Biomedical subjects
A Freeman
Publications and source records attributed to A Freeman.
FDA's new bureau of veterinary medicine.
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Wormy eyes: a veterinary public health problem.
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Measurement of retinal artery blood pressure during anesthesia in children.
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Diabetes in patients treated with asparaginase.
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Multicentre double-blind study of effect of intrathecally administered natural human fibroblast interferon on exacerbations of multiple sclerosis.
In this randomised, double-blind, placebo-controlled, 2-year multicentre study intrathecally administered natural human fibroblast interferon (IFN-B) was effective in reducing exacerbations of multiple sclerosis (MS) in patients with exacerbating/remitting disease. The mean reduction in exacerbation rate of 34 patients who received IFN-B (recipients) was significantly greater during the study than that of 35 patients who received placebo (p less than 0.04). The prestudy exacerbation rates were comparable in recipients and controls, but the rate at the end of the study was significantly lower in recipients than in controls (p less than 0.001). IFN-B was given by nine or ten lumbar punctures over the first 6 months of the study, and patient observations continued for 2 years. IFN-B was well tolerated in 95% of the recipients, and the side-effects experienced were clearly acceptable for the benefits achieved. Low doses of indomethacin reduced the toxicity of IFN-B and played an important role in successful double-blinding.
An entrapped epidural catheter in a postpartum patient.
BACKGROUND AND OBJECTIVES: Epidural catheters are seldom difficult to remove from patients. In fact, a review of the literature demonstrates only a few cases pertaining to epidurals and the unusual complication of catheter entrapment. METHODS: This case report involves an uncomplicated obstetric patient who had an epidural placed for labor and in whom multiple attempts were needed to remove the catheter.
Biologic factors and response to radiotherapy in carcinoma of the cervix.
Ionizing radiation has been used to treat cancers for a century. However, radioresistance remains a major problem in the clinic. Recent advances in the understanding of the molecular events that occur following ionizing radiation leading to DNA damage and repair, apoptosis, and cell cycle arrests suggest new ways in which the radiation response might be manipulated. Seventy-eight cases of carcinoma of the cervix of the same stage (II A and B) were analyzed retrospectively. All patients were treated with radiotherapy (RT) with a dose varying from 35 Gy to 50 Gy with 200 cGy per fraction. Subsequent to the completion of radiotherapy, all patients underwent surgery 4-6 weeks later. On histological examination of the surgical specimens, 51% of the cases (40) showed a complete response to therapy with no viable tumor cells. 49% of cases (38) had residual tumors ranging from a small focus to lesions extending through more than half the thickness of the cervical wall. p53 (mutant), bcl-2, p21 and bax proteins were studied on the paraffin sections of the biopsies (pretreatment) of those patients who failed to respond to RT and compared to similar studies on biopsies of patients who had a complete response to RT. In addition, the minichromosome maintenance (MCM) 2 proliferative marker was also done on all cases. Expression of all proteins was done using immunohistochemsitry. In the radioresistant cases, 15% (six cases) showed positivity for bcl-2 and p21, respectively, and 34% (13 cases) showed mutant p53. None of the radiosensitive tumors were positive for the above proteins. 75% of the radiosensitive tumors (30 cases) were positive for the bax antibody, whereas 81% of the radioresistant tumors (31 cases) were negative for bax. The MCM2 proliferative marker was positive in > 80% of cells in 81.5% of radioresistant tumors (31 cases) as compared to < 40% of cells that were positive in 70% of radiosensitive tumors (28 cases). The P-value for the biological markers was calculated using the chi-squared test, and was highly significant (P < 0.01) for all the parameters tested. However, there was no statistical significance by univariate analysis when the dose of radiation was analyzed with respect to the markers and the histological response. There was also no correlation between the radiation response and timing of surgery. The above data strongly suggest that bax, along with proliferative markers, could play a role in determining which tumors are likely to respond to radiation therapy. The presence of bcl-2, p21 and p53 could also be related to radioresistance of the tumors.
Applications of pharmacogenetics to drug development: the Glaxo Wellcome experience.
The Genetics Directorate was established at Glaxo Wellcome (GW) in 1997. The goals of the Directorate are to identify susceptibility genes for common diseases with large unmet therapeutic need, apply genetic methods for the targeted development of medicines so that the right medicine is developed for the right patient, assist in translating gene discoveries into target selection, and represent genetics accurately internally within GW and externally (to laypersons, the medical community, the business community, government representatives, and regulatory agencies). As part of the goal of developing the right medication for the right patient, GW has added genetic research to its clinical drug studies in every major therapeutic area. GW worked closely with international ethicists experienced in the area of genetic research to develop the process and documents that are currently in use; these undergo frequent, rigorous review in light of the changing regulatory and legal environment and the needs of clinical investigators and patients. The addition of genetic research to clinical studies was accompanied by significant education efforts within GW and for study-site personnel, ethics committees, and regulatory authorities. Feedback from all those involved is an integral part of implementing GW's genetic research and is used to fine-tune the processes and protocol and consent document templates. A recently completed review of the approval rate from ethics committees in several countries has revealed trends in EC/IRB (Ethics Committees/Institutional Review Boards) questions and concerns about genetic research. This article will focus on the lessons learned from incorporating genetic research into clinical studies at over 1,500 international sites and will include summaries of the feedback from investigators, EC/IRBs, and regulatory authorities. It also will include a discussion of the potential applications of SNP (single nucleotide polymorphism) map technologies to pharmacogenetics by increasing the ability to correlate patients' genetic information with their response to medicines.
Psychiatric education improves internists' knowledge: a three-year randomized, controlled evaluation.
Trainees were randomized into four groups: (1) control; (2) consult; (3) liaison; or (4) consult-plus-liaison to evaluate the psychiatric knowledge gained after two different training programs for primary care residents. Consult was a 1-month rotation on the Psychiatry Consultation Service. Liaison consisted of 31-hour workshops over 1 year. Consult-plus-Liaison refers to both training programs, experienced in consecutive years. An oral examination was administered before and after training. The analysis of variance and tests of simple effects revealed significant training effects for both groups. The effect size of training was greater for residents exposed to both programs, compared with either one alone. The two different training programs were both effective in improving the psychiatric knowledge of primary care residents and exposure to both programs proved superior to either one alone.
Clinical dose-response studies with guanfacine (BS 100-141), a new antihypertensive agent.
1. Blood pressure, pulse rate, salivary flow and the degree of sedation were recorded at intervals following oral administration of single doses of guanfacine, a clonidine-like agent, to hypertensive patients. 2. Between 2 and 10 h after administration of guanfacine (3 mg or 5 mg), there were dose-related decrease in lying and standing blood pressure, together with significant reductions in pulse rate and salivary flow. 3. It is concluded that guanfacine lowers blood pressure in hypertensive patients and is probably suitable for twice daily administration, but produces xerostomia and sedation.
Levels of lipid peroxidation products in a chronic inflammatory disorder.
We have examined the plasma levels of the lipid peroxidation products 4-hydroxy-nonenal and malondialdehyde in a carefully controlled study of age and sex-matched subjects with rheumatoid arthritis in whom potentially confounding influences such as disease modifying anti-rheumatic drugs (DMARDs), self-medication and vitamin supplements were eliminated. The plasma concentrations of the antioxidants uric acid and vitamin E were also measured. The results reveal a strong and consistent inverse correlation between the levels of lipid peroxidation products in the plasma and erythrocyte sedimentation rate (ESR). There is no indication that vitamin E or urate function as the major antioxidant agent in arthritis, as has been suggested in more seriously affected patients. It is concluded that there is no evidence that vitamin E is more important, and urate less important as an antioxidant in mild arthritis. The correlation between lipid peroxidation and ESR suggests a more complex relationship than has been assumed.
Staff development program for critical care nurses.
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