Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We assess toxicity related to 6-mercaptopurine in the treatment of inflammatory bowel disease by reporting our experience with 396 patients (120 patients with ulcerative colitis, 276 with Crohn disease) observed over 18 years. Follow-up data for a mean period of 60.3 months were obtained for 90% of the patients. Toxicity directly induced by 6-mercaptopurine included pancreatitis in 13 patients (3.3%), bone marrow depression in 8 (2%), allergic reactions in 8 (2%), and drug hepatitis in 1 (0.3%). These complications were reversible in all cases with no mortality. Most cases of marrow depression occurred earlier in our experience, when the initial drug doses used were higher. Infectious complications were seen in 29 patients (7.4%), of which 7 (1.8%) were severe, including one instance of herpes zoster encephalitis. All infections were reversible with no deaths. Twelve neoplasms (3.1%) were observed, but only 1 (0.3%), a diffuse histiocytic lymphoma of the brain, had a probable association with the use of 6-mercaptopurine. Our data, showing a low incidence of toxicity in 396 patients, coupled with the previously demonstrated efficacy of 6-mercaptopurine in the treatment of inflammatory bowel disease, indicate that the drug is a reasonable alternative in the management of patients with intractable inflammatory bowel disease.
 ...
PMID:6-Mercaptopurine in the management of inflammatory bowel disease: short- and long-term toxicity. 280 19

A 40-year-old woman admitted after a massive overdose of sodium valproate was found to have a serum valproate level of 18,900 mumol/1 which is the highest ever reported. She underwent cardio-respiratory failure, bone marrow suppression and neurological depression, subsequently dying. On post-mortem there was haemorrhagic pancreatitis but no histological evidence of hepatotoxicity. Valproate levels measured in various post-portem tissues and fluids indicated a high level in bile (21,375 mumol/1) suggesting that enteral administration of activated charcoal might be of some benefit by decreasing enterohepatic circulation of the drug.
 ...
PMID:Fatality due to massive overdose of sodium valproate. 311 76

Pancreatic abscess was diagnosed by exploratory celiotomy in 6 dogs. The most common clinical signs included acute onset of lethargy (n = 5), anorexia (n = 6), vomiting (n = 5), and diarrhea (n = 2). Physical examination revealed pain response to abdominal palpation (n = 5), depression (n = 5), icterus (n = 3), fever (n = 3), and cranial abdominal mass (n = 2). Consistent preoperative clinicopathologic abnormalities included leukocytosis with left shift, observance of toxic neutrophils on the blood smear, hyperlipasemia, hyperamylasemia, hyperbilirubinemia, and increased serum alkaline phosphatase activity. In 5 of 6 dogs, abdominal radiography revealed increased soft tissue density in the cranial portion of the abdomen. Ultrasonography performed on 4 dogs confirmed pancreatic mass. In all dogs, exploratory celiotomy revealed a cavitary pancreatic mass that contained sterile, mucopurulent material. Histopathologic diagnoses included acute necrotizing or chronic-active pancreatitis and steatitis. Two dogs were euthanatized at the time of diagnosis, and the remaining 4 were treated by use of pancreatic debridement(s), open abdominal drainage, and intensive administration of fluids and antibiotics. One dog was euthanatized 4 days after surgery, because of progressive pancreatic abscessation. Three dogs recovered and were discharged.
 ...
PMID:Pancreatic abscess in dogs: six cases (1978-1986). 319 66

The therapeutic efficacy of cyclosporine (CsA) as an immunosuppressive agent was complemented by a modest, long-term incidence of toxic complications in 402 renal allograft recipients engrafted one to five years prior to analysis. The overall patient and graft survivals at one year were 97% and 84% (actual), and at five years 92% and 67% (actuarial). The immunosuppressive therapeutic index was excellent: only 12% of allografts were lost from rejection, with 5% of patients succumbing to infection. While infections were common, tending to emanate in the urinary tract or to be viral in etiology, they were generally mild and readily controlled. Only four patients displayed malignancies; none succumbed to this cause. The most common toxic complication was hypertrichosis, which was accentuated in pediatric patients. While tremors occurred in 20% of patients, primarily during the first three months, other neuroectodermal complications of parethesias, depression, somnolence, and seizures were rare. Hepatotoxicity, which was noted in 50% of patients, particularly recipients of cadaveric grafts, generally was first seen as a transaminase elevation, at least partially reversible by dose-reduction and abating by the third year. Associated disturbances of cholelithiasis and pancreatitis were occasionally observed. Nephrotoxicity was the only persistent, long-term complication. Hypertension occurred in 72% of patients during the first month, 36% in the second year, and about 15% thereafter. Hyperuricemia, which occurred in about 30% of recipients during the first two years, was occasionally associated with symptomatic gout. The mean serum creatinine level remained elevated throughout the follow-up period at 1.8-1.9 mg/dl, suggesting persistent, but nonprogressive, drug-induced renal injury. The present analysis documents the relative safety of CsA for long-term therapy, and highlights the need for new approaches to ameliorate drug-induced nephrotoxicity.
 ...
PMID:Complications of cyclosporine-prednisone immunosuppression in 402 renal allograft recipients exclusively followed at a single center for from one to five years. 354 76

It has been substantiated that the use of a new synthetic drug tageflar analogous to L-enkephalin was accompanied by the depression in pancreatic enzyme activity in the blood of rats, acceleration of necrotic and lytic processes in irreversibly damaged exocrine pancreocytes in the course of experimental pancreatitis. The drug promoted microcirculation retention in the injury zone and acceleration of the arrangement and elimination of necrotic glandular tissue. The influence of tagaflar diminished the extent of perifocal necrobiotic zone and suppressed sclerotic processes and pancreatic lipomatosis.
 ...
PMID:[Effect of tageflar, a synthetic analog of L-enkephalin, on the morphogenesis of experimental pancreatitis]. 367 99

Clinical and experimental evidence suggests that myocardial depression occurs during severe pancreatitis, but this evidence is derived from techniques that are not optimal for assessing myocardial contractility (e.g., rate of rise in ventricular pressure [dP/dt]). The slope of the left ventricular (LV) and systolic pressure dimension relationship (Ees), a better indicator of myocardial function, has not been measured in pancreatitis. Ten mongrel dogs underwent surgical instrumentation to monitor systemic arterial and LV pressure, cardiac output, LV dP/dt, and anterior LV wall thickness. End of systole was defined by the peak negative dP/dt. The end-systolic points used to calculate Ees were obtained by aortic and vena caval occlusion. After surgical recovery, pancreatitis was induced via cannulation of the pancreatic duct and injection of autologous bile (1 ml/kg) at 200 mm Hg perfusion pressure. All measurements were taken during a control period and daily after pancreatitis was induced. Pancreatitis was confirmed by a significant increase in serum amylase throughout the study and by autopsy finding of hemorrhagic necrosis. Ees was increased throughout the experimental protocol (1 to 7 days) (p less than 0.05). Myocardial performance as assessed by Ees was significantly increased and myocardial depression did not occur in untreated, conscious dogs with severe pancreatitis. Peak positive LV dP/dt was a poor index of contractility during pancreatitis since it decreased while myocardial contractility was increased. Cardiac depression in pancreatitis noted in other reports was likely due to decreased preload and not to intrinsic cardiac dysfunction.
 ...
PMID:Myocardial depression during acute pancreatitis: fact or fiction? 376 95

Alterations in the pulmonary surfactant system are partly responsible for the respiratory insufficiency seen with acute pancreatitis. In this model of cerulein-induced pancreatitis in rats, we utilized a new stable isotope metabolic tracer technique to examine one aspect of the pulmonary surfactant system and its relationship to associated lung injury. We have demonstrated primary, early depression of lung phospholipid synthesis reflected in both lung tissue and alveolar washings. We suggest that this quantitative change in pulmonary surfactant synthetic rate may partly explain the occurrence of respiratory failure with acute pancreatitis.
 ...
PMID:Lung injury in acute pancreatitis: primary inhibition of pulmonary phospholipid synthesis. 379 93

Some patients with hypertriglyceridemia and acute pancreatitis have marked hypocalcemia and high levels of plasma free fatty acids (FFAs). This study tests the hypothesis that increased plasma FFAs can significantly reduce the calcium level in vivo, a phenomenon which is different from local formation of calcium soaps due to lipolysis of adipose tissue lipids. Free fatty acid elevation was induced in rats by the administration of heparin and by the infusion of triglycerides. The results show that, compared with controls, induction of elevated FFA (from 1.57 +/- 0.08 mEq/L to 5.64 +/- 0.35, mean +/- SEM) causes the concentration of calcium to fall rapidly (from 9.04 +/- 0.06 mg/dl to 8.42 +/- 0.10, p less than 0.001). There is a significant (p less than 0.001) positive correlation between spontaneous baseline concentration of FFA and the responsiveness of calcium concentration to FFA challenge. At near-normal levels of FFA there is a significant (p less than 0.001) correlation between the magnitude of increased FFA concentration and decreased calcium concentration. Additional studies in vivo and in vitro show that elevated plasma triglycerides per se did not interfere with measurement of calcium concentration; however, FFA-albumin complexes bind calcium and lower its measured value. These findings suggest that (a) changes in the concentration of FFA occurring spontaneously may affect measured serum calcium concentration; (b) the observed depression of serum calcium concentration may be due in part to intravascular sequestration of calcium by FFA, but increased flux of circulating calcium-FFA complexes into extravascular and intracellular sites may also be important; (c) the markedly increased FFA concentration in some patients with acute pancreatitis may contribute significantly to hypocalcemia and calcium flux in these patients. As parathyroid hormone secretion, function, or integrity may be impaired in pancreatitis, the depressant effect of FFA could be even greater in that disease than in this model.
 ...
PMID:Depression of serum calcium by increased plasma free fatty acids in the rat: a mechanism for hypocalcemia in acute pancreatitis. 402 61

Two hundred and eighty-nine patients operated on for primary hyperparathyroidism (PHPT) in the years 1956-79 have been followed up for a mean period of 5 years. The aim of the study was to investigate the symptomatology of PHPT and the disappearance of the symptoms after operative treatment. Of the presenting symptoms hypercalcaemic crisis and cystic bone changes were cured, and none of the patients with pancreatitis as presenting symptom had a recurrence. In the renal stone group, 10% of the patients had recurring stones during the follow-up period. The presenting symptom disappeared in 84% of the patients. Thirty-five% of the patients had no presenting symptom and were classified as "asymptomatic", though, on questioning, most of them had various symptoms which disappeared postoperatively. Malaise, fatigue and muscular weakness disappeared in 79% of the patients, upper abdominal pains in 66%, constipation in 63%, pains in the extremities in 51% depression in 65%. Hypertension increased by 28% during the follow-up period; only three of the 90 patients with hypertension has discontinued antihypertensive treatment postoperatively. During the follow-up study, 6% of the patients were hypercalcaemic, though the serum calcium was only slightly elevated in almost all of these patients (mean +/- SD 2.75 +/- 0.09 mmol/l) and most of them had the multiglandular form of PHPT. The renal function did not deteriorate as much as was expected on the basis of earlier reports; only two patients had a serum creatinine over 500 mumol/l.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Long-term effect of surgical treatment on the symptoms of primary hyperparathyroidism. 407 2

Recent controlled clinical trials have documented the development of acute pancreatitis in 5% of patients receiving azathioprine for Crohn's disease, by far the highest incidence of drug-induced pancreatitis recorded to date. In an effort to evaluate the effects of azathioprine on the pancreas, the isolated ex vivo perfused canine pancreas model was used. No significant changes in gross appearance, weight, or serum amylase occurred in azathioprine-treated glands compared to controls. Azathioprine administration, however, resulted in a significant increase in secretory volume (two fold) and bicarbonate output (two fold), and a profound depression of trypsin output compared to controls. These preliminary studies demonstrate that azathioprine has marked effect on pancreatic function in this model.
 ...
PMID:Azathioprine and acute pancreatitis: studies with an isolated perfused canine pancreas. 618 63


<< Previous 1 2 3 4 5 6 7 8 9 Next >>