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Biomedical subjects

W Thomas

Publications and source records attributed to W Thomas.

At least 55 records · Page 3Linked to original sources

Effect of flaxseed consumption on urinary estrogen metabolites in postmenopausal women.

Flaxseed, the richest known source of plant lignans, has been shown to have chemoprotective effects in animal and cell studies. Some of its effects may be mediated through its influence on endogenous hormone production and metabolism. Two competing pathways in estrogen metabolism involve production of the 2-hydroxylated and 16 alpha-hydroxylated metabolites. Because of the proposed differences in biological activities of these metabolites, the balance of the two pathways has been used as a biomarker for breast cancer risk. We examined the effects of flaxseed consumption on urinary estrogen metabolite excretion in postmenopausal women. Twenty-eight postmenopausal women were studied for three seven-week feeding periods in a randomized crossover design. During the feeding periods, subjects consumed their usual diets plus ground flaxseed (0, 5, or 10 g/day). Urinary excretion of the estrogen metabolites 2-hydroxyestrogen (2-OHEstrogen) and 16 alpha-hydroxyestrone (16 alpha-OHE1) as well as their ratio, 2/16 alpha-OHE1, was measured by enzyme immunoassay. Flaxseed supplementation significantly increased urinary 2-OHEstrogen excretion (p < 0.0005) and the urinary 2/16 alpha-OHE1 ratio (p < 0.05) in a linear, dose-response fashion. There were no significant differences in urinary 16 alpha-OHE1 excretion. These results suggest that flaxseed may have chemoprotective effects in postmenopausal women.

Aged↗

Effects of soy intake on sex hormone metabolism in premenopausal women.

Studies suggest that phytoestrogens in soy products may impart hormonal effects that protect women against breast cancer. Limited research suggests that intake of soy products high in isoflavonoid phytoestrogens affects sex hormone metabolism, but it is unknown whether phytoestrogens in soy have any effect on menstrual function or serum sex hormones in women on common hormone therapies, such as oral contraceptives (OC). We studied the effects of soy in 36 premenopausal women, 20 of whom used OC. Subjects consumed their normal diet for two menstrual cycles and added a soy beverage containing 20 g of protein and 38 mg of total isoflavones to their usual diet for another two menstrual cycles. No significant differences were observed in serum estrone, estradiol, sex hormone-binding globulin, dehydroepiandrosterone sulfate, prolactin, or progesterone concentrations with soy feeding in the non-OC or the OC group. No changes in menstrual cycle length or the urinary estrogen metabolite ratio of 2-hydroxyestrone to 16 alpha-hydroxyestrone were seen with soy feeding in the non-OC or the OC group. Levels of urinary estrogen metabolites were significantly different between the non-OC and the OC group. Thus soy consumption had no significant effect on the menstrual cycle, serum sex hormones, or urinary estrogen metabolite ratio in premenopausal OC or non-OC users.

Adolescent↗

[Measures for biomechanically correct positioning of knee joint endoprostheses].

Normal post-operative function, permanent stable fixation and long life for the implant material are determined mainly by the correct biomechanical positioning of the knee joint prosthesis. We have identified six measures within the surgical procedure that are of vital importance for achieving biomechanically correct positioning. Because of their great importance, we call these measures "The Golden Six", and describe their application using the ESKA Resurfacing Knee System (RKS). This system, which is so designed that it enables a maximal bone saving resection technique, makes use of a diagonal screw-fixation of the endoprosthetic elements, resulting in increased primary stability. For the safe and reliable implementation of our measures, we have developed a special set of instruments. Anatomical, kinematic and surgical studies have shown that with the aid of the above-mentioned six measures biomechanically correct positioning of all the implanted elements can be achieved, thus ensuring trouble-free post-operative function of the knee joint and the least possible mechanical stressing of the implanted materials.

Arthroplasty, Replacement, Knee↗

Pharmacologic induction of weight loss to treat type 2 diabetes.

OBJECTIVE: Most individuals with type 2 diabetes are overweight, and weight loss for them is an important therapeutic objective. However, usual weight-loss strategies have generally not produced sustained weight loss. Pharmacologic agents to assist weight loss might be useful, but no long-term data on their effectiveness and safety in patients with type 2 diabetes are available. We therefore initiated a 2-year placebo-controlled trial of the weight-loss medications fenfluramine and phentermine in type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: A total of 44 overweight (> 120% ideal body weight) subjects with type 2 diabetes were enrolled in a randomized, placebo-controlled, double-blind trial of fenfluramine and phentermine. All subjects received intensive nutrition counseling, an exercise prescription, and instruction in behavior modification. Subjects were randomly assigned to 20 mg fenfluramine three times a day and 37.5 mg phentermine daily (n = 23) or dual placebos (n = 21). Diabetes medications were adjusted as necessary to achieve glycemic goals. Changes in weight, glycemia, lipemia, and blood pressure were assessed every 2 months, as were adverse events. In September 1997, when fenfluramine was withdrawn from the U.S. market, fenfluramine was stopped in all subjects. Thus the length of drug treatment varied, but 16 subjects (8 in each group) reached 12 months of treatment. Only data obtained before the withdrawal of fenfluramine are included in this report. RESULTS: A study termination, diabetes medications had been reduced in 1 subject in the placebo group (5%) and 11 subjects in the drug treatment group (52%) (P = 0.005). Drug treatment resulted in significant reductions in body weight, BMI, and HbA1c at all time points through 6 months. Changes in weight at 6 months were -2.7 +/- 1.4 kg (mean +/- SEM) with placebo treatment and -9.6 +/- 1.5 kg with drug treatment (P = 0.003). Even though more subjects in the drug treatment group required reductions in diabetes medications, at 6 months, changes in HbA1c were -0.3 +/- 0.2% with placebo treatment and -1.6 +/- 0.3% with drug treatment (P = 0.002). Fasting plasma glucose and triglycerides were significantly reduced at some time points with drug treatment. No serious adverse events attributable to study medications were observed. CONCLUSIONS: Premature study termination decreased the power of our study at later time points. However, our data suggest that weight loss medications are an effective treatment for type 2 diabetes during active weight loss. Whether the benefit persists after weight loss has stopped remains to be determined.

Appetite Depressants↗

[Use and costs of psycho-oncological liaison services].

The extent to which patients took advantage of psychosocial consultation services in two clinics for internal and oncological disorders was documented over a period of four and a half years to establish, for the sake of future planning, whether there was a demand for psychosocial intervention. During the first year of treatment, consultations between a member of the psychosocial staff and any one patient averaged a total of 13 hours (2 sessions a week, each lasting 28 mins). The number of sessions depended most of all on objectifiable stress factors related to the course of disease or treatment. From records of both directly patient-oriented and team-oriented staff activities, we calculated the staffing requirements and costs of offering a psychosomatic consultation service within the framework of intensive internal-oncological medical care.

Adaptation, Psychological↗

[Problem-based teaching and learning. An opportunity for medical psychology, psychosomatic medicine and psychotherapy?].

All proposals for a reform of the study of medicine recommend problem-based teaching and learning methods. The rapid increase in the number of medical faculties abroad offering experimental courses along these lines is an indicator of their usefulness. The results of empirical research also suggest that departments of medical psychology, psychosomatic medicine and psychotherapy should participate more closely in the introduction and exploration of the advantages of this didactic approach.

Problem-Based Learning↗

People who make a difference. Interview by Wendy L. Bonifazi.

In last year's 20th anniversary issue, Contemporary started an annual tradition of honoring people whose innovative business practices, research, advocacy, and other efforts have shaped long term care. This year's four honorees have created groundbreaking tools for care, campaigned to promote the healthy growth of a fledgling form of care, and championed a vision for improving quality of life for residents.

Aged↗

The synthesis of novel matrix metalloproteinase inhibitors employing the Ireland-Claisen rearrangement.

Matrix metalloproteinase inhibitors of general formula (1) were synthesised by a route involving an Ireland-Claisen rearrangement which enables systematic modification of the substituent alpha to the hydroxamic acid. An analogue (12c) possessing an alpha-cyclopentyl group is a potent broad spectrum inhibitor that displays high and sustained blood levels following oral dosing in both the rat and marmoset ex-vivo bioassays. This compound and analogues are also potent inhibitors of TNF alpha release.

Administration, Oral↗

Physical map of the human chromosome 8p12-p21 encompassing tumor suppressor and Werner's syndrome gene loci.

Detailed physical maps of the human genome are important resources for identification and isolation of genes responsible for diseases and for the study of their structure and function. We constructed a 2.0-Mb high-resolution physical map within the human chromosome 8p12-p21 region extending from marker D8S131 to D8S283. The map comprises a series of contigs mostly P1/PAC clones, which span the loci of potential tumor suppressor genes and the Werner's syndrome gene. Each P1/PAC DNA was defined by its size, restriction sites, terminal sequences, intermarker distances and location relative to major genes and markers. The genes on these P1/PAC DNAs were analyzed by an exon amplification method to determine their locations. The genes newly found by the exon amplification method together with other known genes, including those of glutathion reductase, a general transcription factor, protein phosphatase 2A beta subunit and Werner's syndrome, were precisely mapped within the contigs. These P1/PAC DNAs are useful reagents for the generation of new microsatellite markers to narrow the candidate region of the tumor suppressor gene(s) and/or genes responsible for other diseases, which are believed to exist in this region by linkage analysis.

Animals↗

A haplotype and linkage disequilibrium analysis of the hereditary hemochromatosis gene region.

Hereditary hemochromatosis is a recessive disease of iron metabolism widely distributed among people of European descent. Most patients have inherited the causative mutation from a single ancestor. In the course of cloning the hemochromatosis gene, genotypes were generated for these samples at 43 microsatellite repeat markers that span the 6.5-Mb hemochromatosis gene region. The data used to reconstruct the ancestral haplotype across the hemochromatosis gene region are presented in this paper. Portions of the ancestral haplotype were present on 85% of patient chromosomes in this sample and ranged in size from approximately 500 kb to greater than 6.5 Mb. Only one marker, D6S2239, was identical by descent on all of the patient chromosomes containing the ancestral mutation. In contrast, only 3 of the 128 control chromosomes, or 2.3%, carried the ancestral mutation and the surrounding ancestral haplotype. To test new methods for gene finding using linkage disequilibrium we analyzed the genotypic data with a multilocus maximum likelihood method (DISMULT) and a single point method (DISLAMB), both written to analyze data generated from multi-allelic markers. The maximum value from DISLAMB analysis occurred at marker D6S2239, which is less than 20 kb from the hemochromatosis gene HFE, consistent with the haplotype analysis. The peak of the multi-point analysis was 700 kb from HFE, possibly due to the nonuniform recombination rates within this large region. The recombination rate appears to be lower than expected centromeric of the HFE gene.

Chromosome Mapping↗

Fowlpox virus encodes nonessential homologs of cellular alpha-SNAP, PC-1, and an orphan human homolog of a secreted nematode protein.

The genome of fowlpox virus (FWPV), type species of the Avipoxviridae, is considerably rearranged compared with that of vaccinia virus (the prototypic poxvirus and type species of the Orthopoxviridae) and is 30% larger. It is likely that the genome of FWPV contains genes in addition to those found in vaccinia virus, probably involved with its replication and survival in the chicken. A 7,470-bp segment of the FWPV genome has five open reading frames (ORFs), two of which encode ankyrin repeat proteins, many examples of which have been found in poxviruses. The remaining ORFs encode homologs of cellular genes not reported in any other virus. ORF-2 encodes a homolog of the yeast Sec17p and mammalian SNAP proteins, crucial to vesicular transport in the exocytic pathway. ORF-3 encodes a homolog of an orphan human protein, R31240_2, encoded on 19p13.2. ORF-3 is also homologous to three proteins (YLS2, YMV6, and C07B5.5) from the free-living nematode Caenorhabditis elegans and to a 43-kDa antigen from the parasitic nematode Trichinella spiralis. ORF-5 encodes a homolog of the mammalian plasma cell antigen PC-1, a type II glycoprotein with exophosphodiesterase activity. The ORFs are present in the virulent precursor, HP1, of the sequenced attenuated virus (FP9) and are conserved in other strains of FWPV. They were shown, by deletion mutagenesis, to be nonessential to virus replication in tissue culture. RNA encoding the viral homolog of PC-1 is expressed strongly early and late in infection, but RNAs encoding the homologs of SNAP and R31240_2 are expressed weakly and late.

Amino Acid Sequence↗

Comorbidity of diabetes and eating disorders. Does diabetes control reflect disturbed eating behavior?

OBJECTIVE: This multicenter study was designed to explore the prevalence of clinical and subclinical eating disorders (EDs), the extent of intentional omission of insulin and oral antidiabetic agents, and its relationship to glycemic control in an inpatient and outpatient population of men and women with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: Data have been collected from 12 diabetes medical centers in two German cities. In a questionnaire and interview-based study, a sample of male and female patients (n = 341 type 1, n = 322 type 2) was assessed for the following eating disorders: anorexia nervosa, bulimia nervosa, binge eating disorder, and eating disorder not otherwise specified. For lack of interview data of several patients meeting the screening criteria, prevalence ranges were calculated. RESULTS: The overall prevalence range of current EDs was 5.9-8.0% (lifetime prevalence 10.3-14.0%). When patients were stratified according to type 1 and type 2 diabetes, there was no difference in prevalence of EDs. However, the distribution of the EDs was different in both types of diabetes, with a predominance of binge eating disorder in the type 2 diabetes sample. Type 1 (5.9%) and type 2 (2.2%) diabetic patients reported deliberate omission of hyperglycemic drugs (insulin or oral agents) in order to lose weight. Compared with control subjects, neither the presence of EDs nor insulin omission influenced diabetic control. CONCLUSIONS: There seems to be no difference in prevalence rates of EDs in both types of diabetes; however, distribution of EDs is different. The findings suggest that neither EDs nor insulin omission are necessarily associated with poor control of glycemia. Binge eating disorder seems to precede type 2 diabetes in most patients and could be one of the causes of obesity that often precedes type 2 diabetes.

Adolescent↗

Outcome of coronary artery bypass surgery in diabetic transplant candidates.

Insulin-dependent diabetic (IDDM) patients with end-stage renal disease and coronary artery stenoses > or = 75% have a poor prognosis. However, information is lacking on the morbidity and mortality of the coronary artery bypass operation in this group. We studied 30 consecutive IDDM transplant candidates undergoing a bypass operation to determine the incidence of complications and long-term outcome. Perioperative mortality was 3% and the complication rate was 60%. During follow-up, five patients experienced six myocardial infarctions, the majority within six months of operation. Twenty-one patients underwent successful kidney transplantation after the bypass operation. Overall patient survival was 80%, 73%, and 66% at 1, 2 and 4 yr. In summary, the coronary artery bypass procedure in IDDM transplant candidates has a high morbidity, but the long-term outcome is good. Appropriately counseled IDDM transplant candidates with coronary artery disease should be considered for coronary revascularization and subsequent transplantation.

Coronary Artery Bypass↗