Dose of desferrioxamine and evolution of HIV-1 infection in thalassaemic patients

To study the relationship between the dose of desferrioxamine (DFX) and the progression of the HIV-1 disease in thalassaemia major patients (TMP), 64 seropositive TMP patients were studied. Cumulative incidence of CDC stage IV was calculated using a non-parametric life-table method. The association with the mean daily dose of DFX was tested with a Cox proportional hazards model which was also used to adjust for confounding variables. The median of the mean daily dose of DFX over the seropositive period was 40 mg/kg (range 0-65 mg/kg). Age at seroconversion (P < 0.02) and splenectomy (P < 0.03) were found to be associated with the mean daily dose of DFX. 6.5 years after seroconversion, 11% of those who had been prescribed more than 40 mg/kg of DFX daily had entered stage IV versus 35% of those who had been prescribed a lower dose (P < 0.01). When the dose was taken as a continuous variable it was found that the rate of progression was significantly smaller in TMP receiving a higher dose (P < 0.002), even after adjusting for age and splenectomy (P < 0.02). Although it should be noted that these results were obtained in an observational study, possibly biased by a non-random allocation of the DFX dose, we believe that they are striking enough to support the claim that the role of DFX in the progression of HIV disease should be further evaluated.     

Pediatric HIV-1 infection

Although there is optimism that with the prospective identification and treatment of HIV-1-infected pregnant women the incidence of pediatric infection can be diminished, currently the number of HIV-1-infected children continues to rise. Improvements in early diagnosis provide the potential for early intervention, and the advent of more potent antiretroviral agents provides the hope of better treatment strategies to slow disease progression in HIV-1-infected children.     

Chemokine receptors in HIV-1 and SIV infection

Glucose-6-phosphatase (G6Pase) activity and the rate of glucose cycling are increased in islets from animal models of Type II (non-insulin-dependent) diabetes mellitus. Glucocorticoid treatment further stimulates these processes and inhibits glucose-induced insulin release. To determine whether these effects result from a direct action of glucocorticoids on the beta-cells, we used isolated islets. The islets were from transgenic mice overexpressing the glucocorticoid receptor in their beta-cells to increase the cells' sensitivity to glucocorticoid. Islets from transgenic and non-transgenic control mice utilized and oxidized the same amount of glucose. In contrast, islet G6Pase activity was 70 % higher, glucose cycling was increased threefold and insulin release was 30 % lower in islets from transgenic mice. Hepatic G6Pase activity was the same in transgenic and control mice. Dexamethasone administration increased G6Pase activity and glucose cycling and decreased insulin release in both transgenic and control mouse islets. We conclude that glucocorticoids stimulate islet G6Pase activity and glucose cycling by acting directly on the beta-cell. That activity may be linked to the inhibition of insulin release.     

Long-term survivors of HIV-1 infection

The clinical course and outcome of HIV-1 infection are highly variable. A full spectrum of pathology has been observed, from rapid progression to AIDS within months of HIV-1 seroconversion, to asymptomatic survival for more than a decade. This phenomenon probably reflects the multiphasic and multifactorial nature of the virus-host interactions. Obviously, interest in the extremes now recognized in HIV-1 disease progression is growing, with the hope that mechanisms of protection may be found.     

Clinical manifestations of human immunodeficiency virus infection in Haitian children

OBJECTIVE: This study was designed to describe the characteristics of HIV-1 infection in children in Haiti and to assess its impact on morbidity and mortality. BACKGROUND: Throughout the developing world the female-to-male ratio of HIV-1 infection approaches 1:1, leading to a tremendous burden of vertically transmitted HIV-1 infection. The frequency of transmission, progression of disease and AIDS-defining clinical illnesses are not as well-described in this setting as in the industrial world. METHODS: Children were identified as being HIV-1-seropositive from case findings among family members of individuals presenting for screening at the GHESKIO Centers in Port-au-Prince, Haiti. Children who were seronegative from the same population were also enrolled and both groups were followed at regular intervals. The clinical course and illnesses associated with HIV infection were documented. RESULTS: Rapid progression to symptomatic disease and death was seen and a battery of physical findings enabled a clinician over time to assign with high sensitivity and specificity the diagnosis of AIDS to a child. Although many findings are similar, the presentation of HIV-1 infection in Haiti differed in significant ways from observations in the industrial world. In particular signs of malnutrition, failure to thrive and tuberculosis were more common in the Haitian population. CONCLUSION: Pediatric HIV-1 infection in Haiti differs significantly from the illness in the industrial world. Early mortality poses a particular difficulty in diagnosing and ascribing mortality to HIV-1 infection.     

Global-local analysis in HIV-1 infection.

One hundred twenty-one HIV-seropositive (HIV+) individuals and 85 seronegative controls performed a divided-attention task that engaged automatic and controlled attentional processing. Reaction times (RTs) to global and local targets that varied in probability were measured in 5 conditions. A neutral condition where global and local targets were equally probable was included as baseline. Participants showed expected tradeoffs in RTs as a function of target-level probability, with longer RTs to less probable targets and shorter RTs to more probable targets. However, the HIV+ group showed significantly greater costs compared with controls. Results are consistent with previous findings that HIV+ individuals are selectively impaired on tasks of controlled attentional processing, particularly under conditions of divided attention. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Visual attention in HIV-1 infection.

27 nondemented HIV-seropositive men and 13 seronegative controls performed 2 versions of a spatial attention task that engaged either automatic or controlled attentional processing. Ss also performed a 3rd task requiring divided attention, which tested for potential deficits in attentional resources. HIV-seropositive symptomatic Ss were impaired on the automatic processing task, whereas asymptomatic Ss performed the task normally compared with controls. In contrast, no differences were observed among the 3 groups on the controlled attention task. However, both seropositive groups showed deficits on the divided attention task. These results suggest that deficits in selective attention are present early in the course of HIV-1 infection. The most prominent impairment is seen on tasks that are highly demanding of attentional resources, whereas deficits in automatic processing develop later in the disease process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clinical predictors of HIV-1 infection among preschool children in Dar es Salaam, Tanzania

Seroprevalence of HIV-1 infection was determined in children aged between eighteen months and five years, attending maternal and child health (MCH) clinics in Dar es Salaam, Tanzania. A total of 889 children were eligible for the study, however seven children could not be enrolled because their mothers/guardians absconded and blood could not be drawn from 21 children due to refusal of mothers/guardians and from another 12 children due to technical reasons. Therefore, the participation rate was 95.5%. Of the 849 children screened, 14 (1.65%) were found to have IgG anti HIV-1 antibodies in their sera. The main clinical features found in children with symptomatic HIV-1 disease were weight loss, generalized lymphadenopathy, recurrent fevers, and prolonged diarrhoea. The utility of clinical features suggestive of HIV-1 infection (according to CDC classification) in identifying HIV-1 infection in children was evaluated and found to have high sensitivity (100%), specificity (96.9%) and negative predictive value (100%), but a low positive predictive value (35%). Marked variations in progression to symptomatic phase were noted, whereby some relatively young children had progressed to symptomatic phase (CDC class P-2A), while some older children were still in the asymptomatic stage (CDC class P-1 C). None of the symptomatic HIV-1 infected children presented with neurological disease, severe opportunistic infections, or malignancies. Although reduced mid-upper arm circumference and weight-for-age were associated with HIV seropositivity, these clinical parameters had low positive predictive values compared to the CDC classification.     

Pre-existence and emergence of drug resistance in HIV-1 infection

Antiviral treatment of HIV-1 infection often fails because of the rapid emergence of resistant virus within weeks of the start of therapy. This raises the question of whether resistant viruses pre-exist in drug-naive patients or whether it is produced after the start of therapy. Here we compare the likelihood of pre-existence with the likelihood of production of resistant virus during therapy. We show that provided resistant virus pre-exists, then a stronger therapy may lead to a greater initial reduction of virus load, but will also cause a faster rise of resistant virus. In this case the total benefit of treatment is independent of the degree of inhibition of sensitive virus. If, on the other hand, resistant mutants do not pre-exist, then the emergence of resistance during treatment depends on the efficacy of the drug. If the drug is sufficiently potent to eradicate sensitive virus, then the probability that resistant mutants first appear during therapy is smaller than the probability that they existed before therapy. If the drug cannot eradicate the sensitive virus, then after sufficiently long time resistant mutants will appear. However, mutants that are unlikely to pre-exist may taken long time to appear.     

A case of primary HIV-1 infection

Effects of oleic acid or triolein on lymphatic recovery of docosahexaenoic acid (DHA) given as an ethyl ester were examined in rats with cannulated thoracic ducts. Lymphatic recovery of ethyl DHA given with oleic acid or triolein was significantly higher than in rats given ethyl DHA alone. DHA distributed almost exclusively at the 1- and 3-position of triglyceride in lymph collected at 0-3 h after the administration, when it was given with oleic acid or triolein. A small part of DHA distributed at the 2-position when ethyl DHA was the sole fatty acid given. Oleic acid given as free acid or triolein with ethyl DHA was a major fatty acid at the 2-position. Intramolecular distribution of DHA and oleic acid in lymph triglyceride was similar when ethyl DHA was given with oleic acid or triolein.     

Spread of HIV-1 to children in Cambodia

Beginning November 1, 1995, children under 5 years of age, who were admitted to Kantha Bopha Hospitals and who were suspected tuberculosis cases, were screened for human immunodeficiency virus 1 (HIV-1) using enzyme-linked immunosorbent assay (ELISA). By January 31, 1997, 9026 children, 83% of the under 5-year-olds admitted, had been tested; 290 (3.2%) were positive. Serum samples from 205 children of the 236 seropositive children under the age of 18 months were tested for p24 antigen; 51 (25%) were positive. Mothers of 173 of the seropositive children were tested for antibodies to HIV; 170 were positive, which suggests that the main mode of acquisition of HIV-1 in the children was vertical transmission. If HIV-1 infection occurred only in the 54 seropositive children older than 18 months and in the 51 children younger than 18 months with detectable p24 antigen, the calculated prevalence of HIV-1 in children under 5 years old who were suspected of having tuberculosis when admitted to Kantha Bopha Children's Hospitals would be 1.2%. If the 17% not included in the test were all negative, the prevalence would be 1%. This is an underestimate because some of the children not tested could be positive and because some of the children tested had indeterminate HIV status. HIV testing was extended to all children admitted to the hospital; 715 were younger than 5 years of age, 596 of whom were suspected of having tuberculosis, and 119 of whom were not. The seroprevalences for the 2 subgroups were 3.2% and 0.8%, respectively. None of the 369 older children was seropositive. In 1996, the World Health Organization estimated a seroprevalence of 1.97% in adults 15-49 years old in Cambodia, the highest among Asian countries. The blood bank at Kantha Bopha found 211 (6.6%) HIV-1 seropositives among 3197 donors in 1995 and 211 (7.5%) among 2834 donors in 1996. Similar figures were seen at the National Transfusion Centre in Phnom Penh. A 1996 survey in Cambodia found an HIV-1 seroprevalence of 40.9% in prostitutes and 1.7% in pregnant women. The vertical transmission of HIV-1 to children may increase because the virus appears to have been introduced recently to Cambodia; this is indicated by lack of seropositivity in children older than 5 years of age.     

HIV-1 infection in Juba, southern Sudan

Thirty years of civil war in the Sudan have resulted in the isolation of the southern provinces which border Central and East Africa. Consequently, little is known about the epidemiology of HIV-1 infection in this region. To estimate the prevalence of HIV-1 infection in southern Sudan and the risk factors associated with disease transmission, a seroepidemiologic survey was conducted in the township of Juba. Study subjects invited to participate in this study included medical outpatients, inpatients hospitalized for active tuberculosis, and female prostitutes. A total of 401 subjects participated in the study. HIV-1 infection was confirmed in 25 subjects. The prevalence of HIV-1 infection was 19% (8/42) among tuberculosis patients, 16% (8/50) among prostitutes, and 3% (9/309) among outpatients. A significantly higher prevalence of HIV-1 infection was found among female prostitutes when compared to female outpatients: 16% (8/50) vs. 2% (4/178), P < 0.001. Correspondingly, the prevalence of seropositives was significantly higher among male outpatients reporting a history of sexual relations with prostitutes during the prior 10 years compared to male outpatients denying relations with prostitutes: 14% (5/37) vs. 0% (0/94), P = 0.0011. A history of a sexually transmitted disease (STD) was also associated with HIV-1 infection among male outpatients. The findings of this study indicate that HIV-1 infection is highly prevalent in southern Sudan and that prostitutes and their sexual partners represent a major reservoir of HIV infection in this population. This epidemiologic pattern resembles that seen in the African nations neighboring southern Sudan.(ABSTRACT TRUNCATED AT 250 WORDS)     

Markers and determinants of progression of HIV-1 infection

A 68-year-old man underwent mitral valve replacement because of mitral regurgitation (prolaps of anterior mitral leaflet) using parasternal incision (Delos M. Cosgrove, minimally invasive surgery). He had been treated as pulmonary tuberculosis previously and had undergone esophagus operation using stomach role reconstruction beneath the sternum four years before the mitral valve procedure. We could not select median-sternotomy as an approach due to stomach role beneath the sternum, nor left posterolateral thoracotomy because of the heavy left-side pleural adhesion. Cardio-pulmonary bypass cannulations were performed through the same incision, because severe atherosclerosis was found at the distal arteries of the abdominal aorta.     

The parameters of the immune function in the evolution of HIV-1 infection in institutionalized children in Romania

OBJECTIVE: To describe the evolution of HIV-1 + horizontal infected children nursed in closed community. METHOD: The biological status of 26 HIV-1 + children nursed in Ia?i Orphanage was assessed in dynamic during April. 1993-Feb. 1994. The income age ranged among 1 month-3 years. RESULTS: The following progressive stages could be drawn accordingly to the biological status parameters dynamic: stage 1 ("oligosymptomatic"), stage 2 ("multiform, medium or severe symptomatology"), and stage 3 ("severe immunodepression, with predominant infectious symptomatology, waves evolution"). These stages could not be assimilated to the currently CDC or WHO classifications. The following thresholds of the immunologically parameters separate the stages 1 and 2, and respective stages 2 and 3: CD4% lymphocytes (27% respective 20%); absolute CD4+ lymphocytes (1150/microliter respective 700 + 750/microliter), CD4/CD8 ratio (0.75 respective 0.45), beta 2-microglobulin (1.5 mg/1000 respective 2.5 mg/ 1000). Lymphocytes lacking the markers CD4, CD8, CD19, CD3, ranging between 15 + 20% were also detected by flow-cytometry; these cells could be attributed to the immature subpopulations (typically for dystrophy) or to down-regulation of membrane expression of some markers. Also, a dichotomy in the distribution of the CD2/CD3 surface markers was recorded in the case of lymphocytes. CONCLUSIONS: Immunological features demarcate this epidemiological group versus the current described models for the HIV-1 + child.     

Quantification by additive RT-PCR of HIV-1 RNA plasma levels in different stages of HIV-1 infection

Recent reports have shown an association between an intronic polymorphism of the presenilin-1 (PSEN1) gene and late-onset (age at onset > 65) familial and sporadic (no family history) Alzheimer disease (AD). The reported association was independent of the effect of the only previously identified gene associated with late-onset AD, APOE. Blood samples were obtained from members of 122 multiplex AD families, 42 unrelated cases of AD with positive family histories of dementia, 456 sporadic cases of AD, and 317 controls of similar ages at examination to the cases. These samples were genotyped for an intronic polymorphism of the PSEN1 gene, located 3' to exon 8, and the data analyzed for evidence of association or linkage. The samples were also genotyped for APOE and the data analyzed to see if the association or linkage changed when controlling for APOE genotype. There was no statistically significant increase (at alpha = .01) in allele 1 (199 bp) or genotype 1/1 in the sporadic AD cases, or in a random sample of one affected from each multiplex family, compared to controls. When examining the effect of the PSEN1 polymorphism while controlling for APOE genotype, APOE genotype was strongly associated with AD, but the PSEN1 polymorphism genotype was not. Model-trait dependent (lod score) and independent (Sim1BD) methods detected no evidence of linkage between PSEN1 and AD. In this independent dataset, the previously reported association between the intronic PSEN1 polymorphism and AD cannot be confirmed, and the conclusion that PSEN1 is a major susceptibility gene for late-onset AD is not supported.     

Pancytopenia in children with brucellosis: clinical manifestations and bone marrow findings

Among 276 paediatric cases of brucellosis seen over a 7-year period, 16 patients (5.8%) with pancytopenia were identified. The most frequent presentations were fever, malaise, anorexia, weight loss, arthralgia, and hepatosplenomegaly. Fourteen patients (87.5%) had positive blood and/or bone marrow cultures for Brucella melitensis. Bone marrow aspiration specimens showed hypercellularity in 14 patients and normocellularity in 2. Histiocytes, eosinophils and plasma cells were increased in every marrow aspirate, and haemophagocytosis was observed in 14 patients (87.5%). Non-caseating granulomas were present in the bone marrow biopsy of 11 patients (68.8%). The pancytopenia was transient, and resolved on treatment of the Brucella infection.