Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Streptozotocin (STZ) has shown antitumor activity against various tumors in man, but the clinical usefulness of this drug has been limited, mainly because of renal and gastrointestinal toxicity. Nineteen patients with advanced cancer of various types were given a mean dose of 3.4 g/m2 of STZ by continuous iv infusion over 5-6 days each month for one or two monthly cycles. Basic serum and urine studies were performed immediately before and after each treatment cycle. Following STZ treatment, no significant changes in BUN or creatinine were seen. Four patients in whom initial tests for proteinuria were negative developed grade 1 or 2+ proteinuria after completion of the treatment cycle. No myelosuppression or renal failure was observed. Six patients had no nausea or vomiting, seven patients had nausea only, three patients had nausea and vomiting which were well-controlled with antiemetics, and three patients had uncontrollable nausea and vomiting. Confusion, lethargy, and depression were noted in five patients who had no prior central nervous system abnormalities; these effects appeared during treatment or in the immediate posttreatment period. Two patients with diffuse non-Hodgkin's lymphoma had complete remission, while several other patients had documented improvement. Although central nervous system toxicity may be a limiting factor, prolonged STZ infusions may have significant clinical promise.
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PMID:Continuous streptozotocin infusion: a phase I study. 16 Aug 36

A phase II evaluation of anguidine was carried out in 30 patients with advanced refractory breast cancer. A dose of 5.0 mg/m2 daily for 5 days was explored. The main toxic effects were nausea and vomiting, fever and chills, hypotension, skin erythema, somnolence, confusion, and lethargy. Myelosuppression was minimal. Among these extensively pretreated patients, there was one partial responder and one additional patient who showed improvement (less than a partial response); both responses occurred in soft tissue sites.
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PMID:Phase II study of anguidine in advanced breast cancer. 45 16

A patient was presented with both an aneurysm of the frontobasal branch of the right anterior cerebral artery and an arterio-venous malformation fed by the same artery. A 36-year-old man with sudden headache, nausea and vomiting was admitted to the emergency clinic on July, 4, 1974. On admission, he was slightly lethargic and complained of severe headache. The blood pressure was 112 systolic and 64 diastolic. He showed no abnormal findings except for nuchal stiffness and bloody liquor (pressure 260 mmH2o). A right carotid angiogram revealed an aneurysm, 1.0 cm in diameter, on the frontabasal branch of the right anterior cerebral artery and distal to the aneurysm the artery continued to an arteriovenous malformation. No other vascular lesion was observed by other angiographies. On July, 24, 1974, the parent artery (frontobasal branch) of the aneurysm was clipped and the part of right frontal lobe containing the nidus excisted. The patient's post operative course was uneventful.
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PMID:[Co-existing aneurysm and arteriovenous malformation--case report (author's transl)]. 103 90

The case of a 49-year-old female with a left parietal convexity meningioma associated with an acute subdural hematoma is described. She was admitted because of sudden onset of severe headache accompanied by nausea and vomiting. She was also confused, and 6 hours after admission she developed lethargy, right hemiplegia, and left mydriasis with no pupillary reaction to light. Computed tomography disclosed a round, extra-axial mass in the left parietal region; it was heterogeneously enhanced. Emergency craniotomy, performed after carotid angiography, revealed a tumor with a massive underlying subdural hematoma. The histological diagnosis was meningotheliomatous meningioma, and there were many meningothelial cells within the hematoma.
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PMID:Meningioma associated with subdural hematoma--case report. 169 43

Thirty-five patients with advanced malignant disease have been treated as outpatients with increasing doses (0.1-100 mcg) of interleukin 2 (IL2) by once daily self-administered subcutaneous (s.c.) injection, 5 days weekly for 8 weeks followed by a 4 week observation period. Systemic side effects were not experienced by patients at the 3 lower doses. Three patients required dose reduction from 100 mcg daily because of intolerance (fever, rash, lethargy, nausea and vomiting) and one patient was discontinued because of dyspnoea. We observed immunological effects at the 100 mcg dose (but not at the lower doses). These consisted of (a) a modest sustained lymphocytosis, (b) eosinophilia in six (out of nine) patients and (c) a significant rise in IL2-stimulated peripheral blood lymphocyte activated killer (LAK) cell activity in six (out of nine) patients to a mean of 2.0 times pretreatment levels (P less than 0.01). Two (out of nine) patients with renal cell carcinoma treated with 100 mcg daily had partial responses of duration 4 and 9 months respectively and a further three had disease stabilisation for at least 3 months. Low dose long-term s.c. IL2 is clinically and immunologically active, and in comparison to other IL2 regimens it has minor toxicity and is easy to administer. These characteristics make low dose s.c. IL2 suitable for study in the adjuvant setting.
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PMID:The clinical effects of prolonged treatment of patients with advanced cancer with low-dose subcutaneous interleukin-2 [corrected]. 199 6

Four cases of diabetic ketoacidosis presenting with abdominal pain are reported. Case 1: a 14-year-old boy suffered from sudden onset of mid-abdominal pain, then migrating to the right lower quadrant. Nausea and vomiting occurred subsequently. Appendectomy was performed under the impression of acute appendicitis in an outside surgical clinic. The patient became comatose the next day and then was transferred to our hospital. Diabetic ketoacidosis was diagnosed after the detection of hyperglycemia, glycosuria, and ketonuria on the day of admission. Unfortunately, he expired on the same day in spite of vigorous resuscitation. Case 2: a 9-year-old boy complained of abdominal pain for 10 days. There was no specific finding in the physical examination. Diabetic ketoacidosis was confirmed four days later when conscious disturbance, dehydration, and tachypnea were noticed. Case 3: a 10-year-old girl presented with a history of intermittent abdominal pain for one month. The character of the abdominal pain was nonspecific. Glycosuria was detected in a pediatric clinic. Diabetic ketoacidosis was confirmed after her referral to our hospital. Case 4: a 5-year-old girl suffered from acute abdominal pain for four hours. She was found to have tachypnea, lethargy, and ill-looking. Diabetic ketoacidosis was diagnosed after serial examinations. The abdominal pain in diabetic ketoacidosis may lead the pediatrician into diagnostic error. Therefore, when a child presented with non-specific abdominal pain, a routine urine sugar should be checked in order not to miss the possibility of diabetic ketoacidosis.
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PMID:[Abdominal pain in diabetic ketoacidosis: report of four cases]. 212 98

Twenty-four patients with caudate hemorrhage, in whom such definite organic lesions as arteriovenous malformations or ruptured cerebral aneurysms could not be proved, were analyzed. These cases comprise 2.0% of 1202 cases of hypertensive intracerebral hemorrhage diagnosed by computed tomography and experienced from 1976 through 1987. Thirteen patients were male and 11 were female. Their average age was 61 years. Headache (67%) and nausea and vomiting (50%), which were often the initial symptoms, were similar to those of subarachnoid hemorrhage. The main clinical symptoms were signs of meningeal irritation. Ten patients (42%) had transient disturbance of consciousness, and nine (38%) of these were somnolent; only one patient, who had a massive hematoma, was stuporous. When the hematoma extended to the internal capsule, the patient showed motor disturbance (38%). Two patients (8%) had Horner's sign, five (21%) exhibited diminished activity, and one (4%) suffered anosognosia. The volume of the intracerebral hematoma averaged 4.7 ml and was less than 5 ml in 17 patients (71%). In 20 patients (83%), the hematoma was confined to the head of the caudate nucleus. The hemorrhage tended to rupture into the anterior horn of the lateral ventricle, and in nearly all cases (96%), intraventricular hematoma was observed. Seventeen patients (71%) underwent cerebral angiography. There were no instances of dilation of the recurrent artery of Heubner. Twenty patients (83%) were treated conservatively. Continuous ventricular drainage was employed in four patients (17%), and ventriculoperitoneal shunting in three (13%). However, it was judged retrospectively that continuous ventricular drainage had been necessary in only two cases in which disturbance of consciousness was progressed due to acute hydrocephalus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clinical analysis of 24 cases of caudate hemorrhage]. 248 89

A phase I-II study of human recombinant interferon gamma (rIFN-gamma) was conducted in patients with various advanced cancer refractory to standard chemotherapies. In the phase I study, seven patients received 14 courses of escalating doses ranging from 2 X 10(6)U/m2 to 64 X 10(6)U/m2 by 1-hour intravenous infusion for 5 consecutive days. The toxicities were high fever with chills, anorexia, occasional nausea and vomiting, elevation of serum GOT, and dose-related leukopenia and neurotoxic symptoms such as heavy fatigue with somnolence or lethargy, both of which were reversible. The pharmacokinetics showed that the peak levels of serum rIFN-gamma activity were dose-related but decreased rapidly to below measurable levels within 6 hours after infusion in patients receiving less than 12 X 10(6)U/m2. Considering these data, the dosage of rIFN-gamma 6 X 10(6) U/m2 by daily intramuscular injection for more than 4 weeks was selected for the early phase II study. There was no partial response out of 11 evaluable patients but a stable condition was observed in 2 cases of renal cell carcinoma and one case each of breast cancer and ovarian cancer. All toxicities seen were similar to those observed in the phase I study, but no tachyphylaxis developed with continued dosage. The antitumor effect of rIFN-gamma remains to be evaluated in a further study employing higher doses.
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PMID:[Phase I-II study of recombinant interferon gamma]. 298 59

Eighteen patients with solid tumours were treated with human recombinant interferon-gamma at escalating dose levels starting at 1 X 10(6) units/m2 per infusion and rising through 3 X 10(6), 6 X 10(6), 9 X 10(6) and 22 X 10(6) to a maximum of 110 X 10(6) units/m2 per infusion. The IV infusions were given three times a week over a 4-week period. Side effects were seen in all patients, but were mild except at the highest dose. Acute dose-related effects included pyrexia, tiredness, thirst, chills and rigors. Chronic dose-related effects included anorexia, lethargy, weakness, disorientation, a trace of proteinuria and minimal rises in liver enzymes. In addition, effects were observed which were not related to dose. These included headache, nausea and vomiting, backache, myalgia, flatulence and a mild, transient reduction in neutrophils and erythrocytes. At the highest dose level dose-limiting toxicity was observed, consisting in severe tiredness and anorexia, hypotension, disorientation and changes on the electrocardiograph. Overall, toxicity was similar to that seen with preparations of interferon-alpha, except that no tolerance to the effects of interferon-gamma was noted. We observed less hepatic and haematological toxicity, but also recorded flatulence, handcramps and electrocardiograph changes, which have not been reported with interferon-alpha. When given according to this regimen, doses of 22 X 10(6) units/m2 per infusion of recombinant interferon-gamma were generally well tolerated by the patients.
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PMID:A toxicity study of recombinant interferon-gamma given by intravenous infusion to patients with advanced cancer. 309 8

Recombinant gamma interferon (r-GIFN) demonstrates in vitro and in vivo characteristics that contrast with those of alpha and beta interferons. It has relatively weak antiviral properties, yet relatively potent immunomodulatory effects. A phase I trial was performed with r-GIFN (specific activity 2.6 X 10(6) IU/mg protein), administered as a continuous intravenous (IV) infusion over 24 hours for five days (Cl X 5) and repeated every 28 days. This schedule was chosen based on the short half-life of r-GIFN in animal systems and the in vitro augmentation of biologic effects with continuous exposure to interferons. Twenty-one patients with refractory solid tumors received 46 evaluable courses of therapy. The dose-limiting toxicities included fever, flu-like symptoms, cardiovascular toxicity, and neurotoxicity. The cardiovascular toxicity included hypotension and one episode of cardiac ischemia with chest pain. Neurotoxicity consisted of lethargy and confusion. These toxicities were reversible, and although dose-limiting, occurred sporadically throughout all dosage levels. Mild to moderately severe non-dose-limiting toxicities included nausea and vomiting, leukopenia, and liver function abnormalities. Other infrequent toxicities included hypocalcemia, diarrhea, constipation, and alopecia. The maximally tolerated dose of r-GIFN on this schedule is 0.5 X 10(6) IU/m2/d. Partial responses were seen in one patient with metastatic melanoma and in one patient with renal cell carcinoma. Toxicity and antitumor activity were seen at doses where interferon serum levels could not be detected by radioimmunoassay. In addition, the toxicity and antitumor activity seen were at much lower doses than previously described for shorter infusion schedules of other recombinant gamma interferon preparations. Differences in biologic activity of interferon preparations and/or differences in scheduling may account for this variability. Although this study defines a recommended phase II dose of r-GIFN based on the maximally tolerated dose, the optimal therapeutic index may exist at a lower dosage level.
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PMID:A phase I clinical trial of recombinant DNA gamma interferon. 310 84


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