Evaluation of cardiac size in chronic bronchitis and pulmonary emphysema. The accuracy of interobserver variability of roentgenographic analysis for cardiac size in patients dying with chronic bronchitis and pulmonary emphysema were correlated with pathologic data derived from special studies. Three trained observers were able to accurately and consistently diagnose chronic bronchitis and pulmonary emphysema and to detect cardiomegaly on the chest x-ray film. The best criteria for chronic bronchitis and pulmonary emphysema were those of overinflation; however, none of the roentgenographic criteria usually suggested for the specific diagnosis of right ventricular or left ventricular hypertrophy were found to be reliable. The inaccuracy and interobserver variability in the detection of enlargement of specific chambers make it evident that the usual criteria are not valid and that roentgenographic appraisal of cardiac size in these patients in limited to findings of normalcy or cardiomegaly.


Intermittent left bundle branch block in the athletic heart syndrome. A 30-year-old man with typical findings of the athletic heart syndrome is presented because of the unique feature of intermittent left bundle branch block. Observations during right atrial pacing and exercise support the concept of autonomic control of intraventricular conduction, both adrenergic and cholinergic.


Aortic regurgitation associated with ventricular septal defect. Echocardiographic and hemodynamic observations. Ventricular septal defect is sometimes associated with aortic regurgitation. In this report, an echocardiogram demonstrating dramatic prolapse of the noncoronary cusp into the left ventricular outflow tract and ventricular septal defect in a patient with Down's syndrome and ventricular septal defect, confirmed by angiographic studies, is presented. The echocardiogram supports the concept of anatomic lack of support of the aortic ring due to a deficient septum and hemodynamically significant flow of blood to the right ventricle through the ventricular septal defect, resulting in trauma to aortic cusps and prolapse.


Concentrations of tinidazole in body fluids and tissues in gynaecological patients. The concentrations of tinidazole in various tissues and body fluids were studied in gynaecological patients after a single 2g oral dose. Tinidazole was determined by the agar-diffusion technique using a strain of Clostridium bifermentans. Reliable estimates of concentrations down to 0.5 microng/ml could be obtained. Dichloromethane extraction of tinidazole added to various tissues in known amounts gave a recovery of 100 +/- 10%. Peak serum values of 32-52 microng/ml were reached 3-6h after the administration. The concentrations in peritoneal fluid, obtained at operation 8.5-15h after the intake, varied between 16 and 40 microng/ml. Specimens from the Fallopian tubes yielded 15-26 microng tinidazole/g tissue; similar levels were obtained specimens from myometrium, endometrium, portio, vaginal secretions, omental fat, and cutis. It is concluded that, with the given dose, tinidazole concentrations are achieved in fluids and tissues of the female genital tract that are far in excess of those that should be therapeutical in infections caused by microorganisms know to respond to nitroimidazole treatment.


Disc space infections in children.

Disc space infections in children. Intractable low back pain in children is often due to disc space infections. The clinical presentation, diagnostic workup, and treatment of four cases are presented. Symptoms often occur well before radiographic findings are evident. The diagnosis can only be made by a high degree of suspicion and repeated X-rays. Antecedent causes, such as urinary infection or intravenous administration of narcotics were lacking in this group. Fever or a preceding febrile illness was often, but not invariably, present. Percutaneous biopsies were not usually helpful. Myelography in each instance was normal. Bed rest reduced but did not alleviate the back pain. The institution of appropriate antibiotic therapy resulted in a prompt diminution of pain.


A case of primary undifferentiated sarcoma of the liver. The authors report a case of primary undifferentiated sarcoma of the liver, observed in a 36-year-old man. Diagnosis was established at peritoneoscopy and guided biopsy, and confirmed by autopsy two months later.


Peritoneoscopic evaluation of the effect of chemotherapeutic agents on liver metastases of breast cancer (report of 2 cases). Two cases of breast cancer are presented in which massive liver metastases were proved by biopsies prior to treatment. Use of alternate cyclical hormonal cytotoxic combination chemotherapy (EORTC Clinical Trial, protocol, no 10741/3) was followed by a dramatic disappearance of neoplastic tissue. Peritoneoscopy associated with needle biopsy proved extremely useful to provide objective evaluation of the response to chemotherapy.


Peritoneoscopy in adult polycystic kidney disease: its diagnostic value. The value of peritoneoscopy in the diagnosis of renal polycystic disease was tested in nine patients with adult polycystic disease and one with congenital hepatic fibrosis. The right kidney was visualized in all ten cases and the left in seven. Renal cysts were recognized by peritoneoscopy in eight of the ten patients. Factors impeding visualization of the kidneys and the cysts were: a) fixation of the splenic flexure of the colon; b) non-superficial renal cysts. Of six cases in which intravenous pyelography was not diagnostic, peritoneoscopy was positive in four. No correlation was found between the degree of hepatic and renal cystic involvement.


The value of laparoscopy in the diagnosis of primary cancer of the liver. A retrospective survey organized by the Spanish Association for Digestive Endoscopy among its members has revealed that a correct diagnosis of primary liver cancer could be made by guided biopsy during laparoscopy in 153 of 208 cases. A diagnosis of malignancy was made in 103 of 145 cases of carcinoma associated with cirrhosis and in 50 of 63 cases without cirrhosis, but in the latter, the lesions were endoscopically indistinguishable from metastatic nodules in most instances. Biopsy was positive in 88% of all suspicious cases. Carcinomatous invasion of seemingly benign cirrhotic nodules could be demonstrated in 22 other patients.


Occupational and environmental health hazards in the plastics industry. A brief description of the potential occupational health hazards encountered in the manufacture of plastics (polymers) is given. In general, these hazards are due to the monomers used to make the various plastics, to unreacted monomer contained within the finished products, and to the fillers, stabilizers, pigments, inhibitors, and initiators used in fabricating the finished products. They run the gamut from angiosarcomas of the liver due to vinyl chloride, to dermatitis and asthma-like reactions due to the initiators used with epoxy resins.


Studies on intestinal adenosine triphosphatases. II. Stabilitiies in different rat subcellular fractions. Subcellular fraction (brush border, mitochondria, microsomes and plasma membranes) are isolated from the rat intestinal epithelial cells. A comparison was made between the effect of cold storage, freeze-thawing, heating and of some chemicals (DMSO, DTT, glycerol, sucrose) on the stability of Mg2+ and (Na+-K+) dependent ATPases in these fractions in order to determine possible difference linked to the localization in the enterocyte. Enzymatic activities were found more stable at -20 degrees C than at +4 degrees C. Microsomal (Na+-K+)-ATPase increased in activity until the 8th day, then declined. Brush border (Na+-K+)-ATPase was the least resistant of all fractions. For Mg2+-ATPase, that from mitochondria was that had lost much more activity (84%) in 15 days at +4 degrees C. With freeze-thawing there was a comparable decrease in all activities (20-35%). by heating between 35 and 60 degrees C, Mg2+-ATPase was shown to be more heat resistant than (Na+-K+)-ATPase. The addition of some stabilizing chemicals (DMSO, glycerol, sucrose) improved the heat stability of the two enzymes: better results were obtained with glycerol for Mg2+-ATPase and sucrose for (Na+-K+)-ATPase. These differences might be due to the compositon in membraine lipids or to the nature of the enzymes studied.


Leucocyte energy metabolism. VI. Simultaneous and improved isolation of lymphocytes and polymorphonuclear leucocytes from a single of human blood. A technique, which combines a Ficoll-Rompacon treatment, sedimentation in a Dextran medium and erythrolysis by NH4C1, permitting the simultaneous isolation of polymorphonuclear cells (PMN) and lymphocytes from a single sample of human blood is described. The contamination of the PMN suspensions by other blood cells, including other categories of white cells, is minimal. However, the lymphocyte preparations, free of other white cells, are still contaminated by a non-negligible amount of thrombocytes. It could be shown that the biochemical system studied, the functional behavior and the morphological state of these cells are similar to that of white cells purified with the procedures previously used. Further, a numeration technique, based on DNA estimation, is presented which can be used when the cell count becomes inaccurate by cell agglutination.


Purification and properties of a DNA-dependent ATPase induced by bacteriophage T4. A DNA-dependent ATPase formed after T4 phage infection is purified to apparent homogeneity. The molecular weight of the purified enzyme is 50 000 when determined by glycerol gradient centrifugation and by sodium dodecylsulfate/polyacrylamide gel electrophoresis. The enzyme at an earlier stage in purification (prior to DEAE-cellulose chromatography) exists as a complex with a molecular weight of 100000. However, molecular weight determinations by Sephadex gel chromatography give considerably decreased molecular weights for the complex and for the enzyme after DEAE-cellulose chromatography. The enzyme is stimulated to varying degrees by a variety of single-stranded polydeoxyribonucleotides or by single-stranded DNA, but no chemical change in the polynucleotide has been detected as a result of the enzyme action.


[Effect of narcotics on the enzymatic activity of neuronal and synaptic mitochondria of rat brain]. The action of morphine (20 mg/kg) and phenobarbital (80 mg/kg) on the activity of acetylcholinesterase (ACS) and Mg2+-dependent ATP-ase in fractions of unpurified mitochondria and neuronal mitochondria of the rats brain was studied. It is shown that with prolonged introduction of both morphine and phenobarbital the dynamics of the Mg2+-dependent ATP-ase activity in fractions of neuronal mitochondria and synaptosomes is dissimilar, the synaptosomes fractions then displaying a specific influence of morphine and phenobarbital on the Mg2+-dependent ATP-ase activity, while in the neutronal mitochondria fraction changes occurring in the activity of this enzyme proved to be analogus to those taking place after administration of both morphine and phenobarbital. The ACS activity in the synaptosomes fraction following introduction of both morphine and phenobarbital did not differ from the control one.


[Effect of corticosteroids, vitamins and their combination with thiophosphamide on the indicators of carbohydrate and electrolyte metabolism of animals with experimental tumors]. On a model of transplantable albeolar-mucous RS cancer it is shown that hydrocortisone, desoxycorticosteonre-acetate (DOCA), cyanocobalamine used in combination with folic and nicotinic acids does not lower the cytostatic activity of thiophosphamide and in a number cases even potentiates its action. A relation between changes occurring under the influence of the chemical agents on the energy exchange (a fall of the lactate level) and the linked with it transfer of ions (reduced concentration of magnesium, calcium and a rise in the level of sodium) through the membranes of cancer cells was revealed. Against the background of chemotherapy gycolytic processes in the malignant cells. Evidence was brought to bear that under the influence of thiophosphamide the response of the neoplastic tissue to DOCA becomes perverted (the concentration of potassium goes up and the level of sodium delcines).


[Effectiveness of syrepar in experimental liver dystrophy in albino rats]. In experiments with rats it was found that syrepar is an effective agent in acute dystrophy provoked by carbon tetrachloride. Its daily administration in an amount of 0.1 ml per 100 g of weight subcutaneously improves the general condition of the animals, prevents their destruction, accelerates restoration of the structure and function of the liver. Much earlier and more fully the cholepoietic function of the liver, the ultrastructural organization of hepatocytes, as well as the activity of hepatic enzymes, along with the glycogen content and of cytoplasmatic RNA were re-established.


The distribution of HLA-d (MLC) locus determinants in the Czech population. The distribution of 8 HLA-D determinants in the group of 83 unrelated individuals of the Czech population was ascertained by means of homozygous typing cells using the mixed lymphocyte culture test. In the panel tested, the gene frequencies of HLA-D determinants, the distribution of HLA-D phenotypes and the magnitude of the linkage disequilibrium between the determinants of the HLA-B and HLA-D loci were determined.


The retinoic acid derivative Ro 11-1430 in Acne vulgaris. A controlled multicenter trial against retinoic acid. In a double-blind controlled multicenter trial consisting of 257 patients with acne vulgaris an 8-week topical treatment with the retinoic acid derivative Ro 11-1430 (0.1% lotion) was compared with vitamin A acid (0.05% lotion) and the lotion alone (placebo). In reducing the number of comedones vitamin A acid was superior to Ro 11-1430, which was significantly better than placebo. The reduction in number of papules and pustules was not statistically significant on either treatment. Local side effects, i.e. erythema, desquamation, burning and pruritus occurred more frequently and were more severe on vitamin A acid than on Ro 11-1430 and placebo which did not differ. No correlation was found between incidence and severity of local reactions and therapeutic effect.


Tofranil in the treatment of low back pain. This report describes a double-blind between-group comparison of Tofranil and placebo in fifty-nine patients admitted to the Joint Service Medical Rehabilitation Unit suffering from low back pain. Patients were given 25 mg of either Tofranil or placebo three times a day for four weeks. Fifteen patients were not included in the analysis, nine dropping out for non-trial related reasons, two dropping out complaining of lost libido and four not taking the tablets, or taking additional drugs. One of the patients complaining of lost libido was taking Tofranil and the other was taking placebo. Over the whole sample there was no significant benefit for Tofranil over placebo as regards physical measurements. Both Tofranil and placebo groups showed a significant improvement during the trial on straight leg raise and backward flexion. For lateral flexion the Tofranil group was significantly worse than the placebo group on entering the trial, and during the trial the Tofranil group improved to match the placebo group. The clinician's pain and stiffness assessments and the patients' pain and stiffness assessments show a significant improvement for both the Tofranil and placebo groups during the trial. However, no difference is shown between Tofranil and placebo. The psychological tests show no difference between Tofranil and placebo and only a marinal improvenmet over initial condition. Further analysis according to initial diagnosis showed nothing conclusive. Numerically, the use of Tofranil produced a marked improvement in pain and stiffness in patients with 'disc lesion only' diagnoses, whereas placebo did not produce an improvement. However, this observation was far from reaching statistical significance. Side-effects were not severe for either drug. Additional medication was rarely used.


Effect of fasting and streptozotocin in the obese-hyperglycemic (ob/ob) mouse. Apparent lack of a direct relationship between insulin binding and insulin effects. The decrease of insulin binding to plasma membranes of liver, adipose, and muscle tissues observed in obese-hyperglycemic (ob/ob) mice was reversed towards normal by prolonged fasting or streptozotocin treatment. The extent of this reversal was related to that of the decrease in hyperinsulinemia of the obese mice. In contrast, binding of glucagon to liver plasma membranes was little influenced by fasting or streptozotocin treatment of obese animals. The relationship between insulin binding and metabolic effects of the hormone did not appear to be identical in all tissues. In muscle, insulin binding and insulin effect on glucose uptake and metabolism changed in parallel--i.e., when binding increased, tissue sensitivity to the hormone increased. In the liver, the increase in insulin binding that followed fasting or streptozotocin treatment was not accompanied by any detectable metabolic effect of insulin on hepatic metabolism. A similar situation appeared to prevail in adipose tissue. The varying relationships observed between the state of insulin binding to membranes and the target tissue responsiveness to the hormone probably reflect the multiplicity of the factors operative in these processes and help us to understand why the over-all obese-hyperglycemic syndrome of ob/ob mice cannot be improved simply by decreasing endogenous hyperinsulinemia.


HLA antigens and ulcerative colitis in Japan. The HLA antigens in 44 cases of ulcerative colitis and 271 control individuals in Japan were studied. The NIH tissue typing method was used according to the new leukocyte nomenclature adapted by the WHO Committee. In normal Japanese populations, the HLA antigens, which were of high frequency, were HLA A2(37.3%), A9(60.9%) and B5 (40.6%). On the contrary, the significantly high frequency of HLA B5 was demonstrated in ulcerative colitis, compared with that in control. Moreover, HLA B5 in cases with ulcerative colitis excluding those with proctitis only, was found with higher frequency than that in total cases. Although the most frequent haplotype was HLA A9-B5 in control, so frequent haplotype was not found in ulcerative colitis. A family study revealed no significant diathesis on the hapolytpe of HLA in ulcerative colitis. The relationship between MLC locus and ulcerative colitis was not yet clarified from the study of one family whose two members suffered from ulcerative colitis.


Gastrointestinal involvement in the Sézary syndrome. A case of documented Sézary syndrome, a cutaneous T-cell lymphoma, with gastrointestinal lymphocytic infiltration is presented. The symptom of diarrhea waxed and waned with the course of the disease process. Radiographic studies were normal, and no evidence of malabsorption was elicited. The diagnosis was established by endoscopic and biopsy techniques, with light and electron microscopy of colonic and small bowel biopsies demonstrating extensive infiltration with typical Sézary cells. To our knowledge this is the first reported case of gastrointestinal involvement in the Sézary syndrome.


Histochemical observations on the mycetomes of Pyrilla perpusilla Walker. Histochemical studies of mycetomes and mycetocytes of Pyrilla perpusilla show PAS positive material, what can suggest the presence of glycogen. The mycetocytes failed to stain with alcian blue and methyl green pyronin "Y" indicating the absence of mucopolysaccharides and RNA respectively. The mycetocytes show positive congo red. Millon and Mercury bromophenophenol blue staining thereby proving that they contain glycoprotein, tyrosine and proteins. Positive reaction with Sudan black may show the presence of lipids and lipoproteins.


Histochemical study of polysaccharides in the aortic arch of some birds. The histochemical study of polysaccharides in the aortic arch of the black vulture, turkey, peking duck, goose and duck, showed that a sialo-mucopolysaccharidic complex is present in the vessel wall and consists of: sialic acid, neutral mucopolysaccharides, hyaluronic acid and Chondrotin sulfate. The concentration of mucopolysaccharides, mainly of the acidic ones, decreases from the inner portions of the media towards the adventicia.


Classification of muscle fiber types based on succinic dehydrogenase and myofibrillar ATPase reactions in normal and randomly reinnervated rat skeletal muscles. In the normal and randomly reinnervated plantaris muscle of rat staining for succinic dehydrogenase (SDH) activity differentiates three fiber types (A, B and C), staining for myofibrillar adenosine triphosphatase (ATPase) differentiates three fiber types (alpha, beta and alpha beta). Here we present our finding type A corresponds to alpha beta fibers, B to beta or alpha beta, C to alpha or alpha beta. In normal soleus muscle both classifications were found to be compatible and B fibers correspond to beta and C to alpha fibers. An exception is the small percent of alpha beta fibers which correspond to B type. In randomly reinnervated soleus muscle changes in ATPase activity are not followed by changes in SDH staining and B fibers correspond to alpha, beta or alpha beta types.


[State of disease and social situation of adult hemophiliacs]. 54 adult patients suffering from hemophilia responded to a questionnaire regarding their state of illness and social situation. As far as state of the illness was concerned items pertained to type of hemophilia, factor activity, degree of physical handicap, number of bleedings and hospitalizations as well as etiology of bleedings. Social data contained items on marital status, education, occupation and leisure activities. The handicap of the illness as well as the possibility of positive social integration is underlined by the findings of the study.


DNA synthesis in pancreatic islet and acinar cells in rats with streptozotocin-induced diabetes. The rates of DNA synthesis in islet and acinar cells were compared at different intervals following streptozotocin-induced diabetes. Streptozotocin, injected I.V. at a dosage of 65 mg/kg, consistently produced a diabetic-like state in young rats, ages 33 to 42 days. At two, four, and seven days after streptozotocin administration, no significant difference in DNA synthesis per mm2 of islet and acinar tissue was evident. However, four days after streptozotocin injection, a significant increase over control values was observed in the number of cells per islet incorporating tritiated thymidine. Following streptozotocin administration, beta cells generally appeared degranulated but not necrotic. Transformation of acinar cells or ductal elements to beta cells was not observed, suggesting that proliferating beta cells are the progeny of pre-existing beta cells. This study suggests that a brief, temporary period of compensatory proliferation of beta cells follows the initial insult of the diabetogenic agent streptozotocin in young rats.


Alterations of the glycolytic pathway and adenine nucleotide state in livers of clofibrate treated rats. The influence of clofibrate on the glycolytic pathway in liver was studied. The changes in the activity of glucokinase and hexokinase were not significant. A reduction of phosphofructokinase (p less than 0.05) and pyruvate kinase activity was found (p less than 0.0005) during clofibrate feeding. An in vitro inhibition of these enzymes could not be demonstrated by clofibrate up to a concentration of 2.5 mM. Crossover plots of glycolytic intermediates indicate that the reduced pyruvate kinase activity may influence the glycolytic pathway in vivo. Clofibrate feeding induces a lower ATP:ADP ratio, a lower adenylate energy charge and elevates AMP levels in rat liver. This may possibly stimulate the hepatic glycogenolysis and the glucose utilisation by this organ.


Pituitary-gonadal function in the carcinoid syndrome: effect of parachlorophynylalanine therapy. Six patients with the carcinoid syndrome (C.S) had serum luteinizing hormone (LH) concentrations that were greater than age and sex matched control subjects. The serum follicle stimulating hormone (FSH) and testosterone concentrations of the groups did not differ. Four of the 5 C.S. patients tested had an increase in serum testosterone after human chorionic gonadotropin administration and 5 of the 5 subjects tested had an increase in serum LH after clomiphene citrate administration. One of the 4 subjects treated with the tryptophan hydroxylase inhibitor parachlorophenylalanine (PCPA) had a reduction in serum testosterone. He was also receiving methysergide. The other 3 subjects treated with PCPA did not have any persistent alterations in serum testosterone.


Cardiovascular nuclear medicine: a progress report. Providing insights into the functional state of the myocardium not available from other techniques, cardiovascular nuclear medicine is being applied more and more in coronary care units, where it makes possible frequent monitoring of function, and in exercise testing of outpatients. In addition, a nuclear "stethoscope" that generates a left ventricular volume curve may soon bring this valuable resource into office practice.


Ultrastructural localization of acid protein polysaccharides and calcium in the vacuoles of the chicken thrombocyte. The coexistence of acid protein polysaccharides and calcium in the vacuoles of chicken thrombocytes were studied by means of ultrahistochemical methods and electron probe X-ray microanalysis. The thrombocytes possessed large vacuoles of a surface connected membrane system. After both ruthenium red staining and tannic acid fixation the innersurface coat of vacuoles was always strongly and continously visualized. Electron microscopic X-ray microprobe analysis of antimonate precipitates in thrombocytes fixed in K-antimonate-OsO4 revealed calcium localization on the innersurface of vacuoles. From these facts it seems likely that the vacuoles of the surface connected membrane system may take part in the pool or the transport of calcium.


The value of enzyme histochemical techniques in the classification of fibre types of human skeletal muscle. 2. The histochemical demonstration of myosin adenosine triphosphatase in skeletal muscles from adult patients with or with no diseases of the neuromuscular system. A comparison between results obtained by calcium salt and lead salt techniques. In the present investigation the results of a lead salt technique and two calcium salt techniques for the deomonstration of the activity of myosin adenosine triphosphatase in sections of both normal and pathological human skeletal muscle specimens are compared. It was seen that the histochemical results obtained by the different techniques are similar, especially with regard to the identification of fibre-types. It can be clearly stated, that the alkaline phosphatase activity present in muscle fibers of diseased skeletal msucles revealed only a very slight activity with the substrate ATP, so the alkaline phosphatase activity in general did not disturb the reliability of the different myosin ATPase techniques. Moreover it was found that the presence of the mitochondrial Ca2+ -ion activated ATPase with a high pH-optimum in muscle fibers did not give rise to faulty results. From studies with dinitrophenol it can be concluded that this substance activates the myosin ATPase present in type I fibres especially.


Myocardial Feulgen-DNA levels and capillary vascularization in hypoxia-exposed rats. Male abino rats were exposed to simulated altitude of 18,000 ft (380 Torr) for 1 day to 8 wk. Histological sections of heart ventricles were stained by the Feulgen technique and amounts of Feulgen-DNA were determined cytophotometrically. Heart weights, relative to body weights, increased over controls at all exposure periods, as did myocardial capillary vascularization. Ninety percent of cardiac muscle nuclei were found to contain tetraploid amounts of DNA. All nuclei exhibited a high degree of chromatin dispersion in exposed and unexposed rats, which reflects a highly reactive metabolic state of cardiac cells in both groups. There was no evidence of increased ploidy or increased DNA synthesis associated with hypertrophy after acute or chronic hypoxia exposure. The data suggest that an initial event which could facilitate augmented protein synthesis during hypoxia acclimation appears to be an increased availability of oxygen and/or nutrients brought about by an expansion of the capillary bed and vascular proliferation.


Predominant site of flow limitation and mechanisms of postexertional asthma. To determine if a relationship existed between the site of airway obstruction and the mechanisms of exercise-induced asthma, we studied the predominant site of flow limitation, as determined by the mid-vital capacity ratios of maximal expiratory flow with air (Vmax air) and 80% helium-20% oxygen (Vmax He-O2), before and after physical exertion in 12 asthmatics. These observations were then related to the effects seen after vagal blockade and inhibition of mediator release. Five subjects increased Vmax He-O2/Vmax air ratios suggesting that the predominant site of flow limitation was in large airways. This group had their postexercise bronchospasm abolished by pretreatment with an anticholinergic agent. Seven subjects decreased their flow ratios indicating predominant small airway obstruction. Anticholinergic agents, although producing bronchodilation, did not alter their bronchospastic response to exercise. However, pretreatment with disodium cromoglycate did significantly diminish the response of this group. Thus the airway response to exercise in asthmatics is heterogeneous in terms of predominant site of flow limitation and this factor appears to relate to mechanisms.


Unsaturated fatty acid mutants of Neurospora crassa. Unsaturated fatty acid (ufa) auxotrophs of Neurospora crassa were obtained by treatment of conidia with N-methyl-N'-nitro-N-nitrosoguanidine followed by isolation on media containing polyunsaturated fatty acids suspended in Tergitol NP-40. The 24 mutants for which reisolates were obtained from crosses with wild type were assigned to two complementation classes, ufa-1 and ufa-2, located on linkage group V. Unsaturated fatty acids with varying degrees of unsaturation, chain length, and double-bond position as well as different steric configurations were tested for growth requirements.


Characterization and in vitro translation of polyadenylated messenger ribonucleic acid from Neurospora crassa. Ribonucleic acid (RNA) extracted from Neurospora crassa has been fractionated by oligodeoxythymidylic acid [oligo(dT)]-cellulose chromatography into polyadenylated messenger RNA [poly(A) mRNA] and unbound RNA. The poly(A) mRNA, which comprises approximately 1.7% of the total cellular RNA, was further characterized by Sepharose 4B chromatography and polyacrylamide gel electrophoresis. Both techniques showed that the poly(A) mRNA was heterodisperse in size, with an average molecular weight similar to that of 17S ribosomal RNA (rRNA). The poly(A) segments isolated from the poly(A) mRNA were relatively short, with three major size classes of 30, 55, and 70 nucleotides. Gel electrophoresis of the non-poly(A) RNA indicated that it contained primarily rRNA and 4S RNA. The optimal conditions were determined for the translation of Neurospora mRNA in a cell-free wheat germ protein-synthesizing system. Poly(A) mRNA stimulated the incorporation of [14C]leucine into polypeptides ranging in size from 10,000 to 100,000 daltons. The RNA that did not bind to oligo(dT)-cellulose also stimulated the incorporation of [14C]leucine, indicating that this fraction contains a significant concentration of mRNA which has either no poly(A) or very short poly(A) segments. In addition, the translation of both poly(A) mRNA and unbound mRNA was inhibited by 7-methylguanosine-5'-monophosphate (m7G5'p). This is preliminary evidence for the existence of a 5'-RNA "cap" on Neurospora mRNA.


Lysogenic conversion for multiple characters in a strain of Staphylococcus aureus. Lysogenization of nonlysogenic strains of Staphylococcus aureus was performed with two different bacteriophages, LS1 and LS2, that were unable to plaque on any of the strains of S. aureus tested. Infection of recipient strains was achieved when protoplasts were inoculated with LS1 or LS2 or when bacterial cultures were simultaneously inoculated with a virulent phage together with LS1 or LS2. Lysogenization was demonstrated by changes in phenotypic characters of the host strain and by liberation of bacteriophages from the modified strains as shown by electron microscopic examination. The lysogenic strains differed from the host strains by the following characters: they were coagulase, deoxyribonuclease, and lipase negative; they were untypable by the basic set of phages; they did not ferment mannitol under anaerobic conditions; and they produced only l-(+)-lactic acid by glucose fermentation. Their cell walls contained less glycine and concomitantly more serine than those of the host strains. Furthermore, they were devoid of protein A. Conversely, some antigenic factors as well as the presence of ribitol in the cell wall teichoic acid, indicated a parental relationship between the host strains and the derived lysogenic ones. Phages LS1 and LS2 could be excluded from the lysogenic strains by invading phages, and the revertant nonlysogenic strains recovered all of the characteristics of the initial host strains. It was thus concluded that the phenomenon described was due to lysogenic conversion. The origin of phages LS1 and LS2 is discussed.


Normal iron-enterochelin uptake in mutants lacking the colicin I outer membrane receptor protein of Escherichia coli. The outer membranes of two independent colicin Ia-resistant mutants of Escherichia coli K-12 lack the colicin Ia receptor protein. Such mutants exhibit normal capacity for enterochelin (enterobactin)-mediated iron uptake. It is concluded that the colicin Ia receptor is not involved in iron-enterochelin uptake.


Lanthanide ions and skeletal muscle sarcoplasmic reticulm. I. Gadolinium localization by electron microscopy. The Ca2+-Mg2+-dependent adenosine triphosphatase activity of isolated skeletal muscle sarcoplasmic reticulum was studied in the presence of the lanthanide ion, Gd3+. This ion is a powerful inhibitor, producing half maximal effect at approximately 100 micronM Gd3+. Electron microscopy of the isolated vesicles incubated with 100 micron Gd3+ reveal that electron dense depositis of Gd3+ is taken up within the vesicle's interior. This visualization of Gd3+ is apparently dependent on two factors: (i) the presence of ATP, ADP being ineffective; (ii) sufficient time for most of the ATP to be hydrolysed. Since Gd3+ has about the same ionic radius as Ca2+, and since Ca2+ is normally transported across the sarcoplasmic reticulum membrane and accumulated within the vesicle, it is concluded that the increased charge density of the lanthanide ions is critical to the ion transport mechanism, resulting in their localization at the ATPase site and failure to be transported across the membrane.


Properties of the Na+, K+-stimulated adenosine triphosphatase system associated with the plasma membrane of pig thyroid glands. The enzymatic properties of plasma membrane-bound Na+, K+-ATPase [EC 3.6.1.3], isolated with high specific activity and in good yield from pig thyroid cells, were examined. The enzyme activity required the presence of both Na+ and K+ at physiological concentrations; it exhibited high sensitivity to K+ and an absolute requirement for Na+. It showed highly specific requirement for Mg2+ and ATP. The apparent Km for ATP was 0.14 mM under the assay conditions. Arrhenius plots had a point of inflection at about 22 degrees C, activation energies being 24.2 kcal/mol at 5-22 degrees C and 19.0 kcal/mol at 22-40 degrees C. In addition to ouabain, the ATPase was strongly inhibited by fluoride and the SH-blocking reagent, PCMB. Iodide and TSH had no appreciable effect on the enzyme activity.


Biochemical characterization of the neuron. ATPase and acetylcholinesterase activities of neuronal cell bodies isolated in bulk from the pig brain stem. Nerve cell bodies, large and multipolar, were isolated in bulk with the least possible contamination from the pig brain stem. The activities of two neurobiologically important membrane enzymes, Na+, K+-ATPase, and acetylcholinesterase, in the isolated cell bodies were estimated. Na+, K+-ATPase [EC 3.6.1.4], more accurately called ouabain-sensitive ATPase of the nerve cell body, hydrolyzed 94 micronmoles of ATP per h per 100 mg of protein. This activity was one-fourth that in the brain stem. Nerve cell bodies contained a large amount of Ca2+, 275 micronmoles per 100 mg of protein, about half of which was calculated to exist as compounds other than calcium orthophosphate. However, the Na+, K+-ATPase of the nerve cell bodies was not stimulated by EGTA, in contrast to that of the brain stem. Acetylcholinesterase [EC 3.1.1.7] and cholinesterase [EC 3.1.1.8] activities were estimated separately by the use of the specific inhibitors Persidol and BW 284C51 dibromide. Acetylcholinesterase was almost completely responsible for the hydrolysis of acetylcholine in the nerve cell bodies isolated from the brain stem and little cholinesterase activity was detected. 1300-1400 micronmoles of acetylcholine was hydrolyzed per h per 100 mg of protein of the neuronal cell bodies; this activity was about four times higher than that in the brain stem. The differences between the specific activities of Na+, K+-ATPase, and acetylcholinesterase in theneuronal cell bodies and the brain stem are discussed in the light of electron microscopic analysis of the distribution of these enzymes and the preservation of the plasma membrane of the isolated cell bodies.


Involvement of outer membrane proteins in enterochelin-mediated iron uptake in Escherichia coli. Escherichia coli K-12 grown in iron-deficient media contained a large amount of outer membrane proteins O-2a, O-2b, and O-3, while cells grown in iron-supplemented media contained far smaller amounts of these proteins. The iron uptake by the iron-deficient cells was significantly stimulated in the presence of enterochelin, while that by the iron-rich cells was not. The outer membrane isolated from cells grown in the iron-deficient media showed enterochelin-stimulated binding of iron, while the outer membrane from iron-rich cells and cytoplasmic membranes from both types of cells did not show such binding activity. The amount of iron bound by the outer membrane was almost equivalent to the amount of O-2a, O2b, or O-3, irrespective of the amount of these proteins in the outer membrane, which is controlled by the amount of iron in the medium. Small particles rich in these proteins were prepared from cells by EDTA extraction. The particles were active in enterochelin-mediated iron binding and the amount of iron bound was equivalent to the amount of each of these proteins in the particles. Although the outer membrane of E. coli B was as active in iron binding as that of E. coli K-12, it did not possess an appreciable amount of O-2a. Gel electrophoretic analysis revealed that 9-2b and 9-3 were identical with the proteins missing mutants feuB and feuA, respectively.


Effect of manganese(ous) and sulfate on activity of human placental glucose 6-phosphate-dependent form of glycogen synthase. The human placental glucose-6-P-dependent form of glycogen synthase, in the absence of glucose-6-P, can be activated by MnSO4. Separately, Mn2+ and SO4(2-) have no significant effect. In the presence of glucose-6-P, Mn2+ activates the enzyme, but SO4(2-) inhibits; MnSO4 synergetically increases the enzyme activity. Mn2+ reduces the Ka for glucose-6-P to one-tenth of the control value; SO4(2-) increases the Ka 5-fold; however, MnSO4 has no effect on Ka. MnSO4, like glucose-6-P, increases the Vmax of the enzyme in the presence of its substrate, UDP-glucose; it slightly increases the Km for UDP-glucose. In the presence of glucose-6-P, Mn2+ increases and SO4(2-) decreases the Vmax of the enzyme, but neither has an effect on the Km for UDP-glucose. At physiological concentrations of UDP-glucose and glucose-6-P, either Mn2+ or MnSO4 at concentrations less than 1 mM increases the enzyme activity as much as 8 mM glucose-6-P does. At physiological concentrations of UDP-glucose and glucose-6-P, Mn2+ or MnSO4 reverses the inhibition of the enzyme by ATP.


Interaction between Acanthamoeba actin and rabbit skeletal muscle tropomyosin. The binding of 125I-labeled muscle tropomyosin to Acanthamoeba and muscle actin was studied by ultracentrifugation and by the effect of tropomyosin on the actin-activated muscle heavy meromyosin ATPase activity. Binding of muscle tropomyosin to Acanthamoeba actin was much weaker than its binding to muscle actin. For example, at 5 mM MgCl2, 2 mM ATP, and 5 micronM actin, tropomyosin bound strongly to muscle actin but not detectably to Acanthamoeba actin. When the concentration of actin was raised from 5 micronM to 24 micronM in the presence of 80 mM KCl, the binding of tropomyosin to Acanthamoeba actin approached its binding to muscle actin. As with muscle actin, the addition of muscle heavy meromyosin in the absence of ATP induced binding of tropomyosin in Acanthamoeba actin under conditions were binding would otherwise not have occurred. The most striking difference between the interactions of muscle tropomyosin with the two actins, however, was that under conditions where tropomyosin was found to both actins, its stimulated the Acanthamoeba actin-activated heavy meromyosin ATPase but inhibited the muscle actin-activated heavy meromyosin ATPase.


Reconstitution of adenosine triphosphatase of thermophilic bacterium from purified individual subunits. 1. Five subunits (alpha, beta, gamma, delta, and epsilon) of an ATPase from a thermophilic bacterium PS3 were purified in the presence of 8 M urea by ion exchange chromatography. Then the ATPase activity was reconstituted by mixing the subunit solutions and incubating them at 20-45 degrees, at pH 6.3 to 7.0. 2. Mixtures containing beta + gamma or alpha + beta + delta regained ATP-hydrolyzing activity, but mixtures of alpha + beta and beta + delta did not. Combinations not including beta were all inactive. 3. The ATPase activity reconstituted from alpha + beta + delta was thermolabile and insensitive to NaN3, whereas the activities obtained from mixtures containing beta and gamma were thermostable and sensitive to NaN3, like the native ATPase. 4. The assemblies containing both beta and gamma subunits had the same mobility as the native ATPase molecule on gel electrophoresis, those without the gamma subunit moved more rapidly toward the anode. 5. Subunits epsilon and delta did not inhibit the ATPase activity of either the assembly (alpha + beta + gamma) or the native ATPase.


Reactivation of lipid-depleted Ca2+-ATPase by a nonionic detergent. The Ca2+-ATPase of sarcoplasmic reticulum can be reversibly delipidated by precipitation with polyethyleneglycol in the presence of deoxycholate and glycerol to as low as 4 mol of phospholipid/mol of enzyme polypeptide and can then be reactivated to 90% of its original ATPase activity by the addition of phosphatidylcholine. Furthermore, the preparation exhibits nearly the same activity if the nonionic detergent dodecyl octaoxyethyleneglycol monoether is substituted for the added phospholipid. The delipidated ATPase is soluble in the detergent and retains activity for several days. This is the first report of the Ca2+-ATPase retaining high activity with less than about 30 mol of phospholipid bound per mol of polypeptide.


Investigation of molecular motion of proteoglycans in cartilage by 13C magnetic resonance. 13C nmr spectral parameters were measured for intact bovine nasal cartilage tissue, the purified proteoglycan aggregate, and chondroitin 4-sulfate. A comparison of integrated intensities obtained for four different samples of fresh tissue with an ethylene glycol standard indicated that at least 80% of the total glycosaminoglycan carbons in the tissue contributed to the spectrum. This result was confirmed by intensity measurements obtained at 56 degrees on fresh tissue and at 37 degrees after extensive papain digestion of fresh tissue. Spin lattice relaxation times and nuclear Overhauser enhancements were analyzed in terms of the following models of molecular motion: (a) single correlation time; (b) log X2 distribution of correlation times; and (c) anisotropic motion. The analysis indicates that the segmental motions of glycosaminoglycan chains are characterized by a broad distribution of correlation times centered at about 50 ns. Slow motion contributions to glycosaminoglycan line widths were reduced by dipolar decoupling (gammaH2/2pi = 65 kHz). Collagen intensity was observed in dipolar decoupled spectra, but not in scalar decoupled spectra of intact tissue, showing that the type II collagen in cartilage undergoes anisotropic motion like the type I collagen in tendon. Only glycosaminoglycan resonances were observed in spectra of a solution of proteoglycan aggregate before and after chondroitinase digestion. After subsequent digestion with papain, protein resonances were observed. These results suggest that the protein portions of the proteoglycan aggregate structure, in contrast with the glycosaminoglycan chains, have restricted backbone mobility and consequently a defined backbone structure.


Proteases stimulate proliferation of human fibroblasts. Incubation of primary human fibroblasts in serum-free medium with small concentrations of thrombin, trypsin or plasmin resulted in manyfold increase in total DNA synthesis and in the number of 3H-thymidine labelled cells. Rise in the frequency of mitoses indicates that the proteases stimulated also cell division. Because proteases induced only a fraction of cells to proliferate increase in the total number of cells remained moderate. Calf, horse and rabbit serum inhibited the growth stimulating effect of trypsin but chicken, dog and monkey serum were permissive. Specific inhibitors of proteases prevented the stimulation of cell proliferation suggesting strongly that proteases act in virtue of their enzymatic activity.


Nail biopsy--why, when, where, how?

Nail biopsy--why, when, where, how? The technique and significance of nail biopsies with regard to mycotic and bacterial infections, onychopathy associated with cutaneous and systemic diseases, and benign and malignant ungual neoplasms is discussed.


Correction of depressed scars on the face by a method of elevation. A method of managing depressed scars on the face by elevation of scars and subsequent dermabrasion is described. If the indications for this procedure are correctly established, this method always results in some degree of improvement.


Differentiation of the dementias of old age by ultrasonic doppler flowmetry: a pilot study. At the Bel-Air Psychiatric Clinic, Geneva, Switzerland, the technique of ultrasonic Doppler flowmetry was used to examine the internal carotid arteries of 30 aged patients - 10 with cerebral degenerative dementia, 10 with cerebrovascular dementia, and 10 without dementia. An index of cerebrovascular resistance was calculated. Apparently this index can distinguish a group of vascular dementias from a group of degenerative dementias.


Metacarpophalangeal joint arthroplasty with silicone-Dacron prostheses (Niebauer type): six and a half years' experience. Four hundred and forty-one silicone-Dacron arthroplasties done since 1968 were reviewed. Results were influenced by both durability and immediate fixation of the prosthesis, disease characteristics, speed of progression, the amount of hand stress, the extent of soft tissue release, and postoperative dynamic and protective splinting. Dislocations were eliminated by a woven tie-in holding the prosthesis to bone; prosthetic buckling was eliminated by soft tissue release, sufficient bone removal, and suture of the dorsal capsule to the extensor mechanism. Early prosthetic models fractured easier than did current ones. Seventeen percent of the combined 4, 5, and 6 year follow-up prostheses fractured, and 30% of the 6 year prostheses have fractured. Function was not affected, however, and protheses have not been replaced. We continue to use silicone-Dacron protheses with immediate tie-in to bone.


Steroid sex hormones and prolactin in postmenopausal women with generalized mammary carcinoma during prolonged dexamethasone treatment. The endocrine response to prolonged dexamethasone treatment was investigated in six postmenopausal women with generalized mammary carcinoma. Plasma cortisol levels decreased rapidly and became undetectable whereas significant concentrations of plasma dehydroepiandrosterone and androstenedione persisted throughout the study, even in two ovariectomized patients, indicating a certain degree of autonomy or a greater resistance of adrenal 'androgens' to the inhibition of ACTH secretion. Except in the ovariectomized patients, plasma testosterone did not fall significantly whereas the plasma oestrogens tended progressively towards undetectable concentrations. A similar response was found in six normal postmenopausal women although the disappearance of their oestrogens was relatively rapid. This indicates that much of the testosterone present after the menopause could still be produced by the ovaries whereas the ovarian production of oestrogens becomes negligible. The delayed disappearance of oestrogens in the patients with mammary carcinoma indicates that the persisting adrenal 'androgens' remained efficient precursors of oestrogen synthesis within the peripheral tissues and presumably within the mammary tumour itself. Plasma dihydrotestosterone behaved like the plasma oestrogens. Despite the fall in plasma oestrogens, plasma gonadotrophins did not increase further but plasma prolactin rose progressively. The persistance of steroid sex hormones and the rise of plasma prolactin might explain the poor response to dexamethasone treatment in mammary carcinoma.


Biological actions of human somatotrophin and its derivatives on mouse mammary gland and teleost urinary bladder. These studies are concerned with the structural and functional evolution of the ancestrally related pituitary prolactins and somatotrophins. Prolactin-like biological activities of human somatotrophin (hGH) and its peptide fragments were bioassayed in vitro on the mouse mammary gland and the teleost urinary bladder. Plasmin modified-hGH was as active as hGH in both bioassays. The NH2-terminal 134-residue fragment possessed about 10% of the lactogenic and urinary bladder potency of hGH, whereas the CO2H-terminal 51-residue fragment was inactive at the concentrations observed. These results suggest that the same regions of primary structure are responsible for the prolactin-like actions of hGH on the target organs of lower and higher vertebrates. Alteration of the tertiary structure of hGH, human chorionic somatomammotrophin, and ovine prolactin by performic acid oxidation destroys the mammary gland activities of these hormones.


The identification in adult bone marrow of pluripotent and restricted stem cells of the myeloid and lymphoid systems. The precise relationship between the stem cells for the lymphoid system and those for the blood-forming system is unclear. While it is generally assumed that the hemopoietic stem cell, the spleen colony-forming unit (CFU-S), is also the stem cell for the lymphoid system, there is little evidence for this hypothesis. To investigate the stem cells in these two systems, we irradiated bone marrow cells to induce unique chromosome aberrations in the stem cell population and injected them at limiting dilution into stem cell-deficient recipients. Several months (between 3 and 11) were allowed for the injected cells to repopulate the hemopoietic system. At that time, the bone marrow, spleen, and thymus were examined for a high frequency of cells having the same unique chromosome aberration. The presence of such markers shows that the marker was induced in a cell with extensive proliferative capacity, i.e., a stem cell. In addition, the splenic lymphocytes were stimulated with phytohemagglutinin (PHA) or lipopolysaccharide (LPS) to search for unique chromosomes in dividing T and B cells, respectively. Finally, bone marrow cells were injected into secondary irradiated recipients to determine if the marker occurred in CFU-S and to determine whether or not the same tissue distributions of marked cells could be propogated by bone marrow cells in a second recipient. After examination of 28 primary recipients, it was possible to identify three unique patterns of stem cell regeneration. In one set of mice, a unique chromosome marker was observed in CFU-S and in PHA- and LPS-stimulated cultures. These mice provide direct evidence for a pluripotent stem cell in bone marrow. In addition, two restricted stem cells were identified by this analysis. In three recipients, abnormal karyotypes were found only in myeloid cells and not in B and T lymphocytes. These mice presumably received a marked stem cell restricted to differentiate only into myeloid progeny. In three other recipients, chromosome aberrations were found only in PHA-stimulated cells; CFU-S and cells from LPS cultures did not have cells with the unique chromosome. This pattern suggests that bone marrow contains cells committed to differentiation only into T lymphocytes. For each of the three types of stem cells, secondary recipients had the same cellular distribution of marked cells as the primary recipients. This observation provides further evidence that unique markers can be induced in both pluripotent and restricted stem cells.


H-2 mutation affecting immune response to Thy-1.1 antigen. Mouse thymus, thymus-derived lymphocytes, and brain share an antigen determined by gene at the Thy-1 locus in chromosome 9 (1). Two alleles have been identified at this locus: Thy-1(a), coding for antigen Thy-1.1 (or theta-AKR) present in AKR and seven other strains; and Thy-1(b), coding for antigen Thy-1.2 (or{teta}-C3H) and present in C3H and all the remaining inbred strains. Injection of AKR thymocytes into inbred mice carrying the Thy-1(b) allele results in an immune response that can be measured either serologically by determining the level of antibodies in the recipients' serum (1) or by counting plaque- forming cells (PFC) detectable in spleens of the recipients by means of an assay, with AKR thymocytes as target cells(2). The magnitude of PFC and serum antibody responses after a single thymocyte injection depends on the genetic make-up of the recipient. Three genes controlling the PFC response to the Thy- 1.1 antigen have been identified: Ir-Thy-1A and Ir-Thy-1B, which are closely linked to the major histocompatibility complex (H-2) of the mouse (3-6), and Ir-5, which is located at a distance of 17 cm to the right of the H-2 complex on chromosome 17 (6). Previous genetic mapping with H-2 recombinant strains has indicated that the two Ir-Thy-1 loci are located to the left of the IC subregion (7). Further experiments strongly suggested that either one or both Ir-Thy-1 loci map to the K rather than the I region of the H-2 complex (8). In this report, the study of an H- 2 mutant, CBA-H-2(ka) (M523) (9), and its parental strain, CBA/LacStoY (CBA) provided further evidence that one of these loci apparently resides in the K region and might even be identical with the H-2K locus in that region.


Membrane compartmentalized ATP and its preferential use by the Na,K-ATPase of human red cell ghosts. This paper describes work which begins to define the molecular organization in the region of the membrane that comprises the functional domain of the Na:K pump. The membrane-bound phosphoglycerate kinase (PGK) and Na, K-ATPase appear to be directly linked via a compartmentalized form of ATP. Evidence for the membrane pool of ATP is based on the labeling characteristics of the phosphoproteins by [gamma-(32)P]ATP of ghosts incubated under various conditions. Preincubation of ghosts in the presence of ATP at 37 degrees C, but not at 0 degrees C, completely obscures the formation of the Na-phosphoprotein in ghosts washed and subsequently incubated in the presence of [gamma-(32)P]ATP. In contrast to the Na component, the Mg component of phosphorylation is only slightly altered by preincubation with ATP. ATPase activity measured as (32)P(i) liberated during the subsequent incubation at 0 degrees C, reflects completely the differential effects of preincubation with ATP on (32)P incorporation into phosphoprotein. ATP placed within the pool by preincubation can be removed by operating the Na, K-ATPase or the PGK reaction in the reverse direction by use of exogenous substrates. Alternatively, the membrane pool of ATP can be formed also from exogenous substrates by running the PGK reaction in the forward direction. These results, while providing direct support for a membrane compartment of ATP, also indicate the location of this compartment in relation to the PGK and the Na, K-ATPase. In addition, these results also imply that the Mg and Na components are different enzymatic entities since substrate ATP can be derived from separate sources.


A psychosomatic triad in a bipolar patient. A 56-year-old white male with a rare case of psychosomatic triad occurring during a single depressive episode is presented. The dynamics, course, and treatment are discussed. It is suggested that common psychosomatic mechanisms are interacting with the bipolar illness.


Pathology and time relationship of peripheral nerve changes in experimental diabetes. Structural changes have been studied in peripheral nerves in streptozotocin-induced diabetic monkeys. Teased single nerve fibre preparations were most informative. Abnormalities were present in 32 of 58 nerves examined from 15 diabetic monkeys with varying degree of hyperglycaemia. The earliest change was an increase in the gap at nodes of Ranvier, seen 12 weeks after the diabetic state had been established. Well marked segmental demyelination was seen in distal nerves at 14-16 weeks. Later similar changes were seen in proximal, larger nerves. Evidence of remyelination was present at a later date. Wallerian degneration was seen in only 4 nerves. Changes in the myelin sheath were more prominant than axonal abnormalities at all times. There was no abnormality in the vasa nervorum and only a mild increase in endoneurial and perineurial fibrous tissue. A direct correlation was present between the extent and degree of pathology and both severity as well as duration of hyperglycaemia.


Trinitrotoluene: a review of reported dose-related effects providing documentation for a workplace standard. The scientific and medical literature on TNT was reviewed with emphasis on studies providing correlation between work exposures and adverse health effects. Numerous adverse effects including upper respiratory and gastrointestinal complaints, anemia, liver function abnormalities, and possibly aplastic anemia have been noted at TNT levels below the current standard of 1.5 mg/m3. Mild biological effects, particularly reduction in hemoglobin levels or red blood cell counts, have been noted at exposures as low as 0.2 mg/m3. A workplace standard of 0.5 mg/m3 as an 8 hour time-weighted exposure is suggested for protection against adverse health effects.


Periodontal disease associated with Down's syndrome: an orthopantomographic evaluation. The occurrence of advanced periodontal disease with bone loss in patients with Down's syndrome was studied by orthopantomographic technique to obtain objective and quantitative data. The results were compared to a material of pairs matched according to age, sex, and the severity of mental retardation. Both groups of patients were institutionalized and subject to the same hospital conditions and dental care. Eighty-four percent of the young adults (19 to 39 years of age) with Down's syndrome showed advanced alveolar bone loss of 2.5 mm or more as compared with 27% in the matched pair contorls. The mean bone loss of the mandibular first molars in the study group was detected in 17.8%, and in 3.0% in their controls. No difference in radiographically detectable calculus, decay and/or fillings were observed between the two groups. It is concluded that Down's syndrome is associated with an increased prevalence and severity of periodontal disease, and that this is due to the basic congenital disorder rather than to institutionalization or inadequate oral hygiene.¿


Types of intra- and extrafusal muscle fibre innervated by dynamic skeleto-fusimotor axons in cat peroneus brevis and tenuissimus muscles, as determined by the glycogen-depletion method. 1. The types of intra- and extrafusal muscle fibre innervated by dynamic skeleto-fusimotor (beta) axons were determined by using a modification of the glycogen-depletion method of Edström & Kugelberg (1968) combined with histochemical tests for various enzyme reactions. A single beta axon was prepared in each of the experiments, which were carried out on six peroneus brevis and two tenuissimus muscles. 2. The intrafusal distribution of dynamic beta axons is almost exclusively restricted to bag1 fibres. The bags fibre was depleted in each of twenty-four beta-innervated spindle poles; the only fibres of a different type depleted intrafusally were a bag2 fibre in one pole and a long chain in another. 3. Depletion in the bag1 fibres was usually restricted to one zone in one pole, generally in a mid-polar location. 4. The extrafusal muscle fibres depleted by dynamic beta axons belong to the slow oxidative type as defined by Ariano, Armstrong & Edgerton (1973). The number of such fibres in each motor unit could not be accurately determined, but is almost certainly small. 5. The slow oxidative muscle fibres innervated by dynamic beta axons were not depleted over their entire length. Since there is no reason to assume that they are not twitch fibres, it would seem that the localized depletions result from the conditions required to obtain glycogen depletion, i.e. long periods of motor stimulation applied during the occlusion of the muscle's blood supply. Under similar experimental conditions depletion of glycogen was also restricted to portions of fibres in fast oxidative-glycolytic motor units, but extended over most of the length of the fibres in fast glycolytic units.


Symptoms and signs among relatives of patients with HLA B27 ankylosing spondylitis: Correlation between back pain, spinal movement, sacroilitis, and HLA antigens. In order to determine the prevalence of ankylosing spondylitis and the prevalence and pattern of back pain amongst the relatives of patients with ankylosing spondylitis, 63 first degree relatives of 14 propositi were assessed by means of questionnaire, physical examination, and radiology. There were no significant differences in the responses of the B27 positive and negative relatives in relation to prevalence, severity and character of back pain. Ankylosing spondylitis was found in 6.5 per cent of B27 positive relatives and 3.1 per cent of B27 negative relatives; sacroilitis being present in 12.9 per cent of B27 positive relatives and 6.3 per cent of B27 negative relatives. A family studied is presented as a possible corssover between HLA B locus and disease "predisposition" genes. It is suggested patterns of back pain may not be as discriminating as has been thought.


In vitro studies of skeletal muscle membranes. Effects of denervation on the macromolecular components of cation transport in red and white skeletal muscle. The effects of denervation on the macromolecular components of active monovalent cation transport in skeletal muscle have been studied using purified sarcolemma membranes. A comparison of membrane activities of fast-twitch, slow-twitch, and mixed-fiber muscles was made to determine what role, if any, the motor nerve has in regulating this important aspect of muscle metabolism. A dramatic increase in the basal sarcolemmal Mg++ ATPase activity (three- to fourfold) was found for both major muscle types. An increase in the ouabain-inhibitable (Na+ + K+)-stimulated enzyme was also found, but the effect was substantially less (1.5- to twofold). [3H]-ouabain binding, as an index of glycoside receptor sites, also increased (two- to threefold) midway in the course of denervation. On the other hand, the phosphorylated intermediate activity, a functional component of the transport system, clearly decreased over the same time course and remained below control values for the remainder of the course. This resulted in a two- to threefold increase in the turnover number, suggesting that active transport of cations should increase dramatically with denervation. The membrane protein patterns on SDS gels were less obvious than the changes observed in the functional components. The major effects appeared after only one week and seemed to be restricted to high molecular weight membrane proteins, especially in the 100,000 to 250,000 daltons range. This effect was more prominent in slow-twitch membranes with an apparent semiquantitative decrease in stain at 240,000 daltons. In gels of membranes from fast-twitch muscles a decreased stain in the range of 100,000 to 110,000 daltons occurred, and this became more obvious with longer periods of denervation. The results suggest that considerable influence on the macromolecular components of active cation transport in skeletal muscle is exerted by the motor nerve. No appreciable difference was found in this effect when the two major types of skeletal muscle, fast-twitch and slow-twitch, were compared, suggesting that motor nerve regulation of this membrane property is qualitatively the same.


A facile method of purification of neocarzinostatin, an antitumor protein. A three-step column chromatographic method for the purification of neocarzinostatin (NCS) from a crude preparation was described. The purified material was homogeneous by acrylamide gel electrophoresis, isoelectric focusing, amino terminal analysis, and immunologic criteria. Purified NCS was 40 times as active in the inhibition of growth of Sarcina lutea and twice as active against CCRF-CEM human leukemia cells in vitro as was the starting material. When assayed against P388 and L1210 mouse leukemias in vivo, the purified material showed a median increase in life-span of 119 and 72%, respectively.


Multicellular spheroids: a new model target for in vitro studies of immunity to solid tumor allografts. Multicellular spheroids of EMT6 mammary sarcoma cells of BALB/c origin were incubated with normal spleen cells or alloimmune spleen cells generated in vitro in mixed leukocyte cultures (MLC). After 24 hours, spheroids were trypsinized and assayed for surviving tumor cells by use of a cloning technique. Under these conditions a 60-80% reduction in clone-forming tumor cells was observed after incubation of spheroids with immune lymphocytes as compared to normal lymphocyte controls. This cytotoxic effect occurred in situ, and alloimmune cells sensitized against unrelated antigens were much less cytotoxic than were specifically sensitized cells. In parallel autoradiographic studies, some immune lymphoid cells that had been labeled with tritiated thymidine during the proliferative phase of the MLC could be demonstrated within spheroids after 24 hours. These results suggested that multicellular spheroids will be a useful in vitro model for more detailed analysis of the factors controlling infiltration in in situ destruction of solid tumor grafts.


Assessment of diabetogenic drug activity in the rat: 5,5-diphenyl-2-thiohydantoin. The diabetogenic activity of 5,5-diphenyl-2-thiohydantoin (DPTH) via oral administration was assessed in both normal and streptozotocin diabetic rats. Rats were fed powdered chow diet with and without 0.1% (w/w) DPTH. Food consumption and body weight were recorded every other day; whole blood glucose concentrations were determined at the start of the study and at the midpoint. At sacrifice, liver and pancreas were excised and blood samples were collected. Protein and lipid levels were determined in liver; insulin in pancreas; and glucose, insulin, and lipid in blood. DPTH treatment caused decreased food consumption and body weight gain. The drug dose, calculated from the food consumption data, was 76.5 mg/kg/day for the normal rats and 107 mg/kg/day for the diabetic rats. DPTH increased liver weight and liver lipid content in both normal and diabetic rats, and markedly lowered serum triglyceride concentration in normal rats but not in diabetic rats. Serum fatty acid concentration was not altered by DPTH. DPTH produced a significant elevation of blood glucose concentration of the diabetic rats that was not, however, correlated with altered pancreatic insulin concentration. In vitro, DPTH infusion inhibited insulin secretion by the perfused pancreas.


Dissociation of excitation and contraction in skeletal muscle induced by deuterium oxide and dantrolene-sodium. The effect of D2O and dantrolene-Na (DAN) on the electrical and mechanical responses of single muscle fiber (mouse EDL and frog semitendinosus), Ca2+ uptake and release of sarcoplasmic reticulum (SR) and contractile proteins was investigated to elucidate the coupling mechanism between depolarization and contraction. Both agents inhibited tension development induced by depolarization and caffeine, especially the initial phase of contraction (more pronounced in fast muscle) without affecting excitation of membrane and contractile machinery. The effect of DAN can be antagonized by increasing Ca2+ concentration and lowering the temperature of the medium. Ca2+ uptake and release abilities of isolated SR were not altered significantly in DAN, but were reduced considerably in D2O. These results suggest than there is a Ca2+-mediated trigger mechanism for the rapid release of activator Ca2+ from internal storage (SR). DAN and D2O interfere predominantly the action of the site(s) of this mechanism, probably on the T-tubules. In addition, D2O decelerates Ca2+ release from SR per se.


Purification of histamine receptor, (III) Characterization of receptor rich membrane fraction of small intestinal smooth muscle of the cat. Intracellular localization of histamine receptors in small intestinal smooth muscle of the cat was studied by investigating distribution of marker enzymes in the receptor rich fraction. Distribution of membrane markers coincided with that of the radiochemically labeled receptor fraction. Membrane fraction was further purified and it was concluded that the histamine receptor rich fraction is mainly composed of cell membrane. The chemical composition of the fraction lent support to this conclusion.


Possible involvement of a central noradrenergic system in automutilation induced by clonidine in mice. Automutilation induced by a single large dose of clonidine was potentiated by pretreatment with methamphetamine, caffeine and theophyline, while it was inhibited by acute administration of reserpine, alpha-methyl-p-tyrosine, phenoxybenzamine, phentolamine and chlorpromazine. L-Dopa, 5-hydroxytryptophan and p-chlorophenylalanine had no effect on this abnormal behavior. Biochemical studies on brain monoamines revealed that noradrenaline was markedly increased and dopamine slightly so, but 5-hydroxytryptamine was never changed by clonidine. These results suggest that a central noradrenergic system may be involved in automutilation induced by clonidine in mice.


The mesangial cell in glomerulonephritis. I. Mechanisms of hypercellularity in experimental immune complex glomerulonephritis. One-shot active immune complex glomerulonephritis was induced in rabbits by intravenous bovine serum albumin (250 mg. per kg.) and the mechanism of glomerular hypercellularity investigated. Most of the extra cells were mononuclear with few polymorphonuclear leukocytes. Fibrin was present in severe lesions. Glomerular mitoses were seen in normal kidneys but were more common in hypercellular glomeruli. This is direct evidence of local proliferation. Also, biopsies taken 1 hour after giving tritiated thymidine contained locally labeled cells. The mitotic rate and degree of local labeling both varied in proportion to the degree of hypercellularity. By electron microscopy both mesangial and endothelial cells were identified in mitosis. The majority of the mononuclear cells in the hypercellular glomeruli could not be identified by position or ultrastructure. Infiltration by nonglomerular cells was confirmed by the presence of macrophages, lymphocytes, and plasma cells.


Lymphocyte blastogenic responses to allogeneic leukocytes and autochthonous tumor cells in colorectal carcinoma. The blastogenic reactivity of peripheral blood lymphocytes (PBL) and mesenteric lymph node lymphocytes (LNL) against normal allogeneic leukocytes and autochthonous colorectal carcinoma cells is evaluated in 36 patients, and correlated with the patient's Dukes classification. Mesenteric LNL react significantly better than PBL to allogeneic leukocytes in both Dukes B and C (p less than 0.05). There are too few patients in Dukes A and D to permit statistical evaluation but the trend is the same. By contrast, LNL fail to react to autochthonous tumor cells in all classes, except in a few Dukes B patients. The proportion of PBL reactivity to autochthonous tumor cells seems to increase for Dukes C and D. It is possible that specific lymphocyte reactivity in colorectal carcinoma may be related to the antigenicity and immunogenicity of the tumor.


[The investigation of a low molecular acid stable proteinase inhibitor in the middle ear secretion (author's transl)]. The proteolytic activity of different proteinases during chronic otitis media can be inhibited by alpha-2-macroglobulin and alpha-1-antitrypsin. A new low molecular (13,000) acid stable and polyvalent proteinase inhibitor could be investigated in the middle ear secretion from patients with cholesteatoma and chronic otitis media. We believe that this inhibitor is identical with the low molecular inhibitor of bronchial mucus and the nasal fluid. This inhibitor shows a high anti proteolytic capacity and can inactive trypsin, chymotrypsin, pronase and leucocytic preoteinases. The inhibitor is not detectable in any case. We could find it in 55 cases, three specimens of middle ear secretions obtained no acid stable inhibitor. It is present in the secretion in a masked form by in situ-reaction with leucocytic proteinases. By denaturating deproteinizing it is liberated out of the complex with proteinases and can be measured. The investigations demonstrate that the level of the inhibitor varies during the course of a chronic otitis media. In the postoperative phase the inhibitor concentrations were clearly higher than preoperatively. A steep drop of inhibitor can be observed in cases of chronic otitis with the symptomatology of an acute inflammation. In cases with a chronic inflammation the inhibitor level seems to remain low. The decrease of the inhibitor is explained as a using up effect during reaction between inhibitor and leucocytic proteinases. We believe that this inhibitor in the middle ear secretion results from a limited proteolysis and splitting of inter-alpha-trypsin inhibitor by a proteolytic enzyme, possibly by kallikrein.


[Postmortem changes of fine structure in the auditory pathways (organ of Corti and nucleus cochlearis of the guinea pig (author's transl)]. Autolytic changes in the guinea pig cochlear nucleus were studied by means of light- and transmission electron microscopy from 5 min. up to 5 h post mortem. Hyperchromasy and shrinking of neurons was observed already after 5 min. in areas, where the neurons have a high number of primary afferent nerve endings (Kane 1973). A second mode of post mortem degeneration was found. It was characterized by a swelling of the cell, which showed a diminished stain-ability. This lytic swelling seemed to be less rapid and probably less harmful in the beginning. The cochleae were examined by scanning electron microscopy. In contrary to known damaging agents (like noise or antibiotics) the outer haircells showed hardly any changes in the surface structures up to 1 hour in  the basal coil, while lytic protrusions were observed in outer and inner haircells already after 5 min. in the apical parts. Post mortem changes in the cochlea and in the nucleus cochlearis show two different modes of autolytic degeneration.


[Graphs on the growth of the ice-ball using round cryoprobes at -80 degrees C and -196 degrees C (author's transl)]. Graphs and tables are shown describing the growth especially the depth of the ice-ball in tissue during freezing with round flow and massive probes (2-20 mm diameter). Thus prior to clinical application of cryosurgery the probe diameter and the time of freezing can be estimated corresponding to the size of the tumor. Results are presented for temperatures of the cooling fluid of -196 degrees C (liquid nitrogen) and -80 degrees C.


[Correcture of congenital defects of the wing and the tip of the nose (author's transl)]. Congenital hypoplasia of the nasal wing can appear as a defect (congenital notch) or as a flattening and deficiency of the cartilagineous support. The combination with other deformities is seen frequently, 2 own cases: 1. Congenital notch of the left ala nasi. Operation: forming a window in the wing by incision, implantation of a composite graft from the ear, undisturbed and complete healing. 2. Hypoplasia of both cartilages of the ala nasi, flatness and dropping of the nasal tip, combined with deformities in both middle ears. Operation: Lifting the nasal tip, median suture between the cartilages of the wing in the tip, implantation of some septal cartilage in the latter to fill up the flatness. Both cases showed also after one year a good result.


[Improved correction of saddle nose deformity by means of axial wire-stabilization (author's transl)]. After having made some introductory comments on the problems of saddle nose correction, the author reports about an own improved operating technique characterized by axial wire-stabilization of the implanted cartilage and demonstrates accessible results.


[Rhinoplasty--a mainly aesthetic or functional operation (author's transl)]. Reviewing personal indications for rhinoplasty and subjective estimation of the postoperative result in 202 patients (104 male and 98 female) it is asked, whether rhinoplasty has to be regarded as a mainly aesthetic or functional surgical procedure. The catamnestic study showed, that most patients preoperatively complained about impediment of nasal breathing as well as of deformities of the external nose. In men we found about the same frequency of predominantly functional and aesthetic indications, respectively, whereas in women the aesthetic motivation distinctly prevailed. However, postoperative complaints of male and female patients mainly referred to the shape of the external nose. Many patients don't talk of those complaints before some time has passed: right after surgery 85% of 202 patients stated to be completely satisfied by the postoperative result, but 1/2 to 3 years later we only counted 67% (of 155 inquired cases) still expressing full satisfaction. In only a few cases postoperative dissatisfaction was likely to be caused by noticeable nasal deformities or (even less often) unimproved nasal obstruction. In many patients postoperative dissatisfaction appeared rather due to psychological disturbances than to aesthetic insufficiencies, this being demonstrated by two cases described. Faced with these observations one can call rhinoplasty neither a mainly aesthetic nor a mainly functional operation; rhinoplasty requires improvement and preservation of nasal function as well as a careful consideration of aesthetic principles.


[Corrective operation of the upper lip-columella-region after closure of bilateral clefts (author's transl)]. For the correction of the retracted upper lip and columella after bilateral cleft-operations we use a submental hairbearing flap which cut as a narrow stripe of skin and subdermal tissue and autonomised is swung to the upper lip. The defect to cover results after circumcision of the scarred middle part of the upper lip used as the lower portion of the shortened columella. This method has been used with good results in 4 cases, 3 men and 1 woman.


[Primary covering of oropharyngeal defects after block resection of large malignant tumors (author's transl)]. The covering of defects in ablative oral surgery is associated with particular problems because, in order to avoid the formation of salivary fistulas, a primary closure should be aimed at. Between 1973 and 1975 86 carcinomas of the floor of the mouth, the tongue or the oropharynx were treated by block resection including radical neck dissection without preoperative radiation in 28 Cases the forehead flap and in 20 cases the tongue flap were employed. While the foreheaded flap necessitates the preservation of the ipsilateral A. carotis externa, the tongue flap can be used even if the ipsilateral lingual artery is sacrified. The tongue flap has functional and cosmetic advantages in comparison to the forehead flap. The temporarily transsected mandibula was refixed by compression plates without intermaxillary wiring.


[Use of the temporary osteoplastic epitympanotomy for allogenetic compound middle ear grafts (author's transl)]. The topography and the size of the single middle ear structures and the possibilities of damage are shown, as they face the otosurgeon using the temporary osteoplastic epitympanotomy in connection with middle ear implants. The landmarks and technical aids are named, which make this operation a save and quick approach for the removal of the middle ear pathologies and in the use of allogenetic material.


[Development from skin- to fascia- and to cartilage tympanoplasty (epitympanon-antrum-mastoidplasty) (author's transl)]. Experiences with 8029 endaural tympanoplastes show interruption of the self-cleaning process of the endaural epithelium after 366 tympanoplasties with skin grafts. The self-cleaning process may be preserved after fascia temporalis (2325) and cartilage (5338) plasties, because of overgrowth with local epithelium. 16 years after combined fascia temporalis and cartilage tympanoplasty the pieces of cartilage are almost unchanged but the fascia temporalis is more or less thinned to atrophic scars and according to tubal function it shows adhesive retraction pockets or bulging. For 7 years we have not been using fascia any more, but ear cartilage for the tympano-epitympano-antrum-mastoidplasty. Cartilage material not used is kept in a cartilage bank. Recurrence of cholesteatoma will press the cartilage plasty into the external auditory canal, whereas after osteoplasty of the endaural canal wall the patient runs to an uncertain percentage the same risk as before the operation.


[Concerning "Bellocq's tamponade" (author's transl)]. A nasopharyngeal tamponade is introduced that is more adquate than the traditional Bellocq-tamponades as their disadvantage of outer grooves is avoided by a fastening string that passes through a button at the backside of the tampon and through its centre.


[Surgical treatment of the pneumosinus dilatans of the frontal sinus (author's transl)]. Two cases of pneumosinus dilatans of the frontal sinus with cosmetic deformation are reported. In both cases one big hole without any interfrontal septum has been found. In the first case no efferent ducts of the frontal sinus have been visible, the second one showed only one. Surgical treatment by incision from ear to ear, and forming of a scalp flap with opening of the frontal sinus in the upper margin of the bony bulging. This bulging was left pedicled on the periosteum and fractured in many pieces. Forming of an artificial efferent duct to the nose by an incision below the left eyebrow. Good cosmetic results in both cases. X-rays fotos, pictures of the operation and postoperative results are demonstrated. Examinations of the human growth hormones (HGH) of the 24-years-old German and the 28-years-old Turkish man presented normal values. The author believes in a dysregulation of the efferent ducts.


[Esophageal stenosis in a case of pemphigoid benignum (author's transl)]. The rare complication of Pemphigoid benignum and esophageal stenosis is reported. The problems of diagnosis, pathogenesis and therapy are discussed.


[Facial and head pain from the neurologist's point of view (author's transl)]. Recognizing that pain is not a sensory sensation, but a subjective feeling, the neuroanatomical and neurophysiological aspects are shortly discussed which are the prerequisites of pain as an original phenomenon in higher life. The subcortical feeling of pain is compared with the pain sensation which extends to large parts of the cortex. The experience of pain may be suppressed or increased by the cortex. Since pain as a subjective phenomenon cannot be objectivated directly, the pain analysis has to consider the history of the patient and particularly the anatomical and physiological basis. The clinical diagnosis of facial and head pain differentiates the various pain syndrome which as localized pain are usually caused by externally visible changes from those projected pain phenomena in genuine or symptomatic neuralgias as well as referred pain sensations (e.g. in intracranial or occipitocervical lesions).


[The cervical headache (migraine cervicale) (author's transl)]. Symptoms and etiology of "Migraine cervicale" are discussed. Further more the treatment of the complaints is mentioned.


[Facial and head pain from the otorhinolaryngologist's point of view (author's transl)]. From the  otolaryngologist's point of view, there are multiple causes for the frequent symptom of facial and head pain: headaches due to ear diseases: pain extending to the ear region, with special regard to "referred otalgia" involving the cranail nerves V, IX, X; facial pain due to temporomandibular dysfunction; rhinological causes of facial and head pain, including posttraumatic trigeminal neuralgia and "facial sympathalgies"; the syndrome of the elongated styloid process. The diagnosis and therapy of the "typical" ENT diseases is not described in detail since the paper deals mainly with less known and, regarding their diagnosis and treatment, problematic diseases.


[Sensorineural deafness and cochlear otosclerosis (author's transl)]. The so-called labyrinthine otosclerosis is defined as a focal otosclerotic involvement of the labyrinthine capsule without stapes fixation. It produces a pure sensorineural hearing loss. The histology of this phenomenon is well known. The relative frequency of labyrinthine otosclerosis is between 4 and 40%, as referred in literature. On x-rays, an advanced demineralisation or complete obliteration of labyrinthic bone is suspicious of otosclerosis. There is no typical pattern of sensorineural hearing loss. But not seldom a fair discrimination index contrasts with a severe threshold evaluation in pure tone audiometry. 208 audiogramms of otosclerosic ears verified by stapedectomy were examined. After correction for normal presbyacusis the sensorineural hearing loss due to otosclerosis is twice that of presbyacusis. In otosclerosis tinnitus is often reported as of metallic type, but a characteristic tinnitus does not exist. There is no universal agreement about the relative frequency of vestibular disturbances in otosclerosis. One should diagnose labyrinthine otosclerosis only if several criteria found are not explanable otherwise, and these criteria are explained.


[Toxic diseases of the inner ear (author's transl)]. A clear presentation of toxic diseases of the inner ear under consideration of the endogen and exogen factors is shown by means of tables as well as clinical findings and experimental results obtained in animals.


[Inner ear hearing loss following blunt head injury (author's transl)]. The pathologenesis of inner ear hearing loss after head injury is not uniform. Recent experimental and clinical findings in ophthalmology, neuropathology and neurosurgery indicate that there is not only a direct mechanical caused damage but as well an indirect injury of the inner ear secondary to disturbances of the cerebral blood supply. These cases representing about 30% of the patients are characterized by fluctuating hearing loss, which may increase of decrease even weeks or months after the incident. To assist inner ear microcirculation after head injury we therefore suggest to try an early treatment with medicaments increasing the cochlear blood flow, provided that the general conditions of the patients tolerate this.


[Viscosity of blood and sensorineural hearing loss (author's transl)]. A statistical survey about the results of treatment of Pentoxifyllin (Trental) in acute and long-standing sensorineural hearing losses is given. The pharmacological effect of viscosity lowering in such patients is demonstrated. The role of erythrocytes and their behaviour in relation to the viscosity of blood its showed by means of literature.


[Hearing loss in cardiovascular diseases (author's transl)]. For the  sensory cells of Corti's organ are high susceptible to deficits in O2-supply, all disturbances of blood-flow in the inner ear can deteriorate the hearing function. It is the hypotonic dysregulation of the microcirculation in the stria vascularis, which is much more dangerous for the inner ear auditory receptors than be hypertonic disease. The occurance of acute or progredient hearing loss with symptoms of a sensorineural leason and of tinnitus therefore can be looked as an indication to the beginning of a cardiovascular disease, and necessitates appropriate diagnostic and therapy.


[Venous tinnitus (author's transl)].

[Venous tinnitus (author's transl)]. The etiology of venous tinnitus is discussed. The simple ligation of the internal jugular vein performed under local anaesthesia has resulted in the total disappearance of the hum in three cases.


[The apoplexy of the labyrinth (author's transl)]. Owing to the morphological, physiological and pathophysiological similarities in the vasculature of the brain and the inner ear, the term apoplexy can also be applied to the inner ear. The apoplexy of the labyrinth is defined as an acute and severe panlabyrinthic disturbance with sudden hearing loss or deafness in association with vestibular functional disorders. The apoplexy may occur after hemorrhage as a result of inner ear blood vessel ruptures or after malacias following localised ischemias just as it occurs in the brain. Treatment of such cases were carried out by application of high doses of cortison. The prognosis of these inner ear disturbances is unfavourable.


[Anatomical conditions influencing the therapy of the inner ear (author's transl)]. Morphological factors affecting the course of disturbances of the inner ear are demonstrated. Its important to realise that damaged sensory cells may recover quite a long time after injury. The blood supply and its regulation, possibly by autonomic innervation, are significant in the treatment of the inner ear. The reported findings must be regarded as the combined effort of numerous factors (Biology of the inner ear).


[Treatment of acute inner ear deafness (sudden deafness and acoustic trauma) (author's transl)]. The principal facts concerning therapeutic measures in cases of sudden deafness and acoustic trauma are outlined. Experiment data concerning the pharmacology of inner ear circulation are presented. There is sufficient evidence for a critical evaluation of a few treatments whose effect seems to be proven (experimental increase of inner ear circulation in normal animals) or at least possible (in normal animals no or dubious increase; effective under pathological conditions only?). Experimental and clinical experiences concerning the dextran treatment of sudden deafness and acoustic trauma are reported.


[Therapeutical results of non-acute perceptive hearing loss with vasoactive medicaments (author's transl)]. 67 patients who are suffering from a non-acute perceptive hearing loss were treted by several vasoactive medicaments. Besides pharmacological aspects of derivatives of di-ethyl-amino-ethyl-alcohol and of xanthine were discussed. The therapeutical results were subjected to comparing views.


[Sympathetic trunk treatment or infusion therapy in cases of sudden deafness (author's transl)]. The optimal criterion for registering the result of a sudden-deafness-therapy is a class interval of 25 dB in the audiogram, followed by punctal evaluation of the mean value of the frequencies 0,5/1/2/4/8 kc/sec. Blocking of the sympathetic trunk, as well as infusions using low-molecular dextranes or derivatives of nicotnic acid, furthermore strictly oral treatment as well as combinations of all these, all lead to a statistically proved recovery of hearing. The extent of improvement is ascertainbly smaller with strictly oral treatment than with blocking the sympathetic trunk or with infusions. Hearing is slightly more improved by blocking the sympathetic trunk than by infusional treatment. Statistically however, the difference is not significant. Low-molecular dextran (Rheomakrodex) is not superior to Xantinol-Nicotinate (Complamin). Future investigations in the assessment of therapeutical results should exclusively evaluate unilateral sudden deafness and include the intact second ear into the computation.


[Comparison of nystagmus responses after thermic stimulation (author's transl)]. A model of the vestibulo-oculomotor system allows theoretical considerations concerning unsymmetrical nystagmus responses. For thermic stimulation unsymmetrics are estimated by means of a commonly used formula for relative differences of reactions. It is shown that the relation between these unsymmetrics and the real change of nystagmus intensity is nonlinear and also different for abnormal decrease and increase of intensity, respectively. Possible misinterpretations are avoided, e.g., by analysis of absolute parameters of nystagmus.


[The validity of absolute "standard values" for the evaluation of the thermic vestibular test--results from electronystagmographic investigations with critical comment on the frequency nystagmogram (butterfly scheme) (author's transl)]. The findings presented here on the thermic examination of 100 healthy test persons and the statistical analysis lead up to the conclusion that the single standard deviation from the statistical mean value  of a parameter (Claussen) describing the intensity of a thermic nystagmus reaction does not seem suitable to be assumed as normal range. This is true, too, if these values were achieved from a larger number of healthy persons. On application of the "butterfly scheme" (Claussen) a non-tolerable number of false positive findings resulted. The cause for this is the fact that extravestibular factors, particularly the degree of consciousness, but also the age, influence considerably the absolute value of nystagmus parameters. Furthermore, since the numerical values are not distributed normally, the statement of a standard deviation is not applicable. As an alternative, a procedure is being demonstrated which according to our knowledge was first mentioned by Jongkees. We are suggesting to base the evaluation of the thermic test on the comparison with so-called interquantile ranges of healthy persons. These are percentage ranges within the values of e.g. 80, 90 and 94% of healthy persons are found. In our opinion, in combination with the Jongkees-formula this procedure represents a more favourable criterion for the evaluation of a thermic test.


Prevention of obesity in Avy/a mice by dehydroepiandrosterone. Dehydroepiandrosterone, a mammalian glucose-6-phosphate dehydrogenase inhibitor, prevented Avy/a mice from becoming obese. Decreased accumulation of triacylglycerol accounted for a large portion of the weight difference between treated and control Avy/a mice. Hepatic lipogenesis as measured by 3H2O incorporation into total lipid was less in the dehydroepiandrosterone-treated mice. Dehydroepiandrosterone did not suppress appetite and had no apparent toxic effects at the doses used, and its weight controlling effects were reversible upon withdrawal of treatment.


[Allergy to chromium and nickel in workers employed in margarine production]. The paper presents the cycle of margarine production with special attention to the process of hardening of vegetable oils using nickel formate as catalyst. Test examination (patch tests) was carried out with standard set and nickel formate in 10 workers of hardening department and 24 female workers of packing room. In 2 workers contact dermatitis caused by sensitization to nio nickel formate was observed. In 5 workers was found latent allergy to nickel and in 12 female workers latent allergy to chromium and nickel. In the control group containing intellectual workers, uniform in regard to sex and age, the results of patch tests were negative.


Noninvasive measurement of the intracardiac blood flow by means of ultrasound techniques. A new noninvasive method of measurement of the intracardiac blood flow by means of ultrasound techniques is described. In this system the "M-sequence modulated Doppler method" and the method of ultrasonotomography are used in combination. An arbitrary space within the heart can be selected by ultrasonocardiotomography and the blood flow profiles can be observed by the "M-sequence modulated Doppler method." The new Doppler flow meter system described in this paper can be applied not only for the diagnosis of heart diseases, but also for the study of pathophysiology of the blood flow and of the factors responsible for the dilatation of the heart. Further studies are required from the viewpoints of medicine and engineering to accumulate sufficient data before routine application of the method described in this paper is fully warranted.