Aberrant adrenal tissue in the wall of a hernial sac. An aberrant adrenal, which is a supplementary to the normal adrenal, was found in the apex of hernial sacs in ten out of 350 operated children. This tissue contains adrenal cortex, which tends to atrophy and disappear during childhood, but uncommonly may persist into adult life. Rarely it may secrete abnormally or undergo neoplastic changes. The embryological development is discussed, and the literature briefly reviewed.


Caroli's: a surgical challenge.

Caroli's: a surgical challenge. A patient operated upon for acalculous cholecystitis was later found to have Caroli's disease, congenital ectasis of intrahepatic bile ducts. Cholangitis, calculi and abscesses occurred in both lobes of the liver. Sepsis was not controlled despite open drainage, hepatic segmentectomy and ductal lavage with antibiotics and saline. At autopsy the liver contained a dozen unsuspected cavities filled with calculi, bile and pus. Diagnosis of Caroli's disease is best made by operative cholangiography in patients with atypical biliary disease. Management with antibiotics alone is seldom successful. Hepatic resection is better than drainage procedures for unilateral lesions. In patients with bilateral abscesses and no extrahepatic ductal obstruction or dilation, surgical treatment is often ineffective.


[Etiology of hypertonic dehydration (author's transl)]. A revision of the ethiology in hypertonic dehydration of 80 infants admitted in the Clínica Infantil "La Paz", between 1972--1973 is made. The most important ethiological factors were: hyperconcentrated food (86% in neonates), vomiting, diarrhoea, increase of insensible water loss (respiratory, fever). The etiopathogenic and physiopathologic bases of hyperconcentrated diet in the development of hypertonic dehydration in accordance with "solute overload" to neonatal kidney are discussed. The autoperpetuation mechanisms of hypertonic dehydration are also discussed.


[Clinical evolution and severe complications of hypertonic dehydration in 80 infants (author's transl)]. Authors analyse incidence of age, sex and weight in a group of 80 infants with severe hypertonic dehydration. The highest frequency occurs in the first month of life (50%). They study the clinical manifestations of dehydration, neurological condition, diuresis, escleremia, other pathology, complications and mortality. Causes of death are detailed. Peculiar clinical manifestations are discussed according to different ages, emphasising importance of E.C. component in the first weeks of life. Efficiency of peritoneal dialysis is evaluated.


[Treatment and evolution of shock and acidosis in hypertonic dehydration (author's transl)]. Authors analyse treatment and clinical and analytical evolution of 80 patients with hypertonic dehydration, depending on shock and acidosis. Several considerations concerning treatment and its' influence on evolution of different patients, emphasizing both therapeutic methods: with or without use of peritoneal dialysis, according to the values of initial natraemia, are made.


[Metabolic evolution of hypertonic dehydration treated with fluidotherapy: revision of 40 infants (author's transl)]. Authors study the metabolic evolution of osmolarity, natraemia, chloremia, kaliemia and uremia of 40 infants with hypertonic dehydration. They divide the serie into two groups in accordance with initial value of natraemia: more or less than 170 mEq./l. The slow average decreases by hour of osmolarity, natraemia and chloremia were evaluated, and that justifies good evolution of hypertonic dehydration and minimal neurological repercussion found. Renal function in this metabolic condition is discussed. The usefulness of the fluidotherapic technique employed is demonstrated.


[Metabolic evolution of hypertonic dehydration with combined treatment of fluidotherapy and peritoneal dialysis: revision of 22 infants (author's transl)]. Metabolic evolution of osmolarity, natraemia, chloremia, kaliemia and uremia of 22 infants with severe hypertonic dehydration, treated with fluidotherapy and peritoneal dialysis, is revised. Peritoneal dialysis was prepared in accordance with a special method for this metabolic condition. The serie was divided into two groups, according to initial value of natraemia: more or less than 170 mEq./l. Average decreases per hour of osmolarity, natraemia and chloremia were evaluated, as well as the influence of peritoneal dialysis on body fluids composition. Indication of peritoneal dialysis specially prepared for severe cases is discussed.


[Contribution to acid-base metabolism in hypertonic dehydration by the study of "fraction R" (underterminate anions) (author's transl)]. A study on the value of "R fraction" of plasma electrolites (undetermined anions), in order to know better the metabolic acidosis of the hypertonic dehydration is achieved. "R fraction" value was obtained by the formulae: R fraction = plasma N+ --(plasma Cl- + plasma HCO3-). The mean values in patients with hypertonic dehydration was: 12.4 +/- 8.3 mEq./l., more than the normal standard data of our laboratory: 8.55 +/- 3.4 mEq./l. Authors make two groups in accordance with the "R" value: one with low "R fraction" (25 cases): 4.79 +/- 4.70 mEq./l.; and another with high "R fraction" (32 cases): 20.04 +/- 6.6 mEq./l., and compare the differences (ethiologic, clinic, shock and metabolic) between the two groups. It is confirmed that acidosis in hypertonic dehydration is essentially hyperchloremic. It was speculated on the "anion gap" and the total value of chloride in this dehydration.


[Urea half-live as index of renal failure in hypertonic dehydration (author's transl)]. Evolution of uremic half-time in 27 infants with hypertonic dehydration is studied. Authors establish three groups in accordance with duration of uremic half-time: 1st: less than 24 hours: 5 infants. 2nd: More than 24 hours without renal or uremic pathology: 12 infants. 3rd: More than 24 hours with renal or uremic pathology: 10 infants. Utility of this parameter is discussed, as well as its physiologic bases. The existence of 2nd group makes the value of this control as an organic of functional renal index uncertain.


[Local incidence of different types of dehydration (author's transl)]. A total of 2,298 dehydrated infants, among 9,674 infants admitted to Emergency Unit and Intensive Care Unit of Clinica Infantil "La Paz" between 1970--1974 are analyzed. The annual incidence of the different types of hypotonic, hypertonic and isotonic dehydration is studied. The peculiarities of the data are discussed and compared with those described by other authors. High incidence of hypertonic dehydration (25.4%) is emphasized.


[Atrial septal defect with pulmonary hypertension in infancy (author's transl)]. Four cases of atrial septal defect, "ostium secundum", associated with pulmonary hypertension and congestive heart failure in children under the age of two years are reported. A correct diagnosis could be made before surgery in only two of the case. In one case partial anomalous pulmonary venous connection was incorrectly diagnosed, while ventricular septal defect could not be excluded in the fourth case. The systolic pressure in the pulmonary artery was higher than 50 mm. Hg in all cases. One patient died after catheterization, and total surgical correction was performed in the other three cases, with good results. In all of them, a large atrial septal defect could be seen. There was no evidence of any other associated anomaly. After an average follow up of 4.5 years the three patients that where operated remain asymptomatic. The rarity of this entity, the difficulties in making a correct diagnosis and several pathogenetic aspects of this  abnormality are discussed on the light of these and other cases previously reported in the literature.


[Three cases of mucolipidosis type III (author's transl)]. Three cases of mucolipidosis type III in three siblins ranging in age from 4 to 10 years are reported. One of them was severely involved; the other two in a lesser degree. The enzymatic studies performed are exposed, together with a discussion and interpretation of the findings. The concepts regarding the group of metabolic diseases among which mucolipidosis is nowadays included are reviewed. Some characteristics of the enzymatic disorder, origin of the disease, are finally commented.


[Meconium aspiration syndrome with severe hypoxemia. Treatment with a pulmonary vasodilator (tolarzoline) (author's transl)]. Three patients with Meconium Aspiration Syndrome (S.A.M.) and severe hypoxemia are reported. From the first hours of life they needed mechanical ventilation, showing no improvement in PaO2 in spite of usual respiratory support measures. In one case, pulmonary hypertension and ductal right to left shunt through ductus arteriosus and foramen ovale was objetivated by cardiac catheterization. Following intravenous prefusion of a pulmonary vasodilator (Tolazoline) patients showed a clinical amelioration and a definite increase in PaO2. Results and evolution with the use of this drug are commented.


[Generalized ceroid-lipofuscinosis].

[Generalized ceroid-lipofuscinosis]. A histological verified case of late infantil type of generalized ceroid-lipofuscinosis of Jansky-Bielchowsky syndrome is reported. Paroxismal activity provoked by a low frequency fotostimulation or Pampiglione phenomenon is registrated at the E.E.G. An analysis about the clincial findings and a review of the Pampiglione phenomenon in the medical literature is made, being stimated this phenomenon of a high value for the diagnosis fo the type II or late infantil type of generalized ceroid-lipofuscinosis.


[Hypernatremia and adipsia (author's transl)]. We have studied an infant (female) with a persisting hypernatremia and adipsia, examined for the first time at the age of five months. The funtional test carried out showed an insensibility of the osmoreceptors for very important changes in POsm. carryng with them a lack of response of the ADH. Neuroradiological studies demostrated hydrocephalia secondary to a stenosis of the aqueduct of Silvio. Treatment with chlorpropamide proved effective. The literature is being revised comparing out results with those of other authors.


[Bloom's syndrome. A case with deficit of growth hormone (author's transl)]. A girl with Bloom's syndrome is reported. We have not found chromosomic or inmunoglobulin alterations, in opposition to described by other. We remark, for the first time in medical literature, a deficit of GH secretion without response to several stimulus. The other hormonal explorations were normal. We don't know if, that finding will be of pathogenic importance for the stunted growth of Bloom's syndrome or this is a casual association. Anyway, the good therapeutic results with the exogenous human growth hormone administration, is of a great interest for the investigation of pituitary GH reserve in any case of Bloom's syndrome.


[Mediastinal ganglioneuroma (author's transl)]. One case of a mediastinal ganglioneuroma in a two years old girl is reported. The radiologic features of the tumor are discussed, concerning to the paradoxical tumor volume and its placement. Clinical, radiological and therapeutic considerations about this condition are made.


[Neonatal laceration of liver and spleen (author's transl)]. A very unusual observation of survival after surgical treatment of neonatal maceration of liver and spleen is reported. The patient had a normal birthweight and the only possible etiologic factor was a oxitocin-induced rapid delivery. The literature on this topic is reviewed.


[Bone lymphangiomatosis (author's transl)]. A case of lymphangiomatosis of bone in a 12-years old boy is presented. First bone lessions were seen at 6 1/2 years of age and the case had a progressive course. The only associated lymphatic malformation was a submandibular lymphangioma. The lymphography performed at the patient was normal. Literature about this subject is revised and evolutive possibilities and therapy are described.


[Nephrotic syndrome by diffuse mesangial sclerosis (author's transl)]. This case deals with a 15-month old male child affected with a nephrotic syndrome resulting in grave chronic renal failure, determined histologically as diffuse mesangial sclerosis. The most frequent causes of nephrotic syndrome in the first year of life are analyzed along wiht their diagnostic differential, with special attention to the Finish or microcystic congenital nephrotic syndrome and to diffuse mesangial sclerosis. In the discussion contradictions existing in the bibliography on diffuse mesangial sclerosis are shown in its clinical and developmental aspects as well as the prognostic and even in the pathological anatomy, which leads us to believe that this illness may be more complex than what it appears, and subdividing it into illnesses of different etiology, development and prognosis; or that some of the cases. described as such may not be the same as those described by R. Habib in 1973. In the present case the deposits of C3 and IgM are worth noting, as they were not described in the other 11 cases, also the study done with the electron microscope, which also was not done in the previous cases.


[Tricho-rhino-phalangeal dysplasia type I (Giedion's syndrome) (author's transl)]. A new case of these rare entity is described. Histopathology and ultrastructure of cartilage is studied pointing out some pathogenics aspects.


[Sepsis in neonate, A 291 cases study (author's transl)]. A four-year experience with sepsis in the neonate is described. Clinical picture, laboratory data and mortality of 291 newborn, aged 0-28 days, are analyzed. The rise in the incidence of septicemia in the group of newborn with clinical onset within the first 24 hours of life and the preterm 5. degrees to 9. degrees day of life, was commented. The need to develop a more effective profilaxis toward the reduction of morbidity and mortality is emphasized.


Nerve conduction abnormalities in untreated maturity-onset diabetes: relation to levels of fasting plasma glucose and glycosylated hemoglobin. The role of metabolic abnormalities in the development of diabetic neuropathy is controversial. To investigate the influence of hyperglycemia on nerve conduction, we studied 20 untreated maturity-onset diabetic patients and 23 normal control subjects of similar age. Nerve conduction velocity of motor (median, peroneal, and tibial) and sensory (median and sural) nerves in diabetic patients was significantly slowed and H-reflex latency time prolonged. Levels of fasting plasma glucose in diabetic subjects were correlated with slowed motor conduction velocity of the median, peroneal, and tibial nerves but not with sensory nerve conduction velocities. Levels of glycosylated hemoglobin, an index of long-term glycemia, were correlated with slowing of peroneal motor conduction velocity in diabetic patients. These associations could not be explained by patient age or duration of diabetes. These findings suggest that the degree of hyperglycemia of untreated maturity-onset diabetes contributes to the motor nerve conduction abnormalities in this disease.


Whole body hyperthermia: a phase-I trial of a potential adjuvant to chemotherapy. Fourteen patients with a variety of neoplasms not responsive to standard forms of therapy underwent whole body hyperthermia for a maximum 4 h at 41.8 degrees C. This was a phase-I cancer trial designed to develop whole body hyperthermia as an adjuvant to systemic chemotherapy. Intravenous analgesia was used to sedate patients, obviating the need for general endotracheal anesthesia. Hyperthermia was induced by means of a high-flow water perfusion suit. Cardiovascular performance was evaluated using a flow-directed pulmonary artery catheter. Patients developed a twofold mean increase in cardiac index without evidence of cardiac damage by ECG or creatine phosphokinase (CPK) isoenzymes. An acute fall in serum magnesium and phosphate and an acute rise in arterial pH, serum CPK values, and granulocyte count occurred in all patients. There were no clotting abnormalities. Toxicity included fatigue, diarrhea, nausea, and transient elevations in liver enzymes. Four patients were febrile for 36 h after initial defervescence. Peripheral neuropathy developed in four. These results show that with carefully monitored conditions whole body hyperthermia is feasible.


Hypercalcemia in active pulmonary tuberculosis. We ascertained the incidence of hypercalcemia in 79 consecutive patients with active pulmonary tuberculosis and a control group of 79 patients with chronic obstructive pulmonary disease. Twenty-two patients developed hypercalcemia (serum calcium greater than 10.5 mg/dl) within 4 to 16 weeks after initiation of chemotherapy for tuberculosis. The duration of hypercalcemia ranged from 1 to 7 months, and remission occurred spontaneously in all patients. The mean daily vitamin D supplement was greater in hypercalcemic patients than in the normocalcemic group. There was a positive correlation between daily vitamin D supplement and degree and duration of hypercalcemia. Mean serum calcium in patients with tuberculosis was higher than in patients with chronic obstructive pulmonary disease supplemented with the same dose of vitamin D. Hypercalcemia appears to be related to the activity of pulmonary tuberculosis and the intake of vitamin D; the exact mechanism, however, remains unknown.


Spironolactone-induced hyperchloremic acidosis in cirrhosis. Six patients with alcoholic cirrhosis developed a reversible metabolic acidosis during treatment with the aldosterone antagonist spironolactone. Mean serum bicarbonate concentration decreased significantly with spironolactone therapy (100 to 200 mg/day) from 18.2 +/- 4.5 to 10.9 +/- 3.2 meq/litre (P less than 0.001). Upon withdrawal of spironolactone, serum bicarbonate concentration increased from 10.9 +/- 3.2 to 18.1 +/- 3.5 meq/litre (P less than 0.001). During the development of this hyperchloremic metabolic acidosis, serum potassium concentration rose from 3.7 +/- 0.5 to 5.0 +/- 0.8 meq/litre (P less than 0.005); this reversed after cessation of spironolactone therapy. These effects of spironolactone treatment were not associated with significant alterations in serum creatinine or sodium concentration. Thus, even though an aldosterone antagonist in the treatment of sodium and water retention in cirrhotic patients may prevent hypokalemia and rapid diuresis, it may also induce or worsen another complication: hyperchloremic metabolic acidosis.


Fatal pulmonary hemorrhage after use of the flow-directed balloon-tipped catheter. The flow-directed balloon-tipped catheter is extensively used in intensive care units, catheterization laboratories, operating rooms, and emergency wards. Major complications associated with its use have not been frequently reported. In a recent 2-year period in four hospitals, we identified five cases of fatal pulmonary hemorrhage resulting from balloon-tipped catheters. We review here four additional cases previously cited in the literature and discuss possible mechanisms and predisposing factors associated with this complication and guidelines for safe use of these catheters. Pulmonary artery rupture is probably commoner than previously reported.


A consultant-extender system for breast cancer adjuvant chemotherapy. We have implemented a consultant-extender system that enables community physicians, in cooperation with regional specialists, to deliver adjuvant chemotherapy to patients with node-positive breast cancer. The system employs computer-generated care protocol forms that indicate the data to be collected and the drug dose(s), with the appropriate rules for their administration. This continuous process of monitoring and modifying therapy assures protocol compliance and facilitates quality of care assessment. Seventy-three physicians throughout Alabama delivered appropriate chemotherapy at nearly 97% of 2612 visits by 195 patients. Disease-free intervals of 149 of those patients treated in a prospective clinical trial are indistinguishable from those of comparable patients treated largely within academic centers. This system provides a mechanism for decentralizing speciality care, incorporating community physicians into clinical trials, and improving continuing medical education techniques.


Clinical competence in internal medicine. To describe more explicitly the components of competence required of the internist, The American Board of Internal Medicine has analyzed the medical encounter and defined the major variables involved: the abilities required of the internist, the tasks that must be performed to solve a medical problem, the medical illness, and the patient. The abilities of the internist have been categorized into attitudes and habits, interpersonal skills, motor and technical skills, and intellectual abilities. The latter have been further subdivided into the abilities to acquire and use knowledge, to organize, to synthesize information, and to apply clinical judgment. For each of these abilities statements of clinical competence that relate to the tasks required have been developed. The Board is publishing this paper, an excerpt of a longer document, with the hope that it will be useful to residents, faculty, and practicing internists.


The training of the internist with some messages from practice. Efforts to provide an increased focus on the primary care activities of internists have been characterized by some as requiring a substantial increase in experience with ambulatory patients and significant training time invested in office gynecology, office orthopedics, otorhinolaryngology, and dermatology. These changes have been recommended as more reflective of the "real world" of the internist's practice than intensive experience with seriously ill inpatients. It is argued that such skills in training threaten to reduce clinical scope and deep competence and will thereby reduce rather than enhance effectiveness in the care of ambulatory patients. Deep clinical competence should be the hallmark of the internist, and training programs in internal medicine should be designed to produce this type of physician. In addition, consultant-level general internists should be trained for consultative, teaching, and investigative responsibilities and would be powerful role models for trainees.


Sensorineural hearing loss and pili torti. Twelve patients with pili torti and sensorineural hearing loss have been described since 1965. We present two new families with this combination of symptoms, and a restudy of a third family. The genetic aspects are discussed. Tentatively it is concluded that pili torti is an autosomal dominant with a low penetrance of a pleiotropic manifestation of sensorineural hearing loss.


Aggressive fibromatosis of the tongue.

Aggressive fibromatosis of the tongue. Fibromatoses are uncommon, locally aggressive lesions that may involve the structures of the head and neck. They are most commonly found in and along the fascial planes of the neck muscles but can involve other structures, including the oral cavity, nose, nasopharynx or paranasal sinuses. An unusual case of an extra-abdominal desmoid tumor is presented and a review of the anatomical, clinical and pathological features of these tumors is discussed.


Pathogenesis of sinus empyema.

Pathogenesis of sinus empyema. The crucial event in the pathogenesis of sinus empyema is the ostial obstruction. On the basis of recent reports, some consequences of the obstruction on the local bacterial-host interrelationship have been outlined. The anaerobic gas environment of the empyema is one quality important to the selection of bacteria but probably also to the efficiency of the antibacterial activity of the granulocytes. Release of proteolytic enzymes from neutrophilic granulocytes in the sealed sinus may jeopardize the bacterial engulfment due to proteolytic degradation of opsonins. A longstanding exposure of the sinus mucosa to uninhibited proteolytic enzymes may explain the irreversible lesion of the mucosa in chronic sinusitis.


Intercellular fluid pathways in the organ of Corti of cat and man. The intercellular junctions in the organ of Corti of cat and man were examined with the electron microscope. In contrast to the zone of tight junctions, or zonulae occludentes, which were present at the surface of cells lining the scala media, there was no tight junctional specialization among the cells of the tympanic lamina, perilymphatic lining cells of the scala vestibuli, basal processes of the supporting cells of the organ of Corti or cells of the spiral limbus and spiral ligament. These findings suggest the possibility of fluid continuity between the scala vestibuli and scala tympani all along the cochlear duct. Morphological evidence for an intercellular diffusion barrier was present only at the endolymphatic surfaces of the cochlear duct and between the processes of the basal cells of the stria vascularis in cat and man.


Caloric vestibular test with the use of air. In a group of 28 test subjects the vestibular caloric test was performed with the aid of two different methods. In the first method the ears were irrigated for 30 sec with water with a temperature of 30 C and 44 C and later on with airstream with a temperature of 20 C and 50 C. The wet method proved to be a significant stronger stimulus than the dry method. The authors conclude that the water irrigation is the method of choice for the caloric test. The dry method is only useful when the wet method is undesirable.


Cricothyroid distance and vocal pitch. Experimental surgical study to elevate the vocal pitch. To establish an experimental basis for surgical approximation of the anterior cricothyroid distance which aims at raising the vocal pitch, the relationship between vocal pitch and the cricothyroid distance was analyzed in voices produced with excised human larynges (four male and two female larynges). Within the framework of the experimental conditions, the following conclusions were drawn: 1) The vocal pitch expressed in semitones was almost linearly related to the cricothyroid distance, with an increase of 0.15 to 0.90 semitones per milimeter of cricothyroid approximation. 2) The rise in vocal pitch reached a plateau when the force applied to shorten the cricothyroid distance reached 30 to 50 gm.


Variations of technique in the face-lift operation. Observed variations in face-life technique prompted an analysis of these techniques to determine whether experience correlated with certain aspects of the surgery. A questionnaire was returned by 565 of 1,750 plastic surgeons, quantifying varying techniques in over 121,000 face lifts. The respondents were placed into three groups according to the number of rhytidectomies performed, and correlations were determined.


Impedance screening for preschool children. State of the art. As a test for detecting middle ear disease among preschool children, tympanometry -- as opposed to audiometry -- has three advantageous attributes: a high degree of sensitivity, minimal need for subject cooperation, and total objectivity. For these reasons interest has arisen in tympanometry as a method for screening, i.e., identifying children with previously undetected middle ear disease. However, uncertainty persists concerning the importance of detecting apparently asymptomatic middle ear effusions, and concerning optimal methods, or even the advisability, of treating them. Further, the sensitivity and specificity of tympanometry depend on how the pass-fail cutoff point is defined. Defining this cutoff point so as to achieve high sensitivity may result in excessively low specificity, with the production of large numbers of false-positives who then become overreferrals. Data are presented to show how the validity of the test may be increased to some extent by attention to the gradient of "negative-pressure" tympanograms. At the present time, given the various aforementioned uncertainties, and with adequate validation as to the presence or absence of disease often lacking in reported studies of impedance screening in preschool populations, the cumulative results of these studies do not warrant embarking on large-scale screening programs. What is needed instead is additional research to explore the issue further.


Multicentric ductal and lobular atypia and occult carcinoma in prophylactic subcutaneous mastectomies: a preliminary report. A report is made on 2 patients undergoing prophylactic subcutaneous mastectomy and reconstruction following treatment for carcinoma of the opposite breast. The dangers of augmenting, reducing, or correcting the shape of the remaining breast to match the reconstructed one are also examined.


Aesthetic surgery: how it affects the way patients are perceived by others. Writings on the psychological effects of aesthetic surgery have evidenced a subtle but important difference of opinion. One viewpoint emphasizes the intrapsychic significance of surgery, while another places great weight on the surgical patient's social feedback from peers. This research was designed to determine whether aesthetic surgery, by altering a patient's appearance, can change the social perceptions and dispositions of those who encounter the patient. A controlled experiment was carried out in which subjects viewed preoperative or postoperative photographs and made a variety of judgments of those pictured. The individuals in the postoperative pictures were judged to have more desirable personalities, to be better potential marriage partners, and to have happier lives than the same individuals photographed before surgery. Since all the impressions were from photographs, actual personality was not a factor in this study. The greatly improved social reception given the individuals in the postoperative pictures is explained by the surgical improvement in their appearance. Thus, the surgeon's work should be viewed as altering not only the patient, but also the patient's social world.


Temporary increase in sensorineural hearing loss with hearing aid use. Two cases are presented exhibiting temporary increases in sensorineural hearing loss following hearing aid use. Data suggesting this correlation are shown. There were no contributing middle ear problems during the period surveyed. The most significant changes in hearing thresholds were at frequencies 1000 and 2000 Hz. The use of different hearing aids, with decreased maximum power outputs, was not found to have similar effects on hearing threshold levels. A scheduling regime is recommended for introducing any new hearing aid to a child.


Replantation of the heel in a child.

Replantation of the heel in a child. Complete avulsion of the heel pad and half of the calcaneus constitutes a severe injury. The case presented here emphasizes the need to carefully assess patients with amputated tissue, because even small portions of avulsed tissue that are needed for a specific and important function should have replantation attempted. Failing to consider revascularization as the procedure of choice in some injuries eliminates the potential for primary, ideal reconstruction.


Recurrent nerve locating system.

Recurrent nerve locating system. One recurring problem for otolaryngologists is the patient with vocal cord paralysis after thyroid surgery. We review the literature to assess the magnitude of this problem and to assess presently available techniques for sparing the recurrent laryngeal nerve. We present a new system for intraoperative recurrent laryngeal nerve location during thyroid surgery.


Lipoma of the thumb in a child.

Lipoma of the thumb in a child. Lipomas occur anywhere in the body but are rarely found in the fingers. This report describes a lipoma of the dorsum of the thumb in a 9-year-old boy. We have been unable to find a previously reported case.


Upper airway obstruction associated with regional enteritis. Two patients are presented with upper airway obstruction associated with regional enteritis (Crohn's disease). Two mechanisms for this obstruction are proposed. The first is involvement of the cricoarytenoid joint with the inflammatory process and the second is extensive edema of the upper airway due to submucosal involvement with the disease process. We were unable to find any previous reports of upper airway obstruction associated with regional enteritis. The data from these patients suggests that Crohn's disease should be included in the differential diagnosis of chronic persistent laryngeal edema.


Custom-fabricated silicone implants for contour restoration. A 15-year review is made of contour restoration by custom silicone inlay technique. Eighty-three patients have undergone surgery since 1962. The indications, preparation of moulage and implant, surgical technique, and care of complications are described. The custom silicone technque has proved successful, precise, and relatively free of complications. Tolerance of uncomplicated implants has been permanent.


Remyelination in multiple sclerosis.

Remyelination in multiple sclerosis. Chronic plaques in central nervous system tissue fixed by in situ perfusion for electron microscopy were examined for evidence of remyelination in 2 patients with multiple sclerosis (MS). Fibers with abnormal central myelin sheaths of several types were found at the margins of most of the plaques studied. The most common of these were: (1) the presence of bare stretches of axon between contiguous internodes, (2) the presence of thin paranodes, (3) internodes which changed markedly in thickness along their length due to premature termination of superficial or deep myelin lamellae that ended as hypertrophic lateral loops, and (4) abnormally thin internodes which were of uniform thickness along their length, which were shorter than normal, and which terminated in the form of normal nodal complexes. The finding of internodes of the last type at the edges of many plaques indicates that remyelination by oligodendrocytes can occur in the adult human CNS and that it is common in some cases of MS, although limited in its extent.


Visual evoked potentials and the visuogram in multiple sclerosis. Visual evoked potential (VEP) latency to a sinusoidal grating pattern was measured in each eye of 103 patients with multiple sclerosis (MS) and compared with results in a control group of 56 patients hospitalized for other neurological conditions. Of the 50 patients classified as having definite MS, 90% showed prolonged latency (over 131 msec) in one or both eyes. In each eye of 24 of the MS patients, psychophysical measurement of the detectability of grating patterns was obtained. This test was abnormal in 11 of 13 patients with definite MS, 3 of 4 with probable MS, and 5 of 7 with possible MS. There was no concordance between prolonged VEP latency and visual impairment as revealed by the psychophysical test. Apparently pathways determining VEP latency and spatial contrast detection may be unequally affected in MS.


Delayed pentobarbital administration limits ischemic brain damage in gerbils. The capacity of delayed barbiturate administration to limit brain damage after unilateralcerebral ischemia was examined histologically in gerbils. The right common carotid artery was occluded in 50 animals under brief (3-minute) halothane anesthesia; 18 animals (36%) developed motor abnormalities consistent with stroke. The arterial clasps were removed after 1 hour and the abnormal animals were divided into treatment and placebo groups. Treated gerbils received sodium pentobarbital (70 mg/kg) intarperitoneally 1 hour after clasp removal and a smaller dose (50 mg/kg) 2 hours later; these animals lost corneal reflexes but retained spontaneous respiration and were kept normothermic. Animals in the placebo group received equivalent volumes of normal saline. Except for the period of anesthesia, both groups had similar postischemic motor behavior. Neuropathological examination of animals killed by perfusion-fixation after 24 hours revealed fewer pentobarbital-treated animals with shift of midline structures and with ipsilateral ischemic damage (including infarction). Compared with the placebo group, there was less extensive neuronal ischemic cell change in five regions of the ipsilateral cerebral hemispheres of the pentobarbital-treated animals (p less than 0.05). The results suggest that barbiturates administered as long as 1 hour after the end of an ischemic insult can still limit brain damage.


Clinical and biochemical aspects of trichopoliodystrophy. The clinical and biochemical evaluation of 6 patients with trichopoliodystrophy indicates that the disease process can begin in utero and is related to a selective abnormality in copper metabolism. Examination of 2 infants on the first day of life revealed abnormal neurological signs, a characteristic hair abnormality, and elevated levels of copper and ceruloplasmin. Decreased hepatic copper levels and increased urinary copper excretion were documented during the first week. The 2 neonates demonstrated a progressive decrease in blood copper levels in the first month of life. Four infants identified at ages 2 to 11 months had low values for blood copper and ceruloplasmin. All infants had progressive neurological dysfunction, and 4 of the 6 died at ages ranging from 2 1/2 months to 5 1/2 years. Parenteral copper therapy achieved normal blood and hepatic copper levels in 1 patient, but the copper values in the cerebral cortex and white matter were significantly decreased compared to control specimens.


Cortical activation pattern during saccadic eye movements in humans: localization by focal cerebral blood flow increases. Regional cerebral blood flow (rCBF) was measured in human subjects during saccadic eye movements by a 254-channel dynamic gamma camera. Focal rCBF increases were repeatedly observed in an area within the middle precentral and premotor regions which corresponds to the frontal eye field in humans. Our findings suggest that this region is localized between the "face" and "hand" areas in the precentral gyrus and extends anteriorly out of the primary motor strip into the adjacent premotor zone. In addition, saccades were associated with focal blood flow increases in regions corresponding to the frontal supplementary motor area and to the posterior temporooccipital visual association cortex. Similar changes in patterns of rCBF occurred during contralateral and ipsilateral horizontal saccades and also during vertical saccades, and did not differ between the right and left hemispheres. Focal rCBF increases were observed in the frontal eye field during several additional test procedures including ocular fixation and visual perception of a nonmoving target, auditory stimulation with closed eyes, and reading. It is presumed that these focal flow increases reflect increased localized neuronal activity and metabolic rate and therefore permit visualization of the cortical activation pattern associated with saccadic eye movements in humans.


Pheochromocytoma causing exercise-related headache and pulmonary edema. A 13-year-old hypertensive girl with a history of severe headaches following exercise developed circulatory collapse after "squat jumps." Pulmonary edema was present without evidence of a cerebral mass. The patient died with increased intracranial pressure despite decompressive craniectomy. Neuropathological evaluation revealed diffuse cerebral edema and a pheochromocytoma in the right adrenal gland. Examination of urine revealed elevation of vanillylmandelic acid levels.


Stimulatory effects of drugs for protein synthesis on muscle cell cultures in Duchenne dystrophy. The influence of the membrane-stabilizing agents diphenylhydantoin (DPH) and orgotein (a drug with superoxide dismutase activity) on protein synthesis was studied in cultured human muscle cells obtained from 7 patients with Duchenne muscular dystrophy (DMD) and 14 controls. The cultures were obtained by dissociation and subsequent plating of cells from biopsied quadriceps muscle. These cultures were then labeled with tritiated leucine in the presence and absence of the membrane-stabilizing drugs. Total protein synthesis (cpm/mg noncollagen protein) in first-passage muscle cell cultures from DMD patients showed a 35% decrease, but myosin synthesis revealed normal values. DPH and orgotein increased total protein synthesis by 35 and 50%, respectively, in dystrophic cultured cells, but only by 7 and 8%, respectively, in control cultured cells.


Emery-Dreifuss muscular dystrophy.

Emery-Dreifuss muscular dystrophy. A man had weakness of humeroperoneal distribution associated with limited range of motion of the cervical spine and elbows. At age 25 he developed permanent atrial paralysis, and a cardiac pacemaker was inserted. Although this case was sporadic, most others have been transmitted as an X-linked recessive trait. Mixed patterns in electromyography and muscle histology have caused nosological confusion, but the unique clinical signs seem to define a distinct form of muscular dystrophy, warranting the designation "emery-Dreifuss" type.


Central vestibular involvement in peroneal muscle atrophy: a preliminary report. A family is presented in which 6 out of 8 members were found to have peroneal muscle atrophy. Neurophysiological and histopathological evidence for the hypertrophic form of this disease was obtained in 3 patients. Three patients with peroneal muscle atrophy and 1 unaffected family member had abnormal differential caloric tests. This is the first report of an apparently hereditary dysfunction of the central vestibular system associated with a hereditary neuropathy.


Metabolism of dimethoxymethyl phenobarbital (eterobarb) in patients with epilepsy. The metabolism of dimethoxymethyl phenobarbital (DMMP) was investigated in 6 epileptic patients using deuterium-labeled drug measured by integrated gas chromatography/mass spectrometry. Following an oral dose of 120 mg, none of the parent compound appeared in serum, urine, or saliva in spite of a measurement sensitivity of less than 0.05 nmol/ml. A metabolite, monomethoxymethyl phenobarbital (MMP), was detected in all patients, with peak serum concentrations averaging 1.96 nmol/ml at 1.3 hours. Phenobarbital was the major metabolite detected, and it reached peak levels in 6 to 12 hours. Two of the patients were continued on DMMP therapy for several months and then administered a pulse dose of deuterated drug. Again no DMMP was detectable. Steady-state drug administration had no effect on the kinetics of metabolism of either MMP or phenobarbital although peak serum concentrations were lower for both metabolites. In the urine of 5 patients an unidentified labeled fragment was detected that does not appear in urine from patients taking phenobarbital. From these pharmacokinetic studies it appears likely that the anticonvulsant activity of DMMP results from its metabolic conversion to phenobarbital.


Selective chromatolysis of neurons in the gerbil brain: a possible consequence of "epileptic" activity produced by common carotid artery occlusion. Unilateral (50 to 118 minutes) and bilateral (2 to 33 minutes) carotid artery occlusion in gerbils resulted in two distinct types of neuronal alteration: ischemic cell change (ICC) in selectively vulnerable brain regions, and selective chromatolysis (SC) confined to the deeper layers of the cortex, the Sommer sector of zone h-1, and the paramedian region (PM) of the hippocampus. In typical SC the nucleus was eccentric and the Nissl substance was lost in the central eosinophilic cytoplasm. In electron micrographs this area of cytoplasm showed disruption of smooth and rough endoplasmic reticulum with disaggregation of polyribosomes and accumulation of mitochrondria and various dense bodies. SC was identified at 2 to 3 hours and was still recognizable at five days. When bilateral carotid artery occlusion lasted 5 to 6 minutes, SC was seen in the hippocampal Sommer sector and cerebral cortex, while ICC was restricted to the endfolium (h3-5). Unlike ICC, the frequency of SC was not related to the duration of ischemia but probably to the epileptic seizures (overt and subclinical) initiated by ischemia in the gerbil. These changes must be considered when the gerbil is employed as a model of experimental stroke.


Effects of bicuculline-induced seizures on cerebral metabolism and circulation of rats rendered hypoglycemic by starvation. To evaluate the effects of substrate deficiency on cerebral function, metabolism, and blood flow during seizures, rats were injected intravenously with bicuculline (1.2 mg.kg-1) following a 24-hour period of starvation. During the course of seizures, blood glucose concentrations fell, and when they were reduced to below about 3 mumol.gm-1, cerebral function, metabolism, and blood flow altered. Changes in function involved the transition of an electroencephalographic pattern of bursts and suppression into one of frequent or sparse single spikes. Oxygen consumption, which initially increased at least twofold, fell toward normal or subnormal values in the single-spike period. Cortical blood flow was markedly reduced, and there  was an attenuated response to carbon dioxide administration. Simultaneously, a small but clear fall was detected in the cerebral phosphorylation potential, and concentrations of glycolytic metabolites (including lactate) and citric acid cycle intermediates were reduced. Changes in amino acids and ammonia were somewhat similar to those observed in insulin-induced hypoglycemia, but since the amino acid pool did not fall, the experiments failed to give evidence that amino acids serve as oxidative substrates. The perturbation of cerebral energy state (and of levels of carbohydrate substrates and amino acids) was reversed by glucose administration; but since neither this procedure nor additional bicuculline injections could cause resumption of continuous seizure activity, the results suggest that cellular substrate depletion may have given rise to a sustained disturbance of synaptic transmission.


Symptomatic middle cerebral artery stenosis. The clinical course of 16 consecutive patients with stenosis of the middle cerebral artery angiographically diagnosed between 1970 and 1977 was reviewed. All were managed nonsurgically with medical treatment including anticoagulation. Prior to therapy, transient ischemic attacks had occurred in 15 and cerebral infarction in 11. Initially, none exhibited more than a minor neurological deficit. Follow-up from one month to six years showed a benign course in 14 patients: 13 experienced no subsequent transient attacks or new stroke; 1 had repeated transient attacks for two years but not in the following four years. Two of the 16 developed a severe stroke early in the course, before medical therapy was started. No distinctive clinical or radiographic features were identified that permitted prediction of the outcome. This small series supports the need for a randomized study of bypass efficacy in these patients.


Cranial computed tomography in the diagnosis of systemic lupus erythematosus. The cranial computed tomograms of 29 patients with systemic lupus erythematosus (SLE) were reviewed. Twenty-two patients had a clinical course consistent with central nervous system involvement. Of these, 20 had abnormal CT studies during the course of their CNS symptoms. The most common finding was sulcal enlargement, either with or without ventricular enlargement, and it was prominent in patients with either psychosis or dementia. Infarcts and intracranial hemorrhages were seen as well. Seven CT studies were obtained in SLE patients without a clear diagnosis of CNS involvement. Only one of these was abnormal.


Mechanisms underlying hemispatial neglect. If patients with left-sided hemispatial neglect bisect lines incorrectly because hemianopia or sensory hemiinattention prevents them from seeing how far the line extends to the left, a strategy that ensures their seeing the left side of the line in their normal field should improve performance. If patients have hemispatial hypokinesia, moving the line toward the normal half of body space should improve performance. Six patients with left-sided neglect from right hemisphere infarctions were required to identify a letter at either the right or the left end of a line before bisecting that line. The task was given with the lines placed at either the right, the center, or the left of the body midline. Performance in trials when subjects were required to look to the left before bisecting a line did not differ from when they were required to look right. Performance was significantly better when the line was placed to the right side of the body than to the left. These observations support the hypothesis that patients with hemispatial neglect have hemispatial hypokinesia. An alternative hypothesis is that these subjects had a hemispatial memory defect. Although they saw the left side of the line in their normal field, they were incapable of forming a stable trace and performed as if they did not see the left side of the line.


Position and vibration sensations: functions of the dorsal spinocerebellar tracts? Clinical evidence is presented which establishes for the first time that position and vibration sensations may be carried in the dorsal spinocerebellar tracts. We present a patient who incurred a spinal cord infarction eight months prior to death that caused a Brown-Séquard syndrome with loss of position and vibration senses in the right lower extremity. The infarction spared the right fasciculus gracilis and thus supports the recent observations in human beings (and animals) that conscious proprioception is not a function of the dorsal columns. The vibratory and position losses were best correlated with the portion of the lesion involving the right dorsal spinocerebellar tract. Arguments are furnished based on physiological experiments in animals that conscious proprioception may be carried by Morin's spinocervicothalamic pathway, which forms part of the dorsal spinocerebellar tract in the spinal cord.


Cervical radiculomyelopathy due to calcified ligamenta flava. Two cases of cervical radiculomyelopathy were apparently caused by calcification of the ligamenta flava. Similar cases have not previously been described, although myelopathy due to calcified thoracolumbar ligamenta flava is occasionally reported. Radiological study is necessary for diagnosis. Surgical removal of the calcified masses was followed by improvement in the symptoms. In 1 patient, the disease was associated with pseudogout in the menisci of the knee joints, pubic symphysis, and acetabular lips. The cause and pathogenesis of this rare condition are unknown.


Retroperitoneal neuroblastoma widely metastatic to the central nervous system. A girl with congenital extraadrenal neuroblastoma died at 3 months of age with multiple parenchymal metastases in the brain and spinal cord. The bones of the skull, cranial dura, venous sinuses, and orbits were not involved. Autopsy findings suggest that the tumor penetrated the spinal meninges and disseminated through the cerebrospinal fluid. It is possible that hematogenous metastasis occurred as well. The intracerebral metastases were not identified on a CT scan performed several hours before the child's death.


Resolution of classic migraine after removal of an occipital lobe AVM. A patient had a thirteen-year history of symptoms clinically indistinguishable from classic migraine: a slowly progressive visual fortification spectrum lasting 40 minutes, followed by a five- to six-hour throbbing unilateral headache with nausea and vomiting. After unsuccessful migraine therapy, investigation revealed a large occipital lobe arteriovenous malformation (AVM). Surgical removal of the AVM resulted in immediate and total resolution of all symptoms.


Phosphorylation of the membrane-bound acetylcholine receptor: inhibition by diphenylhydantoin. Purified postsynaptic membranes can be used as a model system to study the regulation of synaptic membrane proteins. These membranes contain protein kinase activity that phosphorylates the acetylcholine receptor (AChR). We find that diphenylhydantoin (DPH) interacts with these membranes to inhibit phosphorylation of the membrane-bound AChR. DPH appears to alter the availability of postsynaptic membrane proteins  for phosphorylation by a synaptic membrane protein kinase. The concentration of DPH that produces half-maximal inhibition of AChR phosphorylation is about 5 x 10(-5) M. This suggests that one of the specific effects of DPH in the nervous system may be related to inhibition of phosphorylation of postsynaptic membrane proteins.


Enzyme treatment of spinal cord transected rats. Russian investigators have recently reported clinical recovery of enzyme treated, spinal cord transected rats. Using the exact protocols of Matinian and Andreasian's two most successful treatment regimens, we repeated their experiments using United States produced pure hyaluronidase and trypsin or trypsin and elastase. Animals were evaluated for return of bladder function, clinical evidence of hind limb motor function, cortical evoked response after sciatic nerve stimulation, and axonal transport of cortically injected tritiated proline by regenerated corticospinal axons. None of the treated animals differed from control animals treated only with the enzyme vehicle. No animals walked, had return of voluntary motor activity, showed cortical evoked response, or had evidence for transport of tritiated proline over regenerated corticospinal axons.


[Adenylate level in the mycelium of Penicillium nigricans Thom. grown on various carbon sources]. Concentrations of ATP and ADP and their dynamics during cultivation (2, 5, 9 and 13 days) of a highly productive strains of P. nigricans on a mineral medium in the presence of various carbon sources, such as glucose, succinate or acetate were studied. It was shown that the levels of ATP and ADP in the mycelium depended on the carbon source: the maximum and minimum ATP concentrations were found on the glucose and acetate media respectively, the maximum and minimum ADP concentrations showed inverse dependence. The concentrations of both adenylates on the same carbon source depended on the strain. The dynamics of the adenylates levels during cultivation showed an analogous dependence on the carbon source and the strain. Thus, the highly productive strain was characterized by a constant ATP level on glucose and succinate and variation on acetate, while the ADP level was characterized by a decrease by the 9th day of cultivation on any of the carbon sources. The low productive strain was characterized by variations in the level of ATP in any media used, stability of the ADP level by the 2nd--9th day of cultivation on the glucose medium and by the 2nd--5th day of cultivation on the succinate medium and a decrease by the 9th day of cultivation on the acetate and succinate media. The ratio of ATP/ADP at the phase of griseofulvin biosynthesis (9 days) markedly increased in both the strains when cultivated on the media with any of the carbon sources.


[Electron absorption and fluorescence spectra of carbonyl--conjugated pentaenes in various media]. It was found that fluorescence intensity of carbonyl-conjugated pentaens of flavofungin flavopentin and brunefungin in solutions depended on the solvent polarity and specific interactions of the antibiotics with the solvents. Addition of cholesterol into the aqueous solutions of these antibiotics resulted in a hypsochrome shift in their absorption spectra and increased fluorescence intensity. The antibiotics were found by their fluorescence in the yeast cells sensitive to them when their content was close to the concentrations resulting in the cell lysis. Low concentrations of the antibiotics resulted in changed localization of the yeast self fluorescence.


[Control over bellows tightness in the hermetic sealing subassemblies of equipment used in the technology of microbiological manufactures]. A universal procedure for controlling the sylphon hermeticity is discussed. Travelling sylphon or membrane diaphragms in combination with a dublicate sylphon are used as a separating element at the border of the separating media, e. g. the medium transporting through the valve and the environmental air. Pneumatic pressure higher than the working pressure of the separating medium is created inside the space between the working and the dublicate sylphons. If the hermeticity of one of the above sylphons is broken, the excessive pressure inside the space between them is reduced which is automatically stated by means of a pneumatic probe. Because of detection of the breach in the hermeticity of one of the sylphons in proper time, when the second sylphon is safe, the contact of the transporting medium with the environmental air is prevented. The described procedure for controlling the hermeticity is universal since it provides the use of the probes working only under the pressure independent of the type and physico-chemical properties of the separating medium. One of the important advantages of the new procedure is also the fact that the working sylphon appears to be empty since the outer with respect to it pressure of the separating medium is practically balanced by the pressure created in the sylphon space.


[Antibiotic sensitivity and the characteristics of transmissive R plasmids in Shigella belonging to various species]. Sensitivity of 241 Shigella strains isolated from patients at various regions of the USSR in 1975--1978 was tested with respect to 14 antibiotics by the method of serial dilutions. 90.5 per cent of the isolates proved to be resistant to the antibacterial drugs and the greater part of 75.9 per cent of them had multiple resistance. The resistance of the Shigella was most pronounced and frequent with respect to tetracycline, streptomycin, levomycetin, as well as ampicillin and carbenicillin. Gentamicin, cephaloridin, polymyxin M, kanamycin, monomycin, neomycin and rifampicin were highly active against the Shigella. More than 50 per cent of the isolates were sensitive to levomycetin, ampicillin and carbenicillin. Differences in the frequency of the resistant strains and the spectrum of the antibiotic resistance of different Shigella subgroups (species) were observed. The study of 173 multiple resistant Shigella strains showed that about 67 per cent of the strains had a capacity for transduction of the resistance markers into the recipient cells of E. coli. The conjugative R-plasmids were most frequent in Sh. boydii and Sh. sonnei (95 and 95 per cent respectively), less frequent in Sh. flexneri and Sh. newcastle (68 and 53 per cent respectively) and least frequent in the mannitol negative Shigella (25 per cent). The capacity for transduction of R-plasmids in the strains carrying the determinants of resistance to 2 or 3 antibiotics was higher than in the strains carrying the determinant of resistance to one antibiotic. The clinical Shigella strains tested mainly had transmissive R-plasmids of fi--character (79 per cent).


[Use of acridine yperite in the selection of Act. nodosus, a producer of amphotericin B]. The effect of acridine-yperite (AY) on Act. nodosus LIA 0861 at various physiological stages of development was studied. It was shown that both the spores and the germs were sensitive to AY. The level of the mutagen effect depended on the exposure time and the physiological state of the Act. nodosus cells during the treatment. The treatment of the spore suspension with AY had an insignificant effect on the strain morphological variation, while the number of the morphologically changed colonies markedly decreased when 5-hour germs were subjected to the mutagen effect. A decrease in the average antibiotic activity of Act. nodosus was observed, when its spores were subjected to the treatment with AY, which was associated with a decrease in the number of the plus variants. The treatment of 5-hour germs increased the average antibiotic activity of the culture which correlated with an increase in the number of the plus variants.


[Toxicity of tobramycin in single and multiple administrations to laboratory animals]. The LD50 of tobramycin sulphate administered intravenously, intraperitoneally, subcutaneously and orally to albino mice was 77 (73--82), 262 (234--294), 560 (500--627) and greater than 10500 mg/kg respectively. With an increase in the rate of intravenous administration tobramycin toxicity increased. When tobramycin sulphate was administered subcutaneously daily in multiple doses equivalent to the daily therapeutic doses from humans (calculated for the body surface) and in the doses 2--3 times higher than the above therapeutic ones, the function of the kidneys, liver and the Preier's reflex did not significantly change. When the doses were 8--10 times higher than the therapeutic ones, an increase in the urea level in the blood serum, disappearance and a decrease in the Preier's reflex were observed. The impairment of the kidney function was accompanied by degenerative changes in the convoluted tubules of the kidneys, ischemia of the renal glomeruli and appearance of protein secretion in their capsule cavities. The picture of the peripheral blood did not suffer significant changes. The studies on the acute and chronic toxicity of tobramycin sulphate prepared at the Institute of New Antibiotics showed that the drug did not differ from the import tobramycin samples.


[Effect of a natural interferon inducer (RFf2) on the formation of vaccinal immunity to tick-borne encephalitis]. The effect of the interferon inductor of the natural origin (RFf2) on formation of vaccinal immunity to vernal encephalitis was studied. A single intraperitoneal administration of the preparation in a dose of 10 gamma per a mouse 2 hours after the first injection of the vaccine resulted in increased resistance of the mice to the lethal dose of the infecting virus which was introduced 14 days after the vaccination completion. The production dynamics of interferon induced by RFf2 and its level in the serum of the immunized mice were the same as those in the non-vaccinated animals. An increased number of the vaccine injections, up to 3 did not result in a significant increase in the immunity with respect to either the level of the antiviral resistance or the level of the virus-neutralizing antibody accumulation.


Antiviral and interferon-inducing properties of 1,5-diamino anthraquinones. A series of anthraquinones with amino substituents at the 1,5 positions were found to induce interferon in mice. A prototype compound, 1,5-bis[(3-morpholinopropyl)amino]-anthraquinone (Ia), was an effective antiviral agent when administered either orally or parenterally. Peak interferon titers were found 12 to 24 h after drug treatment. The minimum oral dose of Ia required to induce serum interferon or to protect mice against a lethal virus infection was 62 mg/kg. Mice tolerated an oral dose of at least 30 times this minimum effective dose. A single dose of Ia given up to 6 days prior to infection had significant protective activity. Biological properties of Ia were compared with those of three other 1,5-diamino anthraquinones, which also induced interferon and demonstrated antiviral activity in mice. The most active compound was 1,5-bis[[2-(diethylamino)ethyl]amino]-anthraquinone (Ib), which protected mice against virus infection at a dose as low as 8 mg/kg (less than 1/60 its maximum tolerated dose). Mice developed hyporeactivity to interferon induction if the same inducer was injected daily, although by alternating between different inducers the loss of interferon responsiveness could be avoided.


Intravenous use of cephradine and cefazolin against serious infections. The relative efficacy and safety of cephradine and cefazolin were compared in 180 patients with a variety of serious infections caused by susceptible organisms. The patients were randomly assigned to one of two groups of 90 patients each. Most patients received 2 to 4 g per day, administered by intravenous injection in four equally divided doses, for a minimum of 4 days. Based on the clinical and microbiological results, the two cephalosporins were found to be comparable in therapeutic effectiveness. Toxicity was not a problem with either drug.


Autoradiographic localization of [3H]gentamicin in the proximal renal tubules of mice. The site of localization of [(3)H]gentamicin within mouse kidney is shown to be the proximal renal tubule by coincidence of the radioactivity, as visualized by autoradiography, and the mucopolysaccharide-rich microvilli characteristic of proximal convoluted tubules, as visualized by histochemical staining.


Susceptibility of gram-negative aerobic bacilli resistant to carbenicillin in a general hospital to piperacillin and ticarcillin. During an 8-month period, 858 gram-negative aerobic rods resistant to carbenicillin (minimum inhibitory concentration, >/=128 mug/ml) were isolated. Susceptibility testing of 233 of these suggested that piperacillin might be active against more of these organisms than would carbenicillin or ticarcillin.


Inappropriate antidiuretic hormone following adenine arabinoside administration. A patient with disseminated herpes zoster developed a syndrome of inappropriate antidiuretic hormone and profound hyponatremia secondary to the administration of adenine arabinoside.


Pharmacokinetics of amoxicillin: Dosage nomogram for patients with impaired renal function. Amoxicillin pharmacokinetics after intravenous administration were studied in patients with normal renal function, with impaired renal function, and during hemodialysis. The average urinary recovery was 68% in patients with normal renal function. Serum half-life was highly correlated (r = 0.967) with creatinine clearance corrected for body weight. Expected half-life was 71 min for a corrected creatinine clearance of 100 ml/min per 70 kg and 16 h in the anephric patient. Average amoxicillin half-life on hemodialysis was 3.6 h. We present a dosage nomogram for making appropriate adjustments to loading dose based on patient weight and maintenance dose based on corrected creatinine clearance.


Methicillin potentiates the effect of gentamicin on methicillin-resistant Staphylococcus aureus. Methicillin-resistant Staphylococcus aureus (MRSA) strains show an unusual type of resistance at 37 degrees C; only a small subpopulation of cells is resistant to the beta-lactam antibiotics. Incubation in the presence of methicillin (MET), however, results in the emergence of a homogenous population highly resistant to MET. The purpose of the present study was to determine whether MET, despite its lack of killing effect on MRSA, would promote the bactericidal effect of gentamicin (GM), as demonstrated for MET-susceptible strains of S. aureus. Eleven epidemiologically distinct strains of MRSA were incubated with MET at various concentrations, in the presence or absence of sub-bactericidal concentrations (1/5 or 1/10 of the minimal bactericidal concentration) of GM, and tested for the synergistic action of both antibiotics by three different methods. Population analysis of the 11 strains in the presence of high concentrations of MET showed that the addition of GM at 1/5 or 1/10 of its minimal bactericidal concentration resulted in marked killing of the 11 strains. Time-kill curves obtained with 32 mug of MET per ml and GM at 1/5 or 1/10 of its minimal bactericidal concentration confirmed this synergistic killing at 24 h. These results were further documented by the checkerboard method on two strains. We conclude that the synergism between MET and GM, previously demonstrated for MET-susceptible S. aureus, holds true for MRSA as well and that it can be demonstrated at sub-bactericidal concentrations of GM.


Protection from gentamicin nephrotoxicity by cephalothin and carbenicillin. In rats, cephalothin exerts a protective effect upon the nephrotoxicity of gentamicin. To examine the possibility that this effect is also observed with carbenicillin, we gave the following (milligrams per kilogram) to rats daily for 14 days: gentamicin alone, 60; gentamicin plus cephalothin, 100, 500, or 1,000; gentamicin plus carbenicillin, 50, 100, 250, 500, or 1,000. A 500-mg/kg dose of cephalothin afforded significant partial protection from gentamicin nephrotoxicity, as did a 100-mg/kg dose of carbenicillin. Increasing doses of either drug failed to increase protection. The data suggest that in rats not only does carbenicillin afford some protection from gentamicin nephrotoxicity, but also that it does so at a lower dose than cephalothin. These findings may in part explain the divergent observations regarding the nephrotoxicity of cephalothin-gentamicin combination therapy in rats and humans.


Netilmicin in gram-negative bacterial infections. Netilmicin, a new semisynthetic aminoglycoside, was used in the treatment of 42 patients with serious gram-negative bacterial infections. Of the 40 evaluable patients, 24 (60%) were cured, and 8 (20%) had a favorable clinical response, for a total clinical response rate of 80%. Eight patients failed to respond; of these, three had undrained abscesses and two had severe granulocytopenia. Three of the patients who failed had organisms in which resistance to netilmicin developed during therapy, and in two of these three netilmicin was the only aminoglycoside to which resistance developed. Of the 37 patients evaluable for toxicity, 8 (22%) developed renal insufficiency. Two patients had mild but persistant elevation in serum creatinine. Three patients had nephrotoxicity while on gentamicin in the past. Pre- and posttherapy audiograms were done on 26 patients; none had hearing loss. Four patients had mild, transient asymptomatic elevations in alkaline phosphatase. The pretreatment clinical isolates were tested for in vitro susceptibility. The median minimal inhibitory concentration of netilmicin, gentamicin, and tobramycin ranged between 0.5 and 2 mug/ml. The median minimal inhibitory concentration of amikacin was approximately twofold higher. No clear in vitro superiority of one aminoglycoside over another was observed.


Activity of 2,4-diaminoquinazoline compounds against Candida species. Forty recent clinical isolates of three different Candida sp. were tested in the microtiter system for susceptibility to two new 2,4-diaminoquinazoline (DAQ) compounds, amphotericin B and flucytosine. The two DAQ preparations showed activity similar to amphotericin B and flucytosine. The geometric mean minimal inhibitory concentrations for these four drugs were as follows: DAQ 1A, 0.64 mug/ml; DAQ 2A, 1.39 mug/ml; amphotericin B, 1.03 mug/ml; and flucytosine, 0.72 mug/ml. An additional seven DAQ compounds were tested but showed less or no activity against 17 Candida isolates. Forty-eight-hour viability studies with DAQ 2A alone or in combination with amphotericin B, flucytosine, or sulfamethoxazole were carried out with one isolate of intermediate susceptibility to each of these agents except sulfamethoxazole. For this isolate the combination of DAQ 2A and sulfamethoxazole was synergistic, and the combination of DAQ 2A and AMB was either synergistic or additive, whereas the combination of DAQ 2A and flucytosine was antagonistic. Although regrowth of cultures exposed to DAQ 2A was noted over a 48-h period, neither degradation of the drug nor development of resistance to the drug could be detected. Swiss white mice receiving DAQ 1A at a dose of 6 mg/kg for 5 days showed no obvious signs of toxicity, including weight loss.


Effect of protein binding on the activity of penicillins in combination with gentamicin against enterococci. To assess the effect of protein binding by human serum on the synergistic interaction of penicillins with gentamicin, time-kill curves were determined for four penicillins alone and in combination with gentamicin against 10 blood isolates of enterococci. Killing curves demonstrated synergism with penicillin G plus gentamicin against all 10 strains in either broth or 50% human serum. In broth the combinations of nafcillin plus gentamicin and oxacillin plus gentamicin were synergistic against 10 of 10 strains and 4 of 10 strains, respectively. However, in serum, nafcillin plus gentamicin was synergistically bactericidal against only two strains and oxacillin plus gentamicin against none. Methicillin plus gentamicin was synergistic against none of the enterococci in either medium. Thus, the semisynthetic, penicillinase-resistant penicillins are unlikely to be effective in the therapy of patients with enterococcal endocarditis.


Activity of antitumor drugs against African trypanosomes. Of 49 compounds known to have antitumor properties, 6 were found to have significant activity against Trypanosoma rhodesiense infections in mice. Activity against the African trypanosomes has not been reported previously for any of these six compounds. In order of decreasing activity these compounds were: (i) imidazole-4-carboxamide, 5-(3,3-dimethyl-1,1-triazene), (ii) inosine diglycolaldehyde, (iii) cis-diamminedichloro-platinum, (iv) streptozotocin, (v) coralyne sulfate, and (vi) 5-fluoro-2'-deoxyuridine. The percentage of "hits" (12.2%) from these known antitumor agents was approximately twice as great as when other means are employed for the selection of compounds for this test system.


Pharmacokinetics of cefamandole in patients with renal impairment. Cefamandole pharmacokinetics were investigated in 24 adult males with stable renal function and creatinine clearances of 0 to 139 ml/min. After intramuscular injection of 1.0 g of cefamandole, peak plasma concentrations were achieved between 1 and 2 h. Maximum plasma concentration and drug half-life increased as creatinine clearance decreased; i.e., with normal renal function the half-life was 1.49 +/- 0.10 h, and in anephrics the half-life was 11.48 +/- 1.91 h. The greatest increase in half-life occurred when the creatinine clearance was less than 20 ml/min. At these levels of renal impairment, there was significant variance in calculated half-life among patients. The maximum urine concentration and rate of cefamandole urinary excretion decreased as renal function declined. Evidence suggesting renal and nonrenal methods of drug elimination is presented. Hemodialysis resulted in increased cefamandole elimination.


Pharmacology of cinoxacin in humans.

Pharmacology of cinoxacin in humans. Cinoxacin was almost completely absorbed when given orally and was found to be approximately 60 to 70% protein bound. Peak serum concentrations were reached within 2 h, and detectable serum concentrations persisted up to 12 h after administration of 0.25-, 0.5-, and 1-g multiple oral doses. Although food delayed the absorption and caused a 30% reduction in mean peak serum concentrations, the overall 24-h urinary recovery was not significantly altered. Approximately 50 to 55% of the drug was excreted in the urine as unchanged drug. At 12 h, urine concentrations were still above the minimal inhibitory concentration for most common gram-negative urinary pathogens. Cinoxacin was well tolerated when administered to 23 volunteers from 10 to 28 days. Resistance among fecal isolates initially susceptible to cinoxacin was not observed in nine volunteers who were administered 0.5 g every 12 h for 4 to 28 days.


Aminoglycoside-modifying enzymes among clinical isolates of Acinetobacter calcoaceticus subsp. anitratus (Herellea vaginicola): explanation for high-level aminoglycoside resistance. Acinetobacter calcoaceticus subsp. anitratus (Herellea vaginicola) is an important cause of nosocomial infection in our hospital where A. calcoaceticus subsp. anitratus is the most frequently isolated gram-negative species resistant to one or more of the aminoglycoside antibiotics. Of 167 strains tested for susceptibility to aminoglycosides, only 6 strains were found that were resistant to >/=128 mug of kanamycin per ml; all others were susceptible to </=32 mug/ml. Five of these six strains were found to produce aminoglycoside-modifying enzymes. Two strains produced a phosphotransferase which mediates resistance to kanamycin and neomycin; three strains produced an acetyltransferase which mediates resistance to kanamycin, tobramycin, and amikacin (minimal inhibitory concentration >/= 128 mug/ml for each drug). No strain with lower level resistance to kanamycin, tobramycin, or amikacin had enzyme activity. Fourteen strains resistant to gentamicin failed to show significant enzymatic modification of that antibiotic. Although agarose gel electrophoresis of deoxyribonucleic acid preparations from the enzyme-producing strains showed plasmid bands in all, no transfer of aminoglycoside resistance could be achieved, nor was it cured by exposure to novobiocin, ethidium bromide, acridine orange, heat, or prolonged storage. Resistance to mercuric chloride, present in 2 of 60 strains, was lost by 1 strain after exposure to novobiocin, and the loss of resistance was associated with an apparent deletion of plasmid deoxyribonucleic acid.


Treatment of experimental Staphylococcus aureus abscesses: comparison of cefazolin, cephalothin, cefoxitin, and cefamandole. Cefazolin (CZ), cephalothin (CF), cefoxitin (CX), and cefamandole (CM) were evaluated in therapy of Staphylococcus aureus infection produced in perforated table tennis balls placed intraperitoneally in rabbits. Four weeks after placement of two balls in each rabbit, a beta-lactamase producing strain of S. aureus was injected into one of the balls. Twenty-four hours later therapy was initiated with 40 mg of CZ or 80 mg of CF, CX, or CM per kg intramuscularly every 6 h. After 24 h of treatment, the mean log(10) colony-forming units per ml were 7.1 for CZ, 6.7 for CF, 6.5 for CX, and 7.2 for CM. After 72 h the mean log(10) colony-forming units per ml were 5.0 for CZ, 4.1 for CF, 3.6 for CX, and 5.6 for CM. After 8 days, the titers were 1.6/ml for CZ, 1.0 for CF, 1.9 for CX, and 3.6 for CM. CZ serum levels were about double CF and CX levels and about two-thirds of CM levels. In sterile ball fluid CZ and CM levels were more than double CF or CX concentrations. Concentrations of all four antibiotics were lower in infected balls.


Cefatrizine activity compared with that of other cephalosporins. Cefatrizine, a new orally administered cephalosporin, was tested against 400 clinical isolates. Cefatrizine had excellent activity against gram-positive cocci, inhibiting all except enterococci at minimal inhibitory concentrations below 1 mug/ml. Cefatrizine inhibited the majority of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Salmonella at concentrations below 12.5 mug/ml. Although cefatrizine was not hydrolyzed by many beta-lactamases, it did not inhibit a number of strains of Enterobacter, Serratia, or indole-positive Proteus. Cefatrizine was more active than cephalothin or cephalexin against E. coli, Klebsiella, Enterobacter, Citrobacter, Salmonella, and Shigella. Its overall activity was less than that of cefoxitin against strains resistant to cephalothin, but its activity against cephalothin-susceptible strains was equivalent to that of cefamandole.


Activities of 5,6-dihydro-5-azathymidine against herpes simplex virus infections in mice. 5,6-Dihydro-5-azathymidine (DHAdT), a nucleoside antibiotic inhibitory for herpes simplex virus (HSV) in cell cultures (H. E. Renis, Antimicrob. Agents Chemother. 13: 613-617, 1978), was evaluated in mice with experimental HSV infections. DHAdT protected mice infected with HSV type 1 (HSV-1) when the virus was inoculated intravenously and the drug was given by subcutaneous or oral routes. The activity observed was dependent on the dose and schedule of treatment. Doses of 100 to 400 mg/kg given three to four times daily (at 4-h intervals) for 4 to 5 days gave greater protection than less frequent treatment for shorter time intervals. DHAdT treatment reduced the rate of isolation as well as the HSV-1 titers in homogenates prepared from spinal cords and brains, whereas the titers in kidney homogenates were only marginally affected. The above treatment regime with DHAdT afforded only partial protection to mice infected intracerebrally with HSV-1 or mice inoculated intravaginally with HSV-1 or HSV-2. The antiviral activity of DHAdT was reversed by the co-administration of thymidine. Under these conditions, DHAdT was not toxic in mice.


Pharmacokinetic properties of netilmicin in newborn infants. Netilmicin and gentamicin susceptibilities of 258 gram-negative organisms and 25 strains of Staphylococcus aureus were nearly identical. The pharmacokinetic properties of netilmicin were evaluated in 101 newborn infants and related to birth weight, gestational age, chronological age, and route of administration. Mean peak serum concentrations of 5.6 to 6.9 and 7.8 to 8.4 mug/ml were observed 30 min after 3- and 4-mg/kg doses, respectively, were given intramuscularly. The peak concentrations were directly related to gestational age. The average serum half-life values varied from 3.4 to 4.7 h and in general were inversely related to birth weight, gestational age, and postnatal age. The pharmacokinetics of netilmicin in 10 infants were similar after intramuscular and intravenous administration. A comparative study of netilmicin and gentamicin in seven neonates revealed greater variability in serum concentrations of gentamicin and a shorter half-life for netilmicin. There was evidence of accumulation of netilmicin in 12 low-birth weight, premature infants who received 4-mg/kg doses for an average of 6.4 days. Serum and urine levels of netilmicin were measured up to 11 days after discontinuation of the drug. These data are well characterized by a two-compartment model. Additional studies of efficacy and long-term toxicity of netilmicin in neonates are necessary.


Factors contributing to resistance to beta-lactam antibiotics in Bacteroides fragilis. Fifteen strains of Bacteroides fragilis, five highly resistant, five moderately resistant, and five susceptible to benzylpenicillin and cephaloridine, were tested for beta-lactamase production. In the highly resistant and the moderately resistant groups of strains, a correlation between formation of beta-lactamase and minimal inhibitory concentrations was demonstrated. In the presence of the beta-lactamase inhibitors clavulanic acid and CP-45,899 at concentrations of 1 mug/ml, the susceptibility to cephaloridine increased fourfold or more in the beta-lactamase-producing strains. Crypticity measurements (beta-lactamase activity broken/intact cells) with cephaloridine as substrate could indicate a diffusion barrier in the cell wall.


HR 756, a new cephalosporin active against gram-positive and gram-negative aerobic and anaerobic bacteria. The in vitro activity of HR 756, 7-[2-(2-amino-4-thiazolyl)-2-(Z)-(methoximino)acetamido] cephalosporanic acid, was investigated against 659 isolates. HR 756 inhibited Neisseria and Haemophilus species at concentrations similar to those needed with ampicillin. It inhibited beta-lactamase-producing N. gonorrhoeae and H. influenzae. HR 756 was the most active compound tested against members of the Enterobacteriaceae, inhibiting most isolates of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Salmonella, Enterobacter, and Shigella at concentrations of less than 0.1 mug/ml. It was twice as active as carbenicillin against Pseudomonas aeruginosa and inhibited Bacteroides fragilis as well as cefoxitin. HR 756 killed E. coli, Staphylococcus aureus, and P. aeruginosa at rates similar to other beta-lactam antibiotics.


Radiometric method for determining the susceptibility of yeasts to 5-fluorocytosine. A rapid method for determining the susceptibility of yeasts to 5-fluorocytosine by using the Bactec radiometric system is described.


BL-S786 (ceforanide), a new parenteral cephalosporin: in vitro studies. BL-S786 (ceforanide) is a new cephalosporin which showed broad-spectrum activity in vitro against 453 clinical isolates. At a concentration of 3.12 mug/ml, it inhibited greater than 75% of isolates of Escherichia coli, Klebsiella spp., Proteus mirabilis, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. Essentially no activity was observed against isolates of Serratia marcescens, and only minimal activity was observed against Enterobacter spp. Its activity was directly related to the size of the inoculum. The minimal bactericidal concentrations were similar to the minimal inhibitory concentrations for isolates of all organisms except S. aureus and S. pyogenes. The minimal bactericidal concentrations were considerably higher than the minimal inhibitory concentrations for these organisms.


The natural history of polymorphous light eruptions. The natural history of chronic, idiopathic polymorphous light eruption (PMLE( was studied in 138 patients, 85 of whom were female. Mean age of onset of the disease was 26.4 years, and the mean duration at the time of the study was 10.5 years. In most cases (57%) the onset of the disease was very sudden. Light hypersensitivity was usually first confined to limited skin areas, but often (88%) extended to further areas during subsequent summers. The light sensitivity tended to increase during the years; at the time of the study, the threshold tolerance to sun was 30 minutes or less for 60% of the patients. A yearly hardening phenomenon was noted by every second patient. Lip or eye symptoms were present in 46% and 49% of the patients, respectively. Two thirds of the patients experienced some general symptoms after sun exposure.


Blastomycosis-like pyoderma.

Blastomycosis-like pyoderma. Seven patients with blastomycosis-like pyoderma had skin lesions of four months' to six years' duration. The criteria for the diagnosis of blastomycosis-like pyoderma include the clinical presentation of large verrucous plaques with multiple pustules and elevated border, pseudoepitheliomatous hyperplasia with abscess histologically, and the growth of at least one pathogenic bacteria from the culture of a tissue-biopsy specimen. The differential diagnosis includes deep fungus infection (especially North American blastomycosis), bromoderma, pyoderma gangrenosum, mycobacterial infections, giant keratoacanthoma, and squamous cell carcinoma. Generally, the patients had one or more conditions that could have affected their systemic or local immunologic competence to infection. We believe that the clinical and histologic features in these cases of blastomycosis-like pyoderma were produced by an unusual, exaggerated, vegetating-tissue reaction to a primary or secondary bacterial infection.


Disseminate and recurrent infundibulofolliculitis. Disseminate and recurrent infundibulofolliculitis is an uncommon pruitic papular follicular eruption that affects the trunk and proximal extremities and occurs almost exclusively in blacks. Little is known about the cause, and treatment has been totally unsuccessful. Extensive laboratory investigations, including histology and direct immunofluorescence in four cases, were unrevealing. Oral vitamin A therapy was effective in controlling five of six cases. We consider this disease to be a specific clinical and pathologic response to an, as yet, unknown cause or causes.


Acute pancreatitis associated with long-term azathioprine therapy. Occurrence in a patient with systemic lupus erythematosus. A  34-year-old woman with a 13-year history of systemic lupus erythematosus had been taking azathioprine (lmuran) for one year in an effort to control her cutaneous lesions and also as a steroid sparing agent. Acute pancreatitis developed, which we could not relate to her lupus, prednisone administration, viral illness, or other causes. We concluded it was due to azathioprine therapy and wish to report this unusual occurrence.


Immunologic features of chronic granulomatous mucocutaneous candidiasis before and after treatment with transfer factor. We report the acquisition of skin test sensitivity to Candida albicans antigen and the ability to produce leukocyte migration inhibition factor (MIF) by a Candida-negative patient with chronic granulomatous mucocutaneous candidiasis after treatment with dialyzable transfer factor (TFd). The TFd was acquired from Candida-positive healthy donors. Three of seven attempts to transfer Candida skin test sensitivity were successful, and the acquired skin reactivity lasted for 12 to 21 days. The acquisition of cellular immunity to Candida was demonstrated in vitro by production of leukocyte MIF. No Candida-induced lymphocyte transformation was observed before or after TFd injection. The TFd did not cause Candida-induced blast transformation when added directly to cultures of lymphocytes from the patient. Pain, tenderness, redness, and edema were observed around the Candida granulomas on each occasion when the skin test to Candida became positive. Two weeks after TDd injection, the proliferative response of peripheral blood lymphocytes increased, as measured by incorporation of tritiated thymidine into lymphocytes within the first hour of in vitro incubation.


Subcorneal pustular dermatosis and crippling arthritis. A 25-year-old woman has suffered with subcorneal pustular dermatosis and a rheumatoid-like arthritis for the past 11 years. Both her skin lesions and arthralgia have abated with institution of dapsone administration and have worsened with interruption or reduction of the dose. The coexistence of arthritis  and subcorneal pustular dermatosis and the response of both to therapy suggest a probable association.


Harlequin ichthyosis with epidermal lipid abnormality. An infant with phenotypic harlequin ichthyosis survived for nine months, then died a crib death. At autopsy, an enlarged, but structurally normal, thymus was found. Light microscopically, the epidermis showed massive hyperkeratosis and variable parakeratosis, and a stain for neutral fat was positive in the upper epidermis and stratum corneum. Electron microscopic study disclosed crystals resembling cholesterol and masses of autophagic vacuoles, many of them glutted with lipid, deposited within cells of the stratum corneum. Biochemically, cholesterol and triglyceride levels in the stratum corneum were sharply elevated (19.8 and 32.0 mg/g of dry weight, respectively). A defect in epidermal lipid metabolism is postulated.


Apocrine cystadenoma. An ultrastructural study. An apocrine cystadenoma was examined with the electron microscope. Two types of cells were identified: secretory cells and basal (myoepithelial) cells. The secretory cells showed abundant granules that had the features of lipid droplets. The lumen of the cyst contained fragments of cytoplasm that appeared to be detached from the apical portions of the secretory cells. This feature suggests an apocrine type of secretory mechanism involving decapitation of the apical parts of the cells. A merocrine type of secretion was also seen. The basal myoepithelial cells showed abundant cytoplasmic filaments, most of which appeared to be tonofilaments. These cells had fewer myofilaments than those seen in normal apocrine gland cells. Annulate lamellae were not seen in this case.


Generalized malignant acanthosis nigricans. We report a case of generalized malignant acanthosis nigricans (AN) secondary to metastasizing squamous cell carcinoma of the cervix uteri. The disease initially manifested in the perineum as condyloma acuminatum-like lesions. Subsequently, most of the cutaneous surface and the mucosa of the vulva, mouth, tongue, and the palpebral conjunctiva became involved. The association of AN with a squamous cell carcinoma is rare, and conjunctival involvement is unusual.


Bowen's disease and squamous cell carcinoma. Occurrence in a patient with psoriasis after topical, systemic, and PUVA therapy. Multiple lesions of Bowen's disease and squamous cell carcinoma on the penis and pubic areas developed in a 32-year-old patient with psoriasis who was undergoing treatment with psoralen and long-wave ultraviolet radiation (PUVA). A cumulative dose of more than 3,700 joules/sq cm of UVA had been administered over a three-year period. This case may be an early warning of possible carcinogenicity of PUVA therapy, alone or as part of sequential therapy with other agents.


Angiolymphoid hyperplasia with eosinophilia. Angiolymphoid hyperplasia with eosinophilia (AHE) is a distinct clinical and pathologic entity that demonstrates proliferation of endothelial cells associated with varying degrees of lymphocytic, histiocytic, and eosinophilic infiltration. Lymphoid hyperplasia with germinal centers often is present in older lesions and the patients may have an associated blood eosinophilia. Multiple deep nodules developed in a young man on the palmar aspect of the left hand, and subsequently the forehead, histologically diagnostic of AHE. Direct immunofluorescence of the tumor removed from the forehead demonstrated granular deposits of IgA, IgM, and C3 associated with small vessels. Cryoglobulins (IgA, IgM, and IgG) were found in the patient's serum. This new information lends support to the hypothesis that AHE is an inflammatory reactive lesion, possibly secondary to an immunologic injury, rather than a true vascular neoplasm with an associated inflammatory reaction.


Cryofibrinogenemia, monoclonal gammopathy, and purpura. Report of a case and review of the literature. A patient with purpura, acral blisters, and ulcerations was evaluated and found to have cryofibrinogenemia and an IgG K light chain monoclonal gammopathy. No other systemic illness was found. The overall incidence of significant cryofibrinogenemia include neoplastic, thrombotic, infectious, and miscellaneous disorders. The patient described was not easily classified. This case is probably best considered primary or idiopathic cryofibrinogenemia.


Norwegian scabies in Bloom's syndrome.

Norwegian scabies in Bloom's syndrome. Norwegian scabies is an unusual Sarcoptes scabiei infestation. It has been reported often in patients who are either severely debilitated or who have congenital or iatrogenic suppression of their immune responses. We report the occurence of Norwegian scabies in a 13-year-old boy with Bloom's syndrome who had impaired humoral and cell-mediated immunity.


Necrotic skin lesions associated with disseminated candidiasis. A 69-year-old woman with Felty's syndrome developed necrotic skin lesions associated with disseminated Candida tropicalis infection. These lesions differed from the previously described erythematous macronodules of disseminated candidiasis, although histologically there was a dermal infiltrate of yeast and pseudohyphae. Clinically, they resembled ecthyma gangrenosum associated with Pseudomonas septicemia. We believe candidiasis should be included in the differential diagnosis of large necrotic skin lesions in the compromised host.


Carcinoma of the pancreas and periampullary region. Over a 21 year period, 245 cases of cancer of the pancreas were operated upon and followed-up at UCLA Hospital. A further 34 cases of periampullary tumor were treated by partial or total pancreatectomy. Apparent clearance of tumors at the time of pancreaticoduodenectomy that was confirmed by subsequent histopathology resulted in a patient survival time of 20.3 months as compared with a figure of 12.9 months when the pathological examination revealed tumor in a resection margin, although the surgeon believed that excision had been complete at the time of operation. Frozen section examination of resection margins is therefore mandatory. The result of performing a pancreaticoduodenectomy in which tumor was seen to be left behind was a survival time of only 6.8 months, which is similar to the survival time of 6.2 months following a palliative biliary bypass. Pancreaticoduodenectomy in patients over the age of 70 resulted in an average survival of only 7.6 months. Of patients having a palliative biliary bypass alone, 13% required subsequent reoperation to bypass distressing duodenal obstruction. A duodenal bypass should therefore be a routine concomitant of a biliary bypass. Total pancreatectomy with duodenectomy for pancreatic cancer gave an increased average survival of 26 months, and it is likely that the frequency of performance of this operation will increase.


Autotransplantation of cryopreserved parathyroid tissue in man. Human cryopreserved parathyroid autografts have been performed in six patients following reoperative parathyroid surgery. All patients were rendered hypoparathyroid by their most recent reoperation. Parathyroid tissue was successfully autotransplanted after as long as eighteen months of cryopreservation. Viability and expected in vivo function of cryopreserved parathyroid tissue may be predicted by in vitro testing of parathyroid hormone secretion in response to varying ambient calcium concentration. Parathyroid cryopreservation with subsequent autotransplantation is a practical solution to the problem of permanent hypoparathyroidism that may follow multiple surgical procedures for persistent hyperparathyroidism.


Patient and operation selectivity. The peripheral vascular laboratory. Careful use of the data from the vascular laboratory has resulted in better patient and operation selectivity in peripheral arterial disease of the lower extremities. Using the combination of segmental pressure measured with an ultrasonic Doppler and flow as approximated by the measurement of the rate of pulsatile volume change with a calibrated plethysmograph, objective criteria were established for arterial insufficiency. Using a two cuff technique, resistance indices were established to distinguish femoropopliteal from aortoiliac disease. The ratio of angiograms to femoropopliteal and aortoiliac operations has been reduced from an earlier value of almost 3/1 to the present value of approximately 1/1.