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Biomedical subjects

S George

Publications and source records attributed to S George.

At least 145 records · Page 8Linked to original sources

Physical mapping of the murine casein locus reveals the gene order as alpha-beta-gamma-epsilon-kappa.

The murine casein locus has been characterized by long-range restriction mapping and the analysis of large fragment genomic clones. Cloned sequences from five mouse casein genes (alpha, beta, gamma, epsilon, kappa) were used to screen a murine (strain 129) genomic library in a bacterial artificial chromosome vector (BAC). Of the nine clones isolated, two contained three casein genes alpha, beta, gamma and gamma, epsilon, kappa, respectively. The following combinations were found in other clones: alpha + beta, beta + gamma; and gamma + epsilon. Thus, the gene order in the locus can be deduced to be alpha-beta-gamma-epsilon-kappa. This order was confirmed by restriction analysis of the clones. A contig map of the clones and flanking sequences has been established by characterizing seven BAC clones, which together span approximately 470 kb. Long-range restriction analysis of genomic DNA indicates that the murine casein locus is confined to a 250-kb partial Xho I fragment. The alpha and beta casein genes were shown to be arranged in a tail-to-tail orientation.

Animals↗

Extended cervicomediastinal thymectomy in the integrated management of myasthenia gravis.

OBJECTIVE: The authors evaluated the response to extended cervicomediastinal thymectomy as a component of the integrated management of patients with myasthenia gravis in a large series of patients from a single institution. The authors evaluated the response to therapy with respect to a graded, multivariate, ordinal scale chosen to reflect the full range of the disease's manifestations. SUMMARY BACKGROUND DATA: A number of series, of varying sizes, describe the response of patients with myasthenia gravis to thymectomy primarily with respect to the bivariate endpoint of the presence or absence of "remission." These studies fail to describe the full spectrum of postoperative disease severity and have been unable to quantify definitively the influence of putative prognostic variables, nor to assess definitively the statistical significance of apparent improvements over time. METHODS: The authors evaluated 202 consecutive patients who underwent trans-sternal thymectomy for symptomatic myasthenia gravis from 1969 through 1996 at the Johns Hopkins Hospital. The response to surgery, combined with postoperative medical therapy, was evaluated by a standardized scale reflecting the full spectrum of the disease. These data were analyzed by a novel mean multivariate regression analysis, which allowed the quantification of the statistical significance of apparent responses over time and the evaluation of the independent influence of each of nine putative prognostic indicators. RESULTS: There was no perioperative mortality and a 33% perioperative morbidity. There was a marked clinical response at 6 months to 1 year after surgery that was sustained for at least 10 years thereafter. The median increment of improvement was two (of five) classes. Eighty-six percent and 83% of the patients had improved by at least one class at 5 and 10 years, respectively. These changes were statistically significant (p < 0.001). Whereas the use of extended cervicomediastinal thymectomy was associated with a greater than twofold chance of improvement, compared to conventional trans-sternal thymectomy, neither the pathologic diagnosis (presence of thymoma) nor the age at surgery proved to be negative predictors of postoperative response. CONCLUSIONS: Extended cervicomediastinal thymectomy is the procedure of choice as a component of the integrated management of myasthenia gravis, with significant improvement seen in the group as a whole, as well as in subgroups of patients with thymoma and those older than 40 years of age.

Adolescent↗

A confidential enquiry into emergency hospital admissions on the Isle of Wight, UK.

OBJECTIVES: To quantify the proportion of potentially avoidable emergency short term admissions to hospital and to identify ways in which they could have been avoided. DESIGN: Confidential enquiry by peer review group. SETTING: St Mary's Hospital, Newport, Isle of Wight. SUBJECTS: All emergency, short term admissions (discharged home within five days) to medicine, general surgery, orthopaedics, gynaecology, ENT, and ophthalmology specialties for 28 (24 hour) days over a six month period in 1994. MAIN OUTCOME MEASURES: Appropriateness of admissions decided by the peer group, the peer group's opinion of ideal management, and the patients' views on the appropriateness of their admission. RESULTS: Altogether 139 cases satisfied the inclusion criteria. Complete data were collected on 123 cases and the peer group considered 81 in the time available. Twenty one of the 81 cases were judged "potentially avoidable". These represent 9.5% (95% CI 6.3%, 13.5%) of short term admissions to the specialties studied. The peer group considered that seven of 10 patients referred by a general practitioner (GP) could have been managed by the GP alone and that the remaining three had been referred appropriately but need not have been admitted had a consultant opinion been available in the accident and emergency (A&E) department. Two of the 10 would have required home support to avoid hospital admission. Five of 11 patients who referred themselves to A&E could have been discharged home without admission and without recourse to a specialist opinion. The remaining six could have been discharged had a consultant opinion been available in A&E. CONCLUSIONS: Urgent consultant opinion, either in A&E or in an outpatient clinic, would have prevented most of these inappropriate admissions, and home support would have expedited the ability to discharge some patients. Further research into the costs and benefits of methods for providing these services is needed urgently.

Adolescent↗

The measurement of morphine in the hair of heroin abusers.

Several techniques have been described for the determination of morphine in hair as a method of monitoring past heroin use. However, although some of the techniques [notably radioimmunoassay (RIA)] may appear relatively simple to perform, any results obtained must be interpreted with caution. In this study, hair specimens from four known heroin abusers were sectionally analysed by a specific RIA for morphine. Prior to analysis, all hair sections were cleaned to remove any possible surface contamination. Five different hair digestion procedures were evaluated to determine the most effective method that could be used to liberate morphine from hair. The greatest analytical recovery was obtained by incubation with 1.0 M sodium hydroxide for 18 h at 55 degrees C, neutralization with 1.0 M hydrochloric acid, and pH adjustment with 0.1 M phosphate buffer (pH 7.0). The morphine concentrations detected in the hair specimens ranged from 0.5 to 13.2 ng/mg of hair. It was also found that the use of shorter length segments (e.g. 1 cm length) gave a clearer, more detailed picture of the historic pattern of heroin use in the four subjects studied.

Acetone↗

Direct neural induction and selective inhibition of mesoderm and epidermis inducers by Xnr3.

During gastrulation in amphibians, secreted factors from Spemann's organizer act on dorsal ectoderm to induce the central nervous system. A number of secreted factors produced by Spemann's organizer have recently been identified. The TGFbeta family member Xnr3 is similar in amino acid sequence to the mouse factor nodal and is expressed in a restricted group of cells in the superficial layer of Spemann's organizer. Xnr3, unlike the related factors nodal, Xnr1 and Xnr2, lacks mesoderm-inducing activity. We report here that Xnr3 can directly induce neural tissue in Xenopus ectoderm explants (animal caps). Injection of animal caps with either Xnr3 RNA or plasmids induces the expression of the pan-neural genes NCAM and nrp1, as well as the anterior neural marker Cpl1. A growing body of evidence suggests that neural induction in Xenopus proceeds as the default in the absence of epidermis inducers. The best candidates for the endogenous epidermis inducers are BMP-4 and BMP-7. The neural inducing activity of Xnr3 can be inhibited by overexpression of BMP-4, as has been observed with the neural inducers noggin, chordin and follistatin. Furthermore, Xnr3 can block mesoderm induction by BMP-4 and activin, but not by Xnr2. The structural basis underlying the divergent activities of Xnr2 and Xnr3 was analyzed using site-directed mutagenesis. Mutations introduced to the conserved cysteine residues characteristic of the TGFbeta family were found to inactivate Xnr2, but not Xnr3. The most unique feature of Xnr3 is the absence of a conserved cysteine at the C terminus of the protein. This feature distinguishes Xnr3 from other TGFbeta family members, including Xnr2. However, we observed that changing the C terminus of Xnr3 to more closely resemble other TGFbeta family members did not significantly alter its activity, suggesting that other structural features of Xnr3 distinguish its biological activity from Xnr2.

Amino Acid Sequence↗

A possible explanation for the increased referral of atopic dermatitis from the Asian community in Leicester.

The population of the city of Leicester contains, in addition to the 'native' population, a large immigrant 'Asian' community originating from the Indian subcontinent. Among referrals to our department, atopic dermatitis (AD) was 3,3 times more common in Asians. We therefore performed a study based on a cohort of consecutive births in Leicester hospitals to investigate the possible ethnic difference in prevalence and to examine possible reasons for an ethnic difference in referral pattern. Parents of 1,800 children were asked at the time of the birth to allow their child to be entered on a register. A year later, parents of a sample of 499 of these children, 158 Asian and 341 non-Asian, were invited for interview and for examination of the children. A total of 413 children were examined. The overall point prevalence of AD was 10.7% (95% confidence interval, 7.7%-13.7%). There was no significant ethnic difference. However, a history of eczema in a first degree relative was found in 14.2% of Asian subjects and 35.1% of non-Asians (P < 0.0001, chi-square test). The data suggest the increased referrals to our clinic from the Asian community may result from a lower level of familiarity with AD.

Adult↗

Predictors of atopic dermatitis in Leicester children.

There is little contemporary data available on the prevalence of atopic dermatitis (AD) or the risk factors associated with this disease. We therefore performed a prospective study of 1-year-old children based on a cohort of consecutive births in Leicester hospitals. Parents of 1800 children born between March and May 1992 were asked at the time of the birth to allow their child to be entered on a register. A sample of 499 of these children were invited for interview and examination at 1 year of age. Data were collected on gestational maturity, birth weight, feeding pattern, family history of eczema and atopy, social class and other parameters. Four hundred and thirteen of the 499 children were examined (83%). The overall point prevalence of AD was 10.7% (95% confidence interval, 7.7%-13.7%). The most significant risk factor for a child developing AD was a parental history of eczema.

Adult↗

Sexual relationships in married dementia sufferers.

OBJECTIVE: To determine the proportion of couples, one of whom suffers from dementia, continuing with a sexual relationship, their level of satisfaction with their sexual relationship and the associations of remaining sexually active. DESIGN: A survey of married couples enrolled in a prospective dementia study. SETTING: Psychiatric services and a memory clinic. SAMPLE: The partners of 47 married patients with mild to moderate dementia. MEASURES: The assessment included the GMS/HAS/SDS package, the Marital Intimacy Scale (with some additional questions regarding sexual relations), the CAMCOG, the Carers Stress Scale, the Cornell Depression Scale and the Burns Symptom Checklist. Dementia was diagnosed according to DSM-III-R, McKhann, McKeith, Hachinski and HAS AGECAT criteria. RESULTS: Forty partners completed the study. Nine (22.5%) continued to have a sexual relationship, all of whom were satisfied with the situation. Twelve (38.7%) of the carers who were not sexually active were dissatisfied with the absence of a sexual relationship. There was a trend for male carers to be more likely to be involved in a continuing sexual relationship. Dissatisfaction with the absence of a sexual relationship was significantly associated with a diagnosis of vascular dementia in the patient and showed a trend towards an association with younger patient age. CONCLUSIONS: Nearly a quarter of married dementia sufferers are involved in a continuing sexual relationship, emphasizing the importance of further research in this area.

Aged↗

Hypomelanosis of Ito with unusual associations.

Hypomelanosis of Ito (HOI) is a neurocutaneous disorder which clinically is a well-characterised disease, in which chromosomal instability may be a component. Various neurological and other non-cutaneous malformations have been reported in association with the characteristic swirling pattern of hypopigmentation. We report two cases of this rare condition, one with hitherto unreported associations.

Abnormalities, Multiple↗

Donor immunization with Haemophilus influenzae type b (HIB)-conjugate vaccine in allogeneic bone marrow transplantation.

Bone marrow transplant patients are at increased risk for infections with polysaccharide encapsulated organisms and respond poorly to polysaccharide vaccines. We evaluated the effect of donor immunization with Haemophilus influenzae type b (HIB) polysaccharide-conjugate vaccine on recipient antibody responses following allogeneic bone marrow transplantation. Thirty-two allogeneic transplant patients and their donors were immunized before transplantation with HIB-conjugate, tetanus toxoid and 23-valent pneumococcal vaccines. Following transplantation, patients received HIB-conjugate and tetanus toxoid vaccines at 3, 6, 12, and 24 months and 23-valent pneumococcal vaccine at 12 and 24 months. Thirty-three patients with unimmunized donors were immunized following transplantation in an identical manner. Patients whose donors were immunized had significantly higher total anti-HIB antibody concentrations at 3 months (P = .0001), 6 months (P = .0001), 12 months (P = .0001), and 24 months (P = .002) after transplant compared with patients whose donors were unimmunized. Higher antitetanus toxoid antibody concentrations were also noted in patients with immunized donors, whereas donor immunization with pneumococcal vaccine had no effect on antibody concentrations following transplantation. Donor immunization with HIB-conjugate vaccine resulted in higher antibody concentrations in patients as early as 3 months after allogeneic transplantation and may be an effective strategy to prevent HIB infections.

Adolescent↗

Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group.

BACKGROUND: Skeletal complications are a major clinical manifestation of multiple myeloma. These complications are caused by soluble factors that stimulate osteoclasts to resorb bone. Bisphosphonates such as pamidronate inhibit osteoclastic activity and reduce bone resorption. METHODS: Patients with stage III multiple myeloma and at least one lytic lesion received either placebo or pamidronate (90 mg) as a four-hour intravenous infusion given every four weeks for nine cycles in addition to antimyeloma therapy. The patients were stratified according to whether they were receiving first-line (stratum 1) or second-line (stratum 2) antimyeloma chemotherapy at entry into the study. Skeletal events (pathologic fracture, irradiation of or surgery on bone, and spinal cord compression), hypercalcemia (symptoms or a serum calcium concentration > or = 12 mg per deciliter [3.0 mmol per liter]), bone pain, analgesic-drug use, performance status, and quality of life were assessed monthly. RESULTS: Among 392 treated patients, the efficacy of treatment could be evaluated in 196 who received pamidronate and 181 who received placebo. The proportion of patients who had any skeletal events was significantly lower in the pamidronate group (24 percent) than in the placebo group (41 percent, P < 0.001), and the reduction was evident in both stratum 1 (P = 0.04) and stratum 2 (P = 0.004). The patients who received pamidronate had significant decreases in bone pain and no deterioration in performance status and quality of life. Pamidronate was tolerated well. CONCLUSIONS: Monthly infusions of pamidronate provide significant protection against skeletal complications and improve the quality of life of patients with stage III multiple myeloma.

Aged↗

Future provision of out of hours primary medical care: a survey with two general practitioner research networks.

OBJECTIVE: To ascertain general practitioners' views about the future provision of out of hours primary medical care. DESIGN: Self completing postal questionnaire survey. SETTING: Wessex and north east England. SUBJECTS: 116 general practitioners in the Wessex Primary Care Research Network and 83 in the Northern Primary Care Research Network. MAIN OUTCOME MEASURES: Intention to reduce or opt out of on call; plans for changing out of hours arrangements; the three most important changes needed to out of hours care; willingness to try, and perceived strengths and limitations of, three alternative out of hours care models--primary care emergency centres, telephone triage services, and cooperatives. RESULTS: The overall response rate was 74% (Wessex research network 77% (89/116), northern research network 71% (59/83)). Eighty three per cent of respondents (123/148) were willing to try at least one service model, primary care emergency centres being the most popular option. Key considerations were the potential for a model to reduce time on call and workload, to maintain continuity of care, and to fit the practice context. Sixty one per cent (91/148) hoped to reduce time on call and 25% (37/148) hoped to opt out completely. CONCLUSIONS: General practitioners were keen to try alternative arrangements for out of hours care delivery, despite the lack of formal trials. The increased flexibility in funding brought about by the recent agreement between the General Medical Services Committee and the Department of Health is likely to lead to a proliferation of different schemes. Careful monitoring will be necessary, and formal trials of new service models are needed urgently.

Adult↗

Comparison of acute aquatic effects of the oil dispersant Corexit 9500 with those of other Corexit series dispersants.

The acute aquatic toxicity of a new Corexit series dispersant, Corexit 9500, was evaluated and compared with that of others in the series using early life stages of two common nearshore marine organisms: the red abalone (Haliotis rufescens) and a kelp forest mysid (Holmesimysis costata). Spiked-concentration testing was performed under closed, flowthrough conditions, with dispersant concentrations measured in real time using UV spectrophotometry. Median-effect concentrations ranged from 12.8 to 19.7 initial ppm for Haliotis and from 158.0 to 245.4 initial ppm for Holmesimysis. The difference in sensitivity of the two types of tests was consistent with patterns seen with other oil dispersants. Also, these data indicate Corexit 9500 to be of similar toxicity to Corexit 9527 and 9554. Corexit 9500 represents a reformulation of a long-time industry "standard," Corexit 9527, to allow use on higher viscosity oils and emulsions. The present data suggest that acute aquatic toxicity concerns surrounding the use of this newer dispersant should not be significantly different from those associated with the use of Corexit 9527.

Animals↗

Pneumococcal conjugate vaccine primes for antibody responses to polysaccharide pneumococcal vaccine after treatment of Hodgkin's disease.

Thirty-nine previously treated Hodgkin's disease (HD) patients were immunized with 7-valent pneumococcal conjugate vaccine (7-OMPC) followed by one dose of 23-valent polysaccharide pneumococcal vaccine (23-PS). To determine the priming effect of 7-OMPC vaccine, their antibody responses to six serotypes contained in both vaccines were compared to those of 57 HD patients who received 23-PS vaccine only. The geometric mean antibody concentrations after immunization with 23-PS vaccine were significantly higher for five of the six measured serotypes in HD patients primed with 7-OMPC vaccine compared with responses in HD patients who received 23-PS vaccine only. The mean of the six antibody concentrations was significantly higher for the primed group at 12.5 micrograms/mL and 7.76 micrograms/mL, respectively (P = .015). Priming with a conjugate vaccine should be considered as a strategy to protect high-risk adults.

Adolescent↗