Hematological Changes in Women and Infants Exposed to an AZT-Containing Regimen for Prevention of Mother-to-Child-Transmission of HIV in Tanzania

Introduction

Tanzanian guidelines for prevention of mother-to-child-transmission of HIV (PMTCT) recommend an antiretroviral combination regimen involving zidovudine (AZT) during pregnancy, single-dosed nevirapine at labor onset, AZT plus Lamivudine (3TC) during delivery, and AZT/3TC for 1–4 weeks postpartum. As drug toxicities are a relevant concern, we assessed hematological alterations in AZT-exposed women and their infants.

Methods and Materials

A cohort of HIV-positive women, either with AZT intake (n = 82, group 1) or without AZT intake (n = 62, group 2) for PMTCT during pregnancy, was established at Kyela District Hospital, Tanzania. The cohort also included the infants of group 1 with an in-utero AZT exposure ≥4 weeks, receiving AZT for 1 week postpartum (n = 41), and infants of group 2 without in-utero AZT exposure, receiving a prolonged 4-week AZT tail (n = 58). Complete blood counts were evaluated during pregnancy, birth, weeks 4–6 and 12.

Results

For women of group 1 with antenatal AZT intake, we found a statistically significant decrease in hemoglobin level, red blood cells, white blood cells, granulocytes, as well as an increase in red cell distribution width and platelet count. At delivery, the median red blood cell count was significantly lower and the median platelet count was significantly higher in women of group 1 compared to group 2. At birth, infants from group 1 showed a lower median hemoglobin level and granulocyte count and a higher frequency of anemia and granulocytopenia. At 4–6 weeks postpartum, the mean neutrophil granulocyte count was significantly lower and neutropenia was significantly more frequent in infants of group 2.

Conclusions

AZT exposure during pregnancy as well as after birth resulted in significant hematological alterations for women and their newborns, although these changes were mostly mild and transient in nature. Research involving larger cohorts is needed to further analyze the impact of AZT-containing regimens on maternal and infant health.     

Effects of zinc deficiency and supplementation on some hematologic parameters of rats performing acute swimming exercise

The aim of the study was to investigate how zinc deficiency and supplementation effect some hematologic parameters of rats performing swimming exercise. Forty adult male Spraque-Dawley rats were divided into 4 groups, zinc deficient swimming group (Group 1, n=10, zinc supplemented swimming group (Group 2, n=10), swimming control group (Group 3, n=10), and control group (Group 4, n=10). Blood samples were taken by decapitation and analyzed for the determination of erythrocyte, hemoglobin level, hematocrit, leukocyte, lymphocyte, platelet count and plasma zinc level at the end of the 4 week experiment. Erythrocyte count of group 1 was the lowest whereas erythrocyte count in group 3 was significantly lower than that in group 2 and 4 (p<0.05). Hemoglobin level of group 1 was significantly lower than that of groups 2 and 4 (p<0.05). Hematocrit was significantly lower in both group 1 and group 3 than both groups 2 and 4 (p<0.05). Lymphocyte count in group 2 was significantly higher than in all other groups (p<0.05). Platelet counts in group 2 was significantly lower than in all other groups (p<0.05). Our findings suggest that zinc deficiency effects the hematologic parameters mentioned negatively whereas zinc supplementation has a positive influence.     

早期脓毒血症患者Gelsolin 与HS-1 蛋白检测及其意义

要目的：探讨脓毒血症患者血小板骨架蛋白Gelsolin和造血系细胞特异性蛋白(HS-1)及其和凝血功能的关系。方法：纳入脓毒 血症患者30 例和对照组健康人群30 例,用双抗体夹心法测定血浆中血小板骨架蛋白,用酶联免疫法测定血清中HS-1 蛋白含 量,采用免疫荧光观察血小板Gelsolin 蛋白的表达,分析Gelsolin、HS-1、血小板计数和凝血功能(PT、APTT)之间的关系。结果：对 照组Gelsolin 主要位于血小板胞浆内,观察组包浆内外及间质内均可见。观察组血小板骨架蛋白Gelsolin、HS-1 水平明显高于对 照组,差异均存在统计学意义(P<0.05)。观察组血小板计数、PT、APTT 水平均低于对照组,差异存在统计学意义(P <0.05)。Galsolin 和血小板计数呈负相关关系,相关系数r = -0.76 (P <0.05),HS-1和血小板计数间呈负相关关系相关系数r = - 0.69 (P<0.05)。结论： 早期脓毒血症患者血小板骨架蛋白Gelsolin 和HS-1表达水平明显升高,与脓毒血症患者血小板大量破坏有关。     

The effect of partial removal of yolk on the chilling sensitivity of zebrafish (Danio rerio) embryos

In a group of 39 patients with ischemic heart and valvular disease (January 1997 to May 1998), three platelet collection methods were compared in terms of safety and effectiveness. The methods were: (i) collection of autologous platelets over several weeks and freezing them for storage until surgery (frozen group, 12 patients); (ii) collection of autologous platelets on the day before surgery and preserving them without freezing (fresh group, 8 patients); and (iii) collection of autologous platelets intraoperatively (intraoperative group, 9 patients). Ten patients served as controls (control group). Blood pressure was not significantly affected by platelet collection in the frozen and fresh groups, but both systolic (P < 0.01) and diastolic blood pressure (P < 0.05) decreased significantly after collecting platelets in the intraoperative group. Similarly, heart rate was unaffected by platelet collection in the frozen and fresh groups, while it increased significantly in the intraoperative group (P < 0.05). Blood loss after 24 h was significantly smaller in the fresh group than in the frozen group (P < 0.05). Total blood transfusion volume was significantly smaller in the frozen and fresh groups than in the intraoperative and control groups (P < 0.05). Bleeding time 2 h postoperatively, when administration of autologous platelets had been completed, was reduced compared with immediately postoperative values in all three groups receiving autologous platelets (P < 0.05). However, only the frozen and fresh groups showed a significantly shorter bleeding time than the control group (P < 0.05). In all three groups receiving autologous platelets, the platelet count was significantly increased after administration of autologous platelets, but only the fresh group had a platelet count that was significantly greater than the control group (P < 0.05). From these results we conclude that the frozen and fresh groups received safer treatment than the intraoperative group. Although hemostasis improved after all three regimes of autologous platelet transfusion, only the frozen and fresh groups had a reduced need for allogeneic blood transfusion compared with the control group. For this reason we conclude that the frozen and fresh groups were also superior to the intraoperative group in terms of effectiveness. However, the recovery of platelets after frozen storage was low, and to obtain a good effect with the freezing method it is necessary to collect and store large volumes of platelets. In terms of simplicity, safety, and efficacy, the fresh method seems to be the preferred technique.     

环孢素A对难治性免疫性血小板减少性紫癜的辅助治疗

目的 探讨环孢素A辅助治疗难治性免疫性血小板减少性紫癜（ITP）的临床疗效及对患者血小板计数和细胞因子的影响。方法 选择2013年1月至2016年12月期间浙江省金华市人民医院收治的难治性ITP患者78例。按照随机数字表分为观察组39例与对照组39例。对照组患者给予利妥昔单抗治疗,观察组在对照组基础上结合环孢素A辅助治疗,两组患者疗程均为3个月。比较两组患者的疗效,治疗前后血小板计数变化,血小板恢复正常时间,治疗前后细胞因子变化及不良反应发生情况。结果 观察组患者治疗总有效率（92.31%）高于对照组（69.23%）,差异有统计学意义（χ2=6.6857,P0.05）。结论 环孢素A辅助治疗难治性ITP患者疗效显著,且可增加患者血小板数量,降低IFN-γ水平,增加IL-4、IL-10水平,提高患者免疫功能。     

Intravenous immune globulin use in patients with human immunodeficiency virus-related thrombocytopenia who require dental extraction.

Five patients with human immunodeficiency virus (HIV)-related immune thrombocytopenia who were undergoing dental extraction were treated with intravenous immune globulin (IVIG). All patients received IVIG, 1 gram per kg, the day before the dental extraction and again the day of the dental extraction. Four patients had a previous history of minor clinical bleeding. The median baseline platelet count before extraction was 20 X 10(9) per liter (range 13 to 44). The median peak platelet count was 100 X 10(9) per liter (range 56 to 528) following infusion. This peak response was achieved by day 2 in 3 patients and by days 5 and 7 in 1 patient each. No patients had complications or toxicity from the infusions or perioperative bleeding. No patients required blood product transfusions for the surgical procedure. In conclusion, IVIG infusion should be considered in patients with HIV-related immune thrombocytopenia requiring surgical procedures when a prompt rise in platelet count is desired.     

The role of cortisol in the peripheral granulocyte response to insulin-induced hypoglycaemia in man

Peripheral blood leukocyte counts and plasma hormonal changes in response to acute insulin-induced hypoglycaemia were examined in 16 patients undergoing assessment of pituitary function. Eight subjects had a normal cortisol secretory response (Group 1), and 8 patients had definite hypopituitarism in whom the cortisol responses were deficient or absent (Group 2). An equivalent degree of hypoglycaemia was achieved in both groups. In Group 1a biphasic rise in leukocyte count occurred following hypoglycaemia, with an early rise in lymphocytes at 15 minutes after the acute hypoglycaemic reaction, and a later rise in granulocytes. A similar rise in lymphocytes was observed in Group 2, but the rise in the granulocyte count was attenuated, increasing from a basal value of 3.6 +/- 0.6 x 10(9) cells/L to a peak of 7.4 +/- 1.1 x 10(9) cells/L, compared with a peak of 11.7 +/- 1.2 x 10(9) cells/L in Group 1 (P less than 0.05). The usual increment in plasma cortisol in response to hypoglycaemia occurred in Group 1, but plasma cortisol did not rise in Group 2. A correlation was observed between the magnitude of the granulocyte rise and the increment in plasma cortisol in individual subjects (r = 0.64, P less than 0.02). This suggests that the rise in peripheral granulocytes following insulin-induced hypoglycaemia in man is mediated by cortisol released from the adrenal gland, following activation of the hypothalamic-pituitary-adrenal axis.     

Platelet Turnover in Stable Coronary Artery Disease – Influence of Thrombopoietin and Low-Grade Inflammation

Background

Newly formed platelets are associated with increased aggregation and adverse outcomes in patients with coronary artery disease (CAD). The mechanisms involved in the regulation of platelet turnover in patients with CAD are largely unknown.

Aim

To investigate associations between platelet turnover parameters, thrombopoietin and markers of low-grade inflammation in patients with stable CAD. Furthermore, to explore the relationship between platelet turnover parameters and type 2 diabetes, prior myocardial infarction, smoking, age, gender and renal insufficiency.

Methods

We studied 581 stable CAD patients. Platelet turnover parameters (immature platelet fraction, immature platelet count, mean platelet volume, platelet distribution width and platelet large cell-ratio) were determined using automated flow cytometry (Sysmex XE-2100). Furthermore, we measured thrombopoietin and evaluated low-grade inflammation by measurement of high-sensitive CRP and interleukin-6.

Results

We found strong associations between the immature platelet fraction, immature platelet count, mean platelet volume, platelet distribution width and platelet large cell ratio (r = 0.61–0.99, p<0.0001). Thrombopoietin levels were inversely related to all of the platelet turnover parameters (r = −0.17–−0.25, p<0.0001). Moreover, thrombopoietin levels were significantly increased in patients with diabetes (p = 0.03) and in smokers (p = 0.003). Low-grade inflammation evaluated by high-sensitive CRP correlated significantly, yet weakly, with immature platelet count (r = 0.10, p = 0.03) and thrombopoietin (r = 0.16, p<0.001). Also interleukin-6 correlated with thrombopoietin (r = 0.10, p = 0.02).

Conclusion

In stable CAD patients, thrombopoietin was inversely associated with platelet turnover parameters. Furthermore, thrombopoietin levels were increased in patients with diabetes and in smokers. However, low-grade inflammation did not seem to have a substantial impact on platelet turnover parameters.     

Characterization of GBV-C infection in HIV-1 infected patients

BACKGROUND: GB virus C, a positive-stranded RNA virus, is classified in the family Flaviviridae. It is currently believed that persistent infection occurs in 25-50% of infected individuals, however, it still remains an "orphan" virus in search of a role in human pathology. Molecular epidemiological studies have demonstrated that GBV-C infection is present in about 1-1.4% of the healthy population in developed countries, that it shares routes of transmission with HIV and HCV and that the prevalence of GBV-C in these populations is higher than in blood donors. On the basis of the sequence variation among the isolates, GBV-C is classified into at least four major genotypes. Preliminary evidence has suggested that GBV-C is a lymphotropic virus that replicates mainly in the spleen and bone marrow. Recently, several reports have investigated the possible beneficial effect of GBV-C co-infection on HIV disease progression to AIDS, reduced mortality in HIV infected individuals and lower HIV viral loads, not leading to a definitive conclusion yet. AIM: To investigate the role of GBV virus C co-infection in two different subsets of HIV-infected patients, and to evaluate the prevalence of GBV-C genotypes in Northern Italy. METHODS: A total of 86 HIV positive patients were examined for GBV-C viremia (years after HIV sera conversion: 12 +/- 5). Control population (Group A): 46 patients (mean age 42 years) with <200CD4/ml during the observation period. Longterm non progressor population (Group B): 40 patients, (mean age 40 years) with >500 CD4/ml for at least 8 years and never treated with HAART. After extraction of viral RNA from plasma samples, amplification of a highly conserved region of 5'UTR was performed by nested RT-PCR. All positive samples were genotyped by sequencing, alignment with published sequences and phylogenetic analysis. CD4 cell count, HIV plasma levels were also evaluated. RESULTS: 9 out of 46 (19.56%) in Group A and 15 out of 40 (37.5%) in Group B had detectable GBV-C viremia (p=0.064, OR 2.47, percent confidence interval 0.94 to 6.51). No statistical difference was observed when disease stage was evaluated between the two groups. In Group B, after regression analysis for CD4 cell count decrease over the period observed, no significant difference was detected between GBV-C positive and negative patients. No significant difference was observed in Group B in HIV viremia and CD4 cell count at time of GBV-C detection between GBV-C infected patients and GBV-C negative patients. All Italian patients were genotype 2, the only African patient carried GBV-C genotype 1. CONCLUSIONS: Although previous results suggest that GBV-C virus may be a favorable marker for long term non progression of HIV disease, whether it plays a direct anti-HIV role or just takes advantage of non progessors' higher CD4 cell count to replicate more efficiently, still remains to be answered. Follow up of untreated patients and further evaluation of virological interactions, between the viruses and the host immune system, will be helpful to shed some light on these observations, offering new prognostic and eventually therapeutical tools for the management of HIV patients.     

ITP in pregnancy: use of the bleeding time as an indicator for treatment

ITP is a relatively common disorder seen in pregnancy. Current recommendations for management of patient with ITP recommend maintaining the platelet count above 50 x 10(9)/L and the bleeding time less than 20 min. It has been well documented that the bleeding time in ITP is disproportionately shortened in many patients relative to the platelet count. We present a prospective study of 24 ITP patients in whom the bleeding time was used as an indicator for therapeutic intervention in pregnancy. Indications for therapy with prednisone and/or intravenous gammaglobulin were the following: significant clinical hemorrhage due to thrombocytopenia; bleeding time of greater than 20 min at the baseline platelet count; for normalization of hemostasis prior to delivery or surgical procedure. Caesarean section was performed only in cases in which there were obstetrical indications for this mode of delivery or when the fetal platelet count (obtained by fetal scalp vein sample) was less than 50 x 10(9)/L. Of 24 patients with ITP, eight had significant thrombocytopenia (platelet count less than 50 x 10(9)/L) throughout pregnancy. Only two patients required prolonged prednisone therapy. Both suffered side effects of chronic prednisone administration. Four patients were treated with prednisone for a short course (10-14 days) at term to improve hemostasis for delivery. One patient was treated with intravenous gammaglobulin at term in an effort to prevent severe neonatal thrombocytopenia. Seven patients required caesarean section; the remaining 17 patients underwent vaginal delivery. Only one minor bleeding complication was seen - a small wound hematoma post caesarean section. In summary, using the bleeding time as an indicator for therapeutic intervention, treatment of ITP in pregnancy can be minimized. Thus, therapy related toxicity can be avoided.     

"Anti-platelet antibodies" in HIV infected haemophiliacs.

We have studied anti platelet antibodies and circulating immunocomplexes in 16 haemophiliacs with mild thrombocytopenia eight of which were infected by human immunodeficiency virus (HIV). No difference in platelet count was observed between HIV+ (143 +/- 31 x 10(9)/l) and HIV- patients (148 +/- 30 x 10(9)/l). On the contrary, HIV+ haemophiliacs had serum platelet bindable IgG (SPBIgG), normal platelet associated IgG (PAIgG), high serum IgG and circulating immunocomplexes (CIC). Considering all 16 patients serum IgG correlated with CIC (r = 0.7 p less than 0.01) and SPBIgG (r = 0.6 p less than 0.01) respectively. We obtained also a positive correlation between serum CIC and SPBIgG (r = 0.51 p less than 0.05). Immunoblotting of patients' sera showed no specific binding to target platelet antigens. In conclusion there is no evidence of HIV related immune thrombocytopenia in our haemophiliacs but the study confirms the appearance of immunocomplexes in the HIV+ subjects.     

不同CRRT治疗时机对脓毒症合并急性肾功能不全患者疗效及预后的影响

目的:探讨不同持续性肾脏替代治疗(CRRT)治疗时机对脓毒症合并急性肾功能不全患者的临床疗效及预后的影响。方法:将我院ICU收治的60例脓毒症合并急性肾功能不全患者,按照CRRT治疗时机分为早期组(1-2期,n=30)和晚期组(3期,n=30)。比较两组患者治疗前后不同时点平均动脉压(MAP)、白细胞(WBC)计数、血红蛋白(HB)、血小板(PLT)计数、急性生理学与慢性健康状况(APACHE)Ⅱ评分等临床资料的变化,机械通气时间,肾功能恢复率及28 d病死率等。结果:与早期组比较,晚期组治疗后WBC计数明显升高(P0.05)。治疗后12 h、24 h、72 h,早期组ACHEⅡ评分较晚期组显著降低(P0.05)。与晚期组比较,早期组机械通气时间显著缩短,肾功能恢复明显升高,28d内病死率也明显降低(P0.05)。结论:脓毒症合并急性肾功能不全患者应早期启动CRRT治疗,最佳介入时间是KDIGO-AKI 3期之前,有助于改善患者预后。     

Differential Adipose Tissue Gene Expression Profiles in Abacavir Treated Patients That May Contribute to the Understanding of Cardiovascular Risk: A Microarray Study

Objective

To compare changes in gene expression by microarray from subcutaneous adipose tissue from HIV treatment naïve patients treated with efavirenz based regimens containing abacavir (ABC), tenofovir (TDF) or zidovidine (AZT).

Design

Subcutaneous fat biopsies were obtained before, at 6- and 18–24-months after treatment, and from HIV negative controls. Groups were age, ethnicity, weight, biochemical profile, and pre-treatment CD4 count matched. Microarray data was generated using the Agilent Whole Human Genome Microarray. Identification of differentially expressed genes and genomic response pathways was performed using limma and gene set enrichment analysis.

Results

There were significant divergences between ABC and the other two groups 6 months after treatment in genes controlling cell adhesion and environmental information processing, with some convergence at 18–24 months. Compared to controls the ABC group, but not AZT or TDF showed enrichment of genes controlling adherence junction, at 6 months and 18–24 months (adjusted p<0.05) and focal adhesions and tight junction at 6 months (p<0.5). Genes controlling leukocyte transendothelial migration (p<0.05) and ECM-receptor interactions (p = 0.04) were over-expressed in ABC compared to TDF and AZT at 6 months but not at 18–24 months. Enrichment of pathways and individual genes controlling cell adhesion and environmental information processing were specifically dysregulated in the ABC group in comparison with other treatments. There was little difference between AZT and TDF.

Conclusion

After initiating treatment, there is divergence in the expression of genes controlling cell adhesion and environmental information processing between ABC and both TDF and AZT in subcutaneous adipose tissue. If similar changes are also taking place in other tissues including the coronary vasculature they may contribute to the increased risk of cardiovascular events reported in patients recently started on abacavir-containing regimens.     

Effects of taprostene, a chemically stable prostacyclin analogue, in patients with ischaemic peripheral vascular disease: a placebo controlled double-blind trial

Thirty patients with ischaemic peripheral vascular disease and intermittent claudication were randomly allocated to receive either placebo or taprostene, a chemically stable prostacyclin analogue, intravenously at a rate of 25 ng/kg/min for 6 hours daily on 5 consecutive days. Taprostene produced a significant (p less than 0.05) increase in absolute walking time compared to placebo on one day after infusion and at 1, 4 and 8 weeks (14% vs 2.8%) later. Taprostene also produced a significant (p less than 0.05) increase in the pain-free walking time compared to placebo in the follow-up period (8 weeks after infusion: 23% vs 3.8%). During the infusion period systolic and diastolic blood pressure decreased (p less than 0.05) and heart rate was accelerated (p less than 0.05) in the taprostene treated group whereas no change was monitored in the placebo group. The ankle/brachial Doppler index was unaffected by taprostene. The platelet half-life was significantly (p less than 0.05) prolonged following taprostene-infusion (72.6 +/- 9.35 vs 77.9 +/- 7.44 hours). However, no change on platelet half-life was found in the placebo group (p less than 0.05). Various measures of platelet function parameters followed in vitro (ADP-induced aggregation, platelet sensitivity to PGI2, PGE1, PGD1 and taprostene, concentrations of platelet factor 4 and beta-thromboglobulin) showed no change with taprostene. Measures of circulating platelet aggregates and endothelial cells count showed no changes during the 2 months follow-up period too. It is assumed that taprostene may be of clinical benefit in patients with ischaemic peripheral vascular disease. However, future investigations have to be carried out to assess the optimal dose regime.     

Study on mechanisms of a haemostatic effect of 1 deamino-8-D-arginine vasopressin (desmopressin) in uraemic patients.

The effect of 1 deamino-8-D-arginine vasopressin (DDAVP) on blood platelet serotonin and some parameters of haemostasis was investigated. DDAVP was administered intravenously in a dose of 0.4 micrograms/kg BW to 16 uraemic patients maintained on chronic haemodialysis in a double-blind crossover study compared with placebo. The bleeding time was significantly shortened after DDAVP administration from 21.3 +/- 8 minutes to 11.5 +/- 6 minutes (p less than 0.001). VIII: Ag increased from 239.1 +/- 94% to 473 +/- 293% (p less than 0.01). Euglobulin lysis time was shortened from 238 +/- 101 to 148 +/- 84 minutes (p less than 0.005). The platelet serotonin level was significantly reduced from 532 +/- 141 to 366 +/- 88 ng/10(9) platelets (p less than 0.02). There were no changes in haematocrit, platelet count, VIII: C levels and blood serotonin concentrations after DDAVP administration. In placebo group there were no changes in all investigated parameters. Our data indicate that DDAVP shortens prolonged bleeding time in uraemic probably by means of the serotonergic mechanism. Further studies are needed to confirm this suggestion.     

The effects of parturition and peripartum complications on the peritoneal fluid composition of mares

Abnormalities in peritoneal fluid are diagnostically useful for managing equine colic; however, their significance in post-dystocia mares is not known. This study was to determine what changes, if any, occurred following obstetrical manipulations. Peritoneal fluid samples were collected from 2 groups of foaling mares to establish control values, and from a third group that had developed clinical abnormalities (CAb,n = 14) or had made an uneventful recovery (CN,n = 36) following fetal extraction. In Group 1 mares, samples were collected before and after induced parturitions (n = 7), and although the total nucleated cell count was increased (P < 0.02) the median values for peritoneal fluid composition remained within the normal reference range. In Group 2 mares, samples were collected after unassisted foalings (n = 10) on postpartum Days 1, 3, 5 and 7, and the peritoneal fluid values remained within the normal reference range. In the Group 3 (CN) mares neither assisted vaginal delivery or fetotomy caused median peritoneal fluid values to rise above the normal reference range. Although remaining within normal limits, the total nucleated cell count was increased (P < 0.01) on Day 2. The median peritoneal fluid total protein value for Group 3 (CAb) mares was greater than the median value for Group 3 (CN) mares on Day 1 (P < 0.05) and Day 2 (P < 0.001). The peritoneal fluid total nucleated cell count in Group 3 (CAb) mares with a uterine tear, vaginal laceration involving the peritoneal cavity, or a ruptured mesocolon was greater than in Group 3 (CN) mares (P < 0.02). The median peritoneal fluid percentage of neutrophils value for Group 3 (CAb) mares was higher than for Group 3 (CN) mares on both Days 1 and 2 (P < 0.02). Elevation of a single peritoneal fluid value in the postpartum mare may be incidental; however, increases in 2 or more of these (total protein > 3.0 g/dl; total nucleated cell count > 15,000 cells/microl; percentage of neutrophils > 80%) is clinically significant.     

Fetal and neonatal exposure to AZT and low-protein diet affects glucose homeostasis: a model with implications for AIDS prevention

Zidovudine (AZT) lowers the perinatal transmission of HIV but can impair mitochondrial function by depleting mitochondrial DNA (mtDNA). AZT therapy and perinatal nutritional deprivation affect the body fat distribution, which influences glucose tolerance. We sought to model intrauterine exposure to AZT in humans to determine whether it interacts with low-protein diet (LPD) to impact on birth weight and glucose homeostasis in the offspring. Pregnant dams and their offspring were given AZT, an LPD, or AZT and an LPD (LPD + AZT). AZT reduced mtDNA copy number in liver and birth weight in the offspring and increased their fasting glucose and insulin (P = 0.021, 0.03, 0.001, and 0.011 respectively) at 6-8 wk of age. LPD decreased litter size and birth weight (P = 0.01 and 0.012). In the LPD + AZT group, birth weight and litter size were reduced compared with untreated controls, and fasting blood glucose and insulin were raised. There was a significant interaction between LPD and AZT on fasting insulin levels (P = 0.025). Islet size was not significantly affected, but the mean beta-cell area/islet was reduced in the LPD + AZT group compared with controls (P < 0.05). Early exposure to AZT interacts with LPD to impair fetal development in this model. This combination appeared to impair the supply of insulin and, hence, glucose homeostasis, perhaps as a result of impaired mitochondrial function. Although it is not certain that this can be extrapolated to humans, maternal nutritional deprivation combined with AIDS therapy could influence both birth weight and onset of diabetes.     

Presence of factors that activate platelet aggregation in mitral stenotic patients' plasma

BACKGROUND: Although the association between mitral stenosis (MS) and increased coagulation activity is well recognized, it is unclear whether enhanced coagulation remains localized in the left atrium or whether this represents a systemic problem. To assess systemic coagulation parameters and changes in platelet aggregation, we measured fibrinogen levels and performed in vitro platelet function tests in plasma obtained from mitral stenotic patients' and from healthy control subjects' peripheral venous blood. METHODS: Sixteen newly diagnosed patients with rheumatic MS (Group P) and 16 healthy subjects (Group N) were enrolled in the study. Platelet-equalized plasma samples were evaluated to determine in vitro platelet function, using adenosine diphosphate (ADP), collagen and epinephrine in an automated aggregometer. In vitro platelet function tests in group N were performed twice, with and without plasma obtained from group P. RESULTS: There were no significant differences between the groups with respect to demographic variables. Peripheral venous fibrinogen levels in Group P were not significantly different from those in Group N. Adenosine diphosphate, epinephrine and collagen-induced platelet aggregation ratios were significantly higher in Group P than in Group N. When plasma obtained from Group P was added to Group N subjects' platelets, ADP and collagen-induced, but not epinephrine-induced, aggregation ratios were significantly increased compared to baseline levels in Group N. CONCLUSION: Platelet aggregation is increased in patients with MS, while fibrinogen levels remain similar to controls. We conclude that mitral stenotic patients exhibit increased systemic coagulation activity and that plasma extracted from these patients may contain some transferable factors that activate platelet aggregation.     

Transient Dissociation between Infectious HIV-1 Titer and Viral RNA during the Early Phase of AZT Treatment

The short-term kinetics of infectious HIV titers, HIV copy numbers and p24-antigen during the first 28 days of AZT monotherapy were evaluated. In three of four patients, infectious HIV was culturable and infectious titers rose 2- and 4-fold compared to baseline values. This increase was neither associated with mutations conferring resistance to AZT nor a switch from NSI to SI phenotypes. Two patients showed an increase of plasma infectivity associated with a reduction of HIV copies and p24-antigen. We conclude that transient dissociations of plasma infectivity and HIV copy numbers occur during early AZT monotherapy.