QUALITY OF LIFE OF PEOPLE LIVING WITH HIV: IDENTIFICATION OF THE DETERMINANTS.

The high prevalence rate of HIV worldwide, including the Republic of Kazakhstan (the RK), in large cities in particular, underlies the tremendous significance of this medical condition for society, economy, demography and healthcare. The objective of this study was to identify the most important determinants of quality of life (QL) of people living with HIV in a large city. The study was carried out in 3 stages. At the first stage, the HIV morbidity and PLH mortality figures over the period of 10 years (2005-2014) in a metropolis (the city of Astana) were analyzed in comparison to the general ones for the Republic. At the second stage, social and demographic charecteristics of the respondents, as well as characretistics of their HIV status and medical activity were received with the use of a 49 question enquiry that we developed. At the third stage, the QL of persons infected with HIV was studied. The general SF-36 questionnaire was the main tool of tracking the QL changes. The sample consisted of 170 respondents selected based random quota sampling. Comparison of the QL levels by gender showed that across the majority of scales of the physical health componentand in general across the physical health component, the QL levels for males were higher than for females. At the same time as for the psychological health component figures, general psychological health component and the majority of scales were higher for females, however, the differences across all the scales were statistically non-significant (р>0.05). The QL figures were higher for individuals with secondary vocational and higher education, as well as for married ones. Comparison of the QL figures showed no interdependence between them and the period of time after HIV status was determined. Addictive substance consumption was identified to decrease the QL of people living with HIV. The study allowed us to identify the role of independent variables influencing the quality of life of people living with HIV in a large city.

Mechanistic differences of various AT1-receptor blockers in isolated vessels of different origin.

The functional inhibitory characteristics of the angiotensin II type 1 receptor blockers (ARB) candesartan; irbesartan; and losartan and its active metabolite EXP 3174 (EXP) were studied in rabbit aortic strips and rat portal vein preparations in vitro. Moreover, plasma-protein binding was determined, and the binding was high (>98. 5%) for all ARBs. These values were needed to relate the concentrations of the ARBs used in vitro to the nonprotein bound concentrations in clinical use. In both vascular preparations, candesartan caused a marked decrease in the maximal contractile response of the angiotensin II (Ang II) concentration-response curve. Losartan, EXP, and irbesartan caused a rightward parallel shift without any major effects on the maximal response to Ang II. The inhibitory effect of candesartan developed slowly (maximal effect after >30 minutes) and lasted >2 hours despite repeated washing of the vessels. The effect of losartan, irbesartan, and EXP had a faster onset, and most of the inhibitory effect disappeared after washing. The duration of the inhibitory effects of the ARBs were not related to lipophilicity of the compounds. Cooling of the rat portal vein preparations to 4 degrees C before administration of candesartan prevented the persistent inhibition of Ang II response seen at 37 degrees C. For the other ARBs studied, the magnitude of inhibition and the speed of recovery of the Ang II response were independent of the incubation temperature before washing. In addition, when candesartan was given to conscious rats, the inhibitory effect on Ang II-induced blood pressure responses persisted during the 24-hour period despite nondetectable plasma concentrations of candesartan at 24 hours. It is concluded that functional inhibitory characteristics of candesartan differ from those of the other ARBs tested. At clinically relevant concentrations, candesartan is an insurmountable and long-lasting antagonist of the vascular contractile responses to Ang II.

Interaction between antidepressants and phosphoinositide signal transduction system in human platelets.

The present study was designed to evaluate the inhibitory effect of antidepressants on thrombin-induced phosphoinositide (PI) hydrolysis. Thrombin 5 units/ml induced a 100%-200% increase in platelet inositol phosphates (IPs) formation. This effect was inhibited in a dose-dependent manner by various heterocyclic antidepressants (IC50 40-170 mumol/L) The monoamine oxidase inhibitor, phenelzine, in concentrations up to 500 mumol/L, was devoid of inhibitory activity. The tricyclic antidepressants, (50 mumol/L) inhibited also thrombin-induced platelet aggregation by 32%-47%. No alteration in thrombin-induced IPs formation was detected in recovered major depressed patients (n = 15) maintained on clomipramine (75-150 mg/day). These results indicate that the heterocyclic antidepressants interfere with the thrombin-linked PI-signaling system. However, the inhibitory effect is achieved only in concentrations above the plasma concentrations obtained with therapeutic doses of these agents.

Decreased platelet peripheral-type benzodiazepine receptors in adolescent inpatients with repeated suicide attempts.

BACKGROUND: Peripheral-type benzodiazepine receptors (PBR) are responsible for mitochondrial cholesterol uptake, the rate limiting step of steroidiogenesis. They have been shown to be increased after acute stress, and decreased during exposure to chronic stressful conditions, and in patients with generalized anxiety disorder and post-traumatic stress disorder. In view of the proven connection between adolescent suicidal behavior and stress, we hypothesized that PBR may be decreased in the suicidal adolescent population. METHODS: We measured [3H] PK 11195 binding to platelet membrane in nine adolescent (age 13-20 years) inpatients with a history of at least three suicidal attempts and ten age-matched psychiatric inpatients with no history of suicide attempts. Suicidality was assessed with the Suicide Risk Scale (SRS), and symptom severity with the Beck Depression Inventory, State-Trait Anxiety Inventory (STAI), Overt Aggression Scale (OAS), and Impulsivity Scale (IS). RESULTS: Suicide Risk Scale scores were significantly higher in the suicidal group. The suicidal group showed a significant decrease in platelet PBR density (-35%) compared to the controls (p < 0.005). CONCLUSIONS: Our results of PBR depletion in adolescent suicide are in accordance with the findings in patients with generalized anxiety disorder and posttraumatic stress disorder and lend further support to the role of PBR in human response to chronic stress in adolescent suicide.

Cytokine production in drug-free and neuroleptic-treated schizophrenic patients.

A line of evidence indicates changes of the immune system in schizophrenic patients. We investigated the production of cytokines by peripheral blood mononuclear cells (PBMCs) in drug-free and neuroleptic-treated schizophrenic patients compared to healthy, normal controls. A significant reduction in interleukin (IL)-2 production was detected in untreated schizophrenic patients (-59.6%; p < .05) as well as in IL-3-like activity (IL-3-LA) production (-27.4%; p < .05) in treated patients compared to controls. No alteration was observed in IL-1 beta production. It seems that schizophrenia is associated with diminished IL-2 production, while neuroleptic treatment interferes with the capacity of immunocompetent cells to synthesize and/or release Il-3-LA. The alteration in cytokine production did not correlate with either the severity of the disorder or the serum prolactin levels.

Platelet imipramine binding and plasma cortisol levels in Israeli civilians during the Gulf War.

[3H] Imipramine binding to platelets and plasma cortisol levels were measured in nine Israeli civilians before, during, and after repeated missile attacks. Hamilton Anxiety Rating Scale (HARS), and Beck Depression Inventory (BDI) were similar before and during the war and decreased significantly after the war. A trend toward increase in platelet imipramine binding values was observed during the war when compared with the postwar values (19%; p = 0.056), and/or when compared with prewar values (26%; p = 0.063). However, one-way analysis of variance with repeated measures did not reveal a significant statistical difference [F (2,6) = p = 2.07; NS] among the three time points. A significant correlation was found between HARS score, but not BDI, and imipramine binding values in the prewar and postwar time points (r = 0.87; 0.71, respectively). Plasma cortisol levels did not alter significantly during the study period.

Alteration of platelet benzodiazepine receptors by stress of war.

Mitochondrial benzodiazepine receptors play a major role in steroidogenesis. The authors determined plasma cortisol levels, platelet levels of mitochondrial benzodiazepine receptors, and anxiety and depression scores in 11 civilians exposed to the Persian Gulf war. The density of mitochondrial benzodiazepine receptors was 22% and 15% lower before and during the war, respectively, than 4 weeks after the end of the war. Relief of stress led to an increase in receptors, which correlated with the improvement in anxiety but not mood.

Altered platelet peripheral-type benzodiazepine receptor in posttraumatic stress disorder.

Peripheral-type benzodiazephine receptors (PBR) are involved in steroidogenesis and are sensitive to stress. Reduced platelet PBR density has been demonstrated in generalized anxiety disorder (GAD), but not in obsessive-compulsive disorder (OCD). We extended this observation to another anxiety disorder, namely, posttraumatic stress disorder (PTSD). Eighteen post-Persian Gulf War PTSD patients and 17 age- and sex-matched controls were included in the study. All subjects were evaluated using the Structured Clinical Interview for DSM-III-R-Patient Version. The severity of symptoms was assessed using the DSM-III-R scale for PTSD, the Impact of Event Scale, the Beck Depression Inventory, and the State-Trait Anxiety Inventory. [3H]PK 11195 was used to label platelet PBR. All psychological parameters (except trait anxiety) were higher in PTSD patients compared to controls. Decreased platelet PBR density (-62%; p < .001) was observed in the PTSD patients compared to controls. The reduction in PBR observed in PTSD patients was in accordance with the findings in GAD patients, but differed from those obtained in OCD patients. It is possible that the receptoral downregulation is an adaptive response aimed at preventing chronic overproduction of glucocorticoids in hyperarousal states.

Platelet peripheral-type benzodiazepine in pregnancy and lactation.

The aim of the present study was to investigate the impact of hormonal changes during pregnancy and lactation on the expression of peripheral-type benzodiazepine receptors in platelet membranes. Platelet peripheral benzodiazepine receptor binding characteristics, Hamilton anxiety and depression rating Scores, and progesterone and prolactin (PRL) levels were evaluated during pregnancy and lactation in 17 pregnant women [first (n = 9) and third (n = 8) trimesters], 10 lactating women, and 8 nonpregnant women. A significant decrease (38-41%) in peripheral benzodiazepine receptor density was observed in women during the third trimester of pregnancy when compared to nonpregnant controls and women in their first trimester of pregnancy. The decrease is peripheral benzodiazepine receptors was parallel to the peak in progesterone and PRL secretion. The reduction in peripheral benzodiazepine receptor expression is hormone-dependent and may play a regulatory role geared to prevent pregnancy-related overactivity of the hypothalamic-pituitary-ovarian, hypothalamic-pituitary-adrenal, and hypothalamic-PRL axes.

Peripheral benzodiazepine receptors on platelets in chronic and detoxified alcoholics.

The effect of chronic alcoholism and detoxification treatment with disulfiram on platelet peripheral benzodiazepine receptors was studied in alcoholic males. Chronic consumption of alcohol did not alter the binding values for [3H]PK 11195, as compared to non-alcoholics. Treatment for 3 weeks with disulfiram resulted in a significant increase in the density of peripheral benzodiazepine receptors, with no alteration in the affinity of these sites to the ligand. These results might be relevant to the cellular and metabolic effects of disulfiram.

Pyruvate-kinase (PK) and creatine-kinase (CK) in normal pregnancy and its implication in genetic counseling of Duchenne muscular dystrophy (DMD).

The activities of pyruvate-kinase (PK) and creatine-kinase (CK) were measured in 50 normal pregnant women in both serum and amniotic fluid. Serum PK activity was found to be significantly higher in pregnant than in nonpregnant women, while serum CK did not differ significantly between the two population samples. In amniotic fluid, very little or no PK or CK activity was found. However, the mean PK activity in amniotic fluid obtained from women carrying male fetuses was significantly higher than in those carrying female fetuses. At the present time, it is concluded that if a woman at risk for having a son with Duchenne dystrophy is seeking genetic counseling when already pregnant her serum PK or CK should be compared with that of normal female pregnant controls. It is also suggested that determination of pyruvate-kinase in fetal blood might be used in addition to CK for prenatal diagnosis of Duchenne muscular dystrophy.

Prenatal diagnosis of neural tube defects: predictive value of AF-AFP in a low-risk population.

Amniotic fluid alpha-fetoprotein (AF-AFP) determinations were performed on 1,215 women who were at low risk for fetal neural tube defects and who were undergoing mid-trimester amniocentesis for cytogenetic indications, primarily age-related aneuploidy. Maternal sera obtained before amniocentesis and amniotic fluids were assayed in duplicate for alpha-fetoprotein by radioimmunoassay. Of the 1,215 low-risk women, eight (0.7%) had significant elevations of AF-AFP (greater than or equal to +5 SD). In none of the cases was the elevation associated with a fetal neural tube defect. Two cases with elevated AF-AFP were associated with chromosome aberrations; one with impending fetal demise; one with fetal blood contamination; and one case was due to a laboratory error. In one case, no source for the elevated AFP was found, and a normal infant was delivered at term. In the final two cases, the cause of the elevated AF-AFP was a fetal abdominal wall defect (one gastroschisis and one omphalocele). The predictive value of an elevated AFP varies with the population screened, and is reduced by routine ultrasonography before amniocentesis, which at least identifies anencephaly. In a low-risk population, an elevated AF-AFP is most often not associated with a fetal neural tube defect. Because of the low predictive value and the nonspecificity of AF-AFP, genetic counselors should reconsider the recommendation of routine AF-AFP in low-risk maternal populations.

Low material serum alpha-fetoprotein levels and congenital diaphragmatic defects.

We report on 2 cases of fetal congenital diaphragmatic defects with normal chromosomes among 105 patients referred for evaluation for low maternal serum alpha-fetoprotein (MSAFP) levels. The mechanism for this striking association is not clear. The association of low MSAFP levels and congenital diaphragmatic defects may have importance for MSAFP screening programs.

Rh isoimmunization related to amniocentesis.

We report on the incidence of Rh isoimmunization after genetic amniocentesis at our institution. In 115 Rh negative women who underwent amniocentesis and subsequently delivered Rh positive infants, there were 4 (3.4%) sensitizations before birth. This was significantly greater than the 1.5% rate of gestational sensitization found in pooled populations of women who did not undergo amniocentesis. We also noted a significant increase in the number of sensitizations that occurred before 28 weeks. The results were consistent with those of previous studies of this issue, and are discussed in relation to current policies for managing Rh negative women who have second trimester amniocentesis.

Painful ejaculation associated with antidepressants in four patients.

BACKGROUND: Painful ejaculation associated with tricyclic antidepressants is rarely reported in the medical literature. METHOD: Painful ejaculation following the administration of imipramine and clomipramine is described in four patients. RESULTS: The phenomenon occurred in all patients during the first 3 weeks of treatment and disappeared within several days when the tricyclic dosage was reduced or the medication was withdrawn. CONCLUSION: Painful ejaculation was apparently evoked by tricyclic antidepressant administration. Clinicians should be aware of this underreported side effect.

Meconium staining of amniotic fluid at midtrimester amniocentesis.

Meconium-stained fluid was found in six of the first 234 amniocenteses performed at the University of Washington Prenatal Diagnosis Center. The taps were done between 16 and 20 weeks from the last menstrual period. Although in each case there was a factor that could have produced fetal distress, in no instance did intrauterine demise occur. All the pregnancies have terminated in the births of healthy children. Therefore, we believe that meconium staining of midtrimester amniotic fluid may in fact reflect a transient episode of fetal compromise but that the finding cannot be used to prognosticate either impending fetal death or the presence of congenital malformations in the newborn.

Fetal puncture during midtrimester amniocentesis.

Four cases of fetal puncture during midtrimester amniocentesis are reported; in one instance the baby apparently sustained temporary neurologic damage. None of the lesions was detected at the initial neonatal examination. From our data and a review of the literature, we estimate that fetal puncture occurs in 1-3% of midtrimester amniotic taps. The implications of the accident are not clear. We conclude that midtrimester amniocentesis should not be considered a routine benigh procedure; and whenever the use of this diagnostic modality is being considered, the prospective parents should be informed of its hazards.

Azathioprine teratogenicity: review of the literature and case report.

An infant born with preaxial polydactyly to a mother taking azathioprine throughout pregnancy is described. Experimental studies in animals reveal a teratogenic role for azathioprine and its main metabolite, 6-mercaptopurine. The skeletal system appears to be the primary tissue target for such action of these drugs. Although no direct cause-effect relationship can be established from the single case presented, the similarity of this anomaly to experimental azathioprine teratogenesis suggests the necessity for further surveillance.

The premature breech: trial of labor or cesarean section?

Sixty-six premature breech deliveries were studied retrospectively. Forty-eight patients were permitted a trial of labor, 47 of whom ultimately delivered vaginally. Eighteen patients underwent cesarean section as soon as possible after their arrival at the delivery suite. When Apgar scores, perinatal mortality rates, cord prolapse, and entrapment of the aftercoming head are considered, cesarean section is probably the safer course of management for the patient with a footling breech infant, especially when the infant weighs 1500 g or less. However, the data indicate that a trial of labor can be safely undertaken in the presence of a premature frank or complete breech presentation.

Ultrasonic placental localization and bloody taps in midtrimester amniocentesis for prenatal genetic diagnosis.

In a prospective study, a small team of obstetricians concurrently performed midtrimester amniocentesis for prenatal genetic diagnosis on 32 patients after ultrasonic placental localization and on 50 patients without prior ultrasound. The use of ultrasound did not affect the red cell count in the fluid samples. Furthermore, the 2 patient groups had similar rates of grossly bloody taps. The average number of viable clones after culture was lower both after bloody taps and when ultrasound had been used, but in neither case was the difference significant. There were no postamniocentesis complications in the entire patient population. These results suggest that ultrasonic placental localization is not helpful in avoiding bloody taps, and that bloody taps may not necessarily be dangerous. Therefore, since the long-range hazards of in utero exposure to ultrasound may not yet be known, it would seem judicious to use preamniocentesis ultrasound selectively and on specific indication, rather than routinely.