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Biomedical subjects

M Cobo

Publications and source records attributed to M Cobo.

At least 19 recordsLinked to original sources
PubMed2006

Dioxin emissions from thermal waste management in Medellín, Colombia: present regulation status and preliminary results.

Preliminary results of a study undertaken to characterize dioxin and furan releases from waste incineration plants operating in Medellín-Colombia are presented. Emission and fly ash samples were collected from representative plants burning medical and industrial residues to characterize PCDD/PCDF levels. Analyses were carried out following European standards for stationary gas emissions EN-1948:1996 and US EPA 1613 (fly ashes). Final extracts were analyzed by both high resolution gas chromatography coupled to high resolution mass spectrometry (HRGC-HRMS) and high resolution gas chromatography coupled to ion trap tandem mass spectrometry (HRGC-ITMS/MS). Preliminary results revealed emission levels of 1-30.3 ng I-TEQ/Nm3 depending on whether or not an air pollution control system (APCS) was installed. Fly ashes contained 8.5-68 ng I-TEQ/g. Critical issues that should be addressed in an assessment and in developing waste management plans in Colombia are discussed.

Carbon↗
PubMed2006

Polymorphisms in DNA repair genes modulate survival in cisplatin/gemcitabine-treated non-small-cell lung cancer patients.

BACKGROUND: Impaired DNA repair capacity may favorably affect survival in cisplatin/gemcitabine-treated non-small-cell lung cancer (NSCLC) patients. We investigated the association of survival with genetic polymorphisms in X-ray repair cross-complementing group 1 and group 3 (XRCC3), xeroderma pigmentosum group D (XPD), excision repair cross-complementing group 1, ligase IV, ribonucleotide reductase, TP53, cyclooxygenase-2, interleukin-6, peroxisome proliferator-activated receptor gamma, epidermal growth factor, methylene-tetra-hydrofolate reductase and methionine synthase. PATIENTS AND METHODS: One hundred and thirty-five stage IV or IIIB (with malignant pleural effusion) NSCLC patients treated with cisplatin/gemcitabine from different hospitals of the Spanish Lung Cancer Group were genotyped for 14 different polymorphisms in 13 genes. Polymorphisms were detected by the TaqMan method, using genomic DNA extracted from baseline blood samples. RESULTS: Median survival was significantly increased in patients harboring XRCC3 241 MetMet: 16 months versus 10 months for patients with ThrMet and 14 months for those with ThrThr (P = 0.01). The risk of death ratio was significantly lower for MetMet than for ThrMet patients (hazard ratio, 0.43; P = 0.01). In the multivariate Cox model, XRCC3 241 remained an independent prognostic factor (hazard ratio: XRCC3 241 MetMet, 0.44; P = 0.01), and XPD 751 and XRCC1 399 also emerged as significant prognostic factors (hazard ratios: XPD 751 LysGln, 0.46, P = 0.03; XRCC1 399 ArgGln, 0.61, P = 0.04). No other association was observed between genotype and survival. CONCLUSION: XRCC3 241 MetMet is an independent determinant of favorable survival in NSCLC patients treated with cisplatin/gemcitabine. A simple molecular assay to determine the XRCC3 241 genotype can be useful for customizing chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Conservative treatment with transurethral resection, neoadjuvant chemotherapy followed by radiochemotherapy in stage T2-3 transitional bladder cancer.

PURPOSE: Organ preservation has been investigated in patients (p) with infiltrating transitional cell carcinoma (TCC) of the bladder over the past decade as an alternative to radical cystectomy. This is a trimodal schedule study, including transurethral resection of bladder tumor (TURB), neoadjuvant chemotherapy and concomitant radiochemotherapy (RTC). PATIENTS AND METHODS: From April 1996 until August 2005, 29 evaluable patients (p) with T2-T3NXM0 bladder cancer were enrolled. After a transurethral resection of bladder tumor (TURB), we administered 2 cycles of induction chemotherapy with CMV (15 p) or Gemcitabine-Cisplatin (14 p) followed by radiotherapy 45 Gy 1.8 Gy/fraction and two cycles of concomitant cisplatin 70 mg/m(2). 2-3 weeks later, a cystoscopy with tumor-site biopsy was performed. If complete histological response, p were treated with consolidation radiotherapy until 64.8 Gy. For p with residual or recurrent tumor, cystectomy was performed. RESULTS: We included 28 men and 1 women (median age 63, range 39-72 years) with PS (ECOG) 0-1. The stage was: 21 p T2; 6 p T3a; and 2 p T3b. Toxicity was higher in CMV compared with Gem- Cis: grade (3/4) neutropenia 4/15 (26%) vs 1/14 (7%); febrile neutropenia 3/15 (20%) vs 1/14 (7%); grade (3/4) trombocytopenia 2/15 (13%) vs 1/14 (7%). Toxicities with concomitant RCT were low-moderate: urocystitis (26%) and enteritis (18%). RESPONSE: microscopically complete TURB was obtained in 20 p (69%), but not in 9 p (31%) (7 microscopic, and 2 macroscopic residual tumor). We found a complete histologic response after induction RCT in 25 p (86%). After a median follow-up of 69.4 months (m) (range: 8-97.7), there were 8 deaths, with a overall survival of 72%. Furthermore 14 of 29 p (48%) were alive with intact bladder, and median survival time with intact bladder was 63.6 m (50.1-77.2); were predictive of best outcome T2 stage vs T3 (p < 0.0001), and complete histologic resection in initial TURB vs residual tumor (p = 0.0004). CONCLUSIONS: Combined treatment provide high response rates and can be offered as an alternative option to radical cystectomy in selected patients with TCC. Patients with T2 stage and complete histologic resection in initial TURB had the best outcome.

Adult↗
PubMed2006

Pharmacogenomics and gemcitabine.

Approximately half of lung cancer patients present with metastases, and a large proportion will develop recurrent disease, with median survival to cisplatin-based chemotherapy of 11 months. No predictive factor of response to cisplatin-based chemotherapy is yet available in clinical practice. The nucleotide excision repair system plays a major role in repairing a variety of distorting lesions, notably platinum-induced DNA adducts. ERCC1 is a leading gene in repairing cisplatin DNA damage. We carried out three different studies examining individually the role of ERCC1, RRM1, and then both, mRNA expression in paraffin-embedded pretreatment bronchial biopsies from gemcitabine/cisplatin-treated advanced non-small-cell lung cancer (NSCLC) patients. Median survival was significantly prolonged in patients with low levels of ERCC1 or RRM1. BRCA1 is involved in homologous recombination repair, and we observed that low levels of BRCA1 mRNA significantly increased survival in gemcitabine/cisplatin-treated patients. Our observations lead us to recommend that tumors be regularly assessed for ERCC1 and BRCA1 mRNA expression in order to customize gemcitabine/cisplatin treatment.

Antimetabolites, Antineoplastic↗
PubMed2006

Successful therapeutic use of rituximab in refractory membranous glomerulonephritis.

We present the case of a 57-year-old man with nephrotic syndrome secondary to idiopathic membranous glomerulonephritis unsuccessfully treated with angiotensin-converting enzyme inhibitor (ACEI), angiotensin II receptor antagonist (ARA), prednisone and chlorambucil. After treatment with rituximab, we observed a progressive decrease of proteinuria and normalization of serum albumin. 18 months after treatment, he remained in remission. No adverse reactions to rituximab were noted throughout follow-up.

Antibodies, Monoclonal↗
PubMed2004

Chronic ethanol intake modifies renin-angiotensin system-regulating aminopeptidase activities in mouse cerebellum.

In developing cerebellum, where critical periods of vulnerability have been established for several basic substances, it has been extensively studied the wide array of abnormalities induced by exposure to ethanol (EtOH). However, little is known about the effects of EtOH consumption on cerebellar functions in adult individuals. Several studies show participation in cognitive activities to be concentrated in the lateral cerebellum (hemispheres), whereas basic motor functions such as balance and coordination are represented in the medial parts of the cerebellum (vermis and paravermis). In addition to the circulating renin angiotensin system (RAS), a local system has been postulated in brain. The effector peptides of the RAS are formed via the activity of several aminopeptidases (AP). The present work analyses the effect of chronic EtOH intake on the RAS-regulating AP activities in the soluble and membrane-bound fractions of two cerebellar locations: the hemispheres and the vermis. We hypothesize that cerebellar RAS is involved in basic motor functions rather than in cognitive activities.

Aminopeptidases↗
PubMed2004

Weekly irinotecan (CPT-11) in 5-FU heavily pretreated and poor-performance-status patients with advanced colorectal cancer.

Irinotecan (CPT-11) is an effective drug in patients with advanced colorectal cancer (CRC). Little is known about its efficacy and safety in previously treated patients with poor performance status. We prospectively evaluated the antitumor efficacy and safety of CPT-11 monotherapy in this setting. Thirty-four patients with poor performance status (Karnofsky score between 60 and 80) and/or progressing on one or more previous 5-FU-based chemotherapy lines for advanced colorectal adenocarcinoma were enrolled in this study. Treatment consisted of irinotecan (CPT-11) at 100 mg/m(2) administered as a 60-min iv infusion every week for four consecutive weeks followed by a 2-wk rest period until disease progression or unacceptable toxicity. The overall objective response rate (WHO criteria) for the 34 patients included was 20.6% [95% confidence interval (CI): 6.3%-34.9%]. Stable disease was obtained in 13 patients (38.2%) and 14 patients (41.2%) progressed. The median time to disease progression was 5.5 mo (range: 0.9-17.5) and the median survival was 8.3 mo (95% CI: 1.7-16.9). Overall, weekly CPT-11 was well tolerated with grade 3/4 neutropenia as the main hematological toxicity (11 patients: 32.4%; 14 infusions: 3.3%), and delayed diarrhea (10 patients: 29.4%; 16 infusions: 3.8%) as the main grade 3/4 non-hematological toxicity. In conclusion, weekly CPT-11 at 100 mg/m(2) for four consecutive weeks followed by a 2-wk rest period showed antitumor efficacy and may be safely administered to heavily pretreated patients with advanced colorectal cancer and a poor performance status. Weekly CPT-11 monotherapy may be considered as a therapeutic option for this population of patients.

Adenocarcinoma↗
PubMed2003

Cardiovascular risk profile in nondiabetic renal transplant patients: cyclosporine versus tacrolimus.

Calcineurin inhibitors (CIs) contribute to cardiovascular risk (CR) in renal transplant (RT) patients. However, the CR profile in RT patients without preexistent diabetes is not well known. We compared CR factors in 191 nondiabetic RT recipients with functioning grafts beyond 1 year, receivingly either CsA (Neoral; n=100) or tacrolimus (Tac; n= 91). Clinical data and pretransplant CR profiles were similar in both groups. There were no differences in acute rejection episodes and graft survival rates during follow-up. The overall proportions of posttransplant diabetes (9% versus 6%), and of hypertension (73% vs 63%) were similar in both groups. Hyperlipidemia was more frequent in the CsA group (58% vs 31%; P=.0001). The cholesterol levels in the CsA group showed at 3 months (232+/-47 vs 202+/-42 m/dL; P=.0001), 6 months (232+/-49 vs 205+/-41 mg/dL; P=.0001), and 12 months (217+/-50 vs 202+/-40 mg/dL; P=.028), despite receiving a greater proportion of lipid-lowering drugs (49% vs 15%; P=.0001). Logistic regression analysis showed that CsA was an independent predictor of posttransplant hyperlipidemia (OR: 5.8, CI 95%; 3.3-10.7; P=.0001) as were age, female gender, pretransplant dyslipidemia, and body mass index (BMI). Interestingly, an interaction was observed between pretransplant BMI and CIs: Among pretransplant normal weight patients (BMI <25 kg/m2), CsA produced a greater incidence of hyperlipidemia than tacrolimus (58% vs 23%; P=.0001) while not among patients who were overweight (BMI >25 kg/m2: pretransplant 58% vs 42%; P=.341). In conclusion, CsA confers a higher risk of hyperlipidemia after RT in nondiabetic patients, particularly those with normal pretransplant weight.

Adult↗
PubMed1998

Is it possible to control hyperphosphataemia with diet, without inducing protein malnutrition?

Dietary intervention, phosphate (P) removal during dialysis and, especially, phosphate binders are current methods for the management of hyperphosphataemia. Ideally, the amount of P absorbed from the diet should equal the amount of P removed during dialysis, and this must occur in the context of an adequate protein intake. We evaluated the relationship between P intake and protein intake in 60 stable chronic uraemic patients (mean age 55+/-15 years, 25% diabetics, 68% males) on standard 4 h haemodialysis. The dietary counselling was relatively free for protein and calories. Nutrient intake was recorded during a 5 day period, and average daily ingestion of P and proteins was calculated using a computerized diet analysis system. A highly significant correlation was observed between protein and P intake. The mean daily ingestion of P and proteins was 998+/-316 mg and 64+/-19 g (1+/-0.4 g/kg/day), respectively. For an optimal protein diet of 1-1.2 g/kg/day, the P intake was 778-1444 mg. The amount of P removed by haemodialysis, extrapolated to an average week, is 250-300 mg/day. Since approximately 40% of P ingested is absorbed from the gut by uraemic patients treated with intestinal P binders, 750 mg of P intake should be the critical value above which a positive balance of P may occur. This value corresponds to a protein intake of 45-50 g per day (>0.8 g/kg body weight/day for a 60 kg patient). In patients undergoing standard chronic haemodialysis, a neutral P balance is difficult to achieve, despite phosphate binder therapy, when protein intake is >50 g. Additional protein restriction, in order to obtain a neutral balance, may impose the risk of protein malnutrition.

Adult↗
PubMed1996

Effects of phenylsuccinate on potassium-stimulated taurine release in cultured neurons and astrocytes and in rat hippocampus in vivo.

Swelling-induced release of taurine was investigated in vivo in hippocampus by microdialysis or in vitro in cultured neocortical neurons or astrocytes. Swelling was induced either by increasing the extracellular K+ concentration or by exposing the cells to hyposmotic conditions. It was found that the drug phenylsuccinate, which inhibits the mitochondrial dicarboxylate carrier as well as biosynthesis of neurotransmitter glutamate, inhibits swelling-induced taurine release both in vivo and in cultured cells. Thus, phenylsuccinate may be used to investigate the mechanism involved in taurine release associated with regulatory volume decrease in cells.

Amino Acids↗
PubMed1993

[Hepatitis C virus antibodies in hospital personnel].

BACKGROUND: The discovery of the hepatitis C virus (HCV) largely responsible for the non A non B hepatitis, and the antiHCV antibody allows epidemiologic data and risk factors of infection related to the same to be known. The aim of the authors was to know the prevalence of the antiHCV in health care staff in relation with a group of extrahospitalary workers. METHODS: A transversal seroepidemiologic study was carried out in physicians, nurses and auxiliaries with seniority of more than one year in the medical, surgical, emergency, and ICU departments and laboratories of the general hospital of reference (1200 beds). RESULTS: Of the 874 participants (93% of the candidates) 19 (2%) had HCV antibodies detected by ELISA; with positive RIBA II and positive LIA test in 14 (1.6%) of them. In 11 sera ARN of HVC was detected by PCR. Of 547 extrahospitalary workers of the control group, 2 (0.4%) had positive markers against HCV (p < 0.05). The GPT of the seropositive individuals was normal in four and equal to or less than 70 U/l in six. Seven cases (50%) also had serologic data of contagion with HCV. In 10 (1.1%) of the health care staff no risk factor other than hospitalary work was found. CONCLUSIONS: Working in departments attending HCV carriers represents an increase in risk which must be taken into account with regard to accidental exposure to fluids of patients admitted to these areas.

Adult↗
PubMed1992

Sclerokeratoplasty with maintenance of the angle.

Using sclerocorneal dissection and angle-support sutures to maintain the angle and its function, we performed 14-mm sclerokeratoplasty with placement of allograft tissue in five eyes of 15 patients. One previously operated-on eye required a second sclerokeratoplasty and three eyes required secondary optical keratoplasty after opacification of the original large graft. Patients were monitored from 11 to 90 months postoperatively. At the last examination, all patients had clear grafts and visual acuity had improved since the preoperative examination. All patients had intraocular pressure maintained within normal range (less than 22 mm Hg, as measured by pneumotonometry) except for two patients in whom transient increases were resolved by tapering of corticosteroid treatment. Our results suggested that sclerokeratoplasty, using angle-support sutures, is an effective treatment for diffuse destructive corneoscleral disease that cannot be managed with a smaller graft.

Adult↗
PubMed1992

Limbic seizure-induced changes in extracellular amino acid levels in the hippocampal formation: a microdialysis study of freely moving rats.

Limbic seizure-activity was induced by injecting kainic acid into the amygdala of rats. Extracellular levels of amino acids were monitored by microdialysis in the hippocampus. No changes were detected in the levels of glutamate and aspartate. The level of glycine also remained unchanged, whereas GABA showed an increase of approximately 35%. The level of glutamine decreased by approximately 30%, and that of serine by approximately 20%. The results indicate that increased turnover may exist in the glutamate transmitter pool. In addition, impairment of GABA-release seems not to be a pathogenetic factor in seizure-induced hippocampal neuron loss. It is concluded that even during sustained seizure-activity, the extracellular level of glutamate, is maintained within narrow limits. A proposed index for excitatory neurodegeneration, glutamate x glycine/GABA, was found to be decreased in this seizure model. We therefore suggest that seizure-induced neuron death is not reflected by alterations in the extracellular levels of glutamate and aspartate, thought to act as direct neurotoxins.

Amino Acids↗
PubMed1990

Results of penetrating keratoplasty by residents.

There is little information regarding the results of penetrating keratoplasty for the novice transplant surgeon. We reviewed 63 consecutive cases of penetrating keratoplasty performed by senior residents at our institution. Of 59 cases with a 1-year follow-up, 76% remained clear; the mean astigmatism was 4.15 diopters, and the median visual acuity was 20/50. The two major postoperative complications were graft rejection and increased intraocular pressure, which occurred in 22% and 16% of cases, respectively. In a well-supervised setting, residents can be introduced to the basic principles of keratoplasty and achieve results comparable with those reported in the literature.

Adolescent↗
PubMed1989

The role of the lateral cortico-cortical prefrontal pathway in self-stimulation of the medial prefrontal cortex in the rat.

Effects of electrolytic and kainic acid lesions at several stereotaxic planes of the lateral cortico-cortical prefrontal efferent pathway on self-stimulation of the medial prefrontal cortex were investigated. Electrolytic bilateral lesion of the sulcal prefrontal cortex, the first terminal area of this pathway, produced no effects on self-stimulation of the medial prefrontal cortex. However, bilateral electrolytic lesion of this pathway at the rostral part of the external capsule produced a permanent abolition of self-stimulation of the medial prefrontal cortex. These effects seemed selective since operant behaviour to obtain water, similar to that performed for self-stimulation and used as a control, was not affected by the lesion except on the 1st, 3rd (P less than 0.01) and 5th (P less than 0.05) days postlesion. Interestingly, bilateral microinjections of kainic acid (10 nmol in 0.8 microliters) at the same stereotaxic planes of the external capsule where electrolytic lesion was produced, had no effects on self-stimulation. These results suggest that fibres-of-passage through the external capsule are responsible for the abolition of self-stimulation. Bilateral electrolytic lesion of the entorhinal cortex, one of the caudal terminal areas of this descending set of fibres, produced a short transient decrease of self-stimulation of the medial prefrontal cortex. These results are discussed on the basis that complex, rather than single circuits are involved in maintaining self-stimulation in this neocortical area.

Animals↗