Search PubMed⌕ Search

Biomedical subjects

H Orozco

Publications and source records attributed to H Orozco.

At least 37 records · Page 2Linked to original sources

Analysis of the local kinetics and localization of interleukin-1 alpha, tumour necrosis factor-alpha and transforming growth factor-beta, during the course of experimental pulmonary tuberculosis.

A mouse model of pulmonary tuberculosis induced by the intratracheal instillation of live and virulent mycobacteria strain H37-Rv was used to examine the relationship of the histopathological findings with the local kinetics production and cellular distribution of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) and transforming growth factor-beta (TGF-beta). The histopathological and immunological studies showed two phases of the disease: acute or early and chronic or advanced. The acute phase was characterized by inflammatory infiltrate in the alveolar-capillary interstitium, blood vessels and bronchial wall with formation of granulomas. During this acute phase, which lasted from 1 to 28 days, high percentages of TNF-alpha and IL-1 alpha immunostained activated macrophages were observed principally in the interstium-intralveolar inflammatory infiltrate and in granulomas. Electron microscopy studies of these cells, showed extensive rough endoplasmic reticulum, numerous lysosomes and occasional mycobacteria. Double labelling with colloid gold showed that TNF-alpha and IL-1 alpha were present in the same cells, but were confined to separate vacuoles near the Golgi area, and mixed in larger vacuoles near to cell membrane. The concentration of TNF-alpha and IL-1 alpha as well as their respective mRNAs were elevated in the early phase, particularly at day 3 when the bacillary count decreased. A second peak was seen at days 14 and 21-28 when granulomas appeared and evolved to full maturation. In contrast, TGF-beta production and numbers of immunoreactive cells were low in comparison with the advanced phase of the disease. The chronic phase was characterized by histopathological changes indicative of more severity (i.e. pneumonia, focal necrosis and extensive interstitial fibrosis) with a decrease in the TNF-alpha and IL-1 alpha production that coincided with the highest level of TGF-beta. The bacillary counts were highest as the macrophages became large, vacuolated foamy cells, and containing numerous bacilli with immunoreactivity to mycobacterial lipids and lipoarabinomannan (LAM). These macrophages displayed poor and scarce TNF-alpha and IL-1 alpha immunostaining but still strong immunoreactivity to TGF-beta. These cytokine production kinetics and the spatial relationship between immunostained cells and lung lesions corroborate the important role of TNF-alpha and IL-1 alpha in the constitution of granulomas and immune protection during the early phase of the infection, and also suggest an important if not primary role for TGF-beta in the immunopathogenesis of the advanced forms of pulmonary tuberculosis.

Animals↗

Pathogenesis of tuberculosis in mice exposed to low and high doses of an environmental mycobacterial saprophyte before infection.

Mycobacteria are ubiquitous in the environment, but they are not part of the normal human microbial flora. It has been suggested that variable contact with mycobacteria can influence susceptibility to mycobacterial pathogens and the efficacy of subsequent Mycobacterium bovis BCG vaccination. To test this, mice were immunized with high or low doses of an environmental saprophyte, M. vaccae, that is intensely immunogenic as an autoclaved preparation. Two months later, they received an intratracheal challenge with M. tuberculosis H37Rv. Recipients of a low Th1-inducing dose (10(7) organisms) were partially protected and maintained a high ratio of interleukin 2 (IL-2)-positive to IL-4-positive cells in the perivascular, peribronchial, and granulomatous areas of the lung, whereas in unimmunized controls the IL-4-positive cells increased markedly between days 21 and 28. In contrast, recipients of the high dose (10(9) organisms), which primes Th2 as well as Th1 cytokine production, died more rapidly than unimmunized controls and showed massive pneumonia from day 7. The ratio of IL-2-positive to IL-4-positive cells in all compartments of the lung rapidly fell to 1 by day 14 for these animals. These events correlated with cytokine mRNA profiles and with increases in the local toxicity of tumor necrosis factor alpha (TNF-alpha), demonstrable only when a major Th2 component was present. These data indicate that cross-reactive epitopes present in an environmental saprophyte can evoke either protective responses or responses that increase susceptibility to M. tuberculosis. The latter are associated with the presence of a Th2 component and increased sensitivity to TNF-alpha.

Animals↗

Distal splenorenal shunt versus 10-mm low-diameter mesocaval shunt for variceal hemorrhage.

BACKGROUND: Portal hypertension surgery remains a good therapeutic choice for well selected patients with variceal bleeding. The distal splenorenal shunt (DSRS) has shown good long-term results and low-diameter shunts have emerged as an alternate choice. METHODS: A prospective, controlled and not randomized study was designed to compare the DSRS (23 patients) and the low-diameter 10 mm ring reinforced PTFE mesocaval shunt (LDMCS) (22 patients) in low-risk electively operated patients (Child-Pugh A-B). The operation was selected according to the anatomical status of the veins. RESULTS: Both groups were comparable. No differences were observed regarding rebleeding, operative mortality and survival. Significative differences were observed regarding encephalopathy and shunt thrombosis (higher in the LDMCS). Postoperative angiography showed better maintenance of portal blood flow in the DSRS group. CONCLUSIONS: Both operations are adequate alternatives for the elective treatment of portal hypertension in low-risk patients. However, the DSRS has more advantages than the LDMCS.

Adult↗

Cytokine gene expression in cirrhotic and non-cirrhotic human liver.

BACKGROUND/AIMS: In order to explore the role of cytokines in the pathogenesis of liver cirrhosis, we analyzed their gene expression in hepatic biopsies from patients with alcoholic liver cirrhosis, post-hepatitis C liver cirrhosis, and with idiopathic portal hypertension without cirrhosis. METHODS: We assessed the gene expression of interleukins 1 beta, 2, 6, 8, and 10, as well as of tumor necrosis factor-alpha, transforming growth factor-beta and interferon-gamma by a quantitative polymerase chain reaction. RESULTS: We found high levels of transforming growth factor-beta in post-hepatitis C liver cirrhosis, high to moderate in alcoholic liver cirrhosis and low in non-cirrhotic specimens. Expression of interleukin-10, tumor necrosis factor-alpha, and interferon-gamma genes was detected in most post-hepatitis C liver cirrhosis, but not in idiopathic portal hypertension or alcoholic liver cirrhosis biopsies. The interleukin1-beta, 6 and 8 gene expression was significantly lower in alcoholic liver cirrhosis compared to post-hepatitis C liver cirrhosis, but higher compared to idiopathic portal hypertension specimens. Thus, post-hepatitis C liver cirrhosis samples showed a high degree of cytokine gene expression, whereas in alcoholic liver cirrhosis it tended to be moderate, and restricted to some cytokines (transforming growth factor-beta, interleukin-1, 6 and 8, but not interleukin-10, tumor necrosis factor-alpha or interferon-gamma). In contrast, most non-cirrhotic specimens showed a restricted and low cytokine gene expression. CONCLUSIONS: These data suggest that transforming growth factor-beta may have an important role in liver fibrosis and inflammation. Interleukin-1 beta, 6, 8, tumor necrosis factor-alpha and interferon-gamma, appear to participate in the pathogenesis of the mild to severe inflammatory phenomena seen in alcoholic and post-hepatitis C liver cirrhosis, respectively. Our data suggest that tumor necrosis factor-alpha does not participate in the hepatocellular damage of alcoholic liver cirrhosis, and indicate that neither interferon-gamma nor interleukin-10, at least at the levels observed in post-hepatitis C liver cirrhosis, are able to counteract the fibrotic/inflammatory process seen in this condition.

Adolescent↗

Comparison of outcomes and complications for open and laparoscopic cholecystectomy in Mexico.

A retrospective analysis of the outcome and surgical complications of two groups of patients undergoing cholecystectomy was performed. Group I consisted of 253 patients who underwent laparoscopic cholecystectomy between 1991 and 1994, and group II was formed by 292 patients who met the same preoperative criteria than patients of group I and underwent open cholecystectomy between 1986 and 1990, prior to the introduction of laparoscopic cholecystectomy in our hospital. General characteristics and associated clinical conditions were similar for both groups. Intraoperative cholangiography was used more frequently in group II whereas preoperative ERCP was performed more frequently in group I patients. There was no operative mortality in any of the groups. There were no statistically significant differences between both groups in terms of type and number of complications.

Cholangiopancreatography, Endoscopic Retrograde↗

Angiographic evaluation after portal blood flow preserving operations.

We carried out a prospective study comparing postoperative portal angiographic characteristics in patients with hemorrhagic portal hypertension treated electively by two different portal blood flow preserving procedures. Between 1986 and 1991, a total of 81 patients underwent operation: 38 selective shunts and 43 Sugiura-Futagawa procedures. Cirrhosis was shown by biopsy in 50 cases, 26 of them secondary to alcoholism. We found rebleeding in 5% of the patients, incapacitating postoperative encephalopathy in 8%, and an operative mortality of 7%. Fifty-two cases were evaluated in the postoperative period with angiography; 21 patients treated with a Sugiura-Futagawa operation were excluded due to portal vein thrombosis shown in the preoperative studies. Postoperative portal vein thrombosis was found in 11 cases (21%) [seven cases in the Warren group (21%) and four cases in the Sugiura-Futagawa group (20%)]. Decreased portal vein diameter was seen in eight cases (15%). The two procedures maintained hepatopedal portal blood flow, and no change was seen in relation to the preoperative state in 66% of the operated patients. We found no significant differences between the two procedures. Selection of procedure depends on the individual characteristics of each patient.

Adult↗

Adrenal changes in murine pulmonary tuberculosis; a clue to pathogenesis?

When mice were infected with virulent Mycobacterium tuberculosis H37Rv by the intra-tracheal route, there was an early phase of adrenal hyperplasia, histologically resembling the adrenocorticotropic (ACTH)-driven changes seen in Cushing's disease. This was followed at 3 weeks by progressive atrophy until the weight of the adrenals was approximately 50% of that seen in control uninfected mice, in spite of the fact that the adrenals were not infected. All layers of the adrenal cortex were affected, but the medulla was normal. Electron microscope studies revealed apoptosis. The switch from adrenal hyperplasia to adrenal atrophy corresponded to onset of an IgG1 response recognising a wide range of mycobacterial components in Western blots. Delayed type hypersensitivity (DTH) responses were seen throughout, but differed in their sensitivity to TNF alpha. Thus if TNF alpha was injected at 24 h into DTH sites elicited during the phase of adrenal hyperplasia, there was no increment in swelling at 48 h. However similar injections of TNF alpha resulted in a doubling of the swelling in DTH sites elicited during the phase of adrenal atrophy. This may be relevant to the pathogenesis of cytokine-mediated tissue damage in the human disease. If 2 months before mice received the intratracheal infection, they were pre-immunised with 1 x 1097) autoclaved Mycobacterium vaccae, a stimulus previously shown to induce a Th1 pattern of response, the early increase in adrenal weight was attenuated and delayed, and the subsequent atrophy did not occur. In sharp contrast, pre-immunisation with 1 x 10(9) autoclaved M. vaccae, known to prime a mixed pattern of cytokine release (IFN gamma and IL-4), resulted in adrenal atrophy that began within 4 days of infection, and was complete by day 14. These results suggested that the pattern of cytokine release provoked by the infection, modulated the adrenal changes, perhaps in synergy with products derived from the organisms themselves. Since we have already shown that profound adrenal changes also occur in human tuberculosis, we now propose that a change somewhere in the cytokine-hypothalamo-pituitary-adrenal axis may underlie the T cell dysfunction and immunologically-mediated tissue damage in this disease.

Adrenal Glands↗

Angiotensin I converting enzyme in glycerol-induced acute renal failure in rats.

Angiotensin I converting enzyme (ACE) activity was measured in serum, urine, and tissues of rats with acute renal failure (ARF) induced by glycerol. Glycerol-injected rats were subdivided in three groups according to the urinary volume: oliguric, nonoliguric, and polyuric. The damage to the proximal tubule was evident by (a) the histological analysis at light and electron microscopy level, (b) the augmented urinary excretion of the enzymes dipeptidyl aminopeptidase IV and N-acetyl-beta-D-glucosaminidase, and (c) the low molecular weight proteinuria pattern. On the other hand, the appearance of the glomeruli at the ultrastructural level was normal. These data suggest that the increased urinary excretion of enzymes and proteins in these rats is a consequence of the tubular injury. ARF was markedly higher in the oliguric rats. Urine ACE activity increased in the rats of the three groups, but statistical significance was reached only in the oliguric rats. Serum ACE activity increased in the oliguric rats and tissue ACE activity did not change. It is concluded that the high urinary ACE in glycerol-treated rats is associated with the damage to the kidney tubules. These data support the contention that urinary ACE may be another marker of injury to the proximal tubule.

Acetylglucosaminidase↗

T-cell lung granulomas induced by sepharose-coupled Mycobacterium tuberculosis protein antigens: immunosuppressive phenomena reversed with cyclophosphamide and indomethacin.

We induced lung granulomas in BALB/c mice by intratracheal instillation of Sepharose beads coated with a Mycobacterium tuberculosis protein extract. Granulomas composed of macrophages and lymphocytes were induced. The granulomatous reaction reached its peak 3-7 days after challenge and lasted for approximately 1 month. Immunolabelling of tissue sections and bronchial washings revealed that granulomas were predominantly composed of T lymphocytes with the cytotoxic-suppressor phenotype (CD8+). Granulomas were associated with a significant decrease in anti-mycobacterial immunity manifested by a drop in delayed-type hypersensitivity reactions and antibody titres. The immunosuppressive phenomena were abolished with cyclophosphamide or indomethacin. Control granulomas induced with methylated bovine serum albumin (BSA) were smaller and composed by similar numbers of CD4+ and CD8+ cells. BSA granulomas did not alter antibody titres but they decreased delayed-type hypersensitivity to BSA which was restored to normal with indomethacin but not with cyclophosphamide. Our findings show that mycobacterial proteins anchored to Sepharose beads are granulomatogenic and that they preferentially recruit CD8+ cells which, together with locally produced prostaglandins, down-modulate cell-mediated and humoral immunity to mycobacterial antigens.

Animals↗

Portal-systemic encephalopathy and gastrointestinal bleeding after cardioselective beta-blocker (metoprolol) administration to patients with portal hypertension.

The use of the non-selective beta-blocker propranolol has been widely recommended to prevent gastrointestinal bleeding in patients with portal hypertension. We conducted a prospective, randomized controlled trial of metoprolol, a selective beta-blocker for prevention of gastrointestinal bleeding from portal hypertension in 29 non-selected patients with liver disease and previous gastrointestinal bleeding. Fifteen patients received placebo treatment for 40 +/- 18 months and 14 patients received metoprolol for 31 +/- 17 months. A sustained reduction in resting pulse was observed in those patients treated with metoprolol. There was no significant difference in acute re-bleeding episodes between the two groups. Of the 14 patients treated with metoprolol, three (21%) re-bled, all three requiring blood transfusion. Four (26.5%) of the 15 patients treated with the placebo re-bled, two cases with acute bleeding and the remaining two cases presented a positive stool guaiac test. All cases who bled during the metoprolol therapy required exclusion from the trial, and surgical procedures or sclerotherapy as well. After both metoprolol or placebo treatments, similar deterioration of standard liver function tests was observed. Further, at the end of the trial, 11 patients on metoprolol (78%) and four of the patients treated with the placebo (27%) required treatment for clinical portal-systemic encephalopathy (p < 0.01). The risk of poor sympathomimetic response after cardioselective beta 1-blocker during acute bleeding episodes and the appearance of hepatic encephalopathy deserve further investigation. The selective beta-blocker metoprolol seems to be an inadequate choice to prevent gastrointestinal re-bleeding in patients with portal hypertension.

Adrenergic beta-Antagonists↗

Survival and quality of life after portal blood flow preserving procedures in patients with portal hypertension and liver cirrhosis.

Between 1979 and 1991, 156 patients with histologically proven liver cirrhosis, good liver function, and bleeding portal hypertension underwent operation with portal blood flow preserving procedures (selective shunts: 101; Sugiura-Futagawa: 55). Long-term results of the procedures and the quality of life of the 145 patients who survived the operation were studied. During the observation period (range 3 to 156 months), 28 patients died. The main causes of death were liver failure and hepatoma. Twenty-three patients were lost for follow-up. Twenty-six patients (18%) developed 1 or more encephalopathic episodes. Four patients (3%) experienced rebleeding. One hundred eight patients (74%) had a good quality of life, and 26 (18%) had a poor quality of life. Eleven (15%) of 73 patients with a history of alcoholism continued drinking. Five-year survival for the selective shunt group was 81% and for the devascularization group was 83%. In 81% of the patients, portal blood flow was maintained. It is concluded that both procedures are effective in the long-term. Most patients are able to rehabilitate from the use of alcohol, and most of them have a good quality of life. For patients with good liver function (whose main problem is bleeding), surgery is the best choice of treatment.

Adult↗

Long-term evolution of asymptomatic cholelithiasis diagnosed during abdominal operations for variceal bleeding in patients with cirrhosis.

To define the risk of complications in cirrhotic patients with asymptomatic cholelithiasis and the possible benefit of incidental cholecystectomy during abdominal operations in these patients, a retrospective cohort of cirrhotic patients who had asymptomatic cholelithiasis and underwent abdominal operations for portal hypertension was analyzed. Of 338 patients operated on during the last 15 years, 34 patients were found with asymptomatic cholelithiasis, all of whom had long-term follow-up. At a mean follow-up of 70.5 +/- 8.6 months (SEM), 28 patients remained asymptomatic (82%), 6 patients have developed symptoms (18%), (4 patients had acute cholecystitis and 2 chronic cholecystitis), and 3 of these patients (8.8%) died due to complications of acute cholecystitis. The results suggest that the risk for the development of complications is low but that the mortality associated with acute episodes of cholecystitis is high. Incidental cholecystectomy is not justified in cirrhotic patients with asymptomatic cholelithiasis, but close follow-up with early elective operation when symptoms supervene should be recommended.

Cholecystectomy↗

A comparative clinical study of idiopathic portal hypertension, extrahepatic portal vein thrombosis, and cirrhosis.

The relationship between idiopathic portal hypertension (IPH) and extrahepatic portal vein thrombosis (EPVT) remains controversial. In a retrospective study, we compared the clinical features of 21 patients with IPH, 27 with EPVT, and 38 with liver cirrhosis (LC). The variables with statistical difference between IPH and EPVT were age (38 +/- 17 years versus 29 +/- 14, respectively; p < 0.05), and 5-year survival (72 versus 92%, respectively; p < 0.05). The other clinical and laboratory variables had similar distribution in IPH and EPVT. LC patients were older than those in the other groups (48 +/- 13 years, p < 0.05), and had a poorer 5-year survival (60%, p < 0.05). Furthermore, LC patients had clinical features of liver failure in a higher proportion than the other groups did. The results suggest that IPH, EPVT, and LC are separate clinical entities.

Adolescent↗

Evidence that human placenta is a site of sex hormone-binding globulin gene expression.

The presence of an androgen-binding component in placenta was investigated in vitro using a tissue culture system of human placental explants. Explants of trophoblastic tissue from normal term placentas were kept in culture under appropriate conditions for at least 48 h in a serum-free medium. The existence of an androgen-binding protein was explored by binding assays, immunohistochemistry studies and Northern blot analyses of placental mRNA. Steady-state polyacrylamide gel electrophoresis and Scatchard plot analyses revealed the presence of a high affinity specific binding component for 5 alpha-dihydrotestosterone in cultured placenta. Immunohistochemical studies performed on intact placenta and on Percoll-gradient purified trophoblastic cells demonstrated the presence of specific immunoreactivity in the cytoplasm of syncytial cells. Northern blot analyses of placental mRNA showed a single hybridizable 32P-labeled human sex hormone-binding globulin (SHBG) cDNA band of approx. 1.6 kb which was identical in size to that obtained with liver mRNA. The results strongly suggest the placenta as an origin of SHBG and point out this tissue as an additional site of SHBG synthesis during pregnancy.

Blotting, Western↗

An alternate low risk technique for esophageal transection in the Sugiura-Futagawa procedure.

The Sugiura-Futagawa procedure is an effective non-shunting operation to treat bleeding esophageal varices. The goal of the esophageal transection is the interruption of submucosal varices. The rate of esophageal fistula reported after transection is 5 to 8 per cent. This complication has high morbidity and mortality rates. The technique and results of an alternate variant of the esophageal transection are described. After devascularization of the esophagus is achieved, the anterior muscular layer is opened, and the entire mucosal cylinder is dissected free from the muscular layer. Without opening the mucosa, a circumferential continuous running suture with fine non-absorbable material is placed, involving both mucosa and submucosa, interrupting the varicose veins. Our experience with this technique has been encouraging, having observed no stenosis or fistulization in 10 patients on whom we operated. Re-bleeding rate is low (10% in this series). The advantages of this modification are: 1) since we do not cut open the mucosal layer, we believe that the risk of fistulization is reduced, and 2) it allows an early initiation of oral feeding, thus reducing the hospital stay.

Esophageal and Gastric Varices↗

Selective splenocaval shunt for bleeding portal hypertension: fifteen-year evaluation period.

BACKGROUND: Splenocaval shunts have been used in this hospital since 1974 as an alternative to the distal splenorenal shunt. This report will detail the long-term results with this operation. METHODS: Thirty-three patients who were subjected to selective splenocaval shunts for treatment of hemorrhagic portal hypertension are reported. Mean age was 48.4 years. Twenty patients were women. Twenty-seven patients were in Child class A and six were in Child class B. RESULTS: There were five postoperative deaths. Two patients experienced rebleeding. One patient had shunt obstruction and one patient had severe clinical encephalopathy. Actuarial survival rate was 54.9% at 5 years and was 47.5% at 15 years. At the time of evaluation 12 patients were alive and well (shortest observation period, 2 months and longest observation period, 173 months). One of these patients has mild encephalopathy. CONCLUSIONS: Selective splenocaval shunts are a good alternative for treatment of hemorrhagic portal hypertension in patients with good liver function.

Actuarial Analysis↗