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

Immunotherapy with subcutaneous rIL-2 and alpha IFN was administered to stage D3 prostate cancer patients after failure of secondary treatment with oral estramustine phosphate. Of a total of 15 patients, 2 are in partial response, with estramustine maintained after 44+ and 36+ weeks, respectively. Response to estramustine was observed initially in 7 of 13 patients, with a median duration of 12 weeks (range 8-20). No response to estramustine was observed in the remaining 6 patients. After the failure of estramustine, 13 patients were treated with immunotherapy. After the first cycle, progression of disease no therapy was given to those patients. A reduction of PSA levels was observed during the first cycle in 2 patients (15.3%); levels subsequently increased during the second cycle of treatment. A partial response was observed in 4 patients (30.7%), with a reduction of PSA levels in 3. The duration of response was 28 and 32 weeks in 2 patients who survived after failure for 18 and 21 weeks, respectively. Two patients are still alive, with continued partial response at 62+ and 42+ weeks. Side effects were represented mainly by a flu-like syndrome, associated with fever and nausea in all patients. The serum concentration of IL-10 was measured in 8 patients under study and in 11 matched controls. Levels higher than mean + 2D of controls before, during, or after immunotherapy were correlated with treatment failure, whereas levels below 6 ng/ml were encountered among the patients who showed a clinical response and a reduction of PSA during treatment. Within the limitations of this pilot study, it appears difficult to distinguish between a spontaneously slowly progressing disease and a true response to therapy.
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PMID:Salvage immunotherapy with subcutaneous recombinant interleukin 2 (rIL-2) and alpha-interferon (A-IFN) for stage D3 prostate carcinoma failing second-line hormonal treatment. 861 53

A phase II trial investigating the anti-tumour effects of recombinant human interleukin 6 (rhIL-6) in patients with metastatic renal cell cancer was carried out. RhIL-6 (150 microgram) was administered as a daily subcutaneous injection for 42 consecutive days on an outpatient basis. Forty-nine patients were studied, 12 with and 37 without previous immunotherapy. Forty patients were evaluable for response. A partial remission was noted in two patients, stable disease in 17 and progressive disease in 21. Toxicity was moderate and reversible and consisted mainly of fever, flu-like symptoms, nausea, weight loss and hepatotoxicity. Anaemia, leucocytosis and thrombocytosis and induction of acute phase protein synthesis were noted in most patients. In 15% of the patients anti-IL-6 antibodies developed, and were neutralising in only one patient. Baseline plasma IL-6 concentrations did not correlate with tumour behaviour before or after rhIL-6 treatment. In conclusion, rhIL-6 can be safely administered on an outpatient basis for prolonged period of time and has moderate, reversible toxicity. Its administration induces IL-6-antibody production in only a minority of patients. Antitmour effects of rhIL-6 in metastatic renal cancer are limited.
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PMID:Recombinant human interleukin 6 in metastatic renal cell cancer: a phase II trial. 861 81

Fifty-one patients with histologically confirmed epithelial stage III or IV ovarian cancer were entered into a study in which gemcitabine 800 mg/m2 was given as a 30 min intravenous infusion in a cycle once a week for 3 weeks followed by a week of rest. Patients were aged 58 years (range 23-70 years) with WHO performance status 0-2, and had received up to two different chemotherapy regimens. Thirty-eight patients had received only one prior platinum-containing chemotherapy regimen whereas 9 had received a first-line regimen on more than one occasion. A further 3 patients had received two different regimens. Of 42 patients evaluable for response, 8 (19%; 95% CI: 9%-34%) were partial responders. Seven of the 8 responders were resistant to first-line platinum-based therapy. Median duration of response was 8.1 months (range 4.4-12.5 months). Median progression-free survival was 2.8 months (range 0.2-12.5 months). Haematological toxicity with gemcitabine was modest, with grade 3 leukopenia (11 patients) and grades 3 and 4 thrombocytopenia (6 patients). Grade 3 non-haematological toxicity included nausea/vomiting (6 patients) and elevated AST/ALT (1 patient), while dose-limiting non-haematologic toxicity consisted of flu-like symptoms (2 patients), peripheral oedema (1 patient) and lethargy (1 patient). The activity and modest haematological and non-haematological toxicity seen with gemcitabine suggest that this agent should be further evaluated in the treatment of patients with ovarian cancer and in combination chemotherapy regimens, primarily in combination with platinum.
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PMID:Phase II study of gemcitabine in previously platinum-treated ovarian cancer patients. 871 27

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

Botulinum toxin has become the initial treatment of choice for the management of essential blepharospasm, hemifacial spasm and other craniocervical dystonias. Numerous studies have confirmed a 90% to 95% response rate. Although a number of common side effects have been reported, the occurrence and incidence of rare local complications remains poorly understood. More importantly, the acute and chronic distant effects of botulinum toxin have not been clearly elucidated. A better understanding of such effects is essential if clinicians are to appropriately advise patients on the use of this therapeutic modality. This article is based on the Duke University experience in the management of over 500 patients with craniocervical spasm disorders, combined with a review of the published literature. These disorders include essential blepharospasm, oromandibular dystonia, hemifacial spasm, and torticollis. The incidence of side effects following more than 6000 treatments with botulinum toxin is presented. Pertinent research relating to the causes of these complications is also reviewed. The most common complications of treatment with botulinum toxin are related to acute local effects resulting from chemodenervation. The most important clinical effect in this group is weakening of the levator muscle resulting in ptosis, and the corneal consequences of lagophthalmos. The latter includes exposure keratitis, dry eyes, blurred vision, and hypersecretion epiphora. Less common local effects include facial numbness, diplopia, and ectropion. Some distant effects are being observed with increasing frequency. These include pruritus, dysphagia, nausea, and a flu-like syndrome. Most significant, however, are the rare reports of generalized weakness and the documentation of EMG abnormalities distant to the site of toxin injection. This has been seen with injections for both blepharospasm and torticollis. Until further studies on the long-term distant complications of botulinum toxin are available, it is recommended that patients receive as few life-time doses of toxin as possible, consistent with adequate management of their spasms. The practice of reinjecting patients routinely every three months, or at the first return of mild spasms should be discouraged.
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PMID:Botulinum-A toxin in the treatment of craniocervical muscle spasms: short- and long-term, local and systemic effects. 882 30

An outbreak of diarrhea due to infection with Cryptosporidium occurred among the staff members and customers who visited one of the 10 public houses or a dancing school in a building in Hiratsuka, Kanagawa Prefecture, at the end of summer in 1994. The epidemiological surveys by a questionnaire revealed that 461 out of 736 persons investigated complained of cholera-like or flu-like illness. The clinical manifestations included mucous and/or watery diarrhea (96.7%), abdominal pain (61.6%), fever (54.2%: lower than 39 degrees C = 84.1%, higher than 39 degrees C = 15.9%), malaise (37.1%), nausea (32.8%) and headache (29.3%). The polluted drinking water was strongly suspected to be the immediate cause of infection. Although several species of pathogenic bacteria were isolated both from stool and water samples, they were not supposed to be linked to the outbreak. No known enteropathogenic virus was found in either of the samples. Oocysts of Cryptosporidium parvum were identified in 12 (48.0%) of the 25 stool samples. The oocysts were also found in tap water and other water samples from a receiving tank which was directly connected with the public waterworks, and an elevated tank on the roof, a wastewater pits, a soil pit and artesianspring water tank. These tanks and pits except for the elevated tank were built adjucent to each other on an underground floor of the building. These tanks and pits were connected with openings in the upperpart of the tank walls. These openings might have functioned to discharge excess of drinking water in the receiving tank to the wastewater pit. The water level of the wastewater pit is kept down below the openings by pumping out the sanitary sewage to the public drain. According to the declaration of the owner of the building, however, the wastewater pump was broken at the time of outbreak. Accidental malfunction of the drainage system caused contamination of drinking water with sanitary sewage through the connecting pipes.
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PMID:[An outbreak of waterborne Cryptosporidiosis in Kanagawa, Japan]. 885 85

Imiquimod is an orally active interferon inducer with anti-tumour activity in experimental animals. In this study the tolerability, toxicity and biological effects of daily oral imiquimod administration were investigated in 21 patients with refractory cancer. Patients were treated with doses of 25 mg, 50 mg, 100 mg or 200 mg on a projected 112 day course. Only three patients completed the course, all at the 50 mg dose. Treatment toxicities were dose related and mainly comprised flu-like symptoms, nausea and lymphopenia. Of the 21 patients, five received dose reductions and in five treatment was discontinued because of treatment-related toxicity. The biological activity of imiquimod was confirmed by significant and sustained rises in peripheral blood mononuclear cell (PBMC) 2-5A synthetase (2-5AS) levels at all doses. At 100 mg and 200 mg these occurred within the first 24 h of administration. Levels of neopterin and beta 2-microglobulin (beta 2M) were also significantly elevated when assessed after three weeks' treatment. Interferon production was not demonstrated within the first 24 h of the initial dose but, following repeated doses, ten of the patients developed detectable serum interferon concentrations with a maximum value of 5600 IU ml-1 recorded. Administration of imiquimod did not have any significant effect on serum levels of tumour necrosis factor (TNF) or interleukin 1 (IL-1), nor did it lead to development of detectable levels of antibodies to interferon. One mixed clinical response was observed after 4 weeks' treatment at 100 mg in a patient with renal cell cancer. Daily administration of imiquimod causes activation of the interferon production system but at higher doses results in unacceptable toxicity. Further investigation of imiquimod as an interferon-inducing agent in cancer patients is suggested at either the lower dose levels or employing alternative dosing schedules.
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PMID:A phase I clinical trial of imiquimod, an oral interferon inducer, administered daily. 891 49

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


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