Long-term outcome of patients with ergonovine induced coronary constriction not associated with ischemic electrocardiographic changes.

OBJECTIVES: This study investigated the long-term outcome of patients with coronary artery constriction induced with ergonovine but not associated with ischemic electrocardiographic changes. METHODS: The ergonovine provocation test was performed in 419 patients with suspected but unproven variant angina. Ergonovine maleate was administered into the coronary arteries at 8 micrograms/min for 5 min during cardiac catheterization. Patients were categorized into three groups according to their response to ergonovine. The positive group contained patients who developed coronary constriction of more than 90% in diameter associated with ischemic electrocardiographic changes and chest pain. The intermediate group contained patients who had coronary constriction of more than 90% but no electrocardiographic changes. The negative group contained patients who had neither significant coronary constriction nor ST segment changes. RESULTS: There were 305 patients, 49, and 65 in the negative, intermediate, and positive groups, respectively. Death occurred in six patients (2%), one (2%), and one (2%) in the negative, intermediate, and positive groups, respectively. Sudden cardiac death occurred in one patient in the negative group. Recurrence of chest pain with effectiveness of sublingual administration of nitroglycerine was observed in 26 patients (9%), 10 (20%), and 11 (17%) in the negative, intermediate, and positive groups, respectively. CONCLUSIONS: Some patients in the intermediate group might show "false negative" response to ergonovine so careful treatment with calcium antagonists should be continued in patients in the intermediate group as well as patients with vasospastic angina.     

Characterization of muscarinic receptor subtypes on rat pancreatic acini: pharmacological identification by secretory responses and binding studies.

In order to identify subtypes of muscarinic receptor on the rat pancreas, the effects of new muscarinic receptor antagonists, [11-[[2-(diethylamino)-methyl]-1-piperidinyl]acetyl]-5, 11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one (AF-DX 116) and 4-diphenylacetoxy-N-methylpiperadine-methiodide (4-DAMP), on amylase secretion stimulated by carbachol and binding of [3H]quinuclidinyl benzilate (QNB) were evaluated using isolated rat pancreatic acini. Atropine, pirenzepine, AF-DX 116 and 4-DAMP inhibited carbachol-stimulated amylase release in a dose-dependent manner. All these antagonists caused a concentration-dependent rightward shift of the dose-response curve for carbachol-stimulated amylase release without altering the maximal response. Schild plots revealed that pA2 values for atropine, pirenzepine, AF-DX 116 and 4-DAMP were 9.15, 6.78, 6.09 and 8.79, respectively. Every slope of Schild plots was not different from unity, suggesting that these antagonists act as competitive inhibitors. These antagonists also inhibited the binding of [3H]QNB in a dose-dependent manner. The inhibition constants were 1.21 x 10(-9) M (atropine), 1.26 x 10(-7) M (pirenzepine), 0.57 x 10(-6) M (AF-DX 116) and 2.75 x 10(-9) M (4-DAMP). Thus, the order of inhibitory potencies was atropine > or = 4-DAMP > pirenzepine > AF-DX 116. These findings suggest that 4-DAMP-sensitive M3 receptor may play an important role in the pancreatic exocrine functions.     

Therapeutic immunization against Helicobacter mustelae in naturally infected ferrets

BACKGROUND & AIMS: Helicobacter infection of the gastric antrum is responsible for a number of gastric disorders. Antibiotic therapy is lengthy and is not always effective. It has been shown previously that oral immunization against Helicobacter felis in mice can prevent colonization after challenge. The aim of this study was to investigate the efficacy of therapeutic immunization in eradicating an established Helicobacter infection and in reducing gastritis. METHODS: Domestic ferrets, confirmed to be infected with Helicobacter mustelae by gastric endoscopy, were orally immunized with varying doses of purified Helicobacter pylori urease in combination with the mucosal adjuvant cholera toxin. Ferrets were assessed 1 week and 6 weeks after treatment for infection and pathology. RESULTS: Therapeutic immunization eradicated Helicobacter colonization in 30% of all immunized ferrets, although there was no difference in efficacy between the varying doses of antigen tested. The difference was statistically significant when compared with animals administered cholera toxin alone or buffer (P = 0.04). The intensity of inflammation was also significantly reduced in immunized animals (P = 0.0003). CONCLUSIONS: Oral immunization with purified H. pylori urease and cholera toxin can eradicate H. mustelae in a natural host pathogen model. Oral immunization of chronically infected animals markedly reduced gastric inflammation. (Gastroenterology 1996 Jun;110(6):1770-5)     

A case of suspected lung metastasis of pancreatic carcinoma with bronchorrhea similar to bronchioloalveolar carcinoma]

There have been only a few reports of bronchorrhea in patients with metastatic pulmonary carcinoma. We report a case of suspected lung metastasis of pancreatic carcinoma with bronchorrhea, which was radiologically similar to bronchioloalveolar carcinoma. A 67-year-old man who had previously undergone surgical resection of pancreatic carcinoma was admitted because of a progressive cough producing copious amounts of serous sputum. A chest radiograph on admission revealed an infiltrative shadow with air bronchograms and ground glass opacities in the left middle and lower lung fields. A chest CT scan revealed a consolidative shadow with air bronchograms and bubble-like lucencies similar to bronchioloalveolar carcinoma in the left lower lobe. The histopathological features of the specimen obtained by transbronchial biopsy revealed adenocarcinoma with a pattern identical to that of the pancreatic carcinoma. Immunohistochemical staining with anti-SP-A antibody was entirely negative but those with anti-CA 19-9, Dupan 2 and CA 50 were positive in both lung and pancreatic tumors. These results strongly suggest that the pulmonary carcinoma was a metastasis of cystic adenocarcinoma of the pancreas. In summary, for a definitive diagnosis of bronchioloalveolar carcinoma, extrapulmonary adenocarcinoma as a primary site should first be ruled out.     

Binding and internalization of recombinant human erythropoietin in murine erythroid precursor cells

Erythropoietin (EPO) biosynthetically labelled with [35S]cysteine was produced from Chinese hamster ovary (CHO) cells containing amplified copies of human EPO cDNA. The glycosylated recombinant [35S]EPO, purified to virtual radiochemical homogeneity, was biologically active. We studied the interaction of this labeled recombinant EPO with erythroid precursor cells from mice made anemic with phenylhydrazine. The [35S]-labeled molecule bound to erythroid precursors in a time- and temperature-dependent manner. The binding was specific for EPO, and neither insulin, transferrin, epidermal growth factor, nor multiplication stimulating activity could compete for EPO binding sites. In the presence of 0.2% sodium azide, which blocks 80% to 90% of internalization, the recombinant molecule bound with an apparent Kd of 750 pmol/L and 100 to 200 binding sites per cell at 37 degrees C. Asialo-EPO was a more effective competitor than sialated EPO for the available binding sites. Thus, the enhanced biological specific activity of asialo-EPO could result from its enhanced binding affinity. We also studied recombinant human EPO labeled with 125I and found that it also bound to the erythroid cells in a saturable and specific manner. After 90 minutes of incubation at 37 degrees C, most of the bound [35S]EPO was internalized, whereas most of the [125I]EPO remained on the cell surface. The reduced internalization of the iodinated molecule could account for the previously reported functional deficit associated with iodination.     

Ischemic hepatitis induced by mesenteric volvulus in a patient with chronic obstructive lung disease

A 66-year-old man with chronic obstructive lung disease was admitted to our hospital, presenting with mesenteric volvulus and mild liver injury. A superior mesenteric angiogram revealed that the arteries supplying the small intestine were twisted in the arterial phase, while the portal vein was not visualized in the late phase. A celiac angiogram demonstrated that portal blood flow from the splenic venous return was maintained. The patient's symptoms had almost resolved the day after admission, and his serum transaminases level had gradually decreased to normal with conservative therapy. A superior mesenteric angiogram on the 13th hospital day showed a normal arteriogram and the portal vein demonstrated blood flow from the superior mesenteric vein. Liver biopsy revealed hemorrhagic necrosis around the central veins, which was compatible with ischemic hepatitis. Since the patient's O₂ saturation level on admission was not low enough to have caused ischemic hepatitis by itself, we suspect that a sudden decrease in portal blood flow was the additional factor that allowed the threshold for the initiation of ischemic liver damage to be reached. Received: January 13, 1999 / Accepted: June 25, 1999     

A paucity of unusual trihydroxy bile acids in the urine of patients with severe liver diseases

To clarify the relationship between the occurrence of unusual trihydroxy bile acids, namely hyocholic acid, ursocholic acid (UCA), and omega-muricholic acid (omega-MCA) in urine and liver disease severity, urinary bile acids were analyzed by gas-liquid chromatography in acute and late phases of acute hepatitis and before and after ursodeoxycholic acid (UDCA) loading in healthy adults and liver cirrhosis patients. In 11 patients with acute hepatitis, the occurrence rates and amounts of unusual trihydroxy bile acids were increased in the late (recovery) phase, as compared with those in the early phase. In 10 patients with severe acute hepatitis who had prothrombin times exceeding 16 seconds, these bile acids had completely disappeared from the urine in the early phase but reappeared in the late phase in those who had a good outcome, though never in a patient who died. After UDCA administration for a week, the amounts of unusual bile acids, especially UCA and omega-MCA, which are thought to be synthesized through 12 alpha- and 6 alpha-hydroxylations, respectively, from UDCA, were clearly increased in 10 healthy adults but only slightly changed in 10 patients with liver cirrhosis. In conclusion, hepatic hydroxylations of dihydroxy bile acids as a detoxification reaction were impaired in severe liver diseases, which may play a role in the intensification and perpetuation of hepatocellular injuries.     

A regurgitant jet and echocardiographic abnormalities in aortic regurgitation: an experimental study

Acute aortic regurgitation was created experimentally in 21 mongrel dogs to examine the relationship of the regurgitant jet to observed echocardiographic findings. The direction of the regurgitant jet was studied by echo contrast injections in the aortic root. Diastolic fluttering of the anterior mitral leaflet (AML) was noted in all 21 dogs irrespective of direction of the jet. Diastolic fluttering of the interventricular septum (IVS) was noted in six of the seven dogs with a tear of the noncoronary cusp and in one of seven dogs with lesions in the left coronary cusp. In all seven dogs with echocardiographically demonstrated IVS fluttering, a regurgitant jet impinged on the anterior part of the IVS. Amplitude of the AML excursion was not significantly different from control when the lesions involved the noncoronary or the left coronary cusps. However, all seven dogs that had a lesion in the right coronary cusp demonstrated a significant reduction in the amplitude of the AML excursion. The regurgitant jet in these dogs impinged uniformly on the AML. We conclude that diastolic fluttering of the AML is uniformly observed and unrelated to the direction of the regurgitant jet, diastolic fluttering of the IVS is caused by the regurgitant jet impinging upon the IVS, and amplitude of the AML may be reduced as a result of a jet impingement of the AML.     

Successful treatment of intractable esophagothoracic fistula using covered self-expandable stent

This report concerns the successful treatment with a covered self-expandable stent of an intractable thoracoesophageal fistula after total esophagectomy for esophageal cancer. Total esophagectomy was performed on a 68-year-old man who presented with a huge esophageal cancer in the lower esophagus. Massive leakage was observed on the 5th day postoperatively. Since high fever and coughing continued, he was diagnosed as having esophagothoracic fistula and pyothorax, after which fenestration of the right chest wall was performed. Although the patient's general condition was getting better, stenosis near the anastomosis (esophagogastrostomy) and the esophagothoracic fistula were resistant to treatment with balloon dilatation and repeated endoscopic mucotomy. Further treatment, consisting of glue or fibrin sealant injection was not effective. After a covered self-expandable stent had been placed endoscopically, however, the fistel was completely cured in 2 months. This new endoscopic approach thus represents a promising option for the treatment of intractable esophagothoracic fistula.     

Serum total bile acid level as a sensitive indicator of hepatic histological improvement in chronic hepatitis C patients responding to interferon treatment

BACKGROUND AND METHODS: Serum total bile acid (TBA) levels are used clinically as a sensitive and reliable index of hepatobiliary diseases. In the present study, to assess the clinical usefulness of determining TBA in interferon (IFN)-treated patients, changes in liver function test values, including TBA and liver histology, were examined in 36 chronic hepatitis C patients for 3 years after a sustained response to IFN treatment. RESULTS: Alanine aminotransferase and gamma-glutamyl transpeptidase values significantly decreased during the period of IFN treatment compared to the same measures before IFN treatment. Albumin, cholinesterase, total cholesterol and platelet count values temporarily decreased during IFN treatment, then increased significantly and reached a plateau 6-12 months after the end of IFN treatment. The zinc sulphate turbidity test and TBA values began to decrease during IFN treatment and continued to decrease during the 3-year follow-up period. The histological activity index of the liver (Knodell's score) significantly decreased, whereas the staging score was unchanged 1 year after the end of IFN treatment. In patients who had a TBA value > 10 micromol/L before IFN treatment, a significant correlation was observed between the decrease of TBA and liver histology grading score. CONCLUSIONS: A decrease in serum TBA level reflected histological improvement in the liver more precisely than did changes in the other liver function test values following IFN therapy.