Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
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Thirteen-week oral repeated dose toxicity of ecabapide, a gastroprokinetic drug, was investigated in dogs at dosage levels of 50, 175 or 600 mg/kg, and in rats at dosage levels of 25, 100, 400 or 1600 mg/kg. In dogs, vomiting, aqueous salivation, body weight gain inhibition, and hemolytic anemia, together with an increase in Heinz body formation, were observed at 175 and/or 600 mg/kg. Histological examination revealed enhanced hemosiderin deposition in the liver and spleen, retention of erythrocytes in the splenic sinus and enhanced erythropoiesis in bone marrow at 175 and/or 600 mg/kg. In the rat study, although increases in serum total protein, albumin and calcium, as well as increased liver and kidney weights, were observed at 400 and/or 1600 mg/kg, no obvious morphological changes were seen. The hemolytic anemia and an increased Heinz body formation were not observed in rats, indicating a species difference. On the basis of these results, the non-toxic dose of ecabapide was considered to be 50 mg/kg in dogs and 100 mg/kg in rats.
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PMID:Thirteen-week repeated oral dose toxicity study of ecabapide, a gastroprokinetic drug, in dogs and rats. 976 Apr 13

Metabolic acidosis is almost invariably a consequence of advanced renal failure, although its severity can vary widely. To evaluate the determinants of the severity of metabolic acidosis, with special interest in determining if there is any difference in the prevalence and severity of metabolic acidosis between patients with and without diabetes, 113 predialysis patients with renal failure were studied. Criteria for inclusion onto the study were: creatinine clearance (Ccr)/1.73 m2 less than 30 mL/min, no alkali therapy within the previous 30 days, and the absence of respiratory diseases. Forty-eight patients had diabetes (33 patients with diabetic nephropathy). The following data were analyzed: demographics; cause of renal failure; hematocrit; serum urea, creatinine, uric acid, albumin, glucose, hemoglobin A1c, bicarbonate, sodium, potassium, chloride, calcium, phosphorus, and alkaline phosphatase levels; anion gap; urinary protein excretion; Ccr/1.73 m2; half of the sum of creatinine and urea clearances (Ccr-Cu); protein-equivalent nitrogen appearance (PNA); and whether the patients received diuretics (75 patients), angiotensin-converting enzyme inhibitors (54 patients), and/or calcium channel blockers (55 patients). After the exclusion of eight patients because of hypochloremia (three patients with and five patients without diabetes), mean serum bicarbonate levels were significantly greater in patients with diabetes than in the rest of the patients (20.7 +/- 2.3 v 18.2 +/- 2. 3 mmol/L; P = 0.0001). The mean anion gap (mmol/L) was also significantly less in patients with than without diabetes (19.70 +/- 3.65 v 22.35 +/- 3.64; P = 0.003). Eleven of 105 patients had serum bicarbonate levels of 23 mmol/L or greater (9 patients with and 2 patients without diabetes). Pure elevated anion gap followed by mixed (high anion gap and hyperchloremia) were the most common types of metabolic acidosis observed in both groups. There were no differences in PNA, diuretic treatment, or vomiting history between patients with and without diabetes. By multiple logistic regression analysis, the best determinants for a serum bicarbonate level greater than 19 mmol/L were: the diagnosis of diabetic nephropathy (odds ratio, 0.107; P = 0.0002), Ccr-Cu (odds ratio, 0.824; P = 0. 014), and age (odds ratio, 0.966; P = 0.046). In conclusion, patients with diabetes with advanced renal failure showed a less severe metabolic acidosis, which cannot be explained by gastrointestinal hydrogen ion losses, drugs, or reduced protein catabolic rate. Patients with diabetes may have a more efficient extrarenal generation of bicarbonate than end-stage renal failure patients without diabetes.
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PMID:Metabolic acidosis in advanced renal failure: differences between diabetic and nondiabetic patients. 1021 45

Serum visceral protein and hematological indices and their behavioral and clinical correlates were determined in women with bulimia nervosa and depressed controls. One hundred and fifty-two women who met DSM-IV criteria for bulimia nervosa and 68 women with DSM-IV major depression completed a structured clinical interview and had blood samples drawn prior to admission to outpatient treatment programs. Albumin and prealbumin concentrations were lower in the depressed women, possibly due to recent weight loss. Elevated transferrin values suggested mild iron deficiency in nearly one-fifth of women with bulimia nervosa. Of women with bulimia nervosa, the 10.7% who had hemoglobin and 5.1% who had vitamin B12 levels below the normal range were not distinguishable on measures of body mass index, binge eating, vomiting, or restriction frequency. The 4.3% with low prealbumin levels experienced significantly more episodes of binge eating and vomiting in the prior fortnight than those with normal values. Frequency of vomiting was also inversely associated with albumin concentration. Hamilton Depression Rating Scale scores were inversely and linearly related to serum vitamin B12. Lower B12 levels in those with alcohol abuse/dependence did not explain the association between B12 and HDRS scores. No hematological indices were related to body mass index, binge eating or restriction frequency, or restriction intensity. In summary, women with bulimia nervosa do not appear to be at greater risk of visceral protein or hematological abnormalities than psychiatric controls. It is suggested that a high frequency of vomiting and alcohol abuse/dependence, increases the risk of subclinical malnutrition in women with bulimia nervosa, and that poor vitamin B12 nutriture may interfere with the functioning of the serotonergic or catecholaminergic systems and contribute to depressive symptoms in bulimia nervosa.
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PMID:Visceral protein and hematological status of women with bulimia nervosa and depressed controls. 1022 89

We report on a 35 year old female with a 26 day history of an intermittent cerebellar syndrome (dysarthria, ataxia of extremities, gait and trunk, nystagmus), mild meningism, cephalgia, recurrent emesis and nausea. Symptoms developed after typically chickenpox exanthema. Examination of the liquor showed mild pleocytosis, elevated protein and increased albumin quotient. Virus was not found by EIA or PCR. There were elevated levels of IgM- and IgG-antibodies to VZV. The EEG showed mild general changes, compatible with an encephalitis. Neuroradiological examinations were unremarkful. The neurological deficits partly regressed in the follow-up of two months. To the best of our knowledge we are the first that describe the paradox of an intermittent cerebellar syndrome after infection with chickenpox without detection of the virus in the liquor. This phenomenon can be related to the unusual combination of cerebellar ataxia and the later occurrence of mild encephalitis.
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PMID:[Cerebellar syndrome after varicella infection without virus identification in cerebrospinal fluid--an important differential ataxia diagnosis]. 1059 44

Gadobenate dimeglumine formulation (E7155), at doses of 0 (physiological saline), 0.25, 0.5, 1 and 2 mmol/kg/day of body weight, was administered intravenously to male and female beagle dogs once daily for 4 consecutive weeks in order to evaluate the subacute toxicity of the test article. Reversibility of toxicity was evaluated during a 4-week recovery period at 1 and 2 mmol/kg/day. No toxicologically significant changes were observed at 0.25 and 0.5 mmol/kg/day. In animals receiving 1 or 2 mmol/kg/day, transient swelling and redness of the facial and eye areas, lethargy, decreased activity, emesis, retching, watery or unformed stool, decreased body weight or body weight gain, decreased food consumption, decreased hematocrit and hemoglobin concentration, increased APTT, increases in plasma ALP, GPT or gamma-GT, decreased plasma inorganic phosphorus, total protein or albumin, increased liver or kidney weight, subacute inflammatory infiltrates, loss of centrilobular hepatocytes or hepatocellular cytoplamic vacuolation in the liver, vacuoles in the epithelial cells of the renal tubles and/or hypocellularity in the bone marrow were seen. The results of toxicokinetic analysis showed that systemic exposure was similar in males and females, and there was no accumulation of the test material over the treatment period, although AUC tended to be enhanced by slightly more than the proportionate dose increase. These effects were recovered or tended to be reversed after a post-dosing period for 4 weeks. In conclusion, the No Observed Adverse Effect Level (NOAEL) was 0.5 mmol/kg/day.
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PMID:[General toxicity study of gadobenate dimeglumine formulation (E7155) (4)--4-week repeated dose intravenous toxicity study followed by 4-week recovery period in dogs]. 1063 79

Records and pedigrees of Soft Coated Wheaten Terriers (SCWT) with protein-losing enteropathy (PLE) or protein-losing nephropathy (PLN) were studied retrospectively. Criteria for inclusion were defined based on analysis of blood (panhypoproteinemia for PLE, hypoalbuminemia for PLN) and urine (proteinuria for PLN) and histopathologic examination of tissue. Two hundred twenty-two affected dogs (female:male ratio = 1.6, P < .001) were clinically identified. Dogs were diagnosed with PLE earlier (P < .005; mean +/- SD age: 4.7+/-2.6 years, n = 76) than with PLN (6.3+/-2.0 years, n = 84) or with both diseases (5.9+/-2.2 years, n = 62). Clinical signs included vomiting, diarrhea, weight loss, pleural and peritoneal effusions, and less commonly thromboembolic disease. Dogs with PLE generally had panhypoproteinemia and hypocholesterolemia; intestinal lesions included inflammatory bowel disease, dilated lymphatics, and lipogranulomatous lymphangitis. Dogs with PLN generally had hypoalbuminemia, proteinuria, hypercholesterolemia, and azotemia; renal lesions typically showed chronic glomerulonephritis/glomerulosclerosis, and less commonly endstage renal disease. Dogs with combined PLE/PLN had intermediate mean values (P < .001) for serum total protein, albumin, globulin, and cholesterol but had a higher mean urine protein:creatinine ratio than did PLN dogs (P < .05); intestinal and renal lesions in these dogs were similar to those in the other groups. Two dogs had incidental mild renal dysplasia. Pedigree analysis from 188 dogs demonstrated a common male ancestor, although the mode of inheritance is unknown. Both PLE and PLN are common diseases in this small breed population. The prognosis is poor. Compared with previously reported intestinal and renal diseases in dogs, a new, distinctive familial predisposition for both PLE and PLN has been recognized in the SCWT breed.
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PMID:Familial protein-losing enteropathy and protein-losing nephropathy in Soft Coated Wheaten Terriers: 222 cases (1983-1997). 1066 20

BACKGROUND: Major complications of modern bariatric operations are infrequent but can be quite disabling to the patient and pose therapeutic challenges to the surgeon. We present our experience with five patients who underwent gastrectomy for complications following gastric reduction procedures. PATIENTS AND METHODS: Between 1991 and 1995, four women and one man, average age 46.8 years (34-66), underwent total gastrectomy and Roux-en-Y end-to-side esophagojejunostomy (4), or near-total gastrectomy with esophagogastrostomy (1). The decision to perform total gastrectomy was based on the poor quality of the remaining gastric pouch and the surgeon's judgement. Preoperative diagnoses included gastric outlet obstruction secondary to anastomotic ulcer or stricture, gastroesophageal reflux with esophagitis, chronic gastrocutaneous fistula, and iatrogenic linitis secondary to gastric wrap with mesh. Preoperatively, the patients complained of intolerable nausea, vomiting, abdominal pain, and dysphagia. RESULTS: in the five patients who underwent total or near-total gastrectomy, there was no operative mortality or morbidity; however, one patient (near-total gastrectomy) has required a second operation for pyloroplasty. Although one patient was lost to follow-up 6 months after surgery, the average follow-up for the remaining four patients is 2 years. These four patients were interviewed and all report complete satisfaction with their surgery and much improvement in their symptoms. Presently, they consume an average of three meals per day (range 2-6), with each meal measuring about 2 cups in size. All report the sensation of satiety after meals. All patients receive supplemental iron, B12, and multivitamins. From a nutritional standpoint, there has not been a significant change in the levels of albumin, total protein, hematocrit, weight and BMI since total gastrectomy. CONCLUSIONS: In our experience, total gastrectomy with Roux-en-Y end-to-side esophagojejunostomy is an appropriate therapy with low morbidity and mortality in highly selected patients with complications resulting from gastric reduction procedures.
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PMID:Gastrectomy for Complications of Bariatric Procedures. 1072 78

The best procedure for the treatment of morbid obesity has not yet been defined. Biliopancreatic diversion is one of the techniques available, but its results have not been sufficiently documented and the addition of a subtotal gastrectomy to the diversion so as to avoid leaving a blind non-functioning stomach, is still questionable. The purpose of this paper is to report our experience with our first 149 consecutive patients who were treated by biliopancreatic diversion with subtotal gastrectomy for morbid obesity. Operative mortality was 3% and morbidity 12%. The weight loss was marked during the first 6 months and decreased during the following 12 months. The weight stabilized at 2 years and there was subsequently a small increase. In only two out of 48 cases was the weight loss less than 25% of the initial weight at 2 years. The undesirable side-effects were diarrhea in 6%, vomiting in 9% and dyspepsia in 4%. The intervention leads to a malabsorption of carotene, iron, albumin and calcium. Except for carotene the deficiencies were corrected by oral supplement. In two patients, with resistant deficiencies, the diversion was reversed. Eighty-eight percent of the patients are satisfied with this intervention. At 2 years, 70% have reached their weight loss objective without any major side-effects or nutritional deficiencies, but in 14% the outcome of the procedure must be considered unsatisfactory. Biliopancreatic diversion with subtotal gastrectomy is a major operation, but it gives encouraging results so far.
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PMID:Biliopancreatic Diversion with Gastrectomy as Surgical Treatment of Morbid Obesity. 1077 39

The aim of this prospective study was to compare epidemiological data and clinical features in children and adults with tick-borne encephalitis (TBE). Patients with aseptic meningitis diagnosed at the University Medical Centre, Department of Infectious Diseases, Ljubljana, Slovenia, from June to August 1997, in whom the diagnosis of TBE was ascertained by the presence of serum IgM antibodies against TBE virus, who were serologically negative for Borrelia burgdorferi sensu lato and had a negative PCR CSF result on enteroviral infection, were included in the study. Out of 213 patients with aseptic meningitis, 80 (37.56%) fulfilled inclusion criteria. There were 20 children and 60 adults. In both groups males predominated. Virtually all patients had headache and fever, and more than 50% suffered from vomiting. The majority of patients in both groups recalled a tick bite, had a biphasic course of the illness, and was found to have obviously expressed meningeal signs. In both groups the median CSF leukocyte count was somewhat lower than 100 x 10(6)/l with a predominance of lymphocytes. Children were more often given antibiotics during the initial phase of TBE than adults (p = 0.0095). Several other statistically significant distinctions (p < 0.05) were found including the frequency of fatigue, malaise, vertigo, photophobia, myalgias, arthralgias, as well as elevated CSF albumin and protein concentration, elevated albumin quotient and IgG quotient; all these findings were more often present in adults. In addition a longer duration of fever, more frequent need for anti-edematous treatment and longer hospitalization were found in adults. Direct comparison of clinical and epidemiological characteristics of TBE in children and adults revealed differences in several clinical and laboratory features and corroborates the previous conclusion that TBE in childhood is a milder illness than TBE in adults.
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PMID:Comparison of the epidemiological and clinical features of tick-borne encephalitis in children and adults. 1078 89

This pilot study evaluates the degree of side effects during high-dose chemotherapy (HD-VIC) plus autologous bone marrow transplant (HDCT) and its possible prevention by the cytoprotective thiol-derivate amifostine. Additionally, the in-patient medical costs of both treatment arms were compared. 40 patients with solid tumours were randomized to receive HD-VIC chemotherapy with or without amifostine (910 mg/m(2)at day 1-3) given as a short infusion prior to carboplatin and ifosfamide. Patients were stratified according to pretreatment. HDCT consisted of an 18 h infusion of carboplatin (500 mg/m(2/)d over 18 h), ifosfamide (4 g/m(2)/d over 4 h) and etoposide (500 mg/m(2)/d) all given for 3 consecutive days. All patients received prophylactic application of G-CSF (5 microg kg(-1)subcutaneously) to ameliorate neutropenia after treatment. Patients were monitored for nephrotoxicity, gastrointestinal side effects, haematopoietic recovery, as well as frequency of fever and infections. The median fall of the glomerular filtration rate (GFR) was 10% from baseline in the amifostine group (105 to 95 ml min(-1)) and 37% in the control patient group (107 to 67 ml min(-1)) (P< 0.01). Amifostine-treated patients revealed a less pronounced increase in albumin and low molecular weight protein urinary excretion. Stomatitis grade III/IV occurred in 25% without versus 0% of patients with amifostine (P = 0.01). Acute nausea/vomiting was frequently observed immediately during or after the application of amifostine despite intensive antiemetic prophylaxis consisting of 5-HT3-receptor antagonists/dexamethasone/trifluorpromazine. However, delayed emesis occurred more often in the control patients. Engraftment of neutrophil (> 500 microl(-1))and thrombocytes (> 25 000 microl(-1))were observed at days 9 versus 10 and 10 versus 12, respectively, both slightly in favour of the amifostine arm. In addition, a lower number of days with fever and a shortened duration of hospital stay were observed in the amifostine arm. The reduction of acute toxicity observed in the amifostine arm resulted in 30% savings in costs for supportive care (Euro 4396 versus Euro 3153 per patient). Taking into account the drug costs of amifostine, calculation of in-patient treatment costs from the start of chemotherapy to discharge revealed additional costs of Euro 540 per patient in the amifostine arm. This randomized pilot study indicates that both organ and haematotoxicity of HD-VIC chemotherapy can be ameliorated by the use of amifostine. Additionally, a nearly complete preservation of GFR was observed in amifostine-treated patients which may be advantageous if repetitive cycles of HDCT are planned. Larger randomized trials evaluating amifostine cytoprotection during high-dose chemotherapy are warranted.
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PMID:A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplantation. 1116 94


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