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Biomedical subjects

Hector Orozco

Publications and source records attributed to Hector Orozco.

6 recordsLinked to original sources

16alpha-Bromoepiandrosterone restores T helper cell type 1 activity and accelerates chemotherapy-induced bacterial clearance in a model of progressive pulmonary tuberculosis.

BALB/c mice with pulmonary tuberculosis develop a T helper cell type 1 response that peaks at 3 weeks, temporarily controlling bacterial growth. Then bacterial proliferation recommences, accompanied by increasing interleukin (IL)-4 levels and decreasing interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and inducible nitric oxide synthase (iNOS) levels. These changes mimic those in the human disease. In a previous study, administration of dehydroepiandrosterone (DHEA) beginning on day 60 after infection reversed these changes and protected the mice. However, DHEA is suboptimal for human use, partly because it is readily metabolized into sex steroids. 16alpha-Bromoepiandrosterone (EpiBr; 16alpha -bromo-5alpha -androstan-3beta-ol-17-one) is a synthetic adrenal steroid derivative that does not enter sex steroid pathways. In the present study, when tuberculous BALB/c mice were treated with EpiBr 3 times/week beginning on day 60, inhibition of bacterial proliferation and increased expression of TNF-alpha, IFN-gamma, and iNOS were observed, although decreased expression of IL-4 was also observed. Moreover, when given as an adjunct to conventional chemotherapy, EpiBr enhanced bacterial clearance. Trials for the use of EpiBr in the treatment of human tuberculosis are now justified.

Adjuvants, Immunologic↗

Pulmonary tuberculosis in BALB/c mice with non-functional IL-4 genes: changes in the inflammatory effects of TNF-alpha and in the regulation of fibrosis.

In BALB/c mice, as in man, progressive pulmonary tuberculosis is accompanied by increasing expression of IL-4. Therefore we have used BALB/c mice with disrupted IL-4 genes (IL-4(-/-)) to investigate the role of IL-4 in pulmonary tuberculosis, with particular emphasis on the toxicity of TNF-alpha and on fibrosis, both of which are neglected aspects of human tuberculosis. Delayed-type hypersensitivity (DTH) sites in IL-4(+/+) mice were sensitive to the toxicity of locally injected TNF-alpha, whereas DTH sites in IL-4(-/-) mice were not. However, intravenous administration of IL-4 to IL-4(-/-) mice restored the sensitivity of the DTH sites to pro-inflammatory effects of TNF-alpha. In late disease, the lungs of IL-4(+/+) mice expressed low IFN-gamma, but high TGF-beta and IL-4, correlating with fibrosis, detected as a high hydroxyproline content. In contrast, TGF-beta peaked 7 days after infection in the lungs of the IL-4(-/-) mice, and then fell to very low levels in the late disease, while IFN-gamma remained high. Accordingly, hydroxyproline content was reduced in infected IL-4(-/-) mice compared to IL-4(+/+) controls. In conclusion, the findings suggest that IL-4 has modestly detrimental effects on the antibacterial efficacy of the Th1 response, and larger effects on the toxicity of TNF-alpha, and on fibrosis.

Animals↗

Iatrogenic intestinal injury concomitant to iatrogenic bile duct injury: the second component.

OBJECTIVE: Bile duct injuries have a frequency of 0.1% to 0.3% even in the most experienced centers. Complex biliary lesions usually require a bilioenteric anastomosis, achieving good long-term results in 80% to 90% of the cases. Besides injuries to the abdominal contents during laparoscopy (by trocars or electrocautery), intestinal complications associated with reconstruction attempts can be observed. We analyzed the concomitant intestinal complications in 251 patients with iatrogenic biliary injuries reconstructed over this 12-year period. METHODS: A retrospective review of patients with biliary tract reconstruction after iatrogenic injury in a tertiary academic health-care center was done. All patients with concomitant intestinal injury were included; type of operation and postoperative outcome were analyzed. RESULTS: Among 251 patients, 35 cases had a concomitant intestinal injury. The most common site of fistulization was the duodenum (18 cases, 50%); 9 cases were associated with long-term subhepatic drains (more than three weeks), and the other 9 cases were associated with a dehiscent hepatoduodenostomy. Faulty Roux-en-Y reconstruction was observed in 5 cases. In 5 cases, fistulization of the jejunum and ileum, secondary to drain placement, was documented, as well as 3 cases with colonic injuries. Two patients had a dehisced Roux-en-Y anastomosis. One had a bilioenteric omega type ileal anastomosis, and 1 had a hepatoileal anastomosis without omega reconstruction. Primary repair of the duodenum with resection of the affected intestinal or colonic segment was done at the same time of biliary repair without related morbidity. CONCLUSIONS: Concomitant gastrointestinal injures were found with an incidence of 15% in our series. The most common site of fistulization is the duodenum. In half of the patients, it was secondary to a dehiscent hepatoduodenostomy, whereas in the other, it was caused by long-term subhepatic drains. Besides faulty Roux-en-Y reconstruction, fistulization was related with long-term drains. Primary repair and resection of the affected segment of jejunum, ileum, and colon can be done during the same operative stage of biliary reconstruction, without significant correlated mortality.

Academic Medical Centers↗

Surgical treatment of non-cirrhotic presinusoidal portal hypertension.

BACKGROUND/AIMS: Non-cirrhotic portal hypertension has a better prognosis than other forms of portal hypertension because of a well-preserved liver function in most cases. These patients are good candidates to receive surgical treatment, which is the therapeutic choice available with the lowest rebleeding rate. Because of abnormalities in the splanchnic vessels due to the nature of the diseases, many of them cannot be shunted. An extensive esophagogastric devascularization, the complete portoazygos disconnection, was evaluated. METHODOLOGY: A retrospective review of files of 31 patients, among 491 operations between 1991 an 2001 was carried out in a tertiary care Academic University Hospital. Patients comprised those with non-cirrhotic bleeding portal hypertension treated by means of complete portoazygos disconnection. Extensive two-stage (thoracic and abdominal) esophagogastric devascularization with modified transection of the esophagus was performed. MAIN OUTCOME MEASURES: recurrence of hemorrhage, encephalopathy and survival. RESULTS: Thirty-one patients were treated. In 17 cases (54%) a hypercoagulable state was demonstrated. No operative mortality was observed (0-30 days) with a total of 62 operations (two stages per patient). No case of encephalopathy was observed and in 3 cases (9%) rebleeding was recorded. The survival curve showed a 5-year survival of 97% and a 10-year survival of 93%. CONCLUSIONS: Complete portoazygos disconnection is an excellent surgical alternative for patients with non-cirrhotic portal hypertension, with a low morbidity and mortality as well as a low rebleeding rate and good long-term survival.

Adult↗

Complete resection of choledochal cyst with Roux-en-Y derivation vs. cyst-enterostomy as standard treatment of cystic disease of the biliary tract in the adult patient.

BACKGROUND/AIMS: Cystic disease of the biliary tract (CDBT) is characterized by varying degrees of dilatation of the biliary system with high morbidity and mortality in which the surgical management is the corner stone of treatment. The cyst-enterostomies (CE) temporarily solve the obstruction to the biliary flow but have a high long-term morbidity. Complete resection of affected bile ducts with Roux-en-Y derivation (CRR-en-Y) is a good procedure with low mortality and complications. The purpose of the study was to analyze the outcome of CRR-en-Y versus CE in the treatment of CDBS in adult patients from 1970 to 2002. METHODOLOGY: Patients who underwent surgical treatment were divided for their analysis into two groups: Group I: CRR-en-Y and Group II: CE. Following features were compared: demography, clinical picture, postoperative morbimortality, outcome and survival. RESULTS: Thirty-four adult patients were analyzed. There were 82% (28) females and 18% (6) males. The age average was 33.58 years (13-84). Seventy percent (30) were "choledochal cyst". Eighty percent (27) were surgically handled: 52% (14) with CRR-en-Y (Group I) versus 58% (13) with CE (Group II). Both groups were comparable. Without operative mortality and low postoperative morbidity in both, CE had more long-term complications: In this group 70% (9) were readmitted: and 7 underwent reoperation. Mean follow-up was 35 months (6-132) versus 152 months (12-408) respectively. CONCLUSIONS: CRR-en-Y is the standard treatment of CDBS in the adult patient.

Adolescent↗