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Biomedical subjects

J Kirk

Publications and source records attributed to J Kirk.

At least 55 records · Page 3Linked to original sources
PubMed1999

Attitudes toward prophylactic oophorectomy and screening utilization in women at increased risk of developing hereditary breast/ovarian cancer.

OBJECTIVES: The aim of this study was to evaluate ovarian cancer screening uptake and attitudes toward prophylactic oophorectomy in women at risk of developing hereditary breast/ovarian cancer. STUDY METHODS: Ninety-five unaffected women, who approached 1 of 14 familial cancer clinics for advice about their breast/ovarian cancer risk and surveillance and prophylactic options, were assessed in a cross-sectional design when they attended the clinic. RESULTS: Among high-risk women ages 30 and over who had not had a prophylactic oophorectomy, 48% reported ever having had an ovarian ultrasound, and among women ages 50 and over 23% had had a serum CA 125 test. Twenty-three percent of women would consider, and 27% would not consider, a prophylactic oophorectomy should the genetic test indicate a germline mutation associated with hereditary breast/ovarian cancer, while 38% were unsure. Twelve percent had already undergone a prophylactic oophorectomy. Interest in prophylactic oophorectomy was associated with increased breast/ovarian cancer anxiety (chi(2) = 5.14, P = 0.023), but not objective cancer risk (chi(2) = 0.40, P = 0.53). CONCLUSION: Findings demonstrate that breast/ovarian cancer anxiety, rather than objective risk, is the major factor which determines women's attitude to prophylactic oophorectomy. Women are likely to benefit from interventions aimed at reducing breast/ovarian cancer anxiety. Research on the impact of prophylactic oophorectomy would be helpful in the development of educational strategies and decision aids to assist women who are trying to make a decision under conditions of uncertainty.

Adult↗
PubMed1999

Clinical and molecular genetic analysis of 19 Wolfram syndrome kindreds demonstrating a wide spectrum of mutations in WFS1.

Wolfram syndrome is an autosomal recessive neurodegenerative disorder characterized by juvenile-onset diabetes mellitus and progressive optic atrophy. mtDNA deletions have been described, and a gene (WFS1) recently has been identified, on chromosome 4p16, encoding a predicted 890 amino acid transmembrane protein. Direct DNA sequencing was done to screen the entire coding region of the WFS1 gene in 30 patients from 19 British kindreds with Wolfram syndrome. DNA was also screened for structural rearrangements (deletions and duplications) and point mutations in mtDNA. No pathogenic mtDNA mutations were found in our cohort. We identified 24 mutations in the WFS1 gene: 8 nonsense mutations, 8 missense mutations, 3 in-frame deletions, 1 in-frame insertion, and 4 frameshift mutations. Of these, 23 were novel mutations, and most occurred in exon 8. The majority of patients were compound heterozygotes for two mutations, and there was no common founder mutation. The data were also analyzed for genotype-phenotype relationships. Although some interesting cases were noted, consideration of the small sample size and frequency of each mutation indicated no clear-cut correlations between any of the observed mutations and disease severity. There were no obvious mutation hot spots or clusters. Hence, molecular screening for Wolfram syndrome in affected families and for Wolfram syndrome-carrier status in subjects with psychiatric disorders or diabetes mellitus will require complete analysis of exon 8 and upstream exons.

Adolescent↗
PubMed1999

A decade of growth hormone treatment in girls with Turner syndrome in the UK. UK KIGS Executive Group.

Fifteen per cent of children treated with growth hormone (GH) are receiving treatment for Turner syndrome, but few results are available on final height in the UK. In this study, data were obtained from the UK KIGS database for 485 girls with Turner syndrome who were treated from 1986, allowing an audit of practice and outcome over 10 years. Over the decade, the mean age of starting growth hormone treatment fell from 10.4 to 8.5 years and the starting dose increased from 0.55 to 0.95 IU/kg/week. The frequency of injections increased from three to six or seven/week. Some girls received suboptimal doses, which also differed depending on whether they were based on weight or surface area. To assess what height gain might be expected at final height, all 52 girls who were prepubertal at the start of treatment, which continued for four years or more, and who had reached final height or had a growth velocity < 2 cm/year were selected. Their mean gain in final height was 5.2 cm and the GH dose was 0.78 IU/kg/week over 5.8 years. Final height gain correlated significantly with duration of treatment, total dose received, and first year response, which itself related to starting dose. This audit shows a changing pattern of treatment over the past decade, which in many instances has been inadequate. When treatment starts before puberty and continues through to final height, with a dose of 30 IU/m2/week in six or seven injections, a mean increase in final height of 5 cm or more would be expected.

Adolescent↗
PubMed1999

Growth in Sotos syndrome.

Although there are several reports on infant and childhood growth in patients with Sotos syndrome, there is little information on the final height achieved and puberty. Growth data on 40 patients (20 female and 20 male) aged 2-31 years were collected. These showed that patients with Sotos syndrome are excessively tall at birth, during infancy, and during childhood. Disproportionately long limbs constitute much of the increase in stature. However, the combination of advanced bone age and early onset of menarche led to a mean (SD) final height of 172.9 (5.7) cm in women. This is within the normal range for the population. Most of the men also attained a final height (mean, 184.3 cm; SD, 6.0) within the normal range, although exceptions were more likely in men than in women. Therefore, these results show that most patients with Sotos syndrome do not require intervention to limit their adult height.

Acromegaly↗
PubMed1998

Cyclin B2-null mice develop normally and are fertile whereas cyclin B1-null mice die in utero.

Two B-type cyclins, B1 and B2, have been identified in mammals. Proliferating cells express both cyclins, which bind to and activate p34(cdc2). To test whether the two B-type cyclins have distinct roles, we generated lines of transgenic mice, one lacking cyclin B1 and the other lacking cyclin B2. Cyclin B1 proved to be an essential gene; no homozygous B1-null pups were born. In contrast, nullizygous B2 mice developed normally and did not display any obvious abnormalities. Both male and female cyclin B2-null mice were fertile, which was unexpected in view of the high levels and distinct patterns of expression of cyclin B2 during spermatogenesis. We show that the expression of cyclin B1 overlaps the expression of cyclin B2 in the mature testis, but not vice versa. Cyclin B1 can be found both on intracellular membranes and free in the cytoplasm, in contrast to cyclin B2, which is membrane-associated. These observations suggest that cyclin B1 may compensate for the loss of cyclin B2 in the mutant mice, and implies that cyclin B1 is capable of targeting the p34(cdc2) kinase to the essential substrates of cyclin B2.

3T3 Cells↗
PubMed1998

Distribution of measles virus in the central nervous system of HIV-seropositive children.

In an autopsy study the distribution of measles virus (MV) in the central nervous system (CNS) of 18 measles-infected children (13 HIV seropositive, 5 HIV seronegative), in Abidjan, Ivory Coast was examined using immunocytochemistry and in situ hybridization. Of these children 17 died from measles giant cell pneumonia. In 3 of the 13 HIV-seropositive patients MV antigens and genomic RNA was detected in the CNS. One of these positive patients had an MV encephalitis with abundant virus throughout most of the CNS. MV was not detected in the CNS of any of the 5 HIV-seronegative patients. These findings, albeit in a small number of cases, would suggest there may be an increased susceptibility to infection of the CNS with MV in HIV-positive children. In this respect entry and growth of MV in the CNS in HIV-seropositive individuals may be similar to the occurrence of measles inclusion body encephalitis in immunocompromised individuals. Furthermore, comparison of the HIV-MV encephalitis patient with two patients with subacute sclerosing panencephalitis (SSPE) demonstrated a paucity of virus in neuronal processes in the HIV-MV encephalitis. Unlike in SSPE, MV maturation by budding through the plasma membrane may occur, thereby minimizing build up of and intracellular movement of incomplete virus.

Adult↗
PubMed1998

Alternative health care: its use by individuals with physical disabilities.

OBJECTIVE: This research investigated the use of alternative therapies by individuals with physical disabilities. DESIGN: A telephone survey of a cross-sectional convenience sample of people with disabilities. SETTING: An urban, outpatient rehabilitation facility specializing in vocational services. PARTICIPANTS: A convenience sample of 401 working-age individuals. MAIN OUTCOME MEASURE(S): Self-reported use of alternative therapy. RESULTS: More of this sample of individuals with physical disabilities than a randomized, national sample of the general population used alternative therapies (57.1% vs 34%) and saw providers of those therapies (22% vs 10%). Among individuals in the current sample, significant positive relationships between use of alternative therapies and education and income levels were discovered. The use of alternative therapies by this sample, however, was not associated with racial identity, gender, or age. Compared with the general population, this study's respondents reported a higher proportion of chronic pain (14% vs 8%) and depression (14% vs 8%), and a lower proportion of severe headache (9.2% vs 13%). Alternative therapies were chosen more often than conventional therapies by those with physical disabilities for pain (51.8% vs 33.9%), depression (33.9% vs 25%), anxiety (42.1% vs 13.1%), insomnia (32.3% vs 16.1%), and headaches (51.4% vs 18.9%). CONCLUSION: Physically disabled individuals are more likely to use alternative therapies than the general population and to see providers for them, have their use recommended by their physicians, and be reimbursed by their health insurance for them. A high prevalence of dysphoria is found among those with disabilities, for which a combination of alternative and conventional therapies is often used.

Adolescent↗
PubMed1998

Cost-minimization and the number needed to treat in uncomplicated hypertension.

The goal of this study was to compare the direct costs associated with the prescription of thiazide diuretics, beta-receptor blockers (beta-blockers), angiotensin converting enzyme inhibitors (ACEI), a-receptor blockers (alpha-blockers), and calcium channel blockers (CCB) for the prevention of stroke, myocardial infarction (MI) and premature death in uncomplicated hypertension. We performed a cost-minimization analysis based on numbers-needed-to-treat (NNT) derived from the metaanalysis of 15 major clinical trials of hypertension treatment, and the average wholesale prices of both the most commonly prescribed and the least expensive drugs in each class. The inclusion criteria for clinical trials were that they be randomized, controlled trials of drug therapy of uncomplicated mild-to-moderate hypertension with stroke, MI, or death as endpoints. The wholesale drug costs and the total direct outpatient treatment costs to prevent a stroke, MI or death among middle-aged and elderly hypertensives were our outcome measures. The estimated wholesale drug acquisition cost to prevent one major event (MI or stroke or death) ranged from $4730 to $346,236 among middle-aged patients, and from $1595 to $116,754 in the elderly; generic diuretic or beta-blocker therapy was more economical than treatment with an ACEI, alpha-blocker, or CCB. The associated 5-year NNT was 86 for middle-aged patients and 29 for elderly patients. Diuretic therapy remained more cost-effective even under the unlikely assumption that the newer drugs were 50% more effective than diuretics at preventing these major events. The costs associated with potassium supplementation did not eliminate the advantage of diuretics. Treatment costs to prevent major hypertensive complications are much lower with diuretics and beta-blockers than with ACEI, CCB, or alpha-blockers, especially in middle-aged patients.

Antihypertensive Agents↗
PubMed1998

Measles virus infection and replication in undifferentiated and differentiated human neuronal cells in culture.

Measles virus (MV) infection of the human central nervous system (CNS) typically involves widespread infection of neurons. However, little is known about how they become infected, how defective virus arises and accumulates, or how virus spreads among the cells of the CNS. In vitro studies of viral interactions with human neuronal cells may contribute to the resolution of such issues. In mixed cultures containing differentiated human neuronal (hNT2) cells and neuroepithelial cells, immunofluorescence studies show that the neurons, unlike both their NT2 progenitors and the neuroepithelial cells, are not initially susceptible to MV infection. This is possibly due to their lack of expression of CD46, a known cell surface receptor for MV. Later in the course of infection, however, both MV proteins and genomic RNA become detectable in their processes, where they contact infected, fully permissive neuroepithelial cells. Such a mechanism of virus transfer may be involved in the initiation and spread of persistent MV infection in diseases such as subacute sclerosing panencephalitis. Furthermore, mutated defective virus may readily accumulate and spread without the need, at any stage, for viral maturation and budding.

Cell Differentiation↗
PubMed1997

Detection of bcr-abl transcripts in Philadelphia chromosome-positive acute lymphoblastic leukemia after marrow transplantation.

Thirty-six patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) were studied for the presence of the bcr-abl fusion mRNA transcript after an allogeneic matched related (N = 12), partially matched related (N = 4), matched unrelated (N = 14), autologous (N = 5), or syngeneic (N = 1) bone marrow transplant (BMT). Seventeen were transplanted in relapse, and 19 were transplanted in remission. Twenty-three patients had at least one positive bcr-abl polymerase chain reaction (PCR) assay after BMT either before a relapse or without subsequent relapse. Ten of these 23 relapsed after a positive assay at a median time from first positive PCR assay of 94 days (range, 28 to 416 days). By comparison, only 2 relapses occurred in the 13 patients with no prior positive PCR assays; both patients had missed at least one scheduled follow-up assay and were not tested 2 months and 26 months before their relapse. The unadjusted relative risk (RR) of relapse associated with a positive PCR assay compared with a negative assay was 5.7 (95% confidence interval 1.2 to 26.0, P = .025). In addition, the data suggest that the type of bcr-abl chimeric mRNA detected posttransplant was associated with the risk of relapse: 7 of 10 patients expressing the p190 bcr-abl relapsed, compared with 1 of 8 who expressed only the p210 bcr-abl mRNA (P = .02, log-rank test). The RR of p190 bcr-abl positivity compared to PCR-negative patients was 11.2 (confidence interval 2.3-54.8, P = 0.003), whereas a positive test for p210 bcr-abl was apparently not associated with an increased relative risk. In separate multivariable models, PCR positivity remained a statistically significant risk factor for relapse after separately adjusting for donor (unrelated and partially matched v matched, autologous, and syngeneic), remission status at the time of transplant, the presence of acute graft-versus-host disease (GVHD), and type of conditioning regimen (total body irradiation dose of < or = 1,200 cGy v > 1,200 cGy). The PCR assay appears to be a useful test for predicting patients at high risk of relapse after BMT and may identify patients who might benefit from therapeutic interventions. The finding that the expression of p190 bcr-abl may portend an especially high risk of relapse suggests a different clinical and biologic behavior between p190 and p210 bcr-abl.

Acute Disease↗
PubMed1997

Serum thyroid hormone concentrations in New Zealand horses.

Total thyroxine and total tri-iodothyronine concentrations were measured in the sera from 125 horses of mixed age, breed and sex, and varied clinical histories. While low serum thyroxine concentrations were detected in 35 horses, the majority of those horses had serum thyroxine values within the reference range when retested. Only one horse had a mildly decreased serum tri-iodothyronine concentration. Those horses in which the serum thyroxine concentration was low when retested had a normal thyrotropin releasing hormone stimulation test. Hypothyroidism was not diagnosed in any horses in this study. The low serum thyroxine concentrations measured in the present study were attributed to either normal fluctuations in serum concentrations in healthy horses, the effect of drugs, or to the effects of non-thyroidal illness. Because thyroid hormone concentrations are altered by many factors, hypothyroidism should not be diagnosed on the basis of a single low value and further testing, preferably including active stimulation of the thyroid gland, should be carried out.

Journal Article↗
PubMed1997

The molecular basis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in compound heterozygous patients: is there correlation between genotype and phenotype?

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most commonly recognized defect of mitochondrial beta-oxidation. It is potentially fatal, but shows a wide clinical spectrum. The aim of the present study was to investigate whether any correlation exists between MCAD genotype and disease phenotype. We determined the prevalence of the 14 known and seven previously unknown non-G985 mutations in 52 families with MCAD deficiency not caused by homozygosity for the prevalent G985 mutation. This showed that none of the non-G985 mutations are prevalent, and led to the identification of both disease-causing mutations in 14 families in whom both mutations had not previously been reported. We then evaluated the severity of the mutations identified in these 14 families. Using expression of mutant MCAD in Escherichia coli with or without co-overexpression of the molecular chaperonins GroESL we showed that five of the missense mutations affect the folding and/or stability of the protein, and that the residual enzyme activity of some of them could be modulated to a different extent depending on the amounts of available chaperonins. Thus, some of the missense mutations may result in relatively high levels of residual enzyme activity, whereas the mutations leading to premature stop codons will result in no residual enzyme activity. By correlating the observed types of mutations identified to the clinical/biochemical data in the 14 patients in whom we identified both disease-causing mutations, we show that a genotype/phenotype correlation in MCAD deficiency is not straightforward. Different mutations may contribute with different susceptibilities for disease precipitation, when the patient is subjected to metabolic stress, but other genetic and environmental factors may play an equally important role.

Acyl-CoA Dehydrogenase↗
PubMed1997

Soldier performance and strenuous road marching: influence of load mass and load distribution.

Fifteen male soldiers performed six maximal-effort, 20-km road marchers. They carried load masses of 34, 48, and 61 kg, using a standard military backpack with frame or an experimental doublepack. March times decreased as mass increased and were faster with the standard pack than with the double-pack. The doublepack resulted in less low back discomfort and a lower incidence of blisters at the highest load, but also resulted in more discomfort in the neck and hips. Neither load mass nor pack type affected soldiers' marksmanship ability, grenade throw accuracy, or cognitive ability. The maximal-effort march itself affected the marksmanship tasks by increasing the post-march vertical shot group dispersion. The concept of distributing the load mass more evenly around the center of mass of the body has both positive and negative aspects and warrants further investigation.

Blister↗
PubMed1997

The enuretic episode--a complete micturition from a bladder with normal capacity? A critical reappraisal of the definition.

Fifty-five normal children, aged between 7 and 12 years, were hospitalised for four consecutive nights. On three of these nights, the subjects received 25 ml/kg body weight of fluid prior to bedtime. Such fluid-loading provoked 28 enuresis-like episodes in 17 children, most of which occurred during the first few hours of sleep. The incidence of these enuretic events decreased with increasing age, more boys than girls were affected, there was a statistically significant correlation between total enuresis volume and nocturia volume, and the micturition was frequently incomplete, leaving large volumes of residual urine in the bladder. It was concluded that if nocturnal urine production exceeds bladder capacity, enuresis may be provoked, even in children who do not normally wet the bed. Furthermore, the definition of nocturnal enuresis as a complete emptying of the bladder during sleep may need revision.

Child↗
PubMed1997

Long-term home studies of water balance in patients with nocturnal enuresis.

A 2-week, home-based study was conducted on 75 children with nocturnal enuresis to monitor the frequency of enuretic episodes and the volume of nocturnal urine production. The objectives of the study were to correlate nocturnal urine production to the occurrence of nocturnal enuresis and response to desmopressin (Minirin, DDAVP) treatment. Furthermore, patient compliance was evaluated. Enuresis episodes and nocturnal urine production was recorded every night during two base-line weeks without treatment and during 2 weeks with 20-40 micrograms desmopressin at bedtime. During both periods fluid intake and micturition volumes were recorded for 2 days. Desmopressin response was defined as > 50% reduction in wet nights during treatment. It was found that patient compliance was acceptable in most patients. Regarding urine output it was found that base-line nocturnal urine production was significantly higher during nights when enuresis occurred than during "dry" nights and significantly higher in desmopressin responders compared with desmopressin non-responders. During treatment with desmopressin, nocturnal urine production in desmopressin responders decreased to levels similar to those of non-responders. The results confirm inpatient circadian studies of urine output and emphasise the importance of nocturnal polyuria in patients with monosymptomatic enuresis. The response to desmopressin was found to correlate with the occurrence of nocturnal polyuria. Home studies were considered to be a useful tool in the characterisation of patients with nocturnal enuresis.

Administration, Intranasal↗