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

Chloroquinoxaline sulfonamide (CQS) is a halogenated heterocyclic sulfanilamide identified by the in vitro human tumor colony-forming assay as an active agent in a variety of human solid tumors. In this phase I study, 182 courses of CQS were administered intravenously every 28 days to 88 patients at doses ranging from 18 to 4870 mg/m2. Hypoglycemia associated with hyperinsulinemia was the dose-limiting adverse effect at 4870 mg/m2. Supraventricular tachyarrhythmias were observed at doses > 4000 mg/m2. Less common reactions included infusion site phlebitis, nausea, anemia, alopecia, perioral numbness, and diarrhea. Cumulative toxicity was not observed. Minor objective antitumor responses were noted in 7 patients; 6 of the 7 responses occurred in patients with non-small cell lung cancer. Results of pharmacokinetic studies were consistent with the preclinical observations that CQS is highly bound to plasma protein. Plasma elimination followed a two-compartment model; the mean t 1/2 alpha was 2.7 +/- 0.3 h and the t 1/2 beta was 52 +/- 6 h (+/- SE). The total body clearance and the volume of distribution at steady state of CQS both increased with the dose (distribution at steady state, 3.7-10.5 liter/m2; total body clearance, 53-264 ml/h/m2 for doses of 18-4060 mg/m2) and may reflect saturation of the protein binding and "free" drug clearance. Although inactive against common animal tumors in preclinical screening systems both in vitro and in vivo, CQS has demonstrated definite activity in the human tumor stem cell colony-forming assays, as well as modest anticancer activity in this phase I study in patients with advanced solid tumors. The pharmacokinetic results and the limiting effect of transient hypoglycemia suggest that considerably higher cumulative doses of CQS could be administered using a more frequent dosing schedule.
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PMID:Phase I clinical and pharmacological study of chloroquinoxaline sulfonamide. 142 6

After her first grand mal seizure a 30-year-old woman was given a fructose infusion by an emergency doctor. On admission to hospital she complained of severe nausea. Ultrasonography revealed hepatosplenomegaly and the gamma-GT concentration was raised to 25 U/l. As hyperinsulinism was suspected an oral glucose tolerance test was suggested, but refused by the patient. She reported marked aversion to all sweet foods. Examination of an endoscopically obtained liver biopsy revealed clear reduction in fructoaldolase activity in liver tissue, i.e. the diagnosis of hereditary fructose intolerance. Three of the patient's siblings were also affected. The widespread use of infusion solutions containing sorbitol and fructose has twice proved acutely hazardous in this patient and is generally life-threatening for persons with an inborn error of metabolism whose pathologic status often remains undiagnosed to an adult age.
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PMID:[Adults with hereditary fructose intolerance: risks of fructose infusion]. 196 93

This study evaluated the effect of gastric bypass on the glucose, insulin, vasoactive intestinal peptide (VIP), neurotensin, and motilin response to orally administered glucose in eight morbidly obese patients before and after operation. Preoperatively, all eight patients remained asymptomatic during an oral glucose tolerance test, which showed glucose intolerance and hyperinsulinism. Plasma VIP, neurotensin, and motilin remained below detectable levels for the entire test. At three months following gastric bypass (21% weight loss), all eight patients became acutely ill during a repeated oral glucose tolerance test and had the following symptoms: facial flushing (eight patients), palpitations (eight patients), nausea (seven patients), abdominal fullness (seven patients), pallor (four patients), diaphoresis (two patients), vomiting (two patients), and diarrhea (two patients). Significant release of neurotensin occurred in seven patients while three patients had release of VIP, further implicating these two peptides as part of the pathophysiologic spectrum of the "dumping syndrome."
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PMID:Neurotensin, vasoactive intestinal peptide, and Roux-en-Y gastrojejunostomy. Their role in the dumping syndrome. 398

A discussion of the side effects of hormonal oral contraceptive (OC) use is presented. Studies show that the estrogen component of OCs works to suppress the release of GRH (gonadotropin-releasing hormone), reducing the serum FSH level. The gestagen component desensitizes the frontal lobe of the pituitary gland to the effect of GRH and suppresses the preovulatory LH peak. OCs can cause subjective side effects such as nausea, headache, depression, which can also be observed during placebo use. Breakthrough bleeding, spotting, silent menstruation, and post-pill amenorrhea are menstrual irregularities which can be linked to OC use; 98% of those who discontinue OC use show normal biphasic menstrual cycles 3 cycles after discontinuation. A constant increase in serum triglyceride levels, small increases in cholesterol and phospholipid levels are observed among OC users. Minor cases of hyperinsulinism are observed among OC users with no history of diabetes; glucose tolerance tests should be regularly administered to OC users who have a risk of diabetes or a history of pregnancy diabetes. Serum levels of proteins are affected by OC use, probably due to the effects of OC use on liver function. Studies have shown an increased risk of thromboembolism and circulatory disorders among OC users, especially those who are over 30 years of age or who smoke. OC use has been linked to development of benign tumors of the liver and the cervix. Gestagens appear to reduce the frequency of endometrial mitosis. Other medications, e.g. analgesics, barbituates, can reduce the effectiveness of OCs. For adolescents, sequence preparations are preferred and should be administered only after a 1 year period of regular menstruation. Thorough check-ups should be performed on OC users twice yearly, and contraindications should be scrupulously observed.
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PMID:[Effects and side effects of hormonal contraceptives]. 741 48

The effects of preexercise hyperinsulinemia on exercising plasma glucose, plasma insulin, and metabolic responses were assessed during 50 min cycling at 62% VO2max. Subjects were fed a 6% sucrose/glucose solution (LCHO) or a 20% maltodextrin/glucose solution (HCHO) to induce changes in plasma insulin. During exercise, subjects assessed perceived nauseousness and light-headedness. By the start of exercise, plasma glucose and plasma insulin had increased. In the LCHO trial, plasma glucose values significantly decreased below the baseline value at 30 min of exercise. However, by 40 min, exercise plasma glucose and insulin values were similar to the baseline value. Exercise plasma glucose and insulin did not differ from baseline values in the HCHO trial. Ingestion of LCHO or HCHO was not associated with nausea or lightheadedness. It was concluded that the hyperinsulinemia induced by preexercise feedings of CHO did not result in frank hypoglycemia or adversely affect sensory or physiological responses during 50 min of moderate-intensity cycling.
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PMID:Glycemic and insulinemic response to preexercise carbohydrate feedings. 816 54

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.
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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

Considerable debate has taken place over the safety and validity of increased protein intakes for both weight control and muscle synthesis. The advice to consume diets high in protein by some health professionals, media and popular diet books is given despite a lack of scientific data on the safety of increasing protein consumption. The key issues are the rate at which the gastrointestinal tract can absorb amino acids from dietary proteins (1.3 to 10 g/h) and the liver's capacity to deaminate proteins and produce urea for excretion of excess nitrogen. The accepted level of protein requirement of 0.8g x kg(-1) x d(-1) is based on structural requirements and ignores the use of protein for energy metabolism. High protein diets on the other hand advocate excessive levels of protein intake on the order of 200 to 400 g/d, which can equate to levels of approximately 5 g x kg(-1) x d(-1), which may exceed the liver's capacity to convert excess nitrogen to urea. Dangers of excessive protein, defined as when protein constitutes > 35% of total energy intake, include hyperaminoacidemia, hyperammonemia, hyperinsulinemia nausea, diarrhea, and even death (the "rabbit starvation syndrome"). The three different measures of defining protein intake, which should be viewed together are: absolute intake (g/d), intake related to body weight (g x kg(-1) x d(-1)) and intake as a fraction of total energy (percent energy). A suggested maximum protein intake based on bodily needs, weight control evidence, and avoiding protein toxicity would be approximately of 25% of energy requirements at approximately 2 to 2.5 g x kg(-1) x d(-1), corresponding to 176 g protein per day for an 80 kg individual on a 12,000kJ/d diet. This is well below the theoretical maximum safe intake range for an 80 kg person (285 to 365 g/d).
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PMID:A review of issues of dietary protein intake in humans. 1677 21

A 45-year-old woman who had undergone total gastrectomy for gastric cancer presented with a history of postprandial hypoglycemic episodes with loss of consciousness after meals. Laboratory findings revealed marked hyperinsulinemia and hypoglycemia after a meal. We first treated the patient with octreotide; however, she was unable to continue the treatment because of adverse effects of the drug, such as nausea and headache. Diazoxide was used next for preventing hyperinsulinemia; however, this was not effective for suppressing the postprandial insulin secretion. Since hypoglycemia following gastrectomy is thought to be caused by rapid delivery of nutrients into the duodenum, we performed a meal tolerance test while varying the timing of administration of miglitol in relation to the meal. Miglitol was administered 30 min before, just before, or both 30 min and just before a meal. In the case of administration just before a meal, insulin secretion was suppressed, although hypoglycemia was not prevented. Administration of the drug 30 min before a meal prevented postprandial hypoglycemia by slowing the increase of the blood glucose and serum insulin levels following the meal to a greater degree than administration just before a meal. Miglitol administration both 30 min and just before a meal caused an even smoother increase in blood glucose and serum insulin levels following the meal. In this report, we propose a new therapeutic approach for reactive hypoglycemia after gastrectomy, namely, administration of miglitol 30 min before meals.
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PMID:Using miglitol at 30 min before meal is effective in hyperinsulinemic hypoglycemia after a total gastrectomy. 2514 87

Massive insulin overdose may be associated with unpredictable and prolonged hypoglycemia. Concerns surrounding the potential provocation of insulin release from beta cells have previously prevented the use of intravenous glucagon as an adjunct to infusion of dextrose in this situation. We describe the case of a 15-yr-old boy with type 1 diabetes mellitus (T1DM) who presented with profound hypoglycemia following an overdose of an unknown quantity of premixed insulin. Owing to an increasing dextrose requirement and a dependence on hourly intramuscular glucagon injections, a continuous intravenous infusion of glucagon was commenced which successfully avoided the requirement for central venous access or concentrated dextrose infusion. Nausea was managed with anti-emetics. Intramuscular and subcutaneous glucagon is effective in the management of refractory and severe hypoglycemia in youth with both T1DM and hyperinsulinism. Concerns regarding the precipitation of rebound hypoglycemia with the use of intravenous glucagon do not relate to those with T1DM. This treatment option may be a useful adjunct in the management of insulin overdose in youth with T1DM and may avoid the requirement for invasive central venous access placement.
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PMID:Intravenous glucagon in a deliberate insulin overdose in an adolescent with type 1 diabetes mellitus. 2522 89

We present the unique case of adult hyperinsulinism hyperammonemia syndrome (HI/HA). This condition is rarely seen in children and even more infrequently in adults. A 27-year-old female with HI/HA, generalized tonic-clonic seizures, staring spells, and gastroesophageal reflux disease presented with diffuse abdominal pain, hypoglycemia, confusion, and sweating. She reported a history of significant nausea, vomiting, and diarrhea, which had been present intermittently over the past year. On examination, she was found to have a soft, nontender, and mildly distended abdomen without splenomegaly or masses. She had a normal blood pressure and was tachycardic (130 bpm). Her initial complete blood count and basic metabolic panel, excluding glucose, were within normal limits. She was found to have an elevated peripherally drawn venous ammonia (171 mmol/L) and near hypoglycemia (blood glucose 61 mg/dL), which were drawn given her history of HI/HA. She was continued on home carglumic acid and diazoxide, glucose was supplemented intravenously, and she was started on levetiracetam for seizure prophylaxis. An upper endoscopy (esophagogastroduodenoscopy [EGD]) was performed and was unremarkable, and biopsies taken were within normal limits. Following the EGD, she underwent a gastric emptying study that showed delayed emptying (216 minutes), consistent with a new diagnosis of gastroparesis, the likely etiology of her initial abdominal pain on presentation. This was subsequently treated with azithromycin oral solution. We present this case to raise awareness of this rarely encountered syndrome and to provide the basic principles of treatment.
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PMID:Hyperinsulinism Hyperammonemia Syndrome, a Rare Clinical Constellation. 2696 38


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