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Biomedical subjects

M Hooper

Publications and source records attributed to M Hooper.

At least 19 recordsLinked to original sources
PubMed2000

Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group.

The purpose of this randomized, double-masked, placebo-controlled study was to determine the efficacy and safety of risedronate in the prevention of vertebral fractures in postmenopausal women with established osteoporosis. The study was conducted at 80 study centers in Europe and Australia. Postmenopausal women (n = 1226) with two or more prevalent vertebral fractures received risedronate 2.5 or 5 mg/day or placebo; all subjects also received elemental calcium 1000 mg/day, and up to 500 IU/day vitamin D if baseline levels were low. The study duration was 3 years; however, the 2.5 mg group was discontinued by protocol amendment after 2 years. Lateral spinal radiographs were taken annually for assessment of vertebral fractures, and bone mineral density was measured by dual-energy X-ray absorptiometry at 6-month intervals. Risedronate 5 mg reduced the risk of new vertebral fractures by 49% over 3 years compared with control (p<0.001). A significant reduction of 61% was seen within the first year (p = 0.001). The fracture reduction with risedronate 2.5 mg was similar to that in the 5 mg group over 2 years. The risk of nonvertebral fractures was reduced by 33% compared with control over 3 years (p = 0.06). Risedronate significantly increased bone mineral density at the spine and hip within 6 months. The adverse-event profile of risedronate, including gastrointestinal adverse events, was similar to that of control. Risedronate 5 mg provides effective and well-tolerated therapy for severe postmenopausal osteoporosis, reducing the incidence of vertebral fractures and improving bone density in women with established disease.

Absorptiometry, Photon↗
PubMed1999

Somatic frameshift mutations in the MBD4 gene of sporadic colon cancers with mismatch repair deficiency.

Defects of mismatch repair are thought to be responsible for carcinogenesis in hereditary non-polyposis colorectal cancer and about 15% of sporadic colon cancers. The phenotype is seen as microsatellite instability and is known to be caused either by mutations in mismatch repair genes or by aberrant methylation of these genes stabilizing their downregulation. Lack of repair of microsatellite sequence errors, created during replication, leads to a mutation-prone phenotype. Where mutations occur within mononucleotide tracts within exons they cause translation frameshifts, premature cessation of translation and abnormal protein expression. Such mutations have been observed in the TGFbetaRII, BAX, IGFIIR, MSH3 and MSH6 genes in colon and other cancers. We describe here frameshift mutations affecting the gene for the methyl-CpG binding thymine glycosylase, MBD4, in over 40% of microsatellite unstable sporadic colon cancers. The mutations all appear heterozygous but their location would ensure truncation of the protein between the methyl-CpG binding and glycosylase domains, thus potentially generating a dominant negative effect. It is thus possible that such mutations enhance mutation frequency at other sites in these tumours. A suggestion has been made that MBD4 (MED1) mutations may lead to an increased rate of microsatellite instability but this mechanism appears unlikely due to the nature of mutations we have found.

Base Pair Mismatch↗
PubMed1999

Effect of a standard exercise protocol on shoulder pain in long-term wheelchair users.

PURPOSE: To analyze the effectiveness of a 6-month exercise protocol on shoulder pain experienced by wheelchair users during functional activities. SUBJECTS: Forty-two wheelchair users, 35 males and seven females: average age of 35 years and an average duration of wheelchair use of 14 years. METHODS: Subjects were randomly assigned to treatment (n=21) and control (n=21) groups. The treatment group received instruction in five shoulder exercises which they performed daily for 6 months. The exercise protocol included two exercises for stretching anterior shoulder musculature and three exercises for strengthening posterior shoulder musculature. OUTCOME MEASURES: All subjects completed a self-report questionnaire and the Wheelchair Users Shoulder Pain Index (WUSPI) initially and at bimonthly intervals during the 6-month intervention. RESULTS: Seventy-five per cent of the subjects reported a history of shoulder pain since beginning wheelchair use. The average initial performance-corrected (PC-WUSPI) score of the 42 subjects was 17.7 (+/-21.3) with a range of 0-103.2 points. Over 83% of the subjects (35 of 42) completed the 6-month study. Subjects in the treatment group decreased their PC-WUSPI score by an average of 39.9%, compared to decreases of only 2.5% in the control group. CONCLUSIONS: These findings supported the effectiveness of this exercise protocol in decreasing the intensity of shoulder pain which interferes with functional activity in wheelchair users.

Adult↗
PubMed1999

Effect of environmental tobacco smoke on peak flow variability.

This study was undertaken to determine whether exposure to various indoor pollutants is associated with a higher prevalence of respiratory symptoms, a diagnosis of asthma, or more variable peak flow rates. Four hundred and twenty-six children aged 8-11 years in four junior schools at three locations recorded respiratory symptoms and diagnosis of asthma using the ISAAC questionnaire. Daily peak flow measurements were taken during two six-week periods (winter and summer). Symptoms in children with and without asthma were not related to gas fires, cookers, smokers, or pets in the home. However, the variability of lung function, expressed as the coefficient of variation, in all children was increased with a household smoker. Environmental tobacco smoke increases airways variability in children with and without asthma. Its effects were not apparent from a questionnaire completed by parents, and the coefficient of variation of serially measured peak flows was a more sensitive indicator of lung function.

Air Pollution, Indoor↗
PubMed1999

Cytomegalovirus seropositivity is associated with the expansion of CD4+CD28- and CD8+CD28- T cells in rheumatoid arthritis.

OBJECTIVE: Previous researchers have found expansion of CD4+CD28- T cells in patients with rheumatoid arthritis (RA) compared to age matched controls, and have identified expanded clones of autoreactive cells within this population. We examine the association of prior cytomegalovirus (CMV) infection (positive serum anti-CMV IgG) with the percentage of CD4+CD28- T cells and CD8+CD28- T cells in patients with RA. METHODS: A total of 45 patients (36 women, 9 men), mean age of 59 years, with definite RA were studied. RESULTS: In this group 28 patients were seropositive for CMV and 17 seronegative. Seropositive and seronegative subjects did not differ significantly in age, sex, medication use, or severity of disease. Joint count, Health Assessment Questionnaire, pain score, patient global assessment, physician global assessment, and presence of extraarticular disease served to assess disease severity. Expression of CD4/CD28/CD57 and CD8/CD28/CD57 on lymphocytes was determined by 3 color flow cytometry. (CD28 and CD57 are reciprocally related.) CD4+CD28-CD57+ T cells were expanded only in CMV seropositive patients. CONCLUSION: The "carrier" phenotype that has been hypothesized based on a 2 population model for the distribution of CD4+CD28- T cells in RA can be explained by prior infection with CMV.

Arthritis, Rheumatoid↗
PubMed1997

Prompt treatment for chemical eye injuries.

A chemical injury to the eye requires prompt and effective treatment to minimise permanent damage. This article describes the types of chemical injury and discusses the treatments available.

Burns, Chemical↗
PubMed1997

Breast enlargement during chronic antidepressant therapy.

Recent reports of mammoplasia during selective serotonin re-uptake inhibitor (SSRI) therapy suggested that this side effect may be more common than previously reported. We examined 59 women receiving > or = 2 months treatment with an SSRI or venlafaxine for changes in breast size in relation to menopausal status, weight gain and duration of drug therapy. Serum prolactin, estradiol and beta-hCG were also measured before and during treatment in a subgroup of patients. Twenty-three out of 59 patients (39%) reported some degree of mammoplasia. Significantly more SSRI vs. venlafaxine patients reported mammoplasia (p < 0.01). Eighty-four percent with mammoplasia had weight gain vs. 30% without mammoplasia (p < 0.001). The rate of mammoplasia was unrelated to age, menopausal status or duration of treatment. Serum prolactin increased during treatment in the paroxetine subgroup (p < 0.03). In conclusion, antidepressant-induced mammoplasia may be more common than previously expected.

Breast↗
PubMed1996

Nursing care of the patient with a tracheostomy.

Patients who require a tracheostomy have particular needs associated with their care to ensure their safety and well-being. In this article, the author describes the reasons why a patient might have a tracheostomy and provides a detailed account of the anatomy, care and complications associated with it.

Body Image↗
PubMed1996

Insulin response in bulimia nervosa as a marker of nutritional depletion.

OBJECTIVE: The aim of this provocation study was to examine insulin, glucose, and cortisol levels in response to a glucose load in bulimia nervosa patients and to relate this to behavior, treatment status, and depressive symptomatology. METHOD: A 3-hr glucose tolerance test was performed in 15 female patients and in 4 controls. Tests were performed at different stages of treatment and following documented engagement in the patient's usual or previous repertoire of bulimic behaviors in the 24 hr prior to testing. Insulin, glucose, and cortisol levels were assayed at baseline and at 30-min intervals following the glucose load. Presence or absence of significant depressive symptomatology was ascertained. RESULTS: Three patterns of insulin response were identified: (1) an exaggerated response, (2) a normative response which resembled that of healthy controls, and (3) a blunted pattern. A reciprocal relationship between peak insulin and mean cortisol levels was seen with higher depression scores associated with blunted insulin response. Patients whose response was exaggerated binged and vomited relatively infrequently and were of stable weight. The insulin response of successfully treated patients, abstinent from binging and vomiting for 4 weeks, was similar to that of normal controls. A blunted response occurred in patients who binged and vomited more frequently, whose weight was unstable, and whose baseline eating was chaotic or nonexistent. DISCUSSION: The exaggerated insulin response was seen as a physiological adaptation to intermittent starvation reversible with treatment, while the blunted insulin response associated with higher cortisol levels was seen to result from more constant nutritional deprivation secondary to greater disturbance of behavior.

Adult↗
PubMed1995

Costimulatory activity of human synovial fibroblasts.

UNLABELLED: T cell activation initiated via the CD3/TCR complex requires signals provided by the interaction between costimulatory receptors on T cells and their corresponding ligands on accessory cells. Human dermal fibroblasts are reported to be deficient in this costimulatory activity and normally cannot serve as accessory cells for activation of resting T cells. We examined the contribution of human synovial fibroblasts to costimulatory activity for resting T cells. METHODS: Synovial fibroblast, dermal fibroblast, and umbilical cord endothelial cell cultures were established. These cell lines were co-cultured with purified peripheral T cells; and T cell activation was assayed using 3H-thymidine. RESULTS: Culturing resting T cells with synovial fibroblasts resulted in T cell proliferation with either mitogenic (periodate) or alloantigenic stimulation. This activation was dependent on the addition of interleukin 1 and/or gamma interferon. CONCLUSION: In contrast to dermal fibroblasts, synovial fibroblasts are able to provide costimulatory activity for activation of resting T cells.

Antigen-Presenting Cells↗
PubMed1993

In vivo analysis of Pim-1 deficiency.

The Pim-1 proto-oncogene encodes a highly conserved serine/threonine phosphokinase which is predominantly expressed in hematopoietic organs and gonads in mammals. Overexpression of Pim-1 predisposes to lymphomagenesis in mice. To develop a further understanding of Pim-1 in molecular terms, as well as in terms of its potential role in hematopoietic development, we have generated mice deficient in Pim-1 function. Pim-1-deficient mice are ostensibly normal, healthy and fertile. Detailed comparative analyses of the hematopoietic systems of the mutant mice and their wild-type littermates showed that they are indistinguishable for most of the parameters studied. Our analyses revealed one unexpected phenotype that correlated with the level of Pim-1 expression: Pim-1 deficiency correlated with a erythrocyte microcytosis, whereas overexpression of Pim-1 in E mu-Pim-1-transgenic mice resulted in erythrocyte macrocytosis. In order to confirm that the observed decrease in erythrocyte Mean Cell Volume (MCV) was attributable to the Pim-1 deficiency, we developed mice transgenic for a Pim-1 gene construct with its own promoter and showed that this transgene could restore the low erythrocyte Mean Cell Volume observed in the Pim-1-deficient mice to near wild-type levels. These results might be relevant to the observed involvement of the Pim-1 gene in mouse erythroleukemogenesis. The surprising lack of a readily observed phenotype in the lymphoid compartment of the Pim-1-deficient mice, suggests a heretofore unrecognized degree of in vivo functional redundancy of this highly conserved proto-oncogene.

Animals↗
PubMed1992

In vitro fertilization in the natural cycle.

In vitro fertilization in the natural or spontaneous reproductive cycle was first described by Edwards and his colleagues in 1980 following the birth of their first natural cycle IVF baby 2 years earlier. Many groups attempted to follow their lead but it was almost ten years later that the next publication of success appeared (Foulot et al, 1989). The concept of IVF in the natural cycle is particularly attractive and so in 1987 our group also started evaluating the technique. Initial success in the patients with tubal lesions was not translated to patients with other infertility indications. Unfortunately the technique as initially developed was relatively inefficient with significant procedural losses at each stage. Over the succeeding four years a number of changes have been introduced and the efficiency considerably improved. Although these changes have improved take-home baby rates, overall pregnancy rates per embryo have not altered and are still lower than spontaneous in vivo pregnancy rates. It is likely that in the future, with current developments in culture techniques and greater understanding of gamete biology, this situation will change significantly.

Female↗
PubMed1990

Consecutive inactivation of both alleles of the pim-1 proto-oncogene by homologous recombination in embryonic stem cells.

Specific genes can be inactivated or mutated in the mouse germ line. The phenotypic consequences of the mutation can provide pivotal information on the function of the gene in development and maintenance of the mammalian organism. The procedure entails homologous recombination in embryonic stem cells, which, on fusion to recipient blastocysts, give rise to chimaeric mice that can transmit the mutant gene to their offspring. Inbreeding can then yield mice carrying the mutation in both alleles allowing the phenotypic analysis of recessive mutations. In addition to mice lacking a particular gene function, cell lines carrying null alleles of normally expressed genes can be instrumental in assessing the function of the gene. These cell lines can either be obtained from homozygous animals or, should the mutation be lethal early in embryonic development, be generated by consecutive inactivation of both alleles by homologous recombination in cultured cells. Here we illustrate the feasibility of this latter approach by the efficient consecutive inactivation of both alleles of the pim-1 proto-oncogene in embryonic stem cells.

Animals↗