Delayed hypersensitivity responses of experimental animals to histoplasmin from the yeast and mycelial phases of Histoplasma capsulatum. Controlled yeast lysate (CYL) and controlled mycelial lysate (CML) histoplasmins were produced from Histoplasma capsulatum grown in a nutritionally lean, chemically defined medium. The lysates were assayed for skin-test activity in guinea pigs sensitized by infection with the homologous organism. In some studies, nonliving vaccine preparations were employed also. Inter-lot biological variation was minimal, and 20 lots of the CYL reagent elicited strong dermal reactions with high specificity. Further, CYL reagents were nonreactive in guinea pigs infected with Coccidioides immitis, whereas the commercial Food and Drug Administration preparations cross-reacted to some degree. The CML histoplasmins were generally less reactive than the CYL preparations and exhibited somewhat more inter-lot variation in sensitivity and specificity. No correlation between potency and protein:polysaccharide ratios were observed with either reagent. An intradermal test with the CYL reagent did not induce significant changes in the complement-fixing titer of sensitized guinea pigs. Such changes in sensitized animals were elicited by a skin test with commercial histoplasmin.


Parameters affecting the enzyme-linked immunosorbent assay of immunoglobulin G antibody to a rough mutant of Salmonella minnesota. An enzyme-linked immunosorbent assay was developed to detect rabbit immunoglobulin G antibodies against purified lipopolysaccharide of the rough Re mutant of Salmonella minnesota. The time necessary for each step was investigated, and this resulted in a test that could be completed in 1 working day. Serial dilutions of rabbit sera drawn throughout immunization with the Re mutant revealed an elimination of the prozone effect upon prolonged immunization. We interpret this to demonstrate an increase in immunoglobulin G affinity for the lipopolysaccharide on prolonged immunization. We propose that the enzyme-linked immunosorbent assay prozone effect be investigated for use as a measure of antibody affinity.


Susceptibility of mice to acute and persistent measles infection. Intracerebral inoculation of neonatal mice with the Edmonston strain of measles virus produced an acute, lethal encephalitis and thymic dysplasia in susceptible mice. There was an age-related development of resistance to infection. This resistance was strain-dependent and appeared to be associated with the extent of virus growth in the brain. Studies on the genetic basis for susceptibility, using hybrid and backcross mice, revealed that the principal determinant of host resistance to acute infection was a dominant gene or genes which segregated independently of the H-2 complex. A small number of survivors of the acute infection showed persistence of measles virus antigens in the cerebellum and spleen for up to 2 months after inoculation. However, the low frequency of this persistence indicated that, at this time, intracerebral inoculation of neonatal mice with the Edmonston strain of measles virus constitutes a difficult model for the study of persistant measles infection.


Infections of congenitally athymic (nude) and normal mice with avirulent and virulent strains of Venezuelan encephalitis virus. Two strains of Venezuelan encephalitis virus that are avirulent for normal BALB/c mice inoculated subcutaneously were also avirulent for infected congenitally athymic (nude) mice of the same strain. Viremias were of similar magnitudes and durations in normal and nude mice. Brain concentrations were higher in nude mice with the one avirulent strain tested, although the periods of detectable virus in brains were similar. No lesions were found in brains, spleens, or lymph nodes by ordinary histopathological examination. Viral neutralizing antibody titers in plasmas at 1 to 3 weeks after infection were lower and more transient in nude than in normal mice, and implantations of thymic tissues into nude mice partially restored their neutralizing antibody responses. Concentrations of spleen cells producing antibodies that lysed sheep erythrocytes 4 days after inoculation of erythrocytes and avirulent virus into nude mice were above the levels of uninfected nude mice. These concentrations were similar in infected and uninfected normal mice. In contrast, two mouse-virulent strains of Venezuelan encephalitis virus killed nude mice faster than normal mice after subcutaneous inoculation. Yet concentrations and durations of virus in bloods and brains were not consistently different between nude and normal mice. There were perivascular monocytes in brains and slight architectural alterations of spleens and lymph nodes. Concentrations of spleen cells producing antibodies hemolytic for sheep erythrocytes 4 days after inoculation with erythrocytes were depressed in nude and normal mice by infection with virulent strains.


Rapid method for identification and enumeration of oral Actinomyces. Serotype-specific antisera prepared against whole cells of Actinomyces viscosus, A. naeslundii, and A. israeli were labeled with fluorescein dye and used to detect and quantitate antigenically related microorganisms in human dental plaque. By relating the DNA content of the dental plaque microflora to the number of Actinomyces present in the plaque samples, a reproducible method was developed for specifically enumerating five serotypic representatives of this genus found in human plaque.


Pathogenesis of fever in delayed hypersensitivity: factors influencing release of pyrogen-inducing lymphokines. In continuing studies on the pathogenesis of fever in states of delayed hypersensitivity, we have investigated the conditions for the release of an endogenous pyrogen (EP)-inducing lymphokine from draining-lymph-node lymphocytes of rabbits with delayed hypersensitivity to bovine gamma globulin. Using doses of 4 X 10(7) to 5 X 10(7) blood leukocytes (BL) as a source of EP, we found that ratios of about 5:1 of viable lymphocytes to BL were required to stimulate the BL to produce detectable amounts of EP in vitro. Both irradiated lymphocytes (1,700 R) as well as those from steroid-treated donors retained their ability to activate BL when incubated with antigen, properties consistent with activated "T" lymphocytes. In experiments to determine effects of temperature and duration of incubation on lymphokine release, the maximum EP-releasing activity was found to be present in supernatants of sensitized lymphocytes incubated with antigen for 18 h at 37 degrees C. These studies have confirmed that sensitized lymphocytes release a soluble, pyrogen-inducing lymphokine when incubated with antigen and further demonstrate that tissue macrophages (Kupffer cells) as well as BL can be activated to produce EP in vitro by this agent.


Pathogenesis of fever in delayed hypersensitivity: role of monocytes. The present studies were designed to investigate the role of monocytes in the pathogenesis of fever in delayed hypersensitivity. Adherent rabbit blood monocytes (from both normal and sensitized donors) were separated on Ficoll-Hypaque gradients and incubated with antigen (Ag; ovalbumin) and sensitized draining-lymph-node lymphocytes (or their supernatants) from rabbits with delayed hypersensitivity, and release of endogenous pyrogen was assayed. Results indicated that monocytes are activated to produce endogenous pyrogen by Ag and suspensions of draining-lymph-node cells or by an agent (lymphokine) in the supernatants of sensitized lymphocytes preincubated with Ag. The release of lymphokine was Ag specific and was correlated with the skin test reactivity of the donor rabbits to the sensitizing Ag. No evidence was found that Ag-antibody complexes or (in the case of sensitized monocytes) cytophilic antibodies play a role in the activity of this lymphokine which appears to act selectively on monocytes rather than on granulocytes.


Bacteriology of human experimental gingivitis: effect of plaque age. Twenty-five subjects with previously excellent hygiene and healthy gingiva developed heavy plaque accumulations and bleeding or nonbleeding gingivitis about certain papilla after 21 days of no oral hygiene. Gingival marginal plaque about a single papilla was collected at 0, 1, 2, and 3 weeks of no oral hygiene in each subject. The plaque was dispersed, serially diluted, and plated on MM10 sucrose agar in an oxygen-free atmosphere. From 50 to 100 colonies from a single high-dilution plate were characterized for each sample. Over 8,500 isolates were partially characterized and placed into one of 29 taxonomic species or groups. The flora was predominantly gram-positive at all time periods. Streptococcal species dominated in the 0- and 1-week-old plaques, i.e. 62 and 43% of the colonyforming units (CFU), but dropped to 26 to 32% of the CFU in the 2- and 3-week-old plaques. Actinomyces species dominated in the older plaques, i.e., 40 to 50% of the CFU. Actinomyces israelii was the most prominent species in the older plaques. Veillonella accounted for 15 to 20% of the CFU at all time periods. Although the other gram-negative species increased with time, collectively they averaged less than 5% of the CFU at week 3. The shift from a Streptococcus-dominated plaque to an Actinomyces-dominated plaque was the most striking microbial change observed as the plaque aged.


Bacteriology of human experimental gingivitis: effect of plaque and gingivitis score. The plaque flora isolated from discrete dentogingival sites during a human gingivitis experiment was analyzed as a function of the plaque score and of the gingivitis score. When the gingivitis score was plotted as a function of the plaque score, a nonbleeding gingivitis was associated with a proportional increase in the Actinomyces sp. at the expense of the Streptococcus sp. In particular, the percentage of Actinomyces israelii increased significantly, while the percent Streptococcus sanguis decreased significantly. A. israelii also increased significantly when a bleeding gingivitis developed. When the plaque score was plotted as a function of the gingivitis score, A. israelii increased significantly as the nonbleeding gingivitis developed, but A. viscosus and Bacteroides melaninogenicus increased significantly when the bleeding gingivitis developed. The availability of a sufficient number of plaques with a plaque score of 2.0 permitted the examination of the interrelationship of gingivitis and flora minus the effect of plaque biomass. The bacteriological profile showed that when bleeding occurred, the levels and proportions of A. viscosus and B. melaninogenicus increased significantly. These findings raise the possibility that proportional changes in the gingival plaque flora may uniquely contribute to the development of gingival inflammation in this experimental model.


Effects of local immunization with glucosyltransferase fractions from Streptococcus mutans on dental caries in hamsters caused by homologous and heterologous serotypes of Streptococcus mutans. Seven serotypes of Streptococcus mutans have been identified. The biochemical, genetic, and serological characteristics of these serotypes have indicated that certain serotypes are quite similar, whereas others are quite distinct. The effect of local immunization with glucosyltransferase (GTF) enzymes from serotypes a, c, or g on infection and disease caused by homologous or heterologous cariogenic S. mutans is reported. Organisms with either similar (a and g) or different (c and g) biochemical and serological characteristics were selected for heterologous challenge. NIH white hamsters were injected four times at weekly intervals with GTF prepared by 6 M guanidine-hydrochloride elution from water-insoluble glucan of serotypes a, c, or g, which resulted in enzyme (homologous) inhibitory activity in sera and salivas. After infection of GTF-immunized and sham-immunized groups of hamsters with cariogenic S. mutans of the same serotype as the injected antigen (homologous infection) or with S. mutans of a different serotype from the injected antigen (heterologous infection), the numbers of streptomycin-labeled S. mutans, caries, and lesions were determined. Immunization with GTF preparations from each of the three serotypes resulted in statistically significant reductions in the extent of infection and disease and number of lesions caused by infections with homologous cariogenic S. mutans. Statistically significant reductions in these three parameters were also observed in groups immunized with enzyme from serotype a (strain E49) and challenged with cariogenic serotype g (strain 6715) organisms; or immunized with enzyme from serotype c (strain Ingbritt) and challenged with cariogenic serotype g (strain 6715) organisms; or immunized with enzyme from serotype g (strain 6715) and challenged with cariogenic serotype c (strain Ingbritt) organisms. These studies suggest that soluble antigen preparations containing GTF from one serotype may elicit a protective immune response against infection with cariogenic S. mutans from many or possibly all serotypes.


Cerebrospinal fluid and serum immunoglobulins and antibody titers in mumps meningitis and aseptic meningitis of other etiology. Cerebrospinal fluid (CSF) and serum from 19 patients with mumps meningitis and 19 patients with meningitis of other etiology were investigated on two or more occasions for at least 1 month after onset. Intrathecal synthesis of immunoglobulin (Ig) G was found in 55%, of IgA in 26%, and of IgM in 24% of the patients. Oligoclonal Ig was demonstrable by agarose gel electrophoresis in 37% of the patients, mostly already during the first week after onset, and could persist for years. Mumps virus antibody synthesis within the central nervous system occurred in 37% of the mumps meningitis patients. The inflammatory reaction within the central nervous system as reflected by mononuclear pleocytosis, Ig synthesis, and oligoclonal Ig was not correlated to the clinical course. The blood-brain barrier was evaluated by determination of the CSF total protein, CSF/serum albumin ratio, and CSF/serum alpha2-macroglobulin ratio. A significant correlation was found among these three parameters. Persistence of the elevated CSF/serum albumin ratio seems to influence prognosis, and this parameter is recommended for evaluation of the blood-brain barrier function.


Chemotaxigenic activity of extracts from the mycelial and spherule phases of Coccidioides immitis for human polymorphonuclear leukocytes. In order to further characterize human host defenses against Coccidioides immitis, extracts of this fungus were tested in vitro for their ability to attract polymorphonuclear leukocytes derived from peripheral blood of uninfected subjects. Soluble substances prepared from the mycelial (saprophytic) and spherule (tissue) phases exhibited, in the presence of serum, dose-dependent chemotactic activity. The dose-response correlations were different. The spherule-derived preparation showed decreased activity at the high concentrations, a diminution not observed with equivalent concentrations of the mycelial filtrate. Chemotactic activity was not observed with either substance in the absence of serum or if heat-inactivated serum was substituted. Because the response of human polymorphonuclear leukocytes to these fungal substances appears complement mediated, a selective cellular defect in this function which antedates exposure to C. immitis seems unlikely.


Antigens of Streptococcus sanguis: purification and characterization of the b antigen. The antigen defining Streptococcus sanguis serotype 2 has been designated the b antigen. This antigen can be detected in extracts, obtained from whole cells by autoclaving (Rantz and Randall extraction), as a single precipitin band using a reference antiserum (M-5). However, the extract can also be shown to contain a teichoic acid using anti-polyglycerol phosphate serum. This teichoic acid does not contain the antigenic determinant for group H specificity. Studies of the b antigen have been hampered because of the difficulty in separating the b antigen from the teichoic acid using ion-exchange and molecular sieve chromatography. However, a relatively pure preparation has been obtained by affinity chromatography using anti-polyglycerol phosphate serum coupled to Sepharose. The isolated b antigen is a typical streptococcal cell wall polysaccharide composed of glucose, rhamnose, and N-acetylglucosamine in a molar ratio of 2.5:1.0:0.1. The antigen appears to have a single antigenic determinant closely related to isomaltose (glucose alpha-1,6-glucoside) based upon hapten inhibition studies.


Effect of cortisol on the growth of Chlamydia trachomatis in McCoy cells. The number of intracytoplasmic inclusions of Chlamydia trachomatis produced in McCoy cell monolayer cultures infected with a constant inoculum of a recently isolated genital strain was compared in cultures of untreated replicating cells and in monolayers which had been incubated in the presence of cortisol at initial extracellular concentrations between 0.0001 and 100 microgram/ml. The effect of adding cortisol was dependent on its concentration, on the time of addition to the tissue culture medium, and on the initial number of McCoy cells seeded to form the monolayer. When a concentration of 1.0 microgram/ml was added at the time of infection with C. trachomatis, the number of inclusions detectable after a further 48 h of incubation was increased by 1.84-fold over those detected in untreated cells. The mean size of inclusions and the ease of their recognition in McCoy cell cultures was also increased by this procedure.


Polymorphonuclear cell function in the various polar types of leprosy and erythema nodosum leprosum. Polymorphonuclear leukocyte motility, both in vivo and in vitro, and reduction of Nitro Blue Tetrazolium was studied in tuberculoid and lepromatous leprosy patients and a group of lepromatous patients with erythema nodosum leprosum (ENL). A profound defect in random migration, chemotaxis, and chemokinesis was found in lepromatous patients with and without complicating ENL, and marked depletion of skin window migration confirmed these in vitro findings. Tuberculoid patients exhibited a mild defect in polymorphonuclear leukocyte motility. Serum inhibitors of normal polymorphonuclear leukocyte chemotaxis were found in all types of leprosy, but sera from lepromatous and ENL patients were most inhibitory. Resting levels of Nitro Blue Tetrazolium reduction were normal in all three groups. Reconstitution of polymorphonuclear leukocyte cells from normal and ENL patients with ENL serum, however, showed increased Nitro Blue Tetrazolium reduction well above the normal range, whereas reconstitution with normal, lepromatous, and tuberculoid sera failed to increase Nitro Blue Tetrazolium reduction above the normal values.


Cytotoxic activity of Aeromonas hydrophila. Most strains of Aeromonas hydrophila tested demonstrated cytotoxic activity on several tissue-cultured cell lines. The cytotoxin is heat-labile, non-dialyzable, and immunologically distinct from that of Shigella dysenteriae and Clostridium perfringens. None of the aeromonas isolates was found to be enterotoxigenic by either tissue culture or rabbit ileal loop assays.


Some aspects of the relationship between body weight and sexual behaviour with particular reference to massive obesity and anorexia nervosa. There is some evidence for the existence of a precise weight/fat threshold for puberty. Following puberty, body weight and shape take on important new psycho-social significances for both males and females. Adolescent females usually strive to reduce their 'fatness' even it is not excessive from a biological standpoint. Super-obesity and anorexia nervosa are two human disorders of weight and fatness, more common in women, and importantly related to disturbances of sexual behavior, metabolic, social and experiential. These latter aspects sometimes at least reflect the presence of several factors which have contributed to the development of the disorders. Anorexia nervosa in particular reflects the adaptive psychosocial needs of the person concerned. Attention to this aspect during treatment will often allow the patient to tolerate the major weight gain required for recovery, thereby at the same time providing a paradigm for aspects of the pubertal process which can then be studied. The results of some such investigations together with related studies of the super-obese are reported here.


The lipoprotein-lipase activity of adipose tissue from different sites in obese women and relationship to cell size. The lipoprotein-lipase activities (LPLA) and fat cell sizes were determined in subcutaneous, adipose tissue from four different sites in a group of 17 obese women. The LPLA per gram and per cell were significantly higher in the adipose tissue from gluteal and femoral sites than in tissue from the abdominal site. The degree of obesity of the subjects, as reflected in the fat cell size, was correlated with the LPLA per cell, so that large cells contained more LPLA per cell than small cells. On the other hand, no correlation was found between the cell size and the LPLA per gram. Intra-individually, the cell weight was related also to the LPLA per gram, so that sites with large fat cells also had high concentrations of LPLA per gram. The interpretation of the results with regard to obesity and to the variation in size of fat depots in an individual is discussed.


An evaluation of the efficacy and acceptability of 'Slender' in refractory obesity. A formula diet 'Slender' was assessed in 55 patients with refractory obesity. During the initial 12 weeks of the study, the subjects were instructed to take a carbohydrate restricted diet designed to provide 1000 kcal (4.2 MJ) per day. They were then advised to replace up to four meals a day with a packet of Slender. Of the 42 subjects completing the study, 21 stopped taking Slender after six weeks and 21 completed 12 weeks. During the pre-Slender treatment, the mean weight gain was 1.7 kg. This contrasts with a mean weight loss during the first six weeks of treatment with Slender of 1.9 kg. Those continuing to take Slender for 12 weeks lost 3.7 kg and subjects who said that they had adhered strictly throughout the trial period had a mean loss of 4.6 kg. The overall results are relatively disappointing but are similar to that which can be achieved with other forms of therapy in comparable patients. If there is use for Slender, and other similar products, it may be the prevention of obesity rather than in the management of the morbidly obese.


Tolerance and cross tolerance to the anorexigenic effect of appetite suppressants in rats. Rats were treated chronically with various anorexigenic substances which were administered orally once (or twice) daily or bidaily. Complete tolerance to the anorectic effect of d-amphetamine, fenfluramine, benfluorex (780 SE), chlorphentermine, and mazindol developed in 11-17 days. Test doses were given at different points of time after withdrawal in order to recognize the presence or absence of direct or cross tolerance. Direct tolerance to fenfluramine and benfluorex persisted for 46 days, whereas tolerance to mazindol was no longer present at day 20. There was lasting bidirectional cross tolerance between chlorphentermine and fenfluramine, transient bidirectional cross tolerance between mazindol and amphetamine, but only unidirectional cross tolerance between amphetamine and fenfluramine.


Multidisciplinary approach to adult obesity therapy. A comprehensive program has been designed to treat medically significant obesity (body mass index greater than 30). The essential components include nutritional education, exercise, mental conditioning, relaxation and assertiveness training. Adherence to this combined program is supported by rapid weight loss utilizing a protein-sparing modified fast. Initial efforts include greater than 18 kg (40 lb) weight loss in three out of four patients and greater than two years maintenance in one out of three patients. The varying success depends on patient adherence to a prolonged education program at least six months to one year directed at modification of lifestyle. Both for lasting safety and effectiveness a professional partnership is required between the physician and patient. Finally the result of therapy appears to be rehabilitation and not cure from the problem of obesity.


Results of the treatment of obesity with a protein-sparing modified fast. Thirty-six obese adults received a protein-sparing modified fast (PSMF) consisting of 1.5 g of meat protein per kilogram of ideal body weight and meeting vitamin, mineral, and fluid requirements. These studies were conducted as short-term inpatient metabolic studies followed by a program of outpatient obesity treatment. Thirty-one patients were contacted from one to 4 1/2 years from initial assessment. Significant weight loss of greater than 9 kg (20 lb) occurred in more than half the patients, and of greater than 40 lb in one-third of patients over the study period. A PSMF for weight reduction, accompanied by instruction in behaviour modification, nutrition, and exercise for maintenance of weight loss may be helpful in the management of obesity.


Physical training in the treatment of obesity. Physical training is useful as a therapeutic means to obtain a decrease in body fat. The success in terms of lost fat is dependent on the ability to adhere to the programme, and probably also on regulatory factors associated with the degree of filling of adipose tissue (adipocyte volume). The rate of weight loss is usually slower than with dietary treatment but physical exercise may be more successful and less uncomfortable in the long run as a means to lose weight and prevent regaining it. Physical training is also effective against the metabolic complications associated with obesity such as decreased glucose tolerance, hyperinsulinemia and hypertriglyceridemia and should therefore be a method of choice to prevent or treat adult onset diabetes mellitus and endogenous hypertriglyceridemia in obesity. The feasibility of training in different groups of subjects seems to be dependent on, among other factors, selection of subjects and design of the training programme.


Jejunoileal bypass in the treatment of morbid obesity. Dietary management of morbid obesity has been uniformally unsuccessful. although abdominal surgery is a drastic therapeutic modality, it may offer the only hope for many morbidly obese patients. In addition to producing weight loss in the vast majority of patients, metabolic complications of obesity have been markedly improved in the post-operative period. Metabolic complications of the procedure are many and varied, but in certain high risk patients the benefits may outweigh the risks.


Gastric bypass for obesity after ten years experience. Over 625 patients having gastric bypass for the treatment of morbid obesity are currently being followed at the University of Iowa. Many innovations have increased operative exposure, greatly reduced operating time, and improved the effectiveness and safety of the operation. Recent weight figures show that a 55 percent loss of excess weight can be expected. Several comparative studies between gastric and jejunoileal bypass show that gastric bypass, while producing identical weight loss, has few of the many complications such as liver failure, renal and gallstone formation, diarrhea, enteritis, that are commonly associated with jejunoileal bypass. Stomal ulcer occurrence has been only 2 percent. Imporvements in diabetes mellitus and hypertension can be expected with weight loss. Other effects of gastric bypass were determined by use of a questionnaire. It is concluded, by surgeons having experience with both gastric and jejunoileal bypass, that gastric bypass is the treatment of choice for morbid obesity when nonoperative measures fail.


The management of hypertension associated with obesity. For the past several decades, treatment of primary hypertension has relied chiefly upon the use of pharmacologic agents. Many hypertensive patients are obese. Evidence is accumulating that their hypertension may be reversed by aggressive and comprehensive regimens for weight reduction. Controlled studies are needed to determine whether there may be particular subtypes of obesity which respond more favorably to such management and to evaluate the long-term benefits of the dietary approach.


Some correlates of the maintenance of weight lost through behavior modification. Using a mail and in-class distributed survey, data were collected from 721 members of Weight Watchers classes some 15 months after they reached their goal weights. The group averaged 73.2 kg (162.1 lb) before losing 19.0 percent of their body weight to reach goal weights averaging 59.6 kg (131.2 lb) in an average of 31 weeks. Fifteen months after reaching goal, 24.6 percent were below goal, 28.9 were within 5 percent of their goal, 17.5 percent were from 6--10 percent above their goal and 28.9 percent were 11 percent or more above goal. Those who maintained their goal weight, as opposed to those who regained, tended to have several things in common: they attended classes after reaching goal weight in the same locations and with the same lecturers that assissted their weight loss; they had lower initial weights: they conceived of themselves as 'overweight' when they were approximately three pounds above goal; they had improved self-concepts; they made more lifestyle changes supporting weight maintenance; and they continued, after goal, use of many of the techniques used to reach goal weight. Each of these factors has implications for planning for more programs designed to produce more lasting weight losses.


Behavioral treatment of obesity: the current status. The introduction of a behavioral approach to the treatment of obesity ten years ago stimulated a large amount of research and clinical application, and has had an influence upon  psychological treatment far beyond the field of obesity. This research has demonstrated that behavior therapy represents a significant improvement over traditional methods of treatment of mild and moderate obesity. Furthermore, ten years of investigation have introduced into psychological treatment research designs and a methodological sophistication without precedent in this field. Although behavior therapy has advanced the treatment of obesity, its results are still of limited clinical significance. Weight losses have been modest and the variability in results large and unexplained even long-term maintenance of weight loss, which, it was originally hoped, would be a particular benefit of the behavioral approach, has not yet been established. On possibility of increasing the effectiveness of behavioral treatments is to combine them with other measures--dietary and pharmacological. Three recent efforts at combining treatments show promise.


Definition, measurement, and classification of the syndromes of obesity. The definition and risks of obesity have been reviewed and a nomogram provided for reference. Organization of information about the syndromes of obesity has been approached from several points of view. An anatomic classification has been developed, in which generalized and localized forms of fat accumulation can be separated. Hypercellularity of the adipose tissue in the childhood-onset forms of obesity is usually, but not always, present. Etiologic mechanisms are also useful in classifying obesity. This nosologic approach has been derived largely from experimental studies but has contributed significantly to understanding of pathogenetic mechanisms in man. Hypothalamic obesity is now thought to result from augmented secretion of insulin. The recessively inherited forms of obesity, on the other hand, appear to result from loss of a thermogenic system involving the ouabain-suppressible thyroid-induced (Na+ + K+) -ATPase which, in turn, accounts for the myriad of defects in these animals. Techniques of cybernetic engineering provide a third approach to classification of the syndromes of obesity. The control of body fat was analyzed as an analogy to the control of temperature in a building. These various approaches, and the new insights which they have provided for understanding the syndromes of obesity, promise to provide new pathways for pharmacologic intervention in the treatment of this problem.


Side reactions in peptide synthesis. VI. A reexamination of the benzyl group in the protection of the side chains of tyrosine and aspartic acid. The acid catalyzed O leads to C migration of the benzyl group in the side chain of tyrosine could be reduced by applying HBr in a mixture of phenol and p-cresol instead of BHr in trifluoroacetic acid for acidolytic deprotection. This side reaction occurs also during the removal of Boc groups. The loss of O-benzyl protection and the formation of 3-benzyltyrosine residues could be suppressed by the application of a 7:3 mixture of trifluoroacetic acid and acetic acid. The acid- and base-catalyzed ring closure of beta-benzylaspartyl residues to aminosuccinyl derivatives was also studied. In this case HBr in trifluoroacetic acid was found to be relatively harmless. Deprotection with HBr in a mixture of trifluoroacetic acid and p-cresol can be applied for peptides that contain both beta-benzylaspartyl and O-benzyltyrosyl residues. An attempt to reduce the rate of the base-catalyzed side reaction by application of hindered tertiary amines was abandoned because the tertiary amines which were effective in this respect let to significant reduction of the rate of the desired reaction, the aminolysis of active esters, as well. A satisfactory solution for the problem was found in the selective catalysis of the active ester reaction with 1-hydroxybenzotriazole or 4-dimethyl-aminopyridine. These catalysts do not enhance the rate of ring closure and in their presence essentially pure beta-benzylaspartyl peptides can be produced in good yield.


Side reactions in peptide synthesis. VII. Sequence dependence in the formation of aminosuccinyl derivatives from beta-benzyl-aspartyl peptides. The base catalyzed ring closure in t-Boc-Asp-X beta-napthylamides was examined in a series of 2-peptide derivatives in which position X was occupied by the neutral and acidic amino acid residues that occur in proteins. Bulkiness and functional groups in the side chain of X have a major effect on the rate of cyclization, e.g. acidic groups slow down the formation of aminosuccinyl derivatives. Rate-enhancing effect can be observed in serine and threonine, while the side reaction is unexpectedly slow when X is methionine.


Benzyloxycarbonylarginine nitrophenyl ester salts: 1-hydroxybenzotriazole catalyzed acylations of amines. Benzyloxycarbonylarginine p-nitrophenyl ester has been prepared by the p-nitrophenyltrifluoroacetate method. The p-nitrophenyl ester derivative was isolated as its crystalline picrate and nitrate salts. The ester salts couple with amino compounds in the presence of 1-hydroxybenzotriazole, but decompose without acylation of amines in the absence of the 1-hydroxybenzotriazole catalyst. Benzyloxycarbonylarginine p-nitrophenyl ester and other activated esters of N-a-sustituted arginine salts may be useful reagents for introduction of trypsin-labile protecting groups into peptide fragments for purpose of polypeptide semi-synthesis. At the same time, side reactions of such carboxyl-activated arginine derivatives may serve as models for side reactions in the couplings of peptide fragments with arginine residues in the carboxyl-terminal position. Peptide fragment couplings of this type may frequently be encountered in semisynthesis of polypeptides from tryptic fragments.


Coacervation properties in sequential polypeptide models of elastin. Synthesis of H-(Ala-Pro-Gly-Gly)n-Val-OMe and H-(Ala-Pro-Gly-Val-Gly)n-Val-OMe. Syntheses of two sequential polypeptides H-(Ala-Pro-Gly-Gly)n-Val-OMe and H-(Ala-Pro-Gly-Val-Gly)n-Val-OMe via the p-nitrophenyl active ester procedure are reported. The two polymers were obtained in good yields and the polymers were shown to be of large molecular weights, n greater than 40. These two polypeptides were synthesized as analogs of the two coacervating sequential polypeptides H-(Val-Pro-Gly-Gly)n-Val-OMe, and H-(Val-Pro-Gly-Val-Gly)n-Val-OMe, in which the Val-l residue is replaced by an Ala-l residue. H-(Ala-Pro-Gly-Gly)n-Val-OMe did not coacervate even at as high a temperature as 100 degrees, and H-(Ala-Pro-Gly-Val-Gly)n-Val-OMe did not coacervate; however, it precipitated irreversibly around 65--70 degrees C. This suggests the critical role of the Val-Pro hydrophobic side chain interaction in coacervation.


Purification and characterization of the surface active proteins of black gram (Phaseolus mungo). The surface active globulin from black gram has been resolved into two components with high foam-forming activity. They were found to be homogeneous by electrophoresis and ultracentrifugal examinations and had high molecular weights around 100,000 daltons. They were rich in acidic as well basic amino acids but low in sulphur amino acids. Heat treatment, proteolysis and treatment with certain inorganic salts such as copper, and mercurous mercury, group specific reagents P-chloromercury benzoate and N-ethylmalemide (PCMB, NEM) and protein denaturants were found to have an adverse effect, while oxidizing agents had no effect. The free sulphydryl content was low (3 and 4 mumol/mol), but essential for full manifestation of surface activity. Other purified proteins also needed free sulphydryl groups.


Sorghum proteinase inhibitors: purification and some biochemical properties. An investigation has been carried out on the proteinase inhibitors of grain sorghum (Sorghum bicolor (L.) Moench). One of the inhibitors has been isolated in a pure form and characterized. The proteinase inhibitor was extracted from the acetone-defatted sorghum meal and purified by selective thermal denaturation, ammonium sulfate fractionation, Sephadex gel filtration and DEAE-cellulose chromatography (DEAE-preparation II). This preparation was demonstrated to be a mixture of three inhibitor components by polyacrylamide disc gel electrophoresis. Further resolution of this mixture into Inhibitors I to III was achieved by QAE-Sephadex chromatography. Sorghum Inhibitor III was homogeneous by the criteria of disc gel electrophoresis and has been more fully characterized. A molecular weight of 25,000 was obtained for Inhibitor III by gel filtration and was in agreement with the value calculated from the amino acid composition of the inhibitor. The N-terminal amino acid residue of Inhibitor III, a single chain protein, was isoleucine. Sorghum proteinase inhibitors inhibit specifically the serine proteinases and are inactive towards the other classes of proteinases. Inhibitor III is primarily a chymotrypsin inhibitor, whereas Inhibitors I and II inhibit both trypsin and chymotrypsin.


Syntheses of monocyclic and bicyclic peptides of tryptathionine and glycine. L-3a-Hydroxy-1.2.3.3a.8.8a-hexahydropyrrolo [2,3-b-]-indole-2-carboxylic acid (Hpi), obtained from L-tryptophan by oxidation with peroxyacetic acid (Savige, 1975), after introduction of the Boc-residue at N-1, is coupled with various glycine peptides of S-trityl-L-cysteine to give the Hpi-peptides 6(a-f). By treatment with absolute trifluoroacetic acid these peptides are converted by an intramolecular thiolysis to the monocyclic thioethers 7(a-f). Two of them, 7e and 7f, can be subjected to a second cyclization by the mixed anhydride method thus yielding the bicyclic tryptathionine heptapeptide 8e and octapeptide 8f. In their structures the bicyclic molecules resemble the mushroom phallotoxins and amatoxins, respectively. They show CD spectra closely related to the naturally occurring bicyclic peptides thus indicating conformational similarities. The CD spectra of the other cyclic peptides synthesized are also presented and discussed.


Inhibition of thrombin and trypsin by tripeptide aldehydes. Inhibitory effects of certain tripeptide aldehydes on both thrombin and trypsin have been found to be strongly substrate-dependent. These compounds should therefore be considered as inhibitors of the particular proteolytic reaction for which they had been designed rather than real enzyme inhibitors, i.e. protein or polypeptide proteinase inhibitors of natural origin.


The need for co-ordination of research in nutrition. On two assumptions, first that the number of dietarily essential nutrients for Man and the common monogastric mammals is 40 and, second, that the effects of at least two dietary levels of each nutrient would have to be examined in order to cover the possible nutrient interactions, then 2(40), or approximately 10(12) diets would need to be prepared. This number is beyond human capacity within any reasonable period of time: moreover, it assumes constancy of the non-essential part of the diet. Very few of the possible nutrient interactions have been studied and, as a supplement to piecemeal studies by individual workers, a co-ordinated research programme is desirable. It is noted that, while considerable attention has been paid to the nutrition of growth, the adult stage has been very neglected: the status of adult man in particular calls for attention. Factors concerned in the planning of co-ordinated research are briefly discussed.


Pancreatic exocrine function in rats with severe retinol deficiency. Starting from the fact that extensive retinol deficiency leads to morphological pancreatic alterations, the secretion of the gland and the specific enzyme activities in the pancreatic tissue were studied in rats fed a retinol-free diet for 70 days. No clear alteration of the exogen stimulated pancreatic secretion and of the enzyme content of the gland was observed.


The effect of medium-chain triglycerides on the bioavailability of vitamin E. Overnight fasted, normal rats were fed a single dose of isotopically labeled vitamin E emulsified in either medium-chain or long-chain triglyceride (MCT or LCT). The animals were sacrificed at various time intervals of up to 72 hours. Levels of radioactivity in the small intestinal wall, liver, plasma, skeletal muscle and adipose tissue were higher in animals in which tocopherol was administered in MCT rather than LCT. Thus, the intestinal absorption of vitamin E was enhanced by solubilization in MCT. These findings are consistent with the theory that the gastrointestinal absorption of dietary tocopherol is dependent upon the simultaneous  digestion and absorption of the fat in which the vitamin is solubilized.


Inhibition of platelet aggregation by alpha-tocopherol and its nicotinate and acetate esters. Two esters of vitamin E, dl-a-tocopheryl nicotinate and dl-a-tocopheryl acetate were found to be more inhibitors than tocopherol itself on platelet aggregation induced by arachidonic acid and collagen. The nicotinate was 1--5 times more potent than the acetate and 2--18 times more potent than the unesterified tocopherol in inhibiting collagen induced aggregation in human citratet platelet-rich plasma.


Resolution of the initial phase controversy in the thiamine-polyphenol reaction. The kinetics of interactions between thiamine and seven polyphenols were followed by two types of thiochrome assays. The assays on the reaction mixture showed the extremely rapid initial phase whereas those on the eluate of the mixture previously treated by the Decalso column did not. The former assay methods also produced higher estimates of thiamine modification than the latter over the period of 3 hours of reaction. Arguments are given to show the probable non-existence of the observed extremely rapid initial phase. Reinterpretation of some past results are also presented.


Studies on metabolism of thiamine chloride ester monophosphate of bis-D-glucosamine. II. Effect of TCMPG in vitamin B1-deficient rats. In order to investigate the metabolism of thiamine chloride ester monophosphate of bis-D-glucosamine (TCMPG) urinary excretion, blood levels and tissue content of thiamine in vitamin B1-deficient rats were measured after intraperitoneal injection of this compound or of thiamine monophosphate or of a mixture of thiamine monophosphate and glucosamine. The greater retention and the higher levels of vitamin observed in the blood and in the tissues of animals treated with TCMPG compared with the control rats confirm the hypothesis that a more efficient utilization of vitamin B1 is obtained by the organism when it is administered salified with glucosamine.


Vitamin C status of institutionalised and non-institutionalised aged. The vitamin C status of 186 elderly subjects living at home and institutionalised in hospital, residential accommodation and sheltered dwelling was studied. Subjects from hospital and home receiving multivitamin supplements regularly were grouped separately. Ascorbic acid deficiency (plasma ascorbic acid less than or equal to 0.3 mg/100 ml) was noted in 47.2, 39.0, 46.2 and 47.4 per cent subjects of home, hospital, residential accommodation and sheltered dwelling, respectively. All subjects receiving multi-vitamin had plasma ascorbic acid (PAA) levels greater than or equal to 0.3 mg/100 ml. The mean levels of PAA appeared higher in females than males and the percentage incidence of low vitamin C status was higher in males than females in the majority of the groups. Leucocyte ascorbic acid (LAA) levels were measured in only 26 subjects of residential accommodation and of these 38.5 per cent had low LAA levels (less than 15 microgram/10(8) cells). The biochemical vitamin C deficiency was not accompanied by any recognised clinical manifestation.


The degradation of tryptophan in severe liver disease. Patients with severe acute or chronic liver disease were found to have a high mean plasma free tryptophan, an abnormal urinary excretion pattern of tryptophan-kynurenine metabolites and low circulating levels of the vitamins required for tryptophan degradation, i.e. pyridoxine, thiamine and ascorbic acid. In patients with decompensated chronic liver disease (DCLD), ineffective vitamin B6(pyridoxine hydrochloride) supplementation with effective thiamine and ascorbic acid supplementation increased urinary 3-hydroxykynurenine, 3-hydroxyanthranilic acid and xanthurenic acid excretion. Effective B6(pyridoxal phosphate) supplementation did not cause a similar change. It is postulated that the combination of increased input into the pathway together with vitamin B6 deficiency may explain the abnormal tryptophan-kynurenine pathway in severe liver disease. Imbalanced or ineffective vitamin supplementation may aggravate the disturbance of tryptophan degradation.


Effect of enzyme combination and dialysis on amino acid patterns released from proteins. Different combinations of gastrointestinal enzymes and dialysis altered amino acid yield and patterns released from proteins but did not negate the "variable ratio effect". That is, as substrate was increased relative to enzymes some amino acids increased, others decreased while still others were unchanged as a function of total quantity released. None of the enzymatic treatments degraded proteins proportional to amino acid composition.


Visual scanning, pattern recognition and decision-making in pulmonary nodule detection. Eye movements were recorded while four subjects searched a set of 60 films, 24 normal and 36 abnormal for pulmonary nodules. Error rates, scanning patterns and the dwell time of fixation clusters on normal and nodule-containing areas of the film were studied. Using the assumption that prolonged dwell time indicates intensive processing of visual data, a model was developed for nodule detection that includes four steps: orientation, scanning, pattern recognition and decision-making. False-negative errors were divided into three classes: scanning errors, recognition errors and decision-making errors. Of 20 false-negative errors, 30% were considered scanning, 25% recognition and 45% decision-making.


Intervertebral disc abnormalities associated with vertebral metastasis: observations in patients and cadavers with prostatic cancer. Abnormalities of intervertebral discs associated with vertebral metastasis from prostatic carcinoma are described in an investigation utilizing patient and cadaveric material. Radiographic and pathologic findings indicate that discal abnormality in this situation relates to three potential processes: intervertebral disc degeneration (intervertebral osteochondrosis); cartilaginous (Schmorl's) nodes; discal invasion by tumor. In most patients with vertebral metastasis, the adjacent intervertebral disc appears normal, a useful radiographic finding suggesting the presence of tumor rather than infection. Occasional patients with vertebral metastasis demonstrate roentgen abnormalities of the adjacent intervertebral disc indicating the occurrence of one or more of the above processes.


A simple method to measure mesenteric arteriovenous shunt flow during arteriography. A quantitative method for external detection of mesenteric arteriovenous shunts was developed. 99mTc-Human Serum Albumin Microspheres (15--30 microns) were injected into the superior mesenteric artery of dogs through an angiographic catheter, followed by external scintillation counting of the liver activity, which represented the shunted spheres. Thereafter, 99mTc-sulfur colloid was injected identically and the liver activity counted again. The liver net count after sulfur colloid represented a 100% shunt, when a correction factor for the actual liver uptake was applied. The a shunt rate was calculated. Eleven animal studies were performed and shunt rates similar to previous in vitro determinations were obtained. This method is suitable for clinical investigation and can conveniently be applied to mesenteric arteriography.


A proposed mechanism for transient increases in arterial pressure and flow during angiographic injections. In a series of animal experiments, we have confirmed the observation that arterial pressure and flow increase distal to the injection site during power injections through non-obstructing catheters. Our data suggest that the phenomenon is secondary to the transient production of turbulence. Thus, for a given injection rate, catheters with smaller end holes create more fluid velocity, which increases the Reynolds number and causes augmentation of downstream pressure and flow. The addition of side holes decreases the fluid velocity of the injectate and minimizes the hemodynamic effects. The discussion deals with factors contributing to the generation of local turbulence, the magnitude of pressure and flow changes caused by the injections, and the clinical implications of these artifacts.


Transcatheter embolization with microfibrillar collagen in swine. Transcatheter embolization of the gastrosplenic and renal arteries was performed in 7 domestic swine with suspensions of microfibrillar collagen (MFC), a recently developed topical hemostatic agent. Embolized vessels remained occluded 2 days following embolization. Recanalization occurred by 14 days, although some occlusion in distal vessel persisted at 3 months. Pathologically a marked granulomatous arteritis was noted at 14 days which resolved by 3 months. Gastric ulcers or infarcts were present in two animals. The severe vasculitis and gastric pathology observed with MFC in this study would seem to preclude its use as a general embolic agent. It may be useful, however, in the preoperative embolization of neoplasms, especially in pediatric patients since its physical characteristics allow it to be easily injected through small diameter catheters.


Clinical application of Compton and photo-electric reconstruction in computed tomography: preliminary results. Although computed tomography has demonstrated some promise in the direction of quantative radiology, valuable information related to the varying response of tissues to x-rays of different energy is still not utilized on a routine basis. Advancements in a method proposed by Alvarez and Macovski for decomposing dual-spectra CT projection data into its material-dependent Compton and photo-electric components are described. Results are presented to demonstrate that such a separation can be performed. Reconstructed images of separated Compton and photo-electric data obtained from clinical scans are shown. With the improvements described, the Compton images begin to approach the quality of conventional reconstructions with evidence of improved polychromatic correction. The photo-electric data, while separable, suffers from unacceptable noise level. Analysis of this difficulty is presented, with recommendations for future improvement by careful selection of the effective energy of the low energy spectrum. The encouraging results suggest that this technique warrants continued development and evaluation.


Imaging characteristics of a small germanium camera. A high purity germanium gamma-camera has been developed and is currently being evaluated. This camera incorporates unique performance parameters such as a 2 mm full-width spatial response function with rejection of multiple-scatter in the detector, a 2.2% FWHM energy resolution for 99 mTc, a 180 nsec paralyzable dead-time, and a 2 mu sec non-paralyzable dead-time. Imaging studies demonstrate the superior capabilities of this instrument.


Renal cell carcinoma: two new cell lines and a serially transplantable nude mouse tumor (NC 65). Preliminary report. Two long-term tissue culture cell lines and a serially transplantable tumor line growing on nude mice were obtained from a renal cell adenocarcinoma (NC 65). Results of the preliminary characterization of these tumor lines are presented. These data include tumor and cell morphology and growth characteristics in vivo and in vitro. In the nude mouse the tumor matastases to axillary and inguinal lymph nodes. The slow growth rates in culture and in the nude mice as well as the maintenance of the original histologic picture indicate that this tumor still reflects properties of the original carcinoma. Chromosomal analysis proves the human origin of the cell lines.


Internal ureteropexy: a simple technique to prevent reflux after ureteroneocystostomy. An experimental study in dogs showed that the implantation of hydroureters onto a denuded area of the bladder muscle led to mucosal regeneration and formation of a submucosal tunnel. Reflux was prevented in all animals when the bladder wall was immobilized at the reimplantation site by fixation to the psoas muscle. Urinary stasis normalized after 10 to 12 reimplantations. Internal ureteropexy would seem to be a most simple and satisfactory technique for preventing reflux when dissection of a submucosal tunnel fails in ureteroneocystostomy. It has been used in three patients with good results.


ECG changes and arrhythmias induced by ionic and non-ionic contrast media during coronary arteriography in dogs. Metrizamide (non-ionic, Nyegaard Co., Oslo, Norway), diatrizoate (ionic) and metrizoate (ionic) were selectively injected into the right or the left canine coronary artery. ECG was recorded and external defibrillation was performed whenever ventricular fibrillation occurred. During left coronary injections metrizamide prolonged the PQ and QT intervals less than did the diatrizoate. During right coronary injections metrizamide affected the QT interval less than either diatrizoate and metrizoate. During right coronary infusions metrizamide caused significantly fewer incidences of ventricular fibrillation than diatrizoate. In clinical coronary arteriography it is assumed that metrizamide would generate fewer AV blocks than diatrizoate and fewer incidences of ventricular fibrillation after right coronary injections than diatrizoate. Changes in the PQ and QT intervals during coronary arteriography can be used as tests to predict the safety of new contrast media.


Reduction in ventricular fibrillation using calcium-enriched Renografin 76. Renografin 76 has been shown to have significant calcium-binding properties in vivo and in vitro. Two contrast media solutions were compared by selective injection into the right coronary artery of dogs. One set of injections was made with commercially available Renografin 76 (referred to as stock Renografin) and another set of injections was made with Renografin 76 to which had been added 24 mMols/liter of calcium chloride dihydrate. Ventricular fibrillation occurred significantly more often with the stock Renografin 76. The nature of the calcium binding and its effects are discussed.


Adrenergic innervation of the ureter.

Adrenergic innervation of the ureter. To determine whether the ureter is innervated by the autonomic nervous system, isolated canine ureters were superfused with modified Tyrode solution, and force developed in response to 100-msec duration stimuli at a rate of 3 per min was monitored. Norepinephrine and phenylephrine significantly increased developed force; the latter more than the former. These increases in developed force were blocked by phentolamine, and propranolol enhanced the stimulatory effect of norepinephrine. In the presence of phentolamine, norepinephrine significantly decreased developed force. Isoproterenol significantly decreased developed force and this significant decrease in contractility was not observed in the presence of propranolol. High intensity, high frequency, short duration stimuli which in themselves were unable to excite quiescent rabbit and canine ureteral segments potentiated contractile force of segments contracting at the basal rate of 3 per min in response to long duration stimuli. When these same high intensity, high frequency, short duration stimuli were applied to ureteral segments pretreated with phentolamine, the developed force of the basally driven preparations decreased. These data suggest the presence of alpha-stimulatory and beta-inhibitory adrenergic receptors in canine and rabbit ureter and provide evidence for adrenergic tissue within the wall of the ureter that can influence contractile force.


Lymph and intrarenal venous blood as indicators of canine renal cortical function. Samplings of canine capsular and hilar lymph, and intrarenal venous blood were investigated as in vivo techniques for detecting renal cortical function in control and NH4Cl pretreated anesthetized animals. The glucose concentration of capsular, but not hilar, lymph was indicative of cortical drainage in both groups. When lymph flow was increased by elevating renal venous pressure, capsular lymph glucose concentration reflected cortical function only in the NH4Cl animals. The glucose concentration of intrarenal venous blood indicated cortical drainage in both the control and NH4Cl animals but the cortical function of a high para-aminohippuric acid extraction was only detectable in the NH4Cl group. Conclusions are that sampling of capsular lymph and intrarenal venous blood may prove to be useful techniques for studying certain in vivo cortical functions but the intrarenal venous technique is less sensitive than capsular lymph collection.


Observation on the metabolism of iopanoyl (Telepaque) glucuronide in dogs treated with antibiotics. The purpose of our investigation was to determine whether iopanoyl glucuronide, the major metabolite of iopanoic acid (Telepaque), undergoes hydrolysis by bacterial beta-glucuronidase in dogs. The conjugated compound was identified and quantitated by elemental analysis, fluorescent excitation analysis, thin-layer chromatography, and high pressure liquid chromatography. The experiments were performed before and after combined antibiotic treatment with neomycin and vancomycin. It was first determined that reabsorption and excretion of sodium iopanoate was only minimally diminished during antibiotic treatment. Known amounts of iopanoyl glucuronide were infused into the small bowel of 4 awake dogs with chronic bile fistula, and bile was collected for 5--8 hours. The excretion of the recirculated conjugated compound was 4--5 times lower during antibiotic treatment.  Incubation of ileal fluid with bile containing iopanoyl glucuronide suggested that beta-glucuronidase hydrolyzes the conjugated compound. Hydrolysis was markedly decreased after pretreatment with antibiotics. These findings suggest that the beta-glucuronidase produced by bacteria may be a major mechanism in enterohepatic recirculation of iopanoyl glucuronide. Mechanisms and possible implications are discussed.


The development of a test system for inhibition of urinary oxalate lithiasis. The production of calcium oxalate deposits on zinc pellets in the bladder of rats was induced by the addition of 0.25 to 1.0 per cent ethylene glycol to their drinking water. Sprague Dawley rats requied more than 0.50 per cent ethylene glycol to produce calcium oxalate exclusively. The quantity of deposits varied widely between test animals, but intermediate operation to check on the amount of deposit showed that each rat at the 0.75 per cent ethylene glycol level maintained its individual rate of deposition within an acceptable standard deviation relative to the mean. At 1 per cent ethylene glycol deposition in the kidneys interfered with deposition on the zinc pellet.


Nephrotoxicity of sodium iopanoate in hydrated and dehydrated dogs. The nephrotoxic effect of sodium iopanoate, infused intravenously in dosages of 1.5, 3 and 6 g over a 2-hour period in eight dogs (22--27 kg) in both the hydrated and dehydrated stages, were investigated. On biochemical, hemodynamic and morphological studies, the nephrotoxic effect was found to be clearly dose-dependent and greater in the dehydrated stage. Previously suggested mechanisms for acute renal failure, such as a direct tubular toxicity, tubular obstruction and hypotension, could not be supported as main factors in the development of acute renal failure post-cholecystography, although they might well have a contributory effect. The primary cause of renal failure post-cholecystography cannot be determined unequivocally from this investigation. However, the observed findings would appear to be consistent with a toxic effect of iopanoate in the small vessels possibly resulting in ischemic tubular necrosis.


Transvenous perfusion cooling of the kidney: a new technique of local renal hypothermia. In an experimental study involving ten dogs, the feasibility of transvenous perfusion cooling of the kidney is proven. The theoretical basis of this new method of regional renal hypothermia is presented; the technique is easy to perform and requires cannulation of the renal vein. The perfusate leaves the kidney either via the capsular veins which have been divided during renal exposure, or through the proposed nephrotomy. Renal vein thrombosis or tearing of the venous vasculature was not observed. The only complication encountered in one instance was hemorrhage from the puncture site of the renal vein.


Transport efficiency of ureteral peristalsis correlated to pacemaker activity of renal pelvis. The transport efficiency of ureteral peristalsis under the control of the pacemaker was examined during renal pelvic perfusion in dogs. Simultaneous recordings of the perfusion rate, renal pelvic pressure, ureteral electromyogram, and bolus volume were made during each period of perfusion at a constant rate. For a graphic representation of transport efficiency of each peristaltic contraction, changes in balance level between the perfusion rate and the bolus volume were registered by a presettable binary counter. A quantitative evaluation of transport efficiency was also made of each group of peristaltic contractions that was classified by its characteristic distribution of the interperistaltic internal. The pacemaker activity of the renal pelvis and its control of ureteral peristalsis were identified in this preparation. Most of the peristaltic contractions excreted the same volume of fluid that had entered the pelviureteral system during the preceding period of nonperistalsis within the range of studied perfusion rates. The transport efficiency defined as interperistaltic interval x perfusion rate/bolus volume showed a small variation around the value 1 for peristaltic contractions in each group.


Protein electrophoretic patterns of canine prostatic fluid. Effect of hormonal manipulation. The effects of castration and estrogen administration on prostatic fluid proteins were compared in two groups of dogs. Prostatic fistulae were created in 10 animals and prostatic fluid secretions stimulated by electroejaculation. After a stabilization period, five animals were administered polyestradiol phosphate and the remaining five were castrated. After 3 months estrogen administration was discontinued and depo-testosterone was administered to the castrate animals. Fluids were collected at weekly intervals throughout the study and prostatic fluid proteins separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. No difference between animal receiving estrogen and castrated animals was noted and administration of testosterone to castrate animals reestablished a normal protein pattern.


Sex steroid imprinting of the immature prostate. Long-term effects. New periods of sex hormone sensitivity in the life cycle of the male rat that occur before the onset of sexual maturation and that determine subsequent responsiveness and growth of the adult prostate have been elucidated. If high doses of estrogen (17 beta-estradiol--500 microgram per day, or estradiol benzoate--250 micrograms per day, or estradiol dipropionate--100 micrograms per day) are administered to intact male rats for 2 days during the 1st week after birth, the prostate, at adulthood, is diminutive in size and is inert to the action of exogenous androgens. In contrast, lower doses of estrogen (17 beta estradiol--100 micrograms per day) administered at 20 and 22 days of age enhance the sensitivity of the adult prostate to testosterone by approximately 50 per cent. Furthermore, it has been determined that continued testicular function is required up to the time of puberty for full prostatic growth.


Enhancement of renal excretion of uric acid during long-term thiazide therapy. The effect of thiazide (hydrochlorothiazide 100 mg per day orally in two divided doses for up to 3 years) on uric acid metabolism was examined in 21 patients with renal stones suffering from renal hypercalciuria or absorptive hypercalciuria. Serum concentration of uric acid increased during thiazide therapy in every patient. In 12 of 21 patients, there was a transient or persistent rise in urinary uric acid of more than 50 mg per day during treatment. The mean urinary uric acid produced by thiazide was positively correlated with the change in the renal clearance of uric acid. Thus, an increase in urinary uric acid was often associated with a rise in uric acid clearance. The results suggest that thiazide may either increase the production of uric acid or decrease the extrarenal disposal of uric acid, in some patients.


Quantitaion of collagen in the wall of contracted schistosomal bladder. Biochemical assay of vesical collagen was carried out in six cases of contracted schistosomal bladders and five controls. It revealed 11.52 and 9.56 per cent of collagen by weight respectively. Detrusor myopathy seems to be more important than fibrosis. Quantitation of the muscle mass in these cases is needed.


Collagen in 155 human bladders.

Collagen in 155 human bladders. The percentage of bladder collagen, as obtained by the dosage of hydroxyproline, was determined in autopsy specimens from 48 female and 107 male cadavers. The average percentage of collagen in the human bladder is 57.4 per cent (+/- 9) of the dry weight of insoluble protein. There is good correlation (r = 0.55) between detrusor and trigone collagen content. There is no significant difference between pre- and postpuberty age groups in relative collagen content. In females more than 50 years of age there is a significant increase in collagen.


In vivo smooth muscle function in normal and obstructed rabbit vas deferens. We characterized smooth muscle function in the rabbit vas deferens in vivo by means of a new strainometer. Intraluminal pressure was measured and smooth muscle tension in the wall was calculated. Our studies revealed a low baseline pressure, no spontaneous contractions, and a constant wall tension. Studies of the effect of vasectomy on in vivo smooth muscle function showed increased intraluminal pressure, diameter, and baseline wall tension, and development of spontaneous contractions with increased wall tension, intraluminal pressure, and diameter with each contraction.


Response of the rabbit vas deferens in vivo to vasoactive drugs. We evaluated the smooth muscle response to the systemic administration of various vasoactive drugs and hormones in vivo in the rabbit vas deferens. Norepinephrine, epinephrine, and urecholine caused contractions of the vas deferens that caused it to shorten and thicken. Isuprel inhibited contractions that were initiated by obstruction of the vas deferens. Catecholamine depletion from guanethidine caused dilation of the vas deferens, increased intraluminal pressures spontaneous contractions, and a spermpacked lumen. The vas deferens in the immature rabbit showed normal response to norepinephrine and obstruction. Estrogen administration prevented the normal dilation and increased peristalsis observed with obstruction.


Cutaneous tubeless ureterostomy as a procedure to study renal function in conscious dogs. We describe the results obtained with a modified technique for single-side cutaneous ureterostomy in awake mongrel dogs. The success of this surgical procedure was evaluated by intravenous pyelography and urinary cultures that ruled out infection. In addition, we investigated the effects of this procedure on the excretory capacity of the kidney with a diverted ureter. Average values for effective renal plasma flow and glomerular filtration rate were comparable to those obtained in the literature and in the constralateral untouched kidney of the same dogs. The results indicate that cutaneous ureterostomy can be used successfully to monitor renal function in awake dogs over periods of weeks or months.


Experimental assessment of graded ureteral obstruction utilizing liquid and gaseous perfusion techniques. Ureteral perfusion studies (Whitaker's test) utilizing both saline and carbon dioxide were performed in nonobstructed canine ureters and in ureters subjected to a standardized partial and high grade obstruction to characterize the pattern of pressure response. Three separate ranges of pressure elevation were identified with each perfusate and a high degree of correlation between saline and CO2 pressures was observed. However, a significant overlap between the pressure range for nonobstructed and partially obstructed ureters was noted. This overlap must be carefully considered in human studies before defining clinically significant obstruction on the basis of an absolute perfusion pressure value.


Histology and ultrastructure of the R-3327 C-F transplantable prostate tumor of Cophenhagen-Fisher rats. The R-3327 C-F tumor is an adenocarcinoma of the prostate maintained by serial transplantation in male Copenhagen-Fisher hybrid rats. The tumor is histologically different from other tumor sublines derived from the original R-3327 tumor discovered in 1961 in an aged Copenhagen rat. Light and electron microscopy have shown that the R-3327 C-F tumor contains a well organized glandular epithelium with myoepithelial cells and a continuous basement membrane, although epithelial cells were much less differentiated than epithelial cells of either dorsal or lateral normal prostate of the rat. Two features of interest were the presence of large, abnormal fibroblasts in stroma, and of lymphocytes embedded in the epithelium. Virus particles have not been observed in the specimens examined by electron microscopy.


The effects of vasectomy on the movement of 14C-urea in the seminiferous tubule of the hamster. 14C-urea entry into the hamster seminiferous tubule (SNT) and cauda epididymidal tubule was observed in intact males and in animals vasectomized for 2 weeks and for 4 months. 14C-urea entry rate and plateau level were significantly increased 4 months postvasectomy. 14C-urea entry into the cauda epididymidis was significantly altered 2 weeks postvasectomy. 2, 4,-dinitrophenol significantly increased 14C-urea concentration in the SNT. This is compatible with the presence of an outward directed energy dependent movement of urea in the hamster SNT. Increasing 14C-urea concentrations in the postvasectomy SNT may be attributable to a failure or inhibition of this physiologic activity.


Comparative polypeptide patterns of representative human and nonhuman adenoviruses. SDS-polyacrylamide slab gel analysis of selected primate and nonprimate adenoviruses has shown these viruses to differ significantly at the polypeptide molecular level. It follows that data derived from study of a single adenovirus serotype are unique to that serotype and are not representative of the adenovirus group as a whole.


[Results of incidence analyses in external hemorrhoids]. The perianal region of 294 healthy persons (151 male, 143 female) of different age was examined and the size, the localization and the number of the skin tags were registered. The frequency increases in women especially at the beginning of the second decade and in men especially at the fourth decade of life. 80% of all women and 60% of all men have skin tags. The size of the skin tag increases while the person becomes older. In the average women have bigger skin tags than men. Most of the skin tags are located in the region of 12 and 6 h lithotomy position.


[The testing of photochemotherapy in various dermatoses]. Experimental PUVA therapy in five different skin diseases showed excellent results in lichen planus and pityriasis lichenoides et varioliformis. Present experience indicates a favourable influence of PUVA also in pityriasis rubra pilaris and in lymphomatoid papulosis. In Darier's disease PUVA leads to acute exacerbation.


[Zinc-deficiency syndrome with acrodermatitis]. The symptoms of the zinc depletion syndrome are demonstrated in two males and two females. The four patients, 23 to 39 years old, were suffering from ileocolitis Crohn. After three to eight weeks of total parenteral nutrition they showed signs of acrodermatitis. Serum zinc was found considerably below normal levels (0,21--0,68 microgram/ml). After oral nutrition was re-initiated the dermatitis healed within four weeks without zinc oxid or zinc sulphate administration. Serum zinc increased to normal levels.


[Orthopedic problems of the lower extremities excluding the hips, in meningomyelocele]. Four types of problems relating to the lower limbs, hips excluded are reviewed in connection with myelomeningocele. These are essentially deformities and instability. Deformities follow three patterns: prenatal due to uterine pressure on paralyzed limbs, postnatal either postural or secondary to muscular imbalance. Various means of preventing these deformities are exposed. Lower limb stabilization by means of more or less extensive bracing according to the level of the initial lesion is described. Emphasis is put on early weight bearing and gait training in these patients. Problems of skin lesions and of spontaneous fractures are mentioned.


[The treatment of the feet in meningomyelocele]. Experiences in management of paralytic foot deformities in 30 children and adolescents with myelomeningoceles are reported. Suitable reconstruction of foot form can be achieved regularly with the help of early manipulation, walking plasters and orthopaedic surgery. However, the impairment of sensation remains unchanged. The polypropylene solid ankle orthosis has proved particularly useful for maintaining good weight-bearing abilities of the foot combined with partial load transfer to sensitive skin regions below the knee joint.


[Own experiences in the orthopedic treatment of meningomyelocele]. 30 myelomeningocele patients which were surveyed at Zurich's Children's Hospital and at the Wilhelm Schulthess Clinic in the years from 1962 to 1976 have been postexamined. Significant for the rehabilitation of these children in respect for the gaining of their best ever possible independence and capability to walk are primarily the neurosegmental level of the lesion, the remaining motor power as well as intelligence and motivation. Of secondary significance is the orthopaedic operation whereby specifically the correction of fixed deformity is important. The quantity of anesthesias should be hold at minimum, bilateral hip-dislocations can be left alone, and psoas-transfers (SHARRARD) should be made on children with strong quadriceps only.


[Hereditary angioneurotic edema. Clinical aspects, pathogenesis and therapy]. A family with hereditary angioedema is presented. In 4 members of the family the diagnosis was confirmed by decreased C1 esterase inhibitor levels. Clinical course and pathogenesis are described briefly. New ways of treatment are discussed, especially injection of purified C1 esterase inhibitor and stimulation of C1 esterase inhibitor synthesis by oral therapy with attenuated androgens.


[Juvenile pernicious anemia with congenital intrinsic factor deficiency and intermediate intrinsic factor secretion in the parents]. A 11 1/2-year-old girl of Turkish origin showed symptoms and signs of pernicious anaemia with low B12 level in blood but normal gastric acid secretion. There were no antibodies to mucosal cells or intrinsic factor. Quantitative determination of intrinsic factor in gastric juice, done by a RIA method, proved absence of the factor. Both parents had normal values for haemoglobin, normal B12-absorption tests and slightly decreased B12 blood levels. The gastric acid secretion was normal in both, but intrinsic factor in the gastric juice was decreased markedly. These findings support the hypothesis that congenital pernicious anaemia, e.g. congenital absence of intrinsic factor, is transmitted by an autosomal recessive trait.


Protein-losing enteropathy due to segmental erosive and ulcerative intestinal disease cured by limited resection of the bowel. Two children suffering from extensive intestinal protein loss due to subacute and chronic segmental small bowel disease are presented. In the first case a tentative diagnosis of chronic erosive and ulcerative non-granulomatous jejunitis as described in adults was made. The second child suffered from subacute erosive and ulcerative segmental transmural ileitis following mechanical ileus. In both instances resection of the involved segments of small intestine promptly cured the enteric protein loss. It is suggested that excessive protein loss due to subacute or chronic segmental erosive and ulcerative intestinal disease may be cured definitively by surgical resection. An explorative laparotomy should be performed if broad internistic investigations do not provide an explanation for the severe and prolonged enteric protein loss.


Hypophosphatemia and hyperparathyroidism in a case of Bartter's syndrome. In an 18-year-old boy with Bartter's syndrome, hypophosphatemia was discovered (2.4 mg/100 ml) with normal serum calcium concentration (9.7 mg/100 ml) and elevated alkaline phosphatase level: 528 mU/ml (normal less than or equal to 150). Skeleton X-rays showed osteomalacia on the pelvic bones and metaphyseal rickets on the wrists. Plasma 25-hydroxycholecalciferol (25-OHCC) concentration was 7.2 ng/ml (normal = 13 +/- 4.4), and serum immunoreactive parathyroid hormone (iPTH) concentration 160 micron1Eq/ml (normal less than or equal to 150). Ca infusion (1500 mg/m2/12 h) induced an increase in serum P level to 3.2 mg/100 ml, in tubular phosphate reabsorption from 72 to 90%, while serum iPTH decreased to 33 micron1Eq/ml. Vitamin D2 administration (45 mg) resulted in increased 25-OHCC concentration to 28 ng/ml and in healing of pelvic osteomalacia. However, there was little change of the radiological aspect of the wrist and of serum phosphorus and iPTH concentrations. In a control 6-year-old hypokalemic girl, administration of parathyroid hormone (8 USP/kg) produced a marked phosphaturic response and an increase in urinary cyclic AMP excretion. These data suggest that hypophosphatemia can be attributed to secondary hyperparathyroidism in the patient with Bartter's syndrome. Hypokalemia does not impair the renal activity of parathyroid hormone.


[Fatal outcome of retinoblastoma. Retrospective study of 22 patients]. 18 patients of 22 lethal cases of retinoblastoma died of recurrence or metastases of the primary tumor, which were mostly located in the head. Two clinical groups can be distinguished. In the patients with recurrence from the side of the enucleated eye, the mean survival time was 26 months, whereas the four children with a relaps originating in the conservatively treated eye survived 23 to 65 months. Two other children died of secondary tumors, and two of unrelated disease.


Value of serum thyroxine measurements for the management of congenital hypothyroidism in children. Fourteen cases of primary congenital hypothyroidism were studied and separated for the analysis purpose into two groups. Group A consisted of 7 children whose hypothyroidism was diagnosed after 1971 and the therapy by thyroid gland extracts evaluated by regular serum thyroid hormone determinations. Group B was made of 7 children whose disease was diagnosed and treated before 1971. Two periods were therefore studied in group B: first period, before any hormonal determinations (as a growth control period for group A), and second period, during which hormonal determinations were made and taken into consideration for the dosage. Although growth patterns were similar in both groups, mean thyroid extracts dose was 63 +/- 25 mg/m2/day (mean +/- SD) during follow-up with hormonal determinations, while it was markedly higher during the first period of group B (125 +/- 76, range 46.1 to 219.9 mg/m2/day). The mean dose of 63 +/- 25 mg/m2 induces a mean level of plasma thyroxine of 82 +/- 32 microgram/1 (mean +/- 1SD), a normal growth (with catch-up growth in the patients who had a retarded growth), and a good psychomotor development. Regular measurements of serum thyroxine during therapy seems to be a valid parameter for determining the dose of thyroid gland extracts necessary for adequate substitution. Serum=1-triiodo-thyronine levels have more fluctuations than thyroxine. Serum TSH mainly prevents the underdose of patients but cannot help in case of overdose. The suggested dose for treatment of such patients is 88 mg/m2/day (= 63 + 1SD).


Liver involvement in cystic fibrosis. A report of 9 cases. 9 out of 204 unselected cystic fibrosis (CF) patients seen at the Department of Pediatrics, University of Berne, Switzerland, over the last 20 years had clinically overt liver disease. In 7 patients liver cirrhosis was demonstrated (3.4%). Focal biliary cirrhosis was the pertinent finding in 3 cases, whereas another 3 showed unspecific nodular cirrhosis. One infant presented with prolonged obstructive jaundice due to partial extrahepatic atresia and delayed passing of meconium. Two other patients had steatosis. A review of the literature dealing with clinical and laboratory findings in CF patients with liver disease is given.


[BCG vaccination, cancer and infectious mononucleosis. A retrospective study of hospitalized patients]. A retrospective study (1966--1976) of patients hospitalized for cancer was carried out to determine a possible relationship with BCG vaccination, with a control group matched for age and sex and a similar study concerning infectious mononucleosis. Among 105 patients with cancer, 54 (51.42%) had been previously vaccinated with BCG, 56 (53.33%) in the control group, and 22 (33.84%) among the 65 patients with infectious mononucleosis (p less than 0.05, x2). The mean age on admission for cancer or infectious mononucleosis among vaccinees is significantly older than among non-vaccinees, suggesting a transient protection afforded by vaccination. These results need to be confirmed by a prospective study with Epstein-Barr virus serology.


[Transient diabetes mellitus in a dystrophic newborn infant]. We report a female small for date neonate, who developed transient diabetes mellitus (TDN) five days after birth and required insulin therapy for five weeks. At the onset of the disease, plasma insulin concentration was extremely low. At four weeks of age, after insulin withdrawal, the patient was still hyperglycemic, and basal insulin values assayed over a period of 24 h were mostly inadequate. Glucagon secretion was not suppressed. Growth hormone levels were lower than those of three small for date infants of the same age. At three months of age, the patient was still intolerant to an oral glucose load, insulin secretion remained inadequate while glucagon paradoxically increased 30 min after glucose challenge. The oral glucose tolerance values were in the normal range at six months of age. We conclude that TDN is caused by a transitory defect of insulin secretion, which would also explain the glucagon response as a consequence of insulin deficiency. We found no evidence associating the insulin antagonists observed in our study with the pathogenesis of this illness.


Endocrine dysfunction in the diencephalic syndrome of emaciation in infancy. A 10-month-old boy with the clinical features of the diencephalic syndrome of emaciation due to a suprasellar spongioblastoma is described. The patient showed high basal levels of growth hormone (GH greater than 80 muU/ml on several occasions). In addition, elevated concentration of plasma testosterone (125.5 ng/100ml) was combined with a relatively high LH-increase to LHRH (45.6 mU/ml). After completion of irradiation basal GH-levels had been normalized, and GH responses to insulin induced hypoglycemia (IIH) and propranolol-glucagon (PG) were adequate. Complete clinical remission of emaciation occurred soon after radiation therapy and went parallel with the normalization of GH-regulation.


A new familial defect in neutrophil bactericidal activity. A 4-year-old boy with recurrent infections and his clinically healthy father showed a severe, isolated defect in bactericidal activity of peripheral neutrophil leukocytes (the mother and the only sister were normal). Lymph nodes, spleen and liver of the child presented a massive infiltration by macrophages. Such infiltration and the segmentary albinism of the hair resemble traits of the Chediak-Higashi syndrome, but some of the most relevant traits of this syndrome are absent, since all other neutrophil functions were normal in our patient.


Hyperornithinemia and gyrate atrophy of choroid and retina. Report of a case. A case of hyperornithinemia and gyrate atrophy of choroid and retina has been observed in a 3-year and 9-month-old girl. She presented also mild mental retardation, delayed language development and speech defects. The restriction of protein intake to a minimum of 0.8 g/kg/day induced a significant reduction of plasma ornithine levels. In some of the previous reports of the syndrome, a deficient ornithine-ketoacid transaminase activity has been found in cultured fibroblasts.


[A case of endothelial splenic cyst in an infant]. The authors report a case of isolated splenomegaly in a healthy 7-year-old boy, not showing any other clinical or biological anomaly. The radiological examination (selective arteriography of left renal artery) and spleenscan were compatible with an intrasplenic process. The splenectomy was performed. The spleen was large (15/20 cm) and demonstrating a cystic lesion in the inferior pole. Histological examination revealed polycystic formations covered with endothelial type cells and associated with angiomatous multifocal lesions. Differential diagnosis of cystic lesions of the spleen is discussed and complete preoperative investigation is stressed.


Silver impregnation methods for reticulum fibers and reticulin: a re-investigation of their origins and specificity. Maresch (1905) introduced Bielschowsky's silver impregnation technic for neurofibrils as a stain for reticulum fibers, but emphasized the nonspecificity of such procedures. This lack of specificity has been confirmed repeatedly. Yet, since the 1920's the definition of "reticulin" and studies of its distribution were based solely on silver impregnation technics. The chemical mechanism and specificity of this group of stains is obscure. Application of Gomori's and Wilder's methods to human tissues showed variations of staining patterns with the fixatives and technics employed. Besides reticulum fibers, various other tissue structures, e.g. I bands of striated muscle, fibers in nervous tissues, and model substances, e.g. polysaccharides, egg white, gliadin, were also stained. Deposition of silver compounds on reticulum fibers was limited to an easily removable substance; the remaining collagen component did not bind silver. These histochemical studies indicate that silver impregnation technics for reticulum fibers have no chemical significance and cannot be considered as histochemical technics for "reticulin" or type III collagen.


The histochemistry of complex carbohydrates in the ovarian follicles of adult mice. In the ovarian follicles of adult mice, complex carbohydrate-containing structures have been studied by means of light microscopic histochemical methods. In the ovarian follicles, the zona pellucida of oocytes, follicular fluid and intercellular matrix of the granulosa layer are found to exhibit positive reactions for complex carbohydrates with 1,2-glycol and acidic groups and alpha-D-mannosyl and alpha-D-glucosyl residues. The present histochemical analyses have revealed that the complex carbohydrates common to the three types of the structures are hyaluronic acid, sulfated glycosaminoglycans other than isomeric chondroitin sulfates and neutral glycoproteins and that sialic acid is a particular moiety of the zona pellucida, whereas isomeric chondroitin sulfates being that of the follicular fluid and intercellular matrix of the granulosa layer. The histophysiological activities of the carbohydrate-containing structures have been discussed with special reference to their histochemical properties determined in the present study.


Concanavalin  A receptors in normal and inflamed oesophageal epithelium. A light and electron microscopic study. We have examined normal and inflamed oesophageal biopsies for the distribution of alpha-D-mannosyl and alpha-D-glucosyl residues using the concanavalin A--horse radish peroxidase--Diamino-benzidine (DAB) technique at the light and electron microscope level. Receptors were found on the epithelial surface and in the nuclear membrane and endoplasmic reticulum. A similar distribution was found with the intrusive lymphocytes and polymorphonuclear leucocytes in the inflamed state. Some of the increased intercellular debris from inflamed biopsies contained concanavalin A receptors.


[Inner ear disturbance following long-term usage of hormonal contraceptives (author's transl)]. Four cases of either unilateral or bilateral irreversible hearing loss are reported in young women following long-term usage of hormonal contraceptives. Two different forms of the hearing disturbance and their causes are described, taking into consideration related neurological, medical and ophthalmologic literature. From this material, guidelines for clinical practise are proposed.


[Disturbances of taste from oral disinfectants (author's transl)]. Oral disinfectants containing chlorhexidine or hexetidine are able to produce disturbances of taste, as demonstrated by Krarup's electrogustometric method and the gustometric method of Harris and Kalmus. Hypo- and dysgeusia are characterized by dissociated disturbances, the most prominent of which concerns the sweet perception. The bitter taste is least affected, whereas the effects on salty and acidic tastes range between that for sweet and bitter. Taste disturbances which include ageusia for 48 h were observed when the tongue was touched with a 20% solution of chlorhexidine. Not only the disinfectants themselves provoked dysgeusia but also other "taste improving" agents (particularly, the volatile oild). In addition to dysgeusia, the authors found disturbances of the mucous membrane sensitivity caused by the test substances.


[Sudden deafness and vestibular failure in the cervical syndrome (author's transl)]. Acute onset deafness with vestibular failure in the cervical syndrome could be due to embolism of the labyrinthine artery. Probably the symptomatology of the cervical syndrome developes independantly. Two patients with sudden deafness and vestibular failure are reported. Embolism of the labyrinthine artery in at least one of these patients appears to have occurred. The prognosis in respect of recovery of function is unfavourable.


[Cortisol blood level in children with subglottic laryngitis (author's transl)]. Clinical observations have shown that fear of suffocation aggravates respiratory tract occlusion in children with subglottic laryngitis (s.l.). In similar situations of emotional stress, changes occur in the function of the adrenal glands. The author's observations lead to the conclusion that rapid intravenous injection of glucocorticoids results in the alleviation of symptoms endangering a child's life so that in a majority of cases a tracheotomy is no longer necessary. Cortisol blood level was estimated by the technique of de Moor as modified by Derech and Golebiowska. These levels were then determined in 20 children with s.l. not treated with glucocorticoids before hospitalization and 10 children in a control group. In children with s.l., high levels of cortisol were detected at the time of admission. In a few cases 100 microgram/100 ml. After symptoms of s.l. subsided, levels of cortisol resembled those of the control group as seen on primary examination. Administration of ACTH induced a more pronounced increase in cortisol level in children with s.l. than in children of the control group.


[Spontaneous ethmoid pneumocele in chronic maxillary and ethmoid sinusitis and polyposis (author's transl)]. A 47 year old man with asthma, allergic rhinitis, and chronic maxillary and ethmoid sinusitis and polyposis, in whom for 2 years intraorbital pressure symptoms are experienced on nose-blowing, sneezing and coughing, is presented. Paranasal sinus X-rays demonstrated an intraorbital pneumocoele that increased in size with Valsalva manoeuvre. The diagnosis, pathology and treatment of intraorbital emphysema and pneumoceles are discussed.


[Testing directional hearing with a modified artificial head recording system (author's transl)]. Previous methods for testing directional hearing are described and a new directional hearing test with a modified artificial head recording system is demonstrated. The new method complies well with natural conditions and allows the possibility of testing different hearing losses. The results of testing in 110 non-exercised subjects are discussed.


VA/Q inhomogeneity and AaDO2 in man during exercise: effect of SF6 breathing. Pulmonary gas exchange was studied in five normal subjects both at rest and during moderate steady-state exercise on a bicycle ergometer while breathing a) room air and b) a mixture of 20.9% O2-balance sulfur hexafluoride (SF6). The alveolar-arterial oxygen pressure differences (AaDO2) widened significantly from rest to exercise. Breathing the O2-SF6 mixture reduced the AaDo2 significantly from 10.9 to 4.2 Torr at rest and from 15.5 to 10.1 Torr during exercise (P less than or equal to 0.01). There were no concurrent changes in metabolism, cardiac output, or heart rate during the SF6 breathing. Possible changes in the anatomic shunt fraction, alveolar-end-capillary equilibration, or the distribution of blood flow cannot account for these observations. We conclude that the AaDO2 increase during exercise reflects an inhomogeneity of ventilation-perfusion ratios (VA/Q) most probably arising within regions of the lung (intraregional inhomogeneity) rather than between regions (interregional inhomogeneity).


Fibrinogen clearance from alveoli.

Fibrinogen clearance from alveoli. In experiments lasting 311 +/- 8 (SE) min, we studied the clearance of 125I-fibrinogen ([125I])RIF) from distal lung units of anesthetized, ventilated dogs. We instilled varying concentrations of isosmolar, citrated [125I]RIF ranging from 0.75 to 4 mg/ml into alveoli of individual dogs, and we monitored clearance by the use of external detectors and blood and lymph sampling. Approximately 9% [125I]RIF passed into proximal airways according to detector signal analysis. Excluding airway flow, whole lung clearance of [125I]RIF occurred by degradation to small molecules that rapidly became evenly distributed in body extracellular water. The degradation appeared to take place within the distal airway and not within the lung interstitium because 131I-fibrinogen, injected intravenously, was degraded less in passing from plasma to right duct lymph. The intra-alveolar kinetics of [125I]RIF had 1.5 reaction order with a specific rate of 1.27 X 10(-5) ml(3/2)-mg(-1/2)-min(-1). The data indicate that fibrinogen clearance from alveoli occurs by both transbronchial bulk flow and intraalveolar degradation.


Cardiovascular effects of whole-body heating in spontaneously hypertensive rats. The cardiovascular response to severe whole-body heating was examined in anesthetized spontaneously hypertensive (SH) (mean BP = 140 Torr) and normotensive (N) rats (mean BP = 96 Torr). Elevation of colonic temperature to 44 degrees C resulted in an initial increase in arterial pressure (mean BP: SH = 199 Torr, N = 124 Torr) with a subsequent severe hypotension. There was little evidence to suggest that this collapse in systemic pressure was related to a direct heat impairment of cardiac function. It was more likely the result of a progressive venodilation which produced venous pooling and decreased venous return. The arterial blood pressure response to exogenous catecholamine challenge decreased at elevated temperatures. This suggests that there was a deterioration of the vasoconstrictor response and indicated a possible effect of heat at the receptor or effector level. There were significant differences between the responses of normotensive and hypertensive rats to whole-body heating suggesting an enhanced cardiovascular sensitivity in hypertensive rats that may partially explain earlier reports of inferior thermoregulation and heat intolerance in these animals.