Clinical observations of the treatment of tardive dyskinesia with haloperidol. In the present study, after briefly describing the clinical characteristics of the neurologic syndromes provoked by the neuroleptic drugs and most particularly of the syndrome of tardive dyskinesia, we refer to the incidence of this latter syndrome and to the results obtained with the administration of haloperidol for a period of 16 weeks in 10 patients suffering from it. From the detailed analysis of 300 chronic schizophrenic patients, we detected this complication in 10 cases, which gives an incidence of 3,3%. With the administration of haloperidol, on the other hand, we obtained an excellent reduction of both the frequency and the intensity of the peristomal movements in nearly all the patients. This reduction was more remarkable in 2 of the patients who had manifested certain complications of the syndrome, mainly a difficulty in swallowing, followed by a considerable loss of weight in the one patient and by an intense perplexity and a tendency towards suicide in the other. The continued suppression of the above dyskinetic phenomena during the whole period of the trial allows us to conclude that haloperidal may be recommended for the maintenance treatment of the syndrome of tardive dyskinesia.


Ambulant treatment of alcohol withdrawal symptoms with carbamazepine: a formal multicentre doubl-blind comparison with placebo. One hundred male out-patients were treated for alcohol withdrawal symptoms with either carbamazepine or placebo in a double-blind, multicentre trial carried out a five Finnish A-clinics (alcoholism treatment centres) in different parts of the country. In both the carbamazepine and the placebo groups two thirds of the patients completed the 7-day treatment successfully, and the final treatment results were considered equally good in both groups. However, the withdrawal symptoms, especially the sleep disturbances, subsided faster in the carbamazepine group than in the placebo group. The change in the total symptom score from the first day of treatment to the second was significantly greater in the carbamazepine group than in the placebo group. The patients' ability to work improved significantly faster in the carbamazepine group.


An evaluation of the double-blind design in a study comparing lithium carbonate with placebo. As part of a study of drug treatment of aggressive behavior to be reported separately, we have evaluated the double-blind procedure in a recently completed comparison of the efficacy of lithium carbonate versus placebo in modifying aggressive behavior in nonpsychotic incarcerated delinquents. We conclude that the side effects of lithium carbonate are sufficient to reveal the medication to most subjects receiving it. Thus, while the study staff could not identify lithium-receivers at better than chance levels, and while subjects who received placebo could not identify their medication at better than chance levels, subjects who received lithium could accurately identify it. On a weekly symptom check list there was no difference between lithium and placebo groups on average lithium target symptoms reported during 4-week pre- and postmedication control periods; however, lithium-receivers reported significantly more target symptoms every week medication was administered. Of 16 subjects who quit the study, 14 had received lithium and nearly all of those who gave reasons for quitting specified side effects, most often nausea. The methodological problems of using lithium in a double-blind design might be overcome by employing a "discontinuation" design, or, speculatively, a double-blind, cross-over design utilizing an "active placebo".


Gonadotropin response to synthetic gonadotropin hormone-releasing hormone (GnRH) in chronic schizophrenia. GnRH stimulation tests were performed in 15 adult male chronic hebephrenic schizophrenics and 15 oligophrenic controls, matched for age and length of hospitalization. GnRH was given at doses of 50, 100 and 150 gamma to five subjects of each type, and FSH and LH levels in the blood were assayed at 0, 10, 20, 30, 60, and 90 minutes. The tests were performed twice in schizophrenics off therapy and after 10, 20 and 30 days of chlorpromazine therapy (4 mg/kg body weight/day, per os). The controls were not given chlorpromazine and were tested only twice. Schizophrenics showed relative increases in both FSH and LH which were greater than those of the controls, and the response persisted longer. Chlorpromazine had no effect on the test.


Piracetam-induced improvement of mental performance. A controlled study on normally aging individuals. A double-blind, intra-individual cross-over comparison of the mental performance of 18 aging, non-deteriorated individuals during two 4-week periods of piracetam (1-acetamide-2-pyrrolidone) and placebo administration was performed using conventional and computerized perceptual-motor tasks. In a majority of these tasks the subjects did significantly better when on piracetam than on placebo, a finding consistent with ratings completed by two independent observers. The findings indicate new avenues for the treatment of individuals with reduced mental performance possibly related to disturbed alertness--a neglected group of psychiatric conditions.


The Tromsøo heart study. Methods and main results of the cross-sectional study. The mortality from coronary heart disease (CHD) in Norway increased rapidly during 1951-70, the highest mortality rates as well as the most rapid increases being found in Northern Norway. Several surveys of CHD were then planned, one of them is reported here. All men, 20-49 years of age, living in the municipality of Tromsøo, Troms county, were called up for examination. In total, 6595 men, 74.4% of those invited, were examined. Cholesterol, triglyceride and Hb values, BP, body weight and height, the percentage of smokers, and cigarette consumption have been tabulated according to area, age, work schedule, health condition, physical activity and ethnic background. The results suggest that the relatively high mortality from CHD in Northern Norway is associated with high serum cholesterol concentrations as well as a relatively high prevalence of smoking. During the screening there were indications of changes in dietary habits in the municipality, presumably as a result of accompanying publicity.


The functional pattern of the transplanted kidney during the first year. Prospective studies on kidney function have been carried out 1-14 months after transplantation in two groups of recipients of renal transplants. Both groups were characterized by immediate graft function. The first group had transplants from living donors, the second had received cadaveric kidneys. In the first group a functional maximum (as measured by 125iothalamate, creatine and 131I-hippuran clearances) was reached during the first three weeks after transplantation, approximating 70% of the donors' bilateral preoperative function. In the second group kidney function was constant during the period of study, the values being almost identical with those observed in the first group. At investigation 12-14 months after transplantation, the two groups were compared with the remaining cadaveric transplants carried out during the period of study, the latter being primarily graft anuric. Graft function in the primarily anuric grafts was found to be poorer than in those with initial function. Graft survival, too, was poorer at one year in the group characterized by primary graft anuria than in the other groups. Graft survival at one year was 68% in cadaveric kidney transplants with good initial function.


Complication rates of selective percutaneous transfemoral coronary arteriography. A review of 1094 consecutive examinations. A review is presented of 1094 selective coronary artery studies during a 3-year period in which 7001 coronary artery injections were performed using the percutaneous transfemoral artery approach as described by Judkins. A total of 24 serious complications occurred, including 11 ventricular fibrillations, 5 asystoles or severe bradycardias, 3 acute myocardial infarctions and 5 cerebral vascular accidents. There were 5 deaths, giving an overall mortality rate of 0.46%. Causes of individual complications are analyzed. The incidence of serious cardiac complications did not differ significantly from that reported in the literature with the Sones technique. The Judkins technique is a simple and reliable method for selective coronary arteriography. In our opinion, the incidence of complications can be kept at an acceptably low level by meticulous examination techniques.


Psychological and social problems encountered in active treatment of chronic uraemia. II. The living donor. Sixty-four kidney donors have been interviewed by a psychiatrist and given the Rorschach test 6 months-6 years after the transplantation. Twenty-three of these donors were also interviewed before the operation. In addition, each case was studied in detail at a case conference. On the basis of the data thus obtained, an analysis was made of the central dynamics of the donors' personalities, of how they had experienced the donation, and of how they had adapted to it. No psychic trauma was observed in 20 of the subjects, and in 5 of these the operation had apparently had a beneficial effect on their psychic well-being. That no trauma was observed in 8 additional donors was due largely to the effects of a multitude of other traumatic life experiences. Mild trauma had been experienced by 24 donors and moderate to severe by 12. In our study, the donation of a kidney to a sibling turned out to be more traumatic than the donation to a child, and a transplantation with an unsuccessful outcome was more often associated with psychic trauma to the donor than was a donation with a successful outcome. Psycho-social factors that substantially lessened the likelihood of trauma were: good inner resources, flexible defence mechanisms, good mental health and mild compulsive traits. Factors that favoured traumatization were: poor living conditions, interpersonal problems, limited inner resources, low self-esteem (narcissistic problems) and severe psychic deviancy. The results clearly show 1) that potential donors ought to be given adequate time not only to consider their decision but also to prepare themselves for the actural donation, and 2) that supportive help should be offered, both before and after transplantation, to donors whose psycho-social profiles reveal them to be vulnerable to traumatization.


Late complications after primarily successful renal transplantation. The occurrence of late renal and extrarenal complications of primarily successful kidney transplantations is surveyed. All cases in which some surgical or clinical complication, a rejection or complication of the treatment of rejection had occurred were omitted. Primarily, 46 out of 177 transplantations (26%) were completely successful. After six months, the continued course was entirely uneventful in 21 of these cases, while in 25 some kind of complication occurred 6-72 months after the primarily successful course, 19 renal in 17 patients and 23 extrarenal in 16. The complications could not be correlated to histocompatibility, sex, age or basic disease. It may be concluded that a favourable course during the first six months gives good hope of an uneventful continuation, although even serious complications may occur occasionally.


Iron absorption after renal transplantation. Gastrointestinal iron absorption has been measured by means of whole body counting in 13 patients after renal allotransplantation. Whole body retention 14 days after oral administration of 10 muCi 59Fe together with a carrier dose of 9.9 mg Fe2+ was used as an expression of absorption. The percentage incorporation in the total erythrocyte mass of administered 59Fe (erythrocyte incorporation) and absorbed 59Fe (red cell utilization) was estimated as well. Geometric mean iron absorption was 12.4 +/- 2.5 (S.D.)% and geometric mean erythrocyte incorporation 11.1 +/- 3.0 (S.D.)% while arithmetic mean red cell utilization was 95.6 +/- 8.6 (S.E.M.)%. None of these parameters differed significantly from those obtained in normal subjects (p greater than 0.2, p greater than 0.1, pgreater than 0.3, respectively). Iron absorption and erythrocyte incorporation in renal transplanted patients did not differ significantly from the values measured in non-dialysed and dialysed patients with chronic renal failure (p greather than 0.1). The correlation between iron absorption and erythrocyte incorporation was highly significant (r = 0.96, p less than 0.001).


Cytostatic treatment of glomerular diseases. III. A double-blind cross-over study of the effect of cyclophosphamide report from a copenhagen study group of renal diseases. Fifty patients with renal glomerular diseases entered a double-blind cross-over study on the effect of cyclophosphamide; 38 had received neither corticosteroids nor cytostatic drugs before joining the study. Cyclophosphamide was given for 4 months in doses decreasing from 3 to 1.5 mg/kg b.wt. Cyclophosphamide caused a 46% decrease in the 24-hour excretion of urinary protein and a decrease in serum  creatinine within the normal range. Albumin, transferrin and IgA in urine, as well as albumin clearance and the sieving coefficient of albumin, changed parallel to the total urinary protein. The initial values of proteinuria and serum complement were of prognostic significance for the effect of cyclophosphamide in serum creatinine. We were unable to demonstrate a prognostic significance for the variables: clinical diagnosis, renal histology, arterial BP, initial values of serum creatinine and IgG, IgA and IgM in serum and urine. ESR appeared to be the most reliable acute phase reactant. No differences were found between the changes in renal histology during cyclophosphamide or placebo.


Day and night work: changes in cholesterol, uric acid, glucose and potassium in serum and in circadian patterns of urinary catecholamine excretion. A longitudinal cross-over study of railway workers. Two groups of railway workers (n = 16 and n = 17) have been followed on their place of work during a period of shifts between day and night work. Catecholamine excretion in the urine and blood levels of lipids, glucose, uric acid, potassium and calcium were followed during the different phases of shift work. Dramatic fluctuations were noted in the diurnal pattern of catecholamine excretion during and after night work. Significant elevations in the serum levels of cholesterol, glucose, uric acid and potassium were observed during the first week after a night shift, and these changes could not be explained on the basis of shifts in the diurnal pattern or changes in dietary or other habits.


Treatment of hypercholesterolaemia and hypertriglyceridaemia with magnesium. A daily intake of 3 g magnesium (as magnesium oxide) for six weeks had no effect on serum cholesterol and serum triglyceride in 17 patients suffering from hypercholesterolaemia and/or hypertriglyceridaemia.


Renal handling of phosphate in relation to serum parathyroid hormone levels. The relation between the renal handling of phosphate, expressed as the maximal tubular reabsorption of phosphate (TmP)/glomerular filtration rate (GFR) index, and the serum concentration of immunoreactive parathyroid hormone (i-PTH) has been ivestigated in 15 patients with a very wide range of GFR, TmP/GFR and i-PTH. Seven patients had well functioning kidney allografts, with GFR ranging from 43.1 to 64.9 ml/min, while eight had varying degrees of chronic nephropathy, with GFR ranging from 26.7 to 2.3 ml/min. The TmP, the i-PTH concentration, the 51Cr EDTA clearance, the extracellular volume and the serum concentrations of calcium and standard bicarbonate were estimated during conditions where tubular reabsorption of phosphate was maximal. An inverse significant correlation was demonstrated between TmP/GFR and i-PTH (p less than 0.001), while none of the other investigated factors correlated to the TmP/GFR index. It is therefore concluded that the parathyroid hormone has a key role in the regulation of the tubular handling of phosphate in patients with impaired renal function.


Comparative study of circumferential nerve suture using the operating microscope. Electrophysiological and histological control. The aim of this work is to try to compare the results of different methods of circumferential small nerve suture according to the degree of magnification and type of microsurgical technique. Four techniques were studied in forty Wistar rats. 1. Microsurgical suture with the Set technique. Magnification 25, accurate suture. 2. Microsurgical suture with simple end to end approximation. Magnification 25, accurate suture. 3. Same technique, but delayed suture. 4. Suture with a simple end to end approximation. Magnification 4. Four stitches for reapproximation. After four months the sutured nerves have been studied both electrophysiologically and histologically. The results show clearly that the so-called set technique associated with an accurate circumferential suture with eight stitches under high magnification gives by far the best results, the regeneration rate of the nerve being higher than 80%. The results in groups 3 and 4 are definitely less good. The simple bringing together of both stumps under low magnification with only four stitches (group 4) gives the worst results with only 20% of regeneration.


Nerve suture without tension, a method for repairing transected peripheral nerves. An analysis of primary epineural end to end sutures of transsected peripheral nerves, operated upon before 1970, showed good motor and sensory function in only 60%. With the new perineural suturing technique without tension and if necessary by using autologous nerves for bridging large nerve defects the good results raised to 87%.


Autogenous cable nerve grafting instead of end to end anastomosis in secondary nerve suture. A comparison of the results of 53 short cable nerve grafts and of 74 classical end to end nerve sutures is presented. The results of treatment with short nerve grafts are much the better. In the author's opinion good results in nerve grafting are related to the lack of tension in the suture line, and therefore to good revascularisation of the repaired nerve trunk. Autogenous cable nerve grafting is the method of choice for secondary repair of peripheral nerves.


Nerve regeneration following primary repair. In nine selected cases a primary nerve repair was done. In all these patients a special suture was used. Applying clinical and neurophysiological tests, regeneration of the motor and sensory nerve fibres was followed for two years. A remarkable difference in growth rates of sensory and motor nerve fibres was observed. The average rate of growth of sensory nerve fibres was 5 mm a day, and of motor nerve fibres it was 1.7 mm a day. At the end of a two years' interval after operation, good recovery from the initial muscular atrophy was observed in all but two cases. Function of previously denervated muscles was nearly normal. Discrimination of points 4-10 mm apart was possible. Normal terminal conduction times along motor nerve fibres were found in five cases. Slightly prolonged times were found in four. Calculated conduction velocities in sensory nerve fibres were half to three quarters of normal times. All patients resumed their previous occupations.


Comparative evaluation of various histological techniques for the rapid diagnosis of brain tumours. Intraoperative procedures for the rapid histological diagnosis of space occupying intracranial processes are required. These currently include three major techniques: 1. crush preparations; 2. frozen sections with prefixation, and 3. frozen sections without prefixation. We have compared these techniques, using identical tissue material. While frozen sections of samples subjected to rapid fixation produce the best specimens, crush preparations are preferred wherever a well equipped laboratory is not available.


Structure and function of chloroplast-type ferredoxins. Comparison of various chloroplast-type ferredoxin sequences, chemical and enzymic modifications, reconstitution experiments, and fluorescence measurement of chloroplast-type ferredoxins have led to the following conclusions. 1. Tyrosine, histidine, and tryptophan residues are not directly involved in the oxidation-reduction mechanism of ferredoxins. The four indispensible cysteine residues in spinach ferredoxin which constitutes a part of the iron-sulfur cluster are located at residues 39, 44. 47 and 77. Two out of six cysteine residues in Spirulina ferredoxin could be easily modified with vinylpyridine without the loss of reconstitutive ability i.e. the apoferredoxin could be converted to the holoform by the addition of iron and sulfide. 2. Spinach ferredoxin was digested with carboxypeptidase A and the terminal alanine could be removed without loss of the spectral properties of native ferredoxin. However, the removal of the terminal three residues gave rise to the loss of reconstitutive ability. 3. The amino groups of spinach ferredoxin were modified by acetic anhydride and four residues were acetylated. The acetylated preparation of ferredoxin had an unique spectrum. Upon the addition of high concentration of ions the spectrum of this derivative resembled the spectrum of native ferredoxin. Acetylferredoxin did not combine with ferredoxin-NADP reductase, but upon the addition of moderate concentrations of cations, it did bind to this enzyme.


Some properties of bovine pineal tryptophan hydroxylase. Bovine pineal tryptophan hydroxylase is a pterin-dependent aromatic amino acid monooxygenase with a broad substrate specificity and with low Km values for the amino acid substrates, L-tryptophan and L-phenylalanine. p-Chlorophenylalanine, an inhibitor of the tryptophan hydroxylation in the brain, also serves as a good substrate of the bovine pineal enzyme. The full activity of this enzyme is detected in vitro only after preincubation with dithiothreitol under reductive conditions. The enzyme is profoundly and more or less specifically inhibited by L-5HTP, the product of tryptophan hydroxylation, suggesting a possible regulatory role of this hydroxylated amino acid. The Km of the enzyme for tetrahydrobiopterin, a presumed natural cofactor, is significantly higher than the expected tissue concentration if the cofactor is assumed to be uniformly distributed in the tissue. These properties of bovine pineal tryptophan hydroxylase are distinguishable from those of the hydroxylase in the brain indicating that the hydroxylation of tryptophan in the brain leading to the synthesis of serotonin and the reaction in the pineal gland leading to the formation of melatonin are catalyzed by different tryptophan hydroxylases and are probably under separate regulatory mechanisms.


A review: the agents and actions of sympathetic nerve and catecholamine inhibition of gastric mucosal function. The role of the sympathetic nerve supply to the gastric mucosa in gastric physiology is discussed. It is concluded that they are inhibitory to gastric acid secretion, mucosal blood flow, pepsin secretion, gastric oxygen consumption and that these nerves also decrease the serum gastrin concentration. Sympathetic nerve stimulation always reduces the mucosal blood flow and it is suggested therefore, that the inhibition of gastric secretion could be secondary to vasoconstriction mediated by noradrenaline release. The evidence for these conclusions is considered alongside the available histological evidence. It is concluded that the remaining hurdle is to place these phenomena within our knowledge of gastric physiology.


Suramin stimulates B-lymphocyte proliferation in the mouse. Suramin, a drug against trypanosomiasis and onchocerciasis, stimulates in vitro mouse B-lymphocytes to transform into blastcells, to incorporate 3H-thymidine and to go into mitosis. Thymus cells (hydro-cortisone-sensitive or resistant) do not respond whereas cells from homozygous nude mice are stimulated. The large majority of the blast-cells have surface immunoglobulins, and the proportion of cells with intracellular immunoglobulin increases during the course of the cultures.


Aspirin therapy in angina pectoris: effects on platelet aggregation, exercise tolerance, and electrocardiographic manifestations of ischemia. If altered platelet function contributes to poorly perfused zones of myocardium in patients with angina pectoris, then specific antiplatelet therapy might improve cardiovascular function and exercise performance. Exercise tolerance on a bicycle ergometer, heart rate-blood pressure product, and ischemic ECG changes at exercise end-point were compared before and during oral aspirin therapy (2.4 Gm. per day for 2 weeks) in 11 normal subjecs and in 11 patients with stable angina pectoris. Platelet aggregation threshold in response to ADP and epinephrine was measured. Untreated patients had increased platelet aggregability when compared to normal subjects...


Maintenance therapy with a new retard tablet preparation of procainamide. The procainamide plasma concentration was followed during maintenance therapy with a new procainamide retard tablet preparation in 23 hospitalized patients suffering from acute or chronic coronary heart disease with complicating ventricular arrhythmias. After initial individually adjusted treatment with Pronestyl every third hour, either orally or intramuscularly, for at least eight dose intervals, the retard tablets were given at 6 hour intervals for 2 to 12 days, or more. In 19 patients with no major fluctuations in their circulatory or renal state, adequate and relatively stable plasma procainamide concentration was obtained upon a constant dose of the retard preparation. On an average, the difference from minimum to maximum concentration was 55 per cent within the 6 hour dose intervals. In four patients with unstable circulation and/or renal function, procainamide therapy had to be disrupted in two because of severe side effects and toxic concentrations, and the dose was adjusted in the remaining two. It is concluded that the formulation of procainamide tablet preparations has simplified procainamide therapy within and outside hospital and improved our possibilities to perform short-and long-term studies on the risk/ benefit ratio of procainamide treatment in patients with severe ventricular arrhythmias.


Disopyramide: serum level and arrhythmia conversion. The response of arrhythmias to oral disopyramide in relation to its serum levels has been documented. Disopyramide (100 mg.) was given orally, 6 or 8 hourly, to 16 patients with coronary or hypertensive heart disease who developed acute but stable cardiac arrhythmias (20 episodes) which persisted, despite bed rest and sedation with intravenous diazepam or diamorphine. Blood was taken when arrhythmia conversion was observed and the serum disopyramide levels were estimated by gas chromatography. Over-all control of arrhythmias was achieved in 13 (82 per cent) patients within 24 hours. Disopyramide-serum levels were as follows: effective for atrial arrhythmias, 2.80 to 3.18 mug per milliliter, and 3.27 to 7.48 mug per milliliter for ventricular; mean effective levels for all arrhythmias, 3.69 mug per milliliter; mean ineffective levels, 2.39 mug per milliliter (p less than 0.01). Side effects (prolongation of PR and QTc, fall of diastolic BP, urine retention) were observed with serum levels of 3.61 to 7.48 mug per milliliter (mean, 5.54 mug per milliliter) but they were not troublesome clinically. It is concluded that disopyramide is effective and safe with serum levels ranging from 2.39 to about 3.60 mug per milliliter, and this can be maintained with 100 mg., 8 hourly. The drug, however, should be given with caution to patients with severe myocardial disease or low arterial pressure and in the presence of an abnormal ECG.


Reduction of hospital mortality rate of acute myocardial infarction with glucose-insulin-potassium infusion. Free fatty acids (FFA), the predominant myocardial energy substrate, are present in increased quantities immediately following acute myocardial infarction (AMI) and may cause deleterious alterations in cardiac rhythm, oxygen consumption, and mechanical performance. In an attempt to suppress FFA and simultaneously increase the availability of carbohydrate as a myocardial substrate, 70 patients with unequivocal AMI were administered a right atrial infusion of glucose-insulin-potassium (GIK) (300 gm. of glucose, 50 U. of regular insulin, and 80 mEq. of KC1 per liter of H2O) at a constant rate of 0.5 to 2.0 ml. per kilogram per hour for 48 hours. A dramatic fall in FFA (944 +/- 57 to 289 +/- 16 muEq per liter, p less than 0.0005) occurred during GIK infusion, and FFA rebounded to 420 +/- 39 muEq per liter (p less than 0.005) when GIK was discontinued. The hospital mortality rate in the 70 GIK recipients was compared to that of 64 untreated patients (controls) from the same coronary-care unit during the previous year. GIK and control groups had similar severity of infarction as assessed by prognostic scales of Killip, Peel, and Norris, respectively. The hospital mortality rate was reduced in the GIK recipients compared to the control group (11/70 vs. 19/64, p less than 0.05). In patients without history of prior myocardial infarction, the mortality rate was reduced four-fold in GIK recipients compared to controls (6 vs. 24 per cent, p less than 0.05). Complications of GIK infusion were infrequent and included chiefly hyperglycemia and hyperkalemia, both of which dictated meticulous monitoring of serum chemistries. The data suggest that suppression of plasma FFA with GIK infusion may be associated with a significant reduction in the hospital mortality rate of acute myocardial infarction.


A method for biological testing of containment systems for viral agents. A technique utilizing coliphage as the test material has been developed and employed to evaluate the effectiveness of a containment system for zonal centrifugation of hepatits viruses. An Andersen Viable Particle Sampler which had been loaded with plates containing a base layer of agar nutrient with an overlay of E. coli- agar suspension was used to sample the test air. The containment system, which includes a HEPA filter, was challenged with an aerosolized suspension of coliphage.


Limitations of the computer in electrocardiographic interpretation. Use of the computer for electrocardiographic interpretation has steadily increased over the past decade. Although acceptance by a majority of physicians has been slower than originally anticipated, it now appears assured. Nevertheless, the approach has limitations. These are primarily a result of the lack of objectivity in clinical electrocardiographic criteria for both measurement and diagnosis. The limitations are best judged by reviewing experience with a variety of programs. Currently this still involves abstracting from the reports of developers. Although not all developers have analyzed every portion of their programs, in general the data from one program apply to others; that is, all are with minor exceptions at the same "state of the art." Awareness of the limits of computer performance allows a physician to use the computer properly in his current electrocardiographic practice.


Diet, nutrition, and cancer.

Diet, nutrition, and cancer. As the second leading cause of death in the United States, cancer is a major public health problem today. Cancer incidence varies worldwide and tends to change with migration. These epidemiological observations have led to the concept that environmental factors may be important in carcinogenesis. Diet and nutrition are receiving increased attention and the National Cancer Institute, as mandated by the Nation Cancer Act Amendments of 1974, is playing a major leadership role in expanding research efforts in the areas of environmental carcinogenesis, and nutrition in relation to cancer. The subject of diet, nutrition, and cancer is complex. Different types of cancer are not necessarily affected by dietary components in the same manner. Although the development of certain neoplasms may be repressed by specific dietary deficiencies, other types, particularly those of the liver and upper gastrointestinal tract, are actually augmented or potentiated by such deficienceis. In extrapolating results from animal experiments to humans, caution must be exercised because of possible differences in species response to the same dietary stimulus and because spontaneous tumors may react differently from experimentally-induced tumors. Diet and nutrition are viewed more appropriately as modifiers, rather than initiators, of tumorigenesis. Caloric intake, type and amount of fat, protein, amino acids, vitamins, minerals, fiber, and other dietary constituents have been studied in regard to their influence on the development of neoplasms. Dietary components may have opposing effects on tumorigenesis, i.e., protective and predisposing, and the consequence to the host will depend on the balance between these opposing forces. Studies conducted to date indicate that the modifying effect of diet and nutrition may be exerted through specific effects on 1) intestinal bacteria and substrates for bacterial metabolism, 2) microsomal mixed-function oxidase system, 3) endocrine system, 4) immunological system, 5) availability of metabolites for cell proliferations, and 6) rate of carcinogen transfer and duration of exposure to the carcinogen. More research is needed to elucidate the interaction between diet and each of these factors and to test the validity of the mechanisms proposed to explain such interactions. These studies will lead not only to a better understanding of carcinogenesis itself but also to a new understanding of the influence of diet on human physiology and metabolism.


Ineffectiveness of human chorionic gonadotropin in weight reduction: a double-blind study. Our investigation was designed to retest the hypothesis of the efficacy of human chorionic gonadotropin (HCG) on weight reduction in obese women in a clinic setting. We sought to duplicate the Asher-Harper study (1973) which had found that the combination of 500 cal diet and HCG had a statistically significant benefit over the diet and placebo combination as evidenced by greater weight loss and decrease in hunger. Fifty-one women between the ages of 18 and 60 participated in our 32-day prospective, randomized, double-blind comparison of HCG versus placebo. Each patient was given the same diet (the one prescribed in the Asher-Harper study), was weighed daily Monday through Saturday and was counselled by one of the investigators who administered the injections. Laboratory studies were performed at the time of initial physical examinations and at the end of the study. Twenty of 25 in the HCG and 21 of 26 patients in the placebo groups completed 28 injections. There was no statistically significant difference in the means of the two groups in number of injections received, weight loss, percent of weight loss, hip and waist circumference, weight loss per injections, or in hunger ratings. HCG does not appear to enhance the effectiveness of a rigidly imposed regimen for weight reduction.


Fecal steroids in diarrhea. I. Acute shigellosis. Fecal bile acid and neutral sterol patterns of five healthy adult male volunteers, who were challenged by a virulent Shigella flexneri 2a (M42-43) strain and developed dysentery were studied. It was observed that cholic acid was increased from 1.9 +/- 0.4% of total bile acid in the feces before infection to 14.5 +/- 2.1% during diarrhea (P less than 0.001). Chenodeoxycholic acid also was increased from 3.2 +/- 0.7 to 8.7 +/- 3.2% in diarrhea but the difference was not significant statistically. Deoxycholic and lithocholic acids constituted 34.1 +/- 4.1 and 40.5 +/- 2.8%, respectively, of total bile acid in the normal controls as compared to 13.9 +/- 2.5 and 24.8 +/- 2.5% for the same subjects during diarrhea (P less than 0.005). Total excretion of bile acids, expressed as mg/kg of body weight per day, were higher in diarrhea (5.4 +/- 1.0) than that in controls (4,2 +/- 1.0) but the difference was not statistically significant. In the neutral sterol fraction, unmodified cholesterol was increased during diarrhea (86.2 +/- 8.7 versus 25.0 +/- 4.8% of total cholesterol metabolites in controls, P less than 0.001). Coprostanol was decreased in shigellosis (12.2 +/- 8.2 versus 65.8 +/- 4.7% in controls, P less than 0.001). Epicoprostanol, coprostanone, and unidentified cholesterol metabolites also were reduced in shigellosis. The effect of diarrhea on the plant sterols was not as consistent. However, unidentified plant sterols were reduced significantly in shigellosis stools. Total excretion of cholesterol metabolites and plant sterols, when expressed as mg/kg of body weight per day, were 6.8 +/- 1.7 and 0.6 +/- 0.2), respectively, in Shigellosis. These values were not significantly different from the corresponding values for controls (10.3 +/- 3.0 and 0.8 +/- 0.2). One subject's stool samples were studied during infection for the sequence of bile acid alteration. A progressive reduction of bacterial activity upon fecal steroids was evident following the initial diarrheal episode. The production of coprostanol was correlated with 7 alpha-dehydroxylation of cholic acid (r = 0.937, P less than 0.001) and chenodeoxycholic acid (r = 0.755, P less than 0.01).


Group B streptococcal meningitis associated with otitis media. A full-term infant of an appropriate size for gestational age was found to have meningitis due to Lancefield group B beta-hemolytic streptococci at 8 weeks of age. On admission, the baby had bulging tympanic membranes Lancefield group B beta-hemolytic streptococci were isolated from aspirate of the middle ear, supporting the importance of otitis media in the pathogenesis of late-onset Lancefield group B beta-hemolytic streptococcal meningitis.


Hyperlipidemia after renal transplantation in children. A cross-sectional survey of 32 children who received renal allografts was undertaken to evaluate lipid profiles in a pediatric transplant population. Ages ranged from 8 to 18 years, and serum creatinine concentrations varied from 0.5 to 5.6 mg/100 ml (mean, 1.4 mg/100 ml). Fifty percent of patients showed an abnormal lipoprotein electrophoresis, and these were evenly divided between type II and type IV patterns. The data suggest that patients with type II pattern tend to be receiving higher doses of prednisone, and increasing levels of cholesterol and triglyceride are also associated with higher corticosteroid dosages. In contrast to the observations of others in dialysis patients, measurements of glucose metabolism such as fasting blood sugar and fasting insulin levels were not associated with lipid abnormalities in this population. Lipid abnormalities following renal transplantation in children are similar to those described in adults, and may contribute to morbidity in the years following successful renal transplantation.


Hyperlipidemia in pediatric hemodialysis and renal transplant patients. Associated with coronary artery disease. Fasting serum cholesterol and serum triglyceride levels were determined in 15 maintenance hemodialysis (MH) and 35 renal transplant (RT) patients. Fourteen of 15 MH patients (93%) had elevated triglyceride levels (greater than 140 mg/100 ml) compared to 11 of 35 RT recipients (31%) (P less than .001). Two of 15 MH patients (13%) had elevated cholesterol levels (greater than 230 mg/100 ml), compared to 18 of 35 RT recipients (51%) (P = .03). In MH patients, a positive correlation was noted between serum triglyceride levels and carbohydrate intake (P = .03). Autopsy material from 12 children who underwent MH or RT was compared to material from 16 age-matched controls; an increased collagenous content of intima, a possible early indicator of coronary artery disease, was noted more frequently (P less than .006) in index patients compared to controls. Our data demonstrate that hyperlipidemia is a frequent finding in pediatric patients treated with MH and RT, and may be associated with premature coronary artery disease.


Aspirin-induced hepatic dysfunction in a patient with adult rheumatoid arthritis. A patient with classical rheumatoid arthritis receiving high doses of aspirin developed significant elevation of serum glutamic oxaloacetic transaminase. This patient had recently been on phenylbutazone and an initial liver biopsy, at the time of elevation of the transaminase revealed nonspecific mild fatty infiltration of the liver compatible with the pathology seen with rheumatoid disease. Because of the severity and activity of her rheumatoid arthritis, and thus the need to know whether aspirin was the etiologic factor in liver dysfunction, the patient was challenged with aspirin. SGOT elevation occurred after a 4-6 day lag period, which promptly remitted when salicylates were discontinued. A liver biopsy at this time revealed evidence for degeneration, regeneration, and mild focal mononuclear infiltration. Although previous reports note salicylate-related hepatocellular dysfunction in patients with systemic lupus erythematosus and juvenile rheumatoid arthritis, these data clearly demonstrate the relationship of ASA to liver dysfunction in a patient with adult onset rheumatoid arthritis. This histologic picture as well as the clinical course of this patient's hepatic abnormality suggest a toxic rather than hypersensitivity etiology for this syndrome.


The endoscopy corner: removal of foreign bodies from the upper intestinal tract with fiberoptic instruments. Endoscopic removal of ingested foreign bodies should be attempted if the object is not spontaneously passed through the pylorus. This can be safely accomplished with the wire snare technic, or with special grasping forceps that are currently available.


Jaundice in pregnancy--1976.

Jaundice in pregnancy--1976. An integrative survey is given of three disease processes, in which recent progress of a fundamental nature has been made, primarily affecting the liver, either coincident with or caused by the gravid state. The three conditions considered include (1) recurrent cholestasis of pregnancy (RCP), (2) viral hepatitis coincident with pregnancy, and (3) acute fatty liver of pregnancy (AFLP). In addition to an assessment of our present knowledge with respect to RCP and AFLP, new genetic hypotheses are proposed. In the latter, the proposal of an ornithine transcarbamylase deficiency, similar to that seen in Reye's syndrome, has potential therapeutic implications that are explored. In light of the currently available information on the interaction between maternal viral hepatitis and the variant forms of vertical maternal-fetal transmission, tentative recommendations regarding management of the newborn are suggested.


The endothelial function of donor corneas: effects of delayed enucleation and refrigeration. The endothelial viability of rabbit corneas subjected to various forms of cadaveric and moist chamber storage was evaluated by means of the specular microscope and the rate of stromal deturgescence during a temperature reversal response. Delays in the postmortem enucleation and refrigeration of potential donor corneas was shown  to be detrimental to the functioning of the endothelium. To best preserve the endothelial function of donor corneas, the eyes should be removed as soon after death as possible and refrigerated at 4 degrees C. Refrigerated cadaveric storage was found not to be a substitute for early enucleation and refrigeration of the corneas. The limitations in the use of the rate of stromal deturgescence during a temperature reversal response as a quantitative indicator of endothelial function are discussed.


A noninvasive method for detection and analysis of metals in the eye. X-ray spectrometry appears to be a reliable and safe method for noninvasive detection and measurement of metals in the eye for clinical and experimental purposes. Preliminary results in rabbits show that the dissolution of small copper intraocular foreign bodies can be detected shortly after their implantation. The dissolution was measured repeatedly and described as a function of time. It is hoped that this method can supply data regarding the nature and the extent of dissociation of intraocular foreign bodies, thus supplementing methods which can give information regarding only their presence and location.


Middle Eastern intestinal lymphoma: report of a case and review of the literature. A 20-year-old Persian man with Middle Eastern lymphoma is described, and 84 additional cases from the literature are reviewed. Basically, the disease is a malignant lymphoma which involves the upper small intestine (duodenum and proximal jejunum). It is associated with clubbing of the fingers, abdominal pain, weight loss, diarrhea, vomiting, and malabsorption, and frequently occurs in a younger age group than "Western Hemisphere" intestinal lymphoma. Some patients also have alpha heavy chain disease. The sex ratio is equal, and the disease occurs only in Middle Eastern and North African Moslems and Jews. Upper gastrointestinal radiographs are frequently diagnostic, and per oral small intestinal biopsy is nearly always diagnostic. Pathologically, the following features are characteristic for Middle Eastern lymphoma: partial or total villous atrophy with only mildly abnormal surface epithelium, sparsity of crypts, lymphatic dilatation, and infiltration of lamina propria by pleomorphic mononuclear cells which pepetrate the muscularis mucosa. The etiology and pathogenesis of this disease are unknown, but several hypotheses are discussed. Treatment by a variety of modalities is far from satisfactory, and the prognosis is much poorer than that observed in patients with the "Western" form of intestinal lymphoma. Other differences between Middle Eastern lymphoma and Western lymphoma are described in detail,


Hypokalemia: causes, consequences and correction. Hypokalemia poses a common diagnostic challenge with many potential etiologies. Multiple factors may contribute to this electrolyte deficiency in any given patient. Gastrointestinal potassium wasting usually is identifiable by an  associated increase in fluid losses via biliary tract or bowel. A urinary potassium excretion of 20 mEq or more per day in the presence of a low serum potassium (less than 3.5 mEq/L) suggests inappropriate potassium wasting. Although diuretic therapy (loop diuretics, thiazides) undoubtedly is the most common cause of a potassium deficit, one also must consider abnormalities of the pituitary-adrenal axis, renal disorders including tumors, other drugs, and a variety of less well-defined entities. Potassium deficiency may produce both functional and structural defects in the kidneys, myocardium, skeletal muscle, central nervous system, and gastrointestinal tract. Treatment is aimed at replacing potassium intravenously or orally or preventing further potassium loss (spironolactone, triamterene); when associated with a metabolic alkalosis (chloride deficiency), the replacement should be potassium chloride.


Circulatory and cellular immune responses to squamous cell carcinoma of the uterine cervix. The sera from 176 patients with cervical cancer were examined by indirect immunofluorescence against cervical cancer cells (imprints of cervical cancer tissue). The mean serum titer in these patients was significantly higher than the titer in two control groups of identical size. These tumor-related antibodies were also higher in titer in sera from a small sample of nine husbands of cancer patients than in 18 control group patients. A cell-mediated immune response was studied with the use of leukocyte-migration inhibition from 39 blood specimens, including 23 patients with invasive epithelial carcinoma, five with intraepithelial carcinoma of the uterine cervix, six with other gynecologic diseases, and five without gynecologic disease. Migration inhibition was demonstrated for squamous cell carcinoma of the uterine cervix, suggesting a common specific cell-mediated response.


Asymptomatic bacteriuria in pregnancy: antibody-coated bacteria, renal function, and intrauterine growth retardation. Asymptomatic bacteriuria (greater than 100,000 microorganisms per milliliter) was found in 70 of 1,400 pregnant women without symptoms referable to the urinary tract (five per cent). With the fluorescent antibody (FA) tests, antibody-coated bacteria were demonstrated in specimens from 35 patients (50 per cent), indicating silent renal bacteriuria. Although confirmation by direct localization methods was not feasible in this group of patients, indirect evidence of renal function impairment associated with the presence of antibody-coated bacteria was suggested by results of the serum creatinine and creatinine clearance tests. The outcome of the pregnancy was compared for patients with bacteriuria (FA-negative or FA-positive tests). An association between the presence of asymptomatic renal bacteriuria and intrauterine growth retardation was noted. Thus, the patient with asymptomatic bacteriuria and a positive FA test is at greater risk of delivering an intrauterine growth-retarded infant.


Bacteriologic effects of prophylactic antibiotics in cesarean section. An eight-hour course of prophylactic clindamycin and gentamicin was given to 54 service patients undergoing cesarean section. Aerobic and anaerobic endometrial cultures obtained from eight patients who developed endometritis after prophylaxis revealed major changes in flora. Compared to infected patients who had received no prophylaxis, the clindamycin-gentamicin group had marked decreases in aerobic and anaerobic cocci and Bacteroides but increases in E. coli and enterococci. However, this regimen was found to be no more effective than the previously reported regimen of ampicillin and kanamycin.


Examination of pharyngeal secretions to determine the etiology of pharyngitis. Wright-stained throat smears from 174 outpatients with a chief complaint of sore throat were examined. In the presence of tonsillar and/or pharyngeal exudate, cervical lymphadenitis, temperature greater than or equal to 24 less than or equal to 72h, examination of the throat smears would have doubled the accuracy of differentiating streptococcal pharyngitis (SP) from nonstreptococcal pharyngitis (NSP). In the presence of one, two, three, or all four of the preceding presenting characteristics, examination of throat smears would have increased the diagnostic accuracy by 46, 50, 13, and 14 per cent, respectively. Examination  of a Wright-stained throat smear may help distinguish SP from NSP among patients in an outpatient setting where follow-up and, therefore, treatment based on culture results may not be optimal.


Intra-amniotic urea and prostaglandin F2 alpha for midtrimester abortion: a modified regimen. A study comparing intra-amniotic urea plus intravenous oxytocin and intra-amniotic urea with 10 mg. prostaglandin F2 alpha was completed. In addition, the results obtained with a further 150 patients receiving urea and prostaglandin are reported. Mean injection-abortion intervals ranged from 15.75 hours for urea-prostaglandin to 18.93 hours for urea-oxytocin. The advantages of urea-prostaglandin and suggested improvements are discussed. Over all, the method appears efficacious though incomplete abortions and cervical laceration are persistent problems.


Mercury toxicity in the pregnant woman, fetus, and newborn infant. A review. This paper reviews the reported cases of mercury poisoning in pregnancy and the data based on sources of contamination, maternal uptake, and distribution. It analyzes current knowledge of placental transfer of various mercury compounds, fetal uptake, and distribution. It identifies the embryopathic and fetal toxic effects of mercury in general while emphasizing the greater toxicity of methylmercury compounds. Since maternal exposure to methylmercury is primarily through fish consumption, it recommends that women of childbearing age should not consume more than 350 Gm. of fish per week. In addition, they should not be occupationally exposed to air concentrations of mercury vapor greater than 0.01 mg. per cubic meter, of inorganic and phenylmercuric compounds greater than 0.02 mg. per cubic meter, or any detectable concentration of methylmercury.


Surgical correction of superior sulcus deformity occurring after enucleation. A prefabricated, sculptured, subperiosteal orbital floor implant was used in six cases of cosmetically unacceptable deep superior eyelid sulcus that occurred after enucleation. The implant provided anterior and superior displacement of orbital contents. Surgical placement was similar to the approach for implant placement in orbital floor fracture and provided satisfactory cosmetic and functional results.


Morphological changes in corneal endothelial cells after penetrating keratoplasty. Fifteen patients who had had a successful penetrating keratoplasty were photographed with the clinical specular microscope and the resulting endothelial photomicrographs were analyzed. The average endothelial cell area was one to six times larger and the average endothelial cell perimeter was one to 2 1/2 times larger than that of a normal cornea of a subject the same age as the donor. In each corneal graft, endothelial cell areas and perimeters clustered tightly around a mean value, although the mean value for different corneas varied significantly. The thickness and transparency of each graft was normal, indicating that within the observed limits the success of the transplantation procedure did not depend on final endothelial cell size or perimeter.


Diet and atherosclerosis.

Diet and atherosclerosis. Because of the statistical establishment of elevated blood lipids as a risk factor in the development of atherosclerotic heart disease, most of the attempts to regulate blood lipids by diet are centered on the fat in the diet. The levels of blood lipids and the course of experimental atherosclerosis can be affected by other dietary components such as type and amount of protein, carbohydrate, and nonnutritive fiber. Interaction among the dietary components further affects serum lipids and atherosclerosis.


Influence of dietary factors on the pancreatotoxicity of ethionine. Choline deficiency enhances greatly the pancreatotoxicity of DL-ethionine. Mice fed DL-ethionine with a choline-deficient diet develop a fatal acute hemorrhagic pancreatic necrosis with fat necrosis (AHPN) in 5 days. Induction of the AHPN is completely prevented by dietary methionine and drastically reduced by dietary methionine and drastically reduced by dietary choline. The amount of proteins, carbohydrates, and fat in the diet influences its consumption by the animals and thus the severity of the pancreatic pathology. The histogenesis of the process is characterized by widespread alterations of the membranous organelles of the acinar cells, especially the endoplasmic reticulum and the zymogen granules. The onset of the hemorrhagic necrosis of the pancreas is due to an endogenous intraparenchymal activation of the zymogenic proteases, including proelastase. The new experimental model of AHPN appears to mimic very closely the clinical course, the anatomic pathologic lesions, and the postulated pathogenesis of the corresponding human disease.


The anthropological value of minor variants of the dental crown. The incidences of 31 minor variants of the dental crown were scored from dental casts of samples taken from six European populations. Although several variants showed significant sex bias in one or other sample, only one (pits instead of furrow on premolar2) consistently favoured one sex. Associations between the variants were sought. Although few consistent associations were demonstrated, there was a possible tendency for extra cusps to occur together throughout the dentition. Distance statistics calculated between the samples were compatible with the expected genetical relationships of the samples, but only modern samples could be used since variants were destroyed by attrition in archeological samples. Before such distances can be considered reliable, it is necessary to know: (i)the extent to which environmental factors such as diet influence variant expression. (ii)whether or not variant bearing teeth are selectively destroyed by caries, which in civilised populations render a high proportion of most dentitions unscoreable.


Distribution of fetal cardiac output: importance of pacemaker location. Important questions exist about the relative roles of changes in heart rate versus extent of myocardial shortening in regulating fetal cardiac output, because increases in heart rate created by left atrial pacing have been shown to increase right ventricular output and decrease left ventricular output. Since the pacemaker site could importantly influence foramen ovale flow and, hence, each ventricle's output, changes in individual ventricular outputs were examined when both the right and left atria were paced at a rate of 270 beats/min in five acute and in eight chronically instrumented fetal lamb studies. With pacing of either atrium, total cardiac output was unchanged compared to control values. However, the right ventricle contributed more to total cardiac output with left atrial pacing (73% acute, 65% chronic) than with right atrial pacing (51% acute, 57% chronic). Converse changes were observed in left atrial pacing (27% acute, 35% chronic) as compared to right atrial pacing (49% acute, 43% chronic). Thus the disparity that exists normally in the contributions of the right and left ventricles to total cardiac output is accentuated with left atrial pacing and minimized with right atrial pacing. Pressure measurements demonstrated changes in the atrial pressure relations that would be expected to alter flow across the foramen ovale depending on the chamber initially activated. Previous experimental differences can, therefore, be attributed to changes in the magnitude of shunting across the foramen ovale and depend on pacemaker location.


Bioassay of endotoxin clearance in vivo and by perfused rat liver. Endotoxin clearances in vivo and by the isolated perfused rat liver were evaluated via bioassay in lead-sensitized rats. A linear relationship between the probit of shock lethality and the endotoxin dose in the probit range of 4-6 was validated. Endotoxin clearance in normal, fed rats displayed a linear relationship between the logarithm of the blood endotoxin concentration and time throughout the period of 15-240 min at doses of 500 and 1,000 mug/ rat; the half-time values were 58-63 min. Decreasing the endotoxin dose to 250 mug resulted in multiphasic clearance curves. Induction of tolerance to endotoxin resulted in marked acceleration of endotoxin clearance. Endotoxin clearance from the isolated perfused rat liver was not influenced by serum or rat blood as compared to clearance from a balanced salt solution. These data suggest that a physiologically stressful dose of endotoxin is slowly cleared from the blood and, therefore, circulates for prolonged periods.


Hypoglycemic depression of RES function. The intravascular removal rates of colloidal carbon and of biologically active endotoxin by the reticuloendothelial system (RES) were evaluated as a function of blood-glucose levels. There was a significant negative correlation of carbon clearance half time on blood glucose in both saline-treated and insulin-treated rats. Insulin hypoglycemia depressed RES carbon clearance with the maximal effect occurring at blood glucose values below 30 mg/dl. Insulin hypoglycemia also severely impaired the intravascular removal of endotoxin as evaluated by lethality bioassay in lead-sensitized rats. It is concluded that blood glucose may modulate RES phagocytic function and that the hypoglycemia of endotoxin shock may augment the shock state due to impairment of RES host defense clearance functions.


Tracking difficulties and paranoid ideation during hashish and alcohol intoxication. In a double-blind study using each subject as his own control, 6 normal subjects smoked 20 mg of THC within 10- and 45-minute periods ("fast" and "slow" conditions, respectively). Each subject also received placebo and doses of alcohol calculated to be as intoxicating as the THC doses. In fast conditions, THC induced greater difficulties with tracking information over time, greater disruptions of self-other interpersonal perceptions, and more persecutory ideation that did alcohol or placebo. Similar but less marked differences were found in the slow conditions. As hypothesized, changes in tracking difficulties, self-other metaperspectives, and persecutory ideation were substantially and significantly correlated.


Free psychotherapy: an inquiry into resistance. Psychotherapy for which the patient is not charged, such as that provided by the Veterans Administration system, can lead to unique conflicts and resistances within treatment. Patients may depreciate the value of therapy, feel obligated to the therapist, or expect him to make inappropriate nonfinancial demands. The authors present five cases illustrating that lack of a fee may become the focus of insoluble resistances to therapy, and suggest that, particularly in training situations, a token fee should be charged to obviate these difficulties.


Overview: research on the psychology of women. I. Gender differences and sexual and reproductive life. There has been a recent and rapid increase in research literature pertaining to women; this revolution in women's studies may be currently unequaled in any other field related to psychiatry. In this first part of a two-part article the author briefly discusses the social and intellectual contexts of research in this area. She reviews recent research on gender differences in behavior and on women's sexual and reproductive lives, including various aspects of the menstrual cycle, menopause, diseases of the reproductive organs, coitus, rape, childbirth, lactation, and fertility control. The second part will cover research on women in families, communities, work, and psychotherapy; and it will attempt to assess limitations of present knowledge and the anticipated directions and impact of future research.


Factors affecting the use of physician services in a rural community. This paper examines the relative importance of various independent variables for predicting five separate measures of physician utilization in a rural community. The independent variables include socioeconomic, demographic, attitudinal, and health status factors. The results are comparable to those of national studies which find that health status is the primary determinant of utilization. Income, price measures, and travel time are notable for their relative unimportance in this rural area. This suggests that resources are more likely to be allocated on the basis of medical need within a given health care market than across a number of market areas.


A simple method of tracking mammals and locating triatomine vectors of Trypanosoma cruzi in Amazonian forest. A simple method of tracking mammals from capture points to their refuges was developed to study Trypanosoma cruzi reservoir-vector associations in Belém forest. A device containing a spool of fine line was carried by released mammals so that the line unwound under minimum tension as the animal proceeded and could be followed the day after release. Twenty-three triatomine bugs of five species were found with 3 of 15 mammals retrieved.


Morbidity of colostomy closure.

Morbidity of colostomy closure. An unexpectedly high morbidity (28 per cent) followed colostomy closure in 100 patients. One patient died postoperatively because of sepsis resulting from disruption of the colon anastomosis. Wound infection (10 per cent), intraperitoneal abscess (1 per cent), bowel obstruction (7 per cent), and fecal fistula (4 per cent) were other significant complications. Wound sepsis was greater after primary than after delayed wound closure. Obstruction did not correlate with the use of either an open or closed technic of anastomosis. Three patients required reoperation for complications. Temporary colostomy was constructed for colon injury in 85 per cent of patients. In view of the considerable morbidity of colostomy closure, alternate technics of managing colon trauma should be considered. Such technics include primary closure and exteriorization of repaired colon. When temporary colostomy is unavoidable, closure is best done by open, two layer anastomosis with delayed wound closure. Colostomy should be recognized as an important procedure associated with significant morbidity.


Technical considerations in elderly renal allograft recipients. Atherosclerosis in renal allograft recipients necessitated modification of vascular anastomoses in 62 per cent of patients older than forty years in contrast with 10 per cent in younger patients. Three forms of vascular disease occurred: atherosclerotic occlusion, tortuosity of vessels, and disruption of plaques by vascular clamps. Successful modifications of the procedure and avoidance of ischemic graft injury are described including relocation of the transplanted ureter.


Sacrococcygeal dermoids and teratomas: historical review. Palpable rectally, when not externally visible, sacrococcygeal teratomas have been recognized since antiquity, but their histologic segregation from other sacrococcygeal masses lagged into the twentieth century. That these tumors are potentially malignant, and that the incidence of this complication increases with age during infancy, was realized early this century, but it is only in the last two decades that the importance of (1) early surgery, (2) excision of the coccyx, and (3) a combined abdominosacral approach for lesions with retroperitoneal extension has been realized.


Johann Friedrich Meckel, the Younger (1781-1833). Meckel's name is well known in the medical world because of the intestinal abnormality that carries his eponym. We are less familiar with his personal life and his far-reaching achievement as a prominent anatomist. Also described is his complex personality as well as the indelible impression he made on his contemporaries.


Repair of large chest wall defects using pedicle flaps. Three cases of chest wall resection illustrate the use of three different full thickness pedicle flaps which can be used to cover almost any area of the anterior chest wall. The medially based acromiothoracic flap was swung inferiorly to cover a lateral defect. Laterally based abdominal wall and axillary flaps were used to cover more medial defects. In case III bilateral axillary flaps were necessary to cover a huge central defect after resection of the anterior sternum and anterior cartilages of seven ribs for a sebaceous carcinoma.


Contiguous cervical and deltopectoral flaps for skin lining and replacement with en bloc resection of cancer of the head and neck. Contiguous cervical and deltopectoral flaps have several advantages in reconstruction of the head and neck after extirpation of cancer. The cervical skin provides an excellent color match for facial skin, and nonhair-bearing skin is available if lining of the oral cavity is required. The deltopectoral flap provides superior coverage for the carotid artery.


The many uses of polyurethane foam.

The many uses of polyurethane foam. Self adherent foam padding has unlimited opportunities for plastic and general surgical use. Skin blisters do occur but less often than with tape. It may also be used over the shoulder and scapula where other types of more invasive immobilization were usually necessary and has also been effectively utilized as postmammoplasty support, as facial and postrhytidectomy dressings, and over leg grafts. Furthermore, it can be used for postpilonidal and axillary pad dressings.


Automatic perimetry in glaucoma visual field screening. A clinical study. Automatic computerized perimetry was compared to careful manual selective perimetry (a variant of that proposed by Armaly) in 181 eyes of 100 patients from a glaucoma open-care unit. The results of the two methods were very similar. Thus all defects found were identified by the automatic perimeter, and one pathologic field was missed by the manual selective perimetry. The automatic examination gave 16% false positive results and the manual 11% when optimally performed. The false positives could be greatly reduced (to 4.4% and 3.3% respectively) by rescreening. In a comparison with "routine" perimetry, the automatic screening is shown to be superior.


[Acupuncture analgesia in China (author's transl)]. As part of an agreement between the Governments of the People's Republic of China and Canada, 10 Canadian Anaesthetists visited China for six weeks during April and May 1974. The delegation observed 87 surgical operations and 19 dental procedures conducted under acupuncture analgesia in 17 large hospital in Peking, Schichiachuang, Nanking, Shanghai and Canton. In this report, observations on acupuncture analgesia made during this visit are presented as well as information obtained in group discussions with Chinese physicians. In the author's opinion, the technique was successful in about 80% of the cases seen; these patients were awake during surgery without visible distress and exhibited a remarkable degree of analgesia immediately after surgery. However, in China, acupuncture analgesia is still considered in the experimental stage and only used in a limited number of standardized, elective surgical procedures, where confidence and the success of this technique have been established. For the successful use of this technique, patient and surgeon must co-operate fully. Acupuncture analgesia poses considerable limitations on the surgeon and requires careful surgical technique; the patient's co-operation must be assured by a suitable preparation. It appears, that acupuncture analgesia should be seen as an alternative to local anaesthesia rather than general anaesthesia; the latter is only used to a limited extent in China. In our present anaesthetic practice, acupuncture would appear to be of only very limited use, however, a further study of this phenomenon should contribute to our knowledge of the function of the nervous system.


Intracranial responses to PEEP.

Intracranial responses to PEEP. Elevated intrathoracic pressure due to positive end-expiratory pressure (PEEP) has the potential for increasing intracranial pressure (ICP) and reducing arterial blood pressure (BP). Such changes could critically reduce cerebral perfusion pressure (CPP = BP - ICP), This possibility was investigated in 15 cats with artificially-produced expanding intracranial masses (intracranial balloon). The interrelationships among ICP and central venous and arterial pressures were observed during application and removal of graded levels of PEEP (5, 10, 15 cm H2O). The electroencephalogram and pupillary diameters were monitored. At various levels of ICP, nine of the cats were given oleic acid intravenously to embolize the lung and cause pulmonary dysfunction. In cats not given oleic acid, PEEP caused a maximal reduction in cerebral perfusion pressure of 45 +/- 4 torr(SEM), accompanied by variable changes in ICP. PEEP application in the absence of oleic acid embolization of the lungs caused electroencephalographic abnormalities in 77% of these cats, while  pupillary diameters increased in 56%. Animals embolized wwith oleic acid had significantly less (P less than .001) severe CPP reductions (mean 21 +/- 4 torr) than did the non-embolized animals, and developed no EEG change due to PEEP. However, increases in pupillary diameter still occurred in 33% of cats given oleic acid when PEEP was applied. In 82% of the PEEP applications (n = 44) in both experimental groups only insignificant increases in intracranial tension occurred (average peak ICP gain less than 1.5 torr). Abrupt increases in ICP exceeding 11 torr (15 cm H2O) occurred in four animals in each group. This happened most frequently (63 per cent) when the intracranial tension before PEEP was above 15 torr. Sudden removal of or reduction in PEEP was accompanied by increases in arterial and intracranial pressures in both groups, although this response was attenuated in the cats given oleic acid. The results indicate a potential for PEEP to evoke neurolgic complications in patients who have intracranial disease and that the presence of pulmonary disease may attenuate these deleterious side effects. Monitoring of neurologic function as well as blood-gas and cardiovascular effects of PEEP in patients who have intracranial disease is suggested.


Mutagenicity of volatile anesthetics: halothane. The mutagenicity of halothane was tested in an in-vitro microbial assay system employing two histidine-dependent mutants of Salmonella typhimurium, TA98 and TA100, Halothane in concentrations ranging from 0.1 to 30 per cent was incubated with bacteria in the presence or absence of a metabolic activation system prepared from either rat liver treated with Aroclor 1254 or human liver. Trifluoroacetic acid, a major metabolite of halothane, and urine from patients anesthetized with halothane also were tested. Halothane, trifluoroacetic acid, and patients'  urines were not mutagenic.


IgE antibodies in bronchopulmonary aspergillosis. Total serum IgE and serum IgE antibodies to A. fumigatus were quantitated in 143 patients with different forms of bronchopulmonary aspergillosis. Total serum IgE levels were elevated in all patients with allergic bronchopulmonary aspergillosis but also in some other forms of bronchopulmonary aspergillosis, thus limiting the diagnostic value of total serum IgE determination in this type of pulmonary mycotic infection. Specific IgE antibodies to A. fumigatus could be demonstrated in all patients with allergic bronchopulmonary aspergillosis, at least during an acute episode of their disease. Only two patients with a different form of bronchopulmonary aspergillos had slightly elevated levels of specific antibodies. Measurement of IgE antibodies specific to A. fumigatus by means of the RAST method, using high quantities of antigen coupled to cellulose discs so that inhibitory factors may not interfere, is a useful aid in the diagnosis of allergic bronchopulmonary aspergillosis.


The intestine in allergic diseases.

The intestine in allergic diseases. In this review I have described the pathophysiology of allergic disorders of the gastrointestinal tract. Situations where the intestine cannot be a complete barrier to foreign allergens and antigens were discussed and etiological factors of gastrointestinal allergy were detailed. Clinical features of gastrointestinal allergy include diarrhea, vomiting, abdominal pain and colic, intestinal hemorrhage and malabsorption as well as symptoms and signs outside the gastrointestinal tract such as chronic rhinitis and asthma in the respiratory system, urticaria, angioedema and eczema as dermatological signs, headache, insomnia, hyperkinesis as central nervous system manifestations, failure to thrive and anaphylaxis as constitutional reactions. Milk allergy was discussed as an example of food allergy. Immunology of the gastrointestinal tract was presented, with examples of four types of hypersensitivity reactions, and gastrointestinal disturbances of immunodeficiency disorders and syndromes were named. Lastly, the autoimmune mechanism and the gut were described, with particular discussion of ulcerative colitis as an example of an autoimmune disease.


Etiologic diagnosis of diarrheal disease of calves:  frequency and methods for detecting enterotoxin and K99 antigen production by Escherichia cola. Escherichia coli isolated from calves in Minnesota and Montana were tested for enterotoxigenicity via bio-assay of cell-free broth culture fluid and for K99 antigen via a serum agglutination test. Infant mice were used to assay for heat-stable enterotoxin (ST), and adrenal cells in culture were used to assay for heat-labile enterotoxin (LT). Forty-six of the 345 E coli isolates produced ST enterotoxin, but none produced LT enterotoxin. Thirty-five of the 46 enterotoxigenic isolates had K99 antigen, and only 9 of 66 nonenterotoxigenic isolates so tested had this antigen. The enterotoxigenicity of 28 additional E coli isolates known or suspected to be calf enteropathogens and provided by investigators from 3 different laboratories was also tested. All isolates from 2 laboratories produced ST but not LT. All isolates from the 3rd laboratory produced LT but not ST. Escherichia coli organisms that were positive in the infant mouse assay also caused positive ligated, jejunal-loop responses in calves and in 9-day-old (but not in 5-week-old) pigs. It was concluded that the infant mouse and adrenal cell tests for ST and LT, combined with the agglutination test for K99, would be useful in the diagnosis of enteric enterotoxic colibacillosis of calves.


Characterization of a calf diarrheal coronavirus. A coronavirus-like agent isolated from feces of a calf with diarrhea and attenuated by consecutive passage in a fetal bovine kidney cell line was characterized as a coronavirus. Negatively stained virions were approximately circular, had a mean diameter of 120 nm, and were covered with wide-spaced, petal-shaped projections about 20 nm long. Virions in ultrathin sections of infected cell monolayers had a mean diameter of 80 nm, lacked surface projections, and were found within cytoplasmic vesicles. Viral antigen was demonstrated by immunofluorescence microscopy to occur only in cytoplasm. Growth of the virus was not inhibited by 5-iodo-2'- deoxyuridine and actinomycin D. The virus was sensitive to ether, chloroform, deoxycholate, and heat treatment. However, thermosensitivity was stabilized in the presence of 1 M MgCl2; at pH 3, the virus was stable. Hemadsorption and hemagglutination were observed with erythrocytes of hamsters, mice, and rats but not with erythrocytes of cats, dogs, goats, sheep, cattle, horses, turkeys, chickens, guinea pigs, rabbits, geese, pigs, and man (type O). However, hemadsorption and hemagglutination were shown to be virus specific, since this could be inhibited by specific antiserum. Both infectivity and hemagglutinating activity were maximal at a particle density of 1.18 g/ml by sucrose density gradient centrifugation, indicating that hemagglutinin was part of the virion.


Indirect fluorescent antibody test for the diagnosis of coronaviral enteritis of turkeys (bluecomb). Frozen sections of intestine obtained from experimentally infected embryos were satisfactory as a suitable antigen in the indirect fluorescent antibody (IFA) test for detection of antibodies to turkey coronaviral enteritis (TCE). Antibodies were detected in infected turkeys at 14 days after infection and persisted for at least 107 days when the 1st experiment was concluded. Antibodies were also detected in infected turkeys at 9 days after infection and persisted for at least 160 days when the 2nd experiment was terminated. The IFA test may be of value as a rapid and economical screening method for TCE antibodies.


Diagnosis of radiosensitive hypothalamic tumors without craniotomy: endocrine and neuroradiologic studies of intracranial atypical teratomas. Three patients with intracranial atypical teratomas presented with symptoms of endocrine dysfunction (diabetes insipidus, hyperprolactinemia, and anterior hypopituitarism) suggestive of a hypothalamic disorder. Computer-assisted tomography done in two of the three cases enabled us to document the presence of a mass and institute radiotherapy, without prior neurosurgical exploration. Computer-assisted tomography also provided a safe and effective method of assessing the effects of radiotherapy.


Treponemal antigens in congenital and acquired syphilitic nephritis: demonstration by immunofluorescence studies. Two patients, a 4-month-old infant girl with congenital syphilis and a 45-year-old man with secondary syphilis, had the nephrotic syndrome with glomerulonephritis. Immunoglobulins and treponemal antigenic material were seen in the glomeruli of both patients by immunofluorescence microscopic studies of renal tissue. Electron micrographs showed subepithelial electron dense deposits along the glomerular basement membrane. This confirms earlier suggestions that the renal injury is of an immune-complex type.


Current concepts of leukemia and lymphoma: etiology, pathogenesis, and therapy. The cellular change (phenotypic) leading to leukemia may involve a disorder of leukocyte maturation, but the etiologic molecular change (genotypic) remains unknown. We present evidence here that human leukemic cells contain type-C viral information and consider the possible significance of this observation in the context of a working hypothesis. We reexamine reticuloendothelial neoplasms in the light of newer immunologic, cytochemical, and ultrastructural methods for identifying cells of the T-lymphocytic, B-lymphocytic, and monocyte-macrophage systems. Use of these methods has led to a challenging concept of malignant lymphomas as neoplasms of various anatomic and functional compartments of the immune system. Functional studies, although still in their inception, have already provided provocative clues in the etiology and pathophysiology of these disorders. Advances in laboratory research have been paralled by dramatic changes in clinical oncology, as evidenced by trends in the treatment of acute lymphocytic leukemia, acute myelogenous leukemia, Hodgkin's disease, and diffuse histocyte lymphoma.


[Gonadotropins].

[Gonadotropins]. The clinical usefulness of plasma LH and FSH radioimmunoassays, both in basal and dynamic  conditions, is briefly discussed. While occasional LH and FSH determinations may indicate only a serious gonad failure, at least when high values are found, dynamic studies before and after LH-RH i.v. injection may suggest a hypothalamic or pituitary lesion. In this regard the LH-RH test is presented as the most evident demonstration of the utility of gonadotropin  radioimmunoassay. Different patterns of response are presented and their correlation with menstrual disorders is discussed in view of different distribution (Tab.1). Moreover, the AA. suggest a primary hypothalamic deficiency in LH-RH in the cases of "deficient" response that, being a constant finding  in different days, became a "normal" response after 3 days therapy with LH-RH infusion and returned to basal levels 2 months later. Equally, an "exaggerated" response consistenly found in some patients with secondary amenorrhea, is suspected to be of hypothalamic origin since "normalization" may be obtained after a  similar LH-RH treatment.


[Plasmid determined lactose positive character in (Enterobacter hafniae) and (Proteus morganii) (author's transl)]. The atypical lactose positive characters have been found to be plasmidmediated in 6 strains of Enterobacter hafniae and 2 strains of Proteus morganii. One of the P. morganii plasmid possesses the fi+ character, all the other plasmids belonging to the fi-group. Both plasmids of P. morganii could be transduced and remained then readily transferably by conjugation. Two of the E. hafniae plasmids were found unstable when harboured in Salmonella typhi grown at 40 degrees centigrade, when they were stable in the same strain grown at 37 degrees. The other plasmids were stable in the original strains, in S. typhi, in Escherichia coli both at 37 degrees and 40 degrees. These results are discussed according to investigation about (lactose plasmids) of which a bibliographic review is presented here.


[A comparative study of different methods of determining the Tm of bacterial DNA (AUTHOR'S TRANSL)]. Melting point curves of DNA are used to calculate average GC content. Four methods of Tm determination are described and are used in the case of all DNA samples studied. The results presented confirme that thermal denaturation curves are asymetrical, and this limits the use of "normal probability paper" and "regression lines" methods. Best reproductibility is obtained by a study of the function (see article) followed by a linear interpolation of the median. This approach yields at the same time interesting information about bacterial DNA. The graphic determination of Tm appears to be the method for choice for routine analysis.


[Characterization by zymograms of R factor-determined beta-lactamases: plasmids of defined and undefined compatibility groups (author's transl)]. An easy biochemical method is described, discriminating the beta-lacta-mases coded by various R factors. Electrophoretic mobility and substrate affinity of beta-lactamases were studied simultaneously for 7 different penicillins and cephalosporins. They are I like R factors assigned into different compatibility groups (N, P, com6, com7, com8, X and com 9), five R factors isolated from piglets faeces and one R factor, RU1, originated from Enterobacter aerogenes. Three electrophoretic types of beta-lactamases were determinated: 1) beta-lactamase which migrates towards the anode (enzyme coded by Bacillus cereus chromosome); 2) beta-lactamase of weak cathodic mobility (e. g. R6K); 3) beta-lactamase which migrates rapidly towards the cathode (e. g. R46, R71). Escherichia coli K12 strains synthesize a penicillinase of this third type, destroying penicillin G. The enzymatic and physicochemical properties are not modified by host bacteria, suggesting the possibility to study the plasmid in wild bacteria.


Studies on the ability of acetylcholine receptors to bind alpha-bungarotoxin after exposure to myasthenic serum. The purpose of the present experiment was to determine if there is a factor in serum of patients with myasthenia gravis (MG) that interferes with binding of (125I)-alpha-bungarotoxin to acetylcholine receptors of normal mouse diaphragm. Diaphragms were incubated aerobically for 1 hour in either Krebs-Henseleit solution, MG serum, or control serum, and then (125I)-alpha bungarotoxin was added for 2 further hours at a concentration of 1 mug/ml. After 12 rinses in Krebs-Henseleit solution for another hour, radioactivity was counted. Binding after exposure to MG serum was compared to that obtained after exposure to Krebs-Henseleit solution or control serum. Sixteen sera from 14 controls, 18 sera from 15 patients with moderate generalized MG, and seven  sera from seven patients on alternate-day prednisone therapy (six with severe generalized MG, one with myasthenic syndrome) were tested by this method. No significant difference in alpha-bungarotoxin binding was observed between normal mouse diaphragm incubated in MG sera and those incubated in control sera.


Antibody-dependent cellular cytotoxicity and B-and T-cell activity in the peripheral blood of myasthenia gravis patients. Antibody-dependent cellular cytotoxicity (ADCC) was found to be significantly decreased in whole blood as well as in purified lymphocyte preparations from myasthenia gravis patients. Decreased ADCC was found not to correlate with the clinical classification nor with the therapy regimen, including immunosuppressive agents. PHA, Con A, and PPD responsiveness of peripheral blood lymphocytes was normal. Likewise no significant decrease was observed in the T-and B-cell distribution in the peripheral blood.


Myasthenia gravis: the role of immunological deficiency. To evaluate further the association between myasthenia gravis and humoral immune deficiency, 92 sera from myasthenic patients were tested so as to determine titers against commensal E. coli, isohemagglutinin titers, and IgG and IgM concentrations. Results were compared with those obtained from normals, disease controls, and W27 positive arthropathy. On the basis of these three investigations it is concluded that subtle immunodeficiency is common in myasthenia gravis, and it is suggested  that an immune defect might explain such diverse associations as thymic disease, HL-A antigens,  and various autoimmune phenomena.


The role of humoral and cellular immune factors in neuromuscular block in myasthenia gravis. The neuromuscular block of myasthenia gravis appears to be due to decreased and abnormal responsiveness of the motor end plates to transmitter, and perhaps a decreased number of functioning end plates. The presence in myasthenic patients of serum globulins that bind to a bariety of cellular and subcellular components, and of thymic abnormalities, has encourage the search for humoral and cellular immune factors that may be responsible for the anatomic and functional defects. Attempts to demonstrate neuromuscular blocking activity in the serum have been inconclusive. While 30% to 48% of myasthenic patients have globulins that react with muscle membrane, striations, ribonucleporotein, and thymic epithelial cells, these globulins have not been shown to react with the end plate or acetylcholine receptor, or to impair neuromuscular transmission. Antinuclear, rheumatoid, antimitochondrial antithyroid, anti-smooth-muscle, and anti-gastric-parietal cell factors are found in the serum of 3% to 16% of myasthenic patients, but these are much more commonly present in other diseases. However, antibodies to acetylcholine receptor from electric tissue, which were recently reported in the serum of three fourths of myasthenic patients, may prove to be more directly related to the neuromuscular block. While the majority of myasthenic patients have thymic abnormalities, including thymoma in 9% of patients and hyperplastic thymus in 66% of patients, the remaining 25% of patients have normal, involuted, or undetectable thymus. Thymectomy has a favorable effect in about two thirds of myasthenic patients, but about one third of patients have no benefit. Thirty-two patients have been described who developed myasthenia gravis after total thymectomy and presumably in the absence of the thymus. Thymus lymphocytes of myasthenic patients have some differences from those of normal subjects, including a greater proportion of B cells, but their significance is not known. Attempts to demonstrate neuromuscular blocking activity in the thymus of myasthenic patients have been inconclusive. Blood lymphocytes of myasthenic patients also have some differences from those of normal subjects, including a lower proportion of T cells. The proportion of both T and B cells increased following thymectomy. While studies on the immunological reactivity of lymphocytes from myasthenic patients have shown some differences from those of normal subjects, neuromuscular blocking activity has not been demonstrated in these cells or in their extracts. There is increasing evidence that the neuromuscular block of myasthenia gravis is due to alteration of the acetylcholine receptor. The recent reports of antibodies to acetylcholine receptor in the serum of myasthenic patients suggests that these may be responsible for the neuromuscular block, but such action, and the cause of antibody release, remain to be determined.


Ultrastructural studies on the acetylcholine receptor at motor end plates of normal and pathologic muscles. The acetylcholine receptors at the mammalian motor end plate have been counted and their distribution there determined ultrastructurally. Electron microscope autoradiography applied to muscles labeled with alpha-(3H)bungarotoxin was used for this purpose. The receptors are distributed asymmetrically along the postsynaptic membrane, being concentrated at the fold crests-that portion nearest to the presynaptic membrane. The density of receptor sites at that region is estimated to be 20,000-25,000 per mum2 of membrane surface. This density holds for the several species and muscle types thus far examined and appears to be a constant parameter of the motor end plate. It determines the limit of responsiveness to acetylcholine. By contrast, the enzyme acetylcholinesterase is found to be  distributed evenly over the folds and may reside in the intersynaptic matrix. When mouse diaphragm end plates from dystrophic animals or animals following 5-day denervation were similarly examined, no significant alterations in either the density or the distribution of the receptor sites were found. Similarly, dystrophic muscles in chickens possess an unaltered number of receptors at their end plates. A model is outlined to correlate receptor and cholinesterase concentrations with known aspects of transmitter release. These findings may have relevance to some of the electrophysiological abnormalities seen in myasthenia gravis.


Macrophage activity and clinical immunology. Origin and kinetics of mononuclear phagocytes. The origin and kinetics of mononuclear phagocytes can only be studied after the cells have been properly characterized. The basis for such a characterization on morphological, cytochemical, functional, and immunological grounds has been discussed. The production and kinetics of mononuclear phagocytes during the normal steady state have been described and compared with the effect of an acute inflammatory stimulus on these parameters. The influence of hydrocortisone and azathioprine was also studied in this connection. The increased production and monocytosis seen during an acute inflammatory response have been shown to be regulated by a humoral factor. The concept of the mononuclear phagocyte system was also discussed and an outline of the participation of mononuclear phagocytes in pathological processes put forward.


Macrophage reactivity in skin window of sarcoidosis patients. We investigated 582 cases of sarcoidosis by the skin-window (Rebuck) method. The number of macrophages appearing in skin windows was significantly increased in 432 patients with sarcoidosis in the active phase. Further, increased numbers of macrophages in the windows were found in patients with a positive Kveim-Siltzbach test, high immunoglobulin levels, increased B lymphocytes, and decreased T lymphocytes. Passive transfer of delayed-type hypersensitivity was weaker and shorter in sarcoidosis patients with increased presence of macrophages than in healthy controls. A close correlation between high macrophage reactivity and the other sepcific immunological factors in sarcoidosis is suggested.


Sarcoid lymphocytes: B- and T-cell quantitation. Bone-marrow-derived B lymphocytes and thymus-dependent T lymphocytes were quantitated in a group of 38 patients with histologically confirmed sarcoidosis. B lymphocytes were identified by detecting surface immunoglobulins (Ig, IgG, IgM, and IgA) and complement receptors. T lymphocytes were identified by E-rosette assay. The untreated patients with both limited and disseminated disease had lymphopenia, reduced T-cell number, and low E/Ig cell ratios. Absolute numbers of circulating E-rosette lymphocytes did not show any correlation with cutaneous anergy. The numbers of Ig-bearing lymphocytes or the sum of the numbers of IgG, IgM, and IgA(GMA)-bearing lymphocytes were elevated in patients with disseminated disease, whereas the numbers of complement receptor lymphocytes were normal in all groups. It is proposed that this discrepancy of results on B-lymphocyte subpopulations might be explained by the presence of antibody or extrinsic antigen-antibody complexes bound to lymphocytes, as supported by elevated GMA/Ig ratios. The numbers of circulating B lymphocytes, as detected by any of three markers employed in this study, showed no correlation with the levels of serum immunoglobulins. The mechanisms of T-cell depletion and increase of immunoglobulin-bearing cells remain to be determined.


Immunological studies in sarcoidosis: a comparison of in vivo and in vitro Kveim tests. No migration inhibition was observed in the 46 patients or the 12 controls when the Danish Kveim antigen was used in the LMAT. No migration inhibition was found  in 23 of the same patients when the LMT was employed using the same antigens (Table 3).


Distribution and function of T- and B-cell subpopulations in sarcoidosis. Some in vitro functions of purified T and B cells from PPD- and Candida albicans-negative sarcoidosis patients were analyzed. It appears that in those patients there is: 1) A decrease in the absolute number of T lymphocytes and an increase in the number of B cells; 2) a rather normal response of T lymphocytes to PHA and Con A; 3) a rather normal capacity of T and B cells to produce MIF in vitro; and 4) an ability of T cells from sarcoid patients (but not B cells) to produce LMF. These results suggest that the frequent deficit in cell-mediated immunity observed in sarcoidosis seems to correlate with a quantitative deficit in T cells. The cause of this T-cell deficit is unknown.


Antibodies to T cells in sarcoidosis.

Antibodies to T cells in sarcoidosis. Antibodies to a proportion of T lymphocytes were detected in the sera of 9 of 15 patients with sarcoidosis. Patients were studied within one year of tissue diagnosis, none were taking steroids, and all had hilar adenopathy with pulmonary infiltrates (Stage II). Antibodies were identified by three assays using a panel of T cells purified (greater than or equal to 90%) from the peripheral blood of healthy donors by the nylon column technique. Nine of fifteen sarcoid inhibited the capacity of normal T cells to adhere to sheep red blood cells (E rosettes) with an average reduction of 33% (range 21-46%) from control values. Antibodies to T cells were also identified using the indirect immunofluorescent method; 7 of 15 sera contained antibodies (IgM and IgG) to a portion of T cells (mean 36%, range 24-52%). Four of these sera were also cytotoxic to a fraction (18-31%) of T cells when incubated (15 degrees, 90 min) in the presence of rabbit complement. The antibodies to T cells identified in the sera of sarcoid patients may account for some of the immunological abnormalities found in this disease.


Intraocular effects of pimaricin.

Intraocular effects of pimaricin. Pigmented rabbits weighing 3 to 6 lbs were given bilateral intraocular injections of 250 to 1,000 mug pimaricin. Following their injection, blood, aqueous and vitreous levels were determined at various time intervals during the first 24 hours and at 24 hour intervals thereafter for one week. In subsequent studies, pigmented rabbits were given bilateral intraocular injections of 5,000 spores of A. fumigatus and 30 hours later received intraocular injections of 250 to 1,000 mug pimaricin. These studies show that 250 mug of intraocular pimaricin is well tolerated in the infected and normal animal eye with therapeutic ocular levels maintained for over 24 hours. Drug levels above 250 mug, although relatively notoxic in the normal eye resulted in irreversible damage to ocular structures in the infected eye that could not be resolved. Thus in the case of fungal endophthalmitis involving the anterior segment which will lead to the ultimate loss of the eye, an injection of 250 mug of pimaricin might preserve useful vision.