Detecting impaired glucose tolerance or type 2 diabetes mellitus by means of an oral glucose tolerance test in HIV-infected patients.

OBJECTIVE: As a proactive diagnosis of diabetes mellitus (DM) may prevent the onset of severe complications, we used an oral glucose tolerance test (OGTT) to check for impaired glucose tolerance (IGT) and DM in patients with long-standing HIV infection and long durations of exposure to antiretroviral drugs with normal fasting plasma glucose (FPG) levels. METHODS: This was a cross-sectional, single-centre study. The homeostatic model assessment for insulin resistance (HOMA-IR) and 2-h post-load glucose levels were used to evaluate patients with known HIV-1 infection since before 1988 and no previous diagnosis of DM for whom data on hepatitis C virus (HCV) and hepatitis B virus (HBV) infection were available. RESULTS: Eighty-four Caucasian patients [67 (80%) male; median age 45.7 years; range 43.8-49.1 years] were able to be evaluated; 65 (77%) were coinfected with HCV, and seven (8%) were coinfected with HBV. Median (interquartile range [IQR]) exposure to antiretrovirals was 12.8 (10.4-16.5) years. Fifteen patients (18%) had a previous AIDS-defining event, 64 (76%) had HIV RNA<50 copies/mL, and the median (IQR) CD4 count was 502 (327-628) cells/µL. The median [IQR] FPG was 81 mg/dL (4.5 mmol/L) [75-87 mg/dL (4.2-4.8 mmol/L)], and the median (IQR) HOMA-IR was 2.82 (1.89-4.02). After OGTT, nine patients (11%) were diagnosed as having IGT (6) or DM (3). A first multivariable analysis showed that CD4 cell count (P=0.038) and HOMA-IR (P=0.035) were associated with IGT or DM, but a second model including only the variables with a P-value of <0.2 in the univariable analysis (CD4 cell count, HBV coinfection, and HOMA-IR) found that only HOMA-IR independently predicted IGT or DM. CONCLUSIONS: In patients with long-standing HIV infection and normal FPG levels, an OGTT can reveal IGT or DM.

In vivo dynamics of the 103N mutation following the withdrawal of non-nucleoside reverse transcriptase inhibitors in HIV-infected patients: preliminary results.

Due to the preferential selection of the fittest HIV mutants, drug-resistant variants are often overgrown by wild-type virus after treatment interruption. Our objective was to investigate the dynamics of the 103N mutation (which usually does not reduce HIV fitness) following the withdrawal of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Patients who were found to have the 103N mutation at or after failure of a NNRTI were selected from an observational database. Two groups of patients were identified: one which continued antiretroviral treatment without NNRTIs (group A) and one which discontinued all anti-retrovirals after failure of an NNRTI (group B). Genotype was obtained by direct sequencing of the replicating plasma virus. Sixty-two subjects tested between July 1998 and December 2002 were included in the analysis, 39 in group A and 23 in group B. At the time of the first resistance test, median (IQR) CD4+ T-lymphocytes and HIV-RNA were 269 (150-449) cells/microL and 25,000 (9,600-83,300) copies/mL. In 31 (50%), 30 (48%), and one case (2%), the 103N mutation was selected by nevirapine, efavirenz, and by delavirdine, respectively. A total of 149 tests were analyzed, with a median (IQR) of 2 (2-3) tests/patient. The median (IQR) interval between failure of NNRTIs and the last resistance test was 11 (5-22) months. Overall, a reversion to wild-type at position 103 was observed in 23/62 (37%) subjects, 14/39 (36%) in group A and 9/23 (39%) in group B. In group A, 14/23 (61%) patients tested within 12 months, 10/16 (63%) of those tested between 12 and 24 months, and 12/14 (86%) of those tested beyond 24 months from NNRTI discontinuation had the 103N mutation. In group B, 14/20 (70%) patients tested within 12 months, 3/4 (75%) of those tested between 12 and 24 months, and none out of two tested beyond 24 months from NNRTI discontinuation had the 103N mutation. In conclusion, following NNRTI discontinuation, in the majority of patients HIV variants carrying the 103N mutation are not overgrown for long by wild-type quasispecies at this position. This suggests that the 103N mutation per se influences minimally the viral fitness in vivo.

Impact of HAART on liver histology of HIV/HCV coinfected patients.

The impact of HAART on the progression of HCV related liver disease is controversial. This retrospective study compares the grading and staging of chronic viral hepatitis in HIV/HCV coinfected subjects treated or not with antiretroviral therapy (ART) including protease inibithors (PI). The liver histology of 44 HIV/HCV coinfected patients on ART for more than 12 months, 26 coinfected patients naïve for ART and 31 HCV monoinfected patients were analysed by the Ishak score. None of the multivariate models calculated to test if liver histopathology (Ishak grading or staging) between HIV/HCV coinfected patients versus HCV monoinfected or antiretroviral-treated versus untreated HIV+ subjects showed any statistical difference. No significant difference between grading and staging was evidenced either in PI treated subjects versus patients on ART without PI.

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.

Plasma folate, vitamin B(12), and total homocysteine and homozygosity for the C677T mutation of the 5,10-methylene tetrahydrofolate reductase gene in patients with Alzheimer's dementia. A case-control study.

BACKGROUND: Elevated total plasma homocysteine (tHcy) levels are considered a risk factor for cerebrovascular disease and may also play an important role in the pathogenesis of Alzheimer's disease (AD). High values of plasma tHcy and low levels of vitamin B(12) and folate are frequently present in AD patients. Moreover, the homozygous mutation (C677T) of the methylene tetrahydrofolate reductase (MTHFR) gene, related to a thermolabile type of the encoded enzyme, causes hyperhomocysteinemia by reducing the 5-methyltetrahydrofolate availability. OBJECTIVE: The aim of the study was to investigate plasma levels of folate, vitamin B(12) and tHcy in patients with AD. These values were also related to the severity and the duration of the disease and to the possible role of the MTHFR genotype (C677T). METHOD: Plasma tHcy levels, homozygosity for the C677T mutation of the MTHFR gene, and folate and vitamin B(12) plasma levels were evaluated in 74 patients with AD (45 men, 29 women, mean age 68 years) and in 74 healthy matched controls (42 men, 32 women, mean age 68 years). RESULTS: AD patients had higher mean (+/- SD) plasma levels of tHcy (20.9 +/- 15 micromol/l compared to 11.8 +/- 5 micromol/l, p < 0.001) and lower mean plasma folate (5.7 +/- 2.1 ng/ml compared to 8.5 +/- 3.2 ng/ml, p < 0.001) and vitamin B(12) (491 +/- 144 pmol/l compared to 780 +/- 211 pmol/l, p < 0.001) concentrations. Homozygosity for the C677T mutation of the MTHFR gene had a similar prevalence among controls (18%) and AD patients (20%). Homozygous AD patients (n = 15) had higher plasma tHcy values than nonhomozygotes, in spite of similar mean plasma folate and vitamin B(12) levels. This difference in plasma tHcy levels was not observed in controls. Patients with levels of plasma tHcy above and of plasma folate below the normal limits were more frequent in the homozygous AD group. The duration of the disease correlated with plasma levels of tHcy (r = +0.832, p < 0.001), plasma folate (r = -0.580, p < 0.05), and vitamin B(12) (r = -0.460, p < 0.05). However, when all the data were corrected for age, serum creatinine levels, and duration of the disease, mean plasma tHcy, folate, and vitamin B(12) levels were not statistically different between controls and AD patients. CONCLUSIONS: Our data suggest that rather than a risk factor for AD, hyperhomocysteinemia is related to its progression and increasing severity. This might be particularly relevant in homozygotes for the C677T mutation of the MTHFR gene and supports the possible need for continuous supplements in this setting.

[Association of visceral Leishmaniosis and pulmonary tuberculosis: description of a patient] / Associazione di Leishmaniosi viscerale e tubercolosi polmonare: descrizione di un caso clinico.

Leishmaniosis, whether localised or disseminated, is mainly correlated to cell-mediated immunodeficiency. Immunodeficient patients are also particularly prone to diseases due to Mycobacterium tuberculosis, in whom either the disseminated form or a localisation of the lungs prevails. We report a rather uncommon association of both pathologies successufully treated with N-methylglucamine antimonium followed by an association of rifampycin, isoniazid and ethambutol. The ethiopathogenetic mechanisms, are described.

Occurrence of the same peroxidative compounds in low density lipoprotein and in atherosclerotic lesions from a homozygous familial hypercholesterolemic patient: a case report.

Oxidative modification of low density lipoprotein (LDL) and its byproducts may play a fundamental role in atherosclerosis. We report an in vitro analysis of LDL peroxidative compounds in an homozygous familial hypercholesterolemic (HFH) patient who subsequently died. During the autopsy, we analyzed lipids extracted directly from different atherosclerotic plaques, and we also provided an immunocytochemical analysis using the specific monoclonal antibody MDA2 (directed against malondialdeyde-lysine epitopes of oxidized LDL). The results showed that the same species of peroxidative compounds were present both in LDL in vitro and in lipids extracted directly from atherosclerotic lesions. Moreover, the immunocytochemistry analysis revealed a positive staining of atherosclerotic plaques, confirming the presence of LDL oxidation-specific epitopes. Although observation of a single case is necessarily limited, our findings are consistent with the hypothesis that oxidative modification of LDL is involved in human atherogenesis.

Prevalence of peripheral arterial disease in an elderly rural population of southern Italy.

Blood pressure was measured at the posterior tibial artery by Doppler ultrasonography in 440 elderly subjects (205 men and 235 women) living in a rural community of Southern Italy, together with the evaluation of traditional risk factors for cardiovascular disease. An ankle/arm systolic pressure ratio below 0.90 was considered as a definite pathological sign of peripheral arterial disease (PAD). About 10% of both men and women had a value below 0.90. Elderly subjects with PAD had higher serum triglyceride levels and a higher ratio between the cholesterol content in atherogenic (VLDL + LDL) versus non-atherogenic (HDL) lipoproteins than subjects free of PAD. The mean blood pressure was also higher in patients with PAD. The prevalence of PAD was much lower than what we have observed in institutionalized old subjects in Southern Italy.

Prevalence of peripheral arterial disease and related risk factors in elderly institutionalized subjects.

Blood pressure was measured at the posterior tibial artery by Doppler ultrasonography in 124 elderly subjects (37 men and 87 women) living in two retirement homes in Naples (Italy). Ankle-to-arm systolic pressure ratios below 0.97 and 0.90 was considered as a probable and definite pathological sign of peripheral arterial disease, respectively. Half of the subjects (48% of men and 51% of women) gave a value below 0.97, while a third (35% of men and 33% of women) had a value below 0.90. By multiple regression analysis, mean blood pressure, plasma cholesterol levels and cigarette smoking were all negatively correlated with ankle systolic pressure values with a progressively lower significance. Most of the patients with pathological Doppler examination were asymptomatic at a questionnaire for intermittent claudication.

Changes in middle cerebral artery blood velocity in uremic patients after hemodialysis.

BACKGROUND AND PURPOSE: Strokes are a frequent complication in uremic patients on dialysis. We wanted to evaluate the effect of this treatment on cerebral hemodynamic parameters, particularly those of patients with carotid stenosis, who are at higher risk for atherothrombotic ischemic events. METHODS: We used transcranial Doppler ultrasonography to evaluate blood velocity of the middle cerebral artery in 18 uremic patients before and after hemodialysis. Carotid stenosis was evaluated by echo-Doppler investigation. Six patients were also studied before and after recombinant human erythropoietin treatment. RESULTS: Dialysis treatment decreased mean blood velocity in all patients (p less than 0.001). Eight of 18 patients (44%) with mild (16-50%), moderate (51-80%), or severe (greater than 80%) carotid stenosis had lower velocity than patients with normal carotid arteries (p less than 0.01), and they experienced a further decrease to even lower levels after hemodialysis (p less than 0.05). In patients treated with recombinant human erythropoietin, hematocrit increased from 28 +/- 8% to 37 +/- 5% (p less than 0.001), and blood velocity had a further decrease by 11%. All changes were associated with modifications toward normality of pH, PaCO2, and hematocrit. CONCLUSIONS: Transcranial Doppler ultrasonography represents a useful method for monitoring cerebral circulation of uremic patients, especially of those at possible risk for ischemia.

Effect of acute administration of L-acetyl carnitine on cerebral blood flow in patients with chronic cerebral infarct.

The effect of L-acetyl carnitine (L-AC) on cerebral blood flow (CBF) was evaluated in 20 patients with chronic cerebrovascular disease, who suffered an ischaemic stroke at least 6 months before the study. All patients performed a CT scan and were investigated with xenon-133 by brain dedicated single photon emission computed tomography (SPECT, Tomomatic 32, Medimatic Inc., Copenhagen). A single high dose (1.5 g) of L-acetyl carnitine was intravenously administered to 10 patients, while sodium acetate as placebo was injected to 10 other subjects. Cerebral blood flow (ml/min x 100 g) was evaluated before and 45 min after the injection. No changes were observed after placebo injection (43 +/- 12 ml/min x 100 g versus 43 +/- 10 ml/min x 100 g). CBF increased (from 42 +/- 9 ml/min x 100 g to 46 +/- 9, P less than 0.05) in both ipsilateral and contralateral hemisphere, the ischaemic area, but not in the stroke corresponding zone. It was concluded that L-acetyl carnitine at the i.v. dosage of 1.5 g acutely enhanced CBF in patients with chronic cerebral infarct.

Hemostatic variables in homozygous familial hypercholesterolemia. Effect of regular plasma cholesterol removal by low density lipoprotein apheresis.

Plasma levels of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) and the in vitro ability of platelets to aggregate and of monocytes to express procoagulant (tissue factor) activity (PCA) were evaluated in five patients who are homozygous for familial hypercholesterolemia (FH) before and after a single and a regular 5-month cholesterol removal by low density lipoprotein (LDL) apheresis. The biweekly procedure resulted in a 25% to 30% reduction (approximately 150 mg/dl) in total and LDL cholesterol (both were greater than 550 mg/dl at the beginning of the study). The basal levels of t-PA antigen and fibrinolytic activity before and after 10 minutes of venous stasis, basal PAI activity, and PAI-1 antigen were comparable to controls and were not affected by LDL apheresis. Likewise, regardless of the cholesterol removal, the PCA of freshly isolated monocytes and that of monocytes incubated with lipopolysaccharide did not differ from control values. Finally, the pre-apheresis sensitivity of platelets to adenosine diphosphate, arachidonic acid, and collagen was 1.5 to 2 times the normal value. This ratio was unchanged throughout the 5-month procedure. We conclude that fibrinolysis and monocyte PCA are normal in FH patients, whereas platelet aggregation is abnormally high, and none of these parameters is significantly affected by a 25% to 30% reduction in total and LDL cholesterol by LDL apheresis. Furthermore, our data suggest that removal of cholesterol from plasma by LDL apheresis is important for gaining insight into the mechanisms involved in the ischemic complications of arteriosclerosis in FH patients.

Cerebral blood flow in patients with chronic cerebrovascular disease: effect of acetyl L-carnitine.

The effect of acetyl-L-carnitine on cerebral blood flow was evaluated in ten patients with cerebrovascular disease, who suffered an ischaemic stroke at least six months before the study. All patients performed a computerized tomograph scan and were investigated by Xenon 133 using a brain dedicated Single Photon Emission Computerized Tomography. Acetyl-L-carnitine was administered intravenously (i.v.) at a dosage of 1.5 g. Cerebral blood flow (ml/min. 100 g) was evaluated before and 45 min after the injection. Cerebral blood flow improved in both the ispilateral and controlateral hemisphere of the ischaemic area, but not in the stroke corresponding zone. It is concluded that acetyl-L-carnitine at a dosage of 1.5 g i.v. improves cerebral blood flow in patients with cerebrovascular disease.

Plasma lipids and geriatric assessment in a very aged population of south Italy.

A very old population of a rural area of Southern Italy with a mean age of 87 years was investigated in order to evaluate serum lipid levels and their possible association with health conditions, such as mental status, social behaviour and physical autonomy. Among 101 subjects with ages above 82 years, 73 were investigated (participation rate 72%, 31 men and 42 women). Mean +/- SD serum cholesterol level was 199 +/- 36 and 210 +/- 40 mg/dl and mean serum triglyceride level was 107 +/- 43 and 148 +/- 74 mg/dl (P less than 0.05) in men and women, respectively. Mean high density lipoprotein (HDL)-cholesterol level was 49 mg/dl in both sexes. All subjects were investigated by means of geriatric and neuropsychometric scales such as Sandoz Clinical Assessment Geriatric Scale (SCAGS), Hachinski Dementia Scale (HDS), Plutchik Geriatric Rating Scale (PGRS) and Indexes of Activity of Daily Living (ADL). When subjects were divided into 3 groups according to levels of serum lipids, HDL-cholesterol appeared to be better related to clinical conditions than total serum cholesterol: the group with the higher HDL-cholesterol level presented better scores at all the administered assessment scales when compared to the groups with lower and modal levels (P range between less than 0.05 and less than 0.001). Subjects in the higher serum cholesterol group presented better scores at PGRS only (P less than 0.01). No relation was observed between serum total triglyceride levels and geriatric assessment scores.