Prevention of opportunistic infections in HIV infection by pentoxiphylline.

BACKGROUND & OBJECTIVES: Levels of tumour necrosis factor (TNF) are increased in patients with HIV infection leading to increased apoptosis and reduced CD4 cell life. Pentoxiphylline is a TNF inhibitor with properties that might make it useful for the treatment of HIV infection. These include improved cell mediated immunity and inhibition of viral replication. We carried out this study to determine the therapeutic utility of pentoxiphylline in improving constitutional manifestations, preventing opportunistic infections and sustaining CD4 counts among asymptomatic HIV infected individuals (i.e., those with no opportunistic infection). METHODS: Individuals with HIV infection who were over 18 yr of age and free of opportunistic infections were recruited in the study and followed up 4 weekly. CD4 counts were measured using a flowcytometer using anti-human CD4 intervals. Pentoxiphylline was prescribed in a dose of 400 mg thrice daily. RESULTS: Thirty three (18 males) patients with HIV infection were studied. During their follow up (mean 12.5 +/- 5.6 months) one patient each developed cryptococcal meningitis and fibrocavitary tuberculosis. Weight increased from 51.3 +/- 7.4 kg at baseline to 55.3 +/- 7.4 kg (P<0.05). Malaise, fatigue and appetite improved in all those with these complaints, except the two with opportunistic infections. Mean CD4 counts were 184 +/- 36.4/microl at baseline and increased to 210 +/- 28.6/microl3 at four weeks (P<0.05). The patients had stable CD4 counts over the follow up period since then, i.e., within 25 per cent of the previous levels. INTERPRETATION & CONCLUSION: Pentoxiphylline therapy in HIV infected individuals, who were free of opportunistic infections, improved their body weight, minimized opportunistic infections, increased and sustained CD4 counts. Given the low cost of the drug it could be recommended for the use in individuals who are at a high risk of developing opportunistic infections.

Beta2 microglobulin as a surrogate marker for HIV infection: good correlation with CD4 counts.

To determine if beta-2 microglobulin (beta2M) levels were elevated in our HIV infected patient population and if it could be used as a surrogate marker for disease progression. Thirty-eight HIV infected individuals and 26 age and sex-matched controls were studied. Measurement of CD4 cell count was carried out on a flowcytometer using anti-human CD4 monoclonal antibody and beta2M was measured by an enzyme immunoassay. Mean levels of HIV infected individuals were 1.29 +/- 0.52 mg/L and were significantly higher than 0.74 +/- 0.07 mg/L, the value of controls (p value <0.01). There was a negative correlation between CD4 counts and beta2M levels (r-value-0.79, p value <0.001). Beta2M levels in HIV infected individuals who have no opportunistic infection are elevated and these levels correlate with the CD4 counts. Beta2M can be used for the clinical follow-up of patients with HIV infection.

Caspase 1 and caspase 8 in HIV infected patients with and without tuberculosis.

BACKGROUND: Caspase 8 is involved in apoptosis mediated by Fas and p55 tumor necrosis factor receptor ligation in HIV infection. Apoptosis is partially mediated by interleukin-1beta-converting enzyme (caspase-1). AIMS: We determined apoptosis, using caspase-1 and caspase-8, among patients with HIV infection, with and without tuberculosis (TB), those with TB alone and healthy individuals. SETTING AND DESIGN: Cross-sectional analysis of caspase-1 and caspase-8 among patients with HIV infection, with and without TB, those with TB alone and healthy individuals. MATERIALS AND METHODS: Nineteen HIV infected patients with TB (HIV+/TB+) and 20 with HIV infection without TB (HIV+/TB-) were studied. Fifteen individuals with TB alone were disease controls (HIV-/TB+) and 20 were healthy controls (HIV-/TB-). Caspases were measured by single-step ELISA using commercially available monoclonal antibodies. STATISTICAL ANALYSIS: Two-way ANOVA and Pearson's correlation coefficient. RESULTS: Mean CD4 counts of HIV+/TB+ were lower than HIV+/TB- (p<0.05). OD value of caspase 1 in HIV+/TB+ was 0.295+0.05, while that in HIV+/TB- it was 0.302+0.18. It was 0.293+0.07 in HIV-/TB+ and in HIV-/TB- the values were 0.287+0.06. OD value of caspase 8 in HIV+/TB+ was 0.307+ 0.07, lower than HIV+/TB- (0.927+0.25). It was 0.008+0.03 in HIV-/TB+ and in HIV-/TB-, 0.074+0.004. Values of caspase 8 in patients with HIV infection (with/without TB) were higher than those with TB alone or healthy individuals (p<0.01). Levels of caspase 8 in HIV+/TB- were higher than patients with HIV+/TB+ (p<0.01). CONCLUSION: Levels of caspase-1 are not different irrespective of presence or otherwise of TB and HIV infection. Fas-related apoptosis is higher in HIV infection. With concomitant TB, levels of caspase 8 were lower as compared with those without TB.

Human immunodeficiency virus infection in a patient with systemic lupus erythematosus.

We describe a 47 years lady with systemic lupus erythematosus (SLE) who was infected with human immunodeficiency virus (HIV), due to transfusion either by blood or platelet concentrate. There was a near remission in the disease and during the course of follow up she developed cryptococcal meningitis. The approach to the diagnosis of HIV infection in a patient with SLE, the effect of SLE on the virus and vice versa and some management issues in this setting are discussed.

Fatal 2,4-D (ethyl ester) ingestion.

2,4-D (2,4-dichlorphenoxyacetic acid) is widely used in agriculture and forestry to destroy broad leaved weeds (herbicide). It has a moderate mammalian toxicity and human poisoning has rarely been reported except following ingestion with suicidal intent. We report two young adults who ingested it with suicidal intent, developed neurological, cardiac, hepatic and renal toxicity and died.

Paucity of anti-hepatitis C virus antibodies in the serum of Indian patients with Sjogren's syndrome and inflammatory myositis.

Several extrahepatic manifestations have been associated with infection with Hepatitis C virus (HCV) infection. It has been associated with Sjogren's syndrome (SS) and inflammatory myositis (IM). The objective was to look at the prevalence of anti-HCV antibodies in the serum of SS and IM patients of Indian origin. Individuals satisfying the European Economic Community criteria for the diagnosis of SS and those satisfying the criteria of Bohan and Peter for the diagnosis of IM were recruited in the study. Routine evaluation for liver functions was made. Anti-HCV antibodies were tested by a third generation ELISA, using microplate HCV3.0 ELISA. Of the 23 patients with SS studied, 14 had extraglandular features. The commonest were anaemia and arthritis in six each, followed by in lymphopenia in two. One patient each had interstitial lung disease, hypothyroidism and chronic active hepatitis. Twenty-two patients with IM were studied alongside. None of the patients had abnormal liver functions. One patient with primary SS tested positive for anti-HCV antibodies. None of the patients with inflammatory myositis tested positive for anti-HCV antibodies. The presence of anti-HCV antibodies in our cohort of patients with SS and IM is low and more in keeping with the generally low prevalence of the infection in the Indian population.

Acute pancreatitis following propoxyfur (Baygon) ingestion.

Elevation of serum amylase and blood glucose is not uncommon following anticholinesterase poisoning. We report a young male who developed acute cholinergic crisis and acute pancreatitis following propoxyfur (Baygon) ingestion and recovered completely with conservative management.

Acute paraplegia following viper bite.

Neurological complications following viper bite are uncommon and are generally as a result of intracerebral or subarachnoid bleed and rarely due to cerebral infarction. We report a young male who following viperine bite developed local tissue swelling, haemorrhagic manifestations due to disseminated intravascular coagulation and later developed acute flaccid paraplegia as a result of dorsal spinal cord involvement.

Helicobacter pylori in Indian HIV infected patients.

Helicobacter pylori is a causative organism for chronic gastritis and associated with peptic ulcer disease. Infection may be asymptomatic as well. Human immuno-deficiency virus infection predisposes to a multitude of opportunistic infections, many of them resulting in gastrointestinal symptoms. We studied the prevalence of H pylori co-infection with HIV and its correlation with gastrointestinal symptoms in HIV infected patients. Seventy-three consecutive HIV infected patients presenting to the medical out patient department of Postgraduate Institute of Medical Education & Research, Chandigarh, India, were included in the study. Antibodies (IgG) to H pylori were tested by ELISA. There were 43 males, 30 females; mean age 26.1 +/- 4.7 years. Risk factors for acquiring HIV infection was predominantly heterosexual exposure. Eleven patients presented with gastrointestinal symptoms. Thirty-five of the 73 (47.9%) patients had serological evidence of H pylori infection. Six of them had gastrointestinal symptoms. These were odynophagia in 5, dyspepsia in 4 and recent diarrhoea in 2. Twenty-four patients with H pylori infection had AIDS. There was no difference in the prevalence of H pylori infection between patients with and without AIDS.

Paradoxical reaction in HIV and tuberculosis coinfection.

Occurrence of paradoxical reaction following institution of antiretroviral therapy to patients with HIV and tuberculosis coinfection who are already on antitubercular therapy is distinctly uncommon. In this report we describe one such case and emphasize that such a reaction does not imply discontinuation of therapy.

Linear scleroderma and autoimmune hemolytic anaemia.

Coexistence of localized scleroderma with other autoimmune disorders is not seen frequently. It has been reported to occur with myasthenia gravis, hemiatrophy and systemic lupus erythematosus. In this report we describe an association wherein linear scleroderma coexisted with autoimmune haemolytic anaemia.

Decline in beta-2 microglobulin levels after antitubercular therapy in tubercular patients with HIV infection.

BACKGROUND: Infection with Mycobacterium tuberculosis results in a state of immune activation, more so, when there is concomitant HIV infection. Beta-2 microglobulin (B2M) is a useful marker to study the state of immune activation among the HIV infected. Objective. To study the modulation of B2M levels among patients with HIV/TB coinfection, to correlate it with the CD4 count and also to study the change in these levels after four weeks of therapy. MATERIAL AND METHODS: Twelve patients with HIV infection and having concomitant TB diagnosed on the basis of positive acid fast bacilli were studied both at baseline and then at four weeks. Fourteen HIV infected individuals who had no overt opportunistic infection at the time of the study were also studied along with fourteen age and sex matched healthy volunteers. CD4 counts were performed using a flowcytometer. B2M was measured using a commercially available ELISA kit. RESULTS: B2M levels in HIV/TB coinfected patients were 1.62+/-0.45 mg/L (range 1-2.7 mg/L) and were significantly higher (p<0.0002) when compared with healthy controls, whose levels were 0.74+/-0.05 mg/L (range 0.48-81 mg/L). The levels in HIV infected individuals free of opportunistic infections were 1.2+/-0.16 mg/L (range 0.78-1.92 mg/L) and were significantly lower than the levels in HIV/TB coinfected (p<0.017), but significantly higher than the levels in healthy controls (p<0.01). Four weeks of antitubercular therapy resulted in a decline in B2M to 1.08+/-0.26 mg/L (range 0.8-1.74 mg/L) and was statistically significant (p<0.012). There was no correlation between the CD4 counts and the pre-treatment levels of B2M among these patients. CONCLUSION: Patients with HIV/TB coinfection had significantly higher levels of B2M than individuals with HIV infection without associated opportunistic infection and healthy controls. Four weeks of anti-tuberculous therapy resulted in a significant decline in these levels.

Suppression of beta 2 microglobulin by pentoxiphylline therapy in asymptomatic HIV infected individuals.

Pentoxiphylline, an inhibitor of tumor necrosis factor-alpha (TNF-alpha) has been used in the treatment of human immunodeficiency virus (HIV) infection. The inhibition of TNF-alpha results in decreased immune activation. Beta 2 microglobulin (beta 2 M) has been used as a surrogate marker to study the progression of HIV infection. The objective of this study was to see if use of pentoxiphylline resulted in any decline in beta 2 M levels. Twenty patients with HIV infection who were free of opportunistic infections at the time of inclusion in the study and 18 age and sex matched controls were studied. beta 2 M was measured using an enzyme immunoassay before and four weeks after the start of treatment with pentoxiphylline. Mean levels of beta 2 M before therapy were 1.51 +/- 0.77 mg/l (range 0.78-3.8 mg/l) and were significantly higher (P < 0.001) than the levels among controls [0.72 +/- 0.06 mg/l (range 0.46-0.88 mg/l)]. beta 2 M levels in patients declined to 0.85 +/- 0.22 mg/l (range 0.72-1.0 mg/l) after four weeks of therapy and this was statistically significant (P < 0.001). Use of pentoxiphylline for four weeks results in a significant decline in the levels of beta 2 M suggesting that the level of immune activation is reduced with the therapy.

Vogt-Koyanagi-Harada syndrome following injury-induced progressive vitiligo.

We report a case of Vogt-Koyanagi-Harada (VKH), Syndrome wherein the patient developed ocular symptoms following injury-induced progressive vitiligo with immunologic evidence from the skin biopsy specimen of the vitiligo. This case supports the hypothesis that the cell-mediated immune process against a common melanocyte antigen plays an important role in the development and progression of the disease.

Common variable immunodeficiency in an adult.

Primary immunodeficiency syndromes are rarely diagnosed among adults. In this report, we describe a young male who had common variable immunodeficiency. He was treated with intravenous immunoglobulin and, on follow up, has been free of opportunistic infections.

Acute alcoholic myopathy, rhabdomyolysis and acute renal failure: a case report.

A case of middle aged male who developed swelling and weakness of muscles in the lower limbs following a heavy binge of alcohol is being reported. He had myoglobinuria and developed acute renal failure for which he was dialyzed. Acute alcoholic myopathy is not a well recognized condition and should be considered in any intoxicated patient who presents with muscle tenderness and weakness.