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Biomedical subjects

L Davis

Publications and source records attributed to L Davis.

At least 37 records · Page 2Linked to original sources

Systemic administration of new therapeutic radioisotopes, including phosphorus, strontium, samarium, and rhenium.

New advances in systemic radionuclide therapy have increased the number of treatment options available for patients with painful osseous metastases. This form of therapy has three major appeals: 1) it addresses all sites of involvement; 2) selective absorption into bone limits irradiation of normal tissues; and 3) as a result, toxicity may be reduced and the therapeutic ratio improved. The clinical experience with radioactive phosphorus, strontium, samarium, and rhenium are reviewed. To date, the best studied and the only Food and Drug Administration approved agent is strontium-89. About 60% to 90% of patients treated with strontium-89 respond with complete or partial relief of pain for a median duration of 6 months. Large, prospectively randomized clinical trials have established the efficacy of strontium-89 as a first-line therapy and as an adjuvant to external-beam radiotherapy. Particularly advantageous is its usefulness in situations in which external-beam radiotherapy options have been exhausted and normal tissue tolerance has been reached. Newer radiopharmaceuticals are still under investigation.

Bone Neoplasms

Cisplatin: a clinical review. Part II--Nursing assessment and management of side effects of cisplatin.

Cisplatin is one of the most active cancer treatment agents available. Unfortunately, however, cisplatin causes many untoward side effects. Nurses play a major role in administering cisplatin and in preventing and managing the adverse effects associated with this drug. In order to maximize the quality of life of patients undergoing cisplatin treatment, nurses need a thorough knowledge of its uses, administration, and side effects. This article is the second of a two-part series about cisplatin. Part I provided a review of the mechanism of action, current uses, and administration guidelines. Part II discusses the most common side effects of cisplatin and the appropriate nursing assessment and management of patients undergoing treatment with this agent. In addition, future directions for the use of cisplatin and the use of alternative agents will be discussed.

Cisplatin

Phase I/II trial of accelerated fractionation in brain metastases RTOG 85-28.

PURPOSE: Radiation Therapy Oncology Group 85-28 represents a Phase I/II trial of accelerated fractionation in patients with brain metastases. METHODS AND MATERIALS: Patients entered had controlled or absent primary with metastases other than brain which were stable or only brain metastases with the primary uncontrolled. Karnosfky status was required to be greater than 60. Patients received 1.6 Gy twice daily separated by 4-8 hr delivered 5 days a week. The entire brain was treated to 32.0 Gy and the boost dose escalated from 16.0 Gy to 22.40 Gy and subsequently 32.00 Gy and 42.40 Gy. RESULTS: We observed no undue toxicity with escalating dose of irradiation. An incremental, although not statistically significant improvement in survival was noted with escalating doses. Median survival ranged from 4.2 months to 6.4 months with escalating dose of irradiation. Median survival also increased in patients with controlled primary tumors, non-lung primaries and solitary metastasis. CONCLUSION: The incremental improvement in survival in patients with good prognostic factors appeared encouraging. The Radiation Therapy Oncology Group will test the 54.4 Gy study against 30 Gy in 2 weeks in a Phase III trial based on the results of this trial.

Adult

Cofactor identification of threonine-serine dehydratase from sheep liver.

L-Threonine-serine dehydratase catalyzes the conversion of L-threonine and L-serine to alpha-ketobutyric acid and pyruvate, respectively. The enzyme has been purified to homogeneity from extracts of sheep liver. In the past, various cofactors have been suggested for threonine dehydratase from both prokaryotic and eukaryotic tissue. While some direct evidence for the presence of pyriodoxal 5'-phosphate in impure preparations is present in the literature no direct evidence for the cofactor in homogeneous dehydrogenase from mammalian tissue has been reported. The threonine dehydratase of sheep liver has been obtained in a homogeneous form and a spectral study provides clear evidence for the presence of pyridoxal 5'-phosphate. Both the physical properties of homogeneous threonine dehydratase and a study of spectral properties of its cofactor are reported in this communication.

Amino Acids

In vitro Ca deposition by rat matrix vesicles: is the membrane association of alkaline phosphatase essential for matrix vesicle-mediated calcium deposition?

1. Phosphatidylinositol phospholipase C (PI-PLC) treatment of rachitic rat matrix vesicles (MVs) released about 80% of membrane-bound alkaline phosphatase (ALP), AMPase, PPiase into the media. 2. About 20% hydrolytic activity was not released from MV membranes by PI-PLC treatment. 3. SDS-polyacrylamide gel electrophoresis and Western blot analysis showed only one immunoreactive protein corresponding to the molecular weight of ALP present in the soluble fraction after PI-PLC treatment. 4. The specific activity of the released ALP was at least 5-fold higher than the residual activity. 5. After PI-PLC treatment, MVs also demonstrated an 80% reduction of AMP- or beta GP-dependent calcium deposition. 6. The soluble fraction containing 80% of ALP activity was unable to support calcium deposition. The mixing of the soluble and insoluble fractions after PI-PLC treatment failed to fully restore calcium-depositing activity.

Alkaline Phosphatase

Reversible disassembly of transcription domains in lymphocyte nuclei during inhibition of RNA synthesis by DRB.

We are investigating the roles of RNA synthesis, chromatin structure and nuclear matrix organization in establishing and maintaining transcription domains, using mitogen stimulated lymphocytes as a model system. In a continuing study, the effects of the RNA polymerase inhibitor DRB and of its removal on nuclear organization have been examined by EM cytochemistry and by immunofluorescence labelling of the nuclear matrix PI1, Sm and nucleolar fibrillarin antigens. Chromatin, interchromatin granules and nucleoli were extensively restructured after DRB, as were matrix antigens. According to cytochemical staining properties, the conformation of DRB-induced condensed chromatin resembled that in partially stimulated lymphocytes. The nucleoplasmic fibrogranular RNP network appeared little altered, but the fibrillar proteinaceous interchromatinic regions, interpreted as representing the nuclear matrix in situ, were more affected. After removal of DRB, nuclei recovered the organization and transcriptional activity of controls within 8 h. These results suggest that the matrix subtending transcription domains remains stable when transcription is arrested, even though the chromatin and individual RNP components of the domains are disorganized. The data further indicate that absence of transcription is not solely accountable for the highly aggregated state of the chromatin in resting lymphocytes.

Animals

An approach to training and retaining primary care physicians in rural Appalachia.

The West Virginia School of Osteopathic Medicine (WVSOM) educated and retained more primary care physicians for practice in rural Appalachia than did any other U.S. medical school from 1978 through 1990. This article describes the most important methods used at WVSOM to place physicians in rural areas: (1) The school has a focused, achievable mission (to provide primary care physicians who are trained to meet the medical needs of rural Appalachia and to improve the health care of the rural Appalachian population) that is agreed upon by the administration, faculty, and students; (2) it participates in a multistate educational exchange program with a similar mission; (3) it emphasizes personalized and interactive recruiting, admission, and placement processes aimed to attract nontraditional, rural students; (4) it provides early and long-term clinical training in rural sites (both hospitals and physicians' offices); (5) it is dedicated primarily to the education of medical students rather than to research or other goals; and (6) it is a freestanding school in a rural environment. The authors state that although WVSOM is unusual in some respects, at least some of its methods may be useful to other medical schools as they seek to produce more primary care physicians for rural and other underserved areas.

Appalachian Region

Attempted experimental modification of the postlaminectomy membrane by local instillation of recombinant tissue-plasminogen activator gel.

A prospective, randomized, blinded trial involving 25 adult mongrel dogs was performed to evaluate whether placement of a fat graft or local instillation of recombinant tissue-plasminogen activator gel (rt-PA) could modify the development of a postlaminectomy membrane. One component of the study involved the performance of a lumbar laminectomy and placement of gel rt-PA, free fat, or no tissue placement over the exposed dura mater. Three months later the animals were killed and sections of spine were removed en bloc, decalcified, and examined histologically. No significant differences were found in the degree of cellular fibrosis or heavy collagen production. A similar laminectomy at another lumbar level was also followed by gel rt-PA, free fat, or no tissue placement. Three months after surgery, surgery was performed again at this level immediately before death. There were no differences in the adhesiveness of the laminectomy membrane to dura mater or roots. It was concluded that the local instillation of gel rt-PA after laminectomy did not inhibit scar formation or scar adherence to the dura mater.

Adipose Tissue

Update: HIV infection and pulmonary host defenses.

Infection with the human immunodeficiency virus (HIV) produces profound alterations in host defense mechanisms throughout the respiratory tract. The extent of alteration of specific defenses varies with the stage or duration of HIV infection in the host. In the upper respiratory tract, HIV-infected individuals have decreased concentrations of salivary immunoglobulin A, which may predispose to colonization of the oropharynx with pathogenic microorganisms. In the lower respiratory tract, host defenses are provided by alveolar macrophages, lymphocytes, and polymorphonuclear leukocytes. Alveolar macrophages can be chronically infected with HIV, and demonstrate a number of compromised host defense functions. The HIV-infected host has a limited capacity to generate soluble signals necessary for activation of alveolar macrophages for microbial killing. CD4 lymphocytes, which are quantitatively depleted during HIV infection, also demonstrate qualitative defects. Proliferation of CD8 lymphocytes, directed against HIV-infected cells in the lung, is associated with the noninfectious pulmonary complications of acquired immunodeficiency syndrome. B lymphocytes from HIV-infected persons show deficient production of opsonizing antibodies, which may predispose to bacterial pneumonias. Defective responses of polymorphonuclear leukocytes in the lung are also likely to contribute to impaired host responses. Collectively, these multiple defects in the defense mechanisms of the respiratory tract explain the unique susceptibility of the HIV-infected host for opportunistic pulmonary infections.

AIDS-Related Opportunistic Infections

Expression of the TAL1 proto-oncogene in cultured endothelial cells and blood vessels of the spleen.

The TAL1 proto-oncogene encodes a basic helix-loop-helix (bHLH) protein that has been implicated in the pathogenesis of T-cell acute lymphoblastic leukemia. Normal expression of TAL1 is observed in erythrocytic, megakaryocytic and mastocytic cells of the hematopoietic lineage. We now report that both RNA transcripts and polypeptide products of TAL1 are present in human umbilical vein endothelial cells cultured in vitro. Moreover, in situ hybridization revealed a restricted pattern of TAL1 expression in endothelial cells in vivo, including vessels within the white pulp and follicles of the spleen. In view of its presumptive role as a transcriptional factor, the TAL1 gene product may serve during normal development as a regulator of endothelial cell growth or differentiation.

Basic Helix-Loop-Helix Proteins

Lack of effect of midazolam on inducibility of arrhythmias at electrophysiologic study.

Midazolam has several advantages over diazepam as a sedative agent in electrophysiologic studies, but its electrophysiologic effects in humans are unknown. Therefore, its effects were studied in 20 patients undergoing electrophysiologic studies. Electrophysiologic variables were measured before and after administration of intravenous midazolam (5 mg). There were no significant changes in the electrophysiologic variables, apart from a minor decrease in sinus cycle length (711 +/- 124 vs 647 +/- 91 ms; p = 0.005). Ease of inducibility of reentrant tachycardia was not significantly altered by midazolam, and tachycardia remained inducible in all patients. The drug was well-tolerated with no significant side effects, apart from a minor reduction (mean 18 mm Hg) in blood pressure (p less than 0.001). Good amnesic effect was achieved in 16 patients, and most patients preferred it to oral diazepam for sedation during the procedure. It is concluded that midazolam can be used safely in patients undergoing electrophysiologic studies without significantly interfering with electrophysiologic variables or the inducibility of reentrant tachycardias.

Adolescent

Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus.

BACKGROUND: The efficacy of conventional treatment with surgery and radiation for cancer of the esophagus is limited. The median survival is less than 10 months, and less than 10 percent of patients survive for 5 years. Recent studies have suggested that combined chemotherapy and radiation therapy may result in improved survival. METHODS: This phase III prospective, randomized, and stratified trial was undertaken to evaluate the efficacy of four courses of combined fluorouracil (1000 mg per square meter of body-surface area daily for four days) and cisplatin (75 mg per square meter on the first day) plus 5000 cGy of radiation therapy, as compared with 6400 cGy of radiation therapy alone, in patients with squamous-cell carcinoma or adenocarcinoma of the thoracic esophagus. The trial was stopped after the accumulated results in 121 patients demonstrated a significant advantage for survival in the patients who received chemotherapy and radiation therapy. RESULTS: The median survival was 8.9 months in the radiation-treated patients, as compared with 12.5 months in the patients treated with chemotherapy and radiation therapy. In the former group, the survival rates at 12 and 24 months were 33 percent and 10 percent, respectively, whereas they were 50 percent and 38 percent in the patients receiving combined therapy (P less than 0.001). Seven patients in the radiotherapy group and 25 in the combined-therapy group were alive at the time of the analysis. The patients who received combined treatment had fewer local (P less than 0.02) and fewer distant (P less than 0.01) recurrences. Severe and life-threatening side effects occurred in 44 percent and 20 percent, respectively, of the patients who received combined therapy, as compared with 25 percent and 3 percent of those treated with radiation alone. CONCLUSIONS: Concurrent therapy with cisplatin and fluorouracil and radiation is superior to radiation therapy alone in patients with localized carcinoma of the esophagus, as measured by control of local tumors, distant metastases, and survival, but at the cost of increased side effects.

Adenocarcinoma

Radiation therapy as a treatment for benign lymphoepithelial parotid cysts in patients infected with human immunodeficiency virus-1.

Patients who are infected with the human immunodeficiency virus (HIV) may develop benign lymphoepithelial cysts within the parotid gland that cause severe facial deformity. Standard treatment for this disorder has been superficial parotidectomy, repeated fine-needle aspirations or observation alone. These approaches are unsatisfactory because elective surgery in immunocompromised patients should be avoided, the cysts recur soon after aspiration, and observation alone for a treatable deforming facial process is unacceptable. Radiotherapy's proven effectiveness in treating other benign disorders of the parotid gland led us to evaluate its usefulness as a treatment for this disorder. Eight patients with parotid enlargement, who were seropositive for HIV, received 8-10 Gy to the parotids in 1 week. Five patients had complete response and three patients had partial response. All were very satisfied with the cosmetic result. Treatment-related toxicity was well tolerated and consisted of mild xerostomia and transient taste loss. In all cases, these side effects resolved within 1 month. Radiation therapy thus appears to be an effective and well-tolerated treatment for AIDS-related parotid enlargement.

Adult

3-substituted-1,2-benzisoxazoles: novel antipsychotic agents.

A series of 3-substituted-6-fluoro-1,2-benzisoxazoles (II) was synthesized and evaluated for potential antipsychotic activity. Many of the compounds displayed potent antipsychotic-like activity in the apomorphine induced climbing in mice (CMA) or spiroperidol binding assays, and compound 42 (HRP 392, 1-[3-(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-4-(2-methoxyphenyl) piperazine) was selected for more detailed antipsychotic evaluation in a battery of preclinical assays. The results of these studies suggests that 42 is a potential antipsychotic drug with less propensity for EPS than some standard neuroleptics in monkeys. The compound was advanced for toxicological evaluation.

Animals