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Biomedical subjects

R French

Publications and source records attributed to R French.

At least 37 records · Page 2Linked to original sources
PubMed2000

Where the philosopher finishes, the physician begins: medicine and the arts course in thirteenth-century Oxford.

In the thirteenth century the English universities were different from others, particularly those in the south of Europe, in two important ways: they taught more natural philosophy and less medicine. But the survival of students' notes from the second half of the century shows that in the formal course of lectures on natural philosophy attention was paid to medicine inside the arts course. The present discussion examines the nature of this medical material and the institutional and intellectual relationship between medicine and philosophy.

Curriculum↗
PubMed1999

Activity of doxorubicin covalently bound to a novel human serum albumin microcapsule.

UNLABELLED: Doxorubicin is widely used in the treatment of human malignancies, however is associated with significant cardiac, bone marrow and gastro-intestinal toxicity. Delivery systems may ameliorate this toxicity and increase treatment specificity by increasing the proportion of drug delivered to sites of disease. We have developed a novel preparation of doxorubicin (Dox) covalently linked to a heat stabilised human serum albumin microparticle (HSAM) carrier (median particle diameter of 4 microm) and assessed its activity in 4 malignant cell lines. MATERIALS AND METHODS: Doxorubicin microcapsules were compared with free doxorubicin in the rat carcinoma cell line, WRC256, and the human lines, OVCAR3, MCF7 and the Dox resistant MCF7/Dox, using a cell counting technique. IC50 were calculated from regression analysis of the resulting survival curves. Endocytosis of the microcapsules by cells in culture was observed. The rate of microcapsule uptake was assessed using dual wavelength filtered fluorescence microscopy and flow cytometry. RESULTS: The mean IC50 following incubation with the Dox microcapsules was around 5 times greater than Dox for WRC256 (p < 0.001), MCF7 (p < 0.01) and for OVCAR3 (p < 0.01). MCF7/Dox was significantly more sensitive to Dox microcapsules than free Dox (p = 0.034). A negative correlation between the rate of microcapsule uptake and the IC50 values for each cell line in culture exists (r = -0.96, p = 0.04). CONCLUSIONS: We conclude that: 1) Doxorubicin microcapsules retain activity in vitro and appear to overcome p-glycoprotein mediated Dox resistance. 2) The observed activity of Dox microcapsules correlates with the rate of particle uptake. Further studies in animal tumour models are in progress.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Inadequate cervical cytology--the need to audit individual smear takers' inadequate rates.

In order to assess the performance of individual smear takers, their rates of inadequate smears, due to insufficient material, were monitored between 1992 and 1996. Although the yearly average clinic inadequate rates were all at acceptable levels, there was great variation of rates between smear takers, ranging from 0% to 19.5%. Identification of individuals with unacceptably high inadequate rates allowed them to undergo further training. Continuous monitoring of these inadequate rates can be used to measure levels of performance amongst all smear takers, but is particularly useful for new smear takers, or those who have required retraining.

Adult↗
PubMed1999

Risk-adjusted measurement of primary cesarean sections: reliable assessment of the quality of obstetrical services.

A two-hospital system reported widely disparate Cesarean section rates in its component institutions. Statistical analysis determined that the apparent discrepancy was due primarily to patient-related factors. When risk-adjusted, both hospitals' rates were indistinguishable from expected rates. Reporting Cesarean section rates without appropriate risk adjustment yields potentially misleading results. Since reliable risk adjustment currently exists only for primary Cesarean sections, primary rates should be reported separately from "raw" rates for other procedures.

Cesarean Section↗
PubMed1999

The importance of capacities in psychoanalysis and the language of human development.

The author explores the human capacity to contain or hold experience--for self and other--by analysing the word capacity itself. Underlying the discussion is the proposition that hidden in the word capacity is a particular perspective on mental mechanisms fundamental to object-relations theory and that specific consideration of the word may, therefore, add to an understanding of these mechanisms. The author suggests that the term may have entered the language of psychoanalysis 'by mistake'. He then looks at its meaning in terms of its etymology, grammatical 'flavour', metaphorical significance and conceptual use, in particular by Bion and Winnicott. It is argued that psychoanalysis is part of, and makes a significant contribution to, a long tradition of learning from experience, in which development is understood as the progressive emergence or evolution of capacities. The underlying meaning of the word suggests that development is expansive rather than linear, step-by-step or cyclical (unlike, for example, stage, level, phase, position or loop). The author suggests that the notion of capacities may provide a framework for applying insights from the theory and practice of psychoanalysis in other organisational and societal contexts.

Humans↗
PubMed1998

An evaluation of partner notification for HIV infection in genitourinary medicine clinics in England.

OBJECTIVE: To evaluate the feasibility and effectiveness of a standardized HIV partner notification programme within genitourinary medicine clinics in England. DESIGN: A prospective survey of HIV partner notification activity over a 12-month period. SETTING: Nineteen genitourinary medicine clinics in England. PATIENTS AND PARTICIPANTS: A total of 501 eligible HIV-positive patients (either newly diagnosed or with whom partner notification had not been undertaken previously) seen during the study period. MAIN OUTCOME MEASURES: The numbers of partners named by patients, and the number of contacts notified, counselled and HIV-tested. RESULTS: Information on overall partner notification activity was obtained by reviewing available medical records of 471 patients; 353 (75%) had discussed partner notification with a health-care worker during the study period and 197 (42%) had undertaken partner notification. Detailed information on outcomes was obtained for only 70 patients who named 158 contacts as being at risk of acquiring HIV. Although 71 (45%) contacts were eventually notified, only 28 were subsequently seen in participating clinics. Almost all contacts (n = 27) requested HIV counselling and testing, and five were diagnosed HIV-positive. Patient referral was the most popular notification method chosen. CONCLUSIONS: This study illustrates some of the practical difficulties that limit HIV partner notification within genitourinary medicine clinics. These include health-care workers' misgivings about undertaking partner notification, insufficient locating information to identify contacts, and migration of newly diagnosed patients, which prevents continuity and completion of notification. Nevertheless, HIV partner notification uncovered previously undiagnosed HIV infections. Further work needs to be undertaken in staff training and policy implementation if higher rates of partner notification and outcome measurements are to be achieved.

Adolescent↗
PubMed1998

Molecular cloning, sequencing, and phylogenetic relationships of a new potyvirus: sugarcane streak mosaic virus, and a reevaluation of the classification of the potyviridae.

The nucleic acid of a serologically distinct potyvirus, originally isolated out of sugar cane from Pakistan, was reverse transcribed and the 3' terminal 2000 bp was PCR amplified, cloned, and sequenced. Phylogenetic comparisons of viruses representing each genus of the Potyviridae show that the Pakistani isolate is most closely related to the rymoviruses wheat streak mosaic virus (WSMV) and brome streak mosaic virus. We therefore propose that this new virus species be named sugar cane streak mosaic virus to reflect its similarity to WSMV. The phylogenetic data also show that the genus Rymovirus contains at least two unique evolutionary lineages. Thus the current taxonomy, based on transmission vector, is paraphyletic. We present an analysis of the taxonomic relationships among members of the family and propose a classification that both resolves the paraphyly and more accurately represents the evolutionary history of the Potyviridae.

Amino Acid Sequence↗
PubMed1998

Dose-limiting neurotoxicity in a phase I study of penclomedine (NSC 388720, CRC 88-04), a synthetic alpha-picoline derivative, administered intravenously.

3,5-Dichloro-2,4-dimethoxy-6-(trichloromethyl)pyridine (penclomedine, NSC 338720, CRC 88-04) is an alpha-picoline derivative with anti-tumour activity in preclinical models. Penclomedine administration by 1-h intravenous infusion on 5 consecutive days was repeated 3 weekly in the absence of dose-limiting toxicity (DLT) or disease progression. Five dose levels were investigated (22.5-340 mg m(-2) day[-1]). Eight men and eight women were entered, median age 59 years (range 39-73 years), with good performance status (ECOG 0/1) in 11 patients. A total of 13 out of 16 patients had received previous chemotherapy. Common toxicity criteria grade (CTCg) II vomiting was recorded at all dose levels. Neurotoxicity (cerebellar ataxia and dizziness) was the DLT, CTCg III toxicity occurring in three out of three patients treated at 340 mg m(-2) day(-1). CTCg III dizziness was noted in one out of three patients at 250 mg m(-2) day(-1). Neurotoxicity developed during the 1-h infusion and persisted for a variable period (maximum 5 h) after infusion. Prophylactic antiemetic drugs appeared to reduce associated vomiting but did not prevent ataxia. No antiproliferative toxicities were noted and no anti-tumour responses were documented. Penclomedine pharmacokinetic studies confirmed preclinical evidence of extensive apparent distribution (93 l m[-2]) and rapid clearance (41 l h[-1] m[-2]). Purkinje cell loss has been identified in preclinical models after intraperitoneal administration (O'Reilly et al, 1996a) and further clinical development of penclomedine will focus on oral administration.

Adult↗
PubMed1998

The effect of pregnancy on survival in women infected with HIV: a systematic review of the literature and meta-analysis.

OBJECTIVE: To investigate the effect of pregnancy on disease progression and survival in women infected with HIV by a systematic review of the literature and meta-analysis. METHODS: Appropriate publications were identified using electronic and hand searching of relevant journals from 1983 to 1996. Studies were included in the review if they were cohort studies, either prospective or retrospective, or case-control studies which investigated disease progression of pregnant women infected with HIV and included a control group of non-pregnant women infected with HIV for comparison. Methodological quality was assessed for each study. Data were extracted for predetermined outcome measures. Sensitivity analyses were performed to explore the association between pregnancy and disease progression for the following study characteristics: clinical setting (developed or developing countries), methodological quality (high or poor) and whether studies had controlled for potential confounding. RESULTS: Seven studies, all prospective cohorts, were eligible to be included in the review. The summary odds ratio for the risk of an adverse maternal outcome related to HIV infection and pregnancy were as follows: death 1.8 (85% CI 0.99-3.3); HIV disease progression 1.41 (95% CI 0.85-2.33); progression to an AIDS-defining illness 1.63 (95% CI 1.00-2.67) and fall of CD4 cell count to below 200 x 10(6)/L 0.73 (95% CI 0.17-3.06). Sensitivity analyses showed that HIV progression in pregnancy was significantly more common in a developing country setting (odds ratio 3.71, 95% CI 1.82-7.75) than in developed countries (odds ratio 0.55, 95% 0.27-1.11) and also significantly more common in high quality studies when compared to low quality ones, odds ratios 3.71 (95% CI 1.82-7.57) and 0.55 (95% CI 0.27-1.11), respectively. However, there appears to be less progression of HIV disease and progression to AIDS when studies attempted to control for confounding by matching or restriction techniques, although this was not statistically significant in either case. CONCLUSIONS: The findings of this review have implications for women infected with HIV who are pregnant or are considering a pregnancy. There does appear to be an association between adverse maternal outcomes and pregnancy in women infected with HIV, although this association is not strong. The relation may be due to the result of bias including residual confounding. Further large scale observational studies with long term follow up are required before this issue can be fully resolved.

Case-Control Studies↗
PubMed1998

The association between maternal HIV infection and perinatal outcome: a systematic review of the literature and meta-analysis.

OBJECTIVE: To investigate the association between maternal HIV infection and perinatal outcome by a systematic review of the literature and meta-analysis. METHODS: Appropriate publications were identified using electronic and hand searching of relevant journals from 1983 to 1996. Studies were included in the review if they were prospective cohorts with pregnant women identified as being HIV-infected with a control group of pregnant women who were not infected with HIV. Methodological quality was assessed for each study. Data were extracted for pre-determined outcome measures. Sensitivity analyses were performed to explore the association between HIV infection and an adverse perinatal outcome for the following study characteristics: clinical setting (developed or developing countries), methodological quality (high or poor) and whether studies controlled for potential confounding. RESULTS: Thirty-one studies were eligible to be included in the review. The summary odds ratio of the risk of pre-defined adverse perinatal outcomes related to maternal HIV infection were as follows: spontaneous abortion 4.05 (95% CI 2.75-5.96); stillbirth 3.91 (95% CI 2.65-5.77); fetal abnormality 1.08 (95% CI 0.7-1.66); perinatal mortality 1.79 (95% CI 1.14-2.81); neonatal mortality 1.10 (95% CI 0.63-1.93); infant mortality 3.69 (95% CI 3.03-4.49); intrauterine growth retardation 1.7 (95% CI 1.43-2.02); low birthweight 2.09 (95% CI 1.86-2.35) and pre-term delivery 1 83 (95% CI 1.63-2.06). Sensitivity analyses showed that the association between infant mortality and maternal HIV infection was stronger in studies conducted in developing countries when compared with developed countries [odds ratios (OR) 3.72 (95% CI 3.05-4.54) and 8.6 (95% CI 0.53-141.05), respectively]; studies of higher methodological quality compared with those of poorer quality [odds ratios 14.57 (95% CI 6.93-30.65) and 3.37 (95% CI 2.74-4.14), respectively] and studies which had used restriction or matching to control for potential confounding factors compared with those that had not [OR 11.60 (95% CI 5.71-23.58) and 3.35 (95% CI 2.73-4.12), respectively]. CONCLUSIONS: The findings of this review have implications for women infected with HIV who are planning a pregnancy or who find themselves pregnant. There appears to be an association, although not strong, between maternal HIV infection and an adverse perinatal outcome. This relationship may be due to bias including uncontrolled or residual confounding. There does, however, appear to be a real and large increase in the risk of infant death in developing countries associated with maternal HIV infection, especially so when there has been an attempt to control for confounding.

Cohort Studies↗
PubMed1998

Interactions between the structural domains of the RNA replication proteins of plant-infecting RNA viruses.

Brome mosaic virus (BMV), a positive-strand RNA virus, encodes two replication proteins: the 2a protein, which contains polymerase-like sequences, and the 1a protein, with N-terminal putative capping and C-terminal helicase-like sequences. These two proteins are part of a multisubunit complex which is necessary for viral RNA replication. We have previously shown that the yeast two-hybrid assay consistently duplicated results obtained from in vivo RNA replication assays and biochemical assays of protein-protein interaction, thus permitting the identification of additional interacting domains. We now map an interaction found to take place between two 1a proteins. Using previously characterized 1a mutants, a perfect correlation was found between the in vivo phenotypes of these mutants and their abilities to interact with wild-type 1a (wt1a) and each other. Western blot analysis revealed that the stabilities of many of the noninteracting mutant proteins were similar to that of wt1a. Deletion analysis of 1a revealed that the N-terminal 515 residues of the 1a protein are required and sufficient for 1a-1a interaction. This intermolecular interaction between the putative capping domain and itself was detected in another tripartite RNA virus, cucumber mosaic virus (CMV), suggesting that the 1a-1a interaction is a feature necessary for the replication of tripartite RNA viruses. The boundaries for various activities are placed in the context of the predicted secondary structures of several 1a-like proteins of members of the alphavirus-like superfamily. Additionally, we found a novel interaction between the putative capping and helicase-like portions of the BMV and CMV 1a proteins. Our cumulative data suggest a working model for the assembly of the BMV RNA replicase.

Animals↗
PubMed1998

Primary and secondary reinforcers in performance of a 1.0-mile walk/jog by adolescents with moderate mental retardation.

Based on visual inspection of data, reinforcement procedures, namely, use of verbal praise and verbal praise plus token exchange, were at least mildly influential in improving performance of 5 youth with moderate mental retardation compared to their initial performance without reinforcers. These findings suggest specific reinforcement may improve the time for aerobic activity by adolescents with moderate mental retardation.

Adolescent↗
PubMed1997

Central interleukin-1 receptors as mediators of sickness.

These data establish that cytokines, such as IL-1, can act on specific receptors within the brain to induce many symptoms of sickness. A number of inflammatory stimuli in the periphery can activate both the transcription and translation of IL-1 within the central nervous system. It will now be important to determine if similar central IL-1 pathways are activated during SLE and whether these central inflammatory cytokines are involved in the neurologic complications that often accompany this disease.

Animals↗
PubMed1997

Conformational control of cyclosporin through substitution of the N-5 position. A new class of cyclosporin antagonists.

Cyclosporin A (CsA) can be regiospecifically alkylated at the NH of Val-5 with reactive bromides in the presence of phosphazene-base P4-t-Bu to yield derivatives 2-5. These are devoid of immunosuppressive activity in vitro but they have binding affinity for cyclophilin A (CypA) similar to that of CsA and thus represent a new class of cyclosporin antagonists. 1H NMR (DMSO-d6) studies have shown that the compounds exist in a single, all trans conformation. A comparison of this NMR data with X-ray crystallographic analysis of a CypA/CsA derivative complex demonstrates that the solution structure does not correspond to the bioactive conformation.

Cyclosporine↗
PubMed1997

HIV partner notification policy and practice within GUM clinics in England: where are we now?

OBJECTIVES: To evaluate the extent to which larger genitourinary medicine (GUM) clinics in England have established local clinic policies for HIV Partner Notification (PN) and to describe the process of HIV PN within this setting. DESIGN: A cross-sectional survey of HIV PN policies and practices within GUM clinics. SUBJECTS AND SETTING: Senior consultants in 59 GUM clinics in England. MAIN OUTCOME MEASURES: The presence of clinic policies for HIV PN, indicators of HIV PN activity (that is, its initiation, documentation, performance and evaluation) and factors hindering the acceptance of HIV PN into clinical practice. RESULTS: Only 18% (10/57) of respondents stated that their clinics had developed their own local policies for HIV PN. Fifteen percent (9/58) of clinics had audited HIV PN activity, 15% had provided specific HIV PN training for doctors and 47% (27/58) for health advisers. Within GUM clinics, health advisers play a key role in the HIV PN process, being responsible for initiating the discussion of partners, patient follow-up and documenting HIV PN activity in patients' notes. Notifying partners was primarily seen as the responsibility of the newly diagnosed HIV positive patient. Although 77% (43/56) of responding consultants believed that HIV PN had become an accepted part of their clinics' practice, the perceived unacceptability of HIV PN to patients and health care workers were seen as important limiting factors. CONCLUSION: In many GUM clinics, local policies on HIV PN have yet to be established and appropriate training for the health personnel provided. Nevertheless, there appears to be wide-spread acceptance of HIV PN in clinical practice with an acknowledgement of its limiting factors. Further research into the acceptability of HIV PN to health care workers and patients in this setting should be undertaken.

Attitude of Health Personnel↗