Galapagos hydrothermal mounds: stratigraphy and chemistry revealed by deep-sea drilling.

The Galápagos mounds sea-floor hydrothermal system is at least 300,000 years old and once produced manganese-poor sediments, which nearly blanketed the area of the present mounds field. Present-day mound deposits are limited manganese-rich exposures, suggesting that the system has changed from rock-to water-dominated and has diminished in intensity with time.

Nutritional and Functional Status in Geriatric Day Hospital Patients - MNA Short Form Versus Full MNA.

OBJECTIVES: The aims of this study were to determine the prevalence of malnutrition in patients of a geriatric day hospital using the Mini Nutritional Assessment short form (MNA-SF) and the full MNA, to compare both tools, and to examine the relationship between nutritional and functional status. DESIGN: Cross-sectional study. SETTING: Geriatric day hospital. PARTICIPANTS: 190 patients (72.1% female, median 80 years) aged 65 years or older. MEASUREMENTS: In consecutively admitted geriatric day hospital patients nutritional status was assessed by MNA-SF and full MNA, and agreement between both tools calculated by Cohen´s kappa. Basic activities of daily living (ADL), instrumental activities of daily living (IADL) and short physical performance battery (SPPB) were determined and related to MNA categories (Chi2-test, Mann-Whitney-U-test). RESULTS: 36.3 % and 44.7% of the patients were at risk of malnutrition, 8.9 % and 5.8 % were malnourished according to MNA-SF and full MNA, respectively. Agreement between both MNA forms was moderate (κ=0.531). No significant associations between MNA-SF and ADL, IADL and SPPB, and between full MNA and SPPB were observed. According to full MNA, the proportion of patients with limitations in ADL and IADL significantly increased with declining nutritional status (ADL: 2.1 vs. 8.2 vs. 18.2 %, p=0.044; IADL: 25.5 vs. 47.1 vs. 54.5 %, p=0.005) with a simultaneous decrease of the proportion of patients without limitations. Well-nourished patients reached significantly higher ADL scores than patients at risk of malnutrition (95 (90-100) vs. 95 (85-100), p=0.005) and significantly higher IADL scores than patients at risk or malnourished (8 (6-8) vs. 7 (5-8) vs. 6 (4-8), p=0.004). CONCLUSION: The high prevalence of risk of malnutrition and the observed association between functional status and nutritional status according to full MNA call for routine nutritional screening using this tool in geriatric day hospital patients.

Development of AIDS in people with transfusion-acquired HIV infection.

OBJECTIVE: To determine the rate of development of AIDS, and the demographic and clinical cofactors for development of AIDS in a group of 117 people with transfusion-acquired HIV infection, who were infected between 1980 and 1985 in New South Wales, Australia. RESULTS: By December 1991, 67 (57%, 95% CI 48-66%) of the study subjects had developed AIDS. The estimated median time to development of AIDS was 7.2 years from the date of infection. There was no significant difference in median age at infection or sex between individuals who did and did not develop AIDS. The median time to development of AIDS was shorter in older individuals (median time to AIDS for age groups 13-39, 40-59 and > 59 was 7.8, 7.1 and 5.4 years, respectively; P = 0.20). A significantly greater proportion of individuals who had never received treatment with zidovudine developed AIDS compared with individuals who had (P = 0.04). But in a statistical analysis which took account of the changing availability of zidovudine over time, there was no significant association between the development of AIDS and treatment with zidovudine (P = 0.44). CONCLUSION: Consistent with other studies, age appeared to increase the rate of progression to AIDS, although not significantly so in this study.

Neutralization of adenovirus infectivity and cytotoxin in various cell cultures.

The neutralization of human adenovirus 5 and 11 by homologous and heterologous rabbit antisera was determined by CPE inhibition in various cell cultures (HeLa, HEL, Vero, secondary kidney cells from cercopithecus, rabbit, mouse), or in HeLa cells made impermissive by IUdR inhibition. The results concerning sensitivity and specificity were similar in all cases. Crude and purified virus showed similar neutralization. Immunofluorescence neutralization in HeLa cell cultures gave similar results; this method is suitable for demonstrating subtle immunological relations between adenovirus types. The neutralization of the early cytopathic factor ('cytotoxin') showed a pattern of cross-reactivity different from the virion; the cytotoxin was found to be active in part of the cell cultures only. It is concluded from the results that the virus function(s) blocked by antibody appear to be identical for the replicative cycle in infection and for the initiation of the abortive infection in non-permissive cells. Hence, either kind of cells may be used for neutralization tests.

Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in isolated rat lung and liver.

The tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a strong lung carcinogen in all species tested. To elicit its tumorigenic effects NNK requires metabolic activation which is supposed to take place via alpha-hydroxylation, whereas N-oxidation is suggested to be a detoxification pathway. The differences in the organ specific metabolism of NNK may be crucial for the organotropy in NNK-induced carcinogenesis. Therefore, metabolism of NNK was investigated in the target organ lung and in liver of Fischer 344 (F344) rats using the model of isolated perfused organs. High activity to metabolize 35 nM [5-3H]NNK was observed in both perfused organs. NNK was eliminated by liver substantially faster (clearance 6.9 +/- 1.6 ml/min, half-life 14.6 +/- 1.2 min) than by lung (clearance 2.1 +/- 0.5 ml/min, half-life 47.9 +/- 7.4 min). When the clearance is calculated for a gram of organ or for metabolically active cell forms, the risk with respect to carcinogenic mechanisms was higher in lung than in liver. The metabolism of NNK in liver yielded the two products of NNK alpha-hydroxylation, the 4-oxo-4-(3-pyridyl)-butyric acid (keto acid) and 4-hydroxy-4-(3-pyridyl)-butyric acid (hydroxy acid). In lung, the major metabolite of NNK was 4-(methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanone (NNK-N-oxide). Substantial amounts of metabolites formed from methyl hydroxylation of NNK, which is one of the two possible pathways of alpha-hydroxylation, were detected in lung but not in liver perfusion. Formation of these metabolites (4-oxo-4-(3-pyridyl)-butanol (keto alcohol), and 4-hydroxy-4-(3-pyridyl)-butanol (diol) can give rise to pyridyloxobutylating of DNA. When isolated rat livers were perfused with 150 microM NNK, equal to a dosage which is sufficient to induce liver tumors in rat, glucuronidation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) was increased when compared to the concentration of 35 nM NNK. Nevertheless, the main part of NNK was also transformed via alpha-hydroxylation for this high concentration of NNK.

Effect of nicotine or cotinine on metabolism of 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) in isolated rat lung and liver.

The scope of the present study was to investigate whether nicotine or cotinine will affect the metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in isolated perfused rat lungs and livers and to study the effect of starvation on pulmonary metabolism of NNK. NNK metabolism was investigated in isolated perfused liver and lung of male F344 rats perfused with 35 nM [5-3H]NNK in presence of a 1400-fold excess of the main tobacco alkaloid nicotine and its metabolite cotinine. In perfused rat livers, nicotine and cotinine inhibited NNK elimination and metabolism and led to a substantial increase of elimination half-life from 14.6 min in controls to 25.5 min after nicotine and 36.6 min after cotinine co-administration, respectively. In parallel, the pattern of NNK metabolites was changed by nicotine and cotinine. The pathway of alpha-hydroxylation representing the metabolic activation of NNK was decreased to 77% and 85% of control values, whereas N-oxidation of NNK and glucuronidation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) was increased 2.6- and 1.2-fold in presence of nicotine and cotinine, respectively. When isolated rat lungs were perfused with 35 nM NNK for 3 h neither the elimination nor the pattern of metabolites were substantially affected due to co-administration of 50 microM nicotine or cotinine. Cytochrome P450 2E1 is known to participate in the activation of NNK and can be induced by starvation. However, isolated rat lungs from male Sprague Dawley rats perfused with [1-14C]NNK at about 2 microM for 3 h, revealed only small differences in pulmonary elimination and pattern of NNK metabolites between fed and starved animals. These results suggest that nicotine and its main metabolite cotinine inhibit the metabolic activation of NNK predominantly in the liver whereas activation in lung, a main target organ of NNK induced carcinogenesis, remained almost unaffected.

Monitoring of cytochrome P-450 1A activity by determination of the urinary pattern of caffeine metabolites in Wistar and hyperbilirubinemic Gunn rats.

Various studies suggest that induction of cytochrome P-450 1A (CYP1A) might be a valuable therapeutic modality for reducing the hyperbilirubinemia of infants with Crigler-Najjar syndrome type I (CNS-I), a severe form of congenital jaundice. To evaluate inducers of CYP1A as possible tools in the treatment of hyperbilirubinemia, a novel assay was established, based on the analysis of the urinary pattern of caffeine metabolites in rats. Wistar rats received [1-Me-(14)C]-caffeine (10 mg/kg i.p.), before and 48h after administration of the potent CYP1A inducer 5,6-benzoflavone (BNF) (80 mg/kg, i.p.). A substantial increase in the fractions of the terminal caffeine metabolites 1-methyluric acid (1-U), 1-methylxanthine (1-X), and a concomitant decrease in the caffeine demethylation product 1,7-dimethylxanthine (1,7-X) was observed after application of BNF. The ratio of the caffeine metabolites (1-U+1-X)/1,7-X may serve as an index of CYP1A activity in rats in vivo. Hyperbilirubinemic, homozygous (jj) Gunn rats are an accepted model for human CNS-I. In male jj Gunn rats treated with BNF or with indole-3-carbinol (I3C, 80 mg/kg, oral gavage), the inducing effect of BNF and 13C on CYP1A activity was confirmed by the urinary pattern of caffeine metabolites, and was parallelled by a decrease in plasma bilirubin levels. These data demonstrate the usefulness of the established caffeine assay for the evaluation of inducers of CYP1A as tools for reducing hyperbilirubinemia and further confirm the potential value of I3C in the treatment of CNS-I.

Evolution and evaluation of a medical psychiatric unit.

In 1991, the first Medical Psychiatric Unit (MPU) in Australia was established at the Royal Prince Alfred Hospital, Sydney. The processes involved in introducing it to the hospital staff and administration, as well as its structure and criteria for admission, are described. Its development was compared to the experiences of others in North America over the past 15 years. The functioning of the MPU over the subsequent 2 years was evaluated by assessing demographic and clinical criteria of patients admitted. Data were obtained from patient medical records and compared with similar data on patients admitted to a General Psychiatric Unit (GPU). It was found that patients of the MPU tended to be older, more often male, and suffering from organic brain syndromes and/or alcohol or drug abuse. Despite the multiplicity of diagnoses and the complexity of treatment procedures, the MPU patients' duration of stay was similar to the GPU patients'. The MPU was found to have achieved goals of clinical and cost-effectiveness. It has become an established subunit within the Department of Psychiatry.

Equivalence of St John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression.

Treatment with St John's wort extract tablets (hypericum Ze 117) and the commonly used slow serotonin reuptake inhibitor (SSRI) fluoxetine was compared in patients with mild-moderate depression with entry Hamilton Depression Scale (HAM-D) (21-item) in the range 16-24, in a randomized, double-blind, parallel group comparison in 240 subjects; fluoxetine: 114 (48%), hypericum: 126 (52%). After 6 weeks' treatment, mean HAM-D at endpoint decreased to 11.54 on hypericum and to 12.20 on fluoxetine (P < 0.09), while mean Clinical Global Impression (CGI) item I (severity) was significantly (P < 0.03) superior on hypericum, as was the responder rate (P = 0.005). Hypericum safety was substantially superior to fluoxetine, with the incidence of adverse events being 23% on fluoxetine and 8% on hypericum. The commonest events on fluoxetine were agitation (8%), GI disturbances (6%), retching (4%), dizziness (4%), tiredness, anxiety/nervousness and erectile dysfunction (3% each), while on hypericum only GI disturbances (5%) had an incidence greater than 2%. We concluded that hypericum and fluoxetine are equipotent with respect to all main parameters used to investigate antidepressants in this population. Although hypericum may be superior in improving the responder rate, the main difference between the two treatments is safety. Hypericum was superior to fluoxetine in overall incidence of side-effects, number of patients with side-effects and the type of side-effect reported.

[Efficient use of sleep pillows in patients suffering from non-organic sleep disorders--a pilot study]. / Effizienter Einsatz von Schlafkissen bei Personen mit nicht-organischen Schlafstörungen--eine Pilotuntersuchung.

OBJECTIVE: Sleep disorders may critically affect working performance and quality of life. Sleep pillows have been traditionally used to overcome such disorders. Scientifically based clinical trials to demonstrate the efficacy are missing. METHODS: 28 patients with problems falling asleep and/or staying asleep not related to psychiatric or organic diseases were investigated in an accredited sleep laboratory. The diagnosis was confirmed by polysomnography. After 2 and 4 weeks of treatment the polysomnography was repeated to document any influences by the sleep pillows. RESULTS: The polysomnographic records showed a monotonic trend to regain an age-related distribution of the non-REM sleep stages. The REM sleep phase increased nearly twofold; however, the norm values were not reached within the 4-week period of treatment. Sleep pillows of intensity 2 were superior to those of intensity 1; a further increase to intensity 3 did not create any additional effect. CONCLUSION: The results demonstrate an effective treatment of non-complicated sleep disorders with sleep pillows, which has been shown with objective measurements in a sleep laboratory.

[Comparison of the bioavailability of beta-aescin after single oral administration of two different drug formulations containing an extract of horse-chestnut seeds]. / Vergleichende Untersuchung zur Bioverfügbarkeit von beta-Aescin nach oraler Einmalverabreichung zweier Rosskastaniensamenextrakt enthaltender, galenisch unterschiedlicher Darreichungsformen.

The relative oral bioavailability of beta-escine (CAS 11072-93-8) from a sugar-coated tablet formulation was compared to a reference preparation available in capsule form in 18 healthy, male volunteers over a 48 h period. The study design was randomized, single-blind and cross-over. Both the test and the reference preparation contained 50 mg standardized horse chestnut seed extract; beta-escine was taken as the reference substance. By means of a newly developed, validated radioimmunosorbent assay (RIA), beta-escine in plasma was determined (blind samples) after oral intake of a single dose of each drug formulation. The confidence limits calculated for the AUC, Cmax and Tmax of the test preparation exceed the upper limit of the specified equivalence range of 80%--125%, but do never fall below the lower limit. Therefore, bioin-equivalence cannot be rejected statistically. All the bioavailability data for the test preparation--measured with the newly developed RIA--exceed the corresponding values for the reference preparation. As the rate of absorption of aesculetinic triterpene glycosides is low, the higher bioavailability of the test preparation is desirable from a therapeutical point of view. Since the reference preparation is classified as being clinically effective, the test preparation must also be estimated as being clinically effective. Adverse drug effects were not observed with either the test preparation or the reference preparation.

Health care provider communicator style and patient comprehension of oral contraceptive use.

PURPOSE: To explore reasons for the incorrect usage of oral contraceptive pills (OCPs) by examining the relationship between patients' abilities to comprehend and/or recall information presented to them by nurse practitioners (NPs) and the communicator style of their NP. DATA SOURCES: A convenience sample of 46 OCP users completed an instrument designed to test their comprehension of OCP use and an instrument designed to measure the communicator style of their NP. CONCLUSIONS: A multiple stepwise regression revealed that attentive and friendly communicator styles were positive predictors and the communicator image and dramatic styles were negative predictors of comprehension. PRACTICE IMPLICATIONS: Unwanted pregnancies that result from non-compliance with OCP regimens can have significant social and financial effects. A lack of understanding of proper OCP use may depend on the style of communication a NP uses to convey crucial information regarding the regimen.

Nutritional status according to Mini Nutritional Assessment is related to functional status in geriatric patients--independent of health status.

OBJECTIVES: The aim of this study was to investigate the relationship between nutritional and functional status in acute geriatric patients including mobility and considering health status. DESIGN: Cross-sectional study. SETTING: Hospital. PARTICIPANTS: 205 geriatric patients (median age 82.0 (IQR: 80-86) years, 69.3% women). MEASUREMENTS: Nutritional status was determined by Mini Nutritional Assessment (MNA) and patients were categorized as well-nourished (≥ 24 points), at risk of malnutrition (17-23.5 points) or as malnourished (< 17 points). Functional status was determined by Barthel Index (BI) and Timed 'Up and Go' Test (TUG) and related to MNA categories. Using binary multiple logistic regression the impact of nutritional status on functional status was examined, adjusted for health status. RESULTS: 60.3% of the patients were at risk of malnutrition and 29.8% were malnourished. Ability to perform basic activities of daily living (ADL) decreased with declining nutritional status. The proportion of patients unable to perform the TUG increased with worsening of nutritional status (45.0% vs. 50.4% vs. 77.0%, p<0.01). After adjusting for age, gender, number of diagnoses, disease severity and cognitive function, a higher MNA score significantly lowered the risk of being dependent in ADL (OR 0.85, 95 % CI 0.77-0.94) and inability to perform the TUG (OR 0.90, 95 % CI 0.82-0.99). CONCLUSION: Nutritional status according to MNA was related to ADL as well as to mobility in acute geriatric patients. This association remained after adjusting for health status.