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Biomedical subjects

C J Hamilton

Publications and source records attributed to C J Hamilton.

At least 19 recordsLinked to original sources
PubMed2006

Impaired muscle strength is associated with fractures in hemodialysis patients.

INTRODUCTION: Fractures are extremely common among hemodialysis (HD) patients. METHODS: To assess if bone mineral density (BMD) and/or tests of muscle strength were associated with fractures, we studied 37 men and 15 women, 50 years and older, on HD for at least 1 year. We excluded subjects with prior renal transplants and women taking hormone replacement therapy. We inquired about low-trauma fractures since starting dialysis. Subjects underwent BMD testing with a Lunar DPX-L densitometer. Tests of muscle strength included: timed up and go (TUG), 6-min walk, functional reach, and grip strength. Lateral and thoracic radiographs of the spine were obtained and reviewed for prevalent vertebral fractures. We used logistic regression to examine associations between fracture (prevalent vertebral, self-reported low trauma since starting dialysis and/or both) and BMD, and fracture and muscle-strength tests. Analyses were adjusted for age, weight, and gender. RESULTS: Mean age was 66+/-9.0 years, mean weight was 72.9+/-15.2 kg, and most (35 of 52) participants were Caucasian. Average duration of dialysis was 40.2 (interquartile range: 24-61.2) months. The most common cause of renal failure was diabetes (16 subjects). There were no differences by gender or fracture. Of the 52 subjects, 27 had either a vertebral fracture or low trauma fracture. There was no association between fractures, hip or spine BMD, or grip strength. In contrast, greater functional reach [odds ratio (OR) per standard deviation (SD) increase: 0.29; 95% CI: 0.13-0.69), quicker TUG (OR per SD decrease: 0.14; 95% CI: 0.11-0.23), and a greater distance walked in 6 min (OR per SD increase: 0.10; 95% CI: 0.03-0.36) were all associated with a reduced risk of fracture. CONCLUSIONS: Impaired neuromuscular function is associated with fracture in hemodialysis patients.

Absorptiometry, Photon↗
PubMed2006

Executive and visuospatial sketchpad resources in euthymic bipolar disorder: Implications for visuospatial working memory architecture.

Visuospatial working memory theory is used to interpret the cognitive impairment in euthymic bipolar disorder. Such patients show deficits in the Corsi Blocks Test (CBT) and executive control. To understand these deficits, 20 euthymic bipolar patients and controls were administered the CBT, Visual Patterns Test (VPT), and a new visual memory task designed to make minimal demands on executive resources. Initial analyses validated the visual memory task and implicated executive involvement in the CBT and VPT. Subsequent analyses on a number of tests confirmed CBT and executive deficits while performance was normal on the VPT and visual memory test. ANCOVA indicated that impaired executive function underpinned patients' CBT performance. Implications for the interface between executive and slave systems of working memory are discussed.

Adolescent↗
PubMed2001

Wingless-type frizzled protein receptor signaling and its putative role in human colon cancer.

We wish to identify new candidate genes involved in the pathogenesis of human colon cancer to better understand the diversity of phenotype presentation that varies from individual to individual. Our working hypothesis is that genetic polymorphism of genes in the Wingless-type (Wnt) frizzled protein receptor pathway is associated with the susceptibility to develop colon cancer. The putative role of the Wnt pathway in sporadic human malignancy of the colon suggests involvement in inherited cancer as well. beta-catenin is the crucial messenger in frizzled receptor signaling, transmitting Wnt-ligand signals such as signals from secreted apoptosis-related proteins to the nucleus. It functions as a genome denunciator by initiating amplification of oncogenes. The net effect of beta-catenin depends on the magnitude of its accumulation in the cytoplasm and, therefore, upon expression profiles of genes in the Wnt pathway. We propose that variations in allelic frequencies of genes involved in the beta-catenin cascade may either promote or impede malignant transformation of the colon. If certain polymorphisms in Wnt signaling through beta-catenin predispose to colon cancer, this might manifest as decreased binding affinity of proteins such as axin or the adenomatous polyposis coli protein to beta-catenin. Association studies are proposed to test the hypothesis, which could serve as an initial step toward understanding the complexity of tumor biology. The clinical rationale in unraveling the genetic susceptibility to cancer lies in identification of a subgroup of individuals who may benefit from beta-catenin targeting agents, which could potentially overcome this genetic instability.

Colorectal Neoplasms↗
PubMed2001

The potential role of estrogen in aromatase regulation in the breast.

Aromatase is expressed in both normal and malignant breast tissues. Aromatase activity in the breast varies over a wide range. Our previous studies have demonstrated that in situ aromatization contributes to the estrogen content of breast tumors to a major extent. Consequently, alterations of aromatase activity could serve as a major determinant of tissue estradiol content. However, the mechanisms and extent of aromatase regulation in breast tissues have not been fully established. We have observed an inverse correlation between tumor aromatase activity and estrogen content in nude mice bearing xenografts of MCF-7 cells transfected with the aromatase gene. To investigate the potential role of estrogen in aromatase regulation in the breast, studies were carried out in an in vitro model. In this model, MCF-7 cells were cultured long term in estrogen-deprived medium and called by the acronym, LTED cells. We found that long-term estrogen deprivation enhanced aromatase activity by 3-4-fold when compared to the wild-type MCF-7 cells. Re-exposure of LTED cells to estrogen reduced aromatase activity to the levels of the wild-type MCF-7 cells. We also measured aromatase activity in 101 frozen breast carcinoma specimens and compared tumor aromatase activities in pre-menopausal patients versus post-menopausal patients and in post-menopausal patients with or without hormone replacement therapy (HRT). Although statistically not significant, there was a trend paralleling that observed in the in vitro studies. Aromatase activity was higher in breast cancer tissues from the patients with lower circulating estrogen levels. Our data suggest that estrogen may be involved in the regulation of aromatase activity in breast tissues.

Animals↗
PubMed2001

Identification of candidate genes in ulcerative colitis and Crohn's disease using cDNA array technology.

Inflammatory bowel disease (IBD) follows a multigenic mode of inheritance, encompassing the clinically discrete phenotypes of ulcerative colitis (UC) and Crohn's disease (CD). The risk of malignant transformation of the colon increases with the duration and extent of IBD and is particularly high for patients with a longstanding history of UC. We wished to identify candidate genes that might be involved in disease pathogenesis based on functional plausibility and their putative role in IBD carcinogenesis. Polyadenylated mRNA (PolyA+ mRNA) preparation from inflamed intestinal mucosa of patients with a longstanding history of UC and CD was performed with subsequent hybridization of alpha phosphorus [alpha-32P]-deoxyadenotriphosphate-labeled complementary deoxyribonucleic acid (DNA) populations to nucleic acid arrays. Of 588 different human gene transcripts arrayed, secreted apoptosis-related protein 1 (Sarp1), frizzled (fz) homologues, and disheveled (dvl) were differentially expressed, being elevated in UC as compared to CD. These genes encode proteins involved in the Wingless-type (Wnt)/beta-catenin signaling pathway. The autonomous expression of Sarp1 and Sarp1-compatible fz receptor genes suggests that the Wnt pathway may be involved in UC carcinogenesis.

Colitis, Ulcerative↗
PubMed1999

Aromatase within the breast.

In situ aromatization and enhanced uptake of estradiol from plasma are two potential mechanisms for maintenance of high concentrations of estradiol found in breast tumors of postmenopausal patients. To test the relative importance of these two mechanisms, a nude mouse model was established by inoculating aromatase (A+) and/or sham (A-) transfected MCF-7 cells into ovariectomized mice. Postmenopausal hormonal status was simulated by providing estradiol Silastic implants which clamped plasma estradiol levels at 5-20 pg/ml. We demonstrated that in situ aromatization rather than the uptake mechanism is the key determinant of tumor estradiol levels and tumor growth rate under conditions reflecting the postmenopausal state. The importance of intratumoral aromatase was also suggested by the findings that long-term estrogen deprivation increases sensitivity to estradiol and enhances aromatase activity in MCF-7 cells. The results of our in vivo and in vitro studies suggest that complete blockade of in situ aromatization in the breast would provide added benefit to postmenopausal breast cancer patients, especially those who relapse from antiestrogen therapy.

Animals↗
PubMed1999

Radial defects and testicular dysfunction: a new syndrome?

We describe two unrelated male patients with radial ray defects and increased serum concentrations of follicle stimulating hormone due to testicular dysfunction. This combination of features has not previously been described. Several mouse genes are known to be involved in preaxial limb development and male fertility, suggesting that the combination of radial ray defects and testicular dysfunction may represent a new syndrome in humans. Abnormalities of spermatogenesis or sperm function may constitute an under-recognized feature of human multiple congenital malformation syndromes.

Adult↗
PubMed1998

In situ aromatization enhances breast tumor estradiol levels and cellular proliferation.

The high concentrations of estradiol (E2) found in breast tumors of postmenopausal women could be the result of enhanced uptake from plasma or in situ aromatization of androgens to estrogens. To test the relative importance of these two mechanisms, a model system allowing precise distinction between each is required. Such a model was established using aromatase (A+)- and sham (A-)-transfected MCF-7 cells inoculated into ovariectomized (OVX) nude mice. To validate the model, the confounding effect of peripheral aromatization was first excluded experimentally. A- cells were inoculated into OVX mice as homoimplants (A- cells on both flanks) or heteroimplants (A- cells on one flank and A+ cells on the other), and growth of A- cells in response to exogenous aromatase substrate, androstenedione (delta4A), was evaluated. A- cells did not grow in either group during the 8 weeks of observation, indicating the lack of peripheral aromatization in OVX mice. The biological effects of in situ aromatization were then directly examined. We found that A+ cells in the heteroimplant group grew rapidly, and that the average weight of A+ tumor was 7.6-fold larger and tissue E2 concentration was 3-4-fold higher than A- tumors grown in the same animals. These results demonstrate that in situ aromatization rather than uptake can be a determinant of tumor E2 content and growth stimulation. An additional experiment was then designed to evaluate the relative importance of in situ synthesis versus uptake under conditions reflecting postmenopausal physiology. Groups of OVX mice bearing A+ cells received E2 Silastic implants to clamp plasma levels at 5, 7, 10, and 20 pg/ml or delta4A by injection. The highest tumor E2 concentration and growth rate were found in the group receiving delta4A. E2 delivered by Silastic implants always produced lower tissue E2 levels and tumor growth rates than resulted from in situ synthesis. These data provide direct evidence that under physiological conditions reflecting those in postmenopausal women, in situ aromatization in breast tumor makes a major contribution to tissue E2 content. As further validation that our experimental paradigm models the postmenopausal state, we studied OVX animals not given delta4A as substrate. A+ cells also grew under these conditions, and the aromatase inhibitor 4-hydroxyandrostenedione reduced both tumor E2 level and growth rate, providing additional evidence of the importance of in situ synthesis. These studies provide the first direct evidence that in situ synthesis of E2 in breast tumors, as opposed to peripheral aromatization and uptake from plasma, can enhance tissue E2 levels and stimulate tumor growth.

Animals↗
PubMed1997

The impact of the woman's age on the success of standard and donor in vitro fertilization.

OBJECTIVE: To study the effect of the age of the woman who provides the oocytes or who receives the embryos on results of IVF-ET. DESIGN: Historical cohort study. Multivariate regression analysis was used to study the age effect continuously and after adjustment for confounding. SETTING: Patients of the University of Southern California, Los Angeles, California. PATIENT(S): Couples who underwent standard (n = 277) or donor IVF-ET (n = 294) between January 1991 and July 1995. INTERVENTION(S): One cycle of standard or donor IVF-ET. MAIN OUTCOME MEASURE(S): Successive IVF outcomes from number of oocytes to ongoing pregnancy and several measures of pregnancy loss. RESULT(S): The number of oocytes decreased with aging of the oocyte provider. More women who received oocytes from donors aged 20 to 23 years had at least one good embryo transferred than women who received oocytes from older donors. The age of the woman who received the embryos had no effect on IVF outcomes. In women > 40 years who underwent standard IVF, the probability of pregnancy decreased. No such relationships were observed for donor IVF, but all the oocyte donors were younger. CONCLUSION(S): An age effect for ongoing pregnancy was only found in women > 40 years who underwent standard IVF independent of the lower number of oocytes and suggests decreasing oocyte quality.

Adult↗
PubMed1997

On mental rotation in three dimensions.

Real three-dimensional models and three-dimensional images were used in a test of mental rotation. Although the 33 men performed better than the 33 women when presented three-dimensional images (14.4 and 11.2), this sex difference disappeared when real models were used (17.5 and 17.3).

Female↗
PubMed1996

A more realistic approach to the cumulative pregnancy rate after in-vitro fertilization.

As most studies overestimate the cumulative pregnancy rate, a method is proposed to estimate a more realistic cumulative pregnancy rate by taking into account the reasons for an early cessation of treatment with in-vitro fertilization (IVF). Three methods for calculating cumulative pregnancy rates were compared. The first method assumed that those who stopped treatment had no chance at all of pregnancy. The second method, the one used most often, assumed the same probability of pregnancy for those who stopped as for those who continued. The third method assumed that only those who stopped treatment, because of a medical indication, had no chance at all of pregnancy and that the others who stopped had the same probability of pregnancy as those who continued treatment. Data were used from 616 women treated at the University Hospital Nijmegen, Nijmegen, The Netherlands. The cumulative pregnancy rates after five initiated IVF cycles for the three calculation methods were in the ranges 37-51% for the positive pregnancy test result, 33-55% for a clinical pregnancy and 30-56% for an ongoing pregnancy. As expected, the first method underestimated the cumulative pregnancy rate and the second overestimated it. The third method produced the most realistic cumulative pregnancy rates.

Data Interpretation, Statistical↗
PubMed1996

Prognostic models for the probability of achieving an ongoing pregnancy after in-vitro fertilization and the importance of testing their predictive value.

The aim of this study was to create reliable models to predict the probability of achieving an ongoing pregnancy during in-vitro fertilization (IVF) treatment: model A, at the start of the first treatment, model B at the time of embryo transfer, and model C, during the second treatment at the end of the first IVF treatment. Prognostic models were created using data from the University Hospital Nijmegen (n = 757) and applied to the data from the Catharina Hospital Eindhoven (n = 432), The Netherlands, to test their predictive performance. The predictions of model B (made at time of embryo transfer) were fairly good (c = 0.672 in the test population). For instance, 93% of the patients who had a predicted probability of achieving an ongoing pregnancy of < 10% did not achieve an ongoing pregnancy. However, the predictions of the other two models (A and C) for Eindhoven were less reliable. The predictive value of model C was fairly high in Nijmegen (c = 0.673). Its poor performance in the test population may be explained partly by differences in effectiveness of the ovulation stimulation protocols and the decision about when to discontinue the cycle. Thus, before using prognostic models at an IVF centre, their reliability at that specific centre should be tested.

Evaluation Studies as Topic↗
PubMed1996

Is there seasonality in human ovulation?

To study seasonality in human ovulation in a direct way, we measured the occurrence of ovulation in infertile patients with spontaneous menstrual cycles (< 6 weeks) who visited the fertility clinic at the University Hospital Nijmegen in the Netherlands for the first time in 1991 or 1992 (n = 407). Ovulation was detected using serial transvaginal ultrasound and midluteal progesterone measurement and was performed during one screening cycle. The frequency of ovulatory cycles per month varied from 73% to 93% (not statistically significant). No seasonal pattern in ovulation was found in subfecund Dutch women with spontaneous menstrual cycles. This finding was not confounded by the effects of age of the women, body mass index, or disorders that could influence ovulation.

Adult↗
PubMed1995

Gonadotropin hyperstimulation influences the 35S-methionine metabolism of mouse preimplantation embryos.

The effects of gonadotropin stimulation on mouse embryo uptake and incorporation of 35S-methionine were studied. We found that the uptake of 35S-methionine was reduced in embryos of stimulated females in both the two-cell and the blastocyst developmental stage. The incorporation of 35S-methionine into protein was not statistically significantly different between the embryos of stimulated and those of unstimulated females. Qualitatively, protein synthesis was equal in both groups as determined with one-dimensional SDS-PAGE. The results are discussed and we conclude that mouse embryo viability in vivo is decreased by ovarian stimulation.

Animals↗
PubMed1995

Sperm functional changes and fertilization in vitro in co-culture with human skin fibroblasts.

This study was undertaken to evaluate the effects of human skin fibroblast monolayers on human sperm function and fertilization in vitro. Sperm function was evaluated using the hamster oocyte penetration assay (HOPA) and zona binding assay (ZBA) in medium alone and in co-culture with human skin fibroblast monolayers and suspensions. The ZBA was also studied in fibroblast conditioned medium and in bovine oviduct cell monolayers and suspensions. Fertilization was measured both in in-vitro fertilization (IVF) couples with a normal semen analysis (first study; randomized) and in IVF couples with subnormal semen analysis (second study; each patient served as its own control). The HOPA results were not significantly different with or without fibroblasts. In all co-culture situations and in conditioned medium the ZBA scored significantly lower than medium alone. No significant differences with respect to IVF were observed between the co-culture and the control group in either study. The mean fertilization rate per patient was approximately 60% in the group with normal semen analysis and approximately 25% in the group with abnormal semen analysis. From this study we conclude that although co-culture with human skin fibroblasts and epithelial cells influences the results of some sperm function tests, it does not influence fertilization in vitro.

Animals↗
PubMed1995

Beyond sex differences in visuo-spatial processing: the impact of gender trait possession.

Much research has emphasized the presence of sex differences in visuo-spatial processes while neglecting individual differences in performance within the two sexes (Archer, 1987). The present study looks beyond sex differences and considers the association of self-perceived gender trait possession with performance in two visuo-spatial tasks. The findings indicate that, in a 3-D mental rotation task, where a substantial sex difference occurred, gender trait possession adds significantly to the overall explanation of performance, the important gender trait variable being a measure of androgyny. With the Group Embedded Figures Task, gender trait measures were the only significant variables in differentiating performance, in this case masculinity was the important gender trait variable. The implication of such results for conventional explanations of individual differences in visuo-spatial processing is discussed.

Adolescent↗
PubMed1994

Controlled comparison of interceed and amniotic membrane graft in the prevention of postoperative adhesions in the rabbit uterine horn model.

OBJECTIVE: To evaluate the effects of Interceed TC7 (Johnson & Johnson Medical, New Brunswick, NJ) and gamma-irradiated human amniotic membrane graft in prevention of postoperative adhesions in the rabbit uterine horn model. SETTING: A conventional animal laboratory. SUBJECTS: Virgin, female New Zealand white rabbits. INTERVENTIONS: Both uterine horns were subjected to clean transverse cuts 1 cm apart at the antimesenteric border. The left uterine horn was left uncovered in each case to act as a control. The right uterine horn was randomly covered with either Interceed TC7 or human amniotic membrane. OUTCOME MEASURES: Adhesion score was evaluated 4 weeks after the initial surgery. Samples of each uterine horn were collected for histopathological studies, and subserosal inflammatory score. RESULTS: Interceed resulted in higher adhesion scores and subserosal inflammation score than the control side (P = 0.03 and 0.05, respectively). A similar difference was found for amniotic membrane when compared with the uncovered control side (P = < 0.01 and 0.01, respectively). CONCLUSION: Interceed TC7 failed to have the preventive effect on adhesion formation it is claimed to possess. Amniotic membrane performed poorly too. Therefore, gentle tissue handling, irrigation and good surgical skills remain the most important prerequisite for adhesion prevention.

Amnion↗