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Biomedical subjects

R Fife

Publications and source records attributed to R Fife.

14 recordsLinked to original sources
PubMed2001

Results of a phase-I/II randomized, masked, placebo-controlled trial of recombinant human interleukin-11 (rhIL-11) in the treatment of subjects with active rheumatoid arthritis.

Interleukin-11 (IL-11) is a pleiotropic cytokine that regulates the growth and development of hematopoietic stem cells and decreases the proinflammatory mediators of cytokine and nitric oxide production. In animal models of arthritis, treatment with recombinant human IL-11 (rhIL-11) reduces both the level of synovitis and the histologic lesion scores in the joints. The goal of this phase-I/II study in adults with rheumatoid arthritis (RA) was to evaluate the safety and clinical activity of different doses and schedules of rhIL-11 in patients with active RA for whom treatment with at least one disease-modifying antirheumatic drug had failed. This was a multicenter, randomized, placebo-controlled trial that evaluated the safety and tolerability of rhIL-11 in 91 patients with active RA. rhIL-11 was administered subcutaneously; patients were randomized into one of five treatment groups (ratio of rhIL-11 to placebo, 4:1). Patients were treated for 12 weeks with either 2.5 or 7.5 microg/kg of rhIL-11 or placebo twice per week or 5 or 15 microg/kg of rhIL-11 or placebo once per week. The status of each subject's disease activity in accordance with the American College of Rheumatology (ACR) criteria was assessed before, during, and after completion of administration of the study drug. Administration of rhIL-11 was well tolerated at all doses and schedules. The most frequent adverse event was a reaction at the injection site. The data suggest a statistically significant reduction in the number of tender joints (P < 0.008) at the 15 microg/kg once-weekly dose schedule but showed no overall significant benefit at the ACR criterion of a 20% response. The trial showed rhIL-11 to be safe and well tolerated at a variety of doses and schedules over a 12-week treatment period in patients with active RA. The only adverse event clearly associated with rhIL-11 administration was reaction at the injection site.

Adult↗
PubMed1996

Effects of functional electrical stimulation on the joints of adolescents with spinal cord injury.

Nineteen adolescent subjects with complete spinal cord injuries resulting in paraplegia or tetraplegia participated in a functional electrical stimulation (FES) program consisting of computerized, controlled exercise and/or weight bearing. The effects of stimulated exercise and standing/walking on the lower extremity joints were prospectively studied. Plain radiographs and MRIs were obtained prior to and following completion of the exercise and standing and walking stages. In addition, the joints of five subjects were studied with synovial biopsies, arthroscopy, and the analysis of serum and synovial fluid for a 550 000 dalton cartilage matrix glycoprotein (CMGP). Pre-exercise joint abnormalities secondary to the spinal cord injury improved following the stimulation program. None of the subjects developed Charcot joint changes. Upon standing with FES, one subject with poor hip coverage prior to participation developed hip subluxation which required surgical repair. No other detrimental clinical effects occurred in the lower extremity joints of subjects participating in an FES program over a 1-year period.

Adolescent↗
PubMed1995

Effect of matrix metalloproteinase inhibitor batimastat on breast cancer regrowth and metastasis in athymic mice.

BACKGROUND: Matrix metalloproteinases (MMPs) are involved in the invasion and metastasis of human cancers by mediating the degradation of extracellular matrix components. Therefore, these enzymes constitute promising targets in the development of anticancer therapies. Batimastat ([(4-N-hydroxyamino)-2R-isobutyl-3S-(thienyl-thiomethyl)succinyl]-L- phenyl-alanine-N-methylamide) is one of a new class of agents designed to inhibit MMP activity. PURPOSE: We asked whether batimastat, given as adjuvant therapy after primary tumor resection, could inhibit local-regional tumor regrowth and the formation of lung metastases in a human breast cancer xenograft model. We also explored possible effects of batimastat on breast cancer cell viability and on the accumulation of specific messenger RNAs (mRNAs). METHODS: Human MDA-MB-435 breast cancer cells were treated in vitro for 6 days with batimastat at concentrations ranging from 0.1 to 10.0 microM, and then viable cell counts were performed. The activity of collagenases, directly associated with cultured MDA-MB-435 cells or released into their culture fluids, was assessed by gelatin zymography after 1 and 3 days of batimastat treatment (drug range, 0.2-2.0 microM). Athymic nude mice were given daily intraperitoneal injections of batimastat (30 mg/kg body weight) after resection of MDA-MB-435 primary tumors grown in their mammary fat pads; the volumes of tumor regrowths and the numbers and volumes of lung metastases were calculated; neovascularization in the regrowths was assessed by immunohistochemical analysis with an antibody directed against CD31, an endothelial cell antigen. The effect of batimastat treatment on the accumulation of mRNAs encoding specific MMPs and the tissue inhibitor of metalloproteinases-2 (TIMP-2) in cultured cells, primary tumors, and tumor regrowths was measured by RNA dot blotting and hybridization with complementary probes. Linear regression analysis, Student's t tests, and chi-squared analysis were used to evaluate the data. RESULTS: The viability of cultured MDA-MB-435 cells was not affected by treatment with batimastat; however, measured activities for the 72-kd and 92-kd collagenases released by these cells were reduced after batimastat treatment. Intraperitoneal injection of batimastat significantly inhibited the local-regional regrowth of resected MDA-MB-435 tumors in athymic nude mice (in comparison with control mice, P = .035), and it reduced the incidence (P < .05), number (P = .0001), and total volume (P = .0001) of lung metastases. Batimastat treatment did not affect cellular levels of MMP or TIMP-2 mRNAs. CONCLUSION: Batimastat inhibits human breast cancer regrowth and metastasis in a nude mouse xenograft model. Potential mechanisms for batimastat's inhibitory activity do not include direct cell toxicity or alteration of MMP or TIMP mRNA levels.

Animals↗
PubMed1985

Alexander's disease.

This is the first pathologic report of an infant at 37 weeks' gestation with Alexander's disease. The findings demonstrate that the disease can arise in utero and be extensive at birth before myelination begins.

Adult↗
PubMed1981

Minoxidil in the management of intractable hypertension.

Eighty-seven patients with intractable hypertension received minoxidil for a mean duration of 27 months (range three months to five years). A significant reduction in mean outpatient blood pressure from 206/129 to 158/98 mmHg (p less than 0.001 for both systolic and diastolic values) was recorded after one month's treatment. In 26 patients who received minoxidil for four or more years a further reduction in mean blood pressure to 147/89 mmHg was achieved. The mean daily dose of minoxidil was 23 mg (range 2.5 to 60 mg). In all patients a beta adrenergic neurone blocker and a diuretic were prescribed with minoxidil to counteract tachycardia and fluid retention. Thirteen patients required the addition of a fourth hypotensive agent. The use of minoxidil led to simpler drug regimens with the majority of patients well controlled on twice daily or once daily schedules. Most patients commented spontaneously on a feeling of improved wellbeing while taking minoxidil which also appeared to be relatively free from side effects commonly encountered with other hypotensive drugs, particularly drowsiness, dizziness and impotence. Fluid retention of 7 kg or more occurred in 18 patients, more commonly in those with renal impairment, but could be controlled by increasing the dose or potency of diuretics. Four patients with end stage renal failure and one patient with normal renal function developed pericardial effusions. Hirsutism was universal and limited the usefulness of the drug in women. We currently recommend minoxidil for hypertensive men who diastolic blood pressure remains greater than or equal to 110 mmHg despite an adequate trial of a beta adrenergic neurone blocker, diuretic and an additional drug, or for patients who find the side effects of such therapy intolerable.

Adolescent↗
PubMed1980

Control of hypertension in out-patients. Experience of the Glasgow Blood Pressure Clinic.

Five hundred and sixty-two patients who had attended the Glasgow Blood Pressure Clinic regularly for 3 years between 1969 and 1978 were studied. The mean BPs for the group were 187/115 mmHg initially, 157/100 mmHg after 6 months, and 153/98 mmHg after 3 years. Twenty-eight per cent had 'normal' systolic pressure and 22% 'normal' diastolic pressure at 3 years. Thirty-seven per cent with mild, 83% with moderate, and 89% with severe systolic pressure elevation had moved into less severe categories by 3 years, as had 30% with mild, 60% with moderate and 84% with severe diastolic evaluation. Those patients with severe hypertension, who did not attain a less grade, had a statistically significant drop in pressure. Four per cent of all patients, however, had moved into a more severe severe grade of systolic pressure evaluation and 6% into a more more severe diastolic pressure grade at 3 years. These results suggest that the hospital Hypertension Clinic can play a useful part in the lowering of BP in out-patients. It is clear, however, that 'normal' BP levels are not achieved in a significant proportion of patients.

Adolescent↗
PubMed1979

Blood-pressure screening and supervision in general practice.

Since April 1975 all men aged 35-69 years registered with four general practices in west central Scotland have had their blood pressure checked whenever they visit the surgery. Although the practice locations range from rural to city centre and observers comprise receptionists, nurses, and doctors, a standard procedure has been adopted for the examination, recording, follow-up, and management of high blood pressure. The results confirm that raised blood pressure is common and often goes undetected. Even when hypertension is known, casual blood pressure readings often exceed accepted normal levels. The findings also show that a population may be routinely examined through normal contact with the family doctor, and that this can provide a convenient, acceptable, and effective means of detecting and reducing raised blood pressure.

Adult↗
PubMed1978

Interrelation of age, obesity, cigarette smoking, and blood pressure in hypertensive patients.

The relations between age, obesity, cigarette smoking, and blood pressure were investigated in 637 men and 835 women who had attended the Glasgow Blood Pressure Clinic with untreated hypertension. In contrast to results of population surveys of mainly normotensive people no relation was found between cigarette consumption and either systolic or diastolic blood pressure. Moreover, contrary to results of epidemiological studies a relation between adiposity and blood pressure was found in only male non-smokers. Thus the relations established for largely normotensive populations do not apply to hypertensive patients.

Adult↗
PubMed1978

Benzothiadazine diuretics and death from myocardial infarction in hypertension.

1. Case records were examined of 66 patients who died while being treated for high blood pressure. 2. The possibility that benzothiadazine diuretics may have some deleterious as well as beneficial effects was investigated. 3. It is possible that the thiazides may have some adverse clinical effects, at least in females, with regard to the incidence of myocardial infarction in hypertensive patients.

Adult↗
PubMed1977

Minoxidil for severe hypertension after failure of other hypotensive drugs.

Forty-four patients with severe hypertension who were resistant to treatment with more conventional hypotensive drugs or could not tolerate the side effects were treated with minoxidil, a potent peripheral vasodilator. A beta-blocking drug and a diuretic were used routinely to control, respectively, the tachycardia and fluid retention caused by minoxidil. During treatment the outpatient supine blood pressure fell from a mean of 221/134 mm Hg to 162/98 mm Hg. Eleven patients required additional or alternative hypotensive agents before blood pressure was adequately controlled. Side effects were minor, although the invariable hirsuties caused by minoxidil was unacceptable to three women. The possibility of cardiotoxic effects, raised by early studies in dogs, has not been excluded, and therefore this drug should be used only in patients with severe hypertension. In such patients minoxidil appears to be most effective.

Adult↗
PubMed1975

Malignant hypertension associated with use of oral contraceptives.

A 26-year-old woman who had been taking an oral contraceptive preparation for two years developed malignant hypertension. Investigation failed to elicit any renal or other cause for her hypertension, but control of blood pressure was obtained by withdrawal of the oral contraceptive agent and antihypertensive therapy. Subsequently, after withdrawal of therapy, the blood pressure remained near normal. The patient had a previous history of hypertension during pregnancy; she was also overweight.

Adult↗
PubMed1975

Early results of heart valve replacement with the Björk-Shiley prosthesis.

The operation on and subsequent course of 88 patients with valve replacements using Björk-Shiley tilting disc prostheses has been reviewed in terms of mortality, clinical results, and valve function. The follow-up period varied between 6 months and 2 years. The hospital mortality was 17% and late mortality 8%. Of those who left hospital, 75% returned to full normal activity and required less (or no) drug therapy other than maintenance anticoagulation. There was one transient embolic episode. Significant intravascular haemolysis does not occur with this prosthesis.

Adult↗
PubMedDate not supplied

Fetal monitoring.

Explore the source record for details and available documents.

Female↗