Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between January 1993 and March 2000, 16 patients underwent carinal resection for lung cancer; primary carcinoma in 15 patients and recurrent disease in 1. Age ranged from 41 to 74 years old, and the mean age was 58 years. Sleeve pneumonectomy was performed in 8 patients, right upper sleeve lobectomy in 7, and only carinal resection for the recurrent lesion in 1 patient. Combined resection of the aorta was performed in 2 patients, superior vena cava, in 5, left atrium and esophageal wall, in 1, and panpleura, in 1. The 30-day mortality rate was 25.0% (4/16) and the morbidity rate was 50% (8/16). The causes of death were pneumonia, airway bleeding without vascular fistula, brain edema and acute cardiac failure. Anastomotic complication including tracheo-pulmonary vascular fistula and stricture occurred in 2 patients. The 5-year survival rate was 23%.
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PMID:[Carinal resection for lung cancer]. 1119 7

The authors analyze a group of 26 patients with oesophageal carcinoma operated in the course of five years with regard to postoperative complications and period of survival. In seven instances they used Ivor-Lewis operation, 17 times Orringer's operation, twice a palliative retrosternal bypass. Twenty one times they used the stomach for replacement of the oesophagus, five times the left hemicolon antiperoristaltically. The preoperative ASA classification was on average 3. The moribidity was 74%. Respiratory complications were most frequent--18x, paresis of the left vocal cord--7x, a fistula in the anastomosis--5x. The hospital mortality was 27%, its causes being cardiac failure, MOF, fistulae in the anastomosis. In seven instances the authors performed tracheostomy. Of 19 surviving patients 13 died after an average period of 10 months. Six patients survive on an average for 11 months.
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PMID:[Evaluation of 26 esophagectomies from the aspects of complications and survival time]. 1121 Jun 6

Disruption of the pancreatic anastomosis with resultant sepsis is the cause of nearly 50% of deaths following pancreaticoduodenectomy (PD). Traditionally, the pancreatic remnant is anastomosed to the jejunum. Pancreaticogastrostomy (PG) was introduced as an alternative by Waugh and Clagett in 1946 and by Park, Mackie, and Rhoads in 1967. The purpose of this retrospective review was to assess the safety of PG at a single institution. Between 1986 and 1998 a total of 102 patients underwent PG following PD. The indications for PD were periampullary carcinoma (n = 89), pancreatitis (n = 7), and miscellaneous (n = 6). Altogether, 80 patients underwent the traditional Whipple procedure and 22 the pylorus-preserving Whipple (PPW) procedure. The PG was performed by a single-layer invagination technique to the posterior gastric wall using interrupted silk sutures. Leaks from the pancreatic anastomosis were detected by measuring amylase in fluid obtained from surgically placed drains. Operative mortality was 3.9% (4/102). The cause of death was uncontrolled upper gastrointestinal hemorrhage, sepsis, pulmonary embolus, and cardiac failure secondary to myocardial infarction. The mean operating time was 6.8 hours. Blood transfusion was given in 43 patients (42%), and the mean amount of the transfusion was 2.6 units. Nonfatal complications occurred in 35 patients (34%), and included leaks from the pancreatic anastomosis in 9 (8.8%), leaks from the biliary-enteric anastomosis in 4 (3.9%), and gastric paresis 7 (6.9%). Other complications included abscess, wound infection, colitis, delirium tremens, and hyperbilirubinemia. Discharge occurred 6 to 47 days (median 12 days) postoperatively and was prolonged in patients suffering from a complication. PD is associated with significant morbidity. PG is a safe alternative to pancreaticojejunostomy for managing the pancreatic remnant.
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PMID:Pancreaticogastrostomy following pancreaticoduodenectomy: review of 102 consecutive cases. 1136 81

The proto-oncogene HER2 presents a novel therapeutic target. We report results in 25 patients with HER2+ advanced prostate cancer treated with the bispecific antibody MDX-H210 15 microg m(-2)by intravenous infusion plus GM-CSF 5 microg kg(-1)day(-1)by subcutaneous injection for 4 days repeated weekly for 6 weeks. Patients with stable disease or better received further cycles of treatment until disease progression or study withdrawal. 1 patient received no treatment and 4 received less than 1 cycle and are included in the toxicity analysis only. Median duration of follow up was 105+ (range 21-188) days. Toxicity was generally NCI-CTG 0-2. There were 2 grade 4 adverse events (heart failure and dyspnoea) and 1 grade 3 event (allergic reaction) resulting in discontinuation of the study medication. There were 9 further grade 3 events not resulting in trial withdrawal. There were no treatment-related deaths. 7/20 (35%) evaluable patients had a >50% PSA response of median duration 128 (range 71-184+) days. 7/12 (58%) patients with evaluable pain had improvements in pain scores. The PSA relative velocity on therapy decreased in 15/18 (83%) assessable patients compared to pre-study. GM-CSF and MDX-H210 is active in hormone refractory prostate carcinoma with acceptable toxicity; further studies are warranted.
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PMID:A phase II study of the bispecific antibody MDX-H210 (anti-HER2 x CD64) with GM-CSF in HER2+ advanced prostate cancer. 1146 Oct 69

Guanylin and uroguanylin are short peptides homologous to heat-stable enterotoxins of Escherichia coli and other enteric bacteria. Guanylin and uroguanylin are synthetized from the respective prepropeptides mainly in gastrointestinal mucosa and are secreted both into intestinal lumen and into the blood. Luminally secreted peptides stimulate chloride and bicarbonate secretion in the intestine through the mechanism involving guanylate cyclase C receptor, cyclic GMP, protein kinase G and cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Bacterial enterotoxins, which have greater potency than endogenous peptides, induce excessive fluid secretion into intestinal lumen leading to secretory diarhea. Uroguanylin is expressed mainly in enterochromaffin cells of duodenum and proximal small intestine whereas guanylin is abundant in goblet cells of colonic epithelium. Uroguanylin and guanylin increase urinary sodium and potassium excretion both as circulating hormones and as paracrine mediators produced within the kidney. Uroguanylin functions as "intestinal natriuretic hormone" which is secreted in response to oral sodium loading and maintains sodium balance during postprandial period. Plasma and urinary concentrations of guanylin and uroguanylin increase in renal failure and heart failure. Guanylin peptides possess antiproliferative activity in intestinal cells culture and their expression decreases in colonic carcinoma indicating that their deficiency may contribute to the pathogenesis of this disease.
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PMID:Guanylin and related peptides. 1159 56

A 47-year-old male Caucasian patient, with no previous relevant medical history, presented in September 1996 with persistent right lower quadrant abdominal pain. A tumor in the cecum was identified and the patient was submitted to ileocecal resection with ileocolic anastomosis. Histological examination showed a moderately differentiated adenocarcinoma. One year later he developed bloody diarrhea, urgency, and loss of weight. Based on clinical presentation and histology of large bowel biopsies, a diagnosis of ulcerative colitis (UC) was established. The previously resected surgical specimen was reevaluated, and lesions resembling UC were identified in the nonneoplastic mucosa. High levels of alkaline phosphatase and gamma-glutamyl transferase were detected. These alterations could be traced back to 1991. Endoscopic retrograde cholangiopancreatography was performed, showing diagnostic features of primary sclerosing cholangitis (PSC), and the patient was put on ursodeoxycholic acid therapy. In March 1999, he started to have progressive dyspnea and signs of cardiac failure. Endomyocardial biopsy was performed showing extensive lesions of endomyocardial fibrosis. This case illustrates a rather silent course of UC in the presence of PSC, and supports the postulated increased risk in the development of proximally located colorectal carcinoma in these patients. Additionally, the development of endomyocardial fibrosis constituted an unexpected finding, not previously reported in this setting.
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PMID:Adenocarcinoma of the cecum as the first manifestation of ulcerative colitis complicated by primary sclerosing cholangitis and endomyocardial fibrosis. 1213 13

We report a combination of unusual myxoid change and extensive lipomatous metaplasia of an adrenocortical carcinoma. The patient was a 38-year-old man with hypertension and heart failure. Radiographic examination revealed the presence of a left adrenal tumor, and adrenalectomy was performed. The tumor weighed 380 g and appeared encapsulated. The cut surface was predominantly gelatinous. Histologically, the tumor was composed of atypical round cells with eosinophilic to vacuolated cytoplasm. The tumor was diagnosed as adrenocortical carcinoma. The stroma accumulated copious mucinous material. In addition, individual to nodular mature adipocytes were admixed throughout the tumor. The transition from carcinoma cells to mature adipocytes was recognized. Myxoid change is a very rare phenomenon in adrenocortical carcinoma, and only 10 similar cases have been reported to date. Lipomatous metaplasia is another peculiar feature of adrenocortical lesions that has been reported only in benign conditions. To our knowledge, this is the first reported case of adrenocortical carcinoma with lipomatous metaplasia.
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PMID:A case of myxoid adrenocortical carcinoma with extensive lipomatous metaplasia. 1256 42

An autopsy case with a widespread mucosal carcinoma of the biliary tree was reported. A biochemical profile of the bile duct damage was noticed in a woman in her seventies during a gastric examination. Imaging procedures depicted irregular dilatations of intrahepatic bile ducts with a bead-like appearance. Elevated levels of serum alkaline phosphatase and gamma-glutamyltransferase with a negative antimitochondrial antibody persisted. The patient was diagnosed as primary sclerosing cholangitis, she was followed up for 4 years under preservative therapies, and died of anasarca and heart failure. Post-mortem examination showed a diffuse mucosal carcinoma of both intrahepatic and extrahepatic biliary passages including the gallbladder with a minimal invasion and scattered foci of adenoma-like area in part. There was no evidence of gallstones or pre-existing sclerosing cholangitis. The striking features of the tumor were extensive papillary growth, mucus secretion and irregular dilatation of bile ducts. The tumor may bear biological and morphological homology with intraductal papillary mucinous tumor of the pancreas.
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PMID:Diffuse mucosal carcinoma of intrahepatic and extrahepatic bile ducts including gallbladder. 1258 48

Oxazepam is one of a number of benzodiazepines used therapeutically as a sedative-hypnotic and antianxiety agent. Toxicology and carcinogenesis studies were performed by administering oxazepam (greater than 99% pure) in feed to male and female Swiss-Webster and B6C3F1 mice for 14 weeks, 57 weeks (Swiss-Webster), or 2 years (B6C3F1). Neurobehavioral assessments were performed during the studies. Genetic toxicology studies were conducted in Salmonella typhimurium and cultured Chinese hamster ovary cells, and peripheral blood samples were analyzed for frequency of micronucleated normochromatic erythrocytes. Supplemental studies were performed to compare the metabolism and toxicokinetics of oxazepam in the two mouse strains, to evaluate the effect on liver cell replication rates, to perform clinical pathology assessments, and to examine the mutation spectrum and frequency of activated H-ras oncogenes in liver neoplasms from the 2-year study with B6C3F1 mice. 14-WEEK STUDY IN SWISS-WEBSTER MICE: Groups of 10 male and 10 female Swiss-Webster mice received oxazepam in feed at concentrations of 0, 625, 1,250, 5,000, 10,000 ppm for 14 weeks. One 625 ppm male and one 10,000 female were killed moribund before the end of the study, and the condition of the female mouse was attributed to oxazepam exposure. Mean body weight gains of exposed groups were similar to those of the controls. Exposed mice displayed chemical-related sedation and lethargy during the first study week, but appeared normal thereafter. In the neurobehavioral studies, reductions in grip strength were evident in both male and female mice at week 2 and persisted in males through week 11. An antianxiety effect was detected in exposed mice in measures of motor activity, startle response, and reactions to thermal stimulus. At necropsy, absolute and relative liver weights were increased in an exposure-related manner and were approximately two-fold greater in 10,000 ppm mice than in controls. Centrilobular hepatocellular hypertrophy was present only in exposed mice, and the severity increased with dose. 14-WEEK STUDY IN B6C3F1 MICE: Groups of 10 male and 10 female B6C3F1 mice received oxazepam in feed at concentrations of 0, Groups of 10 male and 10 female Swiss-Webster mice 625, 1,250, 2,500, 5,000, or 10,000 ppm for 14 weeks. received oxazepam in feed at concentrations of 0, There were no deaths that were clearly related to 625,1,250, 2,500, 5,000, or 10,000 ppm for 14 weeks. oxazepam exposure. Mean body weight gains of One 625 ppm male and one 10,000 ppm female were exposed groups were similar to those of the controls. Exposed mice displayed chemical-related sedation and lethargy during only the first study week. In neurobehavioral studies, reductions in grip strength were evident in males at week 2 but were no longer observed at week 12. An antianxiety effect was noted in exposed mice in measures of motor activity, startle response, and reactions to a thermal stimulus (females). At necropsy, absolute and relative liver weights were increased in an exposure-related manner and were approximately two-fold greater in 10,000 ppm mice than in controls. Centrilobular hepatocellular hypertrophy was present only in exposed mice, and the severity increased with dose. CHRONIC STUDIES: Groups of 60 male and 60 female Swiss-Webster and B6C3F1 mice received oxazepam in feed at concentrations of 0, 2,500, or 5,000 ppm. Additional groups of 60 male and 60 female B6C3F1 mice received 125 ppm in feed to allow for study of a group with projected serum concentrations of oxazepam similar to those achieved in humans taking a therapeutic dose. Ten male and 10 female B6C3F1 mice per group were evaluated at 15 months. Average daily oxazepam consumption varied throughout the studies, and the overall daily average ranged from 10 to 29 mg/kg body weight for the 125 ppm groups, 234 to 512 mg/kg for the 2,500 ppm groups, and 444 to 1,085 mg/kg for the 5,000 ppm groups. Serum oxazepam concentrations determined at 57 weeks in Swiss-Webster mice and at the 15-month interim evaluation of B6C3F1 mice 1 mice were approximately 1 ug/mL in the 125 ppm groups, 4 to 7 μg/mL in the 2,500 ppm groups, and 7 to 10 μg/mL in the 5,000 ppm groups. Neurobehavioral assessments during the chronic studies of each strain of mice were confounded by the poor survival and deteriorating condition of mice with hepatic neoplasia. However, within the limitations of the studies, there were no notable changes in the types of behaviors observed compared to those observed in the 14-week studies, nor was there an enhancement in the degree to which they were exhibited. 57-Week Study in Swiss-Webster Mice: Survival, Body Weights, Feed and Compound Consumption, and Clinical Findings: At 57 weeks, survival of exposed mice was significantly lower than that of controls (males: O ppm, 45/60; 2,500 ppm, 19/60; 5,000 ppm, 10/60; females: 47/60, 28/59, 17/59), causing the study to be terminated. Mean body weights of exposed males were similar to controls until week 17; afterwards, mean body weights of exposed male groups were lower than those of controls. Final mean body weights of exposed males were 9% lower than that of the controls. The mean body weight of 2,500 ppm females was greater than that of the controls throughout the study. Females receiving 5,000 ppm had a mean body weight greater than that of the controls early in the study; after week 29, the mean body weight of this group was similar to that of the controls. Feed consumption by exposed males and females was slightly lower than that by the controls, and females in all groups, including controls, consumed slightly more feed than males throughout the study. Dietary levels of 2,500 and 5,000 ppm oxazepam resulted in average daily compound consumption levels of 270 and 570 mg/kg for males and 320 and 670 mg/kg for females. Hypoactivity and sedation were observed in exposed mice during the first week of the study. There were no other clinical findings associated with oxazepam exposure. Pathology Findings: Systemic amyloidosis was the principal cause of death in mice dying before the study was terminated. The lower survival of mice receiving oxazepam was attributed to an increase in the extent and severity of amyloid deposits in many organs, including the heart and kidney. Atrial thrombosis and pulmonary lesions consistent with chronic heart failure occurred at higher incidences and with greater severity in exposed mice. The incidence of hepatocellular adenomas (males: 1/60, 35/60, 50/60; females: 0/60, 22/59, 47/59) and carcinomas (males: 0/60, 5/60,19/60; females: 1/60, 1/59, 11/59) were increased in exposed mice. The incidences of eosinophilic foci were also increased in exposed mice (males: 0/60, 22/60, 22/60; females: 0/60, 20/59, 14/59), and there was evidence of increased centrilobular hepatocyte hypertrophy (males: 12/60, 46/60, 47/60; females: 3/60, 51/59, 53/59). 2-Year Study in B6C3F1 Mice: Survival, Body Weights, Feed and Compound Consumption, and Clinical Findings: Survival of mice receiving 2,500 and 5,000 ppm was significantly lower than that of controls (males: O ppm, 45/50; 125 ppm, 44/50; 2,500 ppm, 15/50; 5,000 ppm, 0/50; females: 39/50, 41/50, 2/50, 0/50). Mean body weight gains of exposed male and female mice were similar to controls until about week 15 when weight gains for mice exposed to 2,500 or 5,000 ppm slowed in relation to controls, resulting in weight gains approximately 30% to 40% lower than those of the controls throughout the remainder of the study. Mean body weight gain of male mice exposed to 125 ppm was similar to that of the controls, while that of female mice receiving 125 ppm was 10% to 15% lower than that of the controls after about week 45. Feed consumption by exposed males and females was similar to that by controls. Dietary levels of 125, 2,500, and 5,000 ppm resulted in average daily oxazepam consumption levels of 12, 310, and 690 mg/kg body weight for males and 15, 350, and 780 mg/kg for females. In the 5,000 ppm groups, lethargy and sedation were observed in a few mice during the first week of study. Pathology Findings: The early deaths of many of the B6C3F1 mice exposed to oxazepam were attributed to a marked increase in the incidences of hepatoblastoma (males: 0/49, 2/50, 21/50, 13/50; females: 0/50, 1/50, 8/50, 8/50), hepatocellular adenoma (males: 17/49,18/50, 34/50, 32/50; females: 25/50, 35/50, 35/50, 36/50), and hepatocellular carcinoma (males: 9/49, 5/50, 45/50, 50/50; females: 9/50, 5/50, 49/50, 44/50). Moderate hypertrophy of centrilobular hepatocytes occurred in mice receiving 2,500 and 5,000 ppm (males: 0/49, 2/50, 26/50, 43/50; females: 0/50, 2/50,11/50, 29/50). An increase in the incidence of follicular cell hyperplasia of the thyroid gland occurred in all exposed groups of mice (males: 4/49, 22/50, 49/50, 47/50; females: 16/50, 34/50, 49/50, 44/50), and thyroid gland follicular cell adenoma was increased in exposed females (0/50, 4/50, 5/50, 6/50). Testicular atrophy occurred in the 2,500 and 5,000 ppm groups (1/50, 0/50, 25/50, 38/50), and the incidence of epididymal Iymphocyte infiltration was increased in all exposed groups (2/50,14/50, 33/50, 21/50). The frequency of hepatocellular neoplasms with an activated H-ras oncogene in the B6C3F1 mice and the mutation spectrum of the H-ras gene were determined. The mutation spectrum of the H-ras genes in the relatively few neoplasms from exposed mice that did have an activated H-ras did not differ from the spectrum of mutations observed in neoplasms from controls, but the proportion of neoplasms with an activated H-ras gene decreased with increasing oxazepam dose. While 11 of 19 (58%) neoplasms from control mice had an activated H-ras gene, only 1 of 40 neoplasms from mice receiving 2,500 or 5,000 ppm oxazepam exhibited a similar molecular lesion. Thirteen of 37 (35%) neoplasms from mice in the 125 ppm group had an activated H-ras oncogene, suggesting that, although the incidence of all liver neoplasms was not statistically increased compared to controls, there was an increase in a similar subset of neoplasms (lacking an activated H-ras) that occurred with increased incidence at higher doses. SUPPLEMENTAL STUDIES: Because exposure to oxazepam caused increased incidences of liver neoplasms, supplemental short-term studies were performed. Oxazepam given in feed to male B6C3F1 mice at 25, 125, 2,500, or 5,000 ppm for up to 13 weeks was found to cause a dose-related increase in nuclear labeling index in studies measuring the incorporation of bromodeoxyuridine into replicating liver cells. This increase was statistically significant at all but the 25 ppm exposure level and was limited to mice evaluated at 15 days. Cell replication rates in most groups evaluated at 30 days and after were similar to control rates. There was minimal evidence suggestive of hepatocyte necrosis either by light microscopy or in clinical chemistry measures. There was, however, evidence of cholestasis, likely due to physical obstruction of bile canaliculi by swollen hepatocytes. The metabolic fate and toxicokinetics of oxazepam were evaluated in each strain of mice and were compared to published data from human studies. Both mice and humans form glucuronides of oxazepam and form 3- and 4-hydroxy and methoxy derivatives of the phenyl group. Oxidative metabolism of the phenyl group appears to be more prevalent in mice than is reported for humans. Elimination half-lives of parent compound do not differ between Swiss-Webster and B6C3F1 mice and are similar to values reported for humans. GENETIC TOXICOLOGY: Oxazepam was not mutagenic in any of several strains of Salmonella typhimurium, nor did it induce sister chromatid exchanges or chromosomal aberrations in cultured Chinese hamster ovary cells. These in vitro tests were performed with and without S9 metabolic activation. Results from an in vivo mouse peripheral blood micronucleus test performed on the B6C3F1 mice used in the 14-week study were also negative. CONCLUSIONS: Under the conditions of these feed studies, there was clear evidence of carcinogenic activity of oxazepam in male and female Swiss-Webster mice based on increased incidences of hepatocellular adenoma and carcinoma. There was clear evidence of carcinogenic activity of oxazepam in male and female B6C3F1 mice based on increased incidences of hepatoblastoma and hepatocellular adenoma and carcinoma. Increased incidences of hyperplasia of thyroid gland follicular cells in male and female B6C3F1 mice and of follicular cell adenomas in female B6C3F1 mice were also related to oxazepam exposure. Administration of oxazepam to Swiss-Webster mice resulted in centrilobular hepatocellular hypertrophy and increased incidences and severity of systemic amyloidosis. Administration of oxazepam to B6C3F1 mice also resulted in centrilobular hepatocellular hypertrophy. Synonyms: 7-Chloro-1,3-dihydro-3-hydroxy-5-phenyl-2 H - 1,4-benzodiazepin-2-one Trade Names: Tazepam, Wy-3498, Serax
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PMID:NTP Toxicology and Carcinogenesis Studies of Oxazepam (CAS No. 604-75-1) in Swiss-Webster and B6C3F1 Mice (Feed Studies). 1259 20

The paper presents the results of 114 radical cystectomies made in 1996-2002. The age of 114 patients (103 males, 11 females) ranged from 37 to 78 years (mean age 57.5 years). Transient cell carcinoma was diagnosed in 81.5% patients. Supravesical urine derivation was conducted by means of ureterocutaneostomy and transureteroureteronephrostomy in 9 (7.9%) patients, ureterosygmoanastomosis--in 43 (37.7%) patients, artificial orthotopic urinary bladder was created in 7 (6.1%) patients of a gastric segment and in 55 (48.2%) patients of the ileum. Postoperative complications were observed in 28 (24.6%) patients, intestinal obstruction being a prevailing complication. Five patients died: 2 of pulmonary artery thromboembolism, 1 of acute cardiac failure, 1 of sepsis and 1 of gastric bleeding. Continent methods of urine derivation were preferred, such as ureterosygmoanastomosis by Mainz-Pouch II and creation of orthotopic urinary bladder of the stomach or of the ileum.
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PMID:[Short-term results of radical cystectomy]. 1294 19


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