Liver damage associated with perhexiline maleate.

Two patients who developed biochemical and histological evidence of hepatitis while taking the anti-anginal drug perhexiline maleate are described. The pathological changes were those of mild to moderate fatty change together with a hepatitis which resembled alcoholic hepatitis, including in one patient the presence of material which by light microscopy was indistinguishable from Mallory's alcoholic hyalin. However, the predominantly periportal location of this material contrasted with the centrilobular distribution of Mallory's hyaline. One patient showed, in addition, severe atypia of the hepatocytes which was still present in less pronounced form 10 weeks after stopping perhexiline. The other patient had advanced hepatic fibrosis.


Changes in hepatitis B virus DNA polymerase in relation to the outcome of acute hepatitis type B.

Serum levels of hepatitis B virus specific DNA polymerase and hepatitis B e antigen were studied serially in 34 patients with hepatitis B virus infection--20 who had the acute illness and recovered, seven who died with fulminant disease, three who died as a result of subacute hepatic necrosis, and four who went on to develop chronic active hepatitis. DNA polymerase activity was present in 16 (80%) and HBeAg in 13 (65%) of the uncomplicated cases at presentation and in all of those patients from whom the initial sample was obtained before the peak in aminotransferase. Both markers disappeared after 30 days from the onset but DNAP remained persistently positive during a follow-up period of four to 10 months in the four patients who progressed to chronic hepatitis. These results indicate that DNAP and HBeAg are transiently present in all cases of acute hepatitis B. Only their persistence after the acute episode could represent a useful prognostic marker of chronically. In this respect, DNAP was more reliable in our patients than HBeAg. In uncomplicated acute hepatitis, the peak in DNAP levels, which defines the time of maximum virus replication in the liver, preceded the peak in aminotransferase levels. Among the 10 patients who developed massive liver damage after hepatitis B infection, DNAP was detected in five of the seven with fluminant hepatitis, with enzyme levels that were comparable with those observed in uncomplicated acute hepatitis and presentation, but not in the cases of subacute hepatic necrosis. These findings are consistent with the hypothesis that in hepatitis B infection, liver damage, whatever the severity, is not directly related to the degree of virus replication.


Plasma glucagon in diabetes of haemochromatosis: too low or too high?

Glucagon secretion before and during arginine infusions was tested in 11 patients with diabetes associated with haemochromatosis. The results were compared with those obtained in six normal subjects and five patients with haemochromatosis but normal glucose tolerance. The patients with haemochromatosis, regardless of glucose tolerance, exhibited higer level of plasma immunoreactivity for glucagon (antiserum 30-K) suggesting hyperglucagonaemia. However, additional analysis revealed that a considerable amount of this glucagon immunoreactivity was due to cross-reacting material of high molecular weight, the levels of which were significantly higher in patients with idiopathic haemochromatosis. When this was deducted from the total immunoreactivity measured, the resulting values for true glucagon concentrations were similar to those of normal subjects. The data suggest that (1) patients with idiopathic haemochromatosis, whether or not associated with diabetes, exhibit plasma glucagon levels comparable with those of normal subjects; (2) the plasma of the same patients contains significantly more high-molecular-weight substances reacting with glucagon antiserum 30-K than is present in plasma of normal subjects; and (3) 'hyperglucagonaemia' may be erroneously suggested when glucagon is measured with certain antisera reputed to be specific for glucagon.


Relationship between endotoxaemia and protein concentration of ascites in cirrhotic patients.

Endotoxaemia was investigated by the Limulus assay in 42 cirrhotic patients with ascites and in 33 without ascites. The incidence of endotoxaemia in the former group (59.5%) was significantly (P less than 0.05) higher than in the latter (36.4%). Correlation between endotoxaemia and specific gravity and concentrations of total protein, albumin, and globulin in ascitic fluid was studied in the group with ascites. The specific gravity of ascites in 25 patients with endotoxaemia was significantly greater than that in 17 patients without endotoxaemia (P less than 0.01). The concentration of total protein in patients with endotoxaemia (13.95 +/- 7.18 milligram, mean +/- SD) was nearly twice as high (P less than 0.01) as in patients without endotoxaemia (7.49 +/- 3.60 milligram). The protein content of those who showed reactions greater or equal to 2(+) in the Limulus assay (16.78 +/- 7.14 milligram) was a significantly (P less than 0.05) higher than in those with 1(+) reaction (11.26 +/- 6.33 milligram). Moreover, the concentration of albumin in patients with endotoxaemia (7.68 +/- 4.60 milligram) was more than twice that of the patients without endotoxaemia (3.39 +/- 1.58 milligram, P less than 0.01). On the other hand, globulin concentration in patients with endotoxaemia was 1.6 times that of patients without endotoxaemia (P less than 0.01). Similar differences were noted between endotoxaemic and non-endotoxaemic patients in the ascites-to-serum ratio in protein, albumin, and globulin. These results suggest that in liver cirrhosis endotoxaemia may cause an increase in protein concentrations in ascitic fluid, and that it may be a precipitating factor in the formation of ascites.


Patchy enteropathy in childhood.

Two hundred and seventy-eight duodenal biopsy specimens taken consecutively from children using either a single port paediatric Crosby capsule or a double port modification were examined both histologically and by dissecting microscopy, in order to determine the incidence of patchy mucosal lesions. One hundred and six specimens were abnormal and 49 of these were patchy. Patchy lesions occurred most commonly in cow's milk sensitive enteropathy where 66% of 33 specimens were patchy; in comparison all children with undiagnosed coeliac disease taking a normal diet showed a uniformly flat mucosa. Twenty-two per cent of specimens taken using the double port and 10% using the single port capsule were patchy, a statistically significant difference (P = 0.01) using standard errors. Where lesions were uniform, grading by dissecting microscopy correlated well with histological grading; 18 (37%) of specimens were, however, recognised as patchy only on gross appearance. The high incidence of patchy lesions of the proximal small intestine reflected the prevalence of cow's milk protein intolerance and the postenteritis syndrome in these children. The use of the double port capsule and of dissecting microscopy also contributed to the high incidence found.


Amylase activity in human bile.

The mean amylase level in 42 human bile samples was 154 IU/l and there was no significant difference in the amylase activity of 32 paired serum and bile samples. Estimation of the amylase thermolability of bile showed it to be similar to that of serum. This suggests that the amylase activity in bile may have filtered through the liver from the hepatic circulation rather than refluxed from the pancreatic duct. The presence of amylase in human bile provides further evidence that the liver might have a role in the regulation of serum amylase.


Effects of age, antigen deprivation, and allograft rejection on epithelial cell kinetics in mouse colon.

A technique of microdissection of colonic mucosa has allowed the study of mitotic activity, measured by metaphase accumulation following colchicine blockade, in individual crypts of mouse colon. The changes occurring during growth and development of normal colon have been studied and compared with changes found in antigen free colon (colonic isografts) and in cell-mediated immune damage of the bowel (allograft rejection). Metaphase accumulation was steady at two metaphases per hour in baby mouse colon until 18 days after birth. Between 18 and 24 days a rapid, and significant increase in mitotic activity occurred (P less than 0.01), reached adult values, and changed no further. Metaphase accumulation in isografts was similar to normal colon for the first two weeks after transplantation but the rise in mitotic activity in the third week did not occur. Allografts of colon showed two- to three-fold increases in metaphase accumulation when compared with both normal colon and isografts (P less than 0.01). When crypt mitotic activity was compared with the length of crypts measured in histological sections of normal colon, isografts, and allografts, no clear relationship was observed. Both changes in the luminal environment of the gut at the time of weaning and cell-mediated immune reactions in the colonic wall appeared to be associated with increased mitotic activity in colonic crypts.


Colonic adenomas--a colonoscopy survey.

A colonoscopy survey of 620 patients with 1049 colon adenomas showed a predominantly left-sided distribution (77%). Of these lesions 97% were amenable to endoscopic removal or ablation. Sixty per cent of patients presented with rectal bleeding as their major symptom. There was agreement between radiology and colonoscopy in only 62% of patients, as many of the studies were single contrast barium enemas, performed before referral. Forty-eight per cent of adenomas in our series were less than 1.0 cm in diameter. Of the larger adenomas (greater than 2.0 cm in diameter) 66% were situated in the sigmoid colon, and of those containing invasive carcinoma (4.8% of the total) an even higher percentage (94%) were in the sigmoid and low descending colon. With increasing polyp size, there was a greater predominance of villous elements and this was associated with a higher risk of malignant change than the more frequent and generally smaller tubular adenoma. Local colonoscopic excision alone is sufficient treatment for adenomas with malignant change unless they are poorly differentiated histologically and providing adequate resection is demonstrated. Twenty-eight patients treated in this way are alive without recurrence at periods from six to 62 months. Although 65% of patients had only one adenoma, and 90% three or less, there is a risk of developing other benign and malignant colon neoplasms and careful follow-up is required.


Cell proliferation in the human gallbladder epithelium: effect of distension.

DNA synthesis activity in the epithelium of the human gallbladder was studied through in vitro labelling of mucosal specimens with 3H-thymidine and autoradiography. The specimens were taken at the time of a surgical operation. Eight 'normal' gallbladders and six distended gallbladders from patients with carcinomatous obstruction of the common bile duct were examined. Proliferative activity was very low in the normal and significantly higher in the distended gallbladders.


5'-Nucleotidase of L 1210 cells. Cytochemical and kinetic studies.

The activity of 5'-nucleotidase in L 1210 leukaemia cells fixed in situ by glutaraldehyde was established by electron microscopic cytochemistry and biochemical assays. The enzyme activity is localized uniquely on the cell surface. In biochemical assays the time course of phosphate liberation by the suspension of glutaraldehyde fixed cells was linear up to 15 min incubation. The activity was proportional to the number of cells in the suspension, amounting of 0.019 units activity per 10(8) cells.


Effect of starvation on the genetic activity of nucleus and nucleolar organizer.

The investigations of root meristems and hypocotyls of Lupinus albus L. starved, and then fed with 2% sucrose were carried out and several variations in nuclear and nucleolar dimensions, their ultrastructure, template activity of DNA, activities of RNA polymerases and transcriptional activity, were found. As a result of starvation, the surface area of nuclei and nucleoli decreases several times; after 24 hours, in the presence of sucrose, it grows again, but the control state is not achieved. Moreover, in a starved material the area of condensed chromatin in nucleus is increased by 1/3; after feeding, its partial recovery to the initial state is observed. The intensity of binding of 3H AMD in a fed material is increased by 1/3 as compared with the starved one. Transcriptional activity, estimated on the basis of 3H uridine incorporation is decreased in a starved material, especially in the meristematic tissue; feeding intensificates the transcriptional activity whereas the activity of endogenous RNA polymerase, investigated in hypocotyl, is drastically lowered in a starved material. Sucrose feeding does not restore the control state, though the per cent of nuclei and nucleoli revealing the activity of RNA polymerase is much higher in a fed material than in a starved one.


Demonstration of dehydrogenase activities in paraffin sections.

The possibility of demonstrating the activity of respiratory enzymes in paraffin sections was studied. Unfixed pieces of nervous tissue were incubated at 4 degrees C, 20 degrees C, 37 degrees C and 56 degrees C for various periods ranging from 1 to 24 hours. After dehydration, the tissue pieces were mounted in paraffin. The paraffin sections obtained there of were then tested with respect to the range of penetration of the substrate into the incubated tissue samples (as judged from the resulting histoenzymic reaction), and for the distinctness with which the localization of the histochemic reaction could be assessed. From the results it may be concluded that it is possible, under well defined conditions, to demonstrate the activity of dehydrogenases in paraffin sections. The resulting morphological pictures permit a much better localization of the histoenzymic reaction products than those obtained from cryostat sections. Optimal results are obtained when tissue fragments, about 1 mm in diameter are incubated for 24 hours at 4 degrees C.


Ultrastructural alterations in extrinsic eye muscles induced by vincristine.

A comparative morphological analysis of the effects of vincristine on particular types of muscle fibres of the eye and selected trunk muscles of the mouse was performed. Great resistance of the mouse organism to the action of sublethal doses of vincristine has been found. Degenerative changes of great intensity (atrophy of myofibrils, disturbances of the Z line) and the appearance of new changes, not mentioned hitherto among the vincristine myopathies (megamitochondria, intermembranous inclusions, glycogen in mitochondria and very large vacuoles) were observed in the trunk muscles of mice. The eye muscles are seem to be more resistant to the action of vincristine. The intensity of changes in the eye muscles was connected with the types of muscle fibres. Red fibres, rich in mitochondria, underwent relatively greatest changes, whereas the smallest changes were found in tonic fibres, poor in mitochondria and sarcotubular system, i.e. these structures from which spheromembranous bodies, most characteristic of the pathogenic effects of vincristine arise.


[Decrease of ACh response in isolated duodenum from SART stressed (repeated cold stressed) mice (author's transl)].

ACh response in the isolated duodenum from SART stressed (repeated cold stressed) mice was remarkably decreased in comparison to normal mice 5 days after onset of loading SART stress, and maximal contraction in SART stress mice duodenum was about 37% of that in non-stressed mice. Pilocarpine and KCl responses were also considerably decreased, but BaCl2 response was much the same as in the controls. Thus, the contraction system of the muscle is apparently not damaged by SART stress. Though body weights decreased, the daily intake of food incressed in SART stressed mice. Length of small intestine from SART stressed mice was much the same as in controls, but wet weights of small intestines were larger than in controls. Autonomic agonists, antagonists, tranquilizers and other drugs were given intraperitoneally to mice once daily during SART stress, and the ACh responses in the isolated duodenum were investigated. Pretreatment with adrenergic and anticholinergic drugs inhibited the decrease of ACh response, but antiadrenergic and cholinergic drugs had no effects. Pretreatment with tranquilizers such as reserpine, chlorpromazine, carpipramine and imipramine inhibited the decrease of ACh response in the isolated duodenum, but diazepam, meprobamate and benadryl had no influence. Pretreatment of neurotropin, a neurosedative had good inhibitory effects. Our results suggest that SART stressed mice may be in a state of unbalance regarding sympathetic and parasympathetic nerves, particularly with regard to abnormal tension in the parasympathetic nervous system, in part of duodenum. Pretreatment with most of the above drugs had no influence on loss of body weight in SART stressed mice while pretreatment with neurotropin inhibited body weight to a considerable extent.


[The difference of drug sensitivity of tumor cells on N-ethyloxycarbonylaminomethyl-L-isoleucine (A-145 (author's transl)].

N-Ethyloxycarbonylaminomehyl-L-isoleucine (A-145), a novel antitumor amino acid derivative, is an anti-tumor agent effect in cases of Ehrlich ascites rather than against Sarcoma-180. The chemotherapeutic index of A-145 was 14.9 for Ehrlich ascites carcinoma and 4.2 for ascites Sarcoma-180. Experimental studies on ddy mice regarding the difference in susceptibility of these two tumor cell lines to A-145 gave the following results. In in vivo experiments, the uptake of 14C-A-145 by Ehrlich ascites carcinoma was greater than by Sarcoma-180, i. e. the uptake ratio of Ehrlich ascites carcinoma/Sarcoma-180 was 1.52 at 30 min and 2.7 at 24 hr after injection. In in vivo experiments, there was no remarkable difference between Ehrlich ascites carcinoma and Sarcoma 180 in the subcellular distribution of 14C-A-145, and the majority of the radioactivity taken up was distributed in nuclei and cytosol fractions. In in vitro experiments, the uptake of 14C-A-145 by both cell lines was found to be temperature sensitive, glucose dependent, and decreased on addition of KCN, 2, 4-dinitrophenol or iodoacetic acid. In in vitro experiments, competitive inhibition by L-isoleucine on 14C-A-145 uptake into tumor cells was observed in both cell lines, however, in vitro experiments, the inhibitory effect of A-145 on cell growth in cultured Sarcoma-180 was not reversed by L-isoleucine.


[Effects of vitamin B complex in functional changes of the peripheral nerves of alloxan-induced diabetic rats (author's transl)].

Neurophysiological properties of the peripheral nerves of alloxan-induced diabetic rats and effects of vitamin B complex (V) were studied. Alloxan monohydrate was administered to Wistar (38 mg/kg, i.v.) and Sprague-Dawley (SD, 45 mg/kg, i.v.) rats. In Wistar diabetic rats (blood sugar level: more than 400 mg/dl for 6--8 weeks), nerve potentials with 2 peaks were recorded from the tibial and peroneal nerves. The late component had a higher threshold, longer time of recovery from excitation and slower conduction velocities. Large doses of V (B1: 100, B6: 100 and B12: 1 mg/kg, i.p.) administered daily until the experiment inhibited the appearance of the late component. In SD diabetic rats(the same blood sugar content for 6 approximately 8 months), the ventral root potentials had a longer duration, higher threshold and longer time of recovery from excitation. In V administered rats, particularly along with insulin, these changes were prevented. Most efferent fibers of non-treated rats had a refractory period of less than 3.0 msec. The number of fibers with this refractory period was greatly reduced in the diabetic rats. Although rats administered each component of V 100 and V 50 had efferent fibers with similar refractory periods to that of rats in A-S group, those administered V 100 had efferent fibers with significantly shorter refractory periods. Thus, efferent fibers seem to be more sensitive than the afferent ones at the early stages of the long term diabetic state and a large dose of V, particularly along with insulin, depressed these changes.


Clinical use of reverse isolation in a protected environment.

The therapeutic method of reverse isolation in patients using an aseptic environment in the Life Island or Laminar Air Flow Unit apparatus systems is described on the basis of data from the literature and the authors' experience. A historical summary of views on treatment in an aseptic environment is followed by a description of the method of work with the system of reverse isolation, including important technical, operational and other data. The main indications for treatment are given and the authors' experience with the reverse isolation of 36 patients suffering from blood diseases who were treated in this way over the past four years is evaluated. The experience gained confirms data from the literature that reverse isolation is unequivocally successful in reducing the number of infections in immunologically weakened persons. Other aspects have not yet been definitely assessed.


A suicide by ingestion of a mixture of copper, chromium and arsenic compounds.

A suicide resulting from the ingestion of copper, chromium and arsenic is reported. Death was delayed for 36 hours, during which time copper was rapidly eliminated from the body but chromium and arsenic remained in substantial quantities. The different metabolism of these elements is discussed and the tissue levels discovered are compared with the normal levels.


A chromatography system for drug identification.

A classification system is described for drugs using thin-layer chromatography (TLC), gas-liquid chromatography (GLC) and ultraviolet (UV) spectrophotometry. The TLC classifications are based on division of the plate into zones relative to a set of mixed drug standards. The GLC classification is based on Kovats' retention indices. The procedure for classifying drugs is presented, together with a list of over 200 classified drugs.


[Genetic amniocentesis in early pregnancy].

212 amniocentesis were performed at the Gynecological Clinic of the University Graz in cooperation with the Institute for Human Genetics of the same University from 1.7.1974 to 1.4.1978 for prenatal detection of genetic disorders or inherited disorders of metabolism. In 9 cases (4,2%) pathological results or special chromosomal aberrations were found. Five pregnancies (2,3%) had to be interrupted with prostaglandins. One case of Down-Syndrome ended by spontaneous abortion. Three women had a miscarriage following amniocentesis up to 6 weeks afterwards. In two cases (0,9%) a primary connection of puncture and loss of pregnancy could be documented. 4 cases (1,8%) suffered of amniotic fluid leakage after amniocentesis. Three patients delivered healthy term babies. This study demonstrates the high accuracy of the described diagnostic procedures.


[Treatment of ulcerations and skin defects of various etiologies with synthetic skin grafts].

A special form of therapy of ulcerations with synthetic graft is presented, especially the indication and method of this therapy and the possibility of temporary grafting with this material after large excisions of skin tumors.


[Multiple illnesses of the gastrointestinal tract. Part 2: So-called second diseases of the upper abdominal organs].

Today are multiple illnesses, pertaining the internal maladies (illnesses), almost a regularity. You differentiate between combination-illnesses, which represent primarily dependent illnesses and associated illnesses independent from each other. In the following summary illnesses are mentioned, which according to present information, appear more often together or cancel each other out. Of special interest are such procedures, by which a second disorder to the one existing can appear. The patient will experience a change in his illness. The appearance of a so called second sickness is especially to be observed in such organs as liver, gallbladder and pancreas. The study of multiple illnesses is more meaningfull, because statements for the basic research can be met and next to these more aetiologic or pathogenic associated questions lead to the next step, to the clinical symptoms which experience a change, and further to certain therapeutic considerations and consequences. Finally also the prognostic statements change.


[The clinical significance of hormone receptors in the treatment of breast cancer].

The assay of steroid receptors in tumor tissue has been shown to be a useful tool to evaluate the response of disseminated breast cancer to endocrine therapy. Principle and problems of this assay are outlined. An objective response of estrogen-receptor positive tumors to endocrine treatment can be achieved in about 60%. The rate of remissions in the receptor-negative group is below 10%. Possible explanations for false-positive or false-negative receptor assays are discussed. Additionally some possibilities for increasing the accuracy of the method are detailed.


[Early symptoms and diagnosis of multiple sclerosis].

Multiple Sclerosis is one of the most common neurological diseases in North and Central Europe and USA, the prevalence is 0,03-0,06%. The precise aetiological and pathological processes underlying the disease are still unknown. As there is as yet no laboratory test that is specific for Multiple Sclerosis, the diagnosis is still a clinical one. It depends on the history--a majority of patients has a history of remissions--and on the demonstration of objective signs of lesions in the white matter of the central nervous system. There can be found some early symptoms--such as optic neuritis--and some typical combinations of symptoms that make the diagnosis Multiple Sclerosis probable or clinically definit. Among the laboratory tests the investigation of cerebrospinal fluid is most important.


[The treatment of schizophrenic psychoses with hemodialysis].

A very controversial debate, concerning the treatment of schizophrenic psychoses by means of hemodialysis, started approximately in 1977, when American scientists reported outstanding successes with this method. Until now there is no clear evidence of the underlying principle of effectiveness of this method. According to present experiences there are three theories. Already in 1960 there were reports of successful application of hemodialysis in acute schizophrenic psychoses. The authors, among other things, assumed the filtration of a toxic blood substance to be the therapeutic principle. Later, however, changes in the blood circulation during dialysis, especially the improvement of cerebral perfusion, were seen as the real therapeutic factor. The recently reported findings of abnormal endorphin in the dialysate fluid of schizophrenics, brought back the theory of detoxification. At the same time there were claims by different authors, that the positive results were only due to a "changed psychological situation" of the treated patients. Which of these three theories is correct can not be decided yet. Whether blood purification methods have anything to offer for the treatment of some types of schizophrenic diseases requires further research.


[Echocardiographic evaluation of left ventricular function in man].

Comparison of ultrasound and invasive measurements has shown that accuracy and reproducibility of echocardiographic assessment of left ventricular performance are suitable for clinical use. We determined the influence of changes in heart rate, afterload, inotropic state and diastolic cycle length after premature beats and in atrial fibrillation on various ejection phase indices of myocardial contractility in man. Mean and maximal velocity of circumferential fiber shortening (VCF mean' VCF max) showed a slight increase during rapid atrial pacing. In contrast fractional shortening (FS%) and delta-VCF were not influenced by acute changes in heart rate. During intravenous infusion with Dobutamine VCF max and delta-VCF proved to be particular sensitive indices of left ventricular function. After permature beats and in atrial fibrillation the results indicate a linear correlation between all indices of the ejection phase and diastolic cycle length.


[Prevention and therapy of decubitus ulcer. Oxygen availability in the skin as a function of imposed skin pressure].

Pressure is of crucial importance in the formation of decubitus ulcers. In order to elucidate the effect of imposed skin pressure we measured with a new cutaneous oxygen sensor the skin oxygen tension under increasing pressure upon skin tissue on hard sites (bony prominences) and upon soft sites (muscle padded areas). On hard sites the skin oxygen tension fell rapidly under increasing pressure (y = 90.9--0.39 x/r = 0.98) from initially 86.4 +/- 10.6 to 20.2 +/- 12.1 mmHg under an imposing skin pressure of 175 g/cm2. On soft sites a pressure load of 175 g/cm2 decreased the skin oxygen tension only from 82.9 +/- 5.8 to 71.4 +/- 10.0 mmHg. Our results may explain why hard sites (bony prominences) are preferential areas in decubitus ulcer formation.


[Tolerance of the polyvalent adsorbed influenza vaccine Alorbat].

A good local and systemic tolerance of the influenza virus vaccine Alorbat was observed after a single administration in 469 patients or after a second administration within 4--6 weeks in 132 patients. An improved manufacturing process led to a higher purity of the vaccine (less protein) and therefore to a diminuation of systemic reactions. In most cases, the local reactions observed cannot be attributed to a local irritation by the vaccine but rather to mechanical damage to the skin and subcutaneous tissue after injection with a jet injector. None of the side-effects necessitated medical treatment as the systemic reactions regressed within a few hours and the local reactions disappeared spontaneously within a few days.


[Pathology of cardiac insufficiency].

Giving introductory examples of autopsied cases the variable spectrum of the different forms and temporary dynamics of cardiac insufficiency are discribed. In the following chapter the etiology is discussed from the point of view of general pathology. The pathogenesis of cardiac insufficiency is discussed by taking in consideration of the "energy problem". Disturbances of the supply, the production, the utilization and the transposition of energy, which are to be morphologically detectable with various methods looking upon different structures, lead at least to the insufficiency of the myocardial contraction.


[Tuberculosis in children and adolescents in Bavaria].

In 1977 in Bavaria, 7,659 cases (incidents) of tuberculosis were reported. 797 of these cases were children under 15 and 636 were youths between 15 and 20 years of age, that is 1,433 together. The first rise in cases takes place in the age bracket up to 5 years, the second, far greater, between 15 and 25. At the end of 1977 statistics showed the existence (prevalence) of 14,642 tuberculars. Of these, 1,128 were children under 15 and 858 youths between 15 and 20. Administrative districts with the most cases were Lower Bavaria (Niederbayern), Upper Palatinate (Oberpfalz), Upper Franconia (Oberfranken), and Middle Franconia (Mittelfranken). In local epidemics 190 youths and children became ill, infected in a dance hall, a discotheque, and a factory, as well as by a kindergarten teacher. Under these unfavorable circumstances a BCG vaccination is imperative. The Bavarian Home Ministry "publicly recommends" the BCG vaccination for infants as well as for all tuberculin negatives who live with people who have tuberculosis or who are otherwise endangered by tuberculosis, However, under the circumstances described, all children and young adults are still endangered by tuberculosis.


[Experiences with trimethoprim-sulfamethoxazole in ambulatory urologic practice].

The author reports about the treatment of 393 bacterial urinary tract infections with TMP/SMZ. It is shown that the success of treatment significantly depends on the constitution of the efferent urinary passages (obstructive and non-obstructive alterations, unchanged urinary passages) and the kind of organisms but only insignificantly on the duration of treatment. The germinal spectrum and the number of resistant strains of the individual kinds of organisms correspond with the results of other investigators. TMP/SMZ is a very potent antibiotic drug against the most pathogenic urinary organisms at a low rate of side effects.


[Amniotic fluid concentrations of thyroxine, reverse triiodothyronine and lecithins].

In the present study we tried to find out relationships between lung maturation-assessable by aid of lecithin concentrations in amniotic fluid-and fetal thyreoid gland function. In 256 pregnant women amniocentesis was done after 31/0 weeks of gestation, and concentrations of thyroxin, of reverse triiodothyronine and lecithins were measured. While thyroxin and lecithin concentrations proved not to be correlated, the rT3 and lecithin concentrations showed significant correlation (2 p less than 0.001). The curves measured were interpreted as signs of maturity of various organs (lung, thyreoid gland). We found out, that clinical value of measuring thyreoid gland hormones in relation to diagnosis of fetal maturation is of less importance.


[Pentoxifylline medication within the scope of leg-ulcer therapy. Results of a field study using Trental 400].

513 patients with chronic ulcers of the leg were treated with Trental 400 orally in addition to local therapy. Regarding the reduction of the symptoms: ulcer extension, coldness of the leg, paraesthesia, resting pain and improvement of walking distance, 215 patients were classified as considerably improved, 195 distinctly improved, 53 slightly improved and 44 unchanged. Four cases worsened, two cases could not be classified. The possibility of combining oral therapy with local treatment and surgical measures (skin-flaps) is shown in three case reports. Gastro-intestinal tolerance of Trental 400 was good, interactions with concomitantly administered drugs were not reported.


[Maturity determination of the newborn infant].

Uncertain dating of pregnancy and the relative independency of fetal maturation of time require judgement of the maturity state of every newborn infant for obvious practical reasons. Such scoring can be easily performed using external-superficial criteria with acceptable accuracy.


[Methods for the early recognition of gestosis].

The frequency of the severe forms of gestosis (preeclampsia) may be reduced by early recognition of this disease. By predicting hypertensive disorders of pregnancy, maternal and infantile perinatal mortality rates are expected to be lowered. The supine pressor test ("roll-over test") is recommended as an appropriate and simple method for routine screening during primigravid pregnancy. This test is rarely false-negative (2--9%; Bonn 3%), but a high percentage of false-positive results has been found in patients studied in Bonn. The angiotensin sensitivity test shows less false-positive pressor responses, but it is not practical for routine use either as infusion test nor as bolus test. The rate of false-negative results is sufficiently low in both methods. The routine determination of uric acid concentration in serum seems to be of no great value for predicting pregnancy-induced hypertension, compared with the roll-over test or with the angiotensin sensitivity test; however, it gives an additional information (a) in pregnancy women with questionable gestosis, and (b) in the differential diagnosis of pregnancy-induced versus pre-existing essential hypertension.


[Radiodiagnosis in pheochromocytoma].

The diagnosis "pheochromocytoma" is established by the evaluation of catecholamins and their metabolites in urine. Therapy consists in extirpation of the hormone producing tumor. Aim of he X-ray examination is the localization of the tumor before operation. 80% of the pheochromocytomata are located in the suprarenal glands. As there is the possibility of extraadrenal localization (20%) and of multicentric manifestation (11%) the X-ray examination must not be restricted to the suprarenal glands. More than 95% of all pheochromocytomata are well vascularized, therefore abdominal aortography is the best method to search for and localize these tumors. This invasive method necessitates close teamwork of the radiologist and a physician with great experience in this field. This is necessary for the preparation of the patient for aortography and also for the treatment of possible complications during aortography, which are specific for pheochromocytoma and which can be fatal.


[Development and current possibilities of cerebrospinal fluid diagnosis in the routine laboratory. 1. Cytological and microbiological studies and methods of chemical analysis].

Although there are many precisely working procedures for diagnostic examinations of cerebrospinal fluid, very often methods are used which do not fulfill conditions of adequate quality. The aim of this survey of several cytological and chemical methods, of their development during the past 80 years, of their advantages or disadvantages, and of the various difficulties is to contribute to a discussion on improvement of quality and on unification of laboratory methods regarding diagnostic examinations of cerebrospinal fluid. Several procedures to separate protein fractions or single proteins in cerebrospinal fluid will be discussed in the second part of this paper.


[Effects  on platelet functions].

Platelet adhesiveness was measured in a total of 589 healthy volunteers and patients. Patients suffered from heart failure, diabetes mellitus, myocardial infarction and deep vein thrombosis have a significant higher platelet adhesiveness as healthy volunteers. The effect of the socalled stressors on platelet adhesiveness was shown in vivo; the same values of platelet adhesiveness were seen as in patients. Therefore it can be concluded that stressors constitute a risk factor in patients with altered vessel walls.


[Gunshot wounds by military weapons].

The review is based on 34 recent publications. Bullet-wounds by military weapons either in drill or war are to be regarded as special kinds of wounds, needing profound knowledge of wound ballistic. However, the therapy of late developing complications may lead to problems.


[The etiology of necrotizing enterocolitis in the newborn].

Apparently there are different causes for necrotizing enterocolitis (NEC) in the newborn infant. Besides it may be that NEC only is caused by the interaction of several factors such as perinatal complications, medical measures, an aggressive oral alimentation and an adverse colonization of the bowel and that a critical degree of stress is required to initiate enterocolitis. This assumption would help to explain, why one newborn infant can stand an episode of perinatal stress without falling ill, while the other develops the disease a short time later. Probably NEC starts with an intestinal mucosa damage caused by ischemia or local noxae, and only subsequent invasion by the bowel flora into the damaged tissue and gas formation within the bowel wall lead to the picture of necrotizing inflammation and pneumatosis intestinalis.


[Danger to the child and family from civilization and prosperity].

The advances of civilization are more and more endangering the development of the child. The most important problems are traffic accidents, the decay of the family, the falling birth-rate and the increasing abuse of drugs and alcohol as well as suicide in early years of life. The family and the child must be respected in the future to improve the situation. Adults have to accept the age specific problems of the child.


[Complications and psychosomatic problems after tubal sterilization].

From 1969 to 1974, 2080 patients were sterilized, 1702 by the pelviscopic method (electrocoagulation), 375 by laparotomy, and 3 vaginally. About two thirds of the sterilisations by laparotomy were carried out after delivery or during other surgical procedures. 15% of all women were sterilized for medical reasons; the other cases had to be 35 years of age or at least 30 if they had more than 3 children. The overall complication rate was 5% with both methods. Complications during pelviscopy included hemorrhage, bowel injury and burns. Postoperative complications after laparotomy were hemorrhage, thrombosis and wound dehiscence. Only half of the patients could be followed up; there were 4 pregnancies among 1308 women. In more than 50% the sexual relations had improved, in only 3% they had worsened. About 97% of the pelviscopically sterilized patients were satisfied with surgical method chosen and with their present status. It is recommended to allow sufficient time to think the decision over prior to the operation.


[Oral actovegin therapy in cerebrovascular insufficiency. Studies on the therapeutic value of actovegin forte dragees in elderly patients with advanced cerebrovascular insufficiency].

The therapeutic effect of Actovegin forte drag. was investigated in a combined uncontrolled-controlled study on a total of 70 senile patients with mainly considerably advanced cerebral sclerosis (32 patients post-apoplexy) and concomitant diseases (46 patients with heart diseases, 41 patients with hypertonia, 28 patients with diabetes mellitus and others). Evaluation was made according to specific criteria. During six weeks of treatment with Actovegin a statistically significant and clinically relevant improvement of the intellectual faculties, the general condition and the complaints characterized by symptoms of deficiency of memory, exhaustiveness, disorder of sleep and weakness was noted. Even higher doses of the preparation were tolerated well. The effect of Actovegin forte drag. was dose-dependent--the best results were obtained with two dragées three times daily--and was clearly delimited from the effect of a parallel cardiac or circulatory therapy or of any other basic therapy. These results reveal that the therapy with orally administered Actovegin appears to be an appropriate supplement to the parenteral therapy with Actovegin which has so far only been possible. It is particularly suitable for ambulatory and prolonged treatment of senile patients with cerebrovascular insufficiency.


Sinus node disease.

Sinus node dysfunction may be clinically asymptomatic or may lead to serious arrhythmias and sudden death. Symptomatology relates to the resulting brady- or tachyarrhythmias. Clinical and electrocardiographic assessements fail to identify the cause in many patients. Ambulatory electrocardiography establishes the diagnosis in a greater percentage of patients and permits the direct correlation of symptoms with rhythm disturbances. Functional electrophysiologic testing which examines the sinus node response to constant atrial pacing and premature atrial stimulation may be performed for further evaluation of these patients. Sensitivity and specificity of sinus node recovery times (SNRT) and sino- atrial conduction time (SACT) derived by functional testing vary markedly in different reports. This variation may relate to differences in patient population, limitations of testing procedures, and the uncertainties as to the normal limits of SNRT and SACT. As a result, the full value of these tests in diagnosis and in furthering our understanding of sinus node disease remains to be established. At present, permanent pacing remains the definitive treatment in symptomatic patients.


Electrophysiological studies in patients with the Wolf-Parkinson-White syndrome.

Electrophysiologic studies in patients with the Wolff-Parkinson-White (WPW) syndrome are performed for diagnostic and therapeutic reasons. Surface electrocardiographic leads plus intracardiac electrograms from different locations are stimultaneously recorded. Programmed electrical stimulation of the heart permits confirmation of pre-excitation in questionable cases and assessment of the mechanism of the arrhythmias which these patients develop as well as their therapeutic approach. The most frequent form of paroxysmal regular tachycardia observed in WPW is based on an AV-junctional re-entry mechanism utilizing the accessory pathway in the retrograde direction. The second clinically relevant arrhythmia encountered in these patients is atrial fibrillation with very rapid ventricular rates due to almost exclusive A-V conduction by way of the accessory pathway. Ventricular fibrillation may occasionally ensue as a result of these fast ventricular rates during atrial fibrillation. Determination of the antegrade effective refractory period of the accessory pathway may identify the group of patients prone to the development of this complication. The intravenous injection of Ajmaline can by a non-invasive aid in the selection of patients for further electrophysiological evaluation when this drug fails to induce complete antegrade block over the accessory pathway during sinus rhythm. Patients with tachyarrhythmias which are difficult to control with conventional drug therapy should undergo an electrophysiological investigation to select either more effective antiarrhythmic treatment or, in medically refractory patients, appropriate pacing or surgical techniques.


[Hemodynamic studies during temporary, unilateral occlusion of the pulmonary artery (author's transl)].

During pre-operative evaluation of 35 patients prior to pulmonary resection, pressure measurements in the right heart and pulmonary circulation were performed. In addition to pressure values, pulmonary ventilation and partial pressures of the blood gases were assessed before and during unilateral occlusion of the pulmonary artery at rest and during exercise. Statistically significant increased values from regression analysis were obtained for mean pulmonary artery pressure, right ventricular end-diastolic pressure, pulmonary vascular resistance and right ventricular work. The results show that plethysmorgraphic and ergometric studies as well as their combination with blood gas analysis, are not indicative of changes in right ventricular or pulmonary arterial hemodynamics. Prior to pulmonary resection, catheterization should be performed at rest and during exercise to assess these variables.


Effects of possible beta-cell membrane label, metahexamide-isothiocyanate, on insulin release.

To synthetize a specifically and covalently reacting label for the sulfonylurea receptor site, the sulfonylurea metahexmide was converted to its isothiocyano-derivative (MITC), and the effects of MITC on insulin release from the perfused rat pancreas were studied. MITC (2 micrometer) stimulated a large insulin release that persisted after the end of the MITC-infusion. At a higher concentration (50 micrometer) MITC produced only a short lasting stimulation, and thereafter inhibited either the sulfonylurea or the glucose-induced insulin release. It is suggested that the irreversible stimulation of insulin release by MITC reflects the convalent linkage of the label to the sulfonylurea receptor site, while excess isothiocyanate inhibited insulin release by reacting on less specific binding sites involved in the secretion process.


Th activities of perfused livers of control and streptozotocin diabetic rats in the synthesis of some plasma proteins and peptides.

By measuring the incorporation of 14C-DL-leucine a decreased capacity of isolated perfused steptozotocin diabetic rat liver to synthetize plasma total proteins, albumin and the seromucoid fraction was found as compared with a control. The relative rate of synthesis of the seromucoid proteins calculated as proportional to the rate of synthesis of albumin or the total plasma proteins was approximately twice as great as in control liver. 14C-DL-leucine was also incorporated in perfused liver into the nonprotein but non-dialysable sugar-peptide fraction but the synthesis of the glycopeptide components of this fraction was markedly reduced in diabetic rat liver.


The determinants of insulin extraction in the isolated perfused rat liver.

The effect of hepatic blood flow and portal insulin concentration on insulin extraction during one passage through the isolated perfused rat liver was studied. The percentage of insulin extracted was constant over the physiological range of blood flows (4 to 28 ml/min). The total amount of insulin extracted increased as the input concentration was raised from 48 to 4860 microU/ml with the highest level of extraction being approximately 700 microU of insulin per gram of liver per minute. When square wave input pulses of 243 to 4860 microU/ml were presented, about 5% of this insulin was retained and then released by the liver for periods up to 15 minutes after the cessation of the input. The possible roles of glucose and glucagon as regulators of insulin extraction were studied. Glucose (300 mg/dl), as compared with no glucose, led to a significant reduction of insulin extraction (22% vs. 38%, p less than 0.001). Glucagon had no effect on insulin extraction in the presence of constant levels of glucose. It is concluded, therefore, that glucose may increase circulating insulin levels not only by its well known stimulation of insulin secretion by the pancreas, but also by inhibiting insulin extraction by the liver.


Comparison of several insulin-like effects of growth hormone.

Three different insulin-like effects of growth hormone were studied in segments of adipose tissue obtained from hypophysectomized rats. The onset of each response was preceded by a characteristic lag period: antilipolysis was seen only after a 10--15 minute exposure to growth hormone; stimulation of glucose oxidation was significant 20 minutes after exposure to growth hormone and increased leucine oxidation was seen only after 30 minutes. Each of the responses was measurable without a detectable delay when the tissues were exposed to hormone during a prior incubation period. Accelerated leucine oxidation was detected when 0.01 microgram/ml growth hormone was present in the incubation medium; the other responses required a minimum of 0.1 microgram/ml. Inhibitors of protein synthesis of concentrations which decreased the incorporation of 14C leucine into protein by 99% had no effect on either the antilipolytic action of growth hormone or the stimulatory action on glucose oxidation, but abolished the acceleration of leucine oxidation. In contrast to findings in diaphragm muscle, theophylline was without effect on any of the insulin-like actions of growth hormone in adipose tissue, even though it decreased the basal rate of glucose and leucine oxidation.


The influence of maternal somatostatin administration on fetal brain cell proliferation and its relationship to serum gorwth hormone and brain trophin activity.

The effect of maternal somatostatin administration from days 14 to 20 of gestation was examined. Fetal body growth was unchanged but brain cell DNA synthesis per gram of tissue decreased. Maternal serum levels of growth hormone and brain trophin were elevated following treatment conclusion. It was suggested that this was a rebound phenomenon and that short term blockade of pituitary growth hormone release during somatostatin treatment had impaired fetal brain cell DNA synthesis.


Effect of acute hypoxia on blood TSH levels.

The effect of simulated altitude produced by decompression chambers upon the thyroid function was studied in female rats. A significant decrease in blood TSH levels was found when the rats were maintained during 24 hours at a pressure of 0.4 atmosphere, but not at a pressure of 0.7 atmosphere.


Absorption of protamine-insulin in diabetic patients. I. Preparation and characterization of protamine-125I-insulin.

Protamine-125I-insulin with low specific radioactivity was prepared using 125, 127I-insulin, 0.2 I/mole. The preparations were characterized by disc electrophoresis, isoelectric focusing and analytical gel chromatography in order to evaluate the suitability of 125I-insulin as marker for insulin in protamine-insulin. The stability of the preparations was followed up to 90 days at 4 degrees C. The biological and immunological activity was determined in mice, isolated rat fat cells and by radioimmunoassay. It was concluded that both from a chemical and a biological point of view, the protamine-125I-insulin is a satisfactory preparation that might be used in absorption studies.


Is lactate involved in phenformin-induced insulin secretion?

Phenformin at high doses (10 mg/l, 50 mg/l, and 100 mg/l) increased the insulin and lactate output rates by the isolated perfused rat pancreas. Glucagon secretion was not modified. There was a statistically significant correlation between the increase in insulin and lactate output rates induced by phenformin. Intra-pancreatic L (+) lactate concentrations induced by phenformin were in the range of sodium L (+) lactate concentrations which experimentally stimulated insulin secretion by the same preparation. Thiamin pyrophosphate and sodium dichloroacetate, which promote the aerobic metabolism of pyruvate, opposed the phenoformin induced increase in lactate output by the isolated perfused rat pancreas and provoked as well a decrease in insulin release. These results suggest that the increase in insulin secretion following the administration of phenformin at high concentrations can be explained, to a large extent, by the increase in the production of lactate ions.


Use of electrophoresis and gel filtration to characterize human pituitary somatotropin preparations after storage.

Fresh and stored preparations of human pituitary somatotropin examined by different polyacrylamide gel electrophoresis techniques and by gel exclusion chromatography (Ultrogel) clearly demonstrated that the hormone undergoes a structural alteration during storage for 3 years. The formed aggregates were readily quantitated from the gel filtration profile and from polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate (SDS-PAGE). According to gel filtration the amount of aggregates in fresh and stored hormone was determined to be 2 and 10%, respectively, while SDS-PAGE indicated 6 and 14%.


Role of ovarian secretion in the development of dysfunction in the regulation of luteinizing hormone secretion in female rats exposed to constant illumination.

Female rats in constant illumination (LL) fail to show the facilitation of LH release following steroid administration that is characteristic of animals in normal lighting. To determine whether this effect is mediated through changes in ovarian function, rats were spayed either at the time of placement into different lighting schedules (LL or a 14:10 light-dark (LD) schedule) or 10 weeks later, and their plasma LH responses to steroids were compared after an additional 3-week exposure to the experimental lighting conditions. To test the LH response, estradiol benzoate (EB) was injected at 12.00 h and followed 72 h later by injection of progesterone (P) or a second injection of EB. Neither steroid regime revealed differences in LH release between animals ovariectomized at the time of placement into LL and those spayed 10 weeks later. The duration of castration in animals in LD affected the LH response to a priming dose of EB, but not to a second dose of EB or to P. It is concluded that altered ovarian activity is not the factor which mediates the loss of a facilitatory response of LH release following administration of gonadal steroids to rats under constant illumination.


Effect of thiourea on intracranial bone tumour formation in AkR mice.

The effect of administration of thiourea (5 g/kg in diet) alone or simultaneously with thyroxine (1 mg/l in drinking water) on the frequency of hyperplastic benign osteoma of the skull was studied in AkR mice. Animals treated with both thiourea and thyroxine were in hyperthyroidism: the thyroxine dose received was higher that that required to prevent thiourea-induced thyroid gland hypertrophy. A significant increase of the intracranial bone tumour (IBT) frequency was observed both in mice treated with thiourea alone and those which received thiourea and thyroxine simultaneously. Increase of IBT frequency was not due to the antithyroid effect of thiourea but seems due to a direct toxic action of thiourea on the pituitary.


Failure to demonstrate antigonadotrophic activities of arginine vasotocin in the mouse.

Arginine vasotocin (AVT) has previously been proposed to be a pineal hormone which reduces reproductive competency in mammals. The effects of AVT on the growth of immature reproductive organs of the mouse have been studied using blind study techniques. Evidence is presented which fails to support the proposed role of AVT as a mammalian antigonadotrophin.


Binding of d-tubocurarine by gangliosides.

The binding of d-tubocurarine by ganglioside mixtures from chicken and bovine brain as well as by the single gangliosides GGtet1-NeuAc, GGtet2aNeuAc and GGtet3aNeuAc was demonstrated by means of equilibrium gel filtration. The sialyl-oligosaccharide derivatives of GGtet1NeuAc and GGtet2aNeuAc, however, did not bind any d-tubocurarine. A lack of binding was also found for the gangliotetraosyl-ceramide GgOse4Cer, free NeuAc, mucin and sphingomyelin. Under saturation conditions, GGtet1NeuAc bound 0.58, GGtet2aNeuAc 0.92 and GGtet3a-NeuAc 1.23 mol d-tubocurarine per mol ganglioside. Half-maximal binding was achieved between 1 and 1.5 x 10(-5)M d-tubocurarine. Ca2 was found to inhibit the binding of d-tubocurarine to gangliosides (50% at 4 x 10(-4)M Ca2). Mg2 was about 4 times less effective. Acetylcholine caused a 40% inhibition at 4 x 10(-3)M, whereas K and Na had only slight effects even at 5 x 10(-2)M.


Changes in the concentrations of branched chain amino acids in the blood in response to alterations in the composition of a hypocaloric diet.

This report describes an investigation of the effect of an alteration in the amount of protein, carbohydrate and fat in hypocaloric diets on the concentration ratios of valine/(isoleucine + leucine) in the morning fasting blood in healthy men: in some cases the effect of a higher caloric diet was also analysed. During the nutrition periods, each over 10 days, the concentrations of branched chain amino acids and alanine, blood levels of insulin, glucose and free fatty acids and the nitrogen balance were estimated daily. With hypocaloric diets, as well as with hypercaloric diets, supplementation of food protein from 0.6 or 0.8 up to 2.0 g protein per kg body weight (isocalorically) induced a rise of the molar ratios of valine/(isoleucine + leucine) in blood from 0.98 to 1.25 (4600 kJ/d) or 1.06 to 1.45 (14600 kJ/d) respectively. A correlation of molar ratios of valine/(isoleucine + leucine) in the blood and the nitrogen balance could not be established. However, it is suggested that ratios above a limiting value exclude the possibility of a distinct negative nitrogen balance during 7 or 10 days of observation.


Synthesis of giant HnRNA in the epidermal cells of Calliphora and the role of the ring gland.

The appearance of giant HnRNA in the epidermal cells of Calliphora in the transition period from larva to pupa is ecdysone-dependent. In this specific stage of development, the initial increase of this RNA species occurs shortly after the appearance of a small peak of ecdysone. Another main peak of the hormone is a prerequisite for pupation. The removal of the ring gland, the source of ecdysone, prior to the appearance of the second peak of the hormone, was found to have no pronounced effect on HnRNA synthesis for at least 48 h after the operation. It is concluded that the larval pupal differentiation is a two-step process. Initially a gen activation occurs dependent on a low ecdysone titer. This is followed by a second final step of pupal cuticle synthesis and pupation, dependent on the presence of a high concentration of the hormone.


Receptor binding studies on A1-(2-nitro-4-trimethylammoniophenyl)insulin.

The results are presented from receptor binding studies and isolated fat cell assays on A1-(2-nitro-4-trimethylammoniophenyl)insulin. In the former tests, the derivative is shown to have properties similar to native insulin and the fat cell assays afford a value of 76 +/- 4%. The importance of a charged, hydrophilic moiety attached at A1-glycine is discussed in the light of the above findings.


Malignancy-associated DNA-binding protein C3DP from human serum. Further characterization and purification of C3DP retaining its DNA-binding affinity.

C3DP, a malignancy-associated DNA-binding protein from human serum[1], was purified to homogeneity without loss of its DNA-binding affinity. For this purpose normal human serum was submitted to affinity chromatography on Con A-Sepharose and DNA-cellulose and to preparative polyacrylamide gel electrophoresis. The purified C3DP was identified by immunodiffusion and sodium dodecylsulfate polyacrylamide gel electrophoresis and it was shown to bind to DNA by DNA-cellulose chromatography. The isoelectric point of C3DP was determined to 4.9 by isoelectric focusing.


The synthesis of a new phospholipid from the koilin glandular layer of chicken gizzard.

In a previous publication, a new phospholipid was isolated from the keratinoidal layer of chicken gizzard, and on the basis of chemical, spectrometric (IR, NMR, UV) tests and mass analysis, the probable structure of the isolated phospholipid was proposed as 1,2-O-docosylidene-sn-glycero-3-phospho(1'-ribosyl)-ethanolamine (IX). In this paper, on the basis of probable structure, a new phospholipid was synthetized.


Carbohydrate content of human erythrocyte membrane. Variations with ABO-blood group.

The study of the carbohydrates of human erythrocyte membranes has been mainly focused on their glycopeptidic and glycolipidic complexes. Modifications of these carbohydrates have been described in subjects with various pathological states. In order to characterize possible changes of the glycopeptides, or glycolipids obtained from erythrocyte membrane in various pathological situations, the determination of the carbohydrate content of the whole membrane appeared a necessary preliminary. This study concerns the determination of the normal values of the main carbohydrates of whole human erythrocyte membranes, with respect to their blood group. Erythrocyte membranes were prepared from donors of the four ABO blood groups. After acidic hydrolysis, the contents of fucose, mannose, galactose, glucose, glucosamine, galactosamine and N-acetylneuraminic acid in each blood group were determined and compared with one another. The galactosamine content of A, B and AB erythrocyte membranes is significantly higher than that of the O-erythrocyte. For galactose, the differences are significant for the following pairs: A/O; B/O; AB/O; A/B; A/AB. Significant differences in the mannose contents of O-erythrocytes and A, B and AB erythrocytes have also been found. This result suggests that a basic difference, in the core of the oligosaccharide chains, may exist between O and A, B, AB erythrocyte membranes.


myo-Inositol oxygenase from rat kidneys. I: Purification by affinity chromatography; physical and catalytic properties.

Using the technique of affinity chromatography on a myo-inositol-substituted Sepharose, the myo-inositol oxygenase from rat kidneys was purified to homogeneity. The active enzyme contains iron, most probably in its divalent form. Electrophoresis on polyacrylamide gel containing sodium dodecylsulphate causes the cleavage of the enzyme protein into apparently identical subunits with a molecular weight of approximately 17,000. The smallest active unit consists of 4 subunits, and is in a pH-dependent equilibium with species consisting of 8, 12, and 16 subunits, respectively, which all show the same specific enzyme activity. In the presence of oxygen the enzyme is highly unstable; at the early stages of inactivation it can be reactivated by reducing agents like NaBH4. Under anaerobic conditions or under the influence of Fe2-chelating agents, the enzyme is also inactivated; this inactivation is caused by the loss of iron and concomitant cleavage into the subunits. It can be reversed by incubation with FeSO4 in the presence of air. If myo-inositol and FeSO4 are present, the reactivation involves an oligomerization to the species with 16 subunits with the uptake of 8 gram-atoms of iron per mole of this species. The enzyme reaction follows Michaelis-Menten kinetics; the Michaelis constants are 4.5 x 10(-2)M for myo-inositol and 9.5 x 10(-6)M for oxygen.


[Studies on the kinetics of the RNA metabolism in the prostate of normal and castrated rats (author's transl)].

In the prostate of adult Wistar rats the RNA/DNA quotient of the whole organ as well as the amount of RNA and DNA in the nucleus was measured at different times after castration. Furthermore the half-life time for the turnover of the RNA in the nucleus and the cytoplasm was determined for normal and castrated rats with the aid of pulse labelling using [5(-3)H]uridine. A mathematical model was developed to analyze the experimental results. This model enabled us to make differentiated statements on the heterogeneous nuclear RNA (hmRNA) and the remaining RNA in the nucleus. The evaluation of the experimental values gave the following results: 1. By deprivation of androgens the uptake of [3H]uridine into the prostate is lowered. 2. The amount of DNA in the morphologically intact nucleus remains constant at least up to the 12th day after castration. 3. 6 days after castration the amount of hmRNA decreases to 1/10 and that of cytoplasmic RNA to 1/4. 4. The half-life time for the decrease of the whole nuclear RNA is 3.7 d and that of the cytoplasmic RNA 1.7 d. 5. The half-life time for the turnover of hmRNA is 16 min and that of cytoplasmic RNA about 2 days. 6 days after castration the half-life times are unchanged. The experimental results suggest that the observed decrease of nuclear RNA following castration can mainly be attributed to a reduced synthesis of hnRNA, while the decrease of cytoplasmic RNA is first of all caused by an increase in RNA degradation.


Snake venoms. The amino-acid sequence of protein S2C4 from Dendroaspis jamesoni kaimosae (Jameson's mamba) venom.

A major component (S2C4) was purified from Jameson's mamba by gel filtration on Sephadex G-50 and ion-exchange chromatography on CM-cellulose. Protein S2C4 comprises 62 amino acid residues including 8 half-cystine residues. The complete amino acid sequence of the protein has been established. The sequence and the invariant amino acid residues of protein S2C4 resemble a short neurotoxin, a long neurotoxin, a cytotoxin and an angusticeps type protein. However, the position of its four disulphide bridges differs from those encountered in a short neurotoxin or a cytotoxin. Mixtures of protein S2C4 and angusticeps type proteins revealed a marked synergistic effect, in that their toxicity in combination was greater than the sum of their individual toxicities.


Fibronectin (cold-insoluble globulin), VI. Influence of heparin and hyaluronic acid on the binding of native collagen.

Fibronectin of human plasma associated readily with denatured collagen but gave only a weak reaction with the native protein. In the presence of heparin, however, solutions of native collagen type III, and fibronectin produced precipitates at an ionic strength of 0.2. In the presence of fibronectin and optimal additions of heparin, up to 60% of soluble native 125I-collagen type III, but only about 10% of native 125I-collagen type I, were insolubilized. Heparin also enhanced the formation of insoluble complexes from fibronectin and denatured collagen type I and type III. In the absence of collagen 125I-fibronectin was partially precipitated by heparin. Electron micrographs showed filamentous structures. Collagen did not increase the amount of 125I-fibronectin precipitated by heparin unless a critical collagen concentration was exceeded. It is suggested that heparin induced the transition of fibronectin from a globular to an elongated form, capable of forming filamentous precipitates which adsorb native collagen. Hyaluronic acid and putrescine prevented the insolubilization of native collagen type III, by fibronectin and heparin.


[The sequence of beta A - and beta B-chains from carp hemoglobins (Cyprinus carpio L.)].

The primary structures of the beta A - and beta B-chains from the both main components of carp hemoglobins is given. The sequence was established by splitting with known methods and sequencing the products using the hydrophilic and hydrophobic programmes in the sequenator. The carp beta-chains differ from human beta-chains in the exchange of 66 and 67 amino acid residues, respectively; the beta A - beta B-chains differ by 4 amino acids (pos. no. 13, 41, 122 and 143). Both chains have one insertion in the position 121 or 122. The results are discussed.


Planning mental health services for chronic patients.

At the present time, deinstitutionalized services for the chronically mentally ill are less than satisfactory. If planning for the future is to reverse the trend of incomplete service delivery for this population, it must start with the recognition and application of certain fundamental concepts. Effective planning requires idealism, vision, and a sense of reality. Six separate but interrelated dimensions of reality must be taken into account: the need for mental hospital; the importance of precise planning goals; the unique service needs of the chronically mentally ill; the need for interagency planning; the importance of a functioning and sensitive patient tracking system; and appreciation of the attitudinal structure within which services are delivered. Wherever the chronically mentally ill live, whether in the hospital or in the community, their requirements must be made the primary focus in mental health planning.


An assessment of a continuing care program.

In mid-1977 the Kern County (Calif.) Department of Mental Health Services undertook a survey of residents and operators of group and family care homes in the county to obtain their views on how services in the homes might be improved and to assess the level of skills of the patients placed there. A total of 139 former patients and 26 operators agreed to be interviewed. The results showed that few of the patients had overt behavioral problems and most were capable of self-care. For the most part the patients were satisfied with the homes, although problems related to finances and lack of outside activities were cited by both patients and operators. The authors emphasize the importance of including such assessment of consumer satisfaction in planning mental health services.


Extended hospital care as treatment of choice.

A review of the histories of six patients who failed to adapt to community living after hospital discharge identified six factors that are predictive of serious maladjustment in the community. The are the absence of a family or soical network, repeated threats of violent behavior, previous hospitalization, poor previous functioning, inability to take responsibility for medical and mental health treatment, and suffering. Patients identified by two or more factors are likely to be unable to cope with life outside the hospital. The authors question whether attempting to maintain such patients in the community is desirable in terms of economic cost and patient suffering.


Locating drug addicts who have dropped out of treatment.

Staff at a VA-sponsored drug treatment center followed up dropouts one year after they left the program; they were able to locate 80 per cent of those clients. The staff found several contacts useful in locating the difficult-to-find population, including the addicts' mothers, other drug programs, prisons, and the department of motor vehicles. To make it easier for researchers to tract down dropouts, the author suggests that when patients enter a program they should be required to give names, addresses, and telephone numbers of at least two friends or relatives who would know where they were. Staff should emphasize to patients that the information is for research purposes and that confidentiality will be preserved.


Patient as volunteer: an assault on chronicity.

By integrating selected former patients into its regular volunteer program, a South Australian state hospital reduced the hospital stays and the readmissions of a large number of the participants who had previously been seen as failures of the community mental health movement. The author describes the program, its benefits, and some limitations and problems, such as an occasional extra burden on ward personnel. The former patients' new roles as volunteers enabled them to get the support they needed from the hospital but through means more acceptable to them. The program also improved their self-esteem and enabled them to engage in more normalizing social relationships.


Suicidal patients in the emergency room: a guide for evaluation and disposition.

The inexperienced emergency room clinician can find it difficult and frustrating to make decisions about patients who have threatened or attempted suicide. A review of the literature suggests two approaches to the evaluation of suicide-attempters: awareness of demographic and social characteristics that identify patients at high risk of another attempt, and simple numerical rating scales focusing on suicide predictors that help the clinician determine level of risk. The authors discuss how to choose the most appropriate disposition for the suicidal patient and emphasize the need for adequate documentation of the decision in the medical record.


Cost analysis in a CMHC: determining the cost of staff time.

The program evaluation and research unit of a community mental health center developed and field-tested a survey form to measure how employees spend their time. The form is divided into direct patient care activities, which include interviewing and testing, conducting therapy, and prescribing medications, and administrative or support activities, which include filling out charts, attending meetings, and training staff. All staff record daily, for one week, the hours and minutes they spend in each activity. Using that data as a base, the evaluation unit can determine the percentage of time staff spend in each activity and the cost of each activity based on staff members' paychecks.


Rural areas face woes in health care delivery, try model systems.

Health planning such as consolidation and closure of facilities and services to contain costs often contradicts rural populations' needs for increased access to better or even basic services/Model programs to meet these needs are discussed.


Urban hospital fosters cooperative programs to expand rural care.

An urban medical center has found that participation in cooperative programs with surrounding small rural hospitals meets its own need for a broader geographical base of operations and their needs for access to more and specialized services.


Israeli delivery system provides outreach care for nomadic Bedouins.

Israeli's Ministry of health and the Kupat Holim have penetrated cultural barriers, solved logistics, and extended curative and preventive care to a Bedouin population living in Beersheba, outlying villages and small cities, and the Negev Desert.


What P.L. 94-484 means to hospitals and physicians.

In this second and final article on the provisions and impact of the Health Professions Educational Assistance Act of 1976 (P.L. 94-484), the law's effects and recommendations on what can be done to cope with them are discussed.


When enough is enough.

The goals of hospitals and hospices are not necessarily incompatible, and hospice care may be an opportunity for hospitals to further humanize their services.


New accounting system helps control costs.

With the split-cost accounting system, charges are made more equitable and patients pay for exactly what they get/Third-party payers in Massachusetts seem to like the system.


Social Security is still a good deal.

Employees may be paying part of their Social Security benefits through their personal income taxes in the future/The benefits of the system outweigh its drawbacks.


Hospital office leasing is on the rise.

Eighty percent of medical office buildings currently under construction are being built by hospitals.


Checklist for materials managements.

Two-part report from the General Accounting Office shows how to evaluate and improve the materials management function in hospitals.


The 1980s: the rise of HMOs and marketplace competition.

Hospitals that fail to take the leadership in the capitation movement will find themselves competing in traditional ways for a shrinking share of the market.


Marketing: changing prospective patients' behavior.

Opportunities must be seen in terms of exchange values, and the hospital--by improving the perceived advantages of hospital use to groups of patients and physicians--can make the most of its marketing opportunities.


Biomedical challenges: should "human" be redefined?

The advance of biomedical science is raising fundamental questions about the definition of what it is to be human. Theologians and health care professionals must work together in a communal defense of the Church's profound teachings about the holiness and sacramentality of bodied existence and must relate this teaching to current reproductive technologies.


Environmental factors in affective disorders.

What are the factors that may precipitate overt depressive illness in the predisposed patient? The available data indicate that for unipolar disease, at least, the clearest correlations are not with economic or social status or with race, but rather with sex. Women display a lifetime risk about twice that of men in the same population, and the differences in social roles of the two sexes are probably largely responsible.


New concepts of chronic pain and their implications.

When chronic pain fails to respond to therapy, the approach often have been based on outmoded concepts of the nature of pain. The current unified pain theory takes into account recent biochemical advances and can serve as a basis for more effective diagnostic and therapeutic approaches. Various treatment modalities are reviewed in the context of the psychology as well as the physiology of severe intractable pain.


Immunologic mechanisms in nephritogenesis.

At least two different immunopathologic pathways that together account for most clinical nephritis have been delineated. Most common is the situation in which antigen-antibody complexes form in the circulation and lodge in renal basement membranes. The second involves antibodies to specific kidney structures. Both may initiate inflammatory injuries that adversely alter glomerular and tubular function.


Antibiotic-associated colitis.

Pseudomembranous colitis, a relatively uncommon and sometimes severe diarrheal disease, recently has been linked to the administration of a number of broad-spectrum antibiotics. The cause has now been identified as a spore-forming clostridial species not previously recognized as a human pathogen. Since the organism is sensitive to moset commonly used antibiotics, its spores may be the key to the disease.


Insulin treatment of diabetes.

Normal blood glucose levels can be achieved and maintained in many, possibly most, diabetics who need insulin by basing dosage on currently available clinical-laboratory ahd home-monitoring techniques, thereby postponing or minimizing complications.


Trisomy for the distal third of the long arm of chromosome 19 in brother and sister.

Trisomy for the distal third of the long arm of chromosome 19 was observed in a 12-year-old boy and his 9-year-old sister. Both are affected by extremely severe statural and psychomotor retardation. The physical symptoms common to both are dwarfism, micro- and brachycephaly, antimongoloid slant of the eyes, hypertelorism, ptosis, short nose, short philtrum, poorly formed ears, short neck with excess skin, barrel-shaped thorax, diastasis of rectus muscles, kyphosis, sacral dimple, excess of digital arches, pedes valgi, laterally curved big toes, epilepsy and muscular hypotonia. The chromosomal anomaly was transmitted by the mother, who is the carrier of a translocation t(19;20)(19q133;20pter). In the pedigree, extending over four generations, among 30 pregnancies fathered or mothered by 5 carriers resulted in: 6 individuals with normal karyotype, 9 carriers, 2 confirmed and 2 presumptive unbalanced abnormal children, and 10 abortions.


"Complete" trisomy 5p; de novo translocation t(2;5)(q36;p11) with isochromosome 5p. Case report and review of the literature.

A case of complete trisomy 5p due to a de novo translocation t(2;5)(q36;p11) with an isochromosome 5p is described. Complete trisomy 5p has been reported only once (Brimblecombe et al., 1977). The confusing literature relating to partial trisomy 5p is reviewed. Comparison of our case with the patients reported by Brimblecombe et al. (1977) and by Opitz and Patau (1975) is suggestive for a distinct clinical syndrome if (almost) the complete short arm of chromosome 5 is present in a trisomic state. Unfortunately the clinical findings in the case of Brimblecombe (1966, 1977) are poorly documented. The main features of this syndrome are: macrocephaly, psychomotor retardation, hypotonia, postnatal growth failure, tracheobronchial involvement, mongoloid slant of the eyes, epicanthus, low-set ears, depressed nasal bridge, short first toe, and seizures.


Trisomy 6q25 to 6qter in a severely retarded 7-year-old boy with turricephaly, bow-shaped mouth, hypogenitalism and club feet.

Trisomy for a small terminal segment of chromosome 6q produces a characteristic syndrome of malformations and dysmorphic signs which, on the basis of comparison with a previously published case, may be suspected on clinical grounds. The present case concerns a 7-year-old boy, the son of a carrier mother t(6;14)(q25;qter). The main symptoms are: very severe physical and mental retardation, turricephaly, Cupid's bow mouth with narrow lips, almond-shaped eyes with narrow palpebral fissures and ptosis, micropenis with absence of scrotum, club feet, hammer toes, and extension contractures. In addition, there are a great many minor dysmorphic features.


Three cases of sex chromosome mosaicism with a nonfluorescent Y.

Clinical and cytogenetic findings in three patients mosaic for sex chromosomes (45,X0/46,XY; 45,X0/46,XY/46,XYq-, and 45,X0/46,XY/46,XYY), each with a nonfluorescent Y, are presented. Hypotheses for the origin and effect of these chromosome constitutions are discussed.


Congenital glaucoma: genetic models.

Modes of inheritance of congenital glaucoma have been studied. Two methods of analysis, complex segregation analysis and frequency of congenital glaucoma in second- and third-degree relatives, did not permit one to retain a unitary mode of inheritance ofthis malformation. Genetic heterogeneity of congenital glaucoma is proposed. Recurrence risks and guidelines for genetic counseling in specified situations are given.


Evidence for a null allele at the esterase D (EC 3.1.1.1) locus.

Electorphoretic and quantitative assays of esterase D in a Caucasian family demonstrate the inheritance of a null allele, which was observed in the heterozygous state in six individuals.


Heterozygote manifestation in recessive generalized myotonia.

The frequency of heterozygotes of recessive generalized myotonia may be estimated at about 1/108 in the German Federal Republic. Some heterozygotes can be identified by an EMG. However, apart from this, apparently 2%--5% of heterozygotes may show minor subclinical manifestations. Sporadic cases of myotonia with late onset and a history of preceding, extremely prolonged physical stress, undernourishment, and/or prolonged cold exposure may be due to heterozygote manifestations of this otherwise recessive gene. Late onset and sporadic appearance also are features in patients with myotonia associated with hypothyroidism. One male patient displayed myotonia after a protracted diabetic coma. In cases reported in the literature where myotonia developed in association with either propranolol (beta-adrenergic blocking agent) or fenoterolhydrobromide (stimulator of beta receptors) heterozygote manifestation of recessive generalized myotonia is suggested.


Frequency of sister chromatid exchanges in Bloom syndrome fibroblasts reduced by cocultivation with normal cells.

Cocultivation of fibroblast cells from a male patient with Bloom syndrome (BS) and a female control reduced the rate of sister chromatid exchanges in the BS cells from a mean of 54 SCE per metaphase (range 42--65) to 41 (range 24--59). Medium used to culture control cells for 48 h also reduced the rate of SCE (from 40--65 to 33-54), whereas medium used for only 24 h altered the SCE rate only slightly (to 39--61). Dialyzed medium concentrate with molecular cutoff at 15,000 did not alter the SCE rate. These initial studies suggest that normal cells produce an agent, presumably lacking in BS cells, that is capable of mitigating the chromosomal manifestation of the BS mutation (bl) in bl/bl cells.


Trisomy 8p due to the 3:1 segregation of the balanced translocation t(8;15)mat.

An additional small G-like chromosome was found in a newborn female with multiple abnormalities and hemorrhagic diathesis. G banding showed that the index patient was trisomic for the short arm of chromosome 8 and revealed the anomaly t(8;15)(q12;p11) in her mother. The relationship between chromosome 8 and multiple hemorrhages is discussed.


Partial trisomy 18q12, due to intrachromosomal duplication, is not associated with typical 18 trisomy phenotype.

Partial 18q12 trisomy, due to intrachromosomal duplication, was found in a severely mentally retarded boy. The finding of nonspecific dysmorphism in this patient demonstrates that trisomy of band 18q12 is accompanied by neither a full nor an incomplete 18 trisomy phenotype, indicating that this phenotype may be due solely to trisomy of the 18q11 band.


Pure red cell hypoplasia associated with long-arm deletion of chromosome 5.

A further instance of the new hematologic entity of pure red cell hypoplasia with deletion of the the long arm of a chromosome 5(5q-) was seen in a 59-year-old white male. Examination of the bone marrow showed depressed erythroid cells with normal granulocytic and megakaryocytic precursors. Chromosomal analysis showed deletion of a chromosome 5 without any apparent translocation. This karyotype may be associated with acute leukemia.


The 8p- syndrome.

A boy with severe retardation of growth and development, minor dysmorphic features, severe congenital heart disease, and a 46,XY,8p-karyotype is described. The clinical findings of this boy are compared with those of others reported monosomic for a portion of the short arm of chromosome 8. The red cell glutathione reductase (GSR) level is normal in our patient.


Clinical and ultrastructural heterogeneity of type IV Ehlers-Danlos syndrome.

Ehlers-Danlos syndrome (EDS) type IV is a clinically and genetically heterogeneous disorder characterized by thin skin, prominent venous vascular markings, markedly increased bruising, and an increased likelihood of large bowel and large artery rupture. We studied two type IV EDS patients. Both have decreased amounts of type IIII collagen in skin, but ultrastructural examination of dermis showed massive dilation of rough endoplasmic reticulum in dermal fibroblasts in one, but not the other. Both had a major population of collagen fibrils of small diameter. Although previous studies suggested absent synthesis of type III collagen as the hallmark of one type of EDS IV, several abnormalities in metabolism of that type of collagen may be responsible for the phenotype in these disorders. Such disorders are likely to provide better understanding of the function of specific collagens in tissues.


Digital ridge counts and genetic fields.

Principal components analysis of quantitative digital dermatoglyphics in a large Oxfordshire sample, subdivided into male, female, urban, and rural subsamples, suggests several distinguishable components. These appear meaningful biologically in that they resemble factors of limb growth, as suggested by evidence from disturbances in limb extremity development. The components are consistent in all four subsamples and are very similar to those identified in a large sample of Berkshire data. It is suggested that digital quantitative dermatoglyphic variation may provide an example of genetic field theory.


Neuraminidase treatment reveals sialic acid differences in certain genetic variants of the Gc system (vitamin-D-binding protein).

Common and rare Gc phenotypes were analyzed by agarose gel electrophoresis immunofixation and by isoelectric focusing immunofixation before and after neuraminidase treatment. There is a difference between Gc types with double-band and with single-band patterns. Neuraminidase affects only Gc types with a double-band pattern: The double-band pattern is reduced to a single-band pattern. The anodal band disappears after removal of sialic acid by enzymatic cleavage; the cathodal band remains unchanged in its position and becomes stronger. Single-band Gc phenotypes remain unaltered after neuraminidase treatment.


The length of the Y chromosome in Nubian males and its location in metaphase spreads.

A total of 242 metaphase plates from the peripheral blood of Nubian males living near Aswan, Egypt were studied with respect to the length of the Y chromosome and its location in metaphase spreads. The length of the Y was similar to that found in American Negroes, and the Y chromosome was peripherally located in 79 of the 242 cells.


Chromosome deletion [46,XX,del(20)(q11)] in agnogenic myeloid metaplasia.

A woman in the fourth year of agnogenic myeloid metaplasia was found to have partial deletion of the long arm of chromosome 20 [46,XX,del(20)(q11)] in mitoses of presumably immature myeloid cells from unstimulated cultures of peripheral blood and bone marrow. Cytogenetic studies of peripheral blood lymphocytes showed a normal female karyotype.


Ring chromosome 22 in a mentally retarded child and mosaic 45,XX,-15,-22,+t(15;22)(p11;q11)/46,XX,r(22)/46,XX karyotype in the mother.

A ring chromosome 22 is described in a 6-year-old mentally retarded boy, who presented a dysmorphic syndrome. The ring chromosome 22 was inherited from the mother, in whom a 46,XX/46,XX,r(22)/45,XY,-15,-22,+t(15;22)(p11;q11) mosaic karyotype was found, indicating a high degree of instability of the chromosome(s) 22 in this woman.


Partial duplication of the short arm of chromosome 10. Karyotype: 46,XX,dup(10p)(pter to p12::p12::p12 to qter).

A 21-year-old mentally retarded female with 10p12 trisomy is reported. She presented a slight craniofacial dysmorphism very similar to that found in the full 10p-trisomy syndrome. Other features usually found in full 10p trisomy, however, such as failure to thrive and internal malformations, were absent.


Prenatal diagnosis and postnatal follow-up of an abnormal child with two de novo apparently balanced translocations.

By prenatal diagnosis two apparently unrelated reciprocal translocations involving chromosomes 6/15 and 13/14 were revealed in a fetus in whom echography demonstrated an abdominal tumor. Pregnancy continued. At birth the child had dysmorphia and hydronephrosis, for which surgery was performed. The psychomotor development was delayed. These abnormalities may be the result of the loss of a small amount of chromosomal material accompanying these translocations.


Chromosome mutations and chromosome stability in children treated with different regimes of immunosuppressive drugs.

The chromosome mutations and the number of sister chromatid exchanges induced by different kinds of immunosuppressive treatment were investigated in children and adults with certain types of renal diseases. The aim of the study was to find among the treatment schedules those promising good therapeutic results with the least mutagenic effects. A slightly decreased chromosome stability was found in the patients treated by cyclophosphamide therapy.


The effects of inbreeding and of some genetic polymorphisms on blood pressures, pulse rate and hematocrit in Northeastern Brazil.

The possible role of genetic mechanisms, as revealed by inbreeding depression and pleiotropic effects of the ABO, Es D and CA II loci, on blood pressures, pulse rate and hematocrit, was studied in a sample of 7,642 migrant Brazilian individuals of rural origin. It was not possible to confirm previous claims of the effects of ABO blood groups system and inbreeding on diastolic blood pressure. On the other hand, a significant inbreeding depression on pulse rate of about 1.23 bmp/10% F, among adult individuals, was revealed. The observed significant effects of several markers on hemodynamic variables, due to its number, were attributed to chance.


Purine base transport in normal and mutant erythrocytes.

The uptake of adenine and hypoxanthine in HGPRT-deficient and normal human erythrocytes was measured using a rapid filtering centrifugation technique. The transport of hypoxanthine as well as of adenine is impaired in the mutant cells. The transport of hypoxanthine into HGPRT-deficient erythrocytes differs from that into normal cells with respect to a higher accumulation capacity, to lower initial velocities and to the kinetic properties of the translocator. In addition, a higher accumulation capacity and lower initial velocities of adenine uptake could be demonstrated in  mutant cells. A linkage of the purine translocator with purine phosphoribosyltransferases associated with the erythrocyte membrane is discussed.


Human saliva as a source of biochemical genetic markers. I. Techniques.

The number of genetic markers identified in human saliva is still small compared to known genetic markers of blood. Enzyme activities that can be detected in human saliva by spectrophotometric techniques are listed. The methodologies currently available for the detection of biochemical genetic markers by polyacrylamide-gel electrophoresis are summarized.


Anthropometric and physiological properties in the determination of biological distances.

The investigation of anthropometric dimensions of the body and head, lung function tests and blood pressure was carried out in 3 separate groups. The analysis of 'distances' between particular pairs of the analyzed groups was performed by Penrose's CH2 and its components CQ2 and (v-l/v)CZ2. It is pointed to various ways of diversification of particular characteristics, which is likely to depend on different selective inertia of particular traits, that is, on different intensity of the effect of genetic and/or ecological factors on their formation. It is shown that as many different biological characteristics of human groups as possible should be taken into consideration for the calculation of 'distances'.


Inheritance of Indian childhood cirrhosis.

Detailed pedigree charts were prepared from 120 index patients suffering from Indian childhood cirrhosis (ICC). Of the 120 families, 84 were informative for segregation analysis. Since families were ascertained through patients who came to hospital for treatment, the data were analyzed according to a single-selection model. The observed segregation ratio for the entire data was significantly lower than the one expected under the hypothesis of autosomal recessive inheritance (p = smaller than 0.005). On the other hand, the segregation data for families with at least two affected children (multiplex families) were compatible with autosomal recessive inheritance. On this basis, however, at least 50% of all the cases of ICC would have to be of nongenetic origin. Alternatively, analysis of the data by the Falconer method indicated that ICC could be of multifactorial origin with very strong genetic determination (over 85%).


Some aspects of the occurrence of new mutations in haemophilia.

Using the data available on a group of carriers of haemophilia, the mutation rate in the male germ line was compared with that of the female germ line. The mutation rate among the male germ line was about 1-2 times that in the female germ line. An assessment of grandparental ages as a factor in the production of new mutations of haemophilia was also investigated.


Anthropometric differences between sicklers and nonsicklers in Zairian adults.

From a sample of 1,079 male adult Zairians living in regions where falciparum malaria is endemic 212 sicklers and 867 nonsicklers were compared for eight anthropometric variables. The two groups did not differ significantly in their variances. The sicklers had a higher mean for seven variables, but significantly so for head breadth only. These results are discussed in terms of the balance of the possible effects of the AS genotype on growth and of the possible selective effects of death from malaria in infancy.


The importance of stroma in morphogenesis and functional activity of urogenital epithelium.

Urogenital morphogenesis and cytodifferentiation are presented in the context of the epithelial-stromal interaction. The essential role of stroma in the processes is reviewed.


[Cell kinetics in experimental rheumatoid lesions and application in antirheumatic drug research (author's transl)].

The kinetics of chronic inflammatory cellular infiltrates in antiglobulin-induced arthritis, peritonitis and subcutaneous fibrin granuloma were investigated. Only small numbers of the mononuclear cells were labeled after 3H-thymidine impulse labeling, whereas a high labeling index results after 3H-thymidine labeling of the bone marrow. It is concluded that in experimental arthritis the inflammatory so-called cellular hyperplasia consists in bone marrow derived mononuclear cells. In experimental peritonitis glucocorticoid treatment decreases the 3H-thymidine labeling indices. By means of such labeling studies the antiproliferative and antiexsudative properties of steroids were demonstrated quantitatively. Therefore we suggest to make use of experimental cell kinetics for the recognition of anti-rheumatic drugs.