Prevalence of type 2 diabetes in children in Birmingham.
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Adolescent↗
Biomedical subjects
J Kirk
Publications and source records attributed to J Kirk.
WFS1/wolframin mutations, Wolfram syndrome, and associated diseases.
Wolfram syndrome (WS) is the inherited association of juvenile-onset insulin-dependant diabetes mellitus and progressive bilateral optic atrophy. A nuclear gene, WFS1/wolframin, was identified that segregated with disease status and demonstrated an autosomal recessive mode of inheritance. Mutation analysis of the WFS1 gene in WS patients has identified mutations in 90% of patients. Most were compound heterozygotes with private mutations distributed throughout the gene with no obvious hotspots. The private nature of the mutations in WS patients and the low frequencies make it difficult to determine the biological or clinical relevance of these mutations. Mutation screening in patients with psychiatric disorders or diabetes mellitus has also been performed to test the hypothesis that heterozygous carriers of WFS1 gene mutations are at an increased risk following the observation that WS first-degree relatives have a higher frequency of these disorders. Most studies showed no association, however two missense mutations were identified that demonstrated significant association with psychiatric disorders and diabetes mellitus. Population association studies and functional studies of these variants will need to be performed to confirm these preliminary results. The elucidation of functions and functional pathways for the WFS1 gene product and variants will shed light on the effect of such disparate mutations on gene function and their role in the resulting clinical phenotype in WS and associated disorders.
DNA, Mitochondrial↗
Long-term outcomes of genetic counseling in women at increased risk of developing hereditary breast cancer.
This multicenter study evaluated the impact of genetic counseling in 218 women at risk of developing hereditary breast cancer. Women were assessed prior to counseling and 12-month post-counseling using self-administered, mailed questionnaires. Compared to baseline, breast cancer genetics knowledge was increased significantly at follow-up, and greater increases in knowledge were associated with educational level. Breast cancer anxiety decreased significantly from baseline to follow-up, and these decreases were associated with improvements in perceived risk. A significant decrease in clinical breast examination was observed at the 12-month follow-up. Findings suggest that women with a family history of breast cancer benefit from attending familial cancer clinics as it leads to increases in breast cancer genetics knowledge and decreases in breast cancer anxiety. The lowered rates of clinical breast examination indicate that the content of genetic counseling may need to be reviewed to ensure that women receive and take away the right message.
Adaptation, Psychological↗
Feeding problems in Silver-Russell syndrome.
In order to identify the prevalence and severity of feeding problems in children with Silver-Russell syndrome (SRS) the feeding difficulties of 32 children with SRS and 32 age- and sex-matched control children were assessed using the Feeding Assessment Questionnaire (Harris and Booth 1992). Children's ages ranged from 2 to 11 years, with 19 male and 13 female pairs. In a subset of matched pairs, parent-child interaction at mealtimes was examined using video recording; food intake was also assessed over a 3-day period using weighed food diaries. Children with SRS experienced significantly more feeding problems than children without growth disorders. Common feeding problems for children with SRS were poor appetite, fussiness, slow feeding, and problems associated with oral-motor dysfunction. Feeding problems did not significantly affect intake of kilocalories, protein, fat, or carbohydrates. Mealtime interaction between children with SRS and their parents was significantly more negative than interactions between control-group children and their parents. The focus of intervention packages in SRS should be to reduce negative parent-child interactions and reduce parental anxiety about feeding, growth, and weight.
Abnormalities, Multiple↗
Long-term results of surgical excision and skin grafting for a giant hairy naevus of the face: time for a return to conventional wisdom?
In a publication climate demanding modern innovative treatments for congenital giant hairy naevi, we report a case with excellent long-term results following early surgical excision and split-thickness skin grafting.
Adult↗
Familial adenomatous polyposis: more evidence for disease diversity and genetic heterogeneity.
Familial adenomatous polyposis (FAP) is characterised by the presence of profuse colonic carpeting of adenomas throughout the entire colon and rectum. The genetic basis of FAP has been shown to be primarily associated with germline mutations in the APC gene. Notwithstanding, several reports have been published indicating that there is genetic heterogeneity in FAP and that the most likely explanation is the existence of another gene. In this report we further delineate the genotype/phenotype correlation in families that harbour germline mutations in the APC gene and identify some previously unreported changes in the APC gene which predispose to an attenuated disease phenotype. From 53 index patients diagnosed with either FAP or attenuated FAP, 27 harboured changes in the APC gene. The remaining 26 patients were further subgrouped according to their colonic phenotype. There were nine patients with a mixed hyperplastic/adenomatous colonic phenotype and there were 17 patients with an adenomatous colonic phenotype. Evaluation of the disease characteristics of these patients and their families is presented which may aid in the identification of new genes associated with colonic polyposis.
Adenomatous Polyposis Coli↗
New B-type cyclin synthesis is required between meiosis I and II during Xenopus oocyte maturation.
Progression through meiosis requires two waves of maturation promoting factor (MPF) activity corresponding to meiosis I and meiosis II. Frog oocytes contain a pool of inactive "pre-MPF" consisting of cyclin-dependent kinase 1 bound to B-type cyclins, of which we now find three previously unsuspected members, cyclins B3, B4 and B5. Protein synthesis is required to activate pre-MPF, and we show here that this does not require new B-type cyclin synthesis, probably because of a large maternal stockpile of cyclins B2 and B5. This stockpile is degraded after meiosis I and consequently, the activation of MPF for meiosis II requires new cyclin synthesis, principally of cyclins B1 and B4, whose translation is strongly activated after meiosis I. If this wave of new cyclin synthesis is ablated by antisense oligonucleotides, the oocytes degenerate and fail to form a second meiotic spindle. The effects on meiotic progression are even more severe when all new protein synthesis is blocked by cycloheximide added after meiosis I, but can be rescued by injection of indestructible B-type cyclins. B-type cyclins and MPF activity are required to maintain c-mos and MAP kinase activity during meiosis II, and to establish the metaphase arrest at the end of meiotic maturation. We discuss the interdependence of c-mos and MPF, and reveal an important role for translational control of cyclin synthesis between the two meiotic divisions.
Amino Acid Sequence↗
An open-label acceptability study of Norditropin SimpleXx--a new liquid growth hormone formulation.
A new liquid formulation of hGH (Norditropin SimpleXx) has been developed to avoid the need for reconstitution before administration. In addition, the liquid GH formulation has been combined with an advanced pen delivery system, either with or without a needle auto-insertion mechanism. This study was designed to assess the acceptability of the new system compared with the patient's previous system. A total of 103 children with GH deficiency received a daily injection of Norditropin liquid GH for 12 weeks with a choice of a pen/auto-insertion system. Acceptability was determined by nurse-supervised questionnaires administered to the patients and parents. Following treatment, 94% of patients preferred the Norditropin liquid GH system. This preference was irrespective of the previous system in use, patient age or length of GH therapy. More patients found it the less painful system (50% vs 13%), 92% of patients found it more convenient, and the formulation was well tolerated. In conclusion, Norditropin liquid GH was very well accepted and preferred by the majority of patients. It avoided reconstitution which had been a major cause of dissatisfaction with the patients' previous systems, and resulted in greater convenience and reduced levels of pain associated with injection.
Adolescent↗
Equine dysautonomia (grass sickness) is associated with altered plasma amino acid levels and depletion of plasma sulphur amino acids.
To determine whether equine dysautonomia (ED) is associated with alterations in plasma amino acid metabolism, plasma amino acid profiles were determined for horses with acute (n = 10), subacute (n = 6) and chronic (n = 7) ED and for healthy cograzing horses (n = 6) and control horses (n = 10). Horses with acute ED had perturbations in plasma amino acid profiles resembling those of severe protein malnutrition. In addition, horses with ED and cograzing healthy horses had depletion of the plasma sulphur amino acids cyst(e)ine and methionine. As similar plasma amino acid perturbations occur in subacute/chronic cyanide toxicity, the role of cyanogenic glycosides in the aetiology of ED warrants further study. Unfortunately, amino acid analysis cannot be used as a definitive premortem diagnostic test for ED, since there was overlap in the individual amino acid levels of control, cograzing and ED horses.
Acute Disease↗
Self-reported hand dermatitis in California veterinarians.
BACKGROUND: Veterinarians are exposed to allergens, dirt, and chemicals, but there are very few epidemiologic data on dermatoses veterinarians. OBJECTIVE: The aim of this study is to get information about skin diseases in veterinary work. METHODS: A sample of California veterinarians were sent a questionnaire, which was returned by 73% (n = 1,416). RESULTS: History of skin atopy was reported by 11% and respiratory atopy by 63%. Dermatoses during their career were reported by 46%, and hand and/or forearm dermatitis was reported more than once and during the past year by 22% of women and 10% of men. Dermatitis with work-related exacerbating factors was reported by 28%. Almost 1 of 5 veterinarians reported animal-related skin symptoms. Other aggravators were medications (2%), gloves (4%), and other chemicals (7% of respondents). Of those with animal-related dermatitis, 65% reported only 1 animal (dog, 66%; cat, 29%; horse, 9%; and cattle, 8%), and 66% reported the symptoms appeared in minutes after the contact. In logistic analysis, the risk factors for the appearance of hand/forearm dermatitis during the past 12 months and more than once during their career, were: history of skin atopy (odds ratio, 3.5), childhood hand dermatitis (odds ratio, 3.4), history of respiratory atopy (odds ratio, 2.0), and female sex (odds ratio, 1.9). CONCLUSIONS: Veterinarians' skin symptoms were common and often caused by immediate allergy to 1 or few animal species.
Adult↗
Hereditary nonpolyposis colorectal cancer in 95 families: differences and similarities between mutation-positive and mutation-negative kindreds.
Hereditary nonpolyposis colorectal cancer (HNPCC) describes the condition of a disparate group of families that have in common a predisposition to colorectal cancer in the absence of a premalignant phenotype. The genetic basis of this disease has been linked to mutations in genes associated with DNA mismatch repair. A large proportion of families harbor changes in one of two genes, hMSH2 and hMLH1. Approximately 35% of families in which the diagnosis is based on the Amsterdam criteria do not appear to harbor mutations in DNA-mismatch-repair genes. In this report we present data from a large series of families with HNPCC and indicate that there are subtle differences between families that harbor germline changes in hMSH2 and families that harbor hMLH1 mutations. Furthermore, there are differences between the mutation-positive group (hMSH2 and hMLH1 combined) of families and the mutation-negative group of families. The major findings identified in this study focus primarily on the extracolonic disease profile observed between the mutation-positive families and the mutation-negative families. Breast cancer was not significantly overrepresented in the hMSH2 mutation-positive group but was overrepresented in the hMLH1 mutation-positive group and in the mutation-negative group. Prostate cancer was not overrepresented in the mutation-positive groups but was overrepresented in the mutation-negative group. In age at diagnosis of colorectal cancer, there was no difference between the hMSH2 mutation-positive group and the hMLH1 mutation-positive group, but there was a significant difference between these two groups and the mutation-negative group.
Adolescent↗
Cancer in the family: risks and management.
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Australia↗
Breast cancer screening uptake in women at increased risk of developing hereditary breast cancer.
This multicenter study assessed breast cancer screening uptake in 461 unaffected women at increased risk of developing breast cancer on the basis of family history who approached familial cancer clinics for advice about surveillance options. At the time of attending the clinic, 89% and 90% of participants were vigilant with respect to age- and risk-specific recommendations for mammography and clinical breast examination, respectively, and 51% reported practicing breast self-examination monthly or more frequently. The degree to which health outcomes are perceived to be under one's personal control (chi2 = -2.09, p = 0.0037) and breast cancer anxiety (chi2 = 8.11, p = 0.044) were both associated with monthly or more frequent breast self-examination, while there were no associations with sociodemographic characteristics. A significantly lower percentage (56%) of women aged <30 were vigilant with respect to mammography recommendations, compared to 77%, 96% and 98% of women aged 30-39, 40-49 and >50, respectively (chi2 = 37.2, p < 0.0001). These relatively low rates of mammographic screening in young women may reflect concerns about increased cancer risk associated with early and repeated radiation exposure or lack of sensitivity in young women with radiographically dense breasts. If mammographic screening is ultimately shown to lower mortality in women at high risk, there will be a strong case to promote screening in young women. The need for regular mammographic screening would then need to be highlighted and reinforced amongst young women and their referring physicians. Awareness amongst general practitioners, who are largely responsible for referral to screening services, would also need to be increased.
Adolescent↗
Investigation and outcome of neonatal hepatitis in infants with hypopituitarism.
UNLABELLED: Congenital hypopituitarism is a recognized cause of neonatal hepatitis, but the diagnosis may be difficult to establish even if clinically suspected. In order to determine the natural history of this disorder, the outcome of 12 infants with neonatal hepatitis secondary to hypopituitarism is reviewed. The clinical diagnosis of hypopituitarism was established on a combination of features, which include dysmorphism (4 infants), optic nerve hypoplasia (8 infants), micropenis (5 male infants) and recurrent hypoglycaemia (blood glucose < 2.4 mmol/l (8 infants)). Endocrine investigation revealed low free thyroxine (T4) levels (< 10 pmol/l), with normal thyroid stimulating hormone (TSH) levels (0.4-4.5 mU/l) (11 infants), and serum cortisol levels which were inappropriately low (< 200 nmol/l). In 9 of 12 infants, liver disease resolved within 6 wk following treatment with thyroxine, hydrocortisone and, where appropriate, growth hormone, including Cases 9 and 1 in whom diagnosis and treatment were delayed until 3 mo and 3 y of age, respectively. Liver disease resolved spontaneously in two infants prior to starting hormone replacement therapy (Cases 11, 12), and one male infant (Case 10), in whom the diagnosis and hormone replacement therapy were delayed until 5 y of age, developed cirrhosis and portal hypertension and later underwent liver transplantation. CONCLUSION: The diagnosis of hypopituitarism should always be considered in infants with unexplained neonatal hepatitis. Delay in diagnosis and appropriate treatment was associated with persistently abnormal liver function tests and may lead to irreversible liver disease.
Diagnostic Techniques, Endocrine↗
Effect of growth hormone therapy on feeding problems and food intake in children with growth disorders.
UNLABELLED: To assess the effect of therapeutic doses of growth hormone (GH) on the feeding problems, food intake, body fat and mealtime interactions of children with growth disorders, an age-matched group of 46 children with Turner syndrome (TS) or Silver Russell syndrome (SRS) was examined using questionnaire measures and direct observation. The children's body fat was measured using bio-electrical impedance analysis and skinfold thickness measurements. Children receiving GH consumed significantly more energy, protein, fat and carbohydrate than did the children who were not receiving GH, independent of the extent of the child's feeding problems. Children receiving GH had less body fat than did children who were not receiving GH. Children who were not receiving GH distracted their parents from the mealtime significantly more often and received more negative prompting and coaxing from their parents to eat than did children who were receiving GH. This study provides evidence to support the theory that appetite and intake is determined in part by growth and growth potential. Feeding problems seen in children with growth disorders are partly due to parental attempts to impose control over their child's intake, when their child consumes less than the parent believes to be adequate. CONCLUSION: GH has a significant impact on both the food intake and parent-child interaction at mealtimes of children with SRS and TS.
Animals↗
Intention to undergo prophylactic bilateral mastectomy in women at increased risk of developing hereditary breast cancer.
PURPOSE: To assess intention to undergo prophylactic bilateral mastectomy and psychologic determinants in unaffected women at increased risk of developing hereditary breast cancer. PATIENTS AND METHODS: Three hundred thirty-three women who were awaiting their initial appointments for risk assessment, advice about surveillance, and prophylactic options at one of 14 familial cancer clinics participated in a cross-sectional, questionnaire-based survey. RESULTS: Nineteen percent of women would consider and 47% would not consider a prophylactic mastectomy, should genetic testing identify a mutation in a breast cancer-predisposing gene, whereas 34% were unsure and 1% had already undergone a prophylactic mastectomy. In a bivariate analysis, women at a moderately increased risk of developing breast cancer had the highest proportion of subjects reporting that they would consider a prophylactic mastectomy (25%), compared with women at high risk (16%) (chi(2) = 7.79; P =.051). In multivariate analyses, consideration of prophylactic mastectomy strongly correlated with high levels of breast cancer anxiety (odds ratio [OR] = 17.4; 95% confidence interval [CI], 4.35 to 69.71; P =. 0001) and overestimation of one's breast cancer risk (OR = 3.01; 95% CI, 1.43 to 6.32; P =.0036), whereas there was no association with objective breast cancer risk (P =.60). CONCLUSION: A significant proportion of women at increased risk of developing hereditary breast cancer would consider prophylactic mastectomy. Although prophylactic mastectomy may be appropriate in women at high risk of developing breast cancer, it is perhaps less so in those who have a moderately increased risk. Such moderate-risk women are likely to benefit from interventions aimed at reducing breast cancer anxiety and correcting exaggerated breast cancer risk perceptions.
Adult↗
Uptake of influenza vaccination and the reasons for non-vaccination in the high-risk patients of Angus, Scotland.
OBJECTIVE: To ascertain the uptake of influenza vaccination, the main prompts to vaccination and the reasons for non-vaccination in the high-risk patients of Angus, Scotland. DESIGN: Prospective questionnaire survey. SETTING: A small rural district general hospital. SUBJECTS: General medical inpatients and outpatients. RESULTS: The overall uptake of vaccination was 44.8% (n = 250). The main prompts to vaccination were general practitioners (48.2%), the media (11.6%), practice and district nurses (8.9%), friends and relatives (8.9%) and posters at health centres and chemists (7.1%). The main reason for non-vaccination was a lack of awareness of high-risk status (50.7%). CONCLUSION: The uptake of influenza vaccination in the Angus region of Scotland is unsatisfactorily low. This is mostly due to a lack of knowledge regarding high-risk status, although other reasons, including concerns about the side effects of vaccination, are also important.
Female↗
Health care costs associated with chronic hepatitis B.
The long-term health care costs of patients with chronic hepatitis B (CHB) were compared with those of patients without CHB. Patients with laboratory markers for CHB were identified from an HMO database and matched with up to four control patients (either not tested for hepatitis B infection or with negative test results). Cost data were collected retrospectively for both groups of patients for the period up to 30 days before identification of the first marker for hepatitis B (prediagnosis), 30 days before identification of the first marker through 180 days after the identification (peridiagnosis), and 181 days after identification through the end of the six-year study period. Costs were categorized as emergency room, inpatient, short-stay inpatient, laboratory, radiology, office visit, pharmacy, outside claim, or other and were analyzed as ratios of the costs of each patient with CHB to the median of the corresponding control patients. Eighty-eight patients were identified as having CHB; there were 342 control patients. In the seven months surrounding the appearance of their first diagnostic marker, the patients with CHB had costs 3.3 times those of the corresponding control patients and, after the first seven months, 2.9 times those of the control patients per month. Peridiagnosis costs in the categories of laboratory, radiology, office visits, and pharmacy were significantly higher for patients with CHB than for control patients. Except for emergency room costs, postdiagnosis costs per month of the patients with CHB were significantly higher than those of the corresponding control patients. Examination of an HMO database showed that, compared with patients without CHB, patients with CHB had significantly higher health care costs around and after the CHB diagnosis.
Adult↗