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Biomedical subjects

J Carter

Publications and source records attributed to J Carter.

At least 73 records · Page 4Linked to original sources

Maternal and child health after assisted vaginal delivery: five-year follow up of a randomised controlled study comparing forceps and ventouse.

OBJECTIVE: To undertake a five year follow up of a cohort of women and children delivered by forceps or vacuum extractor in a randomised controlled study. DESIGN: Follow up of a randomised controlled trial. SETTING: District general hospital in the West Midlands. POPULATION: Follow up questionnaires were sent to 306 of the 313 women originally recruited at the North Staffordshire Hospital to a randomised controlled study comparing forceps and vacuum extractor for assisted delivery. Two hundred and twenty-eight women responded (74.5%) and all were included in the study; forceps (n = 115) and vacuum extractor (n = 113). MAIN OUTCOME MEASURES: Bowel and urinary dysfunction, child vision assessment, and child development. RESULTS: Maternal adverse symptoms at long term follow up were relatively common. Urinary incontinence of various severity was reported by 47%, bowel habit urgency was reported by 44% (98/225), and loss of bowel control 'sometimes' or 'frequently' by 20% of women (46/226). No significant differences between instruments were found in terms of either bowel or urinary dysfunction. Overall, 13% (20/158) of children were noted to have visual problems. There was no significant difference in visual function between the two groups: ventouse 11/86 (12.8%), compared with forceps 9/72 (12.5%); odds ratio 0.97, 95% CI 0.38-2.50. Of the 20 children with visual problems, a family history was known in 18, and 17/18 (94%) had a positive family history for visual problems. No significant differences in child development were found between the two groups. CONCLUSIONS: There is no evidence to suggest that at five years after delivery use of the ventouse or forceps has specific maternal or child benefits or side effects.

Adult↗

Argument for the surgical staging of apparent early endometrial cancer.

Cancer of the uterine corpus, commonly referred to as cancer of the endometrium or cancer of the uterus, continues to be the most common pelvic genital malignancy affecting western women (1). In 1998 in the United States 36,100 women were diagnosed with this cancer, and there were 6,300 deaths from this condition in that year. Of concern is that despite a relatively stable incidence over the last decade, the annual number of deaths since 1987 from endometrial cancer has more than doubled (2). Many controversies exist in the management of apparent early endometrial cancer. These include: 1. The role of surgical staging which includes pelvic lymphadenectomy. 2. The role of the subspecialist gynaecological oncologist in primary surgical treatment. 3. Indications for vaginal and external beam radiotherapy. 4. Who is at risk for recurrence? 5. The role of laparoscopic approach to the management of this disease. Despite their importance, these and other issues have not been appropriately addressed by prospective randomized studies. Treatment strategies and algorithms have thus been based upon a combination of clinicopathological studies and uncontrolled reviews. The views expressed in this clinical opinion are those of the Sydney Gynaecologic Oncology Group and reflect our philosophy on the current management of this tumour, supported by recent and appropriate peer reviewed scientific literature.

Brachytherapy↗

Effect of repaglinide addition to metformin monotherapy on glycemic control in patients with type 2 diabetes.

OBJECTIVE: To compare the effect of repaglinide in combination with metformin with monotherapy of each drug on glycemic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 83 patients with type 2 diabetes who had inadequate glycemic control (HbA1c > 7.1%) when receiving the antidiabetic agent metformin were enrolled in this multicenter, double-blind trial. Subjects were randomized to continue with their prestudy dose of metformin (n = 27), to continue with their prestudy dose of metformin with the addition of repaglinide (n = 27), or to receive repaglinide alone (n = 29). For patients receiving repaglinide, the optimal dose was determined during a 4- to 8-week titration and continued for a 3-month maintenance period. RESULTS: In subjects receiving combined therapy, HbA1c was reduced by 1.4 +/- 0.2%, from 8.3 to 6.9% (P = 0.0016) and fasting plasma glucose by 2.2 mmol/l (P = 0.0003). No significant changes were observed in subjects treated with either repaglinide or metformin monotherapy in HbA1c (0.4 and 0.3% decrease, respectively) or fasting plasma glucose (0.5 mmol/l increase and 0.3 mmol/l decrease respectively). Subjects receiving repaglinide either alone or in combination with metformin, had an increase in fasting levels of insulin between baseline and the end of the trial of 4.04 +/- 1.56 and 4.23 +/- 1.50 mU/l, respectively (P < 0.02). Gastrointestinal adverse events were common in the metformin group. An increase in body weight occurred in the repaglinide and combined therapy groups (2.4 +/- 0.5 and 3.0 +/- 0.5 kg, respectively; P < 0.05). CONCLUSIONS: Combined metformin and repaglinide therapy resulted in superior glycemic control compared with repaglinide or metformin monotherapy in patients with type 2 diabetes whose glycemia had not been well controlled on metformin alone. Repaglinide monotherapy was as effective as metformin monotherapy.

Australia↗

The art and science of searching MEDLINE to answer clinical questions. Finding the right number of articles.

The current medical environment makes information retrieval a matter of practical importance for clinicians. Many avenues present themselves to the clinician, but here we focus on MEDLINE by summarizing the current state of the art and providing an innovative approach for skill enhancement. Because new search engines appear rapidly, we focus on generic principles that can be easily adapted to various systems, even those not yet available. We propose an idealized classification system for the results of a MEDLINE search. Type A searches produce a few articles of high quality that are directly focused on the immediate question. Type B searches yield a large number of articles, some more relevant than others. Type C searches produce few or no articles, and those that are located are not germane. Providing that relevant, high-quality articles do exist, type B and C searches may often be improved with attention to search technique. Problems stem from poor recall and poor precision. The most daunting task lies in achieving the balance between too few and too many articles. By providing a theoretical framework and several practical examples, we prepare the searcher to overcome the following barriers: a) failure to begin with a well-built question; b) failure to use the Medical Subject Headings; c) failure to leverage the relationship between recall and precision; and d) failure to apply proper limits to the search. Thought and practice will increase the utility and enjoyment of searching MEDLINE.

Clinical Medicine↗

High-dose-rate brachytherapy alone post-hysterectomy for endometrial cancer.

PURPOSE: To evaluate the outcome of post-hysterectomy adjuvant vaginal high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALS: A retrospective analysis was performed on a series of 143 patients with endometrial cancer treated with HDR brachytherapy alone post-hysterectomy from 1985 to June 1993. Of these patients, 141 received 34 Gy in four fractions prescribed to the vaginal mucosa in a 2-week period. The median follow-up was 6.9 years. Patients were analyzed for treatment parameters, survival, local recurrence, distant relapse, and toxicity. RESULTS: Five-year relapse free survival and overall survival was 100% and 88% for Stage 1A, 98% and 94% for Stage IB, 100% and 86% for Stage IC, and 92% and 92% for Stage IIA. The overall vaginal recurrence rate was 1.4%. The overall late-toxicity rate was low, and no RTOG grade 3, 4, or 5 complications were recorded. CONCLUSION: These results are similar to reported international series that have used either low-dose-rate or HDR brachytherapy. The biological effective dose was low for both acute and late responding tissues compared with some of the HDR brachytherapy series, and supports using this lower dose and possibly decreasing late side-effects with no apparent increased risk of vaginal recurrence.

Adult↗

Neurofilament (NF) assembly; divergent characteristics of human and rodent NF-L subunits.

Previous studies have shown that rodent neurofilaments (NF) are obligate heteropolymers requiring NF-L plus either NF-M or NF-H for filament formation. We have assessed the competence of human NF-L and NF-M to assemble and find that unlike rat NF-L, human NF-L is capable of self-assembly. However, human NF-M cannot form homopolymers and requires the presence of NF-L for incorporation into filaments. To investigate the stage at which filament formation is blocked, the rod domains or the full-length subunits of human NF-L, human NF-M, and rodent NF-L were analyzed in the yeast "interaction trap" system. These studies demonstrated that the fundamental block to filament formation in those neurofilaments that do not form homopolymers is at the level of dimer formation. Based on theoretical biophysical considerations of the requirements for the formation of coiled-coil structures, we predicted which amino acid differences were likely to be responsible for the differing dimerization potentials of the rat and human NF-L rod domains. We tested these predictions using site-specific mutagenesis. Interestingly, single amino acid changes in the rod domains designed to restore or eliminate the coiled-coil propensity were found respectively to convert rat NF-L into a subunit capable of homopolymerization and human NF-L into a protein that is no longer able to self-assemble. Our results additionally suggest that the functional properties of the L12 linker region of human NF-L, generally thought to assume an extended beta-sheet conformation, are consonant with an alpha-helix that positions the heptad repeats before and after it in an orientation that allows coiled-coil dimerization. These studies reveal an important difference between the assembly properties of the human and rodent NF-L subunits possibly suggesting that the initiating events in neurofilament assembly may differ in the two species.

Amino Acid Sequence↗

Efficient activation of nucleoside phosphoramidites with 4,5-dicyanoimidazole during oligonucleotide synthesis.

A new activator for the coupling of phosphoramidites to the 5'-hydroxyl group during oligonucleotide synthesis is introduced. The observed time to complete coupling is twice as fast with 4, 5-dicyanoimidazole (DCI) as the activator, compared with 1 H -tetrazole. The effectiveness of DCI is thought to be based on its nucleophilicity. DCI is soluble in acetonitrile up to 1.1 M at room temperature and can be used as the sole coupling activator during routine automated solid phase synthesis of oligonucleotides. The addition of 0.1 M N -methylimidazole to 0.45 M 1 H -tetrazole also results in higher product yields during oligonucleotide synthesis than observed with 1 H -tetrazole alone.

Base Sequence↗

Tuberculosis of the mandible in a child.

The incidence of notification of tuberculosis is increasing in the developed world. The disease has a variable mode of presentation and therefore diagnosis is not easy. We present an unusual case of tuberculosis involving the ramus of the mandible in a six-year-old boy and outline its management.

Child↗

Copper-dependent inflammation and nuclear factor-kappaB activation by particulate air pollution.

Particulate air pollution causes increased cardiopulmonary morbidity and mortality, but the chemical determinants responsible for its biologic effects are not understood. We studied the effect of total suspended particulates collected in Provo, Utah, an area where an increase in respiratory symptoms in relation to levels of particulate pollution has been well documented. Provo particulates caused cytokine-induced neutrophil chemoattractant-dependent inflammation of rat lungs. Provo particulates stimulated interleukin-6 (IL-6) and IL-8 production, increased IL-8 messenger RNA (mRNA) and enhanced expression of intercellular adhesion molecule-1 (ICAM-1) in cultured BEAS-2B cells, and stimulated IL-8 secretion in primary cultures of human bronchial epithelium. Cytokine secretion was preceded by activation of the transcription factor nuclear factor-kappaB (NF-kappaB) and was reduced by treatment of cultures with superoxide dismutase, deferoxamine, or N-acetylcysteine. These biologic effects were replicated by culturing BEAS cells with quantities of Cu2+ found in Provo extract. IL-8 secretion by BEAS cells could be modified by addition of normal constituents of airway lining fluid to the culture medium. Mucin significantly reduced IL-8 secretion, and ceruloplasmin significantly increased IL-8 secretion and activation of NF-kappaB. These findings suggest that copper ions may cause some of the biologic effects of inhaled particulate air pollution in the Provo region of the United States, and may provide an explanation for the sensitivity of asthmatic individuals to Provo particulates that has been observed in epidemiologic studies.

Air Pollution↗

The impact of an information pack on patients with stroke and their carers: a randomized controlled trial.

OBJECTIVES: To assess the impact of information packs on patients with stroke and their carers, and to pilot some of the methodology for a trial of a Family Support Organiser (FSO). SUBJECTS: Seventy-one patients admitted to Oxford hospitals with acute stroke during February-July 1995, and 49 informal carers of these patients. DESIGN: Randomized controlled trial. Intervention group received an Information pack containing various Stroke Association publications one month after their stroke, or at discharge from hospital, whichever was sooner. Control group received nothing. Follow-up was by interview at the place of residence of the patients six months after their stroke. MEASURES: Outcome measures assessed knowledge about stroke; satisfaction with information received; patient behaviour in terms of access to community services and benefits; and health status and quality of life. RESULTS: Patients and carers in the intervention group tended to know more about stroke, but these differences were not significant once adjusted for age. Patients in the intervention group (but not carers) tended to be more satisfied with the information that they had received, but the differences were not significant. There were no differences with regard to any aspects of quality of life in patients in the intervention group, though carers in the intervention group were found to have significantly better mental health (p = 0.04). CONCLUSIONS: While the study was too small to generate firm conclusions, information leaflets may lead to improved knowledge about stroke several months after they have been distributed. This finding is worth following up with larger studies. The stroke knowledge questionnaire that was piloted in this trial seems to be able to detect differences between groups.

Aged↗

Culturally sensitive validation of screening questionnaires for depression in older African-Caribbean people living in south London.

BACKGROUND: We tested the validity of two screens for depression in older African-Caribbean adults, the 15-item Geriatric Depression Scale (GDS) and a new Caribbean Culture-Specific Screen for emotional distress (CCSS). Two independent criteria were used for validity: (a) a psychiatric diagnosis derived from GMS-AGECAT, and (b) a culturally sensitive assessment of mental disorder, derived from a tool developed with local African-Caribbean religious healers. METHOD: One hundred and sixty-four consecutive African-Caribbean primary care users, aged 60 years or older, were screened with the GDS and the CCSS. Diagnostic interviews were carried out on 80% of high scorers and 20% of low scorers. RESULTS: The number of cases detected by the two separate diagnostic approaches was similar. However, the agreement between who was and who was not a case was only modest. At a cut-off of > or = 5, the GDS was an adequate case detector for psychiatric depression, and, at a cut-off of > or = 4, for 'depressed/lost spirit', as defined by culture-specific criteria. It performed as well as the new CCSS. CONCLUSIONS: At a cut-off of > or = 4 the 15-item GDS can be recommended as a case detector for significant forms of depression in older African-Caribbean people living in south London.

Aged↗

Mood response to levodopa infusion in early Parkinson's disease.

Mood response to levodopa infusion was studied in 18 Parkinson's disease (PD) patients during the first year of levodopa therapy before and after 2-hour (1.0 mg/kg/h) levodopa infusions at baseline and 6- and 12-month follow-up. Mood elevation was greatest after a 2-day levodopa holiday at the 6- and 12-month assessments. Age, sex, duration and severity of PD, and ongoing oral levodopa dose did not correlate with mood response. Mood response in these patients differs from that seen in advanced patients, possibly because of sensitization to levodopa's mood effects.

Affect↗

The Mayo Clinic-Canadian Cooperative trial of sulfasalazine in active multiple sclerosis.

OBJECTIVE: To determine whether sulfasalazine is better than placebo in slowing disability progression in MS. METHODS: In this randomized, double-blind, placebo-controlled phase III trial, 199 patients with active relapsing-remitting (n = 151) or progressive (n = 48) MS were evaluated at 3-month intervals for a minimum of 3 years (94% completed 3 years of follow-up; mean follow-up, 3.7 years). MRI studies were performed at 6-month intervals on a subset of 89 patients. RESULTS: Sulfasalazine failed to slow or prevent disability progression as measured by the primary outcome (confirmed worsening of the Expanded Disability Status Scale [EDSS] score by at least 1.0 point on two consecutive 3-month visits). Sulfasalazine influenced favorably a number of secondary outcomes during the first 18 months of the trial (e.g., annualized relapse rate, proportion of relapse-free patients; progressive subgroup only: rate of EDSS progression at 1 and 2 years, median time to EDSS progression) but these positive findings were not sustained into the second half of the trial. CONCLUSIONS: Sulfasalazine does not prevent EDSS score progression in the subset of MS patients studied by this protocol. Treatments may improve relapse-related outcomes in MS, at least temporarily, without providing sustained slowing of EDSS progression. Phase III MS trials should be of sufficient length to determine a meaningful impact on disease course.

Adult↗