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Biomedical subjects

M Francis

Publications and source records attributed to M Francis.

At least 19 recordsLinked to original sources

Benchmarking the current dispensing rate of Welsh hospital pharmacies.

BACKGROUND: There is a need to develop capacity measures for pharmacy services for strategic purposes, to provide guidance on safe working limits and to contribute to the target 40% reduction in serious medication errors by 2005. Attempts have been made to quantify workloads in the form of items/person/hour (i/p/h). However, much of these data are anecdotal, small scale or associated with vague methodology. OBJECTIVE: We estimate national average dispensing rates by collecting accurate data from secondary care dispensaries across Wales. METHOD: Seventeen sites collected hourly data relating to staff time and items dispensed over a 3-day period. The result showed a Welsh national average for non-specialist hospital pharmacy dispensing rates of 9.9 items/person/h (95% CI = 0.9, n = 17). There was a significant positive association between hospital size and telephone interruptions (r(s) = 0.83, P < 0.001) but no correlation between hospital size and dispensing rates (r(s) = 0.06, P = 0.822).

Benchmarking↗

The Adjusting-Paced Serial Addition Test (Adjusting-PSAT): thresholds for speed of information processing as a function of stimulus modality and problem complexity.

A modified computer version of the PASAT (Adjusting-PSAT; ) is described that measures speed of information processing and working memory by means of a temporal threshold rather than number of correct responses. This is accomplished by making the duration of the interval between numbers depend on the correctness of responding-a correct response decreases the interval between digits and an incorrect response increases the interval. Modality of presentation (visual and auditory) was factorially combined with problem difficulty (answers between 2-10 or 2-18). Performance of 60 healthy student volunteers on the Adjusting-PSAT was compared to that obtained on several traditional neuropsychological measures (Digit Span, Trail Making Test, and Symbol Digit Modality Test) and on a test of basic addition skills. The visual version of the test produced a lower threshold than did the auditory version, but problem difficulty did not produce a significant effect. Of the neuropsychological tests, Trails-B (TMT-B) was most highly correlated with thresholds. However, regression analyses revealed that math ability accounted for more variance than did TMT-B. The clinical implications of these finding are discussed.

Acoustic Stimulation↗

Gender differences in plasma levels of lipoprotein (a) in patients with angiographically proven coronary artery disease.

The objective of the study was to assess the association between plasma levels of lipoprotein(a) [Lp(a)] and the presence of angiographically defined coronary artery disease (aCAD). Patients (346 men and 184 women) undergoing selective coronary angiography (SCA) were classified into groups with positive [aCAD(+)] and negative [aCAD(-)] findings and their age, body mass index (BMI), waist circumference, blood pressure, smoking, plasma total, LDL-, HDL-cholesterol (TC, LDL-C, HDL-C), triglycerides (TG), apolipoprotein B (apoB), Log(TG/HDL-C) and TC/HDL-C were determined. Concentration of plasma Lp(a) was estimated using the commercial solid phase two-side immunoradiometric assay of apolipoprotein apo(a). The plasma Lp(a) was significantly higher in both women and men with aCAD(+) compared to those with aCAD(-). While there was no significant difference in the Lp(a) level between men and women with aCAD(-) (median 138 vs. 145 units/l), the women with aCAD(+) had almost twice as high Lp(a) levels as men (median 442 vs. 274 units/l, p<0.001). Women with aCAD(+) had also significantly lower HDL cholesterol levels (1.09 vs. 1.20 mmol/l, p<0.05), higher triglycerides (1.82 vs. 1.46 mmol/l, p<0.05) and Log(TG/HDL-C) than women with aCAD(-). The differences in Lp(a) between positive and negative findings remained highly significant (p<0.001 in women, p<0.05 in men) after the adjustment for age, plasma HDL- and LDL-cholesterol and triglycerides in logistic regression analyses. In logistic regression model the Lp(a) and Log(TG/HDL-C) and smoking in women but smoking and age in men were the most powerful predictors of positive aCAD findings. Our findings suggest that Lp(a) is more strongly associated with aCAD+ in women than in men.

Age Distribution↗

Relaxant effects of parathyroid hormone and parathyroid hormone-related peptides on oviduct motility in birds and mammals: possible role of nitric oxide.

Parathyroid hormone (PTH) and PTH-related peptides (PTHrP) have previously been shown to modulate the contractile state of numerous types of smooth muscle. The effects of N-terminal PTH and PTHrP on spontaneous in vitro contractility of oviducal smooth muscle using tissues from egg-laying Japanese quail (10-15 h post ovulation), 4 and 9 days pregnant mouse uterus were investigated. Myometrial tissues from both species contracted vigorously for several hours, when incubated in organ baths in De Jalon's solution gassed with 5%CO2/95%O2. Contractions were enhanced in high (1.2-2.5 mM) compared with low (0.1-0.5 mM) calcium (Ca) containing media. Bovine PTH(1-34) (bPTH(1-34)), human PTH(1-34 amide) (hPTHrP(1-34) amide), and hPTHrP(1-40) caused similar concentration-related inhibition of contractions in media containing 1.2mM Ca over a range of 10(-9) to 10(-7)M, whereas C-terminal hPTHrP(107-139) was devoid of such activity. Responses to bPTH(1-34) in 4 and 9-day pregnant mouse tissues were similar but hPTHrP(1-40) showed substantial loss of activity in 9-day, compared with 4-day pregnant mouse tissues. Repeated exposure of mouse uterine tissue to the peptides resulted in desensitisation of responses. The EC50 responses of mouse tissues were inhibited by the PTH/PTHrP receptor antagonist, hPTHrP(7-34) amide. Responses to bPTH(1-34) were also inhibited by both non-selective and selective neuronal nitric oxide synthase (NOS) inhibitors N(omega)-nitro-L-arginine methyl ester (0.01-1mM) and 7-nitroindazole (0.01-10 microM), respectively. Both NOS inhibitors were more effective in inhibiting bPTH(1-34)-induced relaxation in the absence of L-arginine compared with in the presence of 1mM L-arginine (a NOS substrate) in the incubation media. It is concluded that relaxant responses to N-terminal PTH and PTHrP peptides are well conserved in oviducal and uterine tissues from avian and mammalian species. The results also suggest that NO may be responsible for mediating relaxant activities of these peptides in pregnant mouse uterine tissue.

Animals↗

Evidence for disturbances of copper metabolism in dystonia: from the image towards a new concept.

The pathogenesis of idiopathic adult onset dystonia (ID) is still unclear. Although neuropathologic studies did not reveal consistent abnormalities, electrophysiologic and neuroimaging findings point toward a disinhibition and overactivity of the frontal motor cortical areas caused by an altered basal ganglia outflow. The lentiform nuclei are assumed to play a major role in this scenario. Recent neurochemical analysis of brain tissue stimulated by transcranial ultrasound studies demonstrated an increased copper content of the lentiform nuclei in patients with ID. The shift of brain copper level may substantially influence neuronal activity causing a reduced inhibitory output from the lentiform nuclei to the motor cortex. The reason for the presumably altered copper metabolism is not clear, but preliminary findings suggest that reduced levels of the Menkes protein, a membrane ATPase exporting copper out of the cells, may be implicated. Disturbances of brain copper metabolism may explain various phenomena of ID; however, it needs to be determined whether these observations represent the basic pathogenetic mechanism of ID or reflect another as yet unidentified pathologic process.

Basal Ganglia↗

Linkage of body mass index to chromosome 20 in Utah pedigrees.

Several linkage studies have hinted at the existence of an obesity predisposition locus on chromosome 20, but none of these studies has produced conclusive results. Therefore, we analyzed 48 genetic markers on chromosome 20 for linkage to severe obesity (BMI> or =35) in 103 extended Utah pedigrees (1,711 individuals), all of which had strong aggregation of severe obesity. A simple dominant model produced a maximum multipoint heterogeneity LOD score of 3.5 at D20S438 (55.1 cM). Two additional analyses were performed. First, a one-gene, two-mutation model (with one dominant mutation and one recessive mutation) increased the LOD score to 4.2. Second, a two-locus model (with one locus dominant and one recessive) generated a multipoint LOD score of 4.9. We conclude that one or more severe obesity predisposing genes lie within an interval of approx. 10 cM on chromosome 20. This study generated significant LOD scores which confirm suggestive linkage reports from previous studies. In addition, our analyses suggest that the predisposing gene(s) is localized very near the chromosome 20 centromere.

Body Mass Index↗

Pleomorphic rhabdomyosarcoma of the uterus in a postmenopausal woman with elevated serum CA125.

BACKGROUND: Pure rhabdomyosarcoma of the uterus is an exceedingly rare tumor. While there are no commonly associated tumor markers, a previously reported case confirmed CA125 production by a pure uterine rhabdomyosarcoma. CASE: We describe a postmenopausal woman who presented with vaginal bleeding and was diagnosed with pleomorphic rhabdomyosarcoma of the uterus. Of particular interest was an elevated serum CA125 level at presentation. Immunohistochemical staining with CA125 antibody, however, showed no activity within the tumor. Despite aggressive therapy, the patient experienced distant nodal metastases and succumbed to the disease within 25 months of diagnosis. CONCLUSION: Our patient illustrates the typical presentation and aggressive behavior of this rare neoplasm. While serum CA125 may be a useful tumor marker in selected patients, elevated levels do not directly reflect tumor burden when associated with negative immunohistochemical staining.

CA-125 Antigen↗

Prognosis after breast recurrence following conservative surgery and radiotherapy in patients with node-negative breast cancer.

BACKGROUND: Breast conservation surgery with radiotherapy is a safe and effective alternative to mastectomy for early-stage breast cancer. This retrospective study examined the outcome of patients with isolated local recurrence following conservative surgery and radiotherapy in node-negative breast cancer. METHODS: Between November 1979 and December 1994, 503 women with node-negative breast cancer were treated by conservation surgery and radiotherapy without adjuvant systemic therapy. RESULTS: After a median follow-up of 73 months the 5-year rate of freedom from local recurrence was 94 per cent. Thirty-five patients developed an isolated local recurrence within the breast as a first event. Thirty-three patients were treated with salvage mastectomy and two patients were treated with systemic therapy alone. The 5-year rate of freedom from second relapse was 46 per cent and the overall 5-year survival rate was 59 per cent for patients who had salvage mastectomy. Patients who developed breast recurrence as a first event had a 3.25 greater risk of developing distant metastasis (P < 0.001) than those who did not have breast recurrence as a first event. CONCLUSION: Salvage mastectomy after local recurrence was an appropriate treatment if there was no evidence of distant metastasis. Breast recurrence after conservative surgery and radiotherapy in node-negative breast cancer predicted an increased risk of distant relapse.

Adult↗

Computed tomography evaluation of the inner ear as a diagnostic, counselling and management strategy in patients with congenital sensorineural hearing impairment.

The value of computed tomography (CT) of the petrous bone in the investigation of congenital sensorineural hearing impairment has been questioned. We have conducted a study to establish the usefulness of CT of the temporal bone in the evaluation and management of a consecutive series of unselected adolescent patients with congenital sensorineural hearing impairment of greater than 50 dB HL. Seventy-one patients (142 ears) were identified and images reviewed to establish the incidence of inner ear malformations. Fifteen ears were found to be abnormal in eight patients (seven bilateral and one unilateral abnormality). Three patients had Mondini abnormalities and one of these also had dilatation of the lateral semicircular canals. There were five patients with dilatation of the vestibular aqueduct. One patient had a unilateral dysplasia of the middle and external ear. A variety of incidental intracranial abnormalities were also discovered. We conclude that CT does have a valuable role in the management of SNHI.

Adolescent↗

Conservative surgery and radiation therapy for invasive lobular carcinoma of the breast.

BACKGROUND: There is debate as to whether infiltrating lobular carcinoma (ILC) can be effectively treated with breast conservative surgery (CS) and radiotherapy (RT) because of a perceived high risk of local recurrence. This retrospective study examined the outcome of patients with ILC treated by CS and RT. METHODS: Between November 1979 and December 1994, 57 women with UICC Stage I or II ILC were treated by CS and RT at Westmead Hospital, New South Wales, Australia. The median age was 55 years (range 28-79). Twelve patients (21%) underwent a re-excision after initial CS. The final margins were clear for 43 patients (75.4%), positive (invasive or in situ) for nine patients (15.8%), and indeterminate for five patients (8.8%). All patients received whole-breast irradiation (45-50.4 Gy) usually supplemented by a boost (10-30 Gy). Fifty-three of 57 patients (93%) had their pathology reviewed at Westmead Hospital. RESULTS: After a median follow up of 69 months (range 36-162) three patients (5.3%) developed a local recurrence. One of 43 patients (2.3%) with known clear margins developed a local recurrence compared with two of 14 patients (14.3%) with positive or indeterminate margins (P = NS). The 5- and 10-year rates of freedom from local recurrence were 96 and 93%, respectively. The 5-year disease-free survival was 85% (node-negative, 92%; node-positive, 66%). Overall survival was 94% at 5 years. No patient developed a contralateral breast cancer. CONCLUSION: Patients with ILC can be effectively treated with CS and RT.

Actuarial Analysis↗

Health effects of the 1991 Kuwait oil fires: a survey of US army troops.

The burning of oil wells in Kuwait in 1991 discharged a high volume of potentially toxic pollutants into the air. To determine whether there were health-related complaints associated with having lived and worked there, questionnaires were administered to 1599 soldiers after their return from a 3-month mission in Kuwait. Symptoms occurring before, during, and after the mission were queried. Compared with baseline, symptoms reported more frequently for the Kuwait period were eye and upper respiratory tract irritation, shortness of breath, cough, rashes, and fatigue. Symptoms were associated with reported proximity to oil fires, and their incidence generally decreased after the soldiers left Kuwait. Oil-fire smoke is one of several possible factors that may have contributed to the reporting of symptoms.

Adult↗

An assessment of fertility in male workers exposed to molinate.

Molinate is a thiocarbamate herbicide used for weed control in rice fields. Since the late 1970s, findings from reproductive toxicology studies of rats have led to concern that molinate might affect human male fertility. Semen samples were collected from 272 formulation and production workers at three US plants. The samples were collected at the end of four alternate monitoring periods of either high or low exposure to molinate. In addition, 222 married workers provided reproductive-history information. Workers' mean exposures to molinate during the monitoring periods ranged from 12.7 micrograms/m3 to 210.9 micrograms/m3. There was no evidence that sperm and serum hormone levels were related to exposure to molinate before the study or exposure during the four monitoring periods. There was also no evidence of a molinate exposure-related effect on the ratio of observed to expected births.

Alabama↗

Evidence for abstract, schematic knowledge of three spatial diagram representations.

Spatial diagram representations such as hierarchies, matrices, and networks are important tools for thinking. Our data suggest that college students possess abstract schemas for these representations that include at least rudimentary information about their applicability conditions. In Experiment 1, subjects were better able to select the appropriate spatial diagram representation for a problem when cued to use general category information in memory about those representations than when cued to use specific example problems given during the experiment. The results of Experiment 2 showed that the superior performance in the general category condition was not based on a comparison of the test problems with examples in memory. The results of Experiment 3 showed that the superior performance was not due to learning that occurred during the experiment or to transfer appropriate processing. The General Discussion section considers the nature of students' representation schemas and the question of why college students have only rudimentary schemas for common and widely applicable diagrammatic representations.

Female↗

Industry-wide study of mortality of pulp and paper mill workers.

A study of pulp and paper mill workers indicated low risks of death from all causes (standardized mortality ratio (SMR) = 0.74) and all cancers (SMR = 0.81) compared with U.S. rates. The leukemia death rate in workers was not higher than the U.S. rate but was higher than the rate in county populations surrounding mills. Workers whose last jobs were in the finishing areas of the mills had an elevated SMR for liver cancer. An internal comparison of occupational characteristics indicated that workers employed in mills using other chemical pulping operations had significantly elevated mortality from all causes, all cancers, heart disease, lymphomas, and brain cancers. Lung cancer mortality was elevated in mills using kraft pulping. The internal comparisons confirmed the association between work in finishing and the risk of liver cancer. This study was designed to investigate whether pulp and paper mill workers have any risks that would indicate the need for studies detailing exposures.

Adult↗

Proliferation and collagen synthesis of human anterior cruciate ligament cells in vitro: effects of ascorbate-2-phosphate, dexamethasone and oxygen tension.

Clinical and experimental studies demonstrate that injured anterior cruciate ligaments (ACL) do not usually heal and that autografts used to repair the ACL rapidly weaken in the early period and take a long time to regain strength. The aim of this study was to develop an in vitro culture system in which environmental and biochemical factors influencing the proliferation and matrix synthesis of cells derived from human anterior cruciate ligaments can be studied. Primary cultures of human ACL cells were obtained by outgrowth from explants of normal ACL obtained at knee replacement for osteoarthritis in Dulbecco's minimum essential medium (DMEM). The effects of the additives 100 microm L-ascorbic acid-2-phosphate (Asc-2-P) and 10 n m dexamethasone (dex) on proliferation and collagen synthesis were assessed after 4, 8 and 12 days in culture. Ligament cells were grown at 0, 5, 10 and 21%p O(2)in the presence of 100 microm asc-2-P and 10 n m dex. DNA content was assessed using the Hoechst dye method and collagen synthesis by the incorporation of 5 mCi/ml [(3)H]proline after 3, 6 and 12 days in culture. At 21%p O(2), the presence of asc-2-P and dex induced significantly greater (P< 0.01, ANOVA) cell proliferation than with either additives alone. Greatest percentage collagen to total protein synthesis was observed when cells were grown in the presence of asc-2-P only. Least proliferation and percentage collagen to total protein synthesis was seen when both additives were omitted. Greatest cell proliferation was seen when cells were grown in 10%p O(2)and 5%p O(2)was associated with increased collagen synthesis. These results suggest that it is possible to study the effects of environmental and biochemical factors on human ACL healing in vitro. Our data suggest oxygen can influence certain biosynthetic activities of ACL cells. Low oxygen tensions lead to an increase in collagen production by ACL cells. However early responses to injury require extensive cell proliferation which may be activated at higher p O(2). Variation of p O(2)in ligaments during healing may therefore be an important modulator of successful repair.

Anterior Cruciate Ligament↗