Desglycinamide-9-arginine-8-vasopressin (DGAVP, Organon 5667) in patients with dementia

Vasopressin peptides have been shown to facilitate learning and memory in both animals and humans; however, the effectiveness in humans is controversial. In a double blind parallel group study, 17 demented subjects (either Alzheimer's or alcoholic) were given either desglycinamide-9-arginine-8-vasopressin (DGAVP) 92 micrograms intranasally TID or an identical placebo for 1 week after having received 1 week of placebo. To our knowledge, this is the first report of DGAVP being used in subjects with dementia. The DGAVP group had a statistically significant improvement on the Buschke list learning of low imagery words. However, for various reasons discussed in the paper, we feel this finding needs to be replicated before any definite conclusions can be drawn. Since there were no other appreciable behavioral effects of this DGAVP regimen, our results should be considered negative. There was no evidence of any DGAVP-related adverse effects, except for possible weight gain.     

Enhanced monoaminergic neurotransmission by desglycinamide-arginine-vasopressin in human subjects

The effect of desglycinamide-arginine-vasopressin (DGAVP) on monoaminergic neurotransmission was studied in human subjects. Samples of cerebrospinal fluid (CSF) were collected during 240 min after DGAVP (2 mg) had been administered intranasally, and monoamine metabolites in CSF were measured with HPLC using electrochemical detection. Levels of homovanillic acid and 5-hydroxyindoleacetic acid increased (P less than 0.05) 150 min after DGAVP administration, whereas levels of 3-methoxy-4-hydroxyphenylglycol were stable during the time monitored. These results suggest that in human subjects the mechanism of action of DGAVP may involve dopaminergic and serotonergic systems.     

Handwashing and antiseptic-containing soaps in hospital

Two aspects of handwashing in hospital were considered. A study was carried out to examine the contamination of bar soap and containers, and the use of antiseptic soaps in reducing the resident flora of the skin. Swabs were collected from soap dishes on six wards and from a bacteriology laboratory on four consecutive days. The unmedicated bar soap was replaced by bar soap containing 2.5% povidone-iodine, and further swabs were collected over a period of seven days. Ninety-two isolates from 48 samples were obtained when unmedicated bar soap was used, and nine isolates from 42 samples when povidone-iodine (Betadine) soap was substituted. The number of organisms recovered when povidone-iodine soap was used was much reduced, and Pseudomonas spp were recovered in low numbers on only one occasion.Six laboratory workers took part in a study to compare bar soap with other agents-povidone-iodine soap, povidone-iodine surgical scrub, povidone-iodine alcoholic solution, chlorhexidine surgical scrub, and alcoholic chlorhexidine. Samples were collected after standard washes and after surgical gloves had been worn for 90 minutes. The effect of multiple washes was assessed by samples collected after six washes with the agent under study (three per day) followed by 90 minutes wearing surgical gloves. The average percentage reduction in normal flora obtained indicated that alcoholic chlorhexidine was superior to the other agents.     

Studies on the mechanism of elevation of serum PIVKA-II levels in alcoholic liver cirrhosis

We measured serum PIVKA-II concentrations in 18 patients with alcoholic liver cirrhosis. Alcoholic liver disease was diagnosed by the history of ethanol intake of more than 900 ml/day for over 10 years. Liver cirrhosis was diagnosed histologically. Infections with hepatitis B and C viruses were ruled out by assaying serum virus markers. No tumor was detected in liver by ultrasonography and computed tomography during observation period. None of the patients studied were positive for alpafetoprotein (AFP). Eight out of 18 (44.4%) patients with alcoholic liver cirrhosis showed elevated serum PIVKA-II levels. In contrast, only eight out of 93 (8.6%) patients with nonalcholic liver cirrhosis had elevated serum PIVKA-II levels. PIVKA-II is well known as a tumor marker of hepatocellular carcinoma (HCC). The rates of positive PIVKA-II found in alcoholic liver cirrhosis approached its rates in HCC. However, the time course for the elevation of serum PIVKA-II levels was different each other in alcoholic liver cirrhosis and HCC. In HCC, serum PIVKA-II "levels" continued to elevate until therapy. In contrast, its elevation was transient and its levels returned to baseline in alcoholic liver cirrhosis. The values of ALT (GPT), gamma-GTP, and ALP correlated poorly with serum PIVKA-II levels in patients with alcoholic liver cirrhosis. To investigate the mechanism by which elevation of serum PIVKA-II levels in patients with alcoholic liver cirrhosis occurred, we studied the effect of vitamin K on production of PIVKA-II and AFP by hepatocytes. Hepatocytes(Alexander PLC/PRF/F cell line) were cultured in the presence of various concentrations of vitamin K (Kaytwo, Eisai, Tokyo). Vitamin K had no effect on AFP production. In contrast, PIVKA-II production was inhibited by addition of vitamin K in a dose dependent manner. Moreover, elevation of serum PIVKA-II levels in patients with alcoholic liver cirrhosis was suppressed by administration of vitamin K (Kaytwo) to these patients. Taken together, these results suggest that vitamin K may have a role in the mechanism of PIVKA-II elevation in sera of these patients. Then, we measured serum concentrations of vitamin K(PK, MK-4, MK-7) in these patients. There was no correlation observed between vitamin K and PIVKA-II in these patients. This result suggests that elevation of serum PIVKA-II in these patients may not be due to vitamin K deficiency. One question not answered here is how serum PIVKA-II levels in these patients are suppressed by treatment with vitamin K (Kaytwo). More detailed analysis of the mechanism of elevation of serum PIVKA-II levels in patients with alcoholic liver cirrhosis is needed.     

The influence of a vasopressin-analogue (DGAVP) on event-related potentials in a stimulus-mismatch paradigm

To assess the influence of DGAVP (des-glycinamide-arginine-8-vasopressin, a synthetic vasopressin analogue) on the processing of stimuli and stimulus deviance in humans in a double-blind cross-over experiment, 13 subjects received 60 IU DGAVP versus placebo intranasally 48, 24, and 1 h prior to the experimental session. Auditory event-related potentials (ERPs) were taken as a tool to investigate central nervous processing in an experimental task that required the subjects to count different kinds of rare tone pips deviating in pitch and probability compared to frequent standard tones. Direction of attention was manipulated by instructing the subject to count a different class of deviating tone pips in each attention condition. DGAVP enhanced the N2 of the ERP to tone pips deviating extremely in pitch from standard tones, whether or not the extremely deviating pips were to be attended to by the subjects. This influence suggests an intensified mismatch processing under DGAVP that may result from a general excitatory effect of this substance on cortical activity.     

Clomiphene citrate does not affect the secretion of alpha3, alphaV and beta1 integrin molecules during the implantation window in patients with unexplained infertility.

BACKGROUND: The expression of integrin molecules on the endometrium suggests that certain integrins may participate in the cascade of molecular events leading to successful implantation. A prospective, controlled study was carried out to investigate the effect of clomiphene citrate (CC) on secretions of beta1, alpha3 and alphaV integrin molecules in the endometrium of patients with unexplained infertility during the implantation window. METHODS: A total of 40 endometrial samples was evaluated in both spontaneous (n = 13) and ensuing clomiphene-treated cycles (100 mg on days 5-9) and also from fertile women serving as controls (n = 14) during postovulatory 7th or 8th day of menstrual cycle. A semiquantitative grading system (H-score) was used to compare the immunohistochemical staining intensities. Endometrial thickness and serum oestradiol and progesterone concentrations were also measured on the day of sampling. RESULTS: Staining of alpha(v) but not beta1 and alpha3 integrins was significantly less intense in infertile cases than fertile control cases (1.42 +/- 0.12 versus 2.21 +/- 0.13 respectively, P = 0.012) and this was not restored to normal concentrations with treatment. CONCLUSIONS: Our study indicated that cc treatment significantly decreased the endometrial thickness and increased oestradiol and progesterone concentrations. However, secretion of alpha(v), beta1 and alpha3 integrin molecules, which might play a role in implantation, was not affected.     

A randomized trial of prednisolone in patients with severe alcoholic hepatitis.

BACKGROUND. Controlled trials have yielded inconsistent results with regard to the efficacy of corticosteroids in the treatment of alcoholic hepatitis. Three meta-analyses suggest that they may be effective in patients with encephalopathy who have severe liver disease. METHODS. We conducted a randomized, double-blind trial comparing 28 days of prednisolone treatment (40 mg per day) with placebo in 61 patients with biopsy-proved alcoholic hepatitis and either spontaneous hepatic encephalopathy (n = 19) or a discriminant-function value higher than 32. The discriminant function used was as follows: 4.6 (prothrombin time-control time [in seconds]) + serum bilirubin (in micromoles per liter)/17. Fifty-seven of the patients had evidence of cirrhosis on biopsy. The primary end point was death within two months. RESULTS. One patient was lost to follow-up after 56 days. Treatment was discontinued in two patients because of drug toxicity. By the 66th day after randomization, 16 of 29 placebo recipients had died (mean [+/- SE] survival, 45 +/- 8 percent), as compared with 4 of 32 prednisolone recipients (survival, 88 +/- 5 percent) (log-rank test, 10.9; P = 0.001). The survival advantage for prednisolone persisted after stratification according to center and the presence of encephalopathy, and after adjustment for prognostic factors in a proportional-hazards model. CONCLUSIONS. Treatment with prednisolone improves the short-term survival of patients with severe biopsy-proved alcoholic hepatitis.     

Brief group therapy in myocardial infarction rehabilitation: three- to four-year follow-up of a controlled trial.

A trial of brief group therapy as part of a rehabilitation program for postmyocardial infarction (MI) patients was carried out. Forty-four patients surviving their first MI were randomly allocated to either group therapy or control group status and were followed over 4 years. An additional group of 17 patients were referred for post-MI group therapy sessions after the termination of the controlled experiment and were followed for 3 years. Patients who received group therapy had significantly less follow-up coronary morbidity and mortality, and returned to work at significant higher percentages than control patients. Although neither group therapy nor control group patients meaningfully altered conventional coronary risk factors, group therapy patients (in the controlled trial) successfully altered selected coronary-prone behaviors. Educational information regarding the physiological and psychological aspects of coronary heart disease, presented in the group therapy sessions, was forgotten over follow-up. It is concluded that the supportive aspects of the group therapy experience played the most important role in determining the rehabilitation advantages seen for treatment patients.     

Disorders of biotransformation during the progression of alcoholic liver disease

Biotransformation capacity was investigated in patients with various degrees of alcoholic liver damage. Aim of the investigation was to study the impairment of biotransformating ability during progression of liver damage. Four groups of patients with various liver diseases (alcoholic fatty liver, chronic persistent hepatitis, chronic active hepatitis, alcoholic cirrhosis) and two groups as controls were studied. The investigations were carried out with exogenous test substances (antipyrine, menthol and sulphadimidine) and by determination of D-glucaric acid excretion. It has been concluded that the depression of biotransformating ability in patients with alcoholic liver diseases is progressing during development of diseases. The changes in various metabolic pathways are different, and they seem to be more marked in the first phase of biotransformation than in the second phases.     

Histological demonstration and frequency of intrahepatocytic copper in patients suffering from alcoholic liver disease

This study was carried out to determine whether stainable copper accumulates in the hepatocytes of patients with alcoholic liver disease. Liver sections from 44 cases of alcoholic cirrhosis and 32 cases of non-cirrhotic alcoholic liver disease were stained by the rubeanic acid, rhodanine and orcein methods. Intrahepatocytic copper granules were found in 13 cases of cirrhosis (30%), but in none of the non-cirrhotic livers. The abundance of granules did not appear to be related either to the activity of the cirrhotic process or to the presence of cholestasis. It may well be that alcoholic cirrhosis is the most common disease associated with excess of intrahepatocytic copper.     

In a flexible antagonist protocol, earlier, criteria-based initiation of GnRH antagonist is associated with increased pregnancy rates in IVF

BACKGROUND: The purpose of the study was to assess ongoing pregnancy rates across groups of patients treated by IVF, which were defined according to criteria aimed at the prevention of premature LH surge and used for initiating GnRH antagonist. METHODS: This is a prospective observational cohort study. During the last 3 years, in IVF-ICSI patients undergoing controlled ovarian stimulation (COS) with the antagonist protocol, the antagonist administration was initiated according to at least one of the following patient-specific criteria: (i) at least one follicle measuring >14 mm; (ii) estradiol levels >600 pg/ml; and (iii) LH levels >10 IU/l. Based upon these criteria, 208 cases of normal responders were analysed and categorized into three groups according to the starting day of the regimen: group D4 (n = 40) for day 4, group D5 (n = 98) for day 5 and group D6 (n = 70) for day 6. The main outcome measure was the ongoing pregnancy rate per started cycle. RESULTS: The total number of patients in the D4 and D5 groups (138 out of 208), who received the antagonist earlier, was considerably larger compared with that of D6 (70 out of 208). Ongoing pregnancy rates were 37.5, 34.7 and 18.6% for groups D4, D5 and D6, respectively. Patients who initiated the GnRH antagonist on days 4 and 5 had statistically significant higher pregnancy rates compared with day 6. Rapid response, causing earlier antagonist administration initiation, according to the proposed criteria for the prevention of premature LH surges, and the absence of premature luteinization, as evidenced by normal progesterone levels on HCG day, were found to be independent positive predictive factors for favourable IVF outcome. CONCLUSIONS: The employment of an algorithm of criteria, aimed at the prevention of premature LH surges in a flexible antagonist protocol, resulted in antagonist initiation earlier than on stimulation day 6 in a significant proportion of patients. In those patients, a higher pregnancy rate was observed.     

Genetic analysis of tolerance to ethanol hypothermia in recombinant inbred mice: Effect of desglycinamide(9)-Arginine(8)-vasopressin

The hypothermic effect of ethanol, tolerance to ethanol hypothermia, and the effect of desglycinamide(⁹)-Arginine(⁸)-vasopressin dicitrate (DGAVP) on ethanol hypothermic tolerance were investigated in Bailey's Recombinant Inbred strains of mice. Strains differed markedly in baseline temperatures and initial sensitivity to ethanol. There were no significant strain differences in tolerance. DGAVP attenuated the strain differences in initial sensitivity to ethanol and blocked tolerance development. These effects were accompanied by changes in the pattern of genetic control.     

Critical study of methods of estimation by an enzymatic method of serum triglycerides (author's transl)]

The authors describe a critical study of two entirely enzymatic methods of determination of serum triglycerides which differ mainly by the choice of hydrolytic agents: esterase and hydrolase by the Roche methods, lipase and esterase in the case of the Boehringer method. The estimation of the resulting free glycerol requires 3 sequential enzymatic reactions (glycerol kinase, pyruvate kinase, lactate dehydrogenase, ending by the measurement of the consumed reduced NAD. The study of the kinetics of the analysis in two stages is carried out using standard solutions of glycerol and with human sera of variable concentration; the optimal conditions of the reaction time and temperature are drawn up. The trials of repeatability and reproducibility from day to day were carried out together with evaluation of the precision. The method was compared with Beohringer's method (n = 50) using hydrolysis of alcoholic potash. The authors conclude on the use of the methods studied.     

Differential cell count of sputum in patients with asthma challenged with allergen provocation

Inhalation of hypertonic saline aerosol is a noninvasive method of obtaining sputum for examination of inflammatory processes in the airways. The aim of our investigation was to evaluate the effect of the bronchial provocation test with Dermatophagoides pteronyssinus on both total and differential cell counts in the sputum of allergic asthma patients. The studies were carried out on 20 mild or moderate allergic asthmatics. In each case the studies were performed on three consecutive days. Sputum was induced on the first day of the study, the next day the bronchial provocation test with the allergen was performed and on the last day the sputum induction was repeated again. Twenty-four hours after the allergen challenge an increase in the total cell count and in eosinophils and a decrease in the percentage of macrophages were found in the induced sputum. The above changes were more marked in the patients demonstrating the dual asthmatic reaction after allergen challenge.     

Circulating immune complexes and complement concentrations in patients with alcoholic liver disease.

A prospective evaluation of circulating immune complexes (CIC) and the activity of the complement system was undertaken in 53 alcoholic patients just before diagnostic liver biopsy. Circulating immune complexes were detected in 39% of patients with alcoholic steatosis (n = 26), 58% of patients with alcoholic hepatitis (n = 12), and 60% of patients with alcoholic cirrhosis (n = 15). No significant difference was found between the three group of patients. The activity of the complement system was within reference limits in the majority of patients and only slight differences were detected between the three groups. No significant differences were observed in liver biochemistry and complement concentrations in CIC-positive and CIC-negative patients. Detection of CIC in patients with alcoholic liver disease does not seem to be of any diagnostic value or play any pathogenic role. The high prevalence of CIC in these patients may be due to a depressing effect of ethanol on clearance of CIC or to increased immunological reactivity, or to both.     

Alcohol-related cirrhosis with pancreatitis. The role of oxidative stress in the progression of the disease

To assess the level of oxidative stress, measured as prooxidant-antioxidant imbalance in the blood of patients with alcohol-related injury of the liver and pancreas, we determined superoxide ion (O2*-) production by neutrophils isolated from the peripheral blood of 3 groups of patients. Patients with compensated alcoholic liver cirrhosis (n=16), with alcoholic chronic pancreatitis (n=20), and with concomitant cirrhosis and pancreatitis (n=10) were included in this study. All patients had consumed at least 70 g of pure alcohol per day over 5 years. They had not abstained before admission to hospital. The control group consisted of 16 healthy non-alcohol-abusive subjects. As antioxidative enzymes (AOE) present in sera play a very important role in the regulation of plasma reactive oxygen species (ROS) levels and in the protection of plasma compounds against ROS action, we also examined the serum activity of catalase (CAT), superoxide dismutase (SOD), total activity, and the glutathione peroxidase (GPx) serum concentration. Neutrophils of patients with concomitant alcoholic liver cirrhosis and pancreatitis exhibited, similarly to the neutrophils of patients with chronic alcoholic pancreatitis, an enhanced ability to produce superoxide anions in vitro. In contrast, neutrophils of patients with alcoholic liver cirrhosis exhibited a defect in resting and PMA-induced superoxide anion production. The AOE activity in the sera of patients was also significantly changed. Total SOD activity was enhanced in all groups of patients with alcoholic liver cirrhosis, chronic pancreatitis and with concomitant injury of both organs. CAT activity was only increased in the sera of patients with liver cirrhosis or pancreatitis, but not in the patients with concomitant cirrhosis and pancreatitis. GPx concentration was only diminished in the patients with chronic pancreatitis. It seems likely that oxidative stress, defined as the imbalance between prooxidant and antioxidant activity, is highest in the blood of patients with chronic pancreatitis and, especially, in patients with concomitant liver cirrhosis and pancreatitis.     

A video analysis of the non-verbal behaviour of depressed patients before and after treatment

Using videotaped interviews of depressive in-patients, which were recorded on day 0 and day 21 of antidepressive pharmacotherapy, the behavioural structure of the syndromal main aspects, retardation and agitation, was analysed. This analysis was done on the basis of non-verbal behaviour only. A factor analysis was carried out on the observational data. Three independent factors, constituting together the clinical picture of endogenous depression, could be defined: one factor of retardation and two different factors of agitation. The importance of such non-verbal analyses for a more differentiated diagnostic evaluation, on the one hand, and to provide more insight into the diagnostic process as such, on the other, is pointed out. Additionally it was found that syndromal complexity decreases in a characteristic manner along with clinical improvement.     

MORPHOLOGIC SPECTRUM OF LIVER DISEASES AMONG CHRONIC ALCOHOLICS A Comparison between Tokyo, Japan and Cincinnati, U.S.A.

To deliniate the histopathological features of liver diseases seen in Japanese alcoholics, 130 Japanese alcoholic patients were studied in comparison with 238 American alcoholic patients. In Japan female alcoholic patients were extremely rare. The male to female ratio was 127 to 3 in Japan and 152 to 89 in U.S.A. Although all aspects of alcoholic liver disease did exist in Japan, typical cases of acute alcoholic hepatitis with alcoholic hyalins were remarkably smaller in number (9.2% in Japan versus 39.5% in the U.S.A.). The severity based on histopathological findings was also less in the Japanese cases. In contrast to this, 46 percent of Japanese alcoholic patients had chronic hepatitis, and the incidence of multilobular cirrhosis was much greater in Japan wherewith higher prevalence of viral hepatitides.     

An improved use of buserelin in ovarian stimulation for in-vitro fertilization

In earlier IVF programmes, subcutaneous buserelin (Suprefact, Hoechst) was initially administered three times per day (200 micrograms x 3); then twice daily (300 micrograms x 2). We now suggest that a single administration of 600 micrograms daily may be equally effective. In a preliminary study, 20 patients were selected on the basis of tubal or idiopathic infertility and received 0.6 ml buserelin subcutaneously once a day, beginning on day 1 or 2 of the cycle. A sufficient pituitary desensitization was obtained on day 10 in 75% of patients and on day 16 for 100% and the ongoing pregnancy rate was 35% per treatment cycle. A randomized study comparing the effect of 600 micrograms of buserelin administered in one (n = 50) or two injections (n = 46), has been carried out and indicates that the results in terms of the ovarian suppression and pregnancy rates, were similar. Therefore, this protocol represents a simplification of the treatment with buserelin.     

The GIFT experience: an evaluation of the outcome of 115 cases

The outcome of a series of 115 patients undergoing GIFT by minilaparotomyis described, their duration of infertility ranging between3 and 19 years. Ovarian stimulation was carried out using clomiphenefrom day 3 and HMG from day 6, and HCG was used to induce follicularmaturation. A maximum of four oocytes, two per oviduct with100 000 spermatozoa, were replaced. Thirtysix pregnancies wereestablished. The highest incidence of pregnancy was obtainedin cases of unexplained infertility (42%) and endometriosis(28%), and the lowest with male factors (13%). The most matureoocytes gave the best results. There were eleven miscarriages(30.5%) and two ectopic pregnancies (5.5%). Eleven of the 23deliveries involved multiple births.