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Biomedical subjects

S Duffy

Publications and source records attributed to S Duffy.

At least 73 records · Page 4Linked to original sources

One thousand initiated cycles of in vitro fertilization in women > or = 40 years of age.

OBJECTIVE: To evaluate the results of IVF in women > or = 40 years of age using their own oocytes. DESIGN: Retrospective study. SETTING: Wolfson and Royal Masonic in vitro fertilization units, London, United Kingdom. PATIENT(S): A total of 1,087 IVF cycles were started in women > or = 40 years of age. INTERVENTION(S): Medical records of patient outcomes were reviewed. MAIN OUTCOME MEASURE(S): Clinical pregnancy, miscarriage, and delivery rates. RESULT(S): Of the 1,087 cycles started in 471 women > or = 40 years of age, 842 reached oocyte retrieval (77.5%) and 702 had embryos transferred (64.6%). The pregnancy rate (PR) was significantly lower in women > or = 40 years of age than in a control group of women <40 years of age (11.3% versus 28.2%). It decreased sharply in women >42 years of age, and no women >45 years of age had a child. Women > or = 40 years of age were more likely to miscarry (27% versus 12.7%). When only one embryo was available for transfer, the PR was 3.3%. When >2 embryos were available for transfer, the PR was similar whether 2 or 3 embryos were replaced. No triplet pregnancy occurred. Women > or = 40 years of age achieved a cumulative PR of 30% after three cycles with a cumulative "take home baby" rate of 21%. CONCLUSION(S): In vitro fertilization is a reasonable treatment for women <45 years of age using their own gametes. Those with a "good response" in their first attempt may be encouraged to complete three cycles with an acceptable chance of conception.

Adult↗

The effects of interaction between familial and reproductive factors on breast cancer risk: a combined analysis of seven case-control studies.

In this paper, a combined analysis was performed to study the interaction between familial risk and reproductive life factors. In particular, the interaction between familial risk and breast cell mitotic activity (BCMA), as assessed by duration of ovarian activity, was investigated because of the potential importance of mitotic activity on genetically susceptible cells. The present analysis included 3152 cases and 4404 controls in seven case-control studies from four countries. The interaction effect was estimated in each study separately, then combined using two different methods: a multivariate weighted average and a Bayesian random-effects model. The main effects of reproductive life factors on the risk of breast cancer were in agreement with the previous findings. In particular, an increased duration of BCMA before the first childbirth and over life was found to increase the risk of breast cancer (P < 0.001). Slightly increasing but non-significant, familial risks were observed with increasing number of children (P = 0.17), increasing age at first childbirth (P > 0.2) and increasing duration of BCMA (P > 0.2). There was no modification in familial risk with age at menarche and no clear pattern with menopause characteristics. A weak influence of reproductive and menstrual factors on the familial risk emerged from the present study.

Adult↗

Innovations in teaching obstetrics and gynaecology--the Theme Afternoon.

The Theme Afternoon is an exciting and popular new innovation in teaching that we have successfully introduced in Obstetrics and Gynaecology. It utilizes many of the elements of the SCORPIO and SPICES models of teaching. In particular, it involves problem-based learning and an integrated approach to teaching. One afternoon per week is set aside for each theme. So far we have introduced Theme Afternoons in Contraception and Sterilization, The Menopause and Hormone Replacement Therapy, Screening for Disease in O&G and Examination Techniques. All Theme Afternoons follow a similar structure: a targeted tutorial, 10 MCQs, a 15-minute coffee break, OSCEs, and role-play with feedback. An evaluation form is completed by each student assessing the session and the tutor. The Theme Afternoon provides the student with stimulation to learn. It has a wide appeal and has been well received by learners. Students learn at a more controlled pace and in a more sheltered environment, which may be less stressful to them. It evaluates well and is flexible in its structure. The changes that occur are student-led and the desire for it to continue is student-driven. It is easily adaptable to other medical specialties or even nonmedical curriculums. We recommend it as a realistic opportunity to raise standards and enthusiasm in medical education.

Education, Medical, Undergraduate↗

Activation of endogenous antioxidant defenses in neuronal cells prevents free radical-mediated damage.

Dopamine (DA) is oxidized to the neurotoxic prooxidant species H2O2, OH., and DA quinones. We tested whether dimethyl fumarate (DMF), an electrophile shown to induce a pleiotropic antioxidant response in nonneuronal cells, could reduce the toxicity of DA metabolites in neural cells. Treatment of the N18-RE-105 neuroblastoma-retina hybridoma cell line with 30-150 microM dopamine led to cell death within 24 h, which increased steeply with dose, decreased with higher plating density, and was blocked by the H2O2-metabolizing enzyme catalase. Pretreatment with DMF (30 microM, 24 h) significantly attenuated DA and H2O2 toxicity (40-60%) but not that caused by the calcium ionophore ionomycin. DMF treatment also elevated total intracellular GSH and increased activities of the antioxidant enzymes quinone reductase (QR), glutathione S-transferase (GST), glutathione reductase, and the pentose phosphate enzyme glucose-6-phosphate dehydrogenase. To assess the protective efficacy of QR and GST, a stable cell line was constructed in which these enzymes were overexpressed. Cell death in the overexpressing line was not significantly different from that in a cell line expressing normal QR and GST activities, indicating that these two enzymes alone are insufficient for protection against DA toxicity. Although the relative importance of a single antioxidant enzyme such as QR or GST may be small, antioxidant inducers such as DMF may prove valuable as agents that elicit a broad-spectrum neuroprotective response.

Animals↗

Flexible outpatient hysteroscopy without anaesthesia: a safe, successful and well tolerated procedure.

The objective of this study was to assess the feasibility and tolerance of diagnostic outpatient flexible hysteroscopy without anaesthesia. Records from 554 consecutive patients were analysed retrospectively. Success rate, reasons for failure, adverse reactions and level of pain were the main outcome measures. Hysteroscopy was successful in 90.5% of patients and well tolerated in 93.3%; 5.4% experienced moderate to severe pain. Inability to negotiate the cervical canal accounted for 47% of failed procedures and poor view for 42%. These results suggest that flexible outpatient hysteroscopy without anaesthesia is a successful and well tolerated procedure.

Adult↗

Mammographic parenchymal patterns and mode of detection: implications for the breast screening programme.

OBJECTIVES: To assess the effects of mammographic parenchymal patterns on the risk of breast cancer detected at first screen, second screen, and in the interval between these two screens. SETTINGS: A nested case-control study within a screening cohort in East Anglia was designed. The study group comprised 502 patients with cancer at the prevalence screening round, 198 patients with interval cancer, and 175 with cancer at the first incidence screen. These patients were matched with 2601 controls. METHODS: The mammographic parenchymal patterns of breast tissue were assessed according to Wolfe's classification. Statistical analysis was by conditional logistic regression. RESULTS: Overall, 67% of patients and 59% of controls were considered to have high risk pattern (P2 + DY) mammogram. The risk associated with P2 or DY mammographic patterns compared with N1 was higher for interval cancers (odds ratios (ORs) 2.2 and 2.4 respectively) than for screen detected cancers (ORs 1.7 and 1.1 respectively). For interval cancers in the first 18 months after the last negative mammogram, the risk was particularly high (ORs 3.8 for P2 and 4.1 for DY compared with N1). The high risk associated with P2 and DY patterns was concentrated on invasive ductal grade III cancers (ORs 2.7 and 3.8) rather than grade I or II cancers (ORs 1.6 and 1.2). CONCLUSIONS: The study strongly suggests that screening effectiveness is reduced for high risk parenchymal patterns which are associated with high grade cancers. Changes should aim at improving screening sensitivity for dense parenchymal patterns, and the diagnosis of high grade tumours.

Aged↗

Family history and the risk of breast cancer: a systematic review and meta-analysis.

An increased risk of breast cancer in women with a family history of breast cancer has been demonstrated by many studies using a variety of study designs. However, the extent of this risk varies according to the nature of the family history (type of relative affected, age at which relative developed breast cancer and number of relatives affected) and may also vary according to age of the individual. The aim of our study was to identify all the published studies which have quantified the risk of breast cancer associated with a family history of the disease, and to summarise the evidence from these studies, with particular emphasis on age-specific risks according to subject and relative age. Seventy-four published studies were identified. The pooled estimate of relative risk (RR) associated with various family histories was as follows: any relative, RR = 1.9 (95% CI, 1.7-2.0); a first-degree relative, RR = 2.1 (CI = 2.0, 2.2); mother, RR = 2.0 (CI = 1.8, 2.1); sister, RR = 2.3 (CI = 2.1, 2.4); daughter, RR = 1.8 (CI = 1.6, 2.0); mother and sister, RR = 3.6 (CI = 2.5, 5.0); and a second-degree relative, RR = 1.5 (CI = 1.4, 1.6). Risks were increased in subjects under age 50 and when the relative had been diagnosed before age 50.

Adult↗

Foot-and-mouth disease virus-infected but not vaccinated cattle develop antibodies against recombinant 3AB1 nonstructural protein.

Foot-and-mouth disease (FMD) vaccines induce antibodies against structural and some nonstructural proteins present in vaccine preparations. To differentiate between FMDV-infected and vaccinated animals, we developed immunochemical assays capable of detecting antibodies against a FMDV nonstructural protein. Recombinant nonstructural 3AB1 protein was expressed in E.coli and in insect cells and used to detect anti-3AB1 antibodies. ELISA and Western blot analysis showed that sera from cattle infected with FMDV reacted with recombinant 3AB1 protein whereas sera from cattle which had been vaccinated against FMDV, mock-infected, or infected with different bovine viruses did not recognize the 3AB1 protein. In contrast, anti-virus infection associated antigen (VIAA) antibodies were present in both FMDV-infected and vaccinated animals. Detection of anti-3AB1 antibodies in sera of experimentally infected cattle obtained between 7 and 560 days postinfection indicated that immunological tests based on the detection of recombinant 3AB1 protein could be used for the diagnosis of FMDV infection.

Animals↗

The relationship between dietary fat intake and risk of colorectal cancer: evidence from the combined analysis of 13 case-control studies.

The objective of this study was to examine the effects of the intake of dietary fat upon colorectal cancer risk in a combined analysis of data from 13 case-control studies previously conducted in populations with differing colorectal cancer rates and dietary practices. Original data records for 5,287 cases of colorectal cancer and 10,470 controls were combined. Logistic regression analysis was used to estimate odds ratios (OR) for intakes of total energy, total fat and its components, and cholesterol. Positive associations with energy intake were observed for 11 of the 13 studies. However, there was little, if any, evidence of any energy-independent effect of either total fat with ORs of 1.00, 0.95, 1.01, 1.02, and 0.92 for quintiles of residuals of total fat intake (P trend = 0.67) or for saturated fat with ORs of 1.00, 1.08, 1.06, 1.21, and 1.06 (P trend = 0.39). The analysis suggests that, among these case-control studies, there is no energy-independent association between dietary fat intake and risk of colorectal cancer. It also suggests that simple substitution of fat by other sources of calories is unlikely to reduce meaningfully the risk of colorectal cancer.

Adult↗

Von Willebrand factor and risk of ischemic stroke.

We carried out a case-control study to determine whether von Willebrand factor (vWF) antigen (and factor VII and tissue plasminogen activator [tPA] antigens) are associated with ischemic stroke. Ninety-five patients with transient ischemic attack or minor ischemic stroke recruited from the Oxfordshire Community Stroke Project and one neurology clinic were compared with 236 controls, group-matched for age and sex, from the same general practitioners as the incident cases. In crude analyses, concentrations of vWF antigen were significantly higher in cases than in controls (p = 0.004). The age- and sex-adjusted odds ratios from lowest (referent) to highest quartile of vWF antigen were 1.00, 1.15, 2.34, and 2.36 (trend test, p = 0.006). Factor VII antigen and tPA antigen were not significantly different between cases and controls. Although adjustment for other potential risk factors abolished the statistical significance of the association between vWF and disease, this was largely due to the influence of history of ischemic heart disease. We conclude that vWF is a potent and independent risk factor for transient ischemic attack, minor ischemic stroke, and, by extrapolation, ischemic stroke in general. The data also suggest that vWF may be a risk factor for both ischemic stroke and ischemic heart disease. We found no evidence to implicate factor VII and tPA as risk factors for ischemic stroke.

Adult↗

A comparison of the effectiveness of 28 kV (grid) versus 25 kV (no grid) mammographic techniques for breast screening.

The purpose of this study was to compare the clinical effectiveness of breast screening using a mammographic technique of 25 kV without a grid, with one of 28 kV with a grid. Effectiveness is judged by cancer detection, interval cancer rates, sensitivity and specificity calculations and tumour characteristics. The doses on standard physics tests given by the three machines when these exposure factors are selected were compared to see whether there is any scientific basis for recommendations on which is the more effective technique. The experiment was undertaken in the prevalence round of a screening programme set up in the UK in 1987. The main comparison is on 25,078 women randomized to one or other technique after March 1989. Comparison can also be made with the preceding 8482 women, who were examined by the 25 kV method, but not randomized and in whom there were a variety of other differences. In the randomized group there was no statistically significant difference in cancer detection. A minor difference in overall numbers without statistical significance was seen in favour of the 28 kV grid technique, but is offset by a greater interval cancer rate in this group. Small cancer detection was equal in the two groups. By contrast, the first 8482 women showed significantly worse screening performance, both in lower overall and small cancer detection rate, and in increased number of interval cancers, for which the explanation is likely to be complex. The dose measurements show that the use of a higher tube potential with the grid mitigates the dose increase that may have been expected. The choice between these two techniques is therefore neither automatically made by greater cancer detection nor made on grounds of dose. There was a minor dose penalty in using the 28 kV technique with grid.

Breast Neoplasms↗

[Seroepidemiologic indicators for the evaluation of campaigns for the control of foot-and-mouth disease].

A sero-epidemiological survey was conducted in two districts in Argentina between 1993 and 1995, to provide additional information on the epidemiology of foot and mouth disease (FMD) in Argentina and to assess the level of immunity in cattle populations, and the circulation of FMD virus. As part of the final stage of this survey, a comparison was made of the results obtained by the enzyme-linked immunosorbent assay (ELISA) and agar gel immunodiffusion techniques. Levels of population immunity against the four types of virus included in the vaccine increased progressively during the period of the survey until, in 1995, at the end of the vaccination period, the percentage of animals possessing adequate levels of protection was approximately 77% in yearlings, and more than 94% in cattle over one year old. During the three-year study, there was a clear tendency for viral activity to diminish, until in 1995 when between 3% and 0.6% were positive to the agar gel immunodiffusion test for the antigen associated with viral infection. By contrast, the ELISA detected antibody in about five times as many animals. The authors show how the increase in the level of population immunity was accompanied by a fall in viral activity.

Animals↗

Detection of virus infection-associated antigen and 3D antibodies in cattle vaccinated against foot and mouth disease.

The analysis of sera obtained from animals vaccinated or revaccinated with inactivated vaccines against foot and mouth disease (FMD) virus showed that these vaccines induced antibodies against the virus infection-associated (VIA) antigen, detectable by agar gel immunodiffusion (AGID). The present study evaluates the antibody response to protein 3D and the VIA antigen (VIAA) of FMD virus induced by different vaccines in a group of 51 calves. This response was detected using AGID and a liquid-phase blocking sandwich enzyme-linked immunosorbent assay (ELISA) for anti-3D antibodies (ELISA-3D). No anti-VIAA or anti-3D antibodies were detected after the initial vaccination. Following revaccination, animals giving positive results were detected by both methods. This immune response disappeared 60-120 days post-revaccination (dprv) according to the AGID method, and 90-180 dprv when ELISA-3D was used. Samples of oesophageal-pharyngeal fluid obtained from animals that remained positive for anti-VIAA antibodies at 90-120 dprv gave negative results for viral isolation, indicating that the transitional antibody response induced by the vaccine was due to the presence of non-structural antigens in the vaccine and not to viral infection. These results indicate that the ELISA-3D method could be used as a complementary method for sero-epidemiological studies as an indirect indicator of viral activity, as long as the age and vaccination status of the animals being sampled are taken into consideration.

Animals↗

Randomized, double-blind, placebo-controlled trial of intravenous ketamine in acute asthma.

STUDY OBJECTIVE: To evaluate the efficacy of IV ketamine in the management of acute, severe asthma. METHODS: This prospective, randomized, double-blind, placebo-controlled clinical trial at an urban teaching hospital emergency department involved 53 consecutive patients aged 18 to 65 with a clinical diagnosis of acute asthmatic exacerbation and a peak expiratory flow of less than 40% of the predicted value after three albuterol nebulizer treatments. All patients received oxygen, continuous nebulized albuterol, and methylprednisolone sodium succinate (Solu-Medrol). Patients then received either ketamine hydrochloride in a bolus of .2 mg/kg followed by IV infusion of .5 mg/kg per hour for 3 hours or a placebo bolus and infusion for 3 hours. Because of the occurrence of dysphoric reactions, the bolus dose was lowered to .1 mg/kg after the first 9 patients; the infusion dose was kept the same. RESULTS: The first nine patients were eliminated from analysis. Repeated ANOVA testing on the remaining 44 patients determined significant improvements over time within each treatment group in peak flow (F=3.637, P=.004). Borg score (F=22.959, P=.001), respiratory rate (F=8.11, P=.0001). and 1-second forced expiratory volume (F=9.076, P=.001). However, no difference could be detected over time between treatment groups (power, 80%). Patients receiving ketamine gave the treatment a rating of 4.3 on a scale of 1 to 5, whereas those receiving placebo scored their treatment 3.7 (P=.0285). The hospital admission rate was not different between treatment groups (P=.1088). CONCLUSION: IV ketamine at a dose low enough to avoid dysphoric reactions demonstrated no increased bronchodilatory effect compared with standard therapy in treating exacerbations of asthma in the ED. Although there was a slight increase in satisfaction in the ketamine group, no clinical benefit in terms of hospital admission rate was noted.

Adolescent↗

In vitro ischemia promotes calcium influx and intracellular calcium release in hippocampal astrocytes.

The intracellular calcium concentration ([Ca2+])i of astrocytes within rat hippocampal slices was measured during simultaneous hypoxia and hypoglycemia to examine the early intracellular signaling events induced by this in vitro model of ischemia. Hypoxia-hypoglycemia for 3.3-7.5 min evoked [Ca2+]i increases in astrocytes iontophoretically loaded with calcium orange (11/14 slices; 2.5 min to peak [Ca2+]i, 5 min to > 60 min duration). Calcium elevations also were observed in the absence of extracellular calcium ([Ca2+]o) (4/4 slices), indicative of Ca2+ release from internal stores. Hypoxia-hypoglycemia depolarized astrocytes (51 +/- 16 mV), suggesting additional contribution from voltage-gated Ca2+ influx. Depolarization of a similar magnitude (51 +/- 4 mV) by 50 mM extracellular potassium ([K+]o triggered [Ca2+]i increases (20/24 slices), which were blocked by removal of [Ca2+]o (8/8 slices) indicating that depolarization promoted Ca2+ influx. Voltage-gated Ca2+ influx and internal release were measured in accurately isolated astrocytes during in vitro ischemia to examine these processes in the absence of surrounding neurons. Hypoxia-hypoglycemia (7.5-34.0 min) induced only modest, slow increases in the basal [Ca2+]i of Fura-2-loaded isolated astrocytes (average 12% increase in Fura-2 ratio R340/380 after 10 min) that were blocked by [Ca2+]o removal. Voltage-gated Ca2+ influx was still functional under ischemia, however, as 50 mM [K+]o evoked [Ca2+]i increases (14/14 cells, delta R340/380 of 48%) approximately equal to preischemic responses. Isolated neurons displayed large irreversible increases in basal [Ca2+]i after 1.5-6.5 min in vitro ischemia (10/12 cells; average delta R 340/380 of 152%). The absence of significant basal [Ca2+]i increases on isolated astrocytes indicates that ischemia-induced Ca2+ influx and internal release in astrocytes within slices depend on signals released from neurons (K+, neurotransmitters). Ischemic [Ca2+]i elevations may constitute a signaling mechanism for postischemic reactive responses.

Animals↗

Postoperative care of the lung transplant recipient.

This article reviews the nursing care of the patient who receives a lung transplant, starting with preparation for admission to the ICU. Issues of oxygenation, airway clearance, hemodynamic and fluid assessment, infection control, incisional assessment, and pain are addressed throughout the hospitalization. Emotional support, discharge and medication teaching, and changes in lifestyle are all important aspects of the rehabilitation phase before discharge.

Humans↗

The tissue and thermal effects of electrosurgery in the uterine cavity.

A brief outline of the physics associated with the production of electrosurgical wave-forms has been described. The conversion of electrical to thermal energy in electrosurgical techniques has demonstrable tissue and thermal actions and these were discussed in greater detail. In vitro electroresection was associated with a narrow ZTN underlying the electrode that did not vary with power output, but was related to duration of exposure. For blend 2 cutting output the mean ZTN ranged from 0.97 to 1.40 mm for a single sweep of the electrode. With longer time increments this ZTN increased to 2.20 mm. Coagulation by desiccation, in vitro, resulted in a depth of destruction of 3.24-3.49 mm that did not vary with power output or duration of exposure. Fulguration only achieved a depth of destruction of up to 1.78 mm that was related to time. This confined-ZTN in the fulguration mode was felt to be too narrow to destroy the deeply seated myometrial gland elements. Thermal transmission through blocks of human uterine tissue, in vitro, has been demonstrated. Resection generated a maximum rise of 5.8 degrees C at 12 mm from the electrode, with desiccation, a maximum of 4.0 degrees C. It was also demonstrated that resection and desiccation have differing thermal profiles, the latter being more confined in nature. Both power output and duration of exposure in resection are important factors, in vitro, with regard to heat generation. Duration of exposure during desiccation is important in terms of heat generation, but not power output. Repetitive electrosurgical insults have a cumulative effect on the thermal profile in vitro. The underlying damage to uterine tissue during electrosurgery in vivo has been established. In electroresection the zone of thermal necrosis was related to duration of exposure, whereas in electrodesiccation the damage appeared confined, self-limiting, and not time-related. The lack of clinically significant demonstrable thermal transmission through the uterus was important. However, excessively prolonged application of electrosurgical energy (greater than 5 seconds) in the narrow regions of the uterus, especially with electroresection, could still be potentially dangerous. The use of the desiccation mode in the cornual regions is recommended for three reasons; the loop electrode has greater potential for perforation in this thin region (because of its diameter); the desiccating mode appeared to have a clearly defined, consistent ZTN that did not alter appreciably; and the thermal imaging of the ball electrode, in vitro, demonstrated the more confined nature of its thermal profile compared to the loop electrode.(ABSTRACT TRUNCATED AT 400 WORDS)

Electrosurgery↗

Is neuroblastoma screening evaluation needed and feasible?

Despite the five million children who have been screened for neuroblastoma in Japan through detection of catecholamine metabolites, it is still uncertain whether screening for this disease is beneficial. The Japanese study has clearly indicated that screening at 6 months or earlier leads to heavy overdiagnosis. It is shown in this paper that screening at a later age may give the same reduction in mortality with possibly less overdiagnosis. However, it is estimated that, even with two screens at 12 and 18 months, the reduction in mortality would not greatly exceed 25%, under realistic hypotheses on the length of the preclinical phase of the disease. The evaluation of the efficacy of this screening strategy would need the recruitment of half a million children per year over 5-7 years and the follow-up of an equal number of controls. Such a trial would improve our knowledge of the natural history of the disease and might help to answer some questions raised recently regarding its biological heterogeneity.

Age Factors↗