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Biomedical subjects

R Rodriquez

Publications and source records attributed to R Rodriquez.

9 recordsLinked to original sources

Contribution of the multidrug efflux pump LfrA to innate mycobacterial drug resistance.

Multidrug resistance (MDR) in bacteria has been associated with efflux pumps that export structurally unrelated compounds and decrease cytoplasmic drug accumulation. To investigate MDR in mycobacteria, we studied the Mycobacterium smegmatis mutant mc(2)11, which is resistant to doxorubicin, tetracycline, rhodamine, ethidium bromide and the hydrophilic fluoroquinolones. A genomic library constructed from this mutant was used to select clones conferring resistance to doxorubicin. Surprisingly, the clone selected encodes the efflux pump LfrA, which has been reported to confer resistance to hydrophilic fluoroquinolones, ethidium bromide, rhodamine, and acriflavine. To define the contribution of LfrA to the innate mycobacterial drug resistance and to the MDR phenotype in mc(2)11, the lfrA gene was disrupted in both the mc(2)11 mutant and the mc(2)155 wild-type parent. LfrA disruption of the wild-type strain decreased resistance to ethidium bromide and acriflavine, and increased accumulation of ethidium bromide. However, disruption of lfrA gene results only in a 2-fold decrease in minimal inhibitory concentrations (MICs) for ciprofloxacin, doxorubicin, rhodamine, and accumulation of [(14)C]ciprofloxacin was unchanged. LfrA disruption of the MDR strain mc(2)11 produced a similar phenotype. Thus, LfrA contributes significantly to the intrinsic MICs of M. smegmatis for ethidium bromide and acriflavine, but not for ciprofloxacin, doxorubicin or rhodamine.

Acriflavine↗

Hydronephrosis in pregnancy: simultaneous depiction of fetal and maternal hydronephrosis by magnetic resonance urography.

Magnetic resonance urographic (MRU) techniques possess image quality and diagnostic capability that are improving with increasingly sophisticated imaging sequences and shorter scanning times. We describe the application of a fast breath-hold MR sequence (HASTE) in the assessment of ureteric obstruction in pregnancy. In the patient presented, HASTE MRU was successful in depicting ureteral anatomy and demonstrated dilation of both ureters below the level of the pelvic brim. This observation suggested distal ureteral obstruction rather than simple hydronephrosis of pregnancy. As a result, bilateral nephrostomies were performed and neonatal prematurity was avoided. Interestingly, in this patient, HASTE MR imaging also showed evidence of concurrent fetal hydronephrosis.

Adult↗

Tirapazamine with cisplatin in patients with advanced non-small-cell lung cancer: a phase II study.

PURPOSE: A phase II study was conducted to evaluate the safety and efficacy of tirapazamine combined with cisplatin for the treatment of patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-four patients with stage IIIB/IV NSCLC were treated with a combination of tirapazamine and cisplatin. Patients received tirapazamine 260 mg/m2 administered intravenously over 2 hours, followed 1 hour later by cisplatin 75 mg/m2 administered over an additional hour, repeated every 21 days. The duration of therapy was meant to be limited to four cycles for nonresponders and eight cycles for responders. RESULTS: Ten of 44 patients (23%) showed a partial response. The estimated median survival for all patients was 37 weeks. Toxicities were treatable and included grade 3 nausea or vomiting (25%), fatigue (27.3%), and muscle cramps (4.5%). No dose reductions were necessary. CONCLUSION: The results show that tirapazamine can safely be added to cisplatin. Both the median survival and response rate observed strongly suggest that tirapazamine with cisplatin is more active than cisplatin alone.

Adult↗

p53 and PCNA expression in advanced colorectal cancer: response to chemotherapy and long-term prognosis.

In a series of 71 patients with advanced colorectal cancer treated with biochemically modulated 5-fluorouracil (5-FU) and methotrexate (MTX), we investigated the relationship between the proliferating-cell nuclear antigen (PCNA) (PC10) and p53 (Pab1801) primary-tumor immunohistochemical expression with respect to clinical response and long-term prognosis. Nuclear p53 expression was demonstrated in 44% of samples (any number of positive tumor cells) while all tumors showed a certain degree of PCNA immunostaining. PCNA immunostaining was correlated with histopathologic grade and p53 expression, while p53 was not correlated with any of the parameters considered. The probability of clinical response to biochemically modulated 5-FU was independent of p53 and PCNA expression. p53 expression (all cut-off values) was not associated with short- or long-term clinical prognosis, whereas patients with higher PCNA primary-tumor expression showed longer survival from treatment and survival from diagnosis, according to univariate and multivariate analysis, particularly in the sub-set of colon-cancer patients. We conclude that the clinical response of advanced-colorectal-cancer patients to biochemically modulated 5-FU and MTX cannot be predicted by PCNA and p53 primary-tumor expression, but high PCNA expression appears to be independently related to long-term prognosis.

Adult↗

Phase II trial of docetaxel (Taxotere) in patients with metastatic melanoma previously untreated with cytotoxic chemotherapy.

A phase II study was undertaken to evaluate the clinical efficacy and safety of docetaxel in patients with malignant melanoma. Between April 1992 and February 1996, 37 patients with metastatic malignant melanoma and no prior chemotherapy were treated with docetaxel 100 mg m-2 administered intravenously over 1 hour every 21 days. Patients were premedicated prior to each course with dexamethasone and diphenhydramine. Toxicity and follow-up were provided. Objective responses were seen in two out of 35 patients evaluable for response, one complete response and one partial response. These two responses were of a duration of greater than two years. The most common toxicity was grade 4 neutropenia, which occurred in 92% of patients; 49% required hospitalization for an episode of neutropenic fever. Additional patients had reversible grade 3-4 toxicities including nausea, vomiting, diarrhea, stomatitis, arthralgias, myalgias, peripheral neuropathy and fatigue. Eighteen patients had hypersensitivity reactions, two were grade 3-4. Fluid retention, grade 1-3 was observed in seven patients. Alopecia occurred in most patients. Docetaxel has definite but low-level activity against malignant melanoma. Further investigation of this drug should be considered in multidrug combination programs.

Adult↗

Endoscopic management of cholangitis: critical review of an alternative technique and report of a large series.

OBJECTIVE: To assess the outcome of endoscopic techniques as the solitary treatment modality for the complete management of ascending, bacterial cholangitis, compared with results of radiological and surgical methods as historical controls. METHODS: Endoscopic techniques were used to decompress bile ducts obstructed by stones (898 patients) or stenosis (49 patients). Endoscopic sphincterotomy (ES) was performed in 839 patients, and either 7-Fr straight stents (79), or nasobiliary tubes (29), were utilized as initial therapy in 108 patients. Of these latter patients, 68 subsequently underwent ES and stone removal, 17 had ES, lithotripsy, and stone removal, 18 were left with stents in place, and 5 were lost to follow-up. Follow-up was conducted by direct patient contact, by telephone, or through the referring physicians. RESULTS: All patients were managed by endoscopic techniques. There were four deaths (0.42%) in the first 30 days (none before 2 wk); no deaths were related to the procedures but were attributed to intercurrent medical problems. Two patients underwent surgery: one pancreatitis, one perforation. Complications were infrequent, occurring in 6% of patients. Bleeding occurred in 3%, pancreatitis in 2.8%, and perforation 0.2%. CONCLUSIONS: Endoscopic management of cholangitis is as effective as surgical or radiological methods for managing bacterial cholangitis, a potentially fatal syndrome, but ERCP and ES have been shown to be safer. Endoscopy is the preferred index technique both for establishing a definitive diagnosis and providing therapy.

Aged↗

Two cases of death involving dicyclomine in infants. Measurement of therapeutic and toxic concentrations in blood.

In two deaths of infants investigated by the Medical Examiner, high levels of dicyclomine were detected in blood. In one of the cases, a level of 0.505 micrograms/ml was found, nearly 10 times reported adult therapeutic blood concentrations, and death was ascribed to an overdose of dicyclomine. Gas chromatography/mass spectrometry was used for the analysis of biological specimens.

Adult↗