Assessment of age-related isoniazid hepatotoxicity during treatment of latent tuberculosis infection.

BACKGROUND: Since the introduction of new recommendations for the treatment of latent tuberculosis infection (LTB1) disregarding age as a limitation, increasing numbers of older individuals are expected to undergo treatment with isoniazid for the prevention of tuberculosis, raising the potential for an increase in isoniazid hepatotoxicity. OBJECTIVE: To compare the frequency of hepatotoxicity requiring withdrawal of isoniazid therapy for LTB1 in patients under and over 35 years of age, managed according to current practice guidelines. DESIGN: A retrospective analysis of 300 patients who underwent isoniazid therapy for LTB1 according to a protocol based on the current practice guidelines. SETTING: Public health clinic of Passaic County, NJMain outcome measures: The frequency of symptomatic isoniazid hepatitis in various age groups. RESULTS: Of 165 patients < 35 years of age, 3(2%) patients developed hepatitis (AST > 3 times the upper limit of normal). Of 135 patients > or = 35 years of age, 4(3%) patients developed hepatitis. Statistical comparison between the two groups failed to show a significant difference (p = 0.705). CONCLUSIONS: No difference was detected in the frequency of isoniazid hepatotoxicity between patients < 35 and > or = 35 years of age. Clinically monitored isoniazid therapy of LTB1 patients > or = 35 years of age may not predispose subjects to an increased risk of hepatotoxicity. Limitations of this work include the small sample size and the retrospective nature of the study.

Serum magnesium levels and acute exacerbation of chronic obstructive pulmonary disease: a retrospective study.

A decrease in serum Mg(+2) is associated with airway hyper-reactivity and impaired pulmonary function. The purpose of this study was to determine if decreased serum Mg(+2) levels in patients with chronic obstructive pulmonary disease (COPD) are associated with acute exacerbations. In a retrospective study, the charted serum Mg(+2) levels in 100 COPD patients were examined. These included 50 patients who presented with an acute exacerbation of COPD and 50 stable patients. Chart review was sequential within both groups. Serum Mg(2+) levels in the stable COPD patients averaged 0.91+/- 0.10 mmol/L (mean+/- SD) with a 95% CI of 0.88 - 0.94 mmol/L. Patients undergoing an exacerbation had significantly lower serum Mg(+2) levels (0.77+/- 0.10 mmol/L; CI, 0.74 - 0.79; p<0.0001). Logistic regression of the dichotomous outcomes as a function of serum Mg(+2) concentration demonstrated a highly significant association (chi(2)=41.26; p<10(-5)). These data were subjected to receiver-operator characteristic (ROC) analysis for decision levels (DL) and the area under the ROC curve was determined to be 0.85+/- 0.04 (CI, 0.78 - 0.93). The optimum DL was determined to lie between 0.80 mmol/L (OR=14.33; sensitivity 70%; specificity 86%) and 0.84 mmol/L (OR=11.16; sensitivity 84%; specificity 68%). These data suggest that at the lower range of the reference interval, serum Mg(+2) levels are associated with an increased risk of exacerbation of symptoms in COPD patients. Furthermore, they suggest a DL that is useful for predicting clinical outcomes in these patients and serving as a target value for therapy.

Acute flaccid paralysis: the spectrum of a newly recognized complication of West Nile virus infection.

OBJECTIVES: Acute flaccid paralysis (AFP) has recently emerged as a major central nervous system complication associated with West Nile virus (WNV) infection. The spectrum of clinical presentations of AFP in WNV infection and its sequelae have not been well-studied. METHODS: We describe three patients with AFP due to WNV infection and review the clinical presentations of 56 patients with this complication derived from published studies. RESULTS: Patients with AFP and WNV presented with a spectrum of illness ranging from single extremity paralysis to quadriparalysis with cranial nerve involvement. Patients commonly developed respiratory failure (54%) and bladder dysfunction (22%). While fever was nearly universal (92%), signs of meningismus were less common (17%). Cerebrospinal fluid (CSF) analysis generally revealed a modest pleocytosis, and imaging studies were not diagnositic. Persistent neurologic impairment occurred in all survivors; overall mortality rate was high (22%) and was associated with both the extent of paralysis and advanced age. CONCLUSION: AFP in the setting of WNV is associated with significant mortality and long-term morbidity.

Monitoring of DNA damage in foundry and pottery workers exposed to silica by the alkaline comet assay.

BACKGROUND: Workers in foundry and pottery are exposed to a mixture of chemicals and silica, which is suspected to cause genetic alterations. METHODS: To investigate the potential hazard associated with the occupational exposure to silica, DNA damage in the peripheral lymphocytes of 30 foundry and 22 pottery workers were examined by the alkaline single-cell gel electrophoresis or Comet Assay, and compared to 52 healthy subjects with no history of occupational silica or chemical exposure. RESULTS: The DNA damage observed in the lymphocytes of both foundry and pottery workers was significantly higher than that in their controls. Cigarette smoking was also related to DNA damage since the DNA damage observed in smoking silica-exposed workers compared with the non-smoking workers was significantly higher. CONCLUSIONS: Occupational exposure of silica from foundry and pottery workplaces has been associated with the increased DNA damage and smoking which represents an additional risk factor and must be avoided.

Alterations in immune parameters in foundry and pottery workers.

To assess the immune competence of workers occupationally exposed to mainly silica, peripheral blood lymphocytes, serum immunoglobulins (IgG, IgA and IgM), C3 and C4 complement protein concentrations of foundry and pottery workers were evaluated and compared to healthy controls with no history of silica and other chemical exposure. The absolute number and percentage of functionally different subsets of peripheral blood mononuclear lymphocytes, i.e. T, T-suppressor and natural killer cells were unchanged. However, T-helper lymphocytes in pottery (P<0.05) and B cells in foundry (P<0.01) workers were significantly lower when compared to their controls. In addition, silica-exposed foundry workers had a significant reduction in the IgG, IgA and IgM levels. No significant differences were observed in the serum complement C3 and C4 levels of the workers. These results suggest that human chronic exposure to mainly silica and other chemicals originating from foundry and pottery settings may be detrimental to the immune system.