Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The management of both diabetic and idiopathic gastroparesis often represents a substantial clinical challenge. In formulating recommendations for therapy, it should be recognized that these are based on less than optimal evidence; in particular, there are substantial deficiencies in current knowledge relating to the pathophysiology of gastroparesis, as well as the natural history of gastrointestinal symptoms, and the majority of pharmacologic trials have been short term and associated with methodologic limitations. Although the etiologic factors differ, the overall management principles are similar in the two conditions. Maintenance of adequate nutrition is pivotal, and parenteral nutrition may be required in severe cases associated with malnutrition. In patients with diabetes, rigorous attempts should be made to optimize glycemic control--hyperglycemia slows gastric emptying and may exacerbate symptoms and attenuate the effects of prokinetic drugs. Despite the relatively poor predictive value of symptoms, it is reasonable to suggest a trial of prokinetic therapy for about 4 weeks, rather than initially establishing the diagnosis by measurement of gastric emptying. However, it should be recognized that there is a substantial placebo response, a lack of evidence to support the cost effectiveness of such an approach, and that most patients will require prolonged therapy. In type 1 diabetic patients, prokinetic therapy may potentially benefit glycemic control, and this forms an additional rationale (albeit not established) for therapy. Some patients with diabetes and idiopathic gastroparesis with severe vomiting are unable to tolerate oral medication; in such cases subcutaneous metoclopramide may prove useful. Patients with intractable symptoms should be hospitalized and given intravenous erythromycin. The repertoire of prokinetic agents available in the United States is limited and includes metoclopramide, erythromycin, and cisapride (available by special program from its manufacturer); all of these drugs are associated with side effects. The use of metoclopramide may represent the first choice for chronic oral therapy, although it has been studied less comprehensively than cisapride. Combination therapy may be potentially more efficacious than the use of single agents. Dehydration and metabolic derangements should be corrected. The choice of chronic medical therapy should be individualized, taking factors such as age, presence of diabetes, concurrent medications, and comorbidities into account. In a small number of patients in whom medical treatment fails, surgery should be considered, and, if performed, done in a specialized center. A number of novel therapies, including gastric electrical stimulation, are currently being evaluated.
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PMID:Idiopathic and Diabetic Gastroparesis. 1284 39

Aberrations in cell cycle control occurs in the majority of human malignancies due to inactivation of tumor suppressor gene Rb by the phosphorylation induced by "hyperactive" cyclin-dependent kinases. Thus, it is quite reasonable to design cdk modulators for the prevention and treatment of human neoplasms. In order to target the cdk complexes, 2 main strategies were considered: to target the ATP binding site of cdks (direct cdk modulators) and to target upstream pathways required for cdk activation (indirect cdk modulators). Examples for the first group include flavopiridol, roscovitine, BMS-387032. Examples for the second group include perifosine, lovastatin, UCN-01. The first example of a direct small molecule cdk modulator tested in the clinic, flavopiridol, is a pan-cdk inhibitor that not only promotes cell cycle arrest but also halts transcriptional elongation, promotes apoptosis, induces differentiation and has antiangiogenic properties. Clinical trials with this agent were performed with at least 3 different schedules of administration: 1 hour infusion, 24 hour infusion and 72 hour infusion. Main toxicities for infusions >/=24 hours are secretory diarrhea and pro-inflammatory syndrome. In addition, patients receiving shorter infusions have nausea/vomiting and neutropenia. Some clinical responses were observed in several patients with refractory malignancies. Based on these encouraging results, a Phase 3 trial comparing standard combination chemotherapy versus combination chemotherapy plus flavopiridol is currently under investigation. The second example of direct small molecule cdk modulator tested in clinical trials is UCN-01 (7-hydroxi-staurosporine). UCN-01 has interesting preclinical features: inhibits ca2+-dependent PKCs, promotes apoptosis, arrest cell cycle progression at G1/S and abrogates checkpoints upon DNA damage. The first Phase I trial of UCN-01 demonstrated a very prolonged half-life. Based on this novel feature, UCN-01 is administered as a 72 hour continuous infusion every 4 weeks (second and subsequent cycles UCN-01 is administered as a 36-hour infusion). Other shorter schedules (i.e., 3 hours) are being tested. Dose-limiting toxicities include nausea/vomiting, hypoxemia and insulin-resistant hyperglycemia. Combination trials with cisplatin and other DNA-damaging agents are being tested. Recently, Phase I trials with two novel small molecule cdk modulators, BMS 387032 and R-Roscovitine (CYC202), have commenced with good tolerability. Phase 2 trials and Phase I trials in combination with standard chemotherapy is being planned with these agents. In summary, novel small molecule cdk modulators are being tested in the clinic with interesting results. Although these small molecules are directed towards a very prevalent cause of carcinogenesis, we need to test them in advanced clinical trials to determine the future of this class of agents for the prevention and therapy of human malignancies.
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PMID:Novel small molecule cyclin-dependent kinases modulators in human clinical trials. 1450 85

Aberrations in cell cycle progression occur in the majority of human malignancies. The main pathway affected is the retinoblastoma (Rb) pathway. The tumor suppressor gene Rb is an important component in the G(1)/S transition and its function is abnormal in most human neoplasms. Loss in Rb function occurs by the hyperactivation of the cyclin-dependent kinases (cdk's). Therefore, modulation of cdk's may have an important use for the therapy and prevention of human neoplasms. Efforts to obtain small-molecule cdk modulators yielded two classes of modulators: direct and indirect modulators. Direct cdk modulators are small molecules that specifically target the ATP binding site of cdk's. Examples for this group include flavopiridol, roscovitine and BMS-387032. In contrast, indirect cdk modulators affect cdk function due to modulation of upstream pathways required for cdk activation. Some examples include perifosine, lovastatin, and UCN-01. The first example of a direct small-molecule cdk modulator tested in the clinic, flavopiridol, is a pan-cdk inhibitor that not only promotes cell cycle arrest but also halts transcriptional elongation, promotes apoptosis, induces differentiation, and has antiangiogenic properties. Clinical trials with this agent were performed with at least three different schedules of administration: 1-, 24- and 72-h infusions. The main toxicities for infusions >/=24-h are secretory diarrhea and proinflammatory syndrome. In addition, patients receiving shorter infusions have nausea/vomiting and neutropenia. A phase II trial of patients with advanced non-small-cell lung carcinoma using the 72-h infusion every 2 weeks was recently completed. The median overall survival for the 20 patients who received treatment was 7.5 months, a survival similar to that obtained in a randomized trial of four chemotherapy regimens containing platinum analogues in combination with taxanes or gemcitabine, or with gefitinib, a recently approved EGFR inhibitor for the treatment of advanced lung cancer. Based on these encouraging results, a phase III trial comparing standard combination chemotherapy versus combination chemotherapy plus flavopiridol is currently under investigation. The second example of direct small-molecule cdk modulator tested in clinical trials is UCN-01 (7-hydroxystaurosporine). UCN-01 has interesting preclinical features: it inhibits Ca(2+)-dependent PKCs, promotes apoptosis, arrests cell cycle progression at G(1)/S, and abrogates checkpoints upon DNA damage. The first phase I trial of UCN-01 demonstrated a very prolonged half-life. Based on this novel feature, UCN-01 is administered as a 72-h continuous infusion every 4 weeks (in second and subsequent cycles UCN-01 is administered as a 36-h infusion). Other shorter schedules (i.e. 3 h) are being tested. Dose-limiting toxicities include nausea/vomiting, hypoxemia, and insulin-resistant hyperglycemia. Combination trials with cisplatin and other DNA-damaging agents are being tested. Recently, phase I trials with two novel small-molecule cdk modulators, BMS 387032 and R-Roscovitine (CYC202), have commenced with good tolerability. In summary, novel small-molecule cdk modulators are being tested in the clinic with interesting results. Although these small molecules are directed towards a very prevalent cause of carcinogenesis, we need to test them in advanced clinical trials to determine the future of this class of agents for the prevention and therapy of human malignancies.
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PMID:Small-molecule cyclin-dependent kinase modulators. 1452 86

A 5-year-old girl with a mild upper airways infection was admitted to the hospital because of sudden vomiting and drowsiness that evolved to stupor; she was dehydrated, hypotensive, and tachypneic; laboratory tests revealed noncompensated lactic acidosis. She also had hypoglycemia followed by hyperglycemia, and progressive bradycardia leading to reversible cardiac arrest. Her clinical condition complicated by sinus bradycardia, ventricular tachycardia, third-degree atrioventricular blockage and lethal asystole. At the final stage of her illness, the serum salicylate concentration was 383.8 mcg/mL. Based on this single data, a retrospective toxicological analysis estimated a theoretical peak level of serum salicylate of approximately 1570 mcg/mL (therapeutic range, 20-250 mcg/mL) although the real amount of aspirin that this child ingested is difficult to calculate because aspirin is a drug that shows a so-called zero order kinetics. At autopsy, the most striking finding was multiple foci of coagulative necrosis involving the entire thickness of the myocardium with scant inflammatory infiltrate composed mainly of macrophages and polymorphonuclear leukocytes. The morphologic characteristics of the myocardial lesion in addition to salicylate blood levels suggests the possibility of an adverse drug reaction of the type acute toxic myocarditis.
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PMID:Aspirin intoxication in a child associated with myocardial necrosis: is this a drug-related lesion? 1469 48

Eight cases of feline pancreatic adenocarcinoma and two cases of pancreatic adenoma were reviewed. The adenomas were incidental findings. Most cats with adenocarcinomas had anorexia (75%) and vomiting (63%), while 38% had abdominal pain, a palpable abdominal mass, and/or jaundice. Diagnostic abnormalities included leukocytosis, hyperglycemia, increased alanine aminotransferase activity, poor serosal detail on abdominal radiography, and an abdominal mass effect on ultrasonography. The majority of cats with carcinomas had metastases (mostly to liver, lung, and small intestine), and all were euthanized or died within 7 days of diagnosis. Clinically, feline pancreatic carcinoma may be difficult to distinguish from feline pancreatitis.
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PMID:Exocrine pancreatic neoplasia in the cat: a case series. 1513 Nov 6

Amitraz is an insecticide/acaricide of formamidine pesticides used worldwide to control ectoparasites in animals. Amitraz poisoning is a rare disorder characterized by central nervous system (CNS) and respiratory depression, bradycardia, hypotension, hypothermia, hyperglycemia,nausea and vomiting. Poisoning may occur either by oral inhalation and dermal route. In this study, we present seven pediatric patients with amitraz poisoning. The initial symptoms were unconsciousness, dizziness and vomiting; and emerged within 30-150 minutes. The length of stay in the intensive care unit (ICU) was between 18-62 hours.
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PMID:Amitraz poisoning: clinical and laboratory findings. 1518 Dec 99

Hypoglycemia is a common complication of virulent canine babesiosis. A study was conducted to determine the prevalence of and potential risk factors for hypoglycemia in canine babesiosis from Babesia canis rossi. Plasma glucose concentration was measured at presentation in 250 dogs with babesiosis, of which 111 were admitted to hospital. The prevalence of hypoglycemia (<60 mg/dL) was 9% (23/250). Twenty-two hypoglycemic dogs required admission, making the prevalence of hypoglycemia in admitted dogs 19.8%. Sixteen dogs had severe hypoglycemia (<40 mg/dL), of which 5 had glucose < 18 mg/dL. Hyperglycemia (>100 mg/dL) was present in 38 dogs, of which 21 were admitted. Risk factors for hypoglycemia identified by univariate analysis were collapsed state (P < .00001), severe anemia (P = .0002), icterus (P = .003), age < 6 months (P = .02), and vomiting (P = .03). After logistic regression analysis, collapsed state (odds ratio [OR] = 18; 95% CI, 1.9-171; P = .01) and young age (OR = 2.8; 95% CI, 0.8-9.7; P = .1) remained significantly associated with hypoglycemia. Toy breeds and pregnant bitches were not at higher risk for hypoglycemia than other dogs. Blood glucose concentration should ideally be measured in all dogs requiring inpatient treatment for babesiosis but is mandatory in collapsed dogs; puppies; and dogs with severe anemia, vomiting, or icterus. Many dogs have probably been misdiagnosed with cerebral babesiosis in the past, and hypoglycemia should be suspected in any dog with coma or other neurological signs.
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PMID:Prevalence and risk factors of hypoglycemia in virulent canine babesiosis. 1518 10

Impaired function of the gastrointestinal tract related to diabetes mellitus (DM) results from diabetic autonomous neuropathy, impaired sensory innervation and a direct effect of chronic hyperglycaemia. Another possible connection between DM and the gastrointestinal tract can be infrequent autoimmune diseases associated with type I DM (celiac disease, autoimmune gastropathy, autoimmune chronic pancreatitis). Functional or organic changes resulting from diabetes can be seen in every organ of the gastrointestinal tract. Some of the diabetic gastrointestinal tract difficulties affect almost 60% of patients with long lasting diabetes. On one side, impaired function of individual organs in diabetics can significantly influence level of diabetes compensation and vice versa. On the other side, unsatisfactory diabetes compensation can result in manifestation of digestive problems. The most frequent and the most serious clinical complication is diabetic gastroparesis (DG). The highest incidence of impaired evacuation and motility of the stomach (and the small intestine) is described in diabetics with long lasting unsatisfactory diabetes compensation, microangiopathic complications, and diabetic neuropathy (55-75% in type I diabetes and 15-20% in type II diabetes). Symptoms accompanying impaired motility and emptying of the stomach (feeling of early fullness, eructation, nausea, vomiting and abdominal pains) can be only temporary or can be missing in some patients. Hyperglycaemia accompanied by slowing down evacuation of the stomach is different in patients with an empty stomach--glycaemia over 7.8 mmol/l, and postprandially--antral motility decreases after blood glucose levels get over 9.7 mmol/l. Treatment options for symptomatic diabetic gastroparesis are limited. Achieving normoglycaemia usually improves diabetic gastroparesis but in up to 80% of cases simultaneous administration of prokinetics is necessary.
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PMID:[Gastrointestinal complications in diabetes mellitus]. 1530 28

Despite the benefits and the widespread use of enteral and tube feeding (ETF) some patients experience complications, which can be divided in three categories: mechanical, e. g., tube blockage or removal; gastrointestinal, e. g., vomiting, diarrhea; and metabolic, e. g., re-feeding syndrome, hyperglycemia. The type and frequency of complications related to tube feeding varies considerably in accordance with the access to the intestinal tract (e. g., nasoenteric vs. percutaneous gastric vs. small bowel), the composition of the formula diet used, and the severity of the underlying disease. For example, tube-related complications have been reported to occur in 0-20 % and gastrointestinal complications in 8-65 % of patients during early postoperative feeding via a needle catheter jejunostomy (NCJ) using comparable techniques. The complication rate can be reduced by careful observance of guidelines on tube feeding including those related to food composition, administration rate, portion size, food temperature, and supervision of the patient. Gastrointestinal side effects (including diarrhea) are without doubt the most frequent.
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PMID:Enteral Nutrition by Endoscopic Means; II. Complications and Management. 1559 64

We report herein the case of a 28-year-old man presenting with hyperglycemic chorea-ballism (HCB) in addition to mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). He was admitted to a local hospital due to weight loss, general fatigue and thirst. The patient had diabetes mellitus, with a blood glucose level of 738 mg/dl and HbA1c of 19.8%. Although insulin therapy improved hyperglycemia, he noticed involuntary movements in the right upper and lower limbs, which subsequently extended to the left side. The patient was thus transferred to our hospital. He displayed short stature (154 cm) and emaciation, and a maternal family history of diabetes mellitus was elicited. He had no history of stroke-like episode, headache, vomiting and seizure. Neurological examination revealed low intelligence (IQ 57), mild sensorineural deafness, and chorea-ballism in the extremities and head without ptosis or eye movement disturbance. Brain computed tomography (CT) demonstrated areas of high density, while T1-weighted magnetic resonance imaging (MRI) revealed extreme hyperintensity and T2-weighted MRI showed hyperintensity in bilateral caudate nuclei, putamina and globi pallidus. HCB was diagnosed. In, CSF, lactate level was increased to 43.9 mg/dl (n, 4-16), pyruvate level was 1.65 mg/dl (n, 0.3-0.9) and total protein concentration was 59 mg/dl. Histological examination of a biopsy sample from the biceps brachii muscle demonstrated ragged-red fibers. An A3243G point mutation in the tRNA(Leu(UUR)) gene was detected, indicating the presence of MELAS. Involuntary movements improved on treatment with haloperidol up to 4.5 mg/day. HCB usually appears in elderly individuals, and cases less than 40-years-old are very rare. The mitochondrial dysfunction in MELAS may accelerate development of HCB.
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PMID:[A case of MELAS presenting juvenile-onset hyperglycemic chorea-ballism]. 1611 32


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