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PubMed2005

Pleural fluid and serum procalcitonin as diagnostic tools in tuberculous pleurisy.

BACKGROUND: Diagnosis of tuberculous pleuritis is difficult because of its nonspecific clinical presentation and decreased efficiency of traditional diagnostic methods. We investigated the use of procalcitonin (PCT) concentration in tuberculous pleuritis diagnosis. METHODS: A prospective clinical study was performed with two different patient groups. A total of 28 patients were included: 18 with tuberculosis and 10 with nontuberculous pleurisy. Serum and pleural fluid PCT concentrations were evaluated before treatment. RESULTS: Serum and pleural fluid PCT concentrations were statistically different between tuberculous and nontuberculous pleurisy groups (P = 0.012 and P = 0.004, respectively), even though they were not elevated in relation to the cut-off level of 0.5 ng/mL. A positive and significant correlation was detected between serum and pleural fluid PCT levels (r = 0.49, P = 0.008). Diagnostic specificity and sensitivity values for serum and pleural fluid PCT in discriminating tuberculous from nontuberculous pleurisy were 80% and 72.2%, and 90% and 66.7% at the 0.081 and 0.113 ng/mL cut-off values, respectively. CONCLUSION: Relative to the current cut-off level of 0.5 ng/mL, PCT concentration is not a useful parameter for the diagnosis of tuberculous pleurisy. Because there were PCT levels in patients with tuberculous pleurisy that were below the current cut-off level but were significantly different from those of the nontuberculous group, the use of PCT should be further investigated.

Adolescent↗

PubMed1996

Activities of total, cytoplasmic, and mitochondrial superoxide dismutase enzymes in sera and pleural fluids from patients with lung cancer.

In this study, total cytoplasmic (Cu,Zn-SOD) and mitochondrial (Mn-SOD) superoxide dismutase activities were measured in sera and pleural fluids from patients with squamous cell carcinoma of the lung. The results were compared with those of control subjects and those of patients with tuberculosis and chronic heart failure. Serum activities were found higher in all patient groups compared to control group. Highest values were however in tuberculosis group. In the correlation analysis, meaningful intra- and inter-correlations were established between enzyme activities in the samples. Results suggest that high serum and pleural fluid SOD activities are not specific biochemical parameters for carcinogenesis and, activities may also increase in some other degenerative diseases such as tuberculosis, chronic heart failure, etc. Therefore, we believe that it is not useful to use serum and pleural fluid SOD activities for diagnostic purposes in cancer. However, the activities of these enzymes in the biological samples might be used as nonspecific prognostic markers in assessing cellular and mitochondrial tissue destruction.

Adult↗

PubMed2000

Adult mortality in slums of Karachi, Pakistan.

OBJECTIVE: Cause-specific death rates are rarely available to guide health interventions for adults in South Asia. We report mortality patterns among Karachi's urban poor. METHODS: We conducted verbal autopsies for adult deaths under active surveillance during 1990-1993 in five urban slums of Karachi. Two physicians assigned underlying cause of death by consensus. Analysis included cause- and category-specific rates, 45Q15s and comparison with 1991 Japanese national statistics. RESULTS: All 345 adult deaths (15-59 years) in the 5 slums (total population 45,389) were included. Male mortality exceeded female (4.4 vs 3.3/1000, p = .02). Noncommunicable diseases claimed 59% of deaths, communicable and reproductive 27% and injuries, 15%. The leading identified death rates (/100,000) among women were: circulatory disorders (66), maternal causes (33), tuberculosis (30), and burns (23); and among men they were: circulatory disorders (124) tuberculosis (30) and road traffic accidents (30). Overall Karachi adult mortality was 3.7 times Japanese rate. Compared to Japan, adults in Karachi had one to two orders of magnitude excess mortality due to maternal causes, tuberculosis and burns. Circulatory disorders and tuberculosis accounted for 47% of excess male mortality; these plus maternal causes and burns accounted for 55% of excess female mortality. CONCLUSION: These mortality levels and patterns compel interventions and research for poor urban adults beyond maternal health. Women's health would equally benefit from tuberculosis control or burn prevention. Men need safer travel. Both need improved cardiovascular health.

Adolescent↗

PubMed2006

Deconfounding microarray analysis - independent measurements of cell type proportions used in a regression model to resolve tissue heterogeneity bias.

OBJECTIVES: Microarray analysis requires standardized specimens and evaluation procedures to achieve acceptable results. A major limitation of this method is caused by heterogeneity in the cellular composition of tissue specimens, which frequently confounds data analysis. We introduce a linear model to deconfound gene expression data from tissue heterogeneity for genes exclusively expressed by a single cell type. METHODS: Gene expression data are deconfounded from tissue heterogeneity effects by analyzing them using an appropriate linear regression model. In our illustrating data set tissue heterogeneity is being measured using flow cytometry. Gene expression data are determined in parallel by real time quantitative polymerase chain reaction (qPCR) and microarray analyses. Verification of deconfounding is enabled using protein quantification for the respective marker genes. RESULTS: For our illustrating dataset, quantification of cell type proportions for peripheral blood mononuclear cells (PBMC) from tuberculosis patients and controls revealed differences in B cell and monocyte proportions between both study groups, and thus heterogeneity for the tissue under investigation. Gene expression analyses reflected these differences in celltype distribution. Fitting an appropriate linear model allowed us to deconfound measured transcriptome levels from tissue heterogeneity effects. In the case of monocytes, additional differential expression on the single cell level could be proposed. Protein quantification verified these deconfounded results. CONCLUSIONS: Deconfounding of transcriptome analyses for cellular heterogeneity greatly improves interpretability, and hence the validity of transcriptome profiling results.

Cell Physiological Phenomena↗

PubMed2004

[Treatment of bronchial obstruction in patients with pulmonary tuberculosis].

Whether the main points of treatment for bronchial obstructive syndrome (BOS) in chronic obstructive lung disease (COLD) can be adapted for patients with pulmonary tuberculosis (PT) was studied. For this purpose, 435 patients with PT with signs of BOS (forced expiratory volume at 1 second (FEV1) < 80% of the normal values) were examined. To establish differences in the efficiency of therapy, according to the activity of a process and to the magnitude of the impaired architectonics of the respiratory system, three main groups of observation were formed: 1) patients with infiltrative PT (IPT); 2) those with fibrocavernous PT (FCPT); and 3) those with posttuberculous pneumosclerosis (PS). According to the severity of BOS, the patients were divided into 3 subgroups: 1) 104 patients with FEV1 > 70% of the normal values; 2) 229 patients with FEV1 69-50%; 3) 102 patients with FEV1 < 50%. The patients with IPT and FCPT received the conventional antituberculous therapy under respective clinical, laboratory, and X-ray control. The patients with PS had no antituberculous therapy. All the patients underwent 3-month clinical and functional monitoring evaluating changes in life quality, by using the respiratory questionnaire of the Saint George hospital. The findings have led to the conclusion that the use of the proposed therapy for bronchial obstructive syndrome in patients with pulmonary tuberculosis was highly effective, promotes the amelioration of the degree of respiratory symptoms in patients with IPT by 2 to 8 times, in those with FCPT by more than 2-3 times, and in those with PS by 1.45-10 times. The differences in the efficiency of bronchodilator therapy depend on the baseline level of bronchial obstruction. In patients with pulmonary tuberculosis concurrent with BO, the use of current inhalation bronchodilator therapy results in a substantial increase in FEV1, which differentiates BOS in PT from COLD. The use of the proposed therapy in the multimodality treatment of patients with pulmonary tuberculosis showed no statistically significant differences in the changes in the degree of X-ray symptoms while this therapy permits acceleration of abacillation in patients with IPT by 16.8% and in those with FCPT by 14.8%. Effective bronchodilator therapy considerably enhances life quality in patients. Thus, early systematic and long-term performance of the bronchodilator therapy, based on the principles of bronchodilator therapy for COLD, in patients with PT concurrent with BOS may substantially enhance the efficiency of treatment in this category of patients.

Antitubercular Agents↗

PubMed1997

Factors influencing completion of treatment among tuberculosis patients in Mbarara District, Uganda.

An organised TB treatment programme was started in Uganda in 1989. A cohort analysis of treatment outcome among 1400 patients seen in Mbarara district in 1995 showed a very low compliance rate of 56% and this study attempted to look at operational factors that may be associated with this low compliance rate. The factors that are associated with enhanced completion of treatment include; being smear positive: use of short course chemotherapy; previous TB treatment; if patient returned for repeat smear; if patient did not change unit; and if patient did not change district. Gender and age were not associated with compliance. On unconditional logistic regression, previous TB treatment and being smear positive were found not to be statistically significant. Change of health unit after intensive phase showed the highest risk, with an adjusted odds ratio of 22.31. Of the significant factors only use of standard chemotherapy and change of health unit after intensive phase can be altered to improve compliance.

Adolescent↗

PubMed2004

Tuberculosis incidence and mortality in aboriginal areas of Taiwan, 1997-2001.

BACKGROUND AND PURPOSE: People living in aboriginal areas of Taiwan are known to be at especially high risk of developing tuberculosis (TB). This study investigated the incidence and mortality of TB in aboriginal areas of Taiwan. METHODS: The TB death statistics and notification data from the National TB Register and Department of Health in 1997-2001 were analyzed. RESULTS: From 1997 to 2001, people living in aboriginal areas bore a disproportionate burden of TB disease in Taiwan, with mortality rates 5.5-6.5 times and incidence rates 3.6-5.2 times higher than those of people living in non-aboriginal areas. Among patients with TB living in aboriginal areas, 381 died, accounting for 5.1% of the 7480 TB deaths in Taiwan. A large proportion of the patients with TB who died were older than 65 years, in both aboriginal (40.2%) and non-aboriginal (78.5%) areas; however, the age of TB patients who died in non-aboriginal areas was significantly older (p < 0.001). TB patients living in the aboriginal areas accounted for 3.6% (2618/71,447) of the total number of reported TB patients in Taiwan, and 32.7% were in the age range from 24-45 years. In contrast, TB patients living in non-aboriginal areas were typically older, with only 20.1% in the 24-45 age range (p < 0.001) and 44.4% older than 65 years (p < 0.001). In terms of incidence and mortality rates, men predominated in both groups; however, this pattern was less prominent in aboriginal areas than in non-aboriginal areas. CONCLUSIONS: The mortality rates and incidence of TB in aboriginal areas are much higher than those in non-aboriginal areas in Taiwan. Concentration of resources and programs to control TB in aboriginal areas may represent the most effective use of resources for fighting TB.

Adolescent↗

PubMed2001

Comparison of the effectiveness of WHO short-course chemotherapy and standard Russian antituberculous regimens in Tomsk, western Siberia.

BACKGROUND: There has been a resurgence of tuberculosis in Russia in the past decade. Traditional Russian services for treatment of tuberculosis are very different from those in the west. We aimed to compare the effects of WHO short-course chemotherapy with standard Russian antituberculous regimens. METHODS: New tuberculosis patients aged 18 years or older were included in a trial and systematically allocated to traditional Russian tuberculosis treatments or WHO short-course chemotherapy in the two largest tuberculosis diagnostic and treatment centres of Tomsk Oblast, western Siberia. Standard WHO tuberculosis outcomes and rates of sputum conversion were used as primary outcomes. Analyses were by intention-to-treat. FINDINGS: 646 new cases were enrolled into the trial, of which 356 patients were given Russian tuberculosis treatment (155 smear positive) and 290 were given WHO short-course chemotherapy (155 smear positive). There was no statistical difference between the proportion cured or completing treatment (63% for both groups [difference in proportion=0%, 95% CI -11 to 11%]); or dying (short-course chemotherapy, 8% vs Russian, 11% [difference in proportion=-3%, 95% CI -9 to 4%]). There was no statistical difference with respect to sputum conversion rate at 6 months (91% vs 85% [difference in proportion=6%, 95% CI -2 to 13%]). Overall, outcomes were worse among patients with multidrug resistant isolates than non-resistant isolates. INTERPRETATIONS: WHO short-course chemotherapy treatment for tuberculosis can work well in Russia.

Adult↗

PubMed2002

Bioequivalence assessment of rifampicin, isoniazid and pyrazinamide in a fixed dose combination of rifampicin, isoniazid, pyrazinamide and ethambutol vs. separate formulations.

Depending on the patient category, tuberculosis requires treatment with 3 to 5 drugs which means that patient's compliance to therapy may not be optimal. To increase patient's adherence to treatment schedules, these drugs can be given as single drug preparations or fixed dose combinations (FDCs) of 2 or more drugs in a single formulation. However, an important issue associated with a rifampicin-containing FDC is its quality. Hence, to avoid spurious formulations entering the market, the World Health Organization and the International Union Against Tuberculosis and Lung Disease have recommended FDCs only of proven bioavailability. In this study, the relative bioavailability of rifampicin, isoniazid and pyrazinamide was assessed in a group of 14 healthy male subjects using the FDC tablet containing 4 drugs versus separate formulations at the same dose levels. The study was designed as an open, crossover trial. A total of 9 blood samples were collected over a period of 24 h. The concentration of rifampicin, its main metabolite desacetyl rifampicin, isoniazid and pyrazinamide in plasma were assessed using HPLC analysis. The pharmacokinetic parameters AUC(0-24) and Cmax were subjected to parametric and non-parametric statistical tests at 90% confidence interval. In addition, time to reach peak concentration (tmax), elimination rate constant (Kel) and terminal elimination half-life (t1/2) for each drug were also calculated. It was concluded that the FDC tablet containing 4 drugs is bioequivalent to separate rifampicin, isoniazid and pyrazinamide formulations at the same dose levels.

Analysis of Variance↗

PubMed2000

Comparison of retroperitoneoscopic nephrectomy with open surgery for tuberculous nonfunctioning kidneys.

PURPOSE: We describe, define and evaluate the role of retroperitoneoscopic nephrectomy for tuberculous nonfunctioning kidneys, and compare the results with those of open nephrectomy in similar cases in a nonrandomized study. MATERIALS AND METHODS: Beginning in July 1994, 9 patients underwent retroperitoneoscopic nephrectomy for tuberculous nonfunctioning kidneys at our center. Data obtained from the records of these patients were compared with those of 9 who underwent open nephrectomy for a similar indication during the same period. Retroperitoneoscopic nephrectomy was initially performed by kidney dissection followed by ligation of the hilar vessels. The technique was subsequently modified and the vessels controlled before dissecting the kidney. Various parameters were compared and statistical analysis was done. RESULTS: The 2 groups were similar in regard to patient age, gender and side of disease. Retroperitoneoscopic nephrectomy was successful in 7 of the 9 patients. Although 2 of our initial patients required conversion to open surgery, the remaining 7 successfully underwent retroperitoneoscopic nephrectomy after modifying the technique. Mean operative time was slightly greater in the retroperitoneoscopy than in the open surgery group (103.3 versus 92.2 minutes). Mean blood loss was less in the retroperitoneoscopy group (101.4 versus 123.3 ml.), mean hospital stay plus or minus standard deviation was significantly shorter (3.2 +/- 0.83 versus 8.88 +/- 3.37 days) and mean time to return to work was significantly less (3 versus 7 weeks). Mean analgesic requirement for opioids and diclofenac sodium was also lower in the retroperitoneoscopic nephrectomy group (0 versus 1.44 +/- 0.72 and 3.8 +/- 1.3 versus 4.3 +/- 1.2 doses, respectively). Minor complications developed in only 2 retroperitoneoscopy cases. CONCLUSIONS: Tuberculosis has been considered a contraindication to retroperitoneoscopic nephrectomy due to a high conversion rate. However, we believe that our modified technique of retroperitoneoscopic nephrectomy is a viable option for managing tuberculous nonfunctioning kidneys. The conversion rate is lower than previously reported. Comparing our results with those of open nephrectomy shows that retroperitoneoscopic nephrectomy is beneficial in all respects except for slightly longer operative time. Because of the benefits of minimally invasive surgery, this approach should be considered in such cases.

Adolescent↗

PubMed2003

Antibodies to diverse lipids in the serum of patients with clinically cured leprosy and tuberculosis.

In this study we looked for the presence of antibodies to cardiolipin, cerebrosides, and whole lipids extracted from M. leprae, M. tuberculosis and M. habana, in the serum of patients with clinically cured lepromatous leprosy (sixteen) or tuberculosis (sixteen), 8 to 12 months after arresting the corresponding multi-drug therapy (MDT). Compared to healthy controls (sixteen), both leprosy and tuberculosis ex-patients had still significant levels of antibodies to the three mycobacterial lipids but no detectable levels of antibodies to cardiolipin or cerebroside lipids. Although leprosy and tuberculosis sera recognized the homologous mycobacterial lipids in a preferential fashion, all of them, on the average, reacted more strongly with the lipids of M. habana. This observation backs up, in a certain way, the proposition of using M. habana as a prospective vaccine for leprosy and tuberculosis.

Adult↗

PubMed1999

Rifapentine: its role in the treatment of tuberculosis.

OBJECTIVE: To review the pharmacokinetics, efficacy, adverse effects, and cost of the newest antitubercular drug, rifapentine. DATA SOURCES: A MEDLINE search using key terms such as rifapentine, rifampin, isoniazid, Mycobacterium tuberculosis, and pyrazinamide was conducted for the time period 1966-November 1998. STUDY SELECTION: Animal data were used for basic information and human studies were selected for inclusion if they were randomized, controlled studies assessing efficacy, or if they were single- or multiple-dose studies assessing the pharmacokinetics of rifapentine. Background articles on the pathophysiology of tuberculosis and cost of care and noncontrolled studies assessing drug interactions were also included. DATA SYNTHESIS: Compared with an oral solution, the relative bioavailability of rifapentine is 70% following oral admninistration of tablets. Food increased bioavailability by 55%. Rifapentine accumulated significantly in human macrophages and its elimination half-life was longer than that of rifampin. Comparative studies of rifapentine and rifampin in humans during intensive- and continuation-phase treatment of tuberculosis suggest that at currently accepted doses, rifapentine was slightly less effective than rifampin. The most significant drug interaction with rifapentine involves indinavir: the maximum concentration and AUC of indinavir are reduced by 55% and 70%, respectively, when rifapentine is coadministered with indinavir. Adverse events of rifapentine may occur less frequently at the currently recommended 600-mg dose as compared with rifampin; however, the difference was not statistically significant. If only drug costs were evaluated during the six-month treatment of tuberculosis, rifapentine is more expensive than rifampin. CONCLUSIONS: Rifapentine can be administered twice weekly during the intensive phase of tuberculosis treatment and then once weekly during the continuation phase of treatment. This may improve patient adherence over some other treatments and possibly reduce costs of treatment by preventing development of resistant tubercular strains due to nonadherence. Rifapentine is well tolerated, with most patients experiencing adverse effects at a similar rate as rifampin. Rifapentine induces cytochrome P450 somewhat less than rifampin, although few drug interaction studies have been done with rifapentine. Its efficacy at the currently approved dosage of 600 mg may be slightly lower than that of rifampin. Studies are needed to determine if equal or greater efficacy can be achieved with higher doses of rifapentine. Rifampin is less expensive than rifapentine. Further pharmacoeconomic studies are needed to evaluate costs of relapse and failure in patients receiving these agents.

Abnormalities, Drug-Induced↗

PubMedDate not supplied

[Coping with the toll of heroin: 10 years of the Barcelona Action Plan on Drugs, Spain].

INTRODUCTION: The epidemic of heroin use began in Barcelona, as in the rest of Spain, in the late 70's, to reach its peak by the end of the 80's. In a first period, responsible officers experimented difficulties to define the specific objectives of opiate control policies. This paper reviews the effects of the adoption of an explicit policy on drug dependence grounded on a wide consensus in the City of Barcelona (Catalonia, Spain). SUBJECTS AND METHODS: Over a period of twelve years, from 1986 to 1997, both demand and offer of care and harm reduction services were analyzed, as well as the evolution of the adverse effects of drug use, such as mortality from acute adverse drug reaction, human immunodeficiency virus (HIV) infection, aids incidence, and incidence of tuberculosis. Data for city residents was compared through four different stages in this period. RESULTS: Despite the lack of data in initial years, relevant changes are apparent. Treatment offer changes clearly, with significant increases in initial treatment, coverage of methadone maintenance programmes, and sterile syringes distribution. Therapeutic compliance of tuberculous intravenous drug users IVDU and risk of HIV infection improve. Emergency service use linked to heroin, overdose, or withdrawal syndrome decreases. Mortality rates decline, although this decline does not reach statistical significance. DISCUSSION: Service offer shows a clear increase, reflected in treatment initiation, while harm reduction services expand. With the development of this process, outcome indicators change, both reflecting changes in the toll of the heroin epidemic (cases of tuberculosis and aids among IVDUs, HIV infection). and changes in a more comprehensive care (better treatment compliance of IVDUs with tuberculosis). There is a lower distortion of emergency services. These changes occur although the predominance of white heroin in Barcelona favors parenteral use.

Acquired Immunodeficiency Syndrome↗

PubMed2003

Improved immunogenicity of DNA vaccination with mycobacterial HSP65 against bovine tuberculosis by protein boosting.

A scientific review for the government of the United Kingdom has recommended that the development of a cattle vaccine against bovine tuberculosis holds the best prospects to control this disease in the national herd. As BCG vaccination of cattle results in variable degrees of protection, novel vaccine strategies that could replace or supplement BCG are required. In this study, the mycobacterial antigen HSP65 was used to determine whether priming cattle with a plasmid DNA vaccine and subsequently boosting with the recombinant protein in adjuvant (heterologous prime-boost approach) would result in improved and more homogenous immune responses over immunising with plasmid DNA or protein in adjuvant alone. The results demonstrated that strong, and compared to protein or DNA vaccination protocols alone, more homogenous, cellular immune responses were induced in cattle vaccinated with the prime-boost regimen. In addition, DNA prime-protein boost vaccination as well as protein vaccination resulted in stronger humoral immune responses with a balanced IgG profile compared to DNA vaccination alone. Importantly, none of the vaccination protocols sensitised cattle to the intradermal tuberculin test suggesting that TB subunit vaccines can be designed to allow the continued use of the tuberculin test to discriminate between vaccinated cattle and those infected with Mycobacterium bovis.

Animals↗

PubMed2001

Modulation of the inflammatory response in the rat TMJ with increasing doses of complete Freund's adjuvant.

OBJECTIVES: Acute inflammation stresses the physiological system, which must respond in order to reestablish homeostasis. The purpose of this study was to determine whether bilateral temporomandibular joint (TMJ) injections of different doses of Complete Freund's Adjuvant (CFA) produced dose-dependent changes in biologic markers of acute inflammation. The ability to establish an animal model with varying degrees of joint inflammation would allow evaluation of agents or conditions that could modulate the severity of the disease. DESIGN: The TMJs of three groups of male Sprague-Dawley rats were injected with CFA containing varying doses of Mycobacterium tuberculosis (MT). A group of non-injected and a group of saline injected rats were used as controls. Food intake, body weights, swelling and chromodacryorrhea were recorded daily. Interleukin-1 beta (IL-1 beta) and corticosterone levels were assayed and condylar cartilage thickness was measured 48 h after injections. RESULTS: Twenty-four hours post-injection, bilateral TMJ swelling and chromodacryorrhea were significantly (P< 0.05) increased following 10 microg of MT and further increased with elevated MT dose. In the CFA groups food intake was attenuated (P< 0.01) 24 and 48 h post-injection and negatively correlated with dose at 24 h. Body weight was also negatively correlated with dose. TMJ retrodiscal tissues IL-1 beta was increased (P< 0.05) in a dose-dependent manner. CFA increased corticosterone (P< 0.05), but this elevation was not dose dependent. Condylar cartilage thickness was decreased in a dose-dependent manner. CONCLUSIONS: These data suggest that an intermediate dose of CFA can be used to effect submaximal levels of TMJ inflammation that will allow experimental modulation in future studies.

Acute-Phase Reaction↗

PubMed2004

[Leukopenia due to anti-tuberculous chemotherapy including rifampicin and isoniazid].

OBJECTIVES: To examine the incidence rate by age and gender of leukopenia caused by chemotherapy including rifampicin (RFP) and isoniazid (INH), and to study the relationships between the leukopenia and the hepatic side effect or other haematological disorders such as thrombocytopenia. SUBJECTS: Out of the tuberculosis patients who were admitted to our hospital in 1987-88, 1991-92, and 1996-2000, 1,525 patients (1,153 men, 372 women) were chosen for our study who had the white blood cell counts (WBC) in the peripheral blood more than 3,000/mm3 before chemotherapy, and underwent haematologic examination at least twice within 3 months after starting chemotherapy. METHODS: The definition of leukopenia was as follows: 1) WBC became less than 3,000/mm3 during chemotherapy for patients with pre-treatment WBC more than 4,000/mm3, or 2) WBC decreased more than 1,000/mm3 in patients with pre-treatment WBC between 3,000 and 4,000/mm3. The incidence rates of leukopenia by age, gender, and regimens of chemotherapy were calculated. The case-control study was done between the control and the leukopenia groups excluding patients suffered from agranulocytosis to clarify the hematological and biochemical characteristics of the leukopenia group. The control patients were chosen in the following way. For each patient with leukopenia, a patient with the same admission year, same gender, same regimen of chemotherapy, and the nearest age was chosen as a control patient. The changes in counts of white blood cell, granulocyte, and platelet, in hemoglobin concentration, and in hepatic enzyme levels before and during chemotherapy were compared between the leukopenia and the control groups. Thrombocytopenia was defined as platelet count less than 15 x 10(4)/mm3 and hepatic dysfunction as either asparate aminotransferase (AST) higher than 31 IU/l or alanine aminotransferase (ALT) higher than 34 IU/l. RESULTS: (1) Incidence rate of leukopenia The leukopenia appeared in 36 patients (14 men, 22 women), two (one man, one woman) of whom showed agranulocytosis. The incidence rate was 1.2% (14/1,153) for men and 5.9% (22/372) for women. The incidence rate of women was higher than that of men in the age groups between 20 to 79 y.o., but no difference was seen in the age groups elder than 80 y.o. There were no differences in the incidence rate among groups treated with HRE (E: ethambutol), HRS (S: streptomycin), and HREZ (Z: pyrazinamide). The chemotherapy was continued in 30 patients after the appearance of leukopenia, and the natural recovery from leukopenia was seen in 19 patients, while the leukopenic state lasted during the chemotherapy in the remaining 11 patients. In two patients who exhibited agranulocytosis all drugs were discontinued. In the remaining 4 patients one or more drugs were discontinued. (2) Case-control study between leukopenia (N = 34) and the control (N = 34) groups There were no differences in age, sputum culture positivity on admission, degree of roentgenographic extent of the disease, ratio of cavity formation, and quantity of daily doses between the two groups. There was also no difference between the days until leukopenia appeared after starting chemotherapy (47.6 +/- 29.5 days) in the leukopenia group, and the days until WBC count became minimum within 3 months after starting chemotherapy (41.7 +/- 21.0 days) in the control group. The negativity of tuberculin skin testing was higher in the leukopenia group [7/14 (50%)] than in the control group [1/10 (10%)], however, the difference was statistically not significant due to rather small size of cases. Before the starting chemotherapy, the counts of WBC (7,230 +/- 1,530 vs 5,500 +/- 1,510/mm3, p < 0.001), neutrophil (5,230 +/- 1,450 vs 4,320 +/- 1,620/mm3, p < 0.05), lymphocyte (1,440 +/- 830 vs 830 +/- 440/mm3, p < 0.001) and platelet (34.9 +/- 12.2 vs 24.1 +/- 6.4 x 10(4)/mm3, p < 0.001) in the peripheral blood and the globulin level (3.71 +/- 0.61 vs 3.35 +/- 0.61 g/dl, p < 0.05) in the serum were significantly higher in the control group than in the leukopenia group. The decrements in the counts of WBC and granulocyte during chemotherapy were larger in the leukopenia group than in the control group (delta WBC: 2,880 +/- 1,530 vs 1,910 +/- 1,520/mm3, and delta Neut: 2,840 +/- 1,510 vs 1,820 +/- 1,380/mm3, p = 0.01, respectively), but the counts of lymphocyte were similar in both groups. The platelet counts also decreased in both groups, but to the mid-normal level in the control group, and to the lowest normal level in the leukopenia group, in which 15 out of 34 patients (44%) showed thrombocytopenia. The levels in the serum of hepatic enzymes such as AST, ALT, and gamma-GTP (gamma-glutamyl aminotransferase) increased during chemotherapy in the leukopenia group, while decreased in the control group, and the facts indicate that in the former not only bone marrow cells but also hepatic cells were impaired by anti-tuberculosis drugs. CONSIDERATIONS: Leukopenia may occur in the course of treatment with anti-tuberculosis drugs, but it is not necessary to stop the chemotherapy immediately, because the WBC count recovers spontaneously or remains under stable leukopenic state during chemotherapy in most cases. But when leukopenia appears, the peripheral blood counts must be checked cautiously, and the chemotherapy should be stopped if the WBC count progressively decreases. The patients who showed leukopenia due to anti-tuberculosis drugs may have had weaker natural and acquired (cell-mediated) immunologic response to tuberculosis infection, and more vulnerable bone marrow cells and hepatic cells to anti-tuberculosis drugs than the control.

Adult↗

PubMed1977

Combined therapy of oral cancer bleomycin and radiation: a clinical trial.

A concurrent randomised controlled clinical trial to evaluate a combination of Bleomycin and radiation as against radiation only in the treatment of advanced oral cancer has been conducted at the Cancer Institute, Madras, since 1971. All T3 and T4 previously untreated oral squamous cell carcinomas with N0, N1 and N2 regional nodes, or N3 nodes confined to the submandibular region, without systemic metastases or gross infiltration of the temporal and infratemporal fossa producing total trismus, and in decent general health were eligible for the trial. Patients with gross active pulmonary tuberculosis were excluded, as were recurrent carcinomas. Age, external fungation of growth or radiological bone invasion were no bar. Randomisation was done by the sealed envelope technique. The study group received concurrent fractionated cobalt 60 teletherapy using two opposing fields and 10-15 mg of Intra-arterial or Intravenous Bleomycin. The controls received fractionated cobalt teletherapy and i.v. or i.m. distilled water on the same protocol as the Bleomycin cases. All cases were evaluated double blind 8 weeks after the end of radiation therapy, and were classified as 'favourable response' or 'failure'. The criterion of 'favourable response' was 'total clinical healing of the tumour within the volume of irradiation with no subsequent recurrence within that volume, whatever the length of follow up'. Anything else was reported as a failure. A long term follow up of 3 years is also available. 136 cases have completed the trial. The favourable response in the study group was 77% as against 20.9% in the control group. The differential response is statistically significant. The present study is the fourth in the series of combined therapeutic trials conducted in advanced oral squamous cell carcinoma since 1958. (Krishnamurthi and Shanta, 1963, 1965, 1967 and 1971). A concurrent randomised controlled clinical trial to evaluate the combination of Bleomycin and radiation as against radiation only in treatment of advanced oral cancer has been conducted at the Cancer Institute, Madras since 1971.

Bleomycin↗

PubMed2004

Tuberculosis in HIV-infected persons in the context of wide availability of highly active antiretroviral therapy.

Highly active antiretroviral therapy (HAART) greatly reduces the risk of developing tuberculosis for HIV-infected persons. Nonetheless, HIV-associated tuberculosis continues to occur in countries where HAART is widely used. To identify the characteristics of HIV-infected persons who develop tuberculosis in the context of the availability of HAART, the current authors analysed data taken from 271 patients diagnosed, in Italy, during 1999-2000. These patients represent 0.7% of the 40,413 HIV-infected patients cared for in the clinical units participating in this current study. From the data it was observed that 20 patients (7.4%) had a previous episode of tuberculosis whose treatment was not completed. Eighty-one patients (29.9%) were diagnosed with HIV at tuberculosis diagnosis, 108 (39.8%) were aware of their HIV status but were not on antiretroviral treatment and 82 (30.3%) were on antiretroviral treatment. Patients on antiretroviral treatment were significantly less immunosuppressed than patients with HIV diagnosed concurrently with tuberculosis, or other patients not on antiretrovirals (median CD4 lymphocytes count: 220 cells x mm(-3) versus 100 cells x mm(-3), and 109 cells x mm(-3), respectively). No significant differences in clinical presentation of tuberculosis according to antiretroviral therapy status were recorded. Failure of tuberculosis control interventions (e.g. noncompletion of treatment) and of HIV care (delayed diagnosis of HIV infection and suboptimal uptake of therapy) may contribute to continuing occurrence of HIV-associated tuberculosis in a country where highly active antiretroviral therapy is largely available. However, a significant proportion of cases occur in patients who are on antiretroviral treatment.

AIDS-Related Opportunistic Infections↗