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Biomedical subjects

E Pearson

Publications and source records attributed to E Pearson.

At least 19 recordsLinked to original sources

Reduced beta cell function in offspring of mothers with young-onset type 2 diabetes.

AIMS/HYPOTHESIS: Animal models indicate that even exposure to mild maternal hyperglycaemia in utero is detrimental to the beta cell function of the offspring, but evidence of this in humans is limited. In Europids who are diagnosed with type 2 diabetes before the age of 50 years, the risk of diabetes in the offspring of the diabetic mothers is greatly increased compared with the risk in those born to diabetic fathers. We hypothesised that offspring born to mothers with young-onset type 2 diabetes would have been exposed to mild hyperglycaemia in utero, so we studied the impact of this on their beta cell function. SUBJECTS AND METHODS: We measured beta cell function using early insulin response (EIR) after oral glucose; insulin resistance using HOMA; and HbA(1c) in 568 non-diabetic adult offspring born to parents with type 2 diabetes (mean age 55.8 years), split according to which parent was affected (in 327 it was the mother) and parental age of diagnosis: <50 years (n=117) or > or =50 years. To reduce the impact of genetic susceptibility, the offspring of affected fathers were used as control subjects. RESULTS: Offspring of mothers with young-onset type 2 diabetes had lower EIR (log EIR 4.32, 95% CI [4.14-4.51] vs 4.63 [4.43-4.83] p=0.02) and higher HbA(1c) (4.89% [4.79-4.99] vs 4.68% [4.57-4.79] p=0.02) than the offspring of fathers with young-onset type 2 diabetes. Insulin sensitivity was similar in the two groups. There were no differences in EIR or HbA(1c) between the offspring born to mothers and fathers who were diagnosed after the age of 50 years. CONCLUSIONS/INTERPRETATION: We conclude that the offspring of mothers with young-onset type 2 diabetes have a reduction in beta cell function. This is consistent with exposure to mild maternal hyperglycaemia programming beta cell function.

Adult↗

Early and late morbidity after vasectomy: a comparison of chronic scrotal pain at 1 and 10 years.

OBJECTIVE: To evaluate the incidence and timing of the onset of chronic scrotal pain after vasectomy in two populations at 1 and 10 years after surgery. PATIENTS AND METHODS: In a retrospective questionnaire-based study two groups of men were compared; 460 who had a vasectomy in 1991-92 (group A) and another 460 who had a vasectomy in 2000-1 (group B; 10 and 1 year after surgery, respectively). Data were collected on immediate complications, and the incidence and nature of chronic scrotal pain. Pain severity was graded using a visual analogue score (VAS). Patients were also asked if they regretted having a vasectomy because of pain. RESULTS: In all, 182 and 220 replies were received from patients in group A and B, respectively. Early complications included haematoma in five (2%) and two (0.9%) patients, respectively, and wound infection in 24 (13%) and 17 (7.7%). Eight patients who had scrotal pain even before vasectomy were excluded from the analysis (two in group A and six in group B). In group A, 25 of 180 (13.8%) had a new onset of scrotal pain of some nature, with eight (4.3%) having a VAS of > 5; one patient had an epididymectomy for this. Three of the 25 regretted having a vasectomy because of pain. In group B, 36 of 214 (16.8%) reported persistent scrotal pain, with 13 (5.9%) having a VAS of > 5. Six of the 36 regretted having a vasectomy because of the pain. The incidence of scrotal pain was not significantly different between the groups (P = 0.48, Fisher's exact test). CONCLUSION: Chronic scrotal pain after vasectomy is more common than previously described, affecting almost one in seven patients. All patients undergoing vasectomy must receive appropriate preoperative counselling about this. The incidence of this complication does not appear to increase with time.

Adult↗

Partner's influence on patient preference for treatment in early prostate cancer.

OBJECTIVE: To determine the partner's influence on the patient's choice of treatment for early prostate cancer, and whether partner characteristics and biases predict the preference. PATIENTS, SUBJECTS AND METHODS: Questionnaires for partners to complete retrospectively were sent to consecutive patients recruited in a study comparing treatment options for early prostate cancer. The partners' perceptions about prostate cancer were explored and the partners asked to comment on the suitability of each treatment option. Partners recorded their influence on the patient's choice using a 10-point visual linear analogue scale. RESULTS: Questionnaires were sent to 116 eligible patients and 82 were returned for analysis (mean partner age 63 years). When asked to recall the treatment options initially discussed, all partners recalled radiotherapy (EBRT), all but one radical prostatectomy (RP), 51% brachytherapy, but only 29% watchful waiting (WW); 41% of partners stated RP as their chosen option, 37% EBRT, 12% brachytherapy and 10% no clear favourite. None preferred WW. Employment and education status were not significant predictors of partners' preference but retired partners and those aged > 65 years were 3 times more likely to prefer EBRT than were their employed and younger counterparts, respectively. The partners' mean (median, SD) self-assessed influence factor was 4.8 (5, 3.4). Of the partners, 88% reported active involvement throughout the process, identifying information-gathering and emotional support as their primary roles. Most deliberately chose not to influence the patient's final decision. CONCLUSION: Partner preference is influenced by pre-existing conceptions about cancer and its treatment. While undoubtedly influential throughout the decision-making process, partners deliberately left the final decision to the patient.

Adult↗

beta-cell genes and diabetes: molecular and clinical characterization of mutations in transcription factors.

beta-Cell transcription factor genes are important in the pathophysiology of the beta-cell, with mutations in hepatocyte nuclear factor (HNF)-1alpha, HNF-4alpha, insulin promoter factor (IPF)-1, HNF-1beta, and NeuroD1/BETA2, all resulting in early-onset type 2 diabetes. We assessed the relative contribution of these genes to early-onset type 2 diabetes using linkage and sequencing analysis in a cohort of 101 families (95% U.K. Caucasian). The relative distribution of the 90 families fitting maturity-onset diabetes of the young (MODY) criteria was 63% HNF-1alpha, 2% HNF-4alpha, 0% IPF-1, 1% HNF-1beta, 0% NeuroD1/ BETA2, and 20% glucokinase. We report the molecular genetic and clinical characteristics of these patients including 29 new families and 8 novel HNF-1alpha gene mutations. Mutations in the transactivation domain are more likely to be protein truncating rather than result in amino acid substitutions, suggesting that a relatively severe disruption of this domain is necessary to result in diabetes. Mutations in the different transcription factors result in clinical heterogeneity. IPF-1 mutations are associated with a higher age at diagnosis (42.7 years) than HNF-1alpha (20.4 years), HNF-1beta (24.2 years), or HNF-4alpha (26.3 years) gene mutations. Subjects with HNF-1beta mutations, in contrast to the other transcription factors, frequently present with renal disease. A comparison of age at diagnosis between subjects with different types and locations of HNF-1alpha mutations did not reveal genotype-phenotype correlations. In conclusion, mutations in transcription factors expressed in the beta-cell are the major cause of MODY, and the phenotype clearly varies with the gene that is mutated. There is little evidence to indicate that different mutations within the same gene have different phenotypes.

Adolescent↗

Agmatine, a novel hypothalamic amine, stimulates pituitary luteinizing hormone release in vivo and hypothalamic luteinizing hormone-releasing hormone release in vitro.

Agmatine, a clonidine displacing substance and imidazoline receptor agonist, was recently isolated from bovine brain and shown to be present in the rat hypothalamus. Since clonidine can stimulate the release of pituitary luteinizing hormone (LH), we tested the hypothesis that agmatine may similarly act in the rat to stimulate the hypothalamic luteinizing hormone-releasing hormone (LHRH)-pituitary LH axis. Administration of agmatine intracerebroventricularly rapidly augmented the release of LH in a dose-related fashion in ovariectomized, ovarian steroid-primed rats. Additionally, agmatine enhanced the in vitro efflux of LH releasing hormone from the median eminence-arcuate nucleus of the hypothalami of rats similarly pretreated with steroids. These studies imply that the endogenous imidazoline receptor agonist, agmatine, may serve as an excitatory neurotransmitter/neuromodulator in the hypothalamic control of LH release and we suggest that the previously reported excitatory effects of clonidine on LH release may be attributed to stimulation by clonidine of imidazoline receptors.

Agmatine↗

Trial of vitamin A supplementation in very low birth weight infants at risk for bronchopulmonary dysplasia.

We performed a randomized, double-blind, controlled trial to determine whether vitamin A supplementation in a group of very low birth weight infants would reduce the incidence of bronchopulmonary dysplasia. Forty-nine infants (birth weight 700 to 1100 gm) requiring mechanical ventilation and supplemental oxygen at 96 hours age were randomly assigned to receive either 2000 IU retinyl palmitate (n = 27) or saline placebo (n = 22) intramuscularly every other day for up to 14 doses. There were no differences between treatment groups in the incidences of bronchopulmonary dysplasia at 31 days of postnatal age (vitamin A group 48%, placebo group 55%; p = 0.776), supplemental oxygen requirement at 34 weeks of postconceptional age, or other complications of prematurity. The vitamin A group had higher mean plasma vitamin A concentrations than the placebo group, but mean plasma vitamin A concentrations were greater than 20 micrograms/dl (suggesting sufficiency) in both groups after the first study week. By study day 28, only one fourth of the infants in either group had plasma vitamin A concentrations less than 20 micrograms/dl. In contrast to an earlier report, we found no change in the incidence of BPD with vitamin A supplementation. Our findings may reflect a low baseline incidence of vitamin A deficiency in the study population and recent changes in the respiratory care of very low birth weight infants. The latter may have lessened the potential impact of vitamin A deficiency on lung disease.

Bronchopulmonary Dysplasia↗

Marketing audit reveals holes and opportunities.

The marketing department is an essential function of the hospital. But do you know if your marketing efforts are meeting your institution's objectives? An audit of the department is as essential as any other part of the marketing plan. The author tells you "how" and "why" you should seek the services of an auditor to examine your marketing function.

Hospital Departments↗

Selective inhibition of nerve growth factor-stimulated protein kinases by K-252a and 5'-S-methyladenosine in PC12 cells.

K-252a, a protein kinase inhibitor isolated from the culture broth of Nocardiopsis sp., inhibits the nerve growth factor (NGF)-stimulated phosphorylation of microtubule-associated protein 2 (MAP2) and Kemptide (synthetic Leu-Arg-Arg-Ala-Ser-Leu-Gly) by blocking the activation of two independent kinases in PC12 cells: MAP2/pp250 kinase and Kemptide kinase. The NGF-stimulated activation of these kinases is inhibited in a dose-dependent manner following treatment of the cells with K-252a. Although these kinases also are activated by epidermal growth factor (EGF) and 12-O-tetradecanoyl-phorbol 13-acetate, K-252a has no inhibitory effect when these agents are used. Half-maximal inhibition of the activation of both kinases was observed at 10-30 nM K-252a. K-252a was shown to directly inhibit the activity of MAP2/pp250 kinase and Kemptide kinase when added to the phosphorylation reaction mixture in vitro; however, half-maximal inhibition under these conditions was observed at greater than or equal to 50 nM K-252a. These data suggest that K-252a exerts its effects at a step early in the cascade of events following NGF binding. The effects of K-252a are similar to those reported for 5'-S-methyladenosine (MTA) and other methyltransferase inhibitors. Treatment of PC12 cells with MTA inhibited NGF-, but not EGF-mediated activation of MAP2/pp250-kinase (Ki greater than 500 microM). MTA, when added to the phosphorylation reaction mixture in vitro, directly inhibited kinase activity (Ki = 50 microM), suggesting that the effects of MTA may be the result of its action on protein kinases rather than methyltransferases.

Adenosine↗

An unusual intranasal foreign body.

We describe a child who had a button battery lodged in her nose for several weeks, with resulting destruction of her nasal septum. A brief review of the pathophysiology of injury due to button batteries and measures to prevent such injuries from occurring are discussed.

Child, Preschool↗

Ecological evaluation of a rehabilitative environment for spinal cord injured people: behavioural mapping and feedback.

A behavioural mapping procedure was used to describe the behavioural profile, pattern of interaction and location of patients and staff in a rehabilitation unit for traumatically spinal cord injured people. Naturalistic observations were randomly obtained by trained observers during two observational periods, using 10 behavioural categories drafted from the observational literature. Feedback of the results was given to staff between the observational periods. Results suggested that patients spent a considerable proportion of their time in solitary and disengaged behaviours. Analysis of the behavioural profile of patients revealed little difference between the therapeutic day and the evening. Patients were also observed to spend large amounts of time in the ward area during the day. These results are at variance with the concept of active rehabilitation, and also raise questions concerning institutionalization. The efficacy of feedback in initiating institutional change is also examined. Comparison is made with previous research and strategies for change are suggested.

Environment↗

[Hemorrhagic erosive gastritis. Therapeutic options].

There were analyzed 68 cases of erosional hemorrhagic gastritis and there incidence on sex and age and it was proofed that the most frequent etiologic causes are alcohol and acetyl salicylic acid. The employed diagnostical methods were evaluated, as well as radiology and endoscopy, which have shown the value of there precocity within the first 24 hours. The medical treatment was analysed in 90% of the cases with good results. The applied surgical treatment was checked about its morbidness an mortality, thus demonstrating the poor results of conservative surgery.

Adolescent↗