Predisposing factors for nevirapine toxicity among AIDS patients with low baseline CD4 count.

The objective of the study was to determine the predisposing factors and incidence of toxicity among AIDS patients treated with a nevirapine (NVP)-based regimen in clinical practice. A retrospective cohort study of representative samples of AIDS patients treated with a NVP-based regimen was performed. A total of 206 adult HIV/AIDS cases with median age (IQR) 33 years (range, 29-38 years), 51% male, treated between January 2004-December 2005, were included. Most (92.2%) of the patients were naïve to antiretroviral drug. The incidence of NVP toxicity was 1.09/100 person-months. The median onset time was 4 weeks post NVP initiation (2.57 weeks for skin toxicity and 12.43 weeks for hepatic toxicity). History of drug allergy and NVP toxicity were significantly associated (p = 0.006), as were sulfamethoxazole allergy and toxicity (p = 0.015). Regarding concomitant medication, concurrent anti-tuberculosis drugs significantly increased the risk of NVP associated liver toxicity (p = 0.001). Therefore, it is important to monitor adverse events from NVP, including liver function tests among HIV/AIDS patients with history of drug allergy, especially against sulfamethoxazole, and those concurrently treated with antituberculosis drugs.

Social harms in injecting drug users participating in the first phase III HIV vaccine trial in Thailand.

OBJECTIVE: To study related social harms due to identification with a group of participants in an HIV-1 vaccine trial who are potentially high risk for HIV/AIDS. MATERIAL AND METHOD: Two thousand five hundred forty six injecting drug users (IDU) were enrolled in a 36-month vaccine trial. Volunteers received education and risk reduction counseling at every six-month study visit. Social harms were not actively solicited, but volunteers were encouraged to report any during the process of counseling at every six-month visit. If a social harm was reported, a questionnaire was administered and the harm was tracked If necessary, clinic staff assisted in resolving the social harm. RESULTS: Thirty-nine social harms were reported by 37 participants; 33 (84.6%) were disturbances in personal relationships, three (7.7%) in employment, one (2.6%) was medically related, one (2.6%) was related to admission in the military and one (2.6%) was related with misbelieve about the vaccine. The most common reason for disturbances in personal relationships was suspicion of HIV infection (n=20). The impact of these harms on quality of life was characterized as minimal by 31 (79.5%) participants, as moderate by seven (17.9%), and as major by one (2.6%). All social harms were documented to be resolved by the end of the study. CONCLUSION: A few participants reported study-related social harms during the course of the trial. Most harm had minimal impact and all could be resolved by the end of the present study.

Outcomes in HIV-infected patients on antiretroviral therapy with tuberculosis.

HIV-infected patients with active tuberculosis (TB) having CD4 counts < 100/mm3 and who were antiretroviral therapy (ART) naïve were reviewed retrospectively to determine the outcomes of their tuberculosis infection. All patients received ART at or after receiving anti-TB treatment. Clinical manifestations, treatment regimens and outcomes were analyzed. Of 101 patients, 62 (61.4%) completed TB treatment. Of these, 53.2% were treated with a 6-month standard TB regimen, while the rest were treated with prolonged TB regimens. The median interval between anti-TB treatment and ART was 68 days (range: 0-381). Among the clinically cured patients 66.1% received rifampin concomitantly with nevirapine, and 32.3% received rifampin concomitantly with efavirenz. The treatment success rate was 75.6%, with a mortality rate of 6.1%. The risk factors for death were resistant TB (p = 0.03) and poor compliance (p < 0.05). Seven point nine percent had multi-drug resistant TB. Possible or probable immune reconstitution inflammatory syndrome (IRIS) was seen in 15 cases (14.9%). No life-threatening IRIS was reported, and it did not affect disease outcome (p = 0.5). A shorter time between anti-TB treatment and ART onset was associated with the occurrence of IRIS (31 days vs 90 days; p < 0.05). Regarding adverse drug effects, 44.6% had side effects due either to anti-TB drugs or ART. Sixty-six point one percent of them occurred within the first 2 months of TB treatment, and 43 (76.8%) had to stop or change either anti-TB treatment or ART. The mortality rate with TB and HIV on ART was low and the occurrence of IRIS did not carry any additional mortality.

Comparison of one week with two week regimens of amphotericin B both followed by fluconazole in the treatment of cryptococcal meningitis among AIDS patients.

BACKGROUND: Amphotericin B treatment in cryptococcosis requires daily hospital visits or admission. Its toxicities and hospital costs have been concerned. Short course amphotericin B regimen warrants to be evaluated. OBJECTIVE: To compare the safety and efficacy of one-week (AmB1) with two-week (AmB2) amphotericin B both followed by fluconazole. MATERIAL AND METHOD: 57 AIDS with cryptococcal meningitis were randomly assigned to either AmB1 or AmB2. Microbiological and clinical clearances were the outcomes of the study. RESULTS: The treatment success at 6 weeks was 63.3% in AmB1 and 70.4% in AmB2 (p = 0.574). Clinical assessment at week 10 and renal toxicities were not significantly different between both regimens. Mortality rate was 14% however, 75% of deaths were in AmB2. CONCLUSION: AmB1 was comparably effective and safe as the standard AmB2 regimen in the treatment of AIDS related cryptococcal meningitis. It can be an alternative regimen to lower hospital based care and improve cost effective for source limiting health care centers.

Serum leptin concentrations in chronic hepatitis.

The objectives of this research were to investigate the leptin levels among Chronic Hepatitis B Virus (HBV), Chronic Hepatitis C Virus (HCV) and non-alcoholic steatosis hepatitis (NASH) diseases of Thai patients compared with controls. Twenty of each HBV, HCV and NASH patients compared with sixty people as the control group from the Outpatient Department at the Hospital for Tropical Diseases, Bangkok, Thailand were investigated. Fasting blood samples were collected for investigation of leptin concentration, liver enzyme function tests and hematological variables. The serum leptin concentration of liver patients was significantly higher than that of control subjects. It might be due to the accumulations of fat cells in liver disease patients. However, there is no relationship between leptin level and other parameters such as BMI, ALT, AST, ALP and hematological variables. Liver enzyme functions levels are much higher in patients groups. White blood cells counts, platelets and hematocrit values are slightly lower in liver disease patients. Therefore, it is concluded that physiological regulation of leptin maintains in relation to body fat, even in chronic viral liver diseases. This finding and the apparent stage suggest the possibility that in the course of chronic viral diseases, serum leptin levels may reflect the extent of liver dysfunction.

Methylenetetrahydrofolate reductase (MTHFR) polymorphism (C677T) in relation to homocysteine concentration in overweight and obese Thais.

We analyzed the association between MTHFR (C677T) gene polymorphism with serum concentrations of homocysteine, folate, and vitamin B12 in 37 male and 112 female overweight/ obese Thai volunteers (BMI > or = 25.00 kg/m2), and compared them with 23 male and 90 female control subjects (BMI = 18.5-24.99 kg/m2). Statistically significant higher levels of serum homocysteine were found in the overweight/obese subjects than the control subjects (p < 0.05). Serum folic acid levels in the overweight/obese subjects were significantly lower than the control subjects (p < 0.05). When the data were grouped according to homocysteine concentration and MTHFR gene polymorphism, there were significantly higher homocysteine concentrations in the overweight/obese subjects than the control subjects in wild type gene polymorphism (CC) in the hyperhomocysteine group (homocysteine >10.0 mmol/l) (p < 0.05), but in genotype polymorphism (CC, CT, TT) there were lower folic acid and vitamin B12 concentrations in the overweight/obese subjects than in the control subjects. In the hyperhomocysteine groups, there was no significant difference in the frequencies of MTHFR (C677T) gene polymorphism between the overweight/obese subjects and the control subjects. Folic acid and gene polymorphism were found to be significantly related to the overweight/ obese and control groups in logistic regression analysis (p < 0.05). The results support the supposition that folic acid is more important than vitamin B12.

Relationship between soluble leptin receptor, leptin, lipid profiles and anthropometric parameters in overweight and obese Thai subjects.

Median, range and 95% confidence interval (CI) for median of age, anthropometric variables, soluble leptin receptor, serum leptin and lipid profile levels of 48 overweight (Body mass index (BMI) = 25.00-29.99 kg/m2) and obese (BMI > or = 30. 00 kg/m2) Thai males and 166 overweight and obese Thai females, compared with 26 males and 81 females in a control group (BMI = 18.50-24.99 kg/m2), were determined The study subjects were persons who turned up regularly for physical check-ups at the Out-patient Department, General Practice Section, Ratchawithi Hospital, Bangkok, aged between 18-60 years. Serum leptin, triglyceride and low density lipoprotein cholesterol/high density lipoprotein cholesterol ratios (LDL-C/ HDL-C ratio) were significantly higher in the overweight and obese males and females. Soluble leptin receptor and HDL-C were significantly lower in the overweight and obese males and females. Cholesterol and LDL-C were significantly higher in the overweight and obese females, but there was no significant difference in the overweight and obese males when compared with the control males. Low soluble leptin receptor levels were found in 38.1% (8/21) of the overweight and obese males, while 31.5% (29/92) were found in the overweight and obese females. Elevated leptin levels were found in 66.7% (32/48) and 89.8% (149/166) of the overweight and obese males and females, respectively. Both low soluble leptin receptor levels and elevated leptin levels were found in 9.5% (2/21) and 29.4% (27/92) of the overweight and obese males and females, respectively. A significant positive correlation was found between soluble leptin receptor and cholesterol, and between weight, BMI, waist, hip and HDL-C, with leptin. Serum soluble leptin receptor levels were significantly negatively correlated with leptin and BMI. The results can elucidate the causes and consequences of obesity, and are expected to aid the provision of care for overweight and obese Thai people.

Gastrointestinal manifestations of septic patients with scrub typhus in Maharat Nakhon Ratchasima Hospital.

Scrub typhus is an acute febrile illness caused by Orientia induced vasculitis, which is common in Asia and the Pacific Islands and is sometimes also encountered in Western countries. Even though it can cause multi-organ dysfunctions, there is limited information regarding the relationship between scrub typhus infection and gastrointestinal dysfunction. Therefore, a cross-sectional study was conducted to discover the gastrointestinal manifestations of septic patients with scrub typhus infection. During the study period, 80 septic cases were recruited, and according to the results of immunofluorescent antibody testing (IFA), 20 (25%) were found to have scrub typhus infection. The most common gastrointestinal symptoms of scrub typhus patients were vomiting 13 (65%), nausea 12 (60%), diarrhea 9 (45%), and hametamesis or melena 5 (25%). Gastrointestinal signs included hepatomegaly 8 (40%), jaundice 7 (35%), and abdominal pain 4 (20%). Elevation of SGOT, SGPT, and alkaline phosphatase were 16 (80%), 14 (70%), and 16 (80%), respectively. Direct bilirubin was elevated in 19 (95%) of the cases and half of the cases had a low serum protein level. Of scrub typhus cases, 8 (40%) had eschars. The sites of eschars were mostly in hidden areas, such as on the back, genitalia and abdomen. Three of the five patients with eschar had hepatomegaly on ultrasound examination. The significant findings of the scrub typhus septic patients with eschar on endoscopic examination were gastritis in two cases, gastritis with gastric erosion in two cases, and one case showed a duodenal ulcer and erosion. The differentiating point for endoscopic findings in scrub typhus compared to the other causes was that the stomach lesions were more frequent and severe than the duodenal lesions. According to our endoscopic findings, physicians should be aware of gastric and duodenal lesions in febrile patients with gastrointestinal symptoms, such as abdominal pain or discomfort and indigestion. Scrub typhus can cause gastrointestinal and liver dysfunction.

Antioxidant enzyme levels in the erythrocytes of riboflavin-deficient and Trichinella spiralis-infected rats.

The erythrocyte antioxidant enzyme levels of catalase, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of riboflavin-deficient and Trichinella spiralis-infected rats were investigated. The rats were deprived of riboflavin at the 8th week of the experiment. At that time, the erythrocyte glutathione reductase activity coefficient (EGR AC), as an indicator of riboflavin status, was > or = 1.30 in rats fed a riboflavin-deficient diet and T. spiralis-infected rats fed a riboflavin-deficient diet showed no biochemical sign of riboflavin deficiency. At the 12th week of the experiment, the levels of catalase, SOD and GSH-Px were significantly lower in the riboflavin-deficient, T. spiralis-infected, and combined riboflavin-deficient and T. spiralis-infected, rats, compared to the control group. This may have been due to an increase in free oxygen radicals caused by riboflavin deficiency and parasitic infection.

Serum copper, zinc, ceruloplasmin and superoxide dismutase in Thai overweight and obese.

The serum copper, selenium, ceruloplasmin, superoxide dismutase (SOD) (specific activities of antioxidant enzymes), anthropometric measurements, including waist/hip ratio 51 male and 190 female overweight subjects (body mass index (BMI) > or = 25.0 kg/m2) compared with a 26 male and 83 female control group (BMI = 18.5-24.9 kg/m2) Thai volunteers who attended the Out-patient Department, General Practice Section, Rajvithi Hospital, Bangkok, for a physical check-up from March to October, 1998, were investigated. There was no age difference between the overweight group and the controls. All of the anthropometric variables, except the height of the overweight group, were significantly higher than those of the normal subjects. The medians of weight and waist/hip ratio of overweight and obese males were significantly higher than those of overweight and obese females. Serum ceruloplasmin, copper were statistically significantly higher in overweight subjects than in the controls. However, serum zinc and superoxide dismutase activity in the overweight group were found to be lower than in the control group. Higher serum ceruloplasmin, copper, zinc and superoxide dismutase activity were shown in the female overweight group than in the male overweight group. Ceruloplasmin was found to correlate positively with copper concentration but negatively related with superoxide dismutase enzyme activity. A negative correlation was found between serum copper and zinc concentrations in both sexes of the overweight and obese subjects. Low SOD activity found in the overweight and obese subjects might be caused by low zinc intake.

Evaluation of attitude, risk behavior and expectations among Thai participants in Phase I/II HIV/AIDS vaccine trials.

The Understanding of volunteers in vaccine trials about their role as study participants and their voluntary commitment during the study are always one of the important concerns apart from evaluation of safety and efficacy of vaccine trials, especially in HIV prophylactic vaccine trials. The apprehension of indirectly risky behavior encouragement and deviated expectations among volunteers should be of concern. The current prospective cohort study aimed to assess and monitor the changes of risk behaviors, attitude and expectations among 164 volunteers from 2 studies of different prophylactic HIV vaccines, the Chiron HIV Thai E gp 120/MF59 +/- the Chiron HIV SF52 gp120 and Aventis Pasteur Live Recombinant ALVAC HIV (vCP1521) priming with VaxGen gp120B/E (AIDSVAX B/E) boosting. 113 males and 51 females with a mean age (+/- SD) of 28.82 +/- 7.97 years old were enrolled from October 1997 to December 1998 and February 2000 to April 2001. Education and risk reduction counseling were regularly performed at every visit and questionnaires about risk behaviors, knowledge, attitudes, social influences and expectations were asked at baseline, 4 months and 12 months. No change of potentially HIV transmission related risk behavior was observed during the studies. There was a statistically significant decrease of risk sexual practices from the beginning of the trials (42.2% vs 1%, p < 0.0001). While 35.2 per cent from 62.2 per cent of the volunteers at the beginning of the study continued sexual practice with an identified single sexual partner at the end of the study (p < 0.0001). All of the volunteers expressed the beneficial expectations as knowledge gain, social contribution, feelings of having gained merit and self-benefits from health check-ups.

Septic shock secondary to scrub typhus: characteristics and complications.

Scrub typhus is an acute febrile illness caused by infection with Orientia tsutsugamushi transmitted by the bite of larval trombiculid mites (chiggers). A prospective study was conducted in septic shock patients in Maharat Hospital, Nakhon Ratchasima Province, Thailand, from 12 November 2001 to 5 January 2002. Of the 51 septic shock patients studied during the 7 week period, 18 (35.3%) were found to have evidence of scrub typhus infection; 3 patients (16.7%) died. In this study, septic shock caused by Orientia tsutsugamushi is the most prominent (35.3%) in endemic area of scrub typhus. Scrub typhus with septic shock patients results in organ failure: respiratory failure, DIC were predominant, followed by renal and hepatic involvement. Two deaths were due to respiratory failure and one death was as a result of combined respiratory and renal failure. Fever was the most common symptom, followed by headache, myalgia and dyspnea; lymphadenophathy and eschar are common signs. Laboratory findings revealed that almost all of the patients had a mild leukocytosis, reduced hematocrit and thrombocytopenia; SGOT, ALP, direct bilirubin (DB), total billirubin (TB), BUN, Cr were elevated; hypoalbuminemia was noted. Urinalysis showed that 88.9% of the patients had albuminuria. 77.8% of patients had abnormal chest X-rays.

Clinical and mycological responses to fluconazole and fluconazole MIC in oropharyngeal candidiasis in HIV-infected patients.

INTRODUCTION: OPC is a common opportunistic infection in HIV-infected patients. Although some patients are asymptomatic, progression of the disease may occur leading to esophageal candidiasis. Fluconazole resistant candidiasis has been reported in several international studies. OBJECTIVES: This study aimed to test the MICs (minimal inhibitory concentrations) to fluconazole of Candida species isolated from mouthwash specimens of 54 HIV positive patients with oral candidiasis. Clinical and mycological responses to fluconazole were also assessed in 16 patients. MATERIAL AND METHOD: This was a prospective study. Mouthwash specimens were cultured on sabouraud dextrose agar twice. Candida species identification was performed and MICs for fluconazole were obtained using NCCLS guidelines. Clinical and mycological responses were assessed on day 14 and 42 in 16 patients who received a 14-day course of fluconazole. RESULTS: 48/54 patients (88.89%) were found to carry pure C. albicans. The other 6 patients (11.11%) had mixed Candida species on cultures. Among these 6 patients, 5 patients had mixed C. albicans and C. glabrata, and 1 patient had C. albicans and C. krusei. Fluconazole MICs of C. albicans, C. glabrata, and C. krusei ranged from 0.125-32 (median=0.250), 4-64 (median=2), and 8 g/L respectively. This study showed that the MICs to fluconazole of oropharyngeal Candida was a good predictor of the therapeutic responses.

Mycobacterium tuberculosis infection among HIV/AIDS patients in Thailand: clinical manifestations and outcomes.

A one year retrospective study, was conducted at Bamrasnaradura Hospital, Nonthaburi Province, Bangkok, Thailand, of 271 subjects with both TB and HIV/AIDS. Single males (median age group 31 to 40 years) were most likely to develop co-infection. The commonest clinical manifestations on initial presentation included a low grade fever, cough, weight loss, lymphadenopathy with pancytopenia, and lung infiltrates. Multi-drug resistant TB (MDR-TB) was found in 26.6% of the subjects which was significantly associated with a past history of anti-TB treatment (p = 0.005; OR=2.5); it was also significantly associated with disseminated TB (p = 0.022; OR=1.9) and mortality (p= 0.013; OR=2.8). Analysis of clinical outcomes showed that 46.7% were lost to follow-up and 13.3% had died by the time of follow-up. Among those who survived, only 11.4% had been successfully treated; the rest had not improved due to relapse (2.9%), therapeutic failure (8.8%), treatment in progress (5.9%), and failure to complete treatment (10.7%).

The effect of cigarette smoking on ceruloplasmin and C3 complement: risk of cardiovascular disease (atherosclerosis).

Serum ceruloplasmin, C3 complement and albumin in 119 male smokers and 65 male non-smoker; from a military unit in Bangkok were investigated in this study. The serum ceruloplasmin concentration was found to be significantly higher in smokers than in non-smokers. However, the serum albumin concentration in smokers was statistically significantly lower than in non-smokers. Significant associations were also found between ages, albumin levels and the quantity of cigarettes smoked. There was a significant positive correlation between serum ceruloplasmin and C3 complement concentrations. An association between the quantity of cigarettes smoked and albumin was also found, as well as a significant relationship between smoking and the quantities of cigarettes smoked to serum ceruloplasmin levels when smoking and the quantity of cigarettes smoked were taken as independent variables, and the serum ceruloplasmin levels as a dependent variable. This might suggest that high concentrations of the acute-phase protein, i.e. ceruloplasmin, might constitute a risk of developing atherosclerosis or cardiovascular disease in smokers.

B vitamins, vitamin C and hematological measurements in overweight and obese Thais in Bangkok.

The dynamic changes of socio-economics leading to the industrialisation of countries are known to affect lifestyle and nutritional behaviours of the population. Review of the literature on the prevalence of obesity showed increasing numbers of the overweight and obese during the past decade. However, information on health and nutritional status of the obese in Thailand has not been widely publicized. This study reveals the vitamin status and hematological picture in 270 overweight and obese Thais in Bangkok, Thailand, compared with 175 normal subjects. No statistically significant differences in haemoglobin and hematocrit were observed in the overweight compared with the control subjects. The prevalence of anaemia was 9.8 per cent among male and 17.2 per cent among female overweight and obese subjects compared with 2.6 per cent and 21.2 per cent in male and female normal controls using the cut-off point of haemoglobin concentration as an indicator of anaemia. Prevalence of hypertension was exhibited in both male and female overweight and obese subjects. Even if there were no statistically significant differences in vitamin B1, B2 and B6 in overweight and obese subjects compared with the controls, high percentages of vitamin C and vitamin B2 deficiencies were observed. Vitamin B2 deficiency was detected in 19.7 per cent of overweight and obese males as well as in 28.7 per cent of overweight and obese females using glutathione reductase activity coefficient (alpha EGR) < 1.5 as the cut-off point. However, clinical signs of vitamin B2 deficiencies were rare. There was also a high percentage of vitamin C (antioxidant vitamin) deficiency in 51.5 per cent of the overweight and obese subjects and 41.7 per cent of the controls, respectively. The results suggest more attention should be paid to health study and nutritional problems for the overweight and obese population, especially concerning vitamins and oxidative stress. Further research is still needed in these aspects.