Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infliximab, a chimeric monoclonal antibody to tumour necrosis factor-alpha, contains murine protein elements and targets the immune system, raising concerns about the potential for immune sensitization and immunosuppressive sequelae. However, long-standing inflammatory disease with high activity and chronic immunosuppressant therapy can also predispose patients to immunosuppressive sequelae. Patients with Crohn's disease, rheumatoid arthritis and other indications received single or multiple doses of infliximab and their condition was followed for up to 3 years. Adverse events, most frequently headache, nausea, and upper respiratory tract infection, were generally mild and occurred in 76% of infliximab-treated patients vs. 57% of placebo-treated recipients. Human antichimeric antibodies developed in 13% of patients, increasing the potential for subsequent infusion reactions. Antibodies to double-stranded DNA developed in a small percentage of patients. Other antinuclear antibodies characteristic of serum lupus erythematosus were not found; no patient developed a true lupus syndrome and no other autoimmune disorders were reported. Infliximab is not associated with typical immunosuppressive sequelae, such as infections and malignancy, or with autoimmune disorders. Infliximab therapy was well tolerated, serious adverse events were infrequent, successfully managed with medication and without sequelae, and overall mortality was within the expected incidence for this patient population.
 ...
PMID:Review article: safety of infliximab in clinical trials. 1059 35

Pheochromocytomas usually arise from the adrenal medulla but may also arise from the carotid body, the retroperitoneum, the urinary bladder, and other locations. We report three cases of pheochromocytoma of the urinary bladder with clinicopathological, immunohistochemical, flow cytometric, and ultrastructural findings. Case 1, a 13-year-old boy presented with hematuria. He underwent partial cystectomy, 31 years later he presented with a tumor in the thoracic vertebra. Case 2, a 35-year-old woman presented with headache, nausea, vomiting, palpitations, and diaphoresis on evacuation. She underwent total cystectomy and regional lymph adenectomy. She survived for 10 years without recurrence or metastasis; however, she died from another disease. Case 3, a 31-year-old man presented with dysuria. He underwent total cystectomy and regional lymph adenectomy. The tumor metastasized to the lymph nodes, and the patient died after 4 years. The urinary bladder tumors in these three cases protruded into the lumen and invaded deeper than the middle of the muscle layer. The tumor of the urinary bladder, metastatic lymph nodes, and thoracic vertebra showed alveolar and trabecular patterns, and tumor cells were surrounded by capillaries. The tumor cells were moderate in size with ovoid nuclei and abundant eosinophilic cytoplasm that contained acidophilic granules reactive to Grimelius stain. Vascular invasion was observed in cases 1 and 2. Immunohistochemically, tumor cells showed reactivity for chromogranin, Leu 7, and S-100 protein. In each of the three cases, the DNA ploidy pattern on flow cytometry was aneuploid. Ultrastructural examination revealed several neurosecretory granules, rough endoplasmic reticulum, and a few mitochondria within the cytoplasm. It is difficult to determine whether pheochromocytoma of the urinary bladder is malignant on the basis of histological, immunohistochemical, and flow cytometric findings. Long-term follow up is necessary.
 ...
PMID:Clinicopathological study of pheochromocytoma of the urinary bladder: immunohistochemical, flow cytometric and ultrastructural findings with review of the literature. 1063 31

Twenty-four patients with chronic hepatitis B virus (HBV), antibody to hepatitis B e antigen (anti-HBe), HBV DNA positivity, and alanine transaminase (ALT) elevation who failed previous interferon alfa (IFN-alpha) therapy were included in a pilot study of combination therapy with ribavirin and IFN-alpha. The patients received daily oral ribavirin (1,000-1,200 mg according to body weight) plus 5 million units (MU) IFN-alpha2b three times a week for 12 months and were followed-up for 12 months. The median viremia level decreased significantly at the end of treatment (1.2 x 10(3) copies/mL) and follow-up (4.0 x 10(2) copies/mL) compared with the baseline (3.0 x 10(6) copies/mL; P <.05). After 12 months, 8 of 24 (33%) patients had cleared HBV DNA and 12 (50%) had normal ALT levels. At the end of the study virological and biochemical response was 50% and 21%, respectively. Thus, virological and biochemical response sustained in 5 of 24 (21%) patients retreated with ribavirin and IFN-alpha; none of them lost hepatitis B surface antigen (HBsAg). Liver histology improved in 2 of 4 sustained responders but in none of the 12 nonresponders with paired biopsies (P =.05). The response was independent of dose and duration of previous treatment, viral load, or the distribution of HBV precore wild-type/mutant variants. However, sustained responders had significantly higher necroinflammation (P =.036) and fibrosis (P =.007) scores. IFN-alpha-related side effects were mild and reversible on discontinuation. In 4 (17%) patients who suffered nausea and diarrhea the ribavirin dosage was reduced by 50% after 1 month of therapy and finally discontinued in all of them. No patient had liver disease decompensation. In summary, combination therapy with ribavirin and IFN-alpha may be efficacious to treat viremic anti-HBe-positive patients with chronic hepatitis B who have failed previous IFN therapy.
 ...
PMID:Pilot study of combination therapy with ribavirin and interferon alfa for the retreatment of chronic hepatitis B e antibody-positive patients. 1065 77

Topotecan is a topoisomerase I inhibitor with significant activity in patients with myelodysplastic syndrome and chronic myelomonocytic leukemia. Pre-clinical data suggest a synergistic activity with DNA damaging agents such as cyclophosphamide, where topotecan might prevent the repair of cyclophosphamide-induced DNA damage. We thus designed a combination including cyclophosphamide 500 mg/m2 every 12 hours given on days 1 to 3; topotecan 1.25 mg/m2/day by continuous infusion on days 2 to 6, and cytosine arabinoside (ara-C) 2 g/m2 over 4 hours daily for 5 days on days 2 to 6 (CAT). Sixty six (63 evaluable) patients were treated. Fifty two patients had refractory (n=12) or relapsed (n=40) acute myelogenous leukemia (AML), and eleven had acute lymphocytic leukemia (ALL) (refractory n=3, relapsed n=8); their median age was 57 years (range, 18 to 79 years). Eleven patients (17%) achieved a complete remission (CR), and two patients (3%) had a hematologic improvement (HI; met all criteria for CR except for platelets < 100x10(9)/L), for an overall response rate of 20%. Responses occurred in 12 of 52 AML patients (23%), including 10 CR (19%) and 2 HI (4%), and in 1 of 11 patients with ALL (9%). Myelosuppression was universal; there were 23 episodes of pneumonia or sepsis and 18 episodes of fever of unknown origin complicating 74 courses of CAT. Non-hematologic toxicity was mostly gastrointestinal, including nausea, vomiting, diarrhea and mucositis, but was severe in only 8%. In summary, the CAT regimen is well tolerated and has significant anti-leukemia activity which warrants further investigation.
 ...
PMID:Cyclophosphamide, ara-C and topotecan (CAT) for patients with refractory or relapsed acute leukemia. 1078 92

We analysed data from a multicentre interferon (IFN) treatment trial to evaluate symptoms in patients with chronic hepatitis C and to identify factors that might predict development of debilitating IFN side-effects. Two hundred and twenty-two patients (120 US, 102 French) received 3 or 5 million units (MU) of IFN-alpha three times weekly (t.i.w.) for 3 months. Those who had detectable hepatitis C virus (HCV) RNA, as detected by the branched DNA signal amplification (bDNA) assay, at 3 months were intensified to daily therapy, while patients who were bDNA negative continued t.i.w. dosing for the subsequent 3 months of treatment. Symptoms were assessed at baseline, and adverse effects were evaluated at 6 months of therapy. Prior to treatment, the most common symptom that interfered with daily functioning was fatigue, occurring in 25% of patients. The frequency of debilitating fatigue, myalgia, arthralgia, headache, the presence of dry eyes and dry mouth, and use of antidepressant medication increased significantly from baseline to 6 months of IFN therapy (all P < 0.01). In multivariate analysis, the development of a debilitating side-effect at 6 months of treatment was associated with the presence of that symptom prior to therapy in all cases. Symptoms and adverse effects varied by gender and country. Compared with patients maintained on t.i.w. dosing, those who were dose intensified to daily IFN reported more debilitating fatigue, malaise, myalgia, arthralgia, fever, nausea, and headache, and the presence of dry mouth (all P < 0.05). In conclusion, patient characteristics, including pretreatment symptoms, gender and nationality, as well as daily IFN dosing are associated with the development of debilitating adverse effects on IFN therapy.
 ...
PMID:Pretreatment symptoms and dosing regimen predict side-effects of interferon therapy for hepatitis C. 1084 63

Cyclic vomiting syndrome (CVS) remains a mysterious disorder despite our increasing knowledge since its classic description by Gee in 1882. Its hallmark feature of recurrent, explosive bouts of vomiting punctuating periods of normal health causes substantial medical morbidity (50% of patients require intravenous therapy), as well as significant time lost from school (20 school absences per year) and work. Limited epidemiologic data indicate that CVS may occur more commonly than previously thought, affecting as many as 1.9% of school-aged children. Besides the relentless vomiting, the child usually has pallor (87%), lethargy (91%), anorexia (74%), nausea (72%), and abdominal pain (80%). There is evidence of clinical and physiologic overlap among CVS, abdominal migraine, and migraine headaches. We propose revised criteria for abdominal migraine that include pain as the predominant and consistent symptom, lack of abnormal screening tests, and in retrospect, either subsequent development of migraines or positive response to antimigraine medication. Besides migraines, other etiologic possibilities include mitochondrial DNA mutations, ion channelopathies, excessive hypothalamic-pituitary-adrenal axis activation, and heightened autonomic reactivity. The differential diagnosis includes idiopathic CVS (88%); gastrointestinal disorders (7%), including serious surgical disorders (e.g., malrotation); and extraintestinal disorders (5%), including serious surgical (brain stem neoplasm) and metabolic disorders (e.g., fatty acid oxidation disorder). Within the idiopathic group, there may be migraine, Sato's neuroendocrine, mitochondrial, and other subgroups. Treatment includes avoidance of triggers, prophylactic medication, supportive care, abortive medication, and family support. In the future, investigation into mitochondrial DNA mutations, ion channel defects, corticotropin-releasing factor, and serotonin and tachykinin receptor physiology and pharmacology may help discover the etiology and pathogenesis of this disorder.
 ...
PMID:Cyclic vomiting syndrome: evolution in our understanding of a brain-gut disorder. 1095 42

A presumably waterborne outbreak of Campylobacter jejuni/coli infection in a subarctic community is described. Drinking water supplied to residents was delivered unchlorinated during a 4-week period. No Campylobacter sp. was recovered from the water supply. Three hundred thirty individuals (15% of the 2,200 exposed) became ill. Diarrhoea, abdominal pain, fever, nausea and joint pain occurred in 81%, 30%, 29%, 43% and 21%, respectively. Nine percent reported swelling of joints, and two cases of reactive arthritis occurred. A Campylobacter sp. was isolated from 9 of 33 individuals who became ill and from 1 of 33 healthy controls. All culture-positive individuals, 46% of culture-negative ill persons and 27% of healthy controls were seropositive. All strains recovered had an identical DNA profile.
 ...
PMID:Outbreak of Campylobacter infection in a subartic community. 1096 26

A 39-year-old man with myotonic dystrophy consulted our hospital for nausea, vomiting and dizziness that occurred after 75 g oral glucose tolerance test (OGTT). Reexamination of OGTT revealed remarkable hyperinsulinemia (622 microU/ml) followed by reactive hypoglycemia (50 mg/dl) and such hypoglycemic symptoms as nausea, vomiting, dizziness and palpitation. DNA analysis of the circulating lymphocytes revealed increased (1,500 times) number of cytosine-thymine-guanine (CTG) trinucleotide repeats in myotonic dystrophy protein kinase (DM kinase) gene. Gel chromatographic analysis of the plasma in combination with sensitive enzyme immunoassay of insulin revealed that the ratio of proinsulin to total immunoreactive insulin was elevated at fasting (12.9%), and was decreased to 8.9% at 60 min after glucose administration. These findings may indicate that biologically active authentic insulin was predominantly secreted after glucose administration in the present case. This is the first case report of myotonic dystrophy with hyperinsulinemia associated with reactive hypoglycemia induced by oral glucose administration.
 ...
PMID:A case of myotonic dystrophy (MD) associated with glucose-induced hyperinsulinemia followed by reactive hypoglycemia and increased number of cytosine-thymine-guanine (CTG) trinucleotide repeats in MD gene. 1103 71

A patient of MELAS is reported. A 28-year-old woman was admitted to Shimada Municipal Hospital because of nausea, vomiting, and right homonymous hemianopsia. She had past history of dizziness and convulsion. A brain magnetic resonance imaging showed an ischemic lesion in the left occipital lobe, which disappeared in the follow-up study. Laboratory examination indicated elevated lactate and pyruvate levels in both blood and cerebrospinal fluid. The muscle biopsy demonstrated ragged-red fibers and strongly SDH-reactive blood vessels. PCR-RFLP analysis of DNA extracted from her muscle and blood as well as her mother's blood revealed a T to C mutation at nucleophile position of 3271 in mitochondrial DNA. She was diagnosed as having MELAS and discharged. One year after the first admission, she re-visited our hospital because of three days' duration of fatigability and generalized muscle pain after alcohol intake. She had severe lactic acidosis, rhabdomyolysis and acute renal failure. Despite a continuous hemodialysis and other intensive efforts, the patient died 20 hours later. Alcohol intake has been reported to induce rhabdomyolysis in myopathy with mitochondrial DNA deletions. The course of this patient suggests that alcohol intake can be an aggravating factor also in MELAS.
 ...
PMID:[A patient of MELAS with 3271 mutation with fatal outcome after alcohol intake]. 1108 93

BACKGROUND: Titanocene dichloride (TD) is an organometallic compound with antiproliferative properties in vitro and promising antitumor activity in preclinical in vivo models. The drug interferes with DNA, blocks the S/G(2) phase of the cell cycle and shows antiangiogenic properties. The purpose of this study was to determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) of a 'split' dose administration schedule (days 1, 3, 5 q 3 weeks). PATIENTS AND METHOD: Patients with progressive advanced cancer and a creatinine clearance > 60 ml/min qualified for a treatment with TD after standard therapies (radio-, chemo-, hormone therapy) failed. A total of 10 patients (4 females, 6 males) with a median age of 58 (range 49-68) years were treated with 80 mg/m(2) TD at days 1, 3 and 5 (repeated at day 22). The drug was administered as light-protected infusion within 1 h. RESULTS: Significant side effects were as follows: nausea/vomiting, appetite loss, renal toxicity (elevation of serum creatinine and proteinuria) and liver toxicity (bilirubin and alkaline phosphatase elevation), but no myelosuppression. At the starting dose (3 x 80 = 240 mg/m(2) TD), renal (3 patients) or liver toxicity (1 patient) of grade 3 was judged as DLT. No further dose escalation was possible. No objective tumor remission was observed. CONCLUSION: The tolerability of TD cannot be improved by splitting the total dose in to three treatments every other day. Compared to previous phase I data using a 3-weekly and a 1-weekly schedule, the 'split' dose administration allowed no further increase of the total drug dose per treatment cycle. Thus, dose intensification by alterations of the application mode does not seem to be possible. Copyright 2000 S. Karger GmbH, Freiburg
 ...
PMID:Phase I Clinical Trial of a Day-1, -3, -5 Every 3 WeeksPhase I Clinical Trial of Day-1, -3, -5 Every 3 Weeks Schedule with Titanocene Dichloride (MKT 5) in Patients with Advanced Cancer. (Phase I Study Group of the AIO of the German Cancer Society). 1144 Dec 64


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>