Methodology of case-control studies in the epidemiology of multidrug-resistant tuberculosis.
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Biomedical subjects
Publications and source records attributed to M Vaquero.
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BACKGROUND: To analyze the main clinical and biological data and the response to therapy in 15 patients with primary gastrointestinal lymphoma (PGIL) from a series of 76 patients with HIV related non-Hodgkin's lymphoma (NHL) diagnosed in a single institution in a 13 years period. PATIENTS AND METHODS: The main clinical, biological and evolutive data were recorded. Pathologic diagnosis of PGIL was made according to the REAL classification. Clinical stage was determined by the Ann Arbor system modified by Rohatiner et al. Response to therapy as well as overall survival (OS) were studied. Results were compared with non-PGIL HIV-related NHL patients. RESULTS: Mean age of the series was 38 years. Thirteen patients were male, and 8 intravenous drug abusers. Then had bad performance status (ECOG 2-4) and 11 B symptoms. All patients had a high grade malignant PGIL and the localization was gastric in 10 cases. The most frequent symptoms were abdominal pain (11 cases), gastrointestinal bleeding (4) and dysphagia (3). Ten patients had advanced stages (IIE2-IV). The median CD4 cell count was lower in PGIL patients (92 x 10(6)/l vs 148 x 10(6)/l; p < 0.05). Thirteen patients received intensive chemotherapy with CHOP regimen (in 5 surgical procedures were previously made). Complete response (CR) was obtained in 4 patients (31%) and 1 of them relapsed. Median OS was 10 months vs 16 months non-PGIL HIV-related lymphoma patients (p < 0.05). CONCLUSIONS: PGIL in HIV patients often presented advanced stages and high grade of malignancy. The most common localization is the stomach, and these patients usually have bad performance status and a low CD4 lymphocyte count. Response to therapy is poor. In our series OS was worse in PGIL patients than in the rest of HIV-related NHL, possibly due to the high degree of immunosuppression in the formers.
BACKGROUND: The molecular prediction of isoniazid (INH) resistance in Mycobacterium tuberculosis is hampered by the need for specialized equipment, expertise, high costs, a limited range of detectable mutations, or several of these factors. The rationale for the study was to find a practical alternative and to demonstrate generally valid problems. METHODS AND RESULTS: DNA extracted from decontaminated sputum pellets was used to amplify a 0.26 kb target sequence within the katG gene. Mutations of codon 315, frequently found in isoniazid-resistant isolates, could be discriminated in a simple agarose minigel format following an AciI digest of the nested polymerase chain reaction (PCR) product. Within a panel of 22 sputum samples, INH resistance could be predicted in 5 of 10 samples containing isoniazid-resistant M. tuberculosis. The protocol is robust, requires little expertise and no specialized equipment, and provides the test results within 2 days. CONCLUSION: The results show the feasibility to rapidly and easily detect mutations highly predictive of isoniazid resistance. Nevertheless, this, like any other molecular resistance prediction test, is affected by often neglected factors, including mutation prevalences, the phenomenon of heteroresistance, and a possible bias toward one's own method.
Typical Cogan's syndrome is a rare disease of young adults consisting of flares of interstitial keratitis and sudden onset of Ménière-like attacks (nausea, vomiting, tinnitus, vertigo and hearing loss). Life-threatening aortic insufficiency develops in 10% of reported cases. Atypical Cogan's syndrome (audiovestibular dysfunction with other types of inflammatory eye disease) is associated with vasculitis in 20% of cases and has a less favourable prognosis than typical Cogan's syndrome.
BACKGROUND: As a consequence of the high cell division rate, telomeric repeat reduction in human tumor cells, giving rise to genetic instability, has recently been described. The aim of this study was to analyze by Southern blot telomeric length alterations in a retrospective group of patients with ovarian epithelial carcinoma. PATIENTS AND METHODS: Tumor and corresponding normal DNA were isolated from paraffin-embedded tissue of 16 patients with ovarian epithelial carcinoma. Telomeric Restriction Fragments (TRF) were studied by Southern blot and densitometric analysis. RESULTS: No telomere alterations were detected in 37.5% of patients (6/16). Of the remaining ten, 5 were found to have telomere reduction and five telomere elongation. No significant correlation was found between clinicopathological variables, response to chemotherapy, survival rate or time to progression, and telomere length alterations. CONCLUSIONS: In ovarian epithelial carcinoma telomere elongation may be a marker of the presence of immortal cells within the tumor, but telomere or the absence of telomeric alterations do not rule out the presence of these cells. Although TRF analysis can be performed in paraffin-embedded tissues, it is not the best indicator of telomerase activity and thus of tumor aggressiveness in early stages of this carcinoma.
BACKGROUND: To analyze the response to eradicative therapy and prognostic factors in 52 patients with primary gastrointestinal lymphoma (PGIL) diagnosed at a single institution in a 13 year period. PATIENTS AND METHODS: The main clinical, biological and evolutive data were recorded. Pathologic diagnosis of PGIL was made according to the Working Formulation. Clinical stage was determined by the Ann Arbor system modified by Mushoff. The results of therapy as well as the influence of such characteristics on complete remission (CR), disease-free survival (DFS) and overall survival (OS) were studied. RESULTS: Mean age of the series was 53 years (SD 15). Thirty patients were males. HIV infection preceded PGIL diagnosis in 10 cases. Seventeen had bad performance status (ECOG 2-4) and 30 B symptoms. The PGIL localization was gastric in 31 cases and 29 had a low grade malignant lymphoma. B phenotype was demonstrated in 98% and 22 patients presented advanced stages (IIE2-IV). Treatment was radical surgery followed by intensive chemotherapy in 32 cases, intensive chemotherapy alone in 17, and surgical resection in 3. CR was obtained in 34 patients and 6 of them relapsed. The projected DFS from CR at 9 years was 72% and OS was 26%. CR and survival were not influenced by PGIL localization and treatment type. The main unfavourable prognostic factors were advanced stage (CR and OS), B symptoms (DFS and OS) and advanced ECOG score (CR, DFS and OS). Previous HIV infection had an independent prognostic influence on both CR and OS. CONCLUSIONS: In patients with PGIL, the achievement of CR, DFS and survival have been independent of the type of eradicative treatment used. Performance status, B symptoms and clinical stage have been the main prognostic factors. HIV infection carried an independent prognostic significance.
Association between lipids and renal disease has been reported recently. Its pathogenic mechanisms remain unknown. The aims of this study were to establish: (1) if a cholesterol-rich diet, alone or associated with nephrectomy, produces nephropathy; and (2) if a treatment with omega-3 polyunsaturated fatty acids (PUFA) reduces glomerulosclerotic lesions. Sixty Sprague-Dawley rats were randomized in two different groups: (A) sham operated rats and (B) uninephrectomized rats. Rats in both groups were divided into three subgroups (A1-3, B1-3) according to the diet they were fed: normal chow diet, cholesterol-rich diet (4.5%) or cholesterol-rich diet supplemented with omega-3 PUFA. Twenty weeks later, serum creatinine, creatinine clearance, serum cholesterol, triglycerides, albumin, proteinuria, mesangial cell score and focal glomerulosclerosis were assessed. Results showed that a cholesterol-rich diet significantly increased serum cholesterol, proteinuria and glomerular lesions and decreased creatinine clearance, especially in nephrectomized rats. Glomerular lesions, serum cholesterol and proteinuria ameliorated when cholesterol-rich diet was supplemented with PUFA. Hypertension was noticed only in nephrectomized rats following a normal chow diet. Simple correlation analysis showed that glomerulosclerosis correlated with renal weight, blood creatinine, cholesterol and proteinuria. In spite of some significant differences in urinary prostaglandins, no correlation with glomerular lesions was found. Multiple logistic regression analysis showed that cholesterol and proteinuria were independent risk factors for induction of glomerular sclerosis. In conclusion, a diet rich in cholesterol induces glomerulosclerosis, especially if it is associated with unilateral nephrectomy. Omega-3 PUFA administration reduces serum cholesterol, proteinuria and glomerular injury.
BACKGROUND: To date, the role of dietary cholesterol as a risk factor for some diabetic nephrophathy, such as mesangial expansion and glomerular lesions, is unknown. Controversy also exists regarding the effects of prostaglandin-induced changes in glomerular haemodynamics on the appearance of glomerulosclerosis. METHODS: We have used obese Zucker rats (OZRs) as a model of early nephrophathy to evaluate the effect of hypercholesterolaemic diet on glomerular prostaglandin secretion and on the development of glomerular lesions. Due to the role of angiotensin II (Ang II) in glomerular haemodynamics, we have also evaluated its effects on glomerular eicosanoid secretion. Furthermore, as it has been suggested recently by clinical studies that angiotensin-converting enzyme inhibitors (ACEIs) reduce serum lipids associated with proteinuria, we have also evaluated the effect of the ACEI, fosinopril, both in vivo and in vitro, using 24 h glomeruli cultures. RESULTS: Results showed that a cholesterol-rich diet significantly increased serum cholesterol, proteinuria and glomerular eicosanoid secretion, and caused macrophage-ED1 cell deposits in the glomerular mesangium. Segmentary lesions only appeared in those rats with the highest percentage of glomerular xanthomatous (macrophage-ED1) cells. Ang II, per se, caused a marked rise in glomerular prosaglandin E2 and thromboxane B2. The inhibition of Ang II synthesis with fosinopril reduced all the parameters listed above, whereas Ang II (10(-6)M) increased the secretion of TxB2 and tended to increase PGE2 secretion in glomerular culture. CONCLUSIONS: In conclusion, exogenous cholesterol per se may contribute to nephropathy by increasing eicosanoid secretion, serum lipid profile, urinary protein excretion and the development of glomerular lesions. Fosinopril reduced all these parameters probably by its effects on Ang II.
OBJECTIVES: There is a need in the United States for culture-equivalent assessment of health-related quality of life, particularly among people who speak different languages and among those with low literacy skills. This report summarizes the adaptation of the Functional Assessment of Cancer Therapy (FACT) Scales for use with Spanish-speaking cancer patients, including those with low literacy. METHODS: The Spanish language version of the general Functional Assessment of Cancer Therapy scale plus five disease-specific subscales (breast, lung, colorectal, head and neck, HIV infection) were translated, reviewed, and revised, then evaluated in interviews with Spanish-speaking patients from the mainland United States and Puerto Rico. An iterative forward-backward-forward sequence of item translation, expert bilingual/bicultural advisor review, pretesting interviews with 92 patients, and further expert advisory input were used to establish semantic, content, and partial technical equivalence. RESULTS: The Functional Assessment of Cancer Therapy-General and five disease-specific subscales were translated successfully into wording that was easily understood and answered, leading to psychometric and scoring data similar to that of the English version. All but one of the 28 Functional Assessment of Cancer Therapy-General items and all of the disease-specific items were seen as culturally relevant. The result is a document that underwent iterative forward-backward translation and evaluation and was pretested successfully with native Spanish-speaking oncology patients living in the Central United States and Puerto Rico. CONCLUSIONS: The Functional Assessment of Cancer Therapy-General and five disease-specific subscales have been translated successfully into Spanish using a thorough translation and initial validation methodology. The methods and data provide a model for preparing a health status questionnaire for cross-cultural validation. The questionnaire is available for use in clinical trials and clinical practice.
BACKGROUND AND OBJECTIVE: The management of non-Hodgkin's lymphomas (NHL) in AIDS is difficult because of the poor bone marrow reserve and immunosuppression of these patients. Combination chemotherapy is the treatment of choice in the subset of patients with good performance status and mild immunosuppression. Several combination chemotherapy regimens have been used in these patients but the results have been poor. We have studied the clinical and biological features, response to treatment, outcome and prognostic factors of 46 patients with NHL and HIV infection, diagnosed in a single institution between January 1988 and June 1997. DESIGN AND METHODS: Forty-six patients with NHL and HIV infection were treated with CHOP. Patients with previously treated systemic NHL, primary CNS NHL, performance status > 2 and active AIDS-defining opportunistic or neoplastic diseases were excluded. The parameters evaluated were: age, sex, risk activity, basic hematologic and biochemical parameters, CD4 lymphocyte count, B symptoms, stage (Ann Arbor), histologic subtype (REAL classification), International Prognostic Index (IPI), response to treatment, relative dose intensity (RDI), relapse free survival (RFS) and overall survival (OS). Uni- and multivariate analyses of prognostic factors were performed. RESULTS: Median age was 35 years and 40 patients were male. CD4 lymphocyte count was lower than 0.1 x 10(9)/L in 18 out of 38 cases, hypoalbuminemia was registered in 24 (52%), serum LDH was higher than 400 U/L in 20 (43%) and beta 2-microglobulin was higher than the normal range in 9 out of 20 patients (45%). Complete response was achieved in 18 patients (40%). Twenty-six patients received G-CSF after chemotherapy. Grade 4 neutropenia and fever were significantly more frequent in patients who did not receive G-CSF. Serum LDH > 400 U/L and hypoalbuminemia were the only parameters associated with a lower probability to achieve complete response (p = 0.015 and p = 0.025, respectively). The median RFS was 26 (6-47) months and no variable was found to have statistically significant influence on it. The median OS was 9.2 (4.5-14) months, and IPI score 1 and ESR < 60 mm/h were the only parameters identified as good prognostic factors in the multivariate analysis (p = 0.03 and 0.049, respectively). INTERPRETATION AND CONCLUSIONS: In spite of patient selection, the response to CHOP treatment in patients with NHL and HIV infection remains poor. Episodes of neutropenic fever are less frequent when G-CSF is administered after CHOP. The IPI score 1 is the most important favorable prognostic factor for survival.
BACKGROUND: Tuberculosis (TB) is again a public health problem un many countries and is considered a re-emerging disease. The fastest possible diagnosis in our patients is essential for TB control programs. ESP is a non-radioactive, totally automated, continuously monitored system designed to detect mycobacteria. METHODS: Clinical evaluation of this new system for the rapid diagnosis of tuberculosis. During 1997 a total of 1,022 clinical sputum specimens were investigated. Specimens were processed in triplicate for ESP, BACTEC 460 TB and Löwenstein-Jensen systems. The validity, isolates of Mycobacterium tuberculosis and time required for detecting M. tuberculosis by the three systems were determined. RESULTS: The sensitivity, specificity, positive predictive and negative predictive values of the new systems were 98%, 99.8%, 98% and 99.8%, respectively. No significant differences were found between the recovery rates by the three systems. The mean time for detection was 10 days (range: 7-13 days) for specimens with positive bacilloscopy and 14 days (range: 10-28 days) for specimens with negative bacilloscopy. The difference was statistically significant between ESP and Löwenstein-Jensen, but not between ESP and BACTEC. CONCLUSIONS: The new system proved to have an excellent sensitivity and specificity, which along with its total automation renders it a system of great clinical interest for the rapid diagnosis of TB and an alternative method for radiometric systems.
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Spinal cord compression is an infrequent event in patients with non-Hodgkin's lymphomas (NHL) and early diagnosis and therapy are required. The main clinical and histologic characteristics as well as the response to therapy in 10 NHL patients with spinal cord compression diagnosed at a single center in a 7-year period are referred. The main initial clinical manifestations were pain in dorsal or lumbar regions (5 cases) and paraparesia or paraplegia (5 patients). Infection by human immunodeficiency virus (HIV) was present in four cases. In 8 patients spinal cord compression was the initial manifestation of NHL. Pathologic diagnosis showed intermediate or high-grade lymphoma in 8 out of 10 cases and immunologic phenotype was B-cell in all cases. Laminectomy followed by radiation therapy and chemotherapy was performed in 4 cases, radiotherapy and chemotherapy in two, isolated chemotherapy in 3 and radiation therapy was administered to the remaining case. Complete response was observed in 4 cases and 6 cases were resistant to treatment. No patient with HIV infection responded to treatment. Six patients had died, median survival time for the whole series being 4 months, and the actuarial probability of survival was 40% at the first year.