Validity of the Montreal Cognitive Assessment and the HIV Dementia Scale in the assessment of cognitive impairment in HIV-1 infected patients.

The gold standard for evaluating cognitive impairments in HIV-infected patients is to administer an extensive neuropsychological assessment. This may, however, be time-consuming and hence not always feasible in the clinic. Therefore, several brief screening tools have been developed. This study determined the validity of the Montreal Cognitive Assessment (MoCA) and the HIV Dementia Scale (HDS) in detecting cognitive impairment using both the Frascati and cognitive impairment, no dementia (CIND) criteria to classify cognitive impairment in HIV-1 infected patients. The MoCA, HDS, and an extensive neuropsychological assessment, covering nine cognitive domains, were administered in a group of 102 HIV-infected patients who were all on cART and virologically suppressed for at least 1 year. Results show that the areas under the curve (AUCs) for both the MoCA and the HDS were statistically significant, using both the Frascati and the CIND criteria as gold standard. However, the AUCs for the MoCA and HDS did not differ significantly, regardless of the used classification criteria (Frascati: z = 0.37, p = 0.35; CIND: z = -0.62, p = 0.27). Sensitivity of both the MoCA and HDS were low for the recommended cutoff scores (Frascati: MoCA (<26) = 0.56, HDS (<11) = 0.26; CIND: MoCA (<26) = 0.55, HDS (<11) = 0.36). Cutoff scores with good sensitivity and adequate specificity could not be determined for both screening instruments. Therefore, the HDS and MoCA are not recommended as sole instruments to diagnose HIV-associated cognitive impairment.

A case-control pilot study on cognitive functioning, symptom validity and psychological wellbeing in HIV-1-infected patients in the Netherlands.

The objective of this study was to examine and relate both cognitive functioning and psychological wellbeing in Dutch HIV-1-infected patients (n = 30) in comparison with a matched healthy control group (n = 30), taking symptom validity into account. Significant differences in performance between patients and controls were found in the domain Working memory (P = 0.036), but not in the other cognitive domains. There was a significant difference in all dimensions of the psychological wellbeing scale, measured with the SCL-90-R (P values between 0.002 and 0.023), except for agoraphobia, cognitive performance difficulty and sleep disturbances. No correlations were found between the performance on the Working memory domain and wellbeing. Future research should focus on unravelling the underlying mechanisms of neurocognitive dysfunction further using neuropsychological tests, including a symptom validity test in combination with neuroimaging techniques in larger samples.

Prevalence of urinary incontinence among community-dwelling adults receiving home care.

We conducted a cross-sectional survey in 2005 to determine the prevalence of and factors associated with urinary incontinence (UI) in adults receiving home care. Of the 2,866 patients surveyed, 46% suffered from UI; 6.5% had stress, 16.6% had urge, 9% had mixed, and 17.6% had functional incontinence. No diagnosis regarding type of UI had been established in 50.2%. Factors associated with UI were advanced age, higher body mass index, and impaired mobility. UI is prevalent in older persons receiving home care, but the lack of diagnosis of type of UI in half of the participants surveyed impedes management of UI.

Synthesis and anti-HIV activity of 1,3,4,5-tetrahydro-2H-1,4-benzodiazepin-2-one (TBO) derivatives. Truncated 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2( 1H)-on es (TIBO) analogues.

4,5,6,7-Tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1 H)-ones (TIBO), 1, have been shown to significantly inhibit HIV-1 replication, as reported in detail in our prior publications. Since our earlier reports, we have modified the TIBO structures 1 by removing the 5-membered ring of 1, generating 1,3,4,5-tetrahydro-2H-1,4-benzodiazepin-2-ones (TBO), 4, a bicyclic series of compounds. Although compounds 4 possess modest activity when compared to TIBO analogues 1, they clearly demonstrated significant anti-HIV-1 activity.

Modeling malaria as a complex adaptive system.

As the resistance of the malaria parasite to antimalarial drugs continues to increase, as does that of the malarial mosquito to insecticides, the efficacy of efforts to control malaria in many tropical countries is diminishing. This trend, together with the projected consequences of climate change, may prove to exacerbate substantially the significance of malaria in the coming decades. In this article we introduce the use of an evolutionary modeling approach to simulate the adaptation of mosquitoes and parasites to the available pesticides and drugs. By coupling genetic algorithms with a dynamic malaria-epidemiological model, we derive a complex adaptive system capable of simulating adapting and evolving processes within both the mosquito and the parasite populations. This approach is used to analyze malaria management strategies appropriate to regions of higher and lower degrees of endemicity. The results suggest that adequate use of insecticides and drugs may reduce the occurrence of malaria in regions of low endemicity, although increased efforts would be necessary in the event of a climate change. However, our model indicates that in regions of high endemicity the use of insecticides and drugs may lead to an increase in incidence due to enhanced resistance development. Projected climate change, on the other hand, may lead to a limited reduction of the occurrence of malaria due to the presence of a higher percentage of immune persons in the older age class.

Glutathione S-transferase as predictor of functional outcome in transplantation of machine-preserved non-heart-beating donor kidneys.

Non-heart-beating (NHB) donors are a valuable source of kidneys for transplantation. The organs, however, sustain substantial warm ischemic damage that may jeopardize the transplantability and result in nonfunction of the grafts. Quantification of warm ischemic time (WIT) and prediction of transplant outcome are essential for the use of NHB donor organs. During machine preservation (MP) the viability of NHB donor kidneys was evaluated through calculating intrarenal vascular resistance and determining lactate dehydrogenase and alpha-glutathione S-transferase (alphaGST) in the perfusate. Thirty-seven functioning (F) and nine nonfunctioning kidneys (NF) were compared. WIT was longer in NF; serum creatinine, donor age, and preservation time were not different. WIT correlated well with alphaGST after 4 and 8 hr of MP (r=0.353, P=0.009, and r=0.346, P=0.011, respectively). When compared with F, intrarenal vascular resistance was increased in NF after 4 and 8 hr of perfusion (P<0.05); at all time points, alphaGST levels were elevated in NF (P<0.05). Lactate dehydrogenase activity was not different between the groups, but could identify immediate functioning grafts within the F group. In conclusion, alphaGST levels correlated strongly with WIT and were also able to distinguish NF from F grafts. alphaGST can adequately predict the functional outcome of NHB donor grafts before transplantation; levels of alphaGST can be used to define reliable safety margins for viability. Therefore, MP is useful in evaluating the viability of NHB donor kidneys, and the parameters discussed will help to select nonviable grafts from this valuable pool of kidneys for transplantation.

New tetrahydroimidazo[4,5,1-jk][1,4]-benzodiazepin-2(1H)-one and -thione derivatives are potent inhibitors of human immunodeficiency virus type 1 replication and are synergistic with 2',3'-dideoxynucleoside analogs.

Tetrahydro-imidazo[4,5,1-jk][1,4]-benzodiazepin-2(1H)-one and -thione (TIBO) derivatives were shown to specifically block human immunodeficiency virus type 1 (HIV-1) replication through a unique interaction with the HIV-1 reverse transcriptase (RT). Through further modification of the lead compounds and structure-activity relationship analysis several new TIBO derivatives that show high potency, selectivity, and specificity against HIV-1 have been obtained. A new TIBO derivative, R86183, inhibits the replication of HIV-1, but not HIV-2, in a variety of CD4+ T-cell lines and peripheral blood lymphocytes, at a concentration of 0.3 to 30 nM, which is at least 4 orders of magnitude lower than the 50% cytotoxic concentration. Whereas an HIV-1 strain containing the Leu-100-->Ile mutation in the RT gene is about 400-fold less susceptible, R86183 still inhibits the replication of an HIV-1 strain containing the Tyr-181-->Cys RT mutation by 50% at a concentration of 130 nM. R86183 inhibits the poly(C).oligo(dG)12-18-directed HIV-1 RT reaction by 50% at a concentration of 57 nM. The antiviral activity of 22 TIBO derivatives in cell culture correlated well with their activity against HIV-1 RT. No such correlation was found for their cytotoxicity. The combination of R86183 with either zidovudine or didanosine resulted in a synergistic inhibition of HIV-1 (strain IIIB) replication. Combination of R86183 with the protease inhibitor Ro31-8959 was found to be additive. Also described is a dilution protocol circumventing overestimation and underestimation of antiviral activity due to adherence to plastic surfaces.

Is increased ammonia liberation after bleeding in the digestive tract the consequence of complete absence of isoleucine in hemoglobin? A study in pigs.

A variable protein-induced toxicity has been reported in liver disease. The aim of this study was to establish the cause of increased ammonia liberation in the gut after intraluminal bleeding. Therefore, blood was sampled from catheterized piglets [20 +/- 0.8 kg (means +/- S.E.); n = 10] to determine ammonia, urea and amino acid levels before and 1, 2, 3 and 6 hr after a standard pig meal (750 gm, 12% protein). After 1 week, this procedure was repeated after ingestion of an isonitrogenous amount of bovine whole blood (400 ml). In a second series of experiments, the same procedures were performed after ingestion of plasma, whole blood, erythrocytes and feed. Electromagnetically measured total intestinal, small and large bowel flow was not significantly influenced by the type of meal ingested. Portal ammonia release was significantly increased 2-fold after a blood meal, whereas intestinal glutamine utilization did not increase. Plasma urea levels were increased 200 to 300% after whole blood and erythrocytes, whereas after ingestion of plasma, urea levels were similar to values in controls. Glutamine utilization was not different among the various groups and occurred predominantly in the small bowel. In the fasted state, small bowel glutamine utilization paralleled ammonia production. In the fed state, this equimolar relationship could not be assessed because luminal glutamine utilization could not be determined. Isoleucine levels decreased to 25% of fasting levels. Analysis of blood constituents revealed a complete lack of isoleucine in the hemoglobin molecule. Net total alpha-amino-nitrogen absorption was doubled after a blood meal.(ABSTRACT TRUNCATED AT 250 WORDS)

gamma-Aminobutyric acid production in small and large intestine of normal and germ-free Wistar rats. Influence of food intake and intestinal flora.

In recent hypotheses concerning the pathogenesis of hepatic encephalopathy, gamma-aminobutyric acid (GABA) is claimed to be produced by the colonic flora, although enzymes necessary to generate GABA have been reported to be present in intestinal mucosa. In this study, using normal and germ-free Wistar rats, we determined GABA levels and amino-grams of arterial blood and of venous effluent from small and large bowel. The data indicate that large and small intestinal mucosa significantly contribute to GABA production. In the fasted state GABA concentrations are greater in the venous effluent of the small bowel than in the venous effluent of the large bowel. Feeding increases the arterioportal differences, and uptake in the small bowel is still significantly higher than in the large bowel. This process is not, or can only be to a minor degree, bacterially mediated, because GABA production in the gut both in the fed and fasted state is of similar magnitude in germ-free and normal animals. gamma-Aminobutyric acid release correlates significantly with glutamine uptake in the small bowel of fasted rats. Only a small fraction of the glutamine taken up is needed to account for GABA release, so that conclusions concerning which amino acids may serve as precursors of GABA cannot be drawn. Further studies are needed to delineate the metabolic pathways leading to GABA synthesis.

Sequential metabolic characteristics following portacaval shunt in rats.

A portacaval shunt (PCS) model is frequently employed to study phenomena inherent in portal-systemic shunting of splanchnic blood. In many species, a PCS induces hepatic insufficiency, accompanied by encephalopathy. Rats operated on with a 'nonsuture' technique tolerate a PCS better and exhibit no or only slight encephalopathy. Age and environment seem to have a large impact on the ability to tolerate a PCS. This explains the discrepancies between the results of different investigators and the varying time periods reported between the PCS operation and the optimal time for experiments. To characterize the PCS model (button technique) in rats with respect to metabolic parameters in our field of interest, we studied three groups of male Sprague-Dawley rats--non-operated (n = 12); sham-operated (n = 12) and PCS (n = 13)--for 4 weeks following surgery. Body weight in the PCS group decreased for 1 week after surgery and then increased at about the same rate as in the control groups. Plasma immunoreactive insulin, plasma immunoreactive glucagon (IRG) and aromatic amino acid concentrations were highest 1 week after surgery and tended to normalize in the next weeks. Plasma branched-chain amino acid (BCAA) concentrations were decreased in the 1st, 2nd and 3rd week after surgery, after which normalization occurred. These data demonstrate that after 3-4 weeks, male Sprague-Dawley rats start to recover from the metabolic disturbances caused by PCS with regard to the parameters measured. Therefore, experiments in this area, especially those relating to BCAA metabolism, should be carried out 2-3 weeks after the shunt operation (button technique).

Venus: new microwave measurements show no atmospheric water vapor.

Two sets of passive radio observations of Venus-measurements of the spectrum of the disk temperature near the 1-centimeter wavelength, and interferometric measurements of the planetary limb darkening at the 1.35-centimeter water vapor resonance-show no evidence of water vapor in the lower atmosphere of Venus. The upper limit of 2 x 10(-3) for the mixing ratio of water vapor is substantially less than the amounts derived from the Venera space probes (0.5 x 10(-2) to 2.5 x 10(-2)). This amount of water vapor cannot produce dense clouds, and it is doubtful that it may contribute significantly to a greenhouse effect.