[Nutrition pumps in pediatrics: a comparative study].

Home enteral nutrition as the sole or as an additional way of feeding children is becoming increasingly popular. It can be used in the form of bolus-feeding, or as drip-feeding, either continuous (24 hours) or semicontinuous (nightly). For the latter method usually a feeding pump is used. In the Netherlands several feeding pumps are available, which were tested in this report. These feeding pumps (Compat, Enteroport, Flexiflo Companion, Flocare 500, Frenta Mat, Frenta-System II, Kangaroo 324, Nutromat Päd S, Nutromat S) were investigated for accuracy, available rate-settings, adequate alarming at interruption of the drip feeding, weight and ease of operation. All pumps were tested stationary, and suitable pumps weighing less than 1000 grams were subsequently tested ambulatory. The nine tested pumps were all fairly easy to operate. Three pumps were not suitable for pediatric use, either because the infusion rate was more than 30% out of range (Flexiflo Companion) or because of inadequate rate settings (Nutromat S and Frentasystem II; respectively 20 and 25 ml/hour minimally). Accuracy for the other pumps was always within 10% of the set rate. One pump, the Enteroport, has a rate setting which is suboptimal for pediatric use. In addition this pump does not alarm when the drip feeding is interrupted. The other pumps (Compat, Frenta Mat, Kangaroo 324, Flocare 500, and Nutramat Päd S) are all suitable for pediatric use, both with respect to the rate settings as to the adequate alarming when the drip feeding is interrupted. The Flocare 500 and the Nutromat Päd S, in addition to the Enteroport, have a weight below 1000 grams.(ABSTRACT TRUNCATED AT 250 WORDS)


Efficiency of grain production and latent image fading in F-18 micro-autoradiography.

In 18F micro-autoradiography using a frozen section method, the grain production was measured relative to the exposure time and radioactivity. The grain production increased until 6-hr exposure, but 7-hr or longer exposure induced a characteristic of latent image fading. However, the ratios of the efficiency of grain production between two different 18F-radioactivities (11.9 and 2.3 mBq/100 microns2) were constant over experimental exposure times, thus indicating that quantitative analysis by grain counting is preserved.


An endocrinological study of persistent pubertal macromastia.

We performed an endocrinological study on three males with persistent pubertal macromastia. The blood testosterone (T) level in these patients was either elevated or at the upper normal limit, estrone (E1) and estradiol (E2) levels were high, and T/E1 and T/E2 ratios were decreased. Persistence of low T/E1 and T/E2 ratios was thought to be the cause of the macromastia. Results of therapy using drugs (cyproterone acetate, tamoxifen citrate, danazol, and clomiphene citrate) were unsatisfactory. Persistent pubertal macromastia is an extreme condition of physiological pubertal gynecomastia, a transient phenomenon in more than half of pubertal males. It is a pathological condition characterized by a great degree of breast enlargement and abnormal endocrinological findings, and its clinical course and treatment are different from those of physiological pubertal gynecomastia.


Is there any effect of volcanic eruptions of Mount Sakurajima on canine lungs exposed naturally?--Morphometric analysis of intrapulmonary particulate deposit amount and histopathological investigations.

In order to see whether any effect of inhalation of volcanic ash and gases from Mt. Sakurajima on canine lungs is observed or not, we examined the amount of intrapulmonary particulate deposits (IPD) and histopathological changes. Twenty-five abandoned or stray dogs (group A) in the areas affected enormously by volcanic ash and gases were examined in comparison with 13 abandoned or stray dogs (group B) in the area scarcely influenced. The amount of IPD was measured by using an image analyzer combined with a microscope. Age-associated increase of IPD values was noted, but mean IPD values were not different between groups A and B. Incidence of goblet cell hyperplasia was not different between the two groups. In none of the cases examined, squamous metaplasia of respiratory epithelia, pulmonary fibrosis, silicotic nodules, emphysematous change, or histopathological findings, which are indicative of bronchial asthma, were observed. In conclusion, obvious effect of volcanic eruption on canine lungs was not observed through both the measurement of IPD value and the histopathological evaluation.


Experimental tracheal allotransplantation using omentopexy: histological process of rejection reaction without immunosuppression.

A large defect in the thoracic trachea was produced by resecting 10 rings of tracheal cartilage in each of 11 adult mongrel dogs. An allograft of the five tracheal rings was interposed in this site via end-to-end anastomosis and then wrapped with the pedicled omental flap. These animals received no immunosuppressive therapy. The pseudostratified tracheal epithelia were remained and the graft revascularization through the omental pedicle proved to be established within about one week after surgery without immunosuppression. Marked mononuclear cell infiltration was observed beneath the epithelia and around the capillaries in the subepithelial layer over one week after surgery, which was followed by phagocytosis of the tracheal cartilages by macrophages. After the completion of rejection reaction, inflammation finally induced scarring or necrosis of the tracheal allograft, resulting in asphyxia or perforation. Only one animal survived 71 days after surgery without graft trouble. However, even in this animal, weak rejection reaction was observed microscopically and the structure of the graft was not that of the normal trachea. We think these results suggest that allotransplantation of trachea induces rejection, and therefore, that the use of immunosuppressants is necessary.


Cytologic assessment of peroperative pleural effusion and prognosis in lung cancer patients who underwent resection.

Twenty-five of 108 lung cancer patients who underwent resection had cytologically positive pleural effusions. The rate at which cancer cells were detected was not related to the amount of the effusion. Almost one third of patients with cancer cells in effusion were alive at the end of the third postoperative year, provided that the pleura itself was free of metastasis at the time of operation. Correlation of the cytologically positive rate of pleural effusion (Y) with the degree of pleural metastasis (X1), the degree of pleural involvement (X2), or the degree of nodal involvement (X3) was analyzed using the Hayashi's quantification method type I. The multiple correlation coefficient was 0.843. Partial correlation coefficients of X1, X2, and X3 were 0.733, 0.446, and 0.653, respectively. Pleural metastasis had the strongest effect on the cytologically positive rate of pleural effusion.


Lung cancer in patients with idiopathic pulmonary fibrosis.

We investigated lung cancer in 99 patients with idiopathic pulmonary fibrosis (IPF). Lung cancer was found in 31 (31.3%) of 99 patients with IPF. Most (87.9%) tumors, including squamous cell carcinoma, were observed in the peripheral region of the lung, whereas the distribution of histologic types of cancers was similar to that seen in ordinary lung cancer. Peripheral tumors were frequently seen in the lower lobe, where fibrotic shadow was prominent. However, the severity of fibrosis was not related with the prevalence or histologic type of lung cancer. Two-thirds of IPF patients having a smoking history of over 40 years developed lung cancer. When compared with nonsmoking IPF control subjects, the relative risk of smoking in IPF patients was 3.5, identical with that reported for smokers in the general population. We suggest that smoking in patients with IPF is an additive risk factor for the development of lung cancer. We also speculate that the high prevalence of peripheral squamous cell carcinoma might be associated with cigarette smoking.


Tissue distribution of 125I-labeled fetal thyroid hormone in nude mice xenografted with Ewing sarcoma.

Biodistribution of fetal thyroid hormone (RT3) was studied in nude mice with Ewing's sarcoma xenografts. At 30 min and 1, 2, 4, 8, and 12 hr after injection, blood, tumor and normal organs were measured to determine the amount of radioactivity per gram of tissue. The amount of radioactivity in the blood of tumor-bearing mice decreased sharply from 7.64% of injected dose per gram of tissue (% ID/g) at 30 min after inoculation to 0.45%/ID/g at 12 hr. The % of injected dose per gram for 125I-labeled RT3 in the tumor reached 1.92 at 1 hr after injection and decreased to 0.22 at 12 hr. The radiolocalization indices for tumor to other organs at 12 hr ranged from 1.35 to 4.43. This study suggests increased localization of RT3 in the Ewing's sarcoma as compared to other tissues in the nude mouse.


Mutations of p53 gene in human colorectal tumor in Japan: molecular epidemiological aspects.

Effects of environmental carcinogens on DNA can be detected, because, while each carcinogenic agent is inherently different, its corresponding "fingerprint" is unique to a specific mutation pattern. The p53 tumor suppressor gene is of particular interest because the relationship between environmental factors and genetic alterations of carcinogenesis can be investigated. In this report, we compared the mutation patterns of the p53 gene in human colorectal tumors from Japanese patients with those from US patients. The results show different rates of transversion and transition among these two populations, which suggests a difference between Japan and the US in the etiological factors underlying colorectal tumorigenesis.


Quantitative investigations of placental terminal villi in maternal diabetes mellitus by scanning and transmission electron microscopy.

The structure of the terminal villi was observed in placentae from non-diabetic mothers and mothers with diabetes mellitus using scanning and transmission electron microscopy. The metabolic condition of maternal diabetes was tightly controlled. In the diabetic group, the diameter of the terminal villi was significantly smaller than in the control group. The ramification pattern of villi, classified into hypo-, moderate- and hyper-ramifications, was shown to be mostly moderate in the non-diabetics whereas most of the diabetic placentae had either hypo- or hyper-ramifications. Mothers with a longer duration of diabetes and complicated with retinopathy tended to have hypo-ramification; in these mothers, the weight of the neonates was significantly less than normal. Moreover, in the diabetic placentae, syncytial knots were found more frequently, the percentage of vasculo-syncytial membranes tended to be lower, and the trophoblastic basement membrane was significantly thicker than in the control. These abnormalities in the diabetic placentae were independent of the methods of delivery; they seem to be related with fetal growth retardation and poor neonatal outcome, which are commonly seen in diabetic pregnancy.


Photocontact dermatitis due to piroxicam: photopatch testing.

I report a case of photocontact dermatitis due to piroxicam gel, a nonsteroidal anti-inflammatory drug. A 62-year-old man developed pruritic eczematous lesions after applying the gel for 2 days. The patient reacted positively to photopatch testing with ultraviolet A and piroxicam (1% and 0.1% in petrolatum). In addition, the patient had positive patch tests to thimerosal, thiosalicylate, and in vitro-irradiated solution of piroxicam plus human serum albumin, but the tests with the mercurial compounds were negative. These results support the close relationship between sensitivity to thiosalicylate component of thimerosal and photosensitivity to piroxicam, as indicated recently.


Effects of long-term running on lymphocyte subpopulations.

Thirteen healthy members (11 males and 2 females; mean age 19.8 years) of an athletic club underwent a long-term exercise program (five 8-km runnings per week for 40 weeks) as regular training for their club. The circulating lymphocyte number, T lymphocyte percentage, and OKT4/OKT8 ratio did not change through the 40-week training period. However, suppressor/inducer (Leu3a+Leu8+) and suppressor T cells (Leu2a+Leu15+) significantly increased. In contrast, helper (Leu3a+Leu8-) and cytotoxic T cells (Leu2a+Leu15-) significantly decreased. On the other hand, there was no change in three males (mean age 18.7 years) without the long-term exercise program. These results suggest that long-term running may induce some change in lymphocyte subpopulations.


Relation between fetal blood gas levels and the outcome of babies in severe preeclampsia.

The purpose of this study is to ascertain that fetal blood gas values obtained by cordocentesis could be a clinical standard to decide whether or not we should terminate pregnancy and switch to exutero salvage for avoiding hypoxic damage. Fetal blood sampling was performed 38 times in 36 cases of severe preeclampsia. The relation between fetal blood gas values and the prognosis of the baby was statistically examined. Six of 36 fetuses of severe preeclampsia died prenatally or postnatally. There were significant differences in delta-values (difference from the normal mean value in each gestational week) of pO2, pCO2, and pH between survivors and non-survivors. delta pO2 value is most reliable to predict fetal prognosis. Since conventional fetal evaluation methods such as fetal heart rate monitoring are unreliable in the early gestational period, fetal gas evaluation is preferable to decide further intervention.


Insulin releasing action of N-terminal peptides of glucagon in dogs.

The relationship between the molecular structure and insulin releasing action of glucagon remains unknown. In order to investigate the direct action of N-terminal peptides of glucagon, glucagon (1-14), and glucagon (1-21) were studied using an in situ local circulation of the canine pancreas. These glucagon fragments as well as glucagon (1-29) were infused into the superior pancreaticoduodenal artery in a dose of 400 pmol for 10 min during the glucose or arginine infusion, and plasma insulin and glucagon in the superior pancreaticoduodenal vein were determined by radioimmunoassay. During the glucose infusion, glucagon (1-14) elicited a slight increase in plasma insulin, whereas glucagon (1-21) and (1-29) revealed significant changes in plasma insulin. In these experiments plasma glucagon did not change significantly following the administration of glucagon (1-14) or (1-21). During the arginine infusion all of the glucagon fragments studied enhanced insulin secretion markedly, whereas glucagon secretion was not affected. Furthermore, graded doses of glucagon (1-14) (50, 150, and 400 pmol) elicited an increase in plasma insulin in a dose-related manner. It is concluded from the present study that the N-terminal peptides of glucagon stimulate insulin release especially during the arginine infusion.


Anti-LFA-1 antibody treatment of a patient with steroid-resistant severe graft-versus-host disease.

For treatment of steroid-resistant severe graft-versus-host disease, a murine monoclonal antibody (25.3) against the alpha chain (CD11a) of the lymphocyte function-associated antigen 1 (LFA-1) was infused into a patient with posthepatitic aplastic anemia who had undergone allogeneic bone marrow transplantation. The monoclonal antibody infusion was well tolerated and resulted in appreciable improvement in symptoms of gastrointestinal illness such as diarrhea and abdominal pain, suggesting that this antibody may be useful for controlling severe acute graft-versus-host disease.


Effects of brief physical exercise on the concentrations of immunoreactive superoxide dismutase isoenzymes in human plasma.

Effects of cycle ergometer exercise (approximately 75% VO2max for 15 min) on the concentrations of immunoreactive Mn- and CuZn-superoxide dismutases (SOD) in plasma were studied on 10 male students. During the experimental period, Mn-SOD concentration did not vary substantially. On the other hand, CuZn-SOD concentration decreased markedly at 15 min and 24 hr after the exercise; that is, CuZn-SOD appeared to differ virtually from Mn-SOD in recovery pattern.


Combination of conventional and endotoxin-specific limulus tests for measurement of polysaccharides in sera of rabbits with experimental systemic candidiasis.

Factor G, the coagulation enzyme from limulus amebocytes, is activated by (1-->3)-beta-D-glucan but not by endotoxin. The endotoxin-specific limulus test, which is devoid of factor G, reacts only with endotoxin. However, the conventional limulus test which includes factors G and C, reacts with not only endotoxin but also with (1-->3)-beta-D-glucan. In this study, the culture supernatant of Candida albicans in RPMI medium activated the conventional limulus test, but not the endotoxin-specific limulus test. All five rabbits inoculated intravenously with Candida albicans (1.0 x 10(7) CFU/rabbit) showed increased levels of reactivity with the conventional limulus test, whereas no elevation in the levels of the endotoxin-specific limulus test was observed in the sera of any infected rabbits. Only one serum sample from rabbit No. 5 on day 8 showed a positive Cand-tectest. The difference in the titers of the two limulus tests was suggestive of a diagnosis of Candida infection.


Recovery of impaired motor function of the upper extremity after stroke.

Manual function score (MFS) of 174 hemiparetic stroke patients was examined every week for 8 weeks after starting the occupational therapy with programs based on MFS recovery profile, and the relation between the time since stroke onset (x) and MFS (y) was approximated by a hyperbolic function, y = A - B/x. The patients were classified into two groups, 125 cases (71.8%) with statistically significant fit of the function (fit group) and 49 without fit (non-fit). Using demographic and neurological variables of each patient, characteristics of the patients with regular recovery were analyzed. The results indicated that the gain of MFS during 8 weeks of the therapy was large in the fit group compared to the non-fit, and the regular recovery could be mostly expected in rather young patients, those with early start of the therapy, and those without ataxia, mental deterioration, and cortical lesions.


Postremission therapy without prednisolone improves survival in adults with acute leukemia.

This prospective randomized clinical trial was to clarify whether postremission therapy without prednisolone (PSL) was more effective than therapy with PSL in improving the 5-year survival of adults with acute leukemia. Thirty consecutive adult patients with newly achieved complete remission were randomized to receive postremission therapy either with or without PSL between September 1985 and September 1988. The patients ranged from 16 to 57 years in age. Patients treated without PSL had a significantly better 5-year survival rate than those receiving PSL according to Kaplan-Meier analysis (53.5% vs 15.3%, p < 0.05). In the group treated without PSL, eight out of 15 patients were alive at 72 months, and seven patients maintained their first complete remission at 72 months. Among patients with acute lymphoblastic leukemia (ALL) who were treated without PSL the median duration of remission was 24 months, and the survival rate at 72 months was 50.0%. On the other hand, the median survival was only 13 months for the 5 patients with ALL treated with PSL. Thus, it is desirable that adults with acute leukemia are treated by postremission therapy without PSL.


Analytical examination of oxidized free and esterified 7-ketocholesterol and related oxysterols in human plasma incubated with copper.

Oxygenated derivatives of cholesterol (oxysterols) have been demonstrated to possess a wide variety of biological properties and evaluated for their abilities to inhibit cholesterol biosynthesis. We investigated a method to analyze copper-catalyzed oxidation products of human plasma cholesterol. Free and esterified oxysterols produced were mainly 7-ketocholesterol, and small amounts of 7 beta-hydroxycholesterol and 5, 6 alpha-epoxy-cholesterol were also identified. Quantitatively, the sterol nucleus of ester was less susceptible to oxidation than that of the free form. This finding suggested that the cholesterol nucleus of ester form was more resistant against oxidative stress than free form. Additionally we demonstrated that the addition of probucol, a powerful antioxidant used clinically to lower blood cholesterol, inhibited this copper-catalyzed oxidation of cholesterol.


Simulation of the profile of water, NaCl, and urea transport in the countercurrent multiplication system between thin ascending limb and inner medullary collecting duct.

We simulated the profiles of water, NaCl, and urea transport in the countercurrent multiplication system between thin ascending limb (TAL) and inner medullary collecting duct (IMCD) by a mathematical model consisting of three compartments (TAL, IMCD, and CNW [capillary network]), using phenomenological coefficients for hamsters. They are separated by two membranes with distinct permeability properties. The primary driving force which generates "single effect" has a lower reflection coefficient for urea than for NaCl in IMCD. The difference in urea and NaCl concentrations between CNW and IMCD provides an effective osmotic driving force which is favorable for water absorption from IMCD without physicochemical osmotic gradient. The entry of water in the CNW reduces the concentration in CNW and generates the concentration gradients which are favorable for these solutes to diffuse out of TAL. Thus, the fluid in IMCD is concentrated and that in TAL is diluted. The results of simulation showed that the concentration gradients were generated along the medullary axis, resulting in excretion of hypertonic urine. In addition, we examined effects of changes in phenomenological coefficients of IMCD on this concentrating system. Decreases in permeability and in reflection coefficient for urea and increase in hydraulic conductivity increased the osmotic gradients along each compartment.


Coarse to fine hair conversion induced by zinc in C57/6J mice.

The cytotoxic effects of excessive zinc is well documented but its effect on cytodifferentiation appears relatively unknown. We show here that chronic administration (25 days) of zinc chloride in C57/6J mice (11 to 56 micrograms/g body weight, 5 times per week), which was lower than the in vitro cytotoxic level, caused a loss of long coarse hairs, which were replaced by short fine (vello) hairs. Histological architecture of the skin appeared normal except for the confinement of hair follicles to the dermis without any extension into the hypodermis.


Structural and functional properties of snake venom prothrombin activators.

In this review we have summarized the current knowledge about the prothrombin activating principles present in the venom of a large number of different snake species. It appears that snake venom prothrombin activators can be classified into four different groups based on their structural properties and on their functional properties in prothrombin activation. Group I activators efficiently convert prothrombin into meizothrombin and their activity is not influenced by the non-enzymatic cofactors of the prothrombinase complex (CaCl2, factor Va and phospholipid). Group II and III activators can cleave both peptide bonds in prothrombin necessary to convert prothrombin into thrombin. The prothrombin-converting activity of Group II activators is strongly stimulated by phospholipids and factor Va in the presence of CaCl2, whereas the activity of group III activators is only stimulated by CaCl2 and phospholipid. Group IV consists of snake venom proteases which do not convert prothrombin into enzymatically active products but cleave peptide bonds in prothrombin, resulting in the formation of inactive precursor forms of thrombin.


Occurrence of tetrodotoxin-binding high molecular weight substances in the body fluid of shore crab (Hemigrapsus sanguineus).

The shore crab (Hemigrapsus sanguineus) is highly resistant to tetrodotoxin (TTX) although it contains no detectable amount of TTX (less than 5 MU/g, where 1 MU is defined as the amount of TTX killing a 20 g mouse in 30 min). Its body fluid was examined for neutralizing effects against the lethal activity of TTX. When the mixture of the body fluid and TTX was injected i.p. into mice, the lethal activity of TTX was significantly reduced; 1 ml of the body fluid was evaluated to neutralize 3.6-4.0 MU of TTX. Higher neutralizing activity (7.2-12.5 MU/ml of the body fluid) was exhibited by i.v. administration of the body fluid into mice before or after i.p. challenge of TTX. The lethal effect of paralytic shellfish poisons was not counteracted by the body fluid. Analysis by gel filtration on Sepharose 6B revealed that the body fluid contained TTX-binding high mol. wt substances (> 2,000,000) responsible for the neutralizing activity of the body fluid against TTX, which accounts for the high resistibility of the crab to TTX. When the crude toxin extracted from the liver of puffer (Takifugu niphobles) was mixed with the body fluid and chromatographed on Sepharose 6B, almost pure TTX was obtained from the fractions containing the TTX-binding high mol. wt substances, suggesting that the TTX-binding high mol. wt substances could be useful in purification of TTX from biological samples.


Toxin composition of resting cysts of Alexandrium tamarense (Dinophyceae).

Paralytic shellfish toxin composition in the resting cysts of the dinoflagellate Alexandrium tamarense was investigated by means of high performance liquid chromatography. A comparison was made between cysts collected from ship ballast tank sediments, natural population of motile vegetative cells collected from the area where ballast water was taken, as well as cultured vegetative cells established from the cysts and the natural plankton bloom. Total toxin concentration of the cysts (595 fmole/cell) was six-fold higher than that of the natural population of vegetative cells. They contained the same ten toxic components but in different relative abundances. The higher proportion of 11-alpha-hydroxysulfate epimers in the cysts suggests that the biosynthesis of toxins is halted at an early stage in cyst formation.


An assessment of potential chemoprotectant activity against ricin toxicity by mechanism based glycosidase inhibitors in macrophage J744A.1 cell cultures.

The abilities of potential chemoprotectants to inhibit cytotoxicity of ricin have been determined in vitro, using the macrophage cell line J744A.1. Six compounds were tested: alpha- and beta-galactopyranosylamine; N-bromoacetyl-alpha-D-galactopyranosylamine; N-bromoacetyl-beta-D-galactopyranosylamine; N-bromoacetylglucopyranosylamine; and N-bromoacetylmannopyranosylamine. Of the six compounds which were tested, only N-bromoacetyl-alpha-D-galactopyranosylamine and N-bromoacetyl-beta-D-galactopyranosylamine exhibited significant activity against ricin toxicity, as indicated by the release of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST). The alpha-isomer provided greater protection against ricin toxicity and also exhibited less inherent cytotoxicity in the absence of ricin, as compared to the beta-isomer. Neither the alpha- and beta-galactopyranosylamines nor the glucose and mannose analogs were promising as potential chemoprotectants.


Inhibition of norepinephrine secretion from digitonin permeabilized PC12 cells by botulinum type D toxin.

Botulinum type D neurotoxin inhibited Ca(2+)-evoked norepinephrine secretion in digitonin permeabilized PC12 cells. Inhibition by the toxin required prior incubation with dithiothreitol (DTT). The inhibition was dependent on both concentration and incubation times of the toxin, and was affected by Ca2+ concentration. With less than 0.7 microM Ca2+ almost complete inhibition was observed; however, above 0.7 microM, Ca2+ stimulated additional norepinephrine release in a dose-dependent manner.


Pyrularia thionin increases arachidonate liberation and prolactin and growth hormone release from anterior pituitary cells.

Pyrularia thionin is a 47 amino acid peptide isolated from the nuts of Pyrularia pubera. This peptide does not have intrinsic phospholipase A2 activity, but it increases the liberation of arachidonate from several tissues. Exposure of anterior pituitary cells to this toxin increases the liberation of arachidonate, increases the cellular levels of lysophospholipids, and decreases cellular phospholipids. Thus, phospholipase A2 is involved in the liberation of arachidonate stimulated by this peptide. Because this toxin also increases stearate liberation from the pituitary cells, either diacylglycerol lipase, phospholipase A1 or lysophospholipase may be directly or indirectly activated by this toxin. In addition to increasing fatty acid liberation, Pyrularia thionin increases the release of prolactin and growth hormone from anterior pituitary cells over the identical concentration ranges that this toxin liberates the fatty acids. Pyrularia thionin increased arachidonate liberation and prolactin release from perifused pituitary cells within 2 min, and following withdrawal of the toxin, arachidonate liberation and prolactin release returned to near basal levels within 6 min. Dopamine, a physiological inhibitor of prolactin release that closes calcium channels, decreased prolactin release stimulated by Pyrularia thionin. However, dopamine had no effect on the arachidonate liberation stimulated by this peptide. Similarly, D-600, an organic calcium channel blocker, decreased the prolactin and growth hormone release stimulated by the toxin without affecting the toxin-stimulated arachidonate liberation. Therefore, Pyrularia thionin increases arachidonate liberation through the rapid activation of phospholipase A2 by a mechanism that is not dependent on calcium uptake via D-600-inhibitable calcium channels. In contrast, the prolactin and growth hormone release stimulated by this toxin requires calcium uptake via D-600 inhibitable calcium channels.


Analysis of Acanthurus triostegus for marine toxins by the stick enzyme immunoassay and mouse bioassay.

The herbivorous convict tang or surgeon fish, Acanthurus triostegus, collected at different locations in the Hawaiian islands, was analyzed for toxicity using a mouse bioassay and a stick enzyme immunoassay (S-EIA) developed to detect ciguatoxin and closely related polyethers. Results of the S-EIA test indicated that about 94% of the samples gave negative readings, while 6% of the fish were positive and thus considered toxic. Fish samples from each location were pooled and the flesh and viscera were successively extracted with hexane, methanol, and water and tested in a mouse bioassay. About one-third of the methanol soluble fractions killed mice within 20 min, 70% killed within 4 hr, and 85% killed within 48 hr. About 40% of the hexane-soluble fractions killed mice within 24 hr and 55% killed within 48 hr. The water-soluble extracts of the flesh and viscera of fish taken from three locations showed relatively high toxicity. Common symptoms for all fractions included convulsions and jumping (especially just prior to death), respiratory distress, hind leg to complete paralysis, loss of body tone, and tremors. Analysis of the data suggests that in the flesh and viscera of A. triostegus there are at least three different nervous system-type toxins, most of which did not appear to react to the S-EIA test.


Effect of oral Saccharomyces boulardii treatment on the activity of Clostridium difficile toxins in mouse digestive tract.

Human antibiotic-associated diarrhoea and pseudomembranous colitis are partly due to toxin production by Clostridium difficile. It is now well documented that Saccharomyces boulardii protects against C. difficile induced diseases. In an attempt to understand better the mechanism of this protective effect, the action of S. boulardii on a crude toxin preparation was studied in vitro and in vivo. The results showed that the yeast had no effect on the toxins in vitro but was able to protect mice inoculated with these toxins. Furthermore, the observation by scanning electron microscopy that the mucosa of S. boulardii protected mice was not damaged suggest that the yeast mainly acts on the intestinal mucosa.


Neutralization of different activities of venoms from nine species of Bothrops snakes by Bothrops jararaca antivenom.

Antivenoms are the usual treatment in cases of systemic envenoming by Bothrops snakes. However, the neutralization of each venom component by the antivenom is not well established. Bothrops jararaca antivenom, produced in rabbits, recognizes the venoms of nine different Bothrops species with high ELISA antibody titres. Western blot analysis showed that almost all antigens present on both homologous and heterologous venoms are recognized. Neutralization tests were performed using whole antivenom or its IgG fraction. The antivenom was able to neutralize the haemorrhagic, coagulant and necrotizing activities of the heterologous venoms in the same antivenom/venom proportion as for the homologous venom. Myotoxic activity was only partially neutralized. Neutralization of the proteolytic activity of heterologous venoms required higher amounts of antivenom than for the homologous venom. Phospholipase and oedema-inducing activities were completely neutralized only in the homologous system.


Toxic activities of venoms from nine Bothrops species and their correlation with lethality and necrosis.

The comparison of seven toxic activities contained in venoms from nine different species of Bothrops and the correlation of each activity with lethality and necrosis was the subject of this study. The haemorrhagic, coagulant, necrotizing, myotoxic, proteolytic and phospholipase activities were not equally distributed among the venoms studied except for the oedema-inducing activity which was almost equally distributed among them. The correlation coefficient was estimated for each activity in relation to lethality and necrosis induced by the venom. Lethality was significantly related to haemorrhagic and oedema-inducing activities, whereas the necrotizing activity showed significant correlation with phospholipase and coagulant activities. Proteolytic activity presented a significant inverse correlation with lethality.


The use of enzyme-linked immunosorbent assay for the quantitation of Calloselasma rhodostoma (Malayan pit viper) venom and venom antibodies.

The specificity and sensitivity of an indirect and two (an 'ordinary' and a 'rapid') double sandwich enzyme-linked immunosorbent assay (ELISA) procedures for the quantitation of Calloselasma rhodostoma (Malayan pit viper) venom were examined. The three assays were equally sensitive and the accuracy of the assays was not substantially affected by individual variation in the venom composition. The specificity of the assays was examined against 26 venoms from snakes of the families Viperidae and Elapidae. While the double sandwich ELISA procedures were sufficiently specific to be used in the clinical immunodiagnosis of C. rhodostoma bite in Malaysia, the indirect ELISA procedure exhibited extensive cross-reactivity with other Malaysian pit viper venoms. Attempts were made to improve the specificity of the indirect ELISA procedure for the quantitation of C. rhodostoma venom. A 'low ELISA cross-reactivity' venom fraction (termed VF52) was isolated from C. rhodostoma venom by repeated Sephadex G-100 gel filtration chromatography. The indirect ELISA procedure using antibodies to VF52 as immunoreagent showed an improvement in specificity. The use of the indirect ELISA procedure for the detection of C. rhodostoma antibodies was also examined and the results show that the assay was sufficiently specific to be used for retrospective diagnosis of C. rhodostoma bite in Malaysia, in particular when VF52 was used as the coating antigen.


Detection of new 7-O-acyl derivatives of diarrhetic shellfish poisoning toxins by liquid chromatography-mass spectrometry.

A novel method for the detection of acylated diarrhetic shellfish poisoning toxins is reported. Direct determination of these compounds is possible using high performance liquid chromatography coupled with ion-spray mass spectrometry. An extract, purified from the digestive glands of toxic mussels (Mytilus edulis) contaminated with okadaic acid, dinophysistoxin-1, and a recently reported analog, dinophysistoxin-2, was also shown to contain small amounts of dinophysistoxin-3, a mixture of 7-O-acyl ester derivatives of dinophysistoxin-1. In addition, acyl ester derivatives of okadaic acid and dinophysistoxin-2 were also detected by direct LC-MS analysis and confirmed by analysis of their hydrolysis products. This is the first report of the detection of other naturally occurring 7-O-acyl esters similar to dinophysistoxin-3.


Active and passive immunization for tetrodotoxin in mice.

This study describes the possibility of active and passive immunization for tetrodotoxin (TTX) poisoning. TTX was conjugated to keyhole limpet hemocyanin and this conjugate was used as an immunogen in rabbits and mice. Mice immunized with the conjugate were protected from a lethal dose of TTX. Passive protection experiments demonstrated that immunoglobulin from rabbit antiserum exhibited a dose-related therapeutic activity in mice after challenge with TTX.


Ethanol toxicity and oxidative stress.

The mechanisms underlying the toxicity of ethanol have been the subject of much study, but are not well understood. Unlike many selective pharmacological agents, ethanol clearly has several major loci of action. One deleterious factor in ethanol metabolism is the potential for generation of excess amounts of free radicals. The extent to which this activity accounts for the overall toxicity of ethanol is unknown. This review outlines the enzymic steps that have the capacity to generate reactive oxygen species. These steps are likely to differ in acute and extended exposures to ethanol. Acetaldehyde catabolism also has the likelihood of contributing to ethanol-related oxidative stress. The review focuses on the ethanol-induced production of excess amounts of pro-oxidant reactive species in both the liver and the central nervous system. The potential of various stages of ethanol catabolism to involve generation of free radicals is described.


Effect of chronic exposure to NO2 in the developing ferret lung.

The effect of chronic exposure to low (0.5 ppm) and high (10 ppm) concentrations of NO2 on the development of the ferret lung was studied in animals exposed 4 h/day, 5 days/week from age 6 weeks through 20 weeks. Morphometric analysis showed significant changes in alveolar dimensions at both concentrations, compared to air-exposed controls. Thickened alveolar walls, increased cellularity and collagen deposition, increased lung size and the appearance of lesions indicative of oxidant damage indicate that even low concentrations of this gas during lung development may have adverse consequences for adult lung function.


The effect of cyclophosphamide administration on the kidney of the rat.

In studies primarily designed to evaluate the effectiveness of chitosan as a treatment for cyclophosphamide-induced hemorrhagic cystitis in the rat, renal papillary necrosis and pyelonephritis were observed. Cyclophosphamide alone produced relatively mild renal changes. The combination of cyclophosphamide and intravesical instillation of acetic acid induced renal papillary necrosis (38 to 83% incidence) along with pyelonephritis, hydroureter and hydronephrosis. Chitosan, instilled in place of acetic acid, partially inhibited the induction of renal papillary necrosis. It appears that the presence of vesico-ureteral reflux with or without associated hydroureter and hydronephrosis is a prerequisite for cyclophosphamide-induced renal damage.


Independence and additivity of cultured hepatocyte killing by Ca2+ overload and ATP depletion.

In two competing models of toxic cell death, hepatocyte killing by chemical hypoxia (CN/IAA) is attributed to ATP depletion and killing by A23187 is attributed to Ca(2+)-induced damage. The independence of these models can be questioned because CN/IAA elevates Ca2+ before killing 1c1c7 hepatoma cells and because the ATP source fructose prevents hepatocyte killing by Br-A23187. In the present studies, cultured mouse hepatocytes were exposed to CN/IAA, A23187, or treatments in combination. A23187 produced toxicity proportional to Ca(2+)-activated DNA fragmentation. CN/IAA caused comparable toxicity but no fragmentation of DNA. Treatments in combination were more toxic than either treatment alone. Aurintricarboxylic acid, a Ca(2+)-endonuclease inhibitor, decreased DNA fragmentation and the toxicity of A23187 and combination treatment without affecting CN/IAA toxicity. ATP plus oligomycin decreased CN/IAA and combination treatment toxicity but not that of A23187. These findings indicate that cultured mouse hepatocytes are killed through mechanisms that are independent and additive in their toxicities.


Inhibition of interleukin-2-stimulated enhancement of human natural killer (NK) cell activity by carbaryl, an anticholinesterase insecticide.

The potency of the anticholinesterase (antiCHE) insecticides as serine hydrolase inhibitors, and evidence for serine hydrolase activity in interleukin-2 (IL2) signalling suggest that the natural killer (NK) cell may be a target for dysregulation by antiCHE insecticides. NK cells are large granular lymphocytes (LGL) that respond to IL2 by proliferating and increasing their cytolytic efficiency. In the present study, we assessed the effects of carbaryl (CA, an antiCHE insecticide) and alpha-naphthol (NA, the major metabolite of CA) on both target cell killing per se and IL2 enhancement of target cell killing by human NK cells. Human LGL, collected from the peripheral blood of normal donors, were cultured for 4 days with human recombinant IL2 (HRIL2), then assayed by a 51Chromium (51Cr) release assay for lytic activity against human K562 cells. When added at the beginning of the culture period, CA inhibited enhancement of cytolytic efficiency in a concentration-dependent manner; at concentrations (0.5 and 5.0 microM) compatible with no cholinergic toxicity. Reduction of the effector/target cell (E/T) ratio in the 51Cr release assay markedly enhanced the observed inhibition by CA. In one experiment, inhibition increased from 6% to 20%, 17% to 35%, and 53% to 73% at 0.5, 5.0, and 50 microM CA, respectively, when E/T was reduced from 10:1 to 2.5:1. This result is consistent with reduced cytolytic efficiency of individual NK cells exposed to CA. NA had no effect at 0.5 or 5.0 microM but caused some inhibition at 50 microM. Neither CA nor NA produced LGL death. When CA or NA was added directly to the 51Cr release assay, inhibition was not observed. The mechanism of inhibition of IL2-stimulated enhancement of target cell killing is not yet known, however, the results are consistent with impairment of IL2 signalling, by CA.


In vitro effects of 'designer' amphetamines on human peripheral blood mononuclear leukocytes proliferation and on natural killer cell activity.

Human peripheral blood mononuclear leukocytes (PBML) proliferation was measured in the presence or absence of amphetamines. Proliferation in response to T-cell mitogen PHA was suppressed from 22 to 34% by d- and dl-amphetamine, respectively, contrarily to 1-form which did not affect proliferation of PHA-stimulated PBML. The 'designer' amphetamines appeared to be more potent inhibitors of PBML proliferation induced by both PHA and PWM stimulation than those of the racemic and isomeric forms of amphetamine. A wide variation was seen in the suppressive actions of the 'designer' amphetamines, and the mean percentages of suppression varied from 12 to 45% compared with the control values. 4-Propoxy-amphetamine (4-PA) was found to be the most active among the 'designer' drugs. In vitro effects of d-, 1- and dl-amphetamine were also studied on natural killer (NK) cell activity. A marked increase in the NK cell activity was observed only in the presence of very low concentrations (10(-12) to 10(-10) M) of dl-amphetamine, however, the activity of the NK cell remained within the control limits in the presence of d- or 1-forms. The findings suggest that the abuse of amphetamines, especially the 'designer' drugs, may adversely affect the activity of immunoregulatory cells and might lead to a compromised immune system in amphetamine abusers.


No increase in carcinogen-DNA adducts in the lungs of monkeys exposed chronically to marijuana smoke.

Rhesus monkeys exposed to marijuana smoke either 7 or 2 days/weeks (HI and LO groups, respectively), or ethanol-extracted marijuana smoke for 7 days/week (EM) or sham treatment (SH) for 1 year were sacrificed 7 months following the last exposure. Pulmonary levels of carcinogen-DNA adducts were determined. Although mean or median adduct levels were not statistically different, 15 of 22 adduct measures were highest in the EM group and lowest 12 of 22 times in the SH group. The levels of aromatic carcinogen-DNA adducts seem no higher in the lungs of animals exposed to marijuana smoke than in untreated animals. Ethanol-extracted marijuana may have effects greater than marijuana itself.


Urinalysis vs. blood analysis, as a tool for biological monitoring of solvent exposure.

Blood and urine samples were collected at the end of an 8-h workshift from 30 male workers exposed to a mixture of n-hexane, ethyl acetate and toluene (each being about 2 ppm as geometric means) and also from 20 nonexposed male workers. Blood samples were analyzed for n-hexane and toluene, and urine samples were analyzed for n-hexane, toluene, 2,5-hexanedione (both with and without hydrolysis) and hippuric acid. Based on the correlation between biological exposure indicators and solvent concentrations in air, sensitivity as an exposure indicator was compared between solvents in blood and solvents or metabolites in urine in terms of the lowest solvent concentration at which the exposed subjects can be statistically separated from the nonexposed. Both n-hexane and toluene in blood were sensitive enough to detect the exposure at 6.1 ppm and 1.4 ppm, respectively. n-Hexane exposure below 2 ppm was detectable also by urinalysis for 2,5-hexadione without hydrolysis. Urinary hippuric acid, however, failed to detect low toluene exposure under the conditions studied. Of additional interest is the fact that toluene in urine correlated significantly with toluene in air, which apparently deserves further study for confirmation.


Delta 5-3 beta-hydroxysteroid acyl transferase activity in the rat brain.

Pregnenolone and dehydroepiandrosterone accumulate in brain as sulfate and fatty acid esters and unconjugated steroids. The steroid fatty acid ester-synthesizing activity was investigated in rat brain microsomes. Endogenous fatty acids in the microsomal fraction were used for the esterification of steroids. The enzyme system had a pH optimum of 4.5 in acetate buffer with [3H]dehydroepiandrosterone as substrate. The apparent Km was 9.2 +/- 3.1 x 10(-5) M and Vmax was 18.6 +/- 3.4 nmol/h/mg protein (mean +/- SEM). The inhibition constants of pregnenolone and testosterone were 123 and 64 microM, respectively. Results were compatible with a competitive type of inhibition. A high level of synthetic activity was found in the brain of 1- to 3-week-old male rats, which rapidly decreased with aging. Saponification of purified [3H]pregnenolone esters yielded pregnenolone and a mixture of palmitate, oleate, linoleate, stearate, and myristate as the predominant fatty acids. Contrasting with the high rates of esterification of several radioactive delta 5-3 beta-hydroxysteroids or 17 beta-hydroxysteroids, no fatty acid esters of either cholesterol, epitestosterone (with a hydroxyl group at position C-17 alpha), or corticosterone (with hydroxyl groups at C-21 and C-11 beta) were formed in the same incubation conditions.


A direct radioimmunoassay for 5 alpha-androstane-3 alpha,17 beta-diol 17-glucuronide.

Synthesis of the 11 alpha-hemiglutaryl derivative of 5 alpha-androstane-3 alpha,17 beta-diol 17-glucuronide (androstane-diol-17G) starting from androsta-4,9(11)-diene-3,17-dione through a 10-step sequence and the preparation of its bovine serum albumin conjugate is described. By using this conjugate, antiserum was raised in rabbits which proved to be very specific for androstanediol-17G. A direct radioimmunoassay using a double antibody procedure is described for the measurement of androstanediol-17G from plasma without prior chromatography.


Nonsteroidal estrogens bearing acyl azide functions: potential electrophilic and photoaffinity labeling agents for the estrogen receptor.

In an effort to develop novel affinity labeling agents for the estrogen receptor, we have synthesized two nonsteroidal ligands, a 1-aroyl-2-aryl tetralin system (1) and a 2-aryl-3-aroylbenzo[b]thiophene system (2). These agents, patterned after the Lilly antiestrogens trioxifene and LY 117018, respectively, embody acyl azide functions as part of a benzoyl chromophore. The acyl azide group has weak acylating activity, suitable for electrophilic affinity labeling, but this function is also photoreactive and, in its particular embodiment within these ligands, it could provide an efficient photochemical route to the highly reactive singlet acyl nitrene. The tetralin system (1) was prepared in nine steps from 6-methoxy-1-tetralone, and the benzothiophene system (2) was prepared in four steps from a known substituted benzo[b]thiophene precursor. In competitive binding assays, both compounds show reasonable binding affinity for the rat and lamb uterine estrogen receptor: estradiol = 100%, 1 = 3%, and 2 = 12%. When assayed by indirect receptor consumption assays, both compounds appear to have substantial capacity for irreversible binding (electrophilic reaction) with the receptor. This reactivity, which suggests that acylation of the receptor has occurred, is photoreversible. The nature of this ligand-receptor interaction is being investigated further.


Synthesis of the sulfates derived from 5 alpha-cholestane-3 beta,6 alpha-diol.

Three new steroid sulfates--3 beta-hydroxy-5 alpha-cholestan-6 alpha-yl sulfate, 6 alpha-hydroxy-5 alpha-cholestan-3 beta-yl sulfate, and 5 alpha-cholestan-3 beta,6 alpha-diyl disulfate--were synthesized. For the syntheses of the key intermediates, 3 beta-hydroxy-5 alpha-cholestan-6 alpha-yl acetate and 6 alpha-hydroxy-5 alpha-cholestan-3 beta-yl acetate, selective protection of hydroxy groups in 5 alpha-cholestane-3 beta,6 alpha-diol was necessary. This problem was solved by using a combination of acetyl, tetrahydropyranyl, and methoxymethyl protective groups, which represents a new approach leading to these hydroxy acetates. Sulfated derivatives of 5 alpha-cholestane-3 beta,6 alpha-diol are present in marine invertebrates and were synthesized for the purposes of biologic testing.


Studies on nuclear binding of dehydroepiandrosterone in hepatocytes.

Experiments were conducted to determine if dehydroepiandrosterone (DHEA) specifically binds to liver nuclei or interferes in the binding of other steroid hormones. Hepatocytes were isolated from obese, female Zucker rats that were treated with and without 0.6% DHEA in their diets for 2 weeks. The hepatocytes were incubated with either [3H]DHEA, [3H]estrone, or [3H]corticosterone. The nuclei isolated from the incubated cells from either control or DHEA-treated rats had no binding with [3H]DHEA, but had the expected binding with [3H]estrone and [3H]corticosterone. Furthermore, increasing concentrations of cold, unlabeled DHEA in the incubation media with [3H]estrone or [3H]corticosterone failed to have any effect on the binding of either of these steroid hormones to the nuclei. These results suggest that DHEA treatment does not exert its effects on cellular metabolism through a receptor-mediated mechanism like other steroid hormones or by interfering in the expression of steroid hormones such as estrone and corticosterone.


Tyrosinase-like activity and estradiol binding in rat uterine nuclear extracts.

Nuclear extracts from the uteri of estradiol-implanted rats contain a tyrosinase-like enzyme that has three activities: monophenolase or cresolase, diphenolase or catecholase, and estrogen binding. When [3H]estradiol was used as a substrate, 3H2O was released from the A ring in the presence of copper and ascorbic acid. The optimal concentrations of these cofactors for the cresolase activity were established. The cresolase activity was lost on attempts at further purification. Estradiol binding was observed in conjunction with the enzymatic activity and was dependent on the presence of ascorbic acid and copper. The most potent inhibitors of 3H2O release from [3H]estradiol were those with a dihydroxyphenol moiety. The reaction was also sensitive to sulfhydryl reagents. These features of the enzyme are distinctive from other oxidases capable of attacking the aromatic ring of estrogens.


A Durkheimian analysis of youth suicide: Canada, 1971 and 1981.

Durkheim hypothesized that suicide varies inversely with the extent of social integration in family, religious, political, and economic life. In this study I examine the relationship between three of these sources of social integration on young Canadians' (aged 15-29) suicide rate for 1971 and 1981: family integration (as measured by divorce), religious integration (as measured by the percent of the population reporting no religious affiliation), and economic anomie (unemployment). The findings of this research provide confirmation for the hypothesis that religious detachment among the young is associated with increased proneness to commit suicide. The effect of family dissolution was positive and significant for both young men and women in 1981 but not in 1971, giving partial confirmation for the family integration explanation of suicide. These results pertaining to unemployment are not consistent with the American-based literature that calls for a significant and positive impact on the odds of self-destruction.


A reliability investigation of the eight clinical scales of the Suicide Opinion Questionnaire.

The Suicide Opinion Questionnaire (SOQ) has been employed in a variety of settings as a measure of attitudes toward suicidal behavior. However there has been a lack of consensus across these studies with regard to the underlying factor structure of the measure. In addition there has been little empirical information reported in the literature regarding the scale's reliability. This article presents a psychometric investigation of the 8-factor clinical model of the SOQ as representing the most appropriate interpretive model for the SOQ. Factor-analytic and internal consistency reliability results failed to support the hypothesized 8-factor model. An alternative factor scheme and suggestions for future research on the SOQ are discussed.


Development of the College Student Reasons for Living Inventory.

Two studies were carried out in an effort to develop and evaluate an instrument designed to assess suicidal risk in college students. Study 1 describes the development of the College Student Reasons for Living Inventory (CSRLI), an instrument that measures the extent to which college students place importance on various reasons for living even when contemplating suicide. The impetus for the current study was provided by Linehan et al., who in 1983 developed the Reasons for Living Inventory for use with adults. In the current study college students generated a series of 84 "reasons for living" items, which were reduced through factor analysis to a final inventory of 46 items. Six factors were extracted as follows: Survival and Coping Beliefs, College and Future-Related Concerns, Moral Objections, Responsibility to Friends and Family, Fear of Suicide, and Fear of Social Disapproval. Five of these factors reflect the same basic themes contained in the Linehan et al. (1983) study. The sixth factor (College and Future-Related Concerns) appears to be unique to college students. Linehan et al.'s Child-Related Concerns factor expectedly did not appear in this college sample. In Study 2 initial evaluation of the CSRLI was carried out through the use of correlational, confirmatory factor, and discriminant analyses. Results indicate that the CSRLI holds promise as an instrument to predict suicidal risk among college students.


Outpatient standards of care and the suicidal patient.

This article is a review of the legal and clinical literature on standards of care for nonhospitalized adult suicidal patients. The authors discuss effective assessment, management and treatment procedures that balance the need for high-quality care by a reasonable and prudent practitioner with the requirements of court-determined and statutory standards. Through a review of malpractice claims data and through an examination of the clinical literature we detail the essential guidelines for sound assessment, intervention, and management procedures. The authors specifically discuss common failure situations in outpatient care (e.g., problems in pharmacotherapy, the decision to hospitalize, inappropriate and dual relationships, the assessment of imminence and lethality, and so on). Details regarding practical considerations in developing an outpatient standard of care are provided, as are suggestions that such a standard of care must include an ongoing assessment of the therapeutic alliance.


Schizophrenia--a high-risk factor for suicide: clues to risk reduction.

Suicide is the chief cause of premature death among schizophrenic persons. The lifetime incidence of suicide for patients with schizophrenia is 10% to 13% compared to a general population estimate of about 1%, and is quite close to that observed among those with major affective disorder. The magnitude of increased risk for suicide among schizophrenics peaks before middle age and declines thereafter, although schizophrenic persons tend to be at increased risk throughout the life span. Among psychiatric patients, schizophrenics are overrepresented among suicides, and often schizophrenics constitute the majority of inpatient suicides. It is important in evaluating suicide risk among schizophrenic persons to assess depression and suicidal ideation especially during index admission and during acute phases of the illness. It is noteworthy that schizophrenic persons often commit suicide as the overall level of psychopathology decreases during a nonpsychotic phase. Research has yielded salient risk factors for suicide in schizophrenic persons and "types" of especially vulnerable patients, even though statistical prediction of individual suicides has not proven effective.


Youth suicides unknown to psychiatric care providers.

Less than 50% of young suicides have consulted psychiatric care providers. Thus the population not found within the psychiatric care sector is described in this paper. Fifty-eight consecutive suicides among adolescents and young adults, studied by psychological autopsies, were classified according to presence or absence of previous psychiatric care. Fifteen of the sixteen subjects without previous care were males, six of these were diagnosed as having an adjustment disorder related to a recent event. Unemployment was less common (p < 0.01), the suicidal processes were shorter (p < 0.001), and previous parasuicide was less frequent (p < 0.001) among nonpatients. Evaluation in accordance with DSM-III-R criteria showed fewer substance abuse disorders (p < 0.01). Open suicidal communication prior to the suicide was less frequent but active methods were used by this population as often as by subjects known to care providers.


Primary sclerosing cholangitis in chronic ulcerative colitis: report of cases in Arabs and review.

Primary sclerosing cholangitis (PSC), a chronic cholestatic liver disease, is increasingly recognized in association with chronic ulcerative colitis (CUC). Two cases of PSC were diagnosed among 78 Arab patients (2.7%) with CUC followed up at Riyadh Central Hospital. Detailed case reports of the patients and review of PSC are presented, in order to draw attention to a hitherto under-diagnosed condition. This is the first report of PSC among Arabs.


HBV--status in professional blood donors in north India.

Present study demonstrates the efficacy and significance of routine screening assays used for HBsAg testing in donor blood in different blood banks of Delhi city. Blood from professional donors already screened in blood banks were cross checked using micro-ELISA technique developed at All India Institute of Medical Sciences and the results were compared. HBsAg carrier rate in these professional donors was found to be 11.7% by micro ELISA as against only 6% reported in blood banks using RPHA and latex agglutination assays. Thus, assays used in blood banks were found to be missing nearly 50% HBsAg positive cases as compared to micro-ELISA. A small group of professional donors was also screened for anti-HBs and results explained in comparison of normal values.


Wuchereria bancrofti induced pancreatitis.

A case of pancreatitis of filarial origin is reported for the first time. The patient presented with chronic pancreatic pain. Laparotomy revealed an inflammed pancreas and fine needle aspiration cytology confirmed pancreatitis. Imprint of a peripancreatic lymphnode revealed a microfilaria. He was successfully treated with Diethyl Carbamazine.


[The functional characteristics of the inhibitory mediator systems in the brain synaptosomes of PP vitamin-deficient rats].

A decrease of the NAD and serotonin level in the brain of rats with PP hypovitaminosis is shown. NAD in concentration of 10(-6) M in vitro exerts a less pronounced inhibiting influence on the neuronal uptake of [14C]serotonin and [14C]GABA by brain synaptosomes of rats with PP hypovitaminosis. GABA content under such conditions increases as compared with the control and correlates with changes in the [14C]GABA uptake system.


[The carbohydrate components of corn prolamins].

This work was aimed to study the patterns of zein glycosylation. Zein proteins included 1-3% of sugars. The affinity of different lectins, such as concanavalin A (Con A), Lens culinaris lectin (LCL) and lectins of Arachis hypogaea (PNA), of Triticum vulgaris (WGA), of Dolichos biflorus (DBA), of Glycin max (SBA), of Lotus tetragonolobus (LTA), of Laburnum anagiroides (LAL), of Ricinus communis (RCA), of Phaseolus vulgaris (PHA) was used to analyze the glycosylation sites. All selected lectins interacted with zein proteins. It may serve a basis for determination of mannose, galactose, fucose and aminosugars. Some lectins were bound only by prolamines of some inbred lines, while others were connected with all lines.


[The composition and physicochemical properties of the blood lipoproteins in rats exposed to external gamma irradiation].

Content of lipids, character of chemiluminescence of blood plasma and certain classes of lipoproteins have been studied. Geometrical parameters, nature and quantity of charged groups of lipoprotein particles accessible for titration have been determined 1 and 30 days after a single external gamma irradiation of rats in a dose of 3 Gy. The used irradiation dose exerts an expressed hyperlipidemic effect retained for one month after irradiation. The disturbances in the spectrum of blood lipids and lipoproteins are of hyper-beta and hyper-prebeta lipoproteinemia character. Considerable disturbances of physicochemical properties of different classes of lipoproteins have been detected. They are exhibited in changes of the pattern of free-radical processes, state of the charge of surface ionogenic groups and geometrical parameters of lipoprotein particles. Changes registered by the methods of potentiometric titration and correlation spectroscopy are most expressed in lipoproteins of very low density and those of low density.


[The relation between oxidative processes and the glycogen content in the heart and liver of rabbits with chronic ischemic heart disease].

While laboratory experimental model of coronary heart disease (according to Frol'kis et al.) is developed, activity of succinate dehydrogenase, alpha-ketoglutarate dehydrogenase, Na+, Ka(+)- and Mg2+ ATPase decreases, but activity of lactate dehydrogenase and concentrations of lactic and pyruvic acids in the heart tissue increase. At the same time concentration of glycogene increases more than twice. As far as we can see there is an evidence of a decrease of glycogene utilization due to change in levels of regulatory processes. Despite a decrease of ATP synthesis by the inhibition of tricarboxylic acid cycle the ATP:ADP relation reduces to ATP, as emphatic inhibition of ATPase in the heart tissues takes place in development of the model of the coronary heart disease. The relation between ATP and ADP is considered as a regulator of glycogene utilization. In the liver tissue activity of succinate dehydrogenase, alpha-ketoglutarate dehydrogenase, Na+, K(+)- and Mg2+ ATPase falls, while concentrations of lactic acid grow. No accumulation of glycogen is observed. It is obvious that there are controversial metabolic processes. Experimental data are discussed.


[The characteristics of nitrogen metabolism in the tissues of rabbits with ammonium toxicosis].

Disturbances of nitrogen metabolism under acute ammonium toxicosis have been studied in tissues of rabbit. A sharp increase of the ammonium content in the blood and tissues of the liver and kidneys is accompanied by an increase in the glutamine and glutamate level in all tissues. The level of urea nitrogen in the blood of rabbits increases. The activity of phosphate-independent and phosphate-activated glutaminase also increases in tissues of the liver and kidneys, while arginase activity decreases as compared with the control, which is connected with fall of the ATP level under hyperammonemia. A nomograph method of representation of the redox state has been used.


[The effect of hypoxic hypoxia on the physicochemical and functional properties of hemoglobin in rats].

The effect of intermittent altitude chamber hypoxia is established to cause an increase in solvability of laboratory rat hemoglobin. Results of immunochemical and fluorescent analysis of the samples of hemoglobin and its component are presented and discussed. They prove that changes in solvability of hemoglobin are determined by the conformational reconstructions of the respiration protein as a result of formation of the complexes with internally erythrocytic metabolites.


[The identification of the sites of tRNA(Ser)(GCU) interaction in bovine liver with homologous aminoacyl-tRNA-synthetase by the chemical modification method].

Interaction of the bovine liver tRNA(GCUSer) having a long variable loop, with the cognate aminoacyl-tRNA synthetase has been studied by alkylation with ethylnitrosourea. It was shown that seryl-tRNA synthetase protects 3'-phosphates of nucleotides 12, 13 in D-stem and 45-47-, 47 G.-, 47 H-variable stem of tRNA(GCUreS) from alkylation. An anticodon loop of tRNA(GCUSer) did not interact with seryl-tRNA synthetase.


[The effect of taurine on the activity of transport ATPases and of energy metabolism enzymes in different tissues of rats with acute hypoxic hypoxia].

The membrane activity of Na+, K(+)-ATPase, Mg2+, Ca(2+)-ATPase, mitochondrial NAD-isocitrate dehydrogenase, mitochondrial and cytosolic L-glycerol-3-phosphate dehydrogenase was determined in the liver and brain of Wistar rats under acute hypoxic hypoxia against the background of preventive taurine administration. It was shown that preliminary taurine treatment prevented a decrease of hypoxia in activity of Na+. K(+)-ATPase and mitochondrial calcium-dependent enzymes, mostly in the liver. Changes in the intracellular calcium content and biomembrane structure have been discussed as the mechanisms of the taurine effect on the enzymes' activity.


[Arachidonic acid metabolism and vitamin E].

Basing on data from literature vitamin E is considered for its possible effect on the exchange of arachidonic acid. It is supposed that vitamin E controls metabolism intensity of arachidonic acid by changing activity of phospholipase A2, cyclooxygenase and lipoxygenase.


[The role of peroxidation processes and antioxidant protection in nitrite-induced hypoxia and its correction with vitamins].

Different doses of sodium nitrite were studied for their action in acute and chronic experiments on rats. Nitrite (NaNO2) hypoxia in rats was simulated to show how the methemoglobin (MtHb) level in blood depends on NaNO2 doses and the method of introduction. Lethal and sublethal doses of NaNO2 (50% of MtHb and more) promoted a decrease of lipid peroxidation (LP) in the liver microsomes, while the average and easy level of hypoxia activated it. Introduction of NaNO2 has led to dose-dependent activation of superoxide dismutase (SOD) in the liver, blood and heart tissues as well as to disturbances in the DNA structure. An average level (40 mg NaNO2 per kg of rat weight daily during one month) of chronic nitrite hypoxia has led to the same changes of metabolism as acute one. Vitamin E normalized LP, but not the MtHb level.


[Effect of physical exercise on aortic blood flow in patients with primary arterial hypertension].

In 40 patients (30 men and 10 women) aged to 21 to 48 years (mean 42 years) with essential hypertension stage II, according to WHO classification, blood flow was recorder in the ascending aorta by Doppler echocardiography. The investigation was done in erect position, at rest, and during 30 seconds of each phase of exercise on moving track. The control group comprised 20 healthy males aged 23-45 years (mean 38 years). In essential hypertension the values of the heart rate (T), maximal (MAX-V) and mean (ME-V) flow velocity, and systolic volume index (SVI) were significantly higher at rest than in controls. In the 3rd minute of exercise the values of heart rate (T), mean flow acceleration (ACC) and minute volume index (COI) were significantly higher in the patients than in controls. At the peak exercise MAX-V, ME-V and COI were significantly lower than in controls. On the other hand, in the 5th minute after the exercise the values of all the analysed blood flow parametres in the aorta were significantly higher in the patients. After the exercise the fall of the integral flow (INTG) and SVI greater in controls than in patients, while the rise of the mean flow acceleration (ACC) was higher in hypertension than in health.


[Evolution of diastolic polycardiographic indicators in hypertrophic cardiomyopathy].

In a group 26 patients with hypertrophic cardiomyopathy the values of certain polycardiographic and haemodynamic indices and their changes in the prolongation of the time of isovolumetric relaxation (IVRT) was noted in 23 patients (88%), with increased value of the percent of the a wave participation of the apexcardiogram (%a) in 24 patients (92%). In the obstructive type the corrected time of left ventricular ejection was significantly prolonged (p < 0.01) in relation to the non-obstructive type. No difference was observed in the values of these parameters depending on the functional class. A weak but significant correlation was demonstrated between the %a and the end-diastolic left ventricular pressure (r = 0.579, p < 0.01). The IVRT value showed an increasing tendency in this prospective study, particularly in patients with progression of clinical symptoms.


[Protein synthesis in the organs and tissues of frogs with local exposure to low temperatures].

Intensity of synthesis of total proteins and spectrum of synthesized proteins has been studied in various organs and tissues of sharp-faced frogs during local profound cooling of one of its limbs. It was shown that the effect of low temperatures on a certain part of a body of a poikilothermic animal has induced both a response of the whole organism and a much more acute response of the cooled tissues. The organism responded by a fall of the whole body temperature and a decrease in the activity of synthesis of total proteins of the viscera. Local cooling of a part of the frog body has induced a more significant decrease in the protein synthesis intensity in the cooled tissues alteration in the spectrum of synthesized proteins and appearance of specific proteins.


[The effect of antibodies against Ca2(+)-ATPase and its hydrophobic fragment on the activity of this enzyme and on the passive transport of Ca2(+)].

It is shown that both Ca(2+)-ATPase and its hydrophobic fragment are immunogenic factors. A region between hydrophobic and hydrophilic parts of Ca(2+)-ATP-ase is immunogenic. These antibodies clearly inhibit inflow and outflow of Ca2+ through a hydrophobic fragment reconstructed into liposomes and do not influence Ca(2+)-ATPase activity.


[The effect of low concentrations of sodium nitrites and nitrates on respiration and oxidative phosphorylation in rat liver mitochondria].

Nitrite incubation in mitochondria and nitrate intoxication of rats have been studied for their effect on aerobic energetic processes in the liver. Sodium nitrite in concentration of 2 mg/l causes an inhibition of ADP-stimulated respiration and provides uncoupling processes of oxidative phosphorylation and respiration in mitochondria, when adding succinate as a substrate. Low doses of nitrate in vivo promote oxygen economization in mitochondria. Intoxication of rats with nitrate in a dose of 50 mg/l for 30 days induces a decrease of the respiration rate after ADP-phosphorylation and an increase of the coefficient of oxidative phosphorylation efficiency (ADP/O). Intraperitoneal administration of adrenalin in a dose of 25 micrograms/100 g to rats after 30-day nitrate intoxication in a concentration of 10 mg/l induces no typical increase of ADP-stimulated respiration and rate of oxidative phosphorylation and succinate oxidation.


[Diurnal fluctuations of arterial blood pressure and heart rate in patients with atrial fibrillation].

In patients with atrial fibrillation and in patients with sinus rhythm aged below and over 40 years 24-hour automatic measurement of systolic and diastolic arterial blood pressure was carried out. The systolic and diastolic arterial blood pressure in atrial fibrillation was higher than in patients with sinus rhythm, both during daily activities and during night rest. The heart rate in those below 40 years showed greater diurnal fluctuations than in atrial fibrillation and patients aged over 40 years. Moreover, circadian systolic and diastolic blood pressure recordings were lower in night hours, similarly as heart rate values an all the studied groups, and only in the group of atrial fibrillation the differences between the parameters recorded during the night and in daytime were not so evident as in the groups with sinus rhythm.


[Thiochrome inhibition of alcohol dehydrogenase].

It is shown that thiochrome inhibits alcohol dehydrogenase. Thiochrome is able to be bound with alcohol dehydrogenase more quickly than other thiamine metabolites. This process is specific and has common features with the process of NAD binding by this enzyme. The inhibition of alcohol dehydrogenase by thiochrome is concurrent to NAD. The constant of alcohol dehydrogenase inhibition by thiochrome is 3.9 x 10(-5) M.


[Repeat surgery of the biliary tract].

On the ground of 67 secondary operations on the bile ducts carried out in 64 patients in the years 1976-1988 the causes, the types of the operations, the frequency and character of complications and the postoperative morality were analysed. A more detailed analysis carried out in patients with high surgical risk, taking into account the advanced age of the patients, coexistence of mechanical icterus, choledochal calculi and opening of the bile ducts. These factors were compared to those present in the whole group of similar cases treated surgically in the analysed time period. The authors stress the importance of modern diagnostic methods which make possible limitation of the number of secondary operations after interventions on bile ducts.


[The effect of malonate on lipid biosynthesis in the liver].

Malonate regulates the liver metabolism and promotes stimulation of the fatty acids synthesis and pyruvate oxidation inhibition. The latter is particularly significant in regulation of aerobic processes and responsible for antihypoxic action of malonate.


[The effect of nitroxyl radicals and sodium nitrite on the methemoglobin content of the blood and on the enzymatic activity of erythrocyte antioxidant protection].

Preliminary introduction of nitroxyl radicals to mice decreases methaemoglobin-forming effect of sodium nitrite and diminishes the content of total SH-groups and restored glutathione as well as the activity of glutathione reductase and total activity of dehydrogenases of the pentosophosphate path of erythrocytes. High level of lipids peroxidation in case of sodium nitrite intoxication remains unchanged under preliminary administration of nitroxyl radicals as well. Activity of the key enzymes of antioxidant protection of erythrocytes, superoxide dismutase and catalase, is not recovered with sodium nitrite intoxication in presence of nitroxyl radicals.


[Evaluation of the results of the treatment of crural trophic ulcers].

The results of treatment of varicose crural ulcers are reported in a group of 85 patients. Cure was achieved in 75 cases. The social and economic aspects of this problem are stressed.


[Injuries of the cervical vertebrae with pathological changes caused by the degenerative process].

The problems related to injuries of the cervical spine with advances degenerative changes are discussed. The most frequent causes of these injuries were falls from height and traffic accidents. In the whole group of 185 patients most were aged over 50 years, and the lower part of the cervical spine was injured most frequently, with the extension mechanism being the usual force in the injury. Nearly half the cases (45%) had complete paralysis including the most severe form of partial injury.


[The kinetics of the inactivation of the soybean trypsin inhibitor by heat processing].

The investigations of kinetics of the thermal degradation of the antinutritious substances in the soya beans were carried out. The mathematical analysis of the obtained experimental data helped to determine the kinetic constants D and Z necessary to calculate the time of heat treatment to obtain the minimal value of the inhibitor at any temperature level.


[A comparative analysis of the proteins from a cell culture and from field plants of the ecdysteroid producer Serratula coronata L].

Differences in the composition and amount of proteins synthesized in the cell culture and leaves of field plants Serratula coronata have been shown. They proceed from differences in intensity of synthesis of secondary metabolites, ecdysteroids, whose content in the cell culture is considerably lower.


[The subcellular localization of carboxypeptidase N in the substantia grisea of the cat brain].

The activity of carboxypeptidase H in the cat grey matter is established to be connected with microsomes. A possibility to involve carboxypeptidase H to the processing of neuropeptide predecessors in the encephalon is discussed.


[Myasthenia gravis in newborn infants--pathological mechanism, clinical symptomatology and therapeutic procedures].

Modern views on the pathological mechanism, clinical symptoms and therapeutic management of neonatal myasthenia gravis are reviewed on the basis of literature reports and own experiences. Particular attention is given to intensive medical care in this condition.


[Neoplastic cavities of the lungs in cancer of the pancreas].

A 51-year-old females patient is reported in whom during pancreatic cancer massive oligosymptomatic and rapidly progressing breakdown of the pulmonary tissue of both apices of the lungs appeared. The cause was the presence of very numerous minute metastases of pancreatic cancer.


[Gastric necrosis caused by incarceration in hiatal hernia].

The described case illustrates the diagnostic difficulties in incarceration of abdominal organs in diaphragmatic hiatus hernia. The absence of characteristic symptoms and sudden deterioration of the general condition are causes of delay in surgical intervention leading, sometimes, to extensive necrosis of organs. The reported patient had extensive necrosis of gastric wall due to its incarceration in diaphragmatic hiatus hernia.


[Free radicals in parasitic invasion].

Highly reactive oxygen species potentially represent a powerful effector mechanism against parasites. They are produced during normal cellular metabolism, especially by activated phagocytes. As can be seen from many studies protozoan and helminth parasites appear to have one or more anti-oxidant enzymes able to scavenge or quench the reactive free-radicals, and there is strong evidence that such enzymes may play crucial role in protecting against host response. Presented there review illustrates that methods to block anti-oxidant protection of parasites may be new field in the search for improved ways to inhibit parasitic survival.


[Comparison of thymidylate synthase properties isolated from the rat tapeworm, hymenolepis diminuta, with properties of enzyme isolated from the host in regenerating rat liver].

Thymidylate synthases (TS) from the tapeworm, Hymenolepis diminuta, and regenerating rat liver have been purified by means of affinity chromatography on immobilized 10-formyl-5,8-dideazafolate and concentrated on immobilized p-aminophenyl-5-fluoro-2'-deoxyuridine monophosphate. Molecular weights of native TS from the tapeworm and regenerating rat liver were 62 kD and 81.5 kD, respectively, and molecular weights of the monomers were 34.4 kD and 34.9 kD, respectively, pointing to dimeric structures of both enzymes. The dependence of TS activity on temperature (Arrhenius plot) was biphasic for the parasite enzyme, with lower activation energy above 32 degrees C, and monophasic for the host enzyme. 2'-deoxyuridine-5'-monophosphate (dUMP) analogues, 5-fluoro-2'-deoxyuridine-5'-monophosphate (5-FdUMP), 2-tio-5-FdUMP,N4-hydroxy-2'-deoxycytidine-5'-monophosphate (N4-hydroxy-dCMP) and N4-hydroxy-5-FdCMP, were competitive with respect to dUMP, slow-binding inhibitors of TS from both sources, with K1 values in 10(-6)-10(-9) M range. 5-FdUMP was distinctly stronger inhibitor of the host than the tapeworm TS, whereas N4-hydroksy-5-FdCMP inhibited stronger the parasite enzyme. Interaction of 5,10-methylenetetrahydrofolate (CH2H4PteGlu) analogue, 10-propargyl-5,8-dideazafolate (pddPteGlu), and its di- and triglutamates with both enzymes were studied. Inhibition of the parasite and host enzymes by pddPteGlu was of mixed-type with respect to CH2H4PteGlu, with K1 values in 10(-8) M range. Introduction of additional glutamate residues changed inhibition type to noncompetitive with respect to Ch2H4PteGlu and lowered K1 values (pddPteGlu3 < pddPteGlu2 < pddPteGlu1).(ABSTRACT TRUNCATED AT 250 WORDS)


[The effect of Ascaris lumbricoides suis and its trypsin inhibitor on the chick embryo].

It has been found that tegument homogenate of Ascaris lumbricoides suis and also trypsin inhibitor isolated from it induce the Leghorn chick embryos mortality when injected into their yolk sac on 4th, 8th or 13th day of incubation. The trypsin inhibitor is one of important components of Ascaris homogenate causing mortality. There is linear interrelationship between the logarithm of dose of homogenate or trypsin inhibitor and the mortality of chickens in %. A significant decrease of mean mass of chicks injected with Ascaris homogenate or trypsin inhibitor in comparison with control groups was observed. There was more frequent occurrence of developmental abnormalities and pathological changes in groups of hatched chicks which received Ascaris homogenate or inhibitor.


[Morphologic features, with particular regard to surface ultrastructure, of Docophoroides brevis (Docophoroididae, Mallophaga)].

Bodies of nymphs and adults of Docophoroides brevis (Docophoroididae), parasite of Diomedea exulans, were studied under light and scanning microscopes. Developmental features of nymphs corresponded with similar features of other Philopteroidea. In adults type and distribution of sensillae were similar to other Ischnocera. Structures pointing to parasite's adaptation to holding itself on host's feathers, were distinguished. They were, besides characteristic claws, the mouth apparatus, groups of hooked processes on tibiae of the II and III pairs of legs, and sculpture of roundish fields on the sides of abdomen sternites. In the shape of male's genital apparatus, protruding to the outside of terminal sclerite, structures helping both partners to contact during copulation were discerned.


[Immunobiology of Cryptosporidium sp].

Immunological aspects of cryptosporidiosis: its immunopathology, antigenicity, perspectives of treatment and diagnosis are reviewed. In particular pathology of this disease in immunodeficient (as a result of AIDS or suppressive drugs chemotherapy) patients is presented.


[Clinical applications and importance of selected, modern results of hearing research].

Inner ear physiology has largely contributed to clinical progress in otolaryngology within the last decade. The cell biological knowledge of basic properties of outer hair cells and their motility in particular helped to explain the unique sharp frequency dispersion in the cochlea and other mechanisms of hearing. Further important aspects with a clinical impact have been e.g. the description of the cellular mechanism in aminoglycoside ototoxicity, a pathophysiological concept of Ménière's disease and the application of otoacoustic emissions in audiological testing of infants.


[Drug therapy of sensorineural hearing loss--critical remarks].

Recent placebo-controlled clinical double-blind trials failed to confirm any beneficial effects of rheological and vasodilative drugs or hemodilution in treatment of inner ear diseases. Furthermore, experimental studies have recently shown that cochlear blood flow was only temporarily improved during infusion of blood flow promoting drugs and cochlear oxygenation was deterioated with most of these drugs. Therefore treatment of basic or accompanying diseases is currently the only effective therapy and prophylaxis and general practitioners as well as internal and neurological specialists should be involved in therapeutical approach of inner ear disorders.


[Modern hearing aid treatment].

Sufficiently good hearing is the most important prerequisite for speech communications between human beings and is crucial for the quality of human life. For this reason, provision of hearing aid is a priority task of the ENT-physician in all cases of hearing impairement which are unimproveable. The following principles must be observed: when it is necessary to provide a hearing aid, this should be done as early as possible, even in monauricular hearing loss. In binauricular hearing loss, hearing aids should be provided for both ears whenever possible and always with the objective of "optimal" care. The organization of hearing aid provision, which has proved very effective in Germany, is explained. Basic types of modern hearing aids are described and a review is given on the technical possibilities of modern hearing aids in solving problems relating to disturbances of hearing.


[Tympanoplasty].

The first goal of tympanoplasty as treatment for chronic otitis media is to obtain a clean, disease-free ear, the second one hearing improvement. Prerequisite for success is the sufficient functioning of the inner ear as well as of the Eustachian tube. Therefore, patients very often have to undergo adjuvant treatment such as adenotomy, rhino-surgery and surgery of the paranasal sinuses. Microsurgery of the ear has become very refined. Thus even after removal of extensive inflammation it is now possible to rebuild the middle ear using various proved as well as newly developed biomaterials. Often a two-stage procedure is advisable for cholesteatoma surgery. In this disease meticulous postoperative care and longterm follow-ups are very important.


[Otosclerosis--diagnosis and therapy].

Otosclerosis (synonym: otospongiosis) is a focal or diffuse spongifying disease of the bony labyrinth. So far pathogenesis is unknown, some recent investigations assume a paramyxovirus infection. But there are no doubts about hereditary and genetic factors, females are twice often affected as males with a maximum incidence between 20 and 40 years. If the disease invades the oval window niche it causes fixation of the stapes with conducting hearing loss. In some cases otospongiosis is associated with and presumably causes cochlear degeneration alone with sensoneurale hearing impairment of varying degree. The surgical technique is now well developed and the operative treatment enables in over 90% a closure of the air-bone gap by using stapes pistons. The medical therapy in cases of sensoneural hearing loss with sodium fluoride is still controversially discussed.


[Diagnosis and therapy of infectious otitis externa. An overview for the non-ENT physician].

Knowledge of the different clinical manifestations of inflammation caused by specific infectious agents of the external ear canal and the auricle makes a successful empirical therapy possible. Initial therapy should always consist of local treatment modalities including repeated cleansing of the aural canal and insertion of a cotton wick carrying local medication. Major advancement of systemic therapy of bacterial external otitis has been obtained by the availability of the new Gyrase-inhibitors (Fluoroquinolones). These antibiotic drugs possess--given orally--strong activity against the entire spectrum of etiologic bacteria and are effective in the difficult to treat malignant external otitis. In systemic therapy of Zoster oticus the antiviral substance Aciclovir can improve otalgia and auricular eruptions. Early Aciclovir treatment is advised in cases of Ramsay Hunt Syndrome to minimize permanent nerve damage.


[Acute otitis media. Current therapeutic and clinical aspects].

Otitis media acuta is defined as an acute inflammation of the pneumatic spaces of the temporal bone, that means the middle ear including the mucous membranes of the mastoid cells and of the Eustachian tube; it is caused mainly by bacteria, rarely by viruses. When treated properly by antibiotics, otitis media acuta heals in the rule within two to three weeks completely. If more than three episodes of otitis media occur within one year, the disease is called recurrent otitis media. Secretory otitis media (mucoserotympanon) may be proceeded by an otitis media acuta, but it can also develop without any fore-going disease. If the inflammation of the middle ear is quite symptomless, it is called an occult otitis media or an occult mastoiditis; the causes are often insufficient antibiotic therapies. In these cases an operative treatment (paracentesis, mastoidectomy, antrotomy, adenoidectomy, ventilating tubes) may be necessary. If the defense of the mucous membranes respectively of the whole body is weak or the antibiotic treatment insufficient, there may develop some other sequelae like chronic otitis media, atelectasis, otitis media chronica adhesive, tympanosclerosis, with or without development of cholesteatoma. The typical clinical symptoms, possible complications and the recommended antibiotic and physical treatment are referred.


Acardius in a triplet pregnancy: cytogenetic and morphological profile.

We describe a rare case of acardius in a triplet pregnancy terminated by Caesarean Section at 32 weeks gestation. Morphological and chromosomal abnormalities of the fetus as well as structural abnormalities of the placenta are presented. Cytogenetic analysis and examination of the single disc triplet placenta provide evidence for the two major theories of pathogenesis of acardius, the twin reversed arterial perfusion (TRAP) sequence and the genetic theory, which we believe are not necessarily mutually exclusive.


The current status of Weinberg's differential rule.

A reanalysis of the data presented in a recent large twin study suggests that opposite-sexed (OS) pairs may be not as exhaustively tested as same-sexed (SS) pairs on genetic markers. This is contrary to an assumption I made in estimating that there are about 8 SS dizygotic pairs to every 7 OS pairs (thus impugning Weinberg's differential rule). If this assumption is false also in regard to the samples I discussed, then that estimate is unsound and Weinberg's rule is unscathed by empirical data. However, regardless of such considerations, there are strong theoretical reasons for questioning the status of Weinberg's rule. It is based on two assumptions, namely that p (the probability that a dizygotic twin zygote is male) is equal and independent for all dizygotic twin zygotes. Data are adduced here to suggest that both assumptions are false. The upshot is that, at present, without testing, we cannot know, of any given population, whether the rule holds or not. Otherwise, though Weinberg's rule may be useful (like Hellin's law) as a rule-of-thumb, it cannot be assumed as a basis for serious scientific argument.


How frequent is heteropaternal superfecundation?

A newly discovered case of heteropaternal superfecundation (HS) is reported. Three HS cases were found in a parentage test database of 39,000 records. The frequency of HS among dizygotic twins whose parents were involved in paternity suits is 2.4%. Although the study population appears similar to the general population with respect to twinning data, inferences about the frequency of HS in other populations should be drawn with caution.


Delayed interval delivery of two remaining fetuses in quintuplet pregnancy after embryo reduction: report and review of the literature.

A case report is presented with a prolonged interval between delivery of 25 days. A quintuplet pregnancy resulted from hormonal stimulation of ovulation. Two fetuses remained after an embryo reduction was performed at 11 weeks gestation. At 22.5 weeks gestation the first twin (310 g) was delivered after spontaneous rupture of membranes. Using tocolytic agents, the second twin (710 g) was born at 26 weeks of gestation. This case is discussed and a review of the literature is given.


Intrauterine death in multiple gestation.

Intrauterine death of one fetus in a multiple gestation is associated with significant morbidity and mortality in the surviving infant. This study is a retrospective review of 38 twin and 3 triplet gestations involving the intrauterine death of at least one fetus. The obstetrical history, placental pathology, autopsy findings, and neonatal history of the surviving infant are reviewed. Three cases involved the recent stillbirth of both twins, the remaining cases involved a surviving infant. In one case, neonatal death of a surviving twin occurred on day 19. In two sets of triplets, two stillbirths occurred, in the third case two infants were liveborn. The incidence of preterm delivery was 34%, which decreased to 18% if fetal cotwin death had occurred before 20 weeks gestation. Cesarean section was the method of delivery in 16 cases. There was an excess of velamentous cord insertions, which was most pronounced in the stillborn twin. Monochorionic placentation was found in 72%, also an excess. Neurological damage was known to have occurred in 19 of the 39 surviving infants. Fifteen of these 19 (79%) were associated with monochorionic placentation. The neurologically damaged twin infants, when compared to the normal infants, had the cotwin die later in gestation (31 vs 16.5 weeks), had a shorter duration between the death of the cotwin and delivery (2.5 vs 21 weeks), and delivered earlier in gestation (36.5 vs 39.5 weeks). The probable cause of neurological damage, in our opinion, was either exsanguination into the dead twin fetus, or disseminated intravascular coagulation which occurred in at least 13 cases. The incidence of antepartum death in a multiple gestation, and the potential for neurological damage is probably higher than previously thought. A review of the literature is presented and the clinical implications of this phenomenon are discussed.


Childhood behavior problems: a comparison of twin and non-twin samples.

This study compares standardized measures of childhood behavior problems in a community-based twin sample with those for normative samples from the general population. Maternal parent ratings on the Child Behavior Checklist (CBCL) for 1824 twins were compared with the CBCL normative sample. The results indicated that twins showed small but consistently higher levels of problem behaviors. These elevations were significant for older children on both internalizing and externalizing behaviors; for younger children the elevations were significant for externalizing but not internalizing behaviors.


Similarity in general cognitive ability, creativity, and cognitive style in a sample of adolescent Russian twins.

Data on five tests of general and specific cognitive abilities, cognitive styles, and creativity, obtained from members of 60 identical and 63 fraternal Russian adolescent twin pairs, are presented. All tests are adaptations of standardized instruments widely used outside of the Soviet Union. Identical and fraternal twin correlations for general cognitive ability yielded a lower estimate of heritability (0.29) than generally found in other countries worldwide (0.52) although the twin correlations themselves are fairly comparable to figures from other countries and cultures--0.83 and 0.69 for Russian identical and fraternal twin pairs, respectively, vs 0.86 and 0.60 for non-Russian identical, and fraternal twin pairs. Twin correlations for other cognitive-related abilities assessed were also comparable to correlations obtained outside the Soviet Union with the exception of creativity which yielded higher within-pair resemblance than reported in previous twin studies.