased Ca absorption in TPTX rats was inhibited by EHDP. Since EHDP inhibits formation of 1,25-(OH)2D3 the effect of PTH on Ca absorption is likely to be mediated through this vitamin D3 metabolite. 4. In normal rats both a low Ca and a low P diet stimulated Ca absorption. In EHDP-treated intact rats low Ca still stimulated Ca absorption, whereas the effect of low P abolished. This indicates that low Ca and low P diets affect Ca absorption through different mechanisms. 5. Intestinal adaptation to a low Ca diet was still observed in EHDP-treated TPTX rats. Thus, in the rat, intestinal adaptation to low Ca diet can occur without PTH.


Diagnosis of rotavirus infection by cell culture. Rotaviruses were detected by electronmicroscopy in 35 of 84 specimens of faeces from infants with diarrhoea, and in 31 by fluorescent staining of tissue cultures infected with help of centrifugation. LLC-MK2 cells were found to be the most sensitive, although primary and secondary human-embryo-kidney and primary calf-kidney cells could also be used. A micromodification of the tissue-culture method provides a relatively simple technique for the diagnosis of rotavirus infection, for the titration of virus infectivity and for estimating neutralising antibodies in serum.


A new polyvalent Pseudomonas vaccine.

A new polyvalent Pseudomonas vaccine. This paper describes the preparation, chemical characterisation and immunogenic properties of a new polyvalent pseudomonas vaccine. New cultural methods were devised which allowed a build-up of the immunogen in the cell wall of the bacteria, and mild extraction techniques were used to remove the immunogens from the cell wall of living bacteria without apparent physical or chemical change which might affect immunogenicity. The polyvalent vaccine comprised 16 component vaccines, each a lipid-protein-carbohydrate complex extracted from one of the 16 different serotypes of Pseudomonas aeruginosa. Single injections into mice of each of the 16 component vaccines induced protection against several strains of homologous serotypes within 3 days of vaccination. The polyvalent vaccine induced similar protection against several strains of each of the 16 serotypes. We would like to thank R. E. Dyster, K. Digby and J. Simmonds for their technical assistance.


The survival of gonococci and meningococci in subcutaneous diffusion chambers in mice. Studies are reported on the survival of gonococci and meningococci in Millipore diffusion chambers implanted subcutaneously in normal mice and in pre-immunised mice. The chambers allowed the passage of nutrients and humoral factors but excluded host cells. After an initial fall in the viable count--attributed to lysis by non-specific serum factors--there was evidence of multiplication of Neisseria gonorrhoeae; the subsequent development of specific antibody led to the disappearance of gonococci 16 days after the chambers were implanted. N. meningitidis behaved differently in the implanted chambers. Meningococci did not appear to be lysed by non-specific humoral factors and so the viable count showed no initial fall. The meningococci survived for 49 days, at which time the entire chamber was rejected.


Sodium aurothiomalate, gold keratinate, and various tetracyclines in mycoplasma-induced arthritis of rodents. Sodium aurothiomalate (ATM), gold keratinate and five different tetracyclines were investigated for activity against M. arthritidis strain ATCC 14124 and M. pulmonis strain JB, both in vitro and in rodents with arthritis caused by these mycoplasmas. In vitro, ATM had only slight activity against M. arthritidis and M. pulmonis, while gold keratinate was virtually inactive against M. pulmonis. In contrast, the tetracyclines were highly active against both mycoplasmas. The tetracyclines and the gold salts were both predominantly mycoplasmastatic. In both rats and mice, parenteral administration of ATM, begun shortly before or after infection of rodents with mycoplasmas, prevented the development of arthritis. ATM or gold keratinate, given subcutaneously to mice already arthritic from infection with M. pulmonis, reduced the severity of the arthritis, even although gold keratinate was inactive aganist this mycoplasma in vitro. Moreover, direct testing of serum, collected from mice treated with gold keratinate, failed to demonstrate antimycoplasmal activity in vitro. These results suggest that the action of gold-containing drugs in mycoplasmal arthritis is due to biological properties of gold other than antimycoplasmal activity. Tetracyclines were also found to be effective in preventing arthritis in rats and mice when given subcutaneously. With high doses, subcutaneous, but not oral, therapy significantly reduced the severity of established arthritis in mice infected with M. pulmonis. The blood levels achieved with the different tetracyclines, when related to their therapeutic activity, indicated that good antimycoplasmal activity and adequate absorption from the gut were not the only properties needed for optimal effectiveness. The results are discussed in relation to treatment of rheumatoid patients with tetracycline HCl.


Thermodynamic analysis of active sodium transport and oxidative metabolism in toad urinary bladder. Measurements of electrical current and oxygen consumption were carried out concurrently under voltage clamp conditions in 11 toad hemibladders. Inhibition of active transport with amiloride then permitted evaluation of the passive conductance and the rate of basal oxygen consumption Jbr, allowing the simultaneous determination of the rates of active sodium transport JaNa and suprabasal oxygen consumption Jsbr-JaNa and Jabr were linear functions of the electrical potential difference over a range of +/-  80 mV. This allowed the comprehensive application of a linear nonequilibrium thermodynamic formalism, leading to the evaluation of the affinity A (negative free energy) of the metabolic reaction driving transport, all phenomenological coefficients, and the degree of coupling q relating transport to metabolism. Values of A determined by two techniques were A1=56.0 +/- 5.8 and A2=58.2 +/- 6.5 kcal per mole. Values of q determined by two techniques agreed well and were less than 1, indicating incompleteness of coupling, and hence lack of fixed stoichiometry between Na transort and O2 consumption. The affinity and the electromotive force of sodium transport ENa are not closely correlated, reflecting the fact that ENa comprises both kinetic and energetic factors.


Gastric cancer: current status of treatment. While carcinomas of the stomach is decreasing in incidence in the Dnited States, it is still a major cause of cancer death. But gastric neoplasms are not decreasing in some other geographic areas. According to some studies, 30% of all cancer in the U.S.S.R. originates in the stomach. The rate of gastric neoplasms is greatest in Japan, and over 54% of all cancer in the male population arises in the stomach. The peak age for development of stomach cancer is between 70 and 80 years; over 60% of all stomach cancer is diagnosed in patients between the ages of 60 and 70, while more than 10% is found in those over 80. The main hope for cure at this time rests with surgical treatment. However, despite increased use of surgery, the 5-year survival rate of approximately 13% for patients diagnosed during 1955-59 has not improved to any degree since that time. The major drugs commonly used to treat gastric cancer are 5-fluorouracil (5-FU) and mitomycin C. Controversy still exists concerning the optimum method for administering 5-FU, the most frequently used drug in the United States. The standard loading-course method was attended by a high risk of severe toxicity and drug-related deaths. Several variations of the loading course have evolved. Currently, the Mayo Clinic group uses a 5-day course of 13.5 mg 5-FU/kg repeated every 5 weeks, with therapy interrupted if stomatitis or diarrhea develops; with this regimen the drug-related mortality rate was reported to be less than 1%. Studies have shown that 5-FU plus radiotherapy can enhance survival in patients with locally unresectable diseases. The overall objective with 5-FU is 20-25% with an average of 4-5 months' duration of response. Despite the many patients treated with 5-FU, rarely has a systematic analysis been done of factors such as age, sex, disease-free interval, histologic grade of the tumor, or sites or metastases, which might predispose to a favourable or unfavorable response. In Japan the most commonly used drug for treatment of gastric cancer is mitomycin C, the second most frequently used drug in the United States. The overall objective response rate with mitomycin C is between 20 and 30%, with the higher response rates being reported in the Japanese data. The average duration of response ranges from 1 to 3 months. The nitrosoureas [1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), 1,3-cis(2-chloroethyl)-1-nitrosourea (CCNU), and methyl CCNU (MeCCNU)] have shown some evidence of activity against gastric cancer. BCNU has yielded an objective response rate of 18% (6/33) and an average duration of response of 4.5 months in gastric cancer patients, most of whom had no prior therapy. Adriamycin recently has been shown to have some antitumor activity, with an approximate response rate of 25%. Combination approaches have been more successful in stomach cancer than in any other gastrointestinal neoplasm. The Japanese have reported higher response rates with a combination of 5-FU, mitomycin C, and cytosine arabinoside...


Potent inhibitory effect of a new antiestrogen (RU 16117) on the growth of 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors. At the daily dose of 24 mug for a period of 4 weeks, RU 16117 (11alpha-methoxyethinyl estradiol), a new antiestrogen, led to 65% reduction of the number of already established dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in female Sprague-Dawley rats. Not only the tumor number but also the tumor size was reduced by RU 16117 in a manner similar to that seen after ovariectomy. The absence of an inhibitory effect of doses of 0.1 to 12.5 mug 17beta-estradiol (E2) per day, a dose-range which covers the low estrogenic activity of the RU 16117 doses used, suggested that the inhibitory effect of RU 16117 was not due to its estrogenic activity. Decreased levels of receptors for E2, progesterone, and prolactin were found in the tumors remaining after ovariectomy; treatment with the dose of RU 16117 sufficient to inhibit tumor growth (24 mug) had a similar inhibitory effect on the levels of E2 and prolactin receptors. These data suggested that a reduction of hormone receptor levels in the tumor tissue could be a mechanism by which RU 16117 acts as a potent inhibitor of the growth of DMBA-induced mammary carcinoma.


Treatment of recurrent and widespread testicular tumor by radical reductive surgery and multiple sequential chemotherapy. There were 37 patients with stages II and III testicular tumors treated by a combination of multisequential chemotherapy and radical reductive surgery. Two protocols were used: 30 patients received bleomycin, vinblastine, platinum, doxorubicin hydrochloride, cyclophosphamide and actinomycin D (protocol A), and 7 patients received bleomycin, vinblastine, vincristine, platinum and actinomycin D (protocol B). A complete clinical remission was achieved in 19 of the 37 patients (51.3 per cent), for an average survival of 12.9 months to date. A partial clinical remission was obtained in 7 patients (18.9 per cent), for an average survival of 14.2 months. Eleven of the patients (29.7 per cent) escaped from therapeutic control. The collective response (complete and partial clinical remissions) represented 70.2 per cent of the patients (26 of 37), with an average survival of 14.8 months. A new approach for the simultaneous excision of metastases in the abdomen and the chest is described and the rational basis for the combination treatment of these tumors is discussed.


Studies of endoparasites of the mourning dove (Zenaida macroura) in the southeast United States. From September, 1973, through November, 1974, 255 mourning doves (Zenaida macroura) were collected in the southeastern United States and examined for endoparasites. Thirteen species of endoparasites were found and included six species of protozoans, one trematode, two cestodes, and four nematodes. New host records included Sarcocystis sp., Echinostoma revolutum, Hymenolepis sp., Aproctella stoddardi, Ascaridia columbae, and Dispharynx nasuta.


Avian hematozoa of some birds from Tchad. A total of 389 birds of 32 species representing 14 families from Tchad were examined for blood parasites. Eighty-nine (22.9%) harbored infections of Haemoproteus (64%), Plasmodium (12.4%), Trypanosoma (1.1%), Atoxoplasma (=Lankesterella) (5.6%), and microfilaria (28.1%). Species of Leucocytozoon were not observed in the present study. The occurrence of the different genera differed markedly between bird families; members of the Ploceidae comprised 85% of the infected birds.


Sarcocystis hemionilatrantis (Sp. N.) life cycle in mule deer and coyotes. Fifteen coyotes (Canis latrans) shed sporulated sporocysts in their feces after eating freshly ground skeletal muscles from a mule deer (Odocoileus hemionus hemionus) infected with microscopic-sized cysts of Sarcocystis. Sporocysts were shed intermittently from 12 to 36 days after ingestion of the infected meat. Sporocyst size averaged 14.4 X 9.3 mum. Eleven mule deer fawns orally inoculated with these sporocysts became infected and 9 of 11 died between post-inoculation days (PID) 27 and 63. Clinical signs of anorexia, weight loss, pyrexia and weakness were evident prior to death. A calf (Bos taurus) and two lambs (Ovis aries) orally inoculated with these sporocysts did not become infected and remained healthy throughout the experiments. Similarly, uninoculated control animals consisting of three mule deer fawns, two lambs and one calf remained healthy during the experiment. Preliminary histologic examinations conducted on selected tissues from all animals revealed microscopic-sized schizogonous stages in macrophages, between muscle fibers and near blood vessels in the esophagus, heart, biceps femoris, semi-membranosus, diaphragm and tongue from seven of eight fawns which died between PID 27 and 39. Developing or mature muscle cysts were not found in fawn tissue until PID 60. Sarcocysts were found in the three infected fawns examined after this time. Muscle cysts or earlier schizont stages were not found in tissues from the inoculated or uninoculated calves and lambs. A single muscle cyst was found in one control fawn; the other two control fawns were negative for both muscle cysts and other schizogonous stages. These results established that the life cycle of this species of Sarcocystis can be completed with coyotes as the definitive host and mule deer as the intermediate host. Based on the demonstrated host specificity and earlier findings, the name Sarcocystis hemionilatrantis is proposed for this parasite of mule deer and coyotes.


Blood parasites of some columbiform and passeriform birds from Chile. Ninety-one birds of 23 species from Chile were examined for haematozoa; 13 birds of seven species harbored species of Haemoproteus, Leucocytozoon, Plasmodium, Trypanosoma and microfilariae. Haemoproteids (representing four species) were the most common parasites and occurred in 10 of the 13 infected birds.


Coccidia of coyotes in eastern Colorado. Eighty-two coyote fecal samples were collected from eastern Colorado and examined for coccidia. Sporocysts of Sarcocystis were observed in 17 of the samples and oocysts of Isospora ohioensis were observed in two samples. Ten fecal samples contained eimerian coccidia thought to be pseudoparasites of the coyote acquired while ingesting heavily infected rabbits.


Mycotic tuberculous aneurysm of the thoracic aorta. Tuberculous mycotic aneurysm has been reported with surprising frequency, especially in the aorta. Because the diagnosis can often be made on clinical and roentgenologic grounds, and because of the very poor prognosis if untreated and surgical curability if recognized, experience with three cases is reported. The aneurysm is generally of the false variety, representing a walled-off perforation of the aorta. Contiguous tuberculosis in the form of lymphadenitis or Pott abscess is generally responsible for the aortic involvement that results in the aneurysm. Miliary tuberculosis, which is often present, is probably a result rather than the cause.


Minimizing the risk of amniocentesis for prenatal diagnosis. Although the risk of amniocentesis in the second trimester of pregnancy is small, untoward sequelae can be further reduced. One hundred twenty amniocenteses were attempted during a two-year period. In eight instances, the patient had to return for a second tap because of bacterial contamination, inadequate number of fetal cells, or inability to obtain amniotic fluid. These eight patients all underwent repated amniocentesis and successful karyotyping. There were no major complications and one minor complication. Two spontaneous abortions were not apparently related to the procedure. In both these cases, fluid could not be obtained because one patient had a blighted ovum with a small sac and the other had large uterine fibromyomas.


[Effect of nitroglycerin on peripheral venous pressure at rest and during exercise in patients with heart diseases (author's transl)]. 1) In "left-sided" cardiac diseases, the effects of nitroglycerin on arterial pressure and heart rate were noted to be modest and disappeared within 15 minutes whereas the effect upon venous pressure, measured on the median cubital vein, lasted for approximately 30 minutes. 2) At 30 minutes after a dose of nitroglycerin there occured a significant depression of venous pressure elevation on exertion in patients with such "left-sided" cardiac diseases as ischemic heart disease, arteriosclerotic heart disease and hypertensive cardiovascular disorder. In patients with mitral insufficiency and aortic stenosis, on the other hand, the exertional venous pressure elevation was significantly suppressed 7 minutes after nitroglycerin although the suppression did not longer exist 30 minutes after administration. 3) The arterial pressure, heart rate, resting venous pressure and venous pressure elevation on exertion were virtually not affected by the administration of nitroglycerin in "right- or both-sided" cardiac disorders. 4) There was no significant change in cardiac output 30 minutes after a sublingual dose of nitroglycerin. The data obtained seem to stress importance of the effect of dilating capacitance vessels in the mechanism of antianginal action of nitroglycerin.


Combined decrease of postheparin-diamine oxidase (histaminase) and postheparin-lipoproteinlipase in inflammatory diseases. Diamine oxidase (DAO, histaminase), according to Schayer, is an essential enzyme in histamine metabolism. It metabolises also a variety of diamines such as putrescine and cadaverine and is generally accepted to be identical with histaminase. Lipoproteinlipase (LL) is assumed to play an essential role in lipid metabolism. In vertebrates, parenterally applied heparin causes a marked dose-dependent rise of the plasma level of both enzymes mainly due to the release from the enzyme containing organs. The plasmatic level changes of DAO and LL after heparin application (200 U/kg b.wt., i.v.) have been studied in 30 patients suffering from 20 different, predominantly inflammatory diseases. In all cases the release of postheparin diamine oxidase (PHD) and of post-heparin lipoproteinlipase (PHLA) was found to be markedly decreased. There existed a highly significant correlation between the degree of the release of both enzymes (r=0.843, p less than 0.0005). In all patients normal levels of plasma insulin were detected. No correlation was found between PHLA and plasma triglycerides levels. Decrease of PHD respectively PHLA was a more sensitive biochemical parameter than were changes of serum glutamic pyruvic transaminase in acute hepatitis and of C reactive protein (CRP) in chronic inflammatory kidney diseases. This finding is most likely a general phenomenon in inflammatory diseases. Besides hormonal regulation inflammation-dependent effects on PHLA have to be discussed.


The establishment of specified-pathogen-free marmosets, Callithrix jacchus. The establishment of 3 specified-pathogen-free marmosets (Callithrix jacchus) during the period May 1969 to January 1973 is described. A brief history of the conventional breeding colony from which the animals were derived is given and hysterotomy and hand-rearing techniques are described.


Apparent resistance of the integument of the inverterbrate Lehmannia poireri to production of papillary tumors by a known chemical carcinogen. Papillary tumors of the skin of the land invertebrate Lehmannia poireri (a gastropod) could not be induced by using a potent vertebrate carcinogen. With the same agent 7,12-dimethylbenz (a) anthracene papillary tumors can readily be induced in mice. The resistance of this invertebrate to a known vertebrate carcinogen is discussed and the ramifications are conjectured.


Coronary artery spasm. medical management, surgical denervation, and autotransplantation. Coronary artery spasm was induced by intravascular administration of ergonovine maleate (Ergotrate) during cardiac catheterization. In 78 patients suspected to have Prinzmetal's angina, no morbidity or death has resulted despite complete occlusive spasm in two and three coronary arteries. Typical EKG changes and akinesia of the myocardium in the distribution of the occluded vessels documented functional myocardial ischemia during spasm. The occlusive spasm is readily reversed by sublingual or intravascular nitroglycerin, and ventricular contractility returns to normal following relief of spasm. Occlusive spasm has been demonstrated in 15 patients with clinical evidence of Prinzmetal's angina. Symptoms have been effectively relieved by coronary vasodilators in 10 patients. Of the 5 patients in whom medical therapy failed, 4 were treated surgically. These 4 patients were in the intensive care unit with protracted, prolonged pain, subendocardial infarctions, and persistent failure of coronary vasodilators. Aorta-coronary bypass grafts have been combined with total cardiac denervation by autotransplantation (one patient) and total cardiac denervation by stripping of the great vessels (3 patients). Two of the patients treated by cardiac denervation died in the early postoperative period. The patient treated by autotransplantation has total relief of symptoms but persistent spasm on angiography. The angiographic demonstration of occlusive coronary spasm remains a valuable diagnostic tool to document definitively the presence of spasm. The surgical results question the value of surgical intervention in this disease.


Cephalothin prophylaxis in cardiac valve surgery. A prospective, double-blind comparison of two-day and six-day regimens. A prospective, double-blind study comparing a 6 day with a 2 day regimen of cephalothin prophylaxis was conducted among 200 patients undergoing prosthetic valve replacement. No cases of endocarditis occurred during the 2 month follow-up. Sternal wound infection developed in 2.8 per cent of the 6 day group and 2.1 per cent of the 2 day group. Pneumonia developed in 8.5 per cent of the 6 day and 5.3 per cent of the 2 day group; most of the bacteria isolated were susceptible to cephalothin. Urinary tract infection developed more frequently in the 2 day group (17.0 versus 8.5 per cent), particularly during the first 6 postoperative days. Three of 11 patients with no detectable cephalothin in their sera at the close of operation developed staphylococcal wound infections, compared with 2 of 175 patients whose sera contained cephalothin at the close of surgery (p = 0.002, Fisher's exact test). A short course of prophylactic antibiotics is prudent, but there is no justification for prolonging their administration.


Nutritional support in cardiac cachexia. A nutritional survey of 350 hospital patients reveals 50 with cardiac disease who had clinically significant protein-calorie malnutrition. Assessment criteria of malnutrition (per cent normal) included triceps skin fold (52 per cent), arm muscle circumference (88 per cent), and impaired delayed hypersensitivity skin testing (i.e., deficiency in cell-mediated immunity), the latter frequently observed in patients with concurrent weight loss. The functional category of cardiac status was not precise in predictin the morbidity and mortality of 14 patients undergoing cardiac valvuloplasty. By contrast, a nutritional/metabolic profile using weight loss, triceps skin fold (35 per cent), arm muscle circumference (27 per cent), and cell-mediated immunity (29 per cent) did identify high-risk patients who could be expected to benefit by concurrent nutritional support (4/4). Further studies are indicated to determine if nutritional support for cardiac cachexia can reduce the levels of morbidity and mortality during mitral and tricuspid valve surgery.


Mapping assignment of the Rh and Duffy blood group genes to chromosome 1. Blood group genes are inherited in a straightforward manner and their products are readily detectable. Because of this they are utilized over a wide area of scientific endeavor and provide excellent markers for use in gene mapping of the human chromosomes. Both the Rh and Duffy blood group genes have now been localized to the number 1 chromosome. Studies of a patient whose red cells exhibit mosaicism for the Rh blood group indicate that loss of the end of the short arm of chromosome number 1 is associated with loss of an Rh gene complex. The Rh gene can, therefore, be assigned with some precision to this region of the chromosome.


Erythrocyte morphology in genetic defects of the Rh and Kell blood group systems. Absence of KX antigen and of normal expression of the Kell system antigens is associated with bizarre red blood cell morphology when observed by either light or scanning electron microscopy. Numerous acanthocytes and dacryocytes have been observed in the peripheral blood smear of an apparently healthy individual with McLeod-phenotype blood, in a male patient with type II chronic granulomatous disease who had a shortened 51Cr red blood cell survival time, and in a minor population of the red blood cells of his carrier mother.


A cost benefit analysis of continued stay certification. A large portion of the resources of the Professional Standards Review Organization Program have been directed toward the review of inpatients to determine their need for continued hospitalization. The primary goal of this review process is the containment of hospital costs through the elimination of unnecessary patient hospitalization. A cost benefit analysis of this review process shows that the potential financial savings accrued are unlikely to offset the costs associated with the review procedure.


Hypopharyngeal diverticulum.

Hypopharyngeal diverticulum. The diagnosis and surgical management of 26 patients with hypopharyngeal diverticulum treated in the Department of Otolaryngology of the Washington University Medical School from 1961 to 1973 is discussed. The surgical technique for external excision of the diverticulum is described in detail. Results and complications are presented. The surgical excision of hypopharyngeal diverticulum is a standard, safe, and proven method of management which can be expected to result in satisfactory long-term results with minimal morbidity.


Ossicular transplants: histologic findings in animals and man. Numerous papers have been published in the past 15 years in which the authors attempted to predict the results of surgical procedures on humans by analyzing the findings in animals undergoing similar procedures. Our experience in analyzing animal and human temporal bones indicates that conclusions drawn on this basis are frequently invalid. We reviewed temporal bones of monkeys and cats that had had a variety of surgical procedures. There is much more middle ear fibrosis, particularly in the epithmpanum, in these animals than one finds in human temporal bones. In a number of animals in which middle ear procedures were performed, hydrops of the inner ear or labyrinthitis occurred. This has not been the experience in human middle ear surgical procedures. An extensive review of the literature indicates that most investigators are of the same opinion. However, there are still those who are performing experiments using ossicular transplants, stapedectomy techniques, etc., who attempt to correlate the findings in animals in anticipation of what the same procedures might do to the human middle and inner ear. It appears from our experience, and that of many other investigators, that the ultimate fate of ossicular repositioning and transplantation in various animals cannot be used to predict what might happen in human beings.


Laryngeal involvement in Von Recklinghausen's disease: a case report and review of the literature. A case of neurofibromatosis involving the larynx is added to the 19 previously reported cases; furthermore, it represents the only reported case of plexiform ganglioneurofibroma of the larynx in Von Recklinghausen's disease. The reported cases of neurofibromatosis with laryngeal involvement in the world literature are discussed and summarized. The main clinical symptoms are dyspnea, dysphonia and dysphagia which occasionally require tracheotomy when the condition is recognized. Elective surgical excision is the treatment of choice.


Pseudomonas mastoiditis.

Pseudomonas mastoiditis. Opportunistic infections of the external auditory canal or the middle ear due to Pseudomonas aeruginosa occurring in patients with low resistance to infection have a 35 percent mortality rate. Once the process extends into the pneumatized temporal bone, eradication becomes more difficult and the mortality rate increases to 72 percent because of the high incidence of involvement of cranial nerves, adjacent intracranial vessels, and meningitis. Treatment is directed towards the underlying condition, administration of systemic carbenicillin and gentamicin, topical colistin therapy, and judicious surgical debridement. Pseudomonas vaccine may be of help. Fifteen cases are presented. Nine follow the pattern of malignant external otitis and six began as a primary acute otitis media.


Carcinoma of the tonsil: results of radical irradiation with surgery reserved for radiation failure. This analysis reviews the treatment results of 58 patients with squamous cell carcinoma of the tonsil who were treated by radical irradiation to the primary, with operation reserved for radiation failures. Postirradiation radical neck dissection was sometimes added as part of the initial treatment plan. The local control and absolute survival rates for T1-T2 lesions were quite good, and complications were minimal. On the other hand, the local control and absolute survival for T3-T4 lesions were only fair, and complications generally more severe, although mandibulectomy for osteonecrosis was not required in this small series. There appears to be no justification for combining operation with radiation in the initial attack for T1-T2 lesions. Although the T1-T2 lesions might as well be cured by operation alone, it would entail the loss of part of the mandible, pharyngeal wall, possibly some tongue and soft palate, and at least one radical neck dissection. At attempt at combining operation and irradiation for some T3 (T4) lesions appears justified by the high failure rate of radical irradiation alone. However, therapeutic zeal should be tempered by the realization that many of these patients are elderly or in poor general health, and an aggressive combined treatment approach may be unrealistic .


[Pathophysiology and disgnosis of autonomous adenoma (author's transl)]. From personal experience in 200 patients and after a careful review of the literature autonomous adenoma of the thyroid is discussed under three aspects: 1. Different ways of its pathogenesis are possible. None of them has been sufficiently proven. 2. Differentiation by scintigraphy into a compensated, partially decompensated stage does not correlate sufficiently with the concentration of thyroid hormones in the blood and the overall clinical picture. The TRH test is negative in about 90% of patients independent of the stage evaluated by scintigraphy. 3. The diagnosis of the disease by modern tools is critically reviewed.


[Influence of vasoactive substances on blood sugar and serum insulin in normal and diabetic carbohydrate metabolism (author's transl)]. The effect of the following vasoactive substances, which are used in the treatment of peripheral arterial occlusive diseases, was investigated in a randomized study in 36 patients with normal and 52 patients with diabetic carbohydrate metabolism by intravenous infusion on the behaviour of blood sugar and serum insulin (IMI) during simultaneous oral glucose tolerance tests (100 g oligosaccharides). The substances used and the doses given were as follows: protein-free calf-blood extract (Actihaemyl, 0,5 ml per kg body weight), bencyclane (Fludilat, 200 mg), naftidrofuryl (Dusodril, 200 mg, pentoxifyllin (Trenal, 200 mg). The results obtained with the simultaneous treatment and oral glucose tolerance test were compared with a second OGTT carried out at an interval of 3-4 days under the same conditions but without administration of the substances (in a cross-over procedure) and the results of these experiments were compared with those obtained from an untreated control group. In subjects with a diabetic metabolic state, Actihaemyl led to a significant reduction of the blood sugar after oral glucose load (p less than 0,05) without producing any change in serum insulin. The same behaviour was exhibited by Fludilat for the total area integral and by Trental for the first 60 min after the oral glucose load. The change in the blood sugar behaviour was only significantly different from the untreated controls with Actihaemyl (p less than 0,05). In subjects with a normal metabolic state neither blood sugar nor serum insulin (IMI) were altered by any of the substances investigated.


[Changes in male sexual function during hemodialysis and after renal transplantation under psychiatric aspects (author's transl)]. 20 patients with well functioning kidneys were investigated psychiatrically and had to judge on their libido and potency prior to the onset of their illness under chronic hemodialysis and after transplantation. The psychometric instrument used was the FPI (Freiburger Persönlichkeits-Inventar). The sexual activity was found to be either significantly reduced or absent in 80% during hemodialysis. Following transplantation more than 50% sexually fully recovered. In patients with persistent sexual dysfunction in the post-transplant period depressive symptoms were found four times as much as in those with a complete recovery. Psychometrically the latter characterized themselves as more active, optimistic but even as less self-critical. Therapeutic aspects are being discussed.


Erythromycin resistant mutations in Bacillus subtilis cause temperature sensitive sporulation. All of several hundred erythromycin resistant single site mutants of Bacillus subtilis W168 are temperature senstive for sporulation. The mutants and wild type cells grow vegetatively at essentially the same rates at both permissive (30 degrees C) and nonpermissive (47 degrees C) temperatures. In addition cellular protein synthesis, cell mass increases and cell viabilities are similar in mutant and wild type strains for several hours after the end of vegetative growth (47 degrees C). in the mutants examined, the temperature sensitive periods begin when the sporulation process is approximately 40% completed, and end when the process is 90% completed. At nonpermissive temperatures, the mutants produce serine and metal proteases at 50% of the wild type rate, accumulate serine esterase at 16% of the wild type rate, and do not demonstrate a sporulation related increase in alkaline phosphatase activity. The eryR and spots phenotypes cotransform 100%, and cotransduce 100% using phage PBS1. Revertants selected for ability to sporulate normally at 47 degrees C (spot), simultaneously regain parental sensitivity to erthromycin. No second site revertants are found. Ribosomes from eryR spots strains bind erythromycin at less than 1% of the wild type rate. A single 50S protein (L17) from mutant ribosomes shows an altered electrophoretic mobility. Ribosomes from spo+ revertants bind erythromycin like parental ribosomes and their proteins are electrophoretically identical to wild type. These data indicate that the L17 protein of the 50S ribosomal subunit from Bacillus subtilis may participate specifically in the sporulation process.


[The estimation of thyroxine, triiodothyronine, thyro-binding-index, and free-thyroxine-index in the newborn (author's transl)]. Because of the importance of early diagnosis of hypothyroidism normal values of thyroxine (T4), thyro-binding-index (TBI), free thyroxine-index (FTI) and triiodothyronine (T3) in the serum of newborns were established. In extremely premature babies as in early fetal life the total thyroxine is relatively low. The lowest serum thyroxine in newborns without hypothyroidism was found in a premature infant with a birth weight of 750 g, i.e. 4.8 mug/100 ml on the 4th day of life. Otherwise the T4 values were quite high during the neonatal period, without signs of hyperthyroidism. Our hypothyroid patients scarcely had higher T4 values (0.8-5.1 mug/100 ml) within the first month of life than older hypothyroid patients. Healthy newborns had a mean T4 value of about 15 mug/100 ml during the first week of life (two standard deviations 6.4-23.6 mug/100 ml). Afterwards the T4 values slowly came down to a mean of about 12 mug/100 ml in the 4th week of life. During the first month of life the FTI of hypothyroid patients was below two standard deviations of normal newborn values, whereas TBI-values showed an overlap. During the first 3 days of life newborns with goiter had T4-values in the lower normal or hypothyroid range without obvious signs of hypothyroidism. FTI was quite low, too, and TBI relatively high (as in hypothyroidism). Within the second week of life all these values normalized mostly after treatment with KI ointment, occasionally without this treatment. Where these values did not normalize, hypohtyroidism was assumed. Triiodothyronine in cord blood was very low (0.47 ng/1.6 ng/ml) during the neonatal period (one to two days after birth almost 2.0 mg/ml). Values in our hypothyroid patients fluctuated widely (zero to slightly elevated values with a mean of 0.78 ng/ml). Therefore, T4 seemed more reliable than T3 for the diagnosis of hypothyroidism (the opposite was true for hyperthyroidism.


[The value of xeroradiography (author's transl)]. Equally good pictures of the bone were proved in 2800 xeroradiographs as in roentgen film, but at the same time the soft parts around the bone and their pathological changes were well portrayed. Additional information is obtained in the radiodiagnosis of the nasal sinus system, the upper airways, the breast and the soft parts of the head, neck and extremities. Xerotomography of the skull and especially of the lungs is superior to film tomogoraphy.


[Health education and personal therapy in self-provoked diseases (author's transl)]. Diseases due to faulty behavior patterns injurious to health-- overeating, alcoholism and nicotine abuse -- are increasing ominously in our consumer society. Those with labile attitudes gather together in courses of treatment and in hospitals where they are usually treated symptomatically and perhaps also given more or less basic information on risk factors. A behavior-therapy effect is, however, only attainable in many cases through the additional longterm experience guidance in self-experienced groups. An appropriate motivation should be attempted by psychotherapeutic methods in the internist hospital treatment which so often comes first and by the occupational therapy institutions in the not frequent criminal offence. Prophylactically we need a medical pedagogic health education from infancy onwards.


[Informative value of control methods for postoperative supervision of medication with aspirin and heparin (author's transl)]. Under the effect of acetylsalicyl lysin, a postoperative hypercoagulability was ascertained with regard to shortened antithrombin and partial prothrombin times. The inhibition of aggregation was easily demonstrable with a high concentration of collagen in the test batch and showed a striking relationship to the occurrence of thrombosis. Under heparin prophylaxis, normal coagulability was maintained. Since disorders of hemostasis due to therapy occur sporadically, early postoperative raising of the dose of heparin should only be done under regular laboratory controll, to which activated PTT and antithrombin time is well suited.