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Biomedical subjects

M Parker

Publications and source records attributed to M Parker.

At least 127 records · Page 7Linked to original sources
PubMed1994

The effects of coumarin and suramin on the growth of malignant renal and prostatic cell lines.

Coumarin is known to exert an anti-neoplastic action in patients with malignant melanoma and renal cell carcinoma. We examined the effects of various concentrations (0, 10, 50, 100, 250, 500 micrograms/ml) of coumarin on the proliferation of two renal cell carcinoma cell lines (786-O and A-498) and two malignant prostatic cell lines (DU145 and LNCaP). After 5 days of treatment, coumarin inhibited the growth of the four cell lines. The LNCaP prostatic cell line was more sensitive than the other cell lines to the inhibitory effects of coumarin. We also examined the effects of various concentrations of suramin (0, 50, 200 and 400 micrograms/ml), and anti-neoplastic compound currently undergoing clinical trials, on the growth of the 786-O and LNCaP cell lines. Both of these were inhibited by suramin at concentrations greater than 100 micrograms/ml. Finally we examined the effects of combined treatment with coumarin and suramin on the growth of LNCaP and 786-O cells. When combined with all concentrations of suramin studied (0, 50, 200 and 400 micrograms/ml), coumarin further inhibited cellular proliferation of the LNCaP and 786-O cell lines. However, the combination of the highest concentration of coumarin (500 micrograms/ml) with suramin at 400 micrograms/ml did not inhibit the proliferation of the cells more than 500 micrograms/ml coumarin alone.

Carcinoma, Renal Cell↗
PubMed1994

Isolation of cDNAs encoding T-BAM, a surface glycoprotein on CD4+ T cells mediating contact-dependent helper function for B cells: identity with the CD40-ligand.

"T-cell B-cell Activating Molecule" (T-BAM) is an activation-induced surface protein on CD4+ T cells that mediates a contact-dependent signal for B cell differentiation and immunoglobulin (Ig) secretion. The T-BAM protein on a helper clone of Jurkat (D1.1) was affinity purified using the anti-T-BAM mAb, 5c8. The NH2-terminal amino acid sequence of purified T-BAM was determined and found to be highly homologous to the predicted NH2-terminal sequence of a T cell ligand to the B cell CD40 molecule (CD40-L). From a D1.1 cDNA library, a clone was isolated that encodes CD40-L by sequence and drives expression of T-BAM protein on transfected cells, demonstrating that the T-BAM and CD40-L genes and proteins are identical. Moreover, transfection of T-BAM was shown to confer to non-lymphoid cells, the ability to induce B cells to upregulate the expression of surface CD23 molecules. In previous studies we showed that T-BAM was expressed predominantly on activated CD4+ and on few if any CD8+ cells. Although the current work confirms that T-BAM is largely restricted to activated CD4+ T cells, we now provide definitive evidence that T-BAM can be expressed by a small population of CD8+ T cells after activation. Importantly, a subset of CD8+ T cells do not express T-BAM after activation and this T-BAM- phenotype is maintained on certain CD8+ T cell clones. Taken together, these data unify the biology and structure of T-BAM and CD40-L and this synthesis has implications for understanding the T cell regulation of the humoral immune response.

Amino Acid Sequence↗
PubMed1994

Mortality after spinal and general anaesthesia for surgical fixation of hip fractures.

One thousand, three hundred and thirty three patients who underwent anaesthesia for surgical fixation of a hip fracture were studied prospectively to assess the effects on outcome of general and spinal anaesthesia. There were no significant differences between the groups in risk factors, length of hospital stay or mortality rates after 30 days or one year. The data presented may be useful for those wishing to audit anaesthetic services provided to patients with hip fracture.

Aged↗
PubMed1994

Gastrointestinal symptoms and diet of members of an irritable bowel self-help group.

A self-administered questionnaire was completed by 103 members of a self-help group for irritable bowel syndrome (IBS) and 130 controls, to compare the presence of IBS symptoms. Dietary fibre prescription, compliance and efficacy were documented in the IBS group. There were significant differences in the frequency of defaecation and number of symptoms present between the two groups. Most of the IBS subjects had been prescribed a high fibre diet but adherence to the diet and symptomatic improvement were poor. In contrast many IBS sufferers were following a range of diets not prescribed by their doctor. The seriousness of the IBS condition was highlighted by the fact that 8% of the IBS group had retired early due to their condition.

Adult↗
PubMed1994

Characterization of the proximal estrogen-responsive element of human cathepsin D gene.

Cathepsin D, a lysosomal proteinase, is induced by estrogens in mammary cancer cells where its concentration is correlated with a higher risk of metastasis. Its gene expression is stimulated by estrogens in MCF7 cells, and we have shown that a short proximal promoter fragment from -365 to -122 is required for this induction. We now characterize, at -261, a nonconsensus estrogen-responsive element (ERE) (E2) with two differences in the distal half of its palindrome, which confers estradiol responsiveness to the heterologous Herpes simplex virus thymidine kinase promoter in transient transfection experiments. This ERE is located in a 21-base pair sequence: 5'GGGCCGGGCTGACCCCGC GGG3', containing a GC-rich region in its 3'-part, which is almost perfectly repeated at -362 (the E1 site). The E2 site was necessary but not sufficient to mediate an estrogen response and required cooperation with the homologous E1 element and/or with general transcription sites located downstream. In vitro, the E2 site but not the E1 site was protected by estrogen receptor (ER) against DNAse I digestion, and gel shift experiments suggested an interaction with the ER as a dimer. Moreover, we showed in vivo that ER DNA binding domain was required to mediate estrogen induction from the cathepsin D ERE. We conclude that estradiol induction of cathepsin D is mediated by interaction of the ER with a nonconsensus ERE that requires synergy with other elements located upstream and/or downstream of this central ERE.

Base Sequence↗
PubMed1994

A prospective evaluation of the signs and symptoms of preterm labor.

OBJECTIVE: To describe the time relation between symptoms, contractions, and the clinical diagnosis of preterm labor. METHODS: We analyzed the records from 57 women who were enrolled in a previously reported trial of home uterine monitoring and who developed preterm labor while using the monitor. In a post hoc descriptive study of signs and symptoms during the 7 days preceding a diagnosis of preterm labor, we reviewed uterine contraction records and study records of the responses to a standard list of questions about potential symptoms of preterm labor. RESULTS: Monitored contraction frequency increased on the day of preterm labor diagnosis, from an average of fewer than three per hour to five per hour, but was not increased on any of the days before the day of diagnosis. Neither symptoms nor contraction monitoring strips indicated any significant changes more than 24 hours before the clinical diagnosis was made. Self-palpated and monitored contractions were the most common symptoms of preterm labor. CONCLUSION: A clinical diagnosis of preterm labor is preceded by an increase in self-palpated and monitored contractions and other symptoms for less than 24 hours.

Adult↗
PubMed1993

Cost analysis of early discharge after hip fracture.

OBJECTIVE: To ascertain the economic impact of an early discharge scheme for hip fracture patients. DESIGN: Population based study comparing costs of care for patients who had "hospital at home" as an option for rehabilitation and those who had no early discharge service available in their area of residence. SETTING: District hospital orthopaedic and rehabilitation wards and community hospital at home scheme. PATIENTS: 1104 consecutively admitted patients with fractured neck of femur. 24 patients from outside the district were excluded. MAIN OUTCOME MEASURES: Cost per patient episode and number of bed days spent in hospital. RESULTS: Patients with the hospital at home option spent significantly less time as inpatients (mean of 32.5 v 41.7 days; p < 0.001). Those patients who were discharged early spent a mean of 11.5 days under hospital at home care. The total direct cost to the health service was significantly less for those patients with access to early discharge than those with no early discharge option (4884 pounds v 5606 pounds; p = 0.048). CONCLUSIONS: About 40% of patients with fractured neck of femur are suitable for early discharge to a scheme such as hospital at home. The availability of such a scheme leads to lower direct costs of rehabilitative care despite higher readmission costs. These savings accrue largely from shorter stays in orthopaedic and geriatric wards.

Aged↗
PubMed1993

Management of advanced ovarian epithelial cancer in the renal transplant patient.

Stage IIIC, grade 1 papillary serous adenocarcinoma of the ovary was diagnosed in a 28-year-old renal transplant recipient. She had been treated with the immunosuppressive agents azathioprine and methylprednisolone for 7 years prior to the discovery of the ovarian cancer. Surgical excision of the tumor was suboptimal due to involvement of the allograft; however, the patient achieved a complete clinical response after eight courses of cisplatin and cyclophosphamide. Since multiagent immunosuppressant therapy may have contributed to the development of the ovarian carcinoma, the intensity of immunosuppression was decreased by discontinuing the azathioprine as soon as the diagnosis of ovarian cancer was made. The methylprednisolone, however, was continued to decrease the possibility of organ rejection. After completion of chemotherapy, the patient was started on a daily regimen of low-dose oral cyclophosphamide as an immunosuppressant. Four months following the completion of cytotoxic therapy, she developed clinically evident disease in the pelvis. Subsequent salvage therapy with carboplatin failed. The patient died from progressive disease 26 months after initial diagnosis. She never developed evidence of renal rejection. Combined modality cancer therapy, preservation of allograft function, and modification of immunosuppressant therapy are important goals in the renal transplant patient with advanced ovarian carcinoma.

Adult↗
PubMed1993

Bilharzia and the boys: questioning common assumptions.

There is insufficient and inadequate information to gauge the impact of schistosomal infection on the health of women. Biomedical research has equated women's health with the study of reproductive performance and reproductive organs and this narrow focus has left a number of important questions unanswered. Attempts to explore the economic and social aspects of schistosomal infection have been minimal and most research has focused on men rather than women. It has two characteristics: first, economists have relied on single performance indicators which are rooted in the cultural traditions of the research workers rather than the participants. Second, questionnaires have been used to elicit perceptions of health and illness; and local, culturally-specific information has not even been used to formulate the questions. Future research assessing the social and economic aspects of infection among women would be enhanced by undertaking inter-disciplinary research, with an ethnographic component; and blending qualitative with quantitative methods. Research assessing the impact of schistosomal infection on daily activities has been undertaken in Omdurman aj Jadida, Sudan. Biomedical and continuous observational data were blended with ethnographic information and the analyses of these data suggest that Schistosoma mansoni exerts a differential impact on female activity patterns. That is, infection by S. mansoni significantly impaired female activities in the agricultural sphere whereas infection by S. mansoni did not have any significant impact on female activities in the domestic sphere. Variations in the nature and extent of work undertaken by these two groups of women as well as differential exposure to solar radiation probably accounts for these recorded differences. The limited and tentative nature of biomedical, economic, sociological and anthropological information assessing the impact of schistosomal infection on the health of women adds to the current controversies about whether schistosomiasis should continue to be given priority as a public health problem. Further research is essential to clarify this important issue.

Activities of Daily Living↗
PubMed1993

Intracardiac teratoma 15 years after treatment of a nonseminomatous germ cell tumor.

A patient presented to our center with a 15-year history of medical, surgical and radiation treatment for a nonseminomatous germ cell tumor and contralateral seminoma. He experienced a cerebral infarction, which led to the diagnosis of an intracardiac tumor. The tumor was resected and found to be a mature teratoma. We discuss the diagnosis and management of this unusual metastatic nonseminomatous germ cell cancer.

Adult↗
PubMed1993

Calcium antagonists and converting enzyme inhibitors reduce renal injury by different mechanisms.

Both glomerular hypertension and hypertrophy have been associated with the development of glomerular injury in models of hypertension and reduced renal mass. The purpose of this study was to examine the effects of antihypertensive therapy on these parameters in the remnant kidney model of progressive glomerular sclerosis. Rats underwent 5/6 nephrectomy and were randomly assigned to receive either no therapy, the calcium entry blocker (CEB), nifedipine, or the angiotensin converting enzyme inhibitor (CEI), enalapril. Administration of either drug was associated with a reduction in systemic blood pressure and in the severity of glomerular injury assessed eight weeks after renal ablation. Micropuncture studies four weeks after ablation revealed that systemic and glomerular capillary pressure were high in untreated remnant kidney rats and reduced by enalapril. Administration of nifedipine was associated with a decline in systemic pressure, however, plasma renin levels increased, causing efferent arteriolar vasoconstriction and persistence of glomerular hypertension. Morphometric analysis showed that kidney weight, glomerular volume and glomerular capillary radius were lower in nifedipine treated rats than in the other two groups, indicating that the CEB, but not enalapril, inhibited the hypertrophic response to ablation of renal mass. Therefore, both CEIs and CEBs reduce glomerular injury in rats with remnant kidneys but they may act by different mechanisms. CEI reduce glomerular capillary pressure while CEBs inhibit compensatory kidney growth.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Geriatric care management reduces Medicare losses.

Healthcare costs for the elderly are rising rapidly in the United States. One way for a hospital to control these rising costs is to implement a geriatric care management system. The goal of a such a system is to change the way the hospital treats medically complex Medicare patients and, thus, reduce unnecessary hospital costs. Such a system requires a process for identifying elderly patients in need of geriatric care management services, treating them efficiently, and assessing the system itself. An effective process usually results in significant cost savings for the hospital as well as improved patient care and satisfaction.

Aged↗
PubMed1993

Ovarian management during radical hysterectomy in the premenopausal patient.

OBJECTIVE: To determine whether the ovaries should be retained or removed in premenopausal women undergoing radical hysterectomies for cervical carcinoma. METHODS: Questionnaires were sent to all women who had radical hysterectomies without further therapy for cervical carcinoma at our institution over a 16-year period. Those who had retained ovarian tissue were asked to have serum gonadotropin levels measured. RESULTS: Eighty-four of 124 eligible women (68%) responded. Sixty-eight respondents were premenopausal at the time of surgery. Thirty-eight had a bilateral salpingo-oophorectomy (BSO), 20 had one ovary preserved, and ten retained both ovaries. Six of 30 (20%) who retained ovaries developed early hormonal failure. Two of these 30 (7%) required oophorectomies subsequently. Twenty-seven of 38 BSO patients (71%) were compliant with their hormone replacement regimens. Fourteen of 15 women (93%) age 40 or younger were compliant, whereas 13 of 23 (57%) over age 40 were compliant (P < .05). Twenty-three of 34 BSO respondents (68%) reported improved or unchanged sexual relations, compared with 24 of 27 (89%) who retained ovaries (P > .05). CONCLUSIONS: Twenty-seven percent of our premenopausal women with retained ovaries have experienced early loss of hormonal function or required subsequent oophorectomies. For an accurate estimate of ovarian longevity, all patients would have to be followed through menopause. Compliance in taking hormone medication was high in our young patients. Sexual function was not adversely affected following castration. A hypothetical cost comparison favored removing, rather than retaining, the ovaries. We recommend that elective BSO be performed on most premenopausal women undergoing radical hysterectomies for cervical carcinoma.

Adult↗
PubMed1993

Permissive and instructive induction of adult rodent prostatic epithelium by heterotypic urogenital sinus mesenchyme.

Adult rodent (rat and mouse) prostatic ducts (PR) were recombined heterospecifically with fetal urogenital sinus mesenchyme (UGM) (mouse UGM plus rat PR or rat UGM plus mouse PR), and the resultant tissue recombinants were grafted under the renal capsule of male athymic mice. For recombination with mouse UGM the ductal tips of each of the 4 rat prostatic lobes [ventral (VP), lateral type 1 (L1), lateral type 2 (L2), and dorsal prostate (DP)] were used. For recombination with rat UGM the ductal tips of each of the 2 mouse prostatic lobes [ventral (VP) and dorso-lateral prostate (DLP)] were used. After 1 month of growth in vivo, the DNA content of UGM+PR recombinants increased substantially (6.1- to 76.8-fold increase) over the combined DNA content of the isolated UGM and PR prior to grafting. Immunocytochemical, polyacrylamide gel electrophoretic and Western blot analyses demonstrated that irrespective of the initial source of the adult prostatic duct, the epithelium of UGM + PR recombinants continued to express its normal lobe-specific secretory proteins as well as secretory proteins specific to other prostatic lobes. For example, rat ventral and lateral type 2 prostate do not normally express DP-1, a rat dorsal-prostatic-specific protein, but after recombination with mouse UGM the induced prostatic epithelium expressed DP-1 as well as C3, a rat ventral-prostatic-specific protein. Sensitive reverse transcriptase-polymerase chain reaction techniques (RT-PCR) verified the expression of mRNA for C3 and DP-1 in such tissue recombinants. Analogous results were obtained for UGM + PR tissue recombinants constructed with prostatic ductal tips from rat L1, L2 and DP and mouse VP and DLP. These findings demonstrate that adult rodent prostatic epithelium retains a responsiveness to its connective tissue environment, and that fetal UGM can permissively induce prostatic ductal growth and morphogenesis while instructively inducing the expression of a new spectrum of prostatic secretory proteins.

Animals↗