Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
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In 1981 and 1982, two US citizens died from Japanese encephalitis (JE) acquired in China. In 1983, the Centers for Disease Control initiated an evaluation of a purified, inactivated, mouse-brain-derived JE vaccine produced and used in Japan since 1966. Two doses of this vaccine given 1-2 weeks apart evoked neutralizing antibody titers greater than or equal to 8 in only 77% of recipients. After three JE vaccine doses administered 1-2 weeks apart, 99% developed titers greater than or equal to 8. When a third dose was given to 29 participants 6-12 months after the primary series, all developed titers greater than or equal to 16. Reported adverse reactions included injection site tenderness (18%), erythema (6%), or swelling (3%); headache (9%); and dizziness, fatigue, sleepiness, nausea, chills, fever, or lower back pain (less than or equal to 5%). On the basis of this study, three doses of BIKEN JE vaccine are recommended for US citizens who may be at risk of exposure to JE virus.
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PMID:Evaluation of the potency and safety of inactivated Japanese encephalitis vaccine in US inhabitants. 232 39

Sixteen previously treated (with only one prior regimen) patients with histologically proven metastatic or locally recurrent colorectal carcinoma were treated with recombinant tumor necrosis factor (rTNF) administered by 30-minute i.v. infusions twice daily for 5 consecutive days every other week for 8 weeks. Patients received 100 micrograms/m2 twice daily on day 1 of cycle 1 with escalation to 150 micrograms/m2 twice daily thereafter. Patients were concomitantly treated with indomethacin 25 mg every 6 hours and acetaminophen 650 mg every 4 hours to obviate fever and chills. Toxicities included: nausea/vomiting (69%), headache (25%), chills (69%), pain at tumor sites (63%), hypotension (31%), and hypertension (38%). Hematologic toxicity included leukopenia less than 2000 cells/mm3 (38%) and thrombocytopenia less than 100,000 cells/mm3 (13%). Liver function abnormalities occurred independently of the site or extent of metastatic disease and inconsistently in each treatment cycle. Four patients developed bilirubinemia greater than 2.5 x baseline values (range, 2.5 to 10.3 U/L); five patients had greater than 2.5 x elevations in alkaline phosphatase (range, 624 to 1663 U/L). Two patients developed retinal vein thrombosis in the absence of hemostatic abnormalities. In both instances, this complication occurred several weeks after completion of therapy. No objective responses were noted in 14 evaluable patients (95% confidence interval: 0 to 0.23). Three patients had stable disease for a median duration of 4.5 months. In conclusion, i.v. rTNF at this dose and schedule has no demonstrable antitumor efficacy. Twice-daily i.v. administration of this agent is associated with more hepatotoxicity than previously reported in trials using subcutaneous or once daily i.v. administration. Retinal vein thrombosis may be a late complication of i.v. rTNF at this dose and schedule.
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PMID:A phase II trial of recombinant tumor necrosis factor in patients with advanced colorectal carcinoma. 238 95

All major types of human interferons (IFNs) have been purified and clinically administered as antitumor agents. We summarize here experience to date with toxicity of IFNs in cancer patients. The acute syndrome consists of fever, chills, myalgias, arthralgias, and headache, with some variation according to type of IFN, route of administration, schedule, and dose. Fatigue, perhaps reflecting CNS toxicity, is the most prevalent nonacute symptom. At high doses, IFNs are neurotoxic; the abnormalities seen by EEG resemble those in diffuse encephalitis. Hematologic toxicity consists mainly of leukopenia, but anemia and thrombocytopenia occur in some patients. Nausea, vomiting, and diarrhea are the main gastrointestinal symptoms. Elevation of serum transaminases seems to reflect liver toxicity. Renal function is well preserved, except for rare instances of acute renal failure. Cardiac toxicity remains questionable, although heart failure and arrhythmias have been associated with the administration of IFNs. Most, if not all, of these effects are reversible or can be ameliorated. With IFN alpha, the type most widely used in clinical studies, doses of 1 million to 9 million units (MU) are generally well tolerated, but doses greater than or equal to 18 MU yield moderate to severe toxicity. Doses greater than or equal to 36 MU can induce severe toxicity and significantly alter the performance status of the patient.
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PMID:Clinical toxicity of interferons in cancer patients: a review. 241 69

A 20-year-old man on oral substitution of pancreatic enzymes after hemipancreatectomy injected an enzyme preparation of fungal origin intravenously after dissolving it in water. Within a few hours chills, headache, nausea and vomiting, fever of 40.8 degrees C, and shock occurred. The acute illness might have been caused by bacteremia, an anaphylactic reaction, or by direct activation of humoral or cellular mediators by the fungal enzymes. A haemostatic disturbance, particularly a drop in plasminogen, was observed. In vitro, the fungal enzyme preparation stimulated elastase release from isolated neutrophils and eliminated plasmatic inhibitors and plasminogen in normal plasma and whole blood. Human neutrophil elastase complexed to alpha 1-antitrypsin was increased in the patient's plasma, while the levels of the complexes thrombin-antithrombinIII and plasmin-alpha 2-antiplasmin, indicating recent coagulation or fibrinolysis, respectively, were not elevated. Thus, an activation of the neutrophils with release of elastase might have contributed to the observed coagulation disturbances.
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PMID:A unique case of intravenous injection of fungal "pancreatic" enzymes causing shock and proteolysis of haemostatic proteins. 246 40

The present investigation was undertaken to establish the relation between climacteric symptoms, ovarian function, ageing, and psychological factors. The subjects were as follows; 1,270 women who received a screening test for cervical cancer and 247 women following hysterectomy. The methods of investigation were Kupperman menopausal index (K-index), Cornell Medical Index (CMI) and YG character questionnaire (YG test). The following results were obtained: 1) the K-index increased until 39 years of age and was constant after 40 years. Five symptoms (chills, nervousness, melancholia, excitability and vertigo) were not influenced by ageing, and seven symptoms (panting, hypesthesia, insomnia, wakefulness, fatigue, palpitation and formication) increased with age. Hot flushes, perspiration, numbness, shoulder stiffness, lumbago, and headache, occurred at peak frequency in the climacteric period. 2) In hot flushes, perspiration, numbness, hypesthesia, shoulder stiffness, lumbago, and formication, a significant difference was found between the control and those patients who had received bilateral oophorectomy. 3) The K-index and CMI score were significantly correlated, and six symptoms (palpitation, panting, excitability, vertigo, wakefulness and formication) in particular were related to CMI. 4) The K-index was lowest in the patients indicated to be the D type by the YG test, and was highest in the patients of the B.E type. Six symptoms (excitability, palpitation, panting, melanchoria, hypesthesia and formication) were thought to be associated with the character of the patients. Results showed that four symptoms (hot flushes, perspiration, numbness, shoulder stiffness and lumbago) were closely related to ovarian function, and three symptoms (panting, excitability, and palpitation) depended largely on mental factors. The relationship between vasomortor symptoms and gonadotropin was investigated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Study on climacteric symptoms in relation to ovarian function ageing and psychologic factors]. 249 39

A clinical trial was conducted to determine the tolerance and toxicity of recombinant tumor necrosis factor (rTNF) and recombinant interferon gamma (rIFN-gamma) when administered concurrently by continuous intravenous infusion to 11 patients with the AIDS-related complex (ARC). In addition, HIV culture, p24 antigen levels, and CD4 positive lymphocytes were monitored to obtain preliminary evidence of antiviral and immunologic effects. Two 5-day treatment cycles were separated by a 9-day washout period. Two patients were entered at each dosage level and each patient received the two 5-day treatment cycles at two sequential dose levels ranging from 1 to 25 micrograms/m2. Two patients did not complete their second treatment cycle--one due to the development of a rash, the second due to central venous catheter discomfort. The occurrence of phlebitis with peripheral vein administration of these agents necessitated administration via central venous catheter. With the exception of a single patient who developed severe headache at the 25 micrograms/m2 dose, severe clinical toxicities were not observed. Fever, chills, headache, and myalgias were the most significant clinical toxicities observed and all were dose dependent. The percentage fall in total granulocytes was dose dependent and ranged from 17% at the 1 microgram/mm2 dose to 48% at both the 15 and 25 micrograms/mm2 dose levels. The mean nadir granulocyte count was 1694/mm3. No significant renal or hepatic toxicity was observed. Of 22 treatment cycles the CD4 cell number was increased in 11, unchanged in 7, and decreased in 4. The mean CD4 cell number did not change significantly (176 +/- 143/mm3 pretherapy versus 279 +/- 305/mm3 posttherapy).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A phase I/II study of recombinant tumor necrosis factor and recombinant interferon gamma in patients with AIDS-related complex. 256 51

Prostaglandin (PG) E2 suppositories have been shown to be effective in uterine evacuation for mid-trimester abortion. At the University of Mississippi Medical Center, vaginal PGE2 suppositories have been used routinely to effect termination of pregnancies following fetal death at any age and in the majority of therapeutic abortions performed at over 14 weeks' gestation. This study evaluated the results of PGE2 treatment in 85 patients seen at the center during an 18-month period, the majority (65%) of whom were delivered because of fetal death. Prior to the procedure, 55% of these patients had a closed cervix and laminarias were inserted. The average time from induction with PGE2 to expulsion of the fetus was 9.3 hours (range, 1.4-23.2 hours), with no significant difference between the groups with and without laminaria unless the cervix was dilated more than 2 cm at the time of admission. 94% of study subjects required 3 or fewer suppositories to effect delivery. Of the 85 patients, 78 (91%) aborted successfully within 24 hours. There were no major complications; the incidence of minor side effects ranged from 12% (for diarrhea) to 21% (for hyperpyrexia). Overall, these findings suggest that medical induction using prostaglandins is a safe, convenient method of evacuating the uterus, particularly in the case of fetal death after 20 weeks. The minor side effects such as nausea and vomiting, fever, diarrhea, headache, and chills can be reduced when patients are premedicated with anti-emetics and antidiarrheal preparations. Moreover, these side effects may be further decreased by the use of newer compounds, such as the 15-methylated prostaglandins, that are believed to induce less reaction in the gastrointestinal tract.
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PMID:Prostaglandin E2 induction of abortion and fetal demise. 256 5

A single, selective study was performed in order to evaluate the efficacy and safety of cefotetan in the treatment of complicated urinary tract infections (UTI). Of 34 pre-treatment isolated strains, 60% were pluri-resistant to other antibiotics (ampicillin, carbenicillin, piperacillin, cefalotin, aztreonam) but only 21.2% to cefotetan. Pseudomonas aeruginosa and enterococci were resistant to cefotetan. Escherichia coli was the common strain isolated (50%). Nineteen adult patients, with complicated UTI caused by sensitive organisms, were treated with a 1 g intramuscular (i.m.) daily dose. Duration of treatment ranged from 5-15 days, with a mean of 13.75 days. Within 24-48 h and 30 days post-therapy, the infection was cured in 84% and 52% of patients, respectively. Reinfection, relapse or super-infection occurred in 42% of the cases. In only one patient, the infecting organism did not respond to treatment. The clinical response was evaluated in only seven patients with symptomatic UTI. Six of them (85.7%) were cured after therapy and the cure persisted at follow-up. In most cases, the adverse reactions were local, mild and negligible. In only 15.8% and 10.5% of patients, side-effects (diarrhoea, headache, abdominal pain, tachycardia, chill, pain and erythema in the injection site) were severe and moderate. In these cases, the adverse reactions were reversible when the therapy was discontinued. The relationship between treatment and side-effects was doubtful in two cases. It is concluded that cefotetan, administered at 1 g i.m. daily dose, is effective in treating complicated UTI caused by sensitive organisms, pluri-resistant to other antibiotics.
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PMID:Efficacy and safety of cefotetan in the treatment of complicated urinary tract infections: clinical experience in a selective and single study. 259 2

Epidemics of a malaria-like illness affected several thousand residents of the Dam Camp, a refugee camp near Hargeysa in Somalia, during 1985, 1986, and 1987. The disease was characterized by fever, chills, sweats, headache, back and joint pains for as long as 10 days in some patients. Blood smears from acutely ill patients were negative for malaria. Of 28 acute and 10 convalescent sera tested by the indirect fluorescent antibody (IFA) and by the hemagglutination inhibition (HI) tests, all were negative for antibody to Rift Valley fever, Crimean-Congo hemorrhagic fever, Sindbis, Chikungunya, yellow fever, and Zika viruses. However, antibody reactive to dengue 2 virus was detected by the IFA test in 39% (15/38), and 11 of 29 (38%) of the same sera were antibody positive by the HI test. Also, IgG antibody reactive to dengue 2 was demonstrated in 60% (17/28) of the same sera by the enzyme immunoassay (EIA), and 14% (4/28) were positive for IgM antibody. Of ten patients for which acute and convalescent sera were available, two developed four fold or greater rises in antibody titer evidencing infection. These data suggested that dengue virus may have been the cause of the epidemic among the Dam Camp refugees.
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PMID:Serological evidence of dengue fever among refugees, Hargeysa, Somalia. 260 May 91

rTNF was administered to 28 patients with advanced metastatic cancers by continuous intravenous infusion for 5 consecutive days every 2 weeks. The dose levels were 30, 40, 70, 110, 180 and 290 micrograms/M2/day. Groups of 3 patients were started at each successive dose level and then on subsequent courses treated with the next dose level through 4 escalations as tolerated. Tumor types were: colon cancer 14; adenocarcinoma of unknown primary, 2; renal cancer, 2; leiomyosarcoma, 2; lung cancer, 1; prostate cancer, 1; thymona, 1; bladder cancer; 1; parotid, 1; Kaposi's sarcoma 2; ovarian 1. Toxicities included fever and chills (usually within the first 8 hours of infusion), fatigue, headache, decreased performance status, hypotension and CNS. All patients experienced leukopenia and thrombocytopenia within 24 hours or less after start of infusion with return of baseline by 72 hours after rTNF was stopped. The fall in these counts averaged 50% and was not dose related. No major changes in liver or renal function, coagulation or blood lipids were seen. Major dose limiting toxicities were fatigue, confusion, thrombocytopenia, seizures, hypotension and decreased performance status. NK cell activity measured against K562 target cells was augmented from about 30% target cell lysis to about 70% target cell lysis over the first 7 days of treatment. Two patients, both with metastatic colon cancer showed transient, objective tumor regression which did not qualify as a partial response. One patient with ovarian cancer had a stable partial response but progressed after 13 courses of treatment. Continuous infusion of TNF can be safely administered to patients with a maximum tolerated dose of only between 30 and 40 micrograms/M2/day.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A phase I trial of recombinant tumor necrosis factor (rTNF) administered by continuous intravenous infusion in patients with disseminated malignancy. 264 24


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