Gene/Protein Disease Symptom Drug Enzyme Compound
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 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper presents clinical data on 41 patients (29 male and 12 female) from Haiti who presented with acquired immunedeficiency syndrome (AIDS). Their mean age was 32 years (range 17-61 years). 4 of thes cases were homosexual or bisexual; none was an illicit drug user or a hemophiliac. In addition, 3 of the female patients had sexual contact with a male partner with AIDS. 4 patients had received blood transfusions before their illness. The most prominent clinical symptom in this series was chronic diarrhea of 2-33 months' duration, which occurrred in 39 patients (95%). Also reporte were marked weight loss (95%), fatigue (95%), prolonger fever (90%), and nodular or maculopapular skin lesions (54%). Opportunistic infections in this series included oroesophageal candidiasis (88%) and intestinal cryptosporidiosis (31%). Tuberculosis developed in 22% of patients. Immunologic evaluation revealed profoundly depressed T-helper cells and an inverted T-helper/T-suppressor cell ratio. Biologic markers included elevated alpha-1 thymosin and beta-2 microglobulin levels, elevated immune complexes, and the presence of acid-labile interferon. Of interest were differences in the clinical expression of AIDS between this series and cases in the US. The Haitian data suggest a higher incidencs of female cases,a predominance of gastrointestinal symptoms rather than respiratory symptoms and lymphadenopathy, a frequent association with tuberculosis, and a relatively low incidence of Kaposi's sarcoma or P. carinii pneumonia compared to the situation in the US. As in the US, where most AIDS cases are concentrated in New York and California, most AIDS cases in Haiti are found in residents of Port-au-Prince and Carrefour, which are centers for male and female prostitution.
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PMID:Acquired immune deficiency syndrome: specific aspects of the disease in Haiti. 639 48

Measurement of health-related quality of life was integrated into a randomized trial (NMSG 4/90) comparing melphalan/prednisone to melphalan/prednisone + interferon alpha-2b in newly diagnosed multiple myeloma. One of the aims of the study was to assess the prognostic significance of quality-of-life scores, using the EORTC QLQ-C30 questionnaire. Univariate analysis showed a highly significant association with survival from the start of therapy for physical functioning as well as role and cognitive functioning, global quality of life, fatigue and pain. In multivariate analysis, physical functioning and W.H.O. performance status were independent prognostic factors (P values = 0.001 for both) when analysed in a Cox regression model with the somatic variables beta-2 microglobulin, skeletal disease and age. The best prediction for survival from the start of therapy was obtained by combining the beta-2 microglobulin and physical functioning scores in a variable consisting of three risk factor levels with an estimated median survival of 17, 29 and 49 months, respectively. At a 12 months landmark analysis, the relative risk for patients with physical functioning score 0-20 v 80-100 was 5.63 (99% CI 2.76-11.49), whereas the relative risk for patients without an objective response to chemotherapy compared to those with at least a minor response was 2.32 (99% CI 1.44-3.74). Quality-of-life assessment may be an independent and valuable addition to the known prognostic factors in multiple myeloma.
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PMID:Health-related quality of life assessed before and during chemotherapy predicts for survival in multiple myeloma. Nordic Myeloma Study Group. 913 39

To evaluate the safety, toxicity, and maximum tolerated dose (MTD) of IFN beta-1a (Rebif, Serono Laboratories, Inc.) in patients with malignant diseases unresponsive to standard therapies and to assess the pharmacodynamics and pharmacokinetics associated with IFN beta-1a administration, an open-label, single-center phase I study was designed. Thirty-four patients were enrolled and treated with IFN beta-1a. All had measurable solid neoplasms or evaluable hematological malignancies. All patients received a single i.v. bolus dose of IFN-beta-1a on day 1, followed 7 days later by daily s.c. injections for 28 consecutive days. Successive groups of three patients received increasingly higher doses (in geometric progression from 1.5 million international units (MIU)/m2 to 24 MIU/m2) until dose-limiting toxicities were noted. Pharmacokinetic and biological studies, including measurement of the activity of 2',5'-oligoadenylate synthetase (2',5'-OAS) in peripheral blood mononuclear cells and serum levels of soluble Tac (CD 25) and beta-2 microglobulin, were performed on patients who agreed to participate. i.v. and s.c. doses of IFN beta-1a up to 24 MIU/m2 were administered. The most frequent adverse events (AEs) were constitutional symptoms. Grade III AEs during i.v. dosing included fever, elevation of bilirubin, and infection unrelated to therapy. No grade IV events were seen. AEs noted during continuous s.c. therapy included fever, liver transaminase increase, albuminuria, fatigue, nausea, myalgia, and rigors. Dose-limiting toxicities were encountered during s.c. dosing at the 24-MIU/m2 and 18-MIU/m2 dose levels and included gastrointestinal toxicity, elevations of aspartate aminotransferase and alanine aminotransferase, and albuminuria. The s.c. MTD was determined to be 12 MIU/m2, although there was great variability in the individual patient's ability to tolerate IFN beta-1a. 2',5'-OAS activity, thought to be indicative of IFN activity, increased within hours after i.v. and s.c. dosing, with the level remaining persistently elevated during the s.c. daily injections. The highest peak level was attained in the 6-MIU/m2 group. There was no evidence that the increase in 2',5'-OAS activity decayed with repetitive dosing, nor was there evidence of accumulation in this pharmacodynamic marker. Serum beta-2-microglobulin levels showed a modest time- and dose-dependent increase after s.c. administration of IFN beta-1a, with the largest increase seen at the 24-MIU/m2 dose level. There were no clear dose-dependent responses noted in soluble Tac serum levels. IFN beta-1a was well-tolerated when administered by a single i.v. bolus injection at doses up to and including 24 MIU/m2. Daily s.c. injections for at least 28 days were well-tolerated at doses up to and including 12 MIU/m2, with some patients tolerating doses twice as high as this. The MTD for the i.v. route could not be clearly determined according to the guidelines of the protocol. However, i.v. bolus doses up to 24 MIU/m2 were relatively well-tolerated. For the s.c. route, the MTD was determined to be 12 MIU/m2, but there was great interpatient variability, with some patients able to tolerate higher doses.
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PMID:A phase I study of recombinant interferon-beta in patients with advanced malignant disease. 1063 30

There is no simple way to prescribe hemodialysis. Changes in the dialysis population, improvements in dialysis techniques, and different attitudes towards the initiation of dialysis have influenced treatment goals and, consequently, dialysis prescription. However, in clinical practice prescription of dialysis still often follows a "one size fits all" rule, and there is no agreed distinction between treatment goals for the younger, lower-risk population, and for older, high comorbidity patients. In the younger dialysis population, efficiency is our main goal, as assessed by the demonstrated close relationship between depuration (tested by kinetic adequacy) and survival. In the ageing dialysis population, tolerance is probably a better objective: "good dialysis" should allow the patient to attain a stable metabolic balance with minimal dialysis-related morbidity. We would like therefore to open the discussion on a personalized approach to dialysis prescription, focused on efficiency in younger patients and on tolerance in older ones, based on life expectancy, comorbidity, residual kidney function, and nutritional status, with particular attention placed on elderly, high-comorbidity populations, such as the ones presently treated in most European centers. Prescription of dialysis includes reaching decisions on the following elements: dialysis modality (hemodialysis (HD) or hemodiafiltration (HDF)); type of membrane (permeability, surface); and the frequency and duration of sessions. Blood and dialysate flow, anticoagulation, and reinfusion (in HDF) are also briefly discussed. The approach described in this concept paper was developed considering the following items: nutritional markers and integrated scores (albumin, pre-albumin, cholesterol; body size, Body Mass Index (BMI), Malnutrition Inflammation Score (MIS), and Subjective Global Assessment (SGA)); life expectancy (age, comorbidity (Charlson Index), and dialysis vintage); kinetic goals (Kt/V, normalized protein catabolic rate (n-PCR), calcium phosphate, parathyroid hormone (PTH), beta-2 microglobulin); technical aspects including vascular access (fistula versus catheter, degree of functionality); residual kidney function and weight gain; and dialysis tolerance (intradialytic hypotension, post-dialysis fatigue, and subjective evaluation of the effect of dialysis on quality of life). In the era of personalized medicine, we hope the approach described in this concept paper, which requires validation but has the merit of providing innovation, may be a first step towards raising attention on this issue and will be of help in guiding dialysis choices that exploit the extraordinary potential of the present dialysis "menu".
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PMID:Prescribing Hemodialysis or Hemodiafiltration: When One Size Does Not Fit All the Proposal of a Personalized Approach Based on Comorbidity and Nutritional Status. 3029 28