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Biomedical subjects

F M Martin

Publications and source records attributed to F M Martin.

At least 19 recordsLinked to original sources
PubMed2004

Vanin-1-/- mice exhibit a glutathione-mediated tissue resistance to oxidative stress.

Vanin-1 is an epithelial ectoenzyme with pantetheinase activity and generating the amino-thiol cysteamine through the metabolism of pantothenic acid (vitamin B(5)). Here we show that Vanin-1(-/-) mice, which lack cysteamine in tissues, exhibit resistance to oxidative injury induced by whole-body gamma-irradiation or paraquat. This protection is correlated with reduced apoptosis and inflammation and is reversed by treating mutant animals with cystamine. The better tolerance of the Vanin-1(-/-) mice is associated with an enhanced gamma-glutamylcysteine synthetase activity in liver, probably due to the absence of cysteamine and leading to elevated stores of glutathione (GSH), the most potent cellular antioxidant. Consequently, Vanin-1(-/-) mice maintain a more reducing environment in tissue after exposure to irradiation. In normal mice, we found a stress-induced biphasic expression of Vanin-1 regulated via antioxidant response elements in its promoter region. This process should finely tune the redox environment and thus change an early inflammatory process into a late tissue repair process. We propose Vanin-1 as a key molecule to regulate the GSH-dependent response to oxidative injury in tissue at the epithelial level. Therefore, Vanin/pantetheinase inhibitors could be useful for treatment of damage due to irradiation and pro-oxidant inducers.

Amidohydrolases↗
PubMed1998

The synthesis of novel matrix metalloproteinase inhibitors employing the Ireland-Claisen rearrangement.

Matrix metalloproteinase inhibitors of general formula (1) were synthesised by a route involving an Ireland-Claisen rearrangement which enables systematic modification of the substituent alpha to the hydroxamic acid. An analogue (12c) possessing an alpha-cyclopentyl group is a potent broad spectrum inhibitor that displays high and sustained blood levels following oral dosing in both the rat and marmoset ex-vivo bioassays. This compound and analogues are also potent inhibitors of TNF alpha release.

Administration, Oral↗
PubMed1992

Primary sclerosing cholangitis.

Primary sclerosing cholangitis is a condition of unknown cause. It is recognized by liver dysfunction and its characteristic radiologic appearance, which is related to portal tract inflammation, bile duct proliferation, and periductal fibroses involving small intrahepatic and large extrahepatic ducts. The disease lasts about 10 years from the time of diagnosis. Primary sclerosing cholangitis is recognized by abnormal results on routine liver function tests or by the development of clinical jaundice. An autoimmune cause has been suggested because of its strong association with inflammatory bowel disease, certain antigens, AIDS, and immunoregulatory abnormalities. Results of medical management of sclerosing cholangitis have been disappointing. Immunosuppressive drugs, copper chelating agents, and antibiotics have failed to alter progression of the disease. Colectomy in patients with inflammatory bowel disease also has no influence. The judicious use of dilations of strictures, bypass procedures, or resection can palliate jaundice in patients with primary sclerosing cholangitis, but liver transplantation is the definitive treatment. Because palliative operations increase the hazards of liver transplantation, percutaneous dilations and stentings are preferred initially. Cirrhosis and portal hypertension are indications for transplantation. In the future, transplantation may be indicated earlier in the course of the disease.

Cholangitis, Sclerosing↗
PubMed1990

Clinical and pathologic correlations in patients with periampullary tumors.

Perioperative data on 87 patients undergoing pancreatoduodenectomy for periampullary tumors were correlated with pathologic study of operative specimens to identify the accuracy of diagnosis and the factors affecting survival. Accuracy of endoscopic retrograde cholangiopancreatography and computed tomography in locating lesions was 75% and 44%, respectively. Histologic diagnosis before or at the time of resection was available in only 61% of the patients. Carcinoma was correctly diagnosed clinically by the pathologist or the surgeon in 95% (83/87) of patients with 4 patients found to have benign disease on final pathologic examination. Intraoperative diagnosis of site of origin was incorrect in 18% (16/87) of patients. In 28% (23/83) of patients, pathologists identified nodal metastatic disease missed by the surgeon. Survival correlated with nodal and margin status and tumor grade. Tumor size demonstrated no predictive capacity. Although preoperative diagnostic accuracy is less than optimal, surgeons can usually diagnose malignant lesions but more often fail to identify tumor origin and nodal disease. We continue to advocate resection for patients with periampullary lesions thought to be malignant and resectable without a positive histologic diagnosis.

Adult↗
PubMed1990

Bleeding stomal varices. The role of local treatment.

The authors reviewed their experience with 12 patients (median age, 38 years; range, 24 to 66 years) who had bleeding stomal varices. Stomal variceal bleeding occurred between 1 and 11 years (median, 5.5 years) after creation of the stoma. Control of bleeding initially consisted of direct pressure; recurrent bleeding occurred in one patient who died before definitive therapy could be performed. The remaining 11 patients underwent a total of 18 additional procedures for control of bleeding stomal varices, including 9 local procedures, 8 portosystemic shunts, and 1 liver transplantation. Seven patients were dead of hepatic failure a median of 4 years (range, 1 to 9 years) after treatment. Recurrent bleeding occurred in three patients after local treatment and in one patient after a portosystemic shunt. Bleeding stomal varices are a manifestation of severe liver disease and portal hypertension. Although local procedures may be effective for initial control of bleeding, recurrent bleeding often occurs. Mortality is high because of the severity of the underlying liver disease.

Adult↗
PubMed1990

Surgical aspects of sclerosing cholangitis. Results in 178 patients.

Of 178 patients with sclerosing cholangitis treated since 1950, 88 patients had associated inflammatory bowel disease, 72 had no such history, and 18 had iatrogenic injury or stone disease. A total of 233 biliary operations were performed, with a 75% rate of temporary improvement after initial operation. Subsequent operations resulted in a lower success rate and a higher mortality rate. Radiologic findings included predominant extrahepatic, intrahepatic, and diffuse disease in 29%, 28%, and 43% of patients, respectively; no survival differences were noted. Seventy-five of one hundred three deaths (73%) were related to liver failure, bleeding, or sepsis. Of 14 patients undergoing portosystemic shunt, 13 died of surgical complications or related disease. Orthotopic liver transplantation was performed in 16 patients and resulted in eight deaths, mainly in patients who had previously undergone extensive surgical treatment. No survival differences were seen between the patients with inflammatory bowel disease, those without the condition, or those who had colectomy. Surgical treatment in patients with sclerosing cholangitis should be minimized. Orthotopic liver transplantation should be offered as the treatment of choice for patients with portal hypertension, refractory cholangitis, advanced cirrhosis, or progressive liver failure.

Adolescent↗
PubMed1989

Liver abscess. The need for complete gastrointestinal evaluation.

The cause of liver abscess is frequently obscure at initial presentation. We reviewed the medical records of 20 patients with pyogenic liver abscess over a 6-year period from 1981 to 1987. Liver abscess was suspected in only 3 patients on admission; the most common initial diagnosis was fever of unknown origin. Subsequently, the origin of the abscess was found to be intestinal in 7 patients, pancreatobiliary in 11 patients, and cryptogenic in 2 patients. Eleven patients underwent percutaneous transhepatic drainage of the abscess as the initial treatment, while open operation was the initial treatment in 9 patients. Percutaneous transhepatic drainage was ultimately successful in only 4 patients (36%). In the absence of an obvious pathologic condition of the biliary tract, all patients should undergo full gastrointestinal evaluation.

Adult↗
PubMed1989

Management of pancreatic fistulas.

Conservative management of pancreatic fistulas resulting from trauma, operation for tumor, or operation for pancreatitis has met with variable success. To assess optimal management strategies and outcome, we reviewed the records of 35 patients with external pancreatic fistulas (26 patients), pancreatic ascites (6 patients), or pancreatic pleural effusion (3 patients). Treatment included no operation in 5 patients, oversewing of the fistula in 7 patients, internal drainage in 11 patients, and resection in 12 patients. One (3%) postoperative death occurred. The overall rate of operative success was 83% (25 patients). The incidence of recurrent fistulas was about the same regardless of the procedure. Patients treated successfully without operation did not have pancreatitis as an underlying disease. Patient selection is of great importance in the decision to resect or to drain and is based in part on imaging the pancreatic duct and fistula.

Adult↗
PubMed1989

Apparent affinity of 1,3-dipropyl-8-cyclopentylxanthine for adenosine A1 and A2 receptors in isolated tissues from guinea-pigs.

1. The classification of adenosine receptor subtypes (A1 and A2) in intact tissues has been based on the order of agonist potency. In this study the apparent affinity of 1,3-dipropyl-8-cyclopentylxanthine (CPX), an antagonist which has been reported to be A1 selective, and the non-selective antagonist 1,3-dimethyl-8-phenylxanthine (8PT) has been evaluated on isolated tissues from the guinea-pig. 2. The isolated tissues used were atria (bradycardic response, proposed A1 sub-type), aorta and trachea (relaxant response, proposed A2 sub-type). 3. Both the xanthines antagonized responses to adenosine in the three tissues but had little or no effect on responses to carbachol (atria), sodium nitrite (aorta) or isoprenaline (trachea). 4. pA2 values for 8PT were similar on the three tissues (6.3-6.7), however, the pA2 value for CPX on the atria (7.9-8.4) was greater than that on the aorta (6.6) or trachea (6.6). 5. These results support the suggestion that the adenosine receptors which mediate bradycardia in the atrium are of the A1 sub-type and that those which mediate relaxation in the aorta and trachea are of the A2 type.

Adenosine↗
PubMed1988

Glucagonoma presenting as morbid obesity.

A case is described that represents the only reported patient with glucagonoma syndrome and morbid obesity. The diagnosis of glucagonoma should be considered in any patient with the classic criteria despite weight gain. The criteria for diagnosis of glucagonoma are 1) the presence of a glucagon-secreting tumor, 2) hyperglucagonemia, and 3) the clinical manifestations of either necrolytic migratory erythema, glucose intolerance, or hypoaminoacidemia.

Adenoma, Islet Cell↗
PubMed1988

Therapeutic colonoscopy in the treatment of colonic pseudo-obstruction.

Colonic pseudo-obstruction has been recognized since Ogilvie described this disease in 1948. Metabolic, surgical, and medical causes have been implicated at various times. Treatment has included surgical decompression by cecostomy and colectomy. Successful nonoperative decompression by colonoscopy was first reported by Kukora and Dent in 1977. Since that report several authors have reported their results using this technique. Presented here is a series of nine patients with colonic pseudo-obstruction treated initially with colonoscopy. Patients presented with a variety of associated conditions, including post operative patients, orthopedic injuries, metastatic carcinoma, and an unusual case after a normal vaginal delivery. Eight patients responded well to colonoscopic decompression. One patient, the second in the series, was unable to be decompressed with colonoscopy and underwent a cecostomy under local anesthesia. Successive colonoscopy may be required to allow restoration of normal colonic function, as was the case in seven of our patients. One death occurred, due to unrelated causes. The authors have found colonoscopy to be a safe and reliable therapy for colonic pseudo-obstruction.

Adult↗
PubMed1986

Vascular endothelium contributes to decreased aortic contractility in experimental sepsis.

In this study, we compared responses to norepinephrine (NE) by thoracic aortic rings isolated from rats made septic by cecal ligation with puncture, and aortic tissue from sham-operated control rats. We also examined the responses of septic and sham-operated rat aortas after removal of the vascular endothelium. Acetylcholine caused relaxation of NE-induced contractions in septic and sham tissue with an intact endothelium but had no effect on tissue with the endothelium removed experimentally. In preparations with intact endothelium, septic tissue manifests a significantly diminished maximal contractile response to NE (424 +/- 62 (SE) mg tension/mg tissue) in comparison to sham tissue (747 + 30). Tissues with the endothelium removed show no significant maximal contractile difference between septic (688 +/- 23) and sham (669 +/- 32) preparations, or the equivalent sham tissue with an intact endothelium. No difference in the log ED50 for sham tissue (-7.33 +/- 0.12 M) and septic tissue (-7.53 +/- 0.15) with intact endothelium existed. Removal of the endothelium from both septic and sham tissue shifted the dose response curves to the left, disclosing a significant difference in the ED50 between sham (-8.88 +/- 0.14) and septic (-8.18 +/- 0.20) tissue. In conclusion, a significant impairment of vascular contractility in response to NE, with no change in ED50, persists in septic vascular tissue in vitro, and the sepsis-induced defect in contractility is mediated, at least in part, by vascular endothelium, since removal of the endothelium partially restores the NE-stimulated contraction to normal.

Acetylcholine↗
PubMed1985

Cadmium-induced lung injury: cell kinetics and long-term effects.

The effects of exposure to CdCl2 aerosols followed by hyperoxia were studied in mouse lung. Special emphasis was placed on analysis of cell proliferation following injury. Male Balb/c mice were exposed to aerosols of 4.9 micrograms Cd/liter for 1 hr while controls were exposed to water aerosols. Immediately after, half of each group was placed in 80% O2 for 6 days, while the rest were left in room air. Three endpoints were used to assess lung injury; measurement of hydroxyproline, [14C]thymidine incorporation into DNA, and histopathology. Parenchymal and bronchiolar labeling indices were determined following autoradiography. A 1-hr exposure to CdCl2 aerosols caused marked cell proliferation in the lung with the peak of cell labeling occurring at Day 5. In animals exposed to both CdCl2 + 80% O2, the cell labeling peak was delayed until Day 9. Cell differentiation studies showed a delay in the peak of type II epithelial cell and endothelial cell division when CdCl2 exposure was followed by the 80% O2 treatment. On Day 15 most of the labeled cells were identified as interstitial cells in both treated groups. Bronchiolar cell labeling was suppressed at the early time period in the Cd + O2 group. With time, the histologically visible lung lesions tended to resolve in animals exposed to CdCl2 or CdCl2 and 80% O2, whereas total pulmonary hydroxyproline remained at all times (3, 6, and 12 months) significantly higher in Cd-treated animals when compared to controls. It was concluded that acute lung injury by a toxic inhalant can be amplified if there is an initial delay in pulmonary cell proliferation following an acute insult.

Aerosols↗
PubMed1983

Potentiating effects of oxygen in lungs damaged by methylcyclopentadienyl manganese tricarbonyl, cadmium chloride, oleic acid, and antitumor drugs.

The intraperitoneal administration of methylcyclopentadienyl manganese tricarbonyl (MMT) and cyclophosphamide, exposure to an aerosol of cadmium chloride, intravenous administration of oleic acid, and intratracheal instillation of bleomycin to young female BALB/c mice or CD/CR rats result in acute lung injury. Pulmonary morphology and lung collagen content were examined in animals treated with these chemicals alone or in combination with an elevated oxygen concentration (80%) in the inspired air. In mice, the development of fibrosis could be significantly enhanced if animals treated with MMT, cadmium chloride, cyclophosphamide, or bleomycin were exposed to 80% oxygen immediately following exposure to these agents. In rats only cyclophosphamide- and bleomycin-induced acute lung injury was potentiated by hyperoxia, resulting in significant enhancement of lung collagen content. The pathogenesis responsible for this differential species response of pulmonary injury to hyperoxia remains to be investigated.

Animals↗