Demographic pattern and clinical characteristics of patients with smear- positive pulmonary tuberculosis in kuwait.

OBJECTIVE: The aim of this study was to document various clinical factors that are likely to be of help in the control of tuberculosis in Kuwait. SUBJECTS AND METHODS: Details of patients with sputum positive for acid-fast bacilli in the period from January 1998 to December 2000 were collected retrospectively from the case records and population statistics from government sources. The data were then tabulated and analyzed. RESULTS: Of the 526 cases, 83.5% were expatriates and 16.5% Kuwaiti; 373 (70.9%) were male. Of the expatriates, 66.7% were from Asia and the Far East, 5.7% were > or =60 years. The annual incidence was 8.34 per 100,000 population. The lowest incidence was observed in the Jahrah governorate with an overall incidence of 5 (2.0 among Kuwaitis and 6.4 among expatriates) per 100,000 population. The highest incidence overall (10.2) and among Kuwaitis (4.1) was observed in the Farwaniya governorate, while the highest incidence among expatriates was seen in the Capital governorate (13.4). Radiologically, 94 (19.5%) had minimal, 246 (51.5%) had moderately advanced and 141 (29.3%) far-advanced disease. The majority of the patients (72%) had only + status for AFB in the smear. Hypercalcemia (25.7%), hyponatremia (22.15%) and hyperglycemia (29.9%) were common in the patients. Mean serum albumin was low (28.7 +/- 5.5 g/l). Two hundred and forty-seven (47.2%) were declared cured while 116 (22.2%) completed treatment. Comparison between nationals and expatriates showed a significant difference only for age, smoking status, defaulter rate and place of residence. CONCLUSION: The lowest regional incidence was found in the Jahrah governorate. Both biochemical abnormalities and radiologically advanced presentations were common. Disease pattern and response to treatment was purely individual and did not differ with respect to nationality or race.

HLA-DR binding prediction and experimental evaluation of T-cell epitopes of mycolyl transferase 85B (Ag85B), a major secreted antigen of Mycobacterium tuberculosis.

OBJECTIVE: To identify T-cell epitopes of Ag85B by analysis of its sequence for prediction to bind HLA-DR alleles and evaluate the predicted peptides for recognition by T cells in antigen-induced proliferation assays. MATERIALS/SUBJECTS AND METHODS: The complete sequence of Ag85B was analyzed for HLA-DR binding prediction to 51 HLA-DR alleles by using a virtual matrix-based prediction program (ProPred). Synthetic peptides covering the sequence of mature Ag85B were also analyzed for binding to HLA-DR alleles, and evaluated for recognition in antigen-induced proliferation assays with Ag85B-specific T-cell lines established from the peripheral blood mononuclear cells of 10 HLA-DR-heterogeneous tuberculosis patients. RESULTS: The ProPred analysis of the full-length Ag85B (325 aa), signal peptide (40 aa) and the mature protein (285 aa) predicted their binding to 100, 76 and 98% of the 51 HLA-DR alleles, respectively. The analysis of 31 synthetic peptides for binding to HLA-DR alleles showed that 4 of them could bind >50% HLA-DR alleles, and were considered promiscuous. Testing of Ag85B-specific T-cell lines with synthetic peptides showed that all of the T-cell lines responded to one or more peptides of Ag85B, and 9 of the 10 cell lines responded to one or more of the four peptides considered promiscuous for binding to HLA-DR alleles. CONCLUSION: The ProPred program was useful in predicting the HLA-DR alleles binding regions of Ag85B and identifying the promiscuous peptides recognized by T cells.

Flexible fiberoptic bronchoscopy. Diagnostic yield.

OBJECTIVE: Fiberoptic bronchoscopy is a minimally invasive procedure with a high diagnostic yield. The aim of this study was to document the usefulness of the procedure in the diagnosis of various respiratory disorders in a Middle East country. METHODS: Data on all bronchoscopies carried out in Chest Diseases Hospital, Kuwait from January 1996 to December 1998 were retrospectively collected. RESULTS: Out of 968 cases, only 620 (64%) patients had a full follow up. Suspected pulmonary tuberculosis (TB) (51.6%), unresolving pneumonia (16.1%), hemoptysis with a normal chest radiograph (8.4%), lung mass (7.7%) and hilar lymphadenopathy (3.2%) were the most common indications. Eleven percent of patients who underwent bronchoscopy had a normal chest radiograph, the reason being hemoptysis in 75.4%, inhalation injury in 21.8% and suspected upper airway obstruction in 2.9%. In smear negative suspected TB cases, 22.5% proved to have active disease. Acid fast bacillus was identified in bronchoalveolar lavage, either by smear or culture, in 44 (73.3%) patients with suspected pulmonary TB and in 6 (54.5%) patients with miliary shadows. An underlying cause was identified in 28 (28%) patients with unresolving pneumonia. Ninety-four percent of cases with clinical impression of bronchogenic carcinoma could be diagnosed. Transbronchial biopsy was diagnostic in 79% patients with diffuse parenchymal lung disease. No complications other than transient hypoxemia and controllable bleeding were noticed. CONCLUSION: Generally, the indications for flexible fiberoptic bronchoscopy remained similar to elsewhere. Unlike western series, the majority of the cases were for the diagnosis of pulmonary infections especially TB.

Percutaneous multiple-site parietal pleural biopsy: description and evaluation of a new and safe technique.

STUDY OBJECTIVES: (1) To describe a new percutaneous pleural biopsy technique to obtain multiple-site parietal pleural biopsy specimens in patients with pleural effusion (PE), and (2) to evaluate its effectiveness and safety compared to current techniques. DESIGN: Prospective interventional study. SETTING: University teaching hospital. PATIENTS: Consecutively referred for evaluation of exudative PE. INTERVENTION: With the patient in a semirecumbent position, a 9F sheath was inserted by the Seldinger technique into the pleural cavity on the midaxillary line under local anesthesia and fluoroscopic guidance. An 8F bioptome was introduced through it, and biopsy specimens were taken from several sites on the costal and diaphragmatic pleura. After biopsy, PE was completely evacuated, and the sheath was removed. RESULTS: During the 2-year pilot study, we procured, on average, 14 adequate pleural specimens from each of the 28 patients (age range, 15 to 81 years) on the first attempt. Histopathologic examination revealed tuberculous pleuritis (18 patients), metastatic adenocarcinoma (1 patient), and nonspecific pleuritis (9 patients). Postprocedure, 25 patients had rapid symptomatic improvement without recurrence of PE. No major complications occurred during or after the procedure (mean follow-up period, 2 years). CONCLUSIONS: Our new biopsy procedure can be performed easily, safely, and with increased diagnostic sensitivity and patient comfort. Unlike other biopsy techniques, it provides adequate multiple-site pleural biopsy specimens, in all cases, on the first attempt without any morbidity and mortality. It has a therapeutic potential to provide rapid symptomatic relief and treatment by pleurodesis. We recommend this procedure for patients whose conditions remain undiagnosed after undergoing needle biopsy or for those who cannot tolerate it, before considering more aggressive diagnostic interventions. This is the best alternative when thoracoscopy or thoracotomy are not available or when patients are at high risk for complications from them.

In vitro effects of astaxanthin combined with ginkgolide B on T lymphocyte activation in peripheral blood mononuclear cells from asthmatic subjects.

This study was undertaken to identify novel approaches to pharmacological treatment of asthma. Here we hypothesize that the platelet-activating factor receptor antagonist ginkgolide B (GB) in combination with the antioxidant carotenoid astaxanthin (ASX) suppresses T cell activation comparably to two commonly-used antihistamines: cetirizine dihydrochloride (CTZ) and azelastine (AZE). Peripheral blood mononuclear cells from asthmatics, cultured 24 h with either 50 microg/ml phytohemaglutinin (PHA) or PHA plus selected dosages of each drug are analyzed by flow cytometry for CD25+ or HLA-DR+ on CD3+ (T cells). Results are reported as stimulation indices (SI) of %CD3+CD25+ cells or %CD3+HLA-DR+ cells in cultures treated with PHA alone versus these subpopulations in cultures treated with both PHA and drugs. Combinations of ASX and GB exhibited optimal suppression at 10(-7) M GB + 10(-8) M ASX for CD3+CD25+ (SI = 0.79 +/- 0.04, P = 0.001) and 10(-7) M GB + 10(-7) M ASX for CD3+HLA-DR+ (SI = 0.82 +/- 0.05, P = 0.004). In conclusion, suppression of T cell activation below fully stimulated values by GB, ASX, and their combinations was comparable and for some combinations better than that mediated by CTZ and AZE. These results suggest that ASX and GB may have application as novel antiasthmatic formulations.

Variations in the occurrence of the S315T mutation within the katG gene in isoniazid-resistant clinical Mycobacterium tuberculosis isolates from Kuwait.

The worldwide threat of drug-resistant tuberculosis (TB) to human health has led to the development of molecular methods for rapidly determining the resistance of clinical Mycobacterium tuberculosis isolates to the two front-line antituberculous drugs, isoniazid and rifampin. The prevalence of the S315T mutation within the katG gene, which confers clinically significant resistance to isoniazid, was determined in isoniazid-resistant clinical M. tuberculosis isolates recovered from TB patients in Kuwait. A total of 67 isoniazid-resistant and 18 susceptible clinical M. tuberculosis isolates were tested. The mutation S315T was found in 46 (69%) of the 67 resistant strains, whereas none of the susceptible strains contained this mutation. The prevalence of this mutation was highest (32 of 40, 80%) in isolates recovered from patients of South Asian origin and lowest in isolates from patients of Middle Eastern origin (8 of 18, 44%). The genotyping performed on isolates carrying the S315T mutation showed that the isolates belong to several different types as they exhibited unique DNA banding patterns. The results point to a varying prevalence of the S315T mutation within the katG gene in clinical M. tuberculosis isolates recovered from patients of different ethnic groupings within the same country. The results also suggest that detection of the S315T mutation in the katG gene may be used as a rapid screening method for identifying isoniazid-resistant clinical M. tuberculosis isolates recovered from majority of patients in some ethnic groupings.

Molecular fingerprinting of isoniazid-resistant Mycobacterium tuberculosis isolates from chest diseases hospital in Kuwait.

Touchdown double-repetitive-element-PCR (DRE-PCR) was carried out for typing 38 consecutive isoniazid-resistant Mycobacterium tuberculosis strains isolated at Chest Diseases Hospital, Kuwait, during 1998-2000. The polymorphism at codon 463 in the katG gene was also determined and correlated with genotypic relationships among the isolates. The isolates exhibited 21 distinct patterns in DRE-PCR. Nearly half of the isolates (18 of 38) exhibited unique patterns. Majority of isolates (16 of 20) yielding multiple DNA fragments in DRE-PCR were unique strains while most of the isolates (16 of 18) yielding a single DNA fragment in DRE-PCR clustered together. The prevalence of L463 in the katG gene was much higher in isolates from Middle Eastern (mostly Kuwaiti) patients than is reported for this ethnic group. The data indicate the possibility of some strains of South Asian/Southeast Asian origin spreading among local populations.