Gene/Protein Disease Symptom Drug Enzyme Compound
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Hantavirus pulmonary syndrome (HPS) is a viral infection from a new strain of Hantavirus. The Hantavirus was first discovered in North America in 1993 after an outbreak of fatal illness on a Navajo Indian reservation in New Mexico. Since then, 122 cases of HPS (with a high mortality rate of more than 50%) have been reported in 23 states, with the highest prevalence in the Four Corners area. The reservoir for Hantavirus is small rodents, mostly field mice, vole, and chipmunks. It is transmitted through inhalation of airborne virus from dry rodent excreta and saliva. A North American strain of Hantavirus, named ain nombre virus (SNV), primarily affects the lungs, causing rapid accumulation of fluids and leading to noncardiogenic pulmonary edema, pleural effusion, and acute respiratory distress syndrome (ARDS). In the prodromal stage, HPS presents with flu-like symptoms, nausea, vomiting, and gastrointestinal pain and is often mistaken on the first visit for other infectious diseases or gastroenteritis. In the second acute stage, rapid respiratory deterioration begins: HPS is often misdiagnosed for pneumonia, idiopathic ARDS, and pulmonary edema. HPS treatment with an experimental antiviral intravenous drug, ribavirin, is under investigation. Practitioners must possess through clinical knowledge on the diagnoses, pathology, treatment, and course of the disease to reduce the mortality and morbidity rate of this rare but serious infection. A case report based on a recent HPS death in New York State on Long island in April 1995 is presented.
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PMID:Hantavirus pulmonary syndrome: epidemiology, prevention, and case presentation of a new viral strain. 878 77

We report a case of acute pancreatitis with diabetic ketoacidosis associated with increased serum myoglobin concentration, acute renal failure, and disseminated intravascular coagulation. A 49-year-old man suffering from diarrhea, vomiting, and somnolence was admitted to the hospital. He had had flu-like symptoms for 4 days prior to the onset of these symptoms. He was a habitual drinker and had been consuming 360 ml-900 ml of the drink "shochu" (distilled spirits containing 28% alcohol) daily for 30 years. Laboratory data on admission revealed elevated serum levels of pancreatic enzymes, including amylase, trypsin, lipase, pancreatic secretory trypsin inhibitor (PSTI), phospholipase A2 (PLA2), and elastase-1, as well as elevated levels of glucose (373 mg/dl), ketone bodies (3675 mumol/l), and myoglobin (229.8 ng/ml). Treatment with subcutaneous insulin and intravenous administration of electrolyte fluid and the systemic protease inhibitor, gabexate mesilate, was begun immediately. Early after the initiation of treatment, there was an increase in serum creatinine (4.9 mg/dl), and thromobocytopenia (15000/microliters) was observed. The patient completely recovered from renal failure and acute pancreatitis, but required insulin therapy. Alcohol ingestion and dehydration are thought to have played a major role in the triggering of the acute pancreatitis. We examined the relationship among acute pancreatitis, diabetic ketoacidosis, and hypermyoglobinemia in the literature.
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PMID:Acute pancreatitis with diabetic ketoacidosis associated with hypermyoglobinemia, acute renal failure, and DIC. 884 91

Early Phase II clinical studies with bropirimine (U-54461S) having interferon (IFN) inducing and direct antiproliferative activities were conducted in patients with various solid tumors or hematologic neoplasm at 34 institutions nationwide. To investigate the safety and efficacy of the treatment, bropirimine was orally administered to the patients at the dose of 1g every two hours, three times a day for three consecutive days with a four day drug-free interval. Among the 65 patients registered, 60 patients were eligible and 44 patients completed bropirimine treatment in accordance with the respective protocols. Complete response (CR) was observed in 7 cases, and partial response (PR) was observed in 4 cases, so the efficacy rate was 25.0% (7 CRs + 4 PRs/44). Classified by target tumors, the efficacy rates were 12.9% (6 CRs/14) in bladder CIS, 33.3% 1 CR/3) in superficial bladder cancer. 11.1% 1 PR/9) in renal cell carcinoma, and 42.9% (3 PRs/7) in malignant lymphoma, respectively. Adverse drug reactions frequently observed were influenza-like symptoms such as fever (60.0%) and generalized malaise (21.7%), gastrointestinal symptoms like anorexia (56.7%) and nausea/vomiting (43.3%), and adverse effects on the circulatory system such as tachycardia (15.0%) and abnormalities in ECG (11.7%). Most of these symptoms were relieved or improved. Abnormalities in laboratory tests observed frequently were adverse effects on the liver such as elevations in GPT (33.3%), in GOT (31.7%), and in LDH (18.3%) or on the blood system like a decrease in RBC (18.3%), leukopenia (26.7%), or neutropenia (25.0%). In conclusion, bropirimine treatment proved to be effective for bladder CIS in particular, suggesting that it will be promising for use in the treatment of the disease.
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PMID:[Bropirimine (U-54461S) early phase II clinical studies--to investigate the efficacy and safety of bropirimine treatment on various malignant tumors (urological, hematologic, and dermal cancers)]. 902 Sep 48

Late Phase II clinical study with bropirimine (U-54461S), a novel oral antitumor agent that has interferon inducing and anti-proliferative activities, was conducted in patients with bladder CIS at 38 institutions nationwide. To investigate the efficacy and safety of the treatment, bropirimine was administered to the patients at the dose of 750 mg every two hours, three times a day, for three consecutive days with four-day drug withdrawal, based on the results of the preceding clinical studies up to early phase II. Among the 48 patients registered, 41 patients were evaluable for antitumor efficacy. Complete response (CR) was observed in 17 of them, no change (NC) in 18 patients, and progressive disease (PD) in 6 patients; so the efficacy rate was 41.5%. Classified by patient background, the efficacy rates were 58.3% (7/12) in patients with primary bladder CIS, 34.5% (10/29) in those with secondary bladder CIS, 45.5% (10/22) in those with Grade 3, and 23.8% (5/21) in those previously given chemotherapeutic agents or BCG by intravesical or other routes. Adverse drug reactions frequently observed were influenza-like symptoms such as fever and generalized malaise and gastrointestinal symptoms like anorexia and nausea/vomiting; these symptoms were all Grade 2 or milder. Abnormalities in laboratory tests, such as an elevation in GOT/GPT, neutropenia, and leukopenia were observed. These adverse effects were all tolerated by the patients. From the above results, bropirimine was considered to be a useful oral agent for the treatment of bladder CIS.
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PMID:[Bropirimine (U-54461S) late phase II clinical study for carcinoma in situ of the bladder. Japan Bropirimine Study Group]. 902 Sep 49

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of gemcitabine are reviewed. Gemcitabine is a deoxycytidine-analogue antimetabolite with activity against some solid tumors. Gemcitabine is phosphorylated intracellularly to difluorodeoxycytidine triphosphate, which terminates DNA-chain elongation and competitively inhibits DNA polymerase and ribonucleotide reductase. After i.v. administration, gemcitabine is rapidly distributed into total body water. The drug is deaminated in the plasma to inactive difluorodeoxyuridine; both gemcitabine and difluorodeoxyuridine are primarily renally eliminated. In clinical studies, gemcitabine reduced pain and improved function in patients with advanced pancreatic cancer. Gemcitabine has shown some activity against non-small-cell lung cancer, particularly when combined with cisplatin or ifosfamide. The agent has also shown modest activity against advanced ovarian and breast cancer. Adverse effects include dose-limiting myelosuppression, flu-like symptoms, nausea, vomiting, and rash. Gemcitabine has FDA-approved labeling for use in the treatment of locally advanced and metastatic pancreatic cancer. The recommended dosage for this indication is 1000 mg/m2 (as the hydrochloride salt) i.v. given over 30 minutes weekly for seven weeks, followed after one week of rest by 1000 mg/ m2 i.v. given over 30 minutes weekly for three weeks every four weeks. Gemcitabine palliates symptoms in patients with advanced or metastatic pancreatic cancer. More study is needed to determine gemcitabine's role in the treatment of non-small-cell lung cancer, ovarian cancer, and breast cancer.
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PMID:Gemcitabine: a cytidine analogue active against solid tumors. 911 4

rHuTNF was locally applied to 26 patients with diverse advanced tumours and malignant pleural effusions following maximum possible drainage of their pleural cavities. 46 instillations (an average of 1.8 per patient) with doses between 0.10 mg and 0.50 mg were carried out. The total doses ranged from 0.15 mg to 1.01 mg per patient. 41% of the instillations resulted in flu-like symptoms, 35% fever/chill, 24% fatigue/malaise, 11% nausea/vomiting and 11% chest pain. All toxicities were fully reversible and could be treated successfully. There was no apparent relation between dose and side-effects. Of those patients treated primarily with TNF, 87% did not suffer from any recurrent effusion within 4 weeks after treatment. In patients who had already been treated employing other methods, this figure was 86%. Complete drainage of the pleural cavity was not absolutely necessary before application of TNF. Intrapleural instillation of TNF appears to be an effective method for achieving pleurodesis with relatively few side-effects and can be successful even after other methods have failed. It is a method which can also be applied to patients who have a poor general state of health.
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PMID:Recombinant tumour necrosis factor in the local therapy of malignant pleural effusion. 913 93

The aim of this study was to determine the objective tumour response rate and duration of response and toxicity of linomide (Roquinimex) treatment in patients with disseminated renal cell carcinoma, pretreated or not pretreated with immunotherapy. From March 1991 to July 1992, 72 patients with metastatic and progressive renal cell cancer were entered of whom 9 (12%) were not evaluable for response. Linomide was given orally, twice weekly, 5 mg during the first week with dose escalation to 10 mg during the second week and 15 mg thereafter. Treatment was continued until disease progression or unacceptable toxicity. No haematological toxicity but slight anaemia was observed. A significant WBC (white blood cell count) increase (P < 0.0001, paired T-test) was found during treatment. The most often reported non-haematological side-effects were: flu-like syndrome (54%, grade III-IV 7%), nausea/vomiting (41% and 3%, respectively) and neurotoxicity (34% and 2%). Most side-effects were of mild or moderate intensity (WHO grade 1 or 2). The objective overall response rate was 4%: 1 CR and 2 PRs. Stable disease was reported for 28 patients (40%). The duration of response was 17, 22 and 30 (CR) months. Median time to progression was 5 months. Linomide at the given dose and schedule is well tolerated, but has limited antitumour activity in metastatic renal cell carcinoma.
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PMID:An EORTC phase II study of the efficacy and safety of linomide in the treatment of advanced renal cell carcinoma. 915 38

During the months of September 1993 through February 1994, an outbreak of hemorrhagic fever occurred in the city of Jayapura, the provincial capital of Irian Jaya, Indonesia. Seventy-two patients (age range = 1-41 years) with suspected dengue hemorrhagic fever (DHF) were enrolled into the outbreak investigation conducted during October-November 1993. The pediatric patient population consisted of 36 individuals ages 1-12 years of age with a similar male to female ratio. From clinical histories obtained from the children diagnosed with DHF (n = 23), the predominant complaints were fever (100%), headache (96.7%), vomiting (47.8%), abdominal pain (39.1%), back/bone pain (39.1%), cough (39.1%), sore throat (21.7%), convulsions (17.4%), and eye pain (13.0%). Clinical findings of the same pediatric patients included a positive tourniquet test result (100%), thrombocytopenia (100%), hemoconcentration (100%), skin petechiae (43.5%), epistaxis (39.1%), and maculopapular rash (26%). All four of the children diagnosed with DHF grade IV had hepatomegaly, pleural effusion, ascites, cold perspiration, and confusion. Serologic data demonstrated that a majority (46 of 70, 68.7%) of the individuals assessed did not have significant levels of IgM specific for dengue viruses at the time of their admission. However, the nine successful dengue virus isolations were only from these serononreactive cases (19.6%). From the other patients assessed, 11.4% had a primary (or first exposure) serologic response to dengue virus antigen (predominantly IgM); 17.1% had a secondary (or subsequent exposure) serologic response to the same dengue antigens (predominantly IgG response) and 5.7% (four adults) had indeterminate serologic data that could not differentiate between reactivity to dengue or Japanese encephalitis virus antigen preparations. Virus culture of blood samples produced nine dengue virus isolates: DEN- 1 (2), DEN-2 (1), and DEN-3 (6). Japanese encephalitis and influenza viruses were not isolated from blood and pharyngeal specimens, respectively, from any of the patients. Thus, this first reported outbreak of DHF in Irian Jaya, Indonesia was found to be attributed to dengue viruses types 1, 2, and 3.
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PMID:The first reported outbreak of dengue hemorrhagic fever in Irian Jaya, Indonesia. 924 17

Lower levels of plasma total cholesterol have been observed during severe infection, but it is not known whether the minor illnesses encountered in the general population are also associated with reduced cholesterol. This paper examines the relation between minor illness and plasma lipids, using 7- and 10-year follow-up data from more than 3,000 generally healthy participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. At both 7 and 10 years, approximately 8.5% of participants stated they had been "ill with cold, flu, fever, or vomiting in the past 24 hours." In both cross-sectional and longitudinal analyses, the plasma total cholesterol was about 5 mg/dl lower (p < 0.006) and high density lipoprotein cholesterol about 1.2 mg/dl lower (p < 0.12) in those who reported minor illness than in those who did not. Plasma triglycerides did not vary with minor illness. The authors conclude that reductions in plasma total, low density, and high density lipoprotein cholesterol mark an acute phase response even during minor illness. These reductions may bias surveys over a limited geographic area during a short period because the proportion with minor illness may vary locally. Because this effect should be stronger with more precise illness diagnosis, clinicians should avoid making measurements for cholesterol management when illness may alter plasma lipid levels and the resulting decisions.
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PMID:Reduced cholesterol is associated with recent minor illness: the CARDIA Study. Coronary Artery Risk Development in Young Adults. 932 33

Monthly disease summary sheets from 1986-1992 of 60 dispensaries, clinics and hospitals in Narok district, Kenya were reviewed for the occurrence of brucellosis and other diseases with "flu-like symptoms". Diseases with these symptoms accounted for about 52% of the 1,037,875 cases reported for the time period. These were classified as malaria (79.3%), rheumatism (7.1%), PUO (2.4%), and brucellosis (0.8%). Brucellosis was diagnosed by a positive Rose Bengal (RB) test routinely conducted in seven out of the 60 health units. In these units, 55% of flu-like cases were classified as malaria and 21.2% as brucellosis. Individual case records of patients at four dispensaries using the RB test during 1991-92 were assessed for specific predictor symptoms. For 625 RB tested patients, a positive test result was associated with joint pain, headache, and the combinations of joint pain with headache and lameness with headache. A logistic regression model correctly predicted the RB test result in 62.3% of the time. For the 465 patients examined by the blood smear examination, identification of malaria parasites was associated with, headache, joint pain and combinations of emesis with pale mucous membranes. This regression model correctly predicted positive results 67.2% of the time. Both models indicate that selected clinical predictors represented significantly increased odds of being positive to the respective tests. However, for both diseases, clinical signs alone appear insufficient for reliable diagnosis and differentiation probably due to resemblance in symptomatology between these two and other diseases.
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PMID:Criteria for better detection of brucellosis in the Narok District of Kenya. 933 12


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