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Biomedical subjects

L Davis

Publications and source records attributed to L Davis.

At least 19 recordsLinked to original sources

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

Protein synthesis within neuronal growth cones.

This study investigates the capacity of neuronal growth cones to synthesize protein locally and independently of their cell body. Isolated growth cones were prepared from cultures of neurons from the snail Helisoma by transecting neurites proximal to the growth cone. The capacity for protein synthesis was tested by radiolabeling cultures with 3H-leucine and analyzing the resultant autoradiograms. Isolated growth cones displayed incorporation of 3H-leucine that was inhibited by treatment with the protein synthesis inhibitors anisomycin and pactamycin, indicating that ribosomal-dependent translation occurs in growth cones. Ultrastructural analyses of growth cones demonstrated the presence of polyribosomes, the machinery for protein synthesis. The density of polyribosomes varied between growth cones, even between different growth cones on the same neuron, suggesting that growth cones express a range of protein synthetic capabilities. That different types of growth cones possess differing capabilities for protein synthesis is suggested in autoradiograms of 3H-leucine incorporation by the growth cones of axonal and nonaxonal neurites; incorporation was radically reduced in axonal growth cones in comparison with non-axonal growth cones. Finally, growth cones that were isolated for 2 d prior to radiolabeling incorporate 3H-leucine in a eukaryotic ribosomal-dependent manner, suggesting that the capacity for translation is long-lived in growth cones. Taken together, these studies reveal a capacity for protein synthesis confined totally to the neuronal growth cone proper. The synthesis of proteins in growth cones could afford a mechanism for the alteration of growth cone structure or function. This is in accord with the view that growth cones participate autonomously, to at least some extent, in the processes of synaptogenesis and the construction of neuronal architecture.

Animals

Primary central nervous system lymphoma in acquired immune deficiency syndrome. A clinical and pathologic study with results of treatment with radiation.

Primary central nervous system (CNS) lymphoma occurs frequently in patients with the acquired immune deficiency syndrome (AIDS). Seventeen patients with AIDS and biopsy-proven CNS lymphoma were treated with whole-brain radiation. At presentation, most patients were severely debilitated from previous AIDS-related illnesses. Patients generally had focal neurologic symptoms such as seizures and paralysis. Headaches and mental status changes, often noticed after hospital admission, seldom brought our patients to seek medical attention. Computed tomography (CT) scan showed low-density, contrast-enhancing, mass lesions with variable amounts of peritumor edema. Size, location, and pattern of contrast enhancement of the lesions varied. No specific pattern was seen that could be used to distinguish between CNS lymphoma, toxoplasmosis, or other CNS diseases that occur in patients with AIDS. Biopsy results showed angiocentric, high-grade, large cell tumors with frequent necrosis. Immunohistochemical analysis showed B-cell phenotype with small amounts of T-cells, presumably reactive. All patients received irradiation to the whole brain with parallel opposed fields. A variety of doses and treatment regimens were used. Mean survival was only 72 days. Survival was longer in patients with higher pretreatment Karnofsky scores. The correlation between dose and survival was not significant. At completion of therapy, most patients showed improvement in Karnofsky score and had partial improvement in neurologic symptoms. CNS lymphomas in patients with AIDS are responsive to radiation. Posttreatment CT scans showed regression of tumors. Autopsy examinations showed regression of tumors, but also showed concurrent CNS infections, AIDS encephalopathy, and radiation-induced changes within the normal CNS tissue. Opportunistic infections rather than cerebral herniation or uncontrolled lymphoma was the most common cause of death.

Acquired Immunodeficiency Syndrome

Recommendations for the management of low risk obstetric patients.

Specific interventional procedures have enjoyed widespread popularity in the United States in the routine management of low risk obstetric patients without the benefit of clinical studies attesting to their utility. A review of the literature was conducted to survey obstetric practice with regard to amniotomy, intravenous fluids, third stage administration of oxytocics, episiotomy and continuous fetal monitoring.

Amnion

Clinical trials with etanidazole (SR-2508) by the Radiation Therapy Oncology Group (RTOG).

Following the completion of a phase I study of etanidazole (SR 2508), a new hypoxic cell sensitizer, the RTOG, began a phase II/III trial. The objectives of the study were to determine the toxicity and efficacy of SR 2508, combined with conventional radiotherapy for the management of unresectable stage III and IV head and neck squamous carcinomas. During the first step (or the Phase II portion) of the study, 33 patients received radiotherapy plus SR 2508 (RT + SR 2508). The incidence of drug toxicities was modest; including 24% grade I peripheral neuropathy (PN), 6% grade II PN, 27% grade I or II nausea and vomiting, 9% allergy and 15% reversible neutropenia. Because observed toxicities were deemed acceptable, the second step (or phase III portion) was then activated. Patients were randomized to receive either RT or RT + SR 2508. As of November 20, 1989, a total of 242 patients have been entered onto the Phase III portion of the study. One hundred twenty-two patients were randomized to the RT + SR 2508 arm and 120 patients were randomized to the RT alone arm. The analyses presented in this report are based on data available. The incidence of drug toxicities has been low, with 18% grade I or II PN, 26% nausea and vomiting (including one grade III), 14% allergy (including one grade III) and 13% reversible neutropenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Squamous Cell

Short courses of antibiotics in selected febrile neutropenic patients.

To evaluate their policy of discontinuing broad spectrum antibiotics in patients with negative cultures who become afebrile but remain neutropenic, the authors retrospectively reviewed the charts of all pediatric patients diagnosed with cancer between 1980 and 1986. Two hundred seventy-one children had 385 admissions for infectious complications during the study period. In 39 of those episodes (9%), the patients had negative cultures, became afebrile, and were discharged with absolute neutrophil counts of less than 1000 cells/mm3 (mean 390 cells/mm3). They received relatively short courses of antibiotics with a median duration of 4 days. Only four of these patients became febrile during the followup period and there were no fatalities. Given the benign course of these patients, recommendations for prolonged antibiotic courses should be reconsidered.

Anti-Bacterial Agents

Where physicians practicing in Appalachia in 1978 to 1990 were trained and how they were distributed in urban and rural Appalachia.

Medical school graduates who graduated from 1978 to 1986 were analyzed to determine the health professions' ability worldwide to educate and place primary care physicians in rural areas of Appalachia. These data indicate that the University System of West Virginia--consisting of the West Virginia School of Osteopathic Medicine, West Virginia University Medical School, and Marshall University Medical School--produced the most primary care physicians who began practicing in rural Appalachia during the 1980s. The West Virginia School of Osteopathic Medicine successfully retained 106 (26%) of its graduates in primary care practices throughout rural Appalachia, with 77 of them in rural West Virginia, making the institution the nation's leading provider of primary care physicians practicing in rural Appalachia and West Virginia during this eight-year study period. With the exception of West Virginia, these and additional data support concerns of medical educators and public health officials that physicians in Appalachia are distributed disproportionately, more to urban than to rural counties.

Appalachian Region

Papillary thyroid carcinoma concentrating both Tc-99m sodium pertechnetate and I-131 iodide. Case report and review of the literature.

Thyroid carcinoma concentrating both Tc-99m sodium pertechnetate and radioactive iodine is a rare occurrence. This report describes such a case. It is somewhat different from previous reports in that the carcinoma had tracer uptake equal to that of the remaining normal thyroid gland on both isotope studies. It also occurred in the pediatric age group and followed external radiation therapy. A review of the pertinent literature is presented.

Adolescent

Using DRGs to pay for inpatient substance abuse services: an assessment of the CHAMPUS reimbursement system.

In October 1988, the Civilian Health and Medical Program of the Uniformed Services (CHAMPUS) introduced a prospective payment system based on diagnostic-related groups (DRGs) to pay for substance abuse services. These services were initially excluded from the new payment system because of concerns that a DRG-based system may have a large and poorly understood financial impact on individual hospitals. This report assesses the performance of a DRG system in explaining variation in costs at the individual patient level and evaluates how well this payment system predicts resource use across hospitals. Overall, the substance abuse DRGs explained only 4.2% of the total variance in charges. It was found that the Medicare DRG-based system had to be modified to reflect the characteristics of the younger CHAMPUS population by splitting DRG 435 to account for the increased costliness of beneficiaries younger than 21 years. In addition, the study revealed substantial variation in the impact of the DRG system on hospital revenue. These differences largely reflected significant differences between general and specialty hospitals.

Adult

Suppressor effects in the relations of psychological variables to resting blood pressure.

The role of suppressor effects in obscuring the relation of psychological variables and blood pressure was studied. Forty-five nonmedicated patients in a family practice rated themselves relative to their peers on a series of characteristics. Two of these, trapped and lonely, exhibited marked suppressor effects in their relationship with each other and resting blood pressure. Self-ratings of lonely exhibited a moderately strong positive association with ratings of trapped (r = .63) while only ratings of lonely showed a significant correlation with resting systolic blood pressure (r = .31). Yet when the suppressor effects of the ratings on feeling lonely were removed in the regression analyses, the ratings on feeling trapped showed a significant positive association with resting systolic pressure (r = .42). Similarly, while neither ratings on feeling lonely or on feeling trapped showed separately a significant association with resting diastolic pressure, when suppressor effects were removed in the regression analyses, the ratings of trapped were significantly associated with diastolic pressure in a positive direction (r = .34) and ratings of lonely were significantly associated in a negative direction (r = .33). The significance of this specific suppressor effect and the implications of suppression for psychosomatic research are discussed.

Adult

Programmed cell death as a new target for prostatic cancer therapy.

To increase survival of men with metastatic prostatic cancer, a modality that can effectively eliminate androgen independent cancer cells is desperately needed. By combining such an effective modality with androgen ablation, all of the heterogeneous populations of tumour cells within a prostatic cancer patient can be affected, thus optimizing the chances of cure. Unfortunately, such effective therapy for the androgen independent prostatic cancer cell is not yet available. This therapy will probably require two types of agents, one having antiproliferative activity affecting the small number of dividing androgen independent cells, and the other able to increase the low rate of cell death among the majority of non-proliferating (ie interphase) androgen independent prostatic cancer cells present. Androgen dependent prostatic epithelial cells can be made to undergo programmed death by means of androgen ablation, even if the cells are not in the proliferative cell cycle. Androgen independent prostatic cancer cells retain the major portion of this programmed cell death pathway, only there is a defect in the pathway such that it is no longer activated by androgen ablation. If the intracellular free Ca2+ is sustained at an elevated level for a sufficient time, androgen independent cells can be induced to undergo programmed death. The long term goal is therefore to develop some type of non-androgen ablative method that can be used in vivo to induce a sustained elevation in Ca2+ in androgen independent prostatic cancer cells. To accomplish this task, a more complete understanding of the biochemical pathways involved in programmed cell death is urgently needed. At present, studies are focusing on the mechanism involved in the Ca2+ elevation in the normal and malignant androgen dependent cell induced following androgen ablation and the role of the TRPM-2 protein in this process.

Adenocarcinoma