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Biomedical subjects

W Thomas

Publications and source records attributed to W Thomas.

At least 73 records · Page 4Linked to original sources

[Total hip replacement in presence of acetabular dysplasia type II according to the AAOS classification.].

GOAL OF SURGERY: Incorporation of the acetabular cup in ideal position in patients with a primary dysplastic acetabulum. Two thirds of the surface of the cup must be covered by bone. INDICATIONS: Joint replacement in patients with acetabular dysplasia type II according to the AAOS classification. CONTRAINDICATIONS: Presence of acetabular dysplasia types I and III according to the AAOS classification. PREOPERATIVE WORK UP: Radiographic measurement of the acetabular depth and width using templates. POSITIONING AND ANAESTHESIA: Supine, affected side of pelvis slightly elevated. General or spinal anaesthesia. Special set of instruments mandatory. SURGICAL TECHNIQUE: Insertion of an acetabular cup through a lateral approach. Reaming of the acetabulum and filling of the defect under compression with a mixture of autogenous, morcellized bone from the resected femoral head and fibrin glue. Coverage of the transplanted bone with a pedicled capsular flap. POSTOPERATIVE MANAGEMENT: Phlebitis prophylaxis. Walking with 2 forearm crutches on the first postoperative day. Removal of stitches after 10 days. Thereafter gradual increase of weight bearing (10 kg every second day, use a bathroom scale to check loading). Once full weight bearing and full muscle control have been reached, use of 1 crutch is allowed. Radiographic control after 6 weeks, 3,6 and 12 months and yearly thereafter. POSSIBLE COMPLICATIONS: Perforation of the bony acetabulum. Fracture of the anterior or posterior acetabular rim. Thrombophlebitis, lung embolism, infection and/or periarticular ossification. RESULTS: Between 1986 and 1994 the technique has been used in 140 hips with congenital dysplasia (type II according to the AAOS classification) and secondary osteoarthritis. 132 hips were regularly assessed and the mean of follow-up was 6.2 years (1 to 9 years). The mean age of the mostly female patients was 48 years (28 to 62 years). Only porous surfaced metallic cups without cement were used. The following complications were observed: thrombophlebitis 1, superficial infection 1, transient paresis of the fibular nerve 1 and transient irritation of the femoral nerve 3 (see Table 2). Additional complications such as thigh pain, periarticular ossification and resorption of the bone graft are listed in Table 3. Complete bony incorporation of the bone grafts was seen in 122 hips. Resorption up to 8 mm occurred in the remaining 10 hips.

English Abstract↗

Mutation and haplotype analyses of the Werner's syndrome gene based on its genomic structure: genetic epidemiology in the Japanese population.

The correlation between mutations in the Werner's syndrome (WRN) gene and the haplotypes of surrounding markers was studied in Japanese patients. We have elucidated the genomic structure of WRN helicase, and found five additional mutations, designated mutations 6-10. Mutations 4 and 6 were found to be the two major mutations in this population; these mutations comprised 50.8% and 17.5%, respectively, of the total in a sample of 126 apparently unrelated chromosomes. Almost all the patients homozygous for mutation 4 shared a haplotype around the WRN gene, consistent with the view that they are derived from a single ancestor. This important advantage demonstrated in the identification of the WRN gene suggests that the Japanese present a unique population for the cloning of other disease genes. The conserved haplotype was observed across 19 loci, extending a distance estimated to be more than 1.4 Mbp around the WRN gene. This haplotype is rare among random Japanese individuals. Unexpectedly, all the nine patients homozygous for mutation 6 shared a haplotype that was identical to this haplotype at 18 of these 19 markers. These results suggest that mutations 4 and 6 arose independently in almost identical rare haplotypes. The remaining mutations (1, 5, 7, 8, 9, and 10) occurred rarely, and were each associated with different haplotypes.

DNA Helicases↗

Glucose measurement in patients with diabetes mellitus with dermal interstitial fluid.

Although measurement of capillary blood glucose remains the standard method of self-monitoring for persons with diabetes mellitus, a less-invasive method of monitoring would be desirable. Measurement of dermal interstitial fluid glucose might meet this need. To test this possibility, plasma glucose, capillary blood glucose (current standard), and dermal interstitial fluid glucose were measured in 17 subjects with type I diabetes during a 5-hour pre- and postprandial period when plasma glucose was changing rapidly. The objective was to assess the ability of dermal interstitial fluid glucose to accurately predict plasma glucose over a wide range of potential glucose concentrations. Dermal interstitial fluid glucose was highly correlated with plasma glucose (r = 0.95, p < 0.0001). The mean absolute and percent differences between dermal interstitial fluid glucose and plasma glucose were 1.2 mmol/L (21 mg/dl) and 10.6%, respectively. The kinetics of dermal interstitial fluid glucose and plasma glucose were similar. There was no significant difference between dermal interstitial fluid glucose and plasma glucose in mean glucose excursion, peak glucose concentration, or time to peak glucose concentration. The correlation between dermal interstitial fluid glucose and plasma glucose was as strong as the correlation between capillary blood glucose and plasma glucose. In conclusion, dermal interstitial fluid glucose can be used to estimate plasma glucose, and has the potential to be used for monitoring patients with diabetes mellitus.

Adult↗

Long-term follow-up of patients receiving injection therapy for erectile dysfunction.

OBJECTIVES: During the last decade, vasoactive intracavernosal pharmacotherapy (VIP) has been used extensively for the treatment of erectile dysfunction. However, there is concern about high discontinuation rates and the possibility of long-term complications. Because of few long-term studies on VIP, we investigated efficacy, side effects, satisfaction index, and drop-out rate for injection therapy in patients who started treatment more than 5 years ago. METHODS: Questionnaires were mailed to 108 patients who were started on VIP more than 5 years ago, between November 1984 and July 1989. The hospital records and data from the 100 responders (93%) were reviewed. RESULTS: Only 32% of the patients continue to use VIP. Most (56%) of those who discontinued did so during the first year. The patients cited one or more of the following reasons for discontinuation: desire for a permanent modality of therapy (29%), lack of a suitable partner (26%), fear of needles (23%), poor response (23%), fear of complications (22%), and lack of sexual spontaneity (21%). This study, which has one of the longest follow-up periods in the literature, has significant new findings in three areas: discontinuation rates fall after 2 years, long-term complications are relatively minor, and patients who discontinue therapy are significantly older or have a poor initial impression of VIP. Paradoxically, discontinuing VIP was apparently unrelated to side effects or etiology of erectile dysfunction, and 82% of patients would still recommend VIP to a friend. CONCLUSIONS: This study conclusively shows that because of high initial satisfaction and relatively minor side effects, VIP should remain as one of the initial options for long-term treatment of erectile dysfunction. However, despite seemingly doing well, patients often discontinue therapy, and therefore should be followed closely so that alternative therapy can be offered.

Adult↗

Atherosclerotic vascular complications in diabetic transplant candidates.

Serious vascular complications limit the success of renal transplantation in diabetic patients. Nearly half of diabetic transplant recipients die within 3 years after transplantation from a vascular complication. However, it has been difficult to determine before transplantation which patients are likely to do poorly. Because atherosclerosis is a systemic disease, we hypothesized that diabetic transplant candidates with pretransplant coronary artery disease would be at high risk for vascular complications even if asymptomatic at the time of pretransplant evaluation. Our hypothesis was that insulin-dependent (IDDM) transplant candidates with coronary artery disease identified with pretransplant coronary angiography would have an increased number of vascular events (amputation, cerebral vascular accident [CVA], or myocardial infarction [MI]) within 3 years of follow-up. We prospectively studied 198 consecutive diabetic transplant candidates grouped on the basis of coronary artery disease. Group 1 patients had no stenosis that was 50% or greater, group 2 patients had one or more stenoses between 50% and 74%, and group 3 patients had one or more stenoses of 75% or greater. During median follow-up of 41 months, 64 patients experienced 98 amputations, 28 MIs, and seven CVAs. At 36 months of follow-up, 55% of group 3 patients, 30% of group 2 patients, and 11% of group 1 patients had experienced a vascular event (P < 0.001). Cox regression confirmed the association of coronary artery disease with subsequent vascular events. Patients with coronary artery disease had a sevenfold increased risk of amputation and a fourfold increased risk of myocardial infarction. Six of seven CVAs occurred in patients with coronary artery disease. We conclude that coronary artery disease identified at pretransplant evaluation is associated with an increased risk of noncoronary vascular complications within 3 years after evaluation.

Adult↗

Human CD8+ T cell responses to EBV EBNA1: HLA class I presentation of the (Gly-Ala)-containing protein requires exogenous processing.

Epstein-Barr virus (EBV)-induced cytotoxic T lymphocyte (CTL) responses have been detected against many EBV antigens but not the nuclear antigen EBNA1; this has been attributed to the presence of a glycine-alanine repeat (GAr) domain in the protein. Here we describe the isolation of human CD8+ CTL clones recognizing EBNA1-specific peptides in the context of HLA-B35.01 and HLA-A2.03. Using these clones, we show that full-length EBNA1 is not presented when expressed endogenously in target cells, whereas the GAr-deleted form is presented efficiently. However, when supplied as an exogenous antigen, the full-length protein can be presented on HLA class I molecules by a TAP-independent pathway; this may explain how EBNA1-specific CTLs are primed in vivo.

Alanine↗

A 1.1-Mb transcript map of the hereditary hemochromatosis locus.

In the process of positionally cloning a candidate gene responsible for hereditary hemochromatosis (HH), we constructed a 1.1-Mb transcript map of the region of human chromosome 6p that lies 4.5 Mb telomeric to HLA-A. A combination of three gene-finding techniques, direct cDNA selection, exon trapping, and sample sequencing, were used initially for a saturation screening of the 1.1-Mb region for expressed sequence fragments. As genetic analysis further narrowed the HH candidate locus, we sequenced completely 0.25 Mb of genomic DNA as a final measure to identify all genes. Besides the novel MHC class 1-like HH candidate gene HLA-H, we identified a family of five butyrophilin-related sequences, two genes with structural similarity to a type 1 sodium phosphate transporter, 12 novel histone genes, and a gene we named RoRet based on its strong similarity to the 52-kD Ro/SSA lupus and Sjogren's syndrome auto-antigen and the RET finger protein. Several members of the butyrophilin family and the RoRet gene share an exon of common evolutionary origin called B30-2. The B30-2 exon was originally isolated from the HLA class 1 region, yet has apparently "shuffled" into several genes along the chromosome telomeric to the MHC. The conservation of the B30-2 exon in several novel genes and the previously described amino acid homology of HLA-H to MHC class 1 molecules provide further support that this gene-rich region of 6p21.3 is related to the MHC. Finally, we performed an analysis of the four approaches for gene finding and conclude that direct selection provides the most effective probes for cDNA screening, and that as much as 30% of ESTs in this 1.1-Mb region may be derived from noncoding genomic DNA.

Amino Acid Sequence↗

Control of lymphatic and hematogenous metastasis of a rat mammary carcinoma by the matrix metalloproteinase inhibitor batimastat (BB-94).

We examined the effects of the synthetic matrix metalloproteinase inhibitor batimastat (BB-94) on lung colonization and spontaneous metastasis of a rat mammary carcinoma, HOSP.1P. This tumor expresses both latent and active forms of the matrix metalloproteinases MMP-2 and MMP-9, although the former, as in human breast cancer, is the most prominent. Administration of batimastat (6 x 30 mg/kg i.p.) inhibited by up to 80% both the number and median weights of HOSP.1P lung colonies following i.v. inoculation of cells. This implies an effect both on seeding efficiency and subsequent tumor development. In spontaneous metastasis assays, limited treatment with batimastat (commencing when s.c. tumors were established and continuing until 5 or 14 days after their surgical removal) significantly inhibited lung metastasis but had little effect on lymphatic metastasis. However, when treatment was initiated 2 days prior to surgery and continued until day 70, 100% of animals survived to day 120 when there was no evidence of metastatic disease. All control animals (n = 25) in two separate experiments died before day 100 with lymphatic, lung, and extrapulmonary metastases. Taken together, these data suggest that lymphatic dissemination by HOSP.1P tumor cells is less susceptible to inhibition by batimastat than vascular invasion, but that long-term treatment can effectively prevent the outgrowth of putative micrometastases in both lymph nodes and lungs, allowing sustained tumor-free survival.

Animals↗

Maternal intake of cruciferous vegetables and other foods and colic symptoms in exclusively breast-fed infants.

OBJECTIVE: We sought to assess relationships among components of maternal diet and the presence of colic symptoms among exclusively breast-fed infants aged < or = 4 months. DESIGN: Data were collected by means of a mailed questionnaire that solicited information on the presence of symptoms of colic in infants and maternal intake of 15 foods (including four cruciferous vegetables) during the week before completion of the questionnaire. SUBJECTS: Exclusively breast-feeding women (n = 272) and their 273 infants aged < or = 4 months. STATISTICAL ANALYSES PERFORMED: Dietary variables were analyzed categorically by logistic regression. Two-by-two tables were used to calculate relative risks. RESULTS: Relative risks (RRs) and 95% confidence intervals (CIs) for colic symptoms by food items the mothers consumed ranged from 0.7 (CI = 0.3 to 1.5) for beef to 2.0 (CI = 1.1 to 3.5) for cow's milk. Maternal intake of cabbage (RR = 1.3, CI = 1.1 to 1.5), cauliflower (RR = 1.2, CI = 1.0 to 1.4), broccoli (RR = 1.3, CI = 1.0 to 2.2), cow's milk (RR = 2.0, CI = 1.1 to 3.5), onion (RR = 1.7, CI = 1.1 to 2.5), and chocolate (RR = 1.5, CI = 1.0 to 2.2) were significantly related to colic symptoms. Maternal intake of more than one cruciferous vegetable was associated with an RR of 1.6 (CI = 1.1 to 2.4) for infants experiencing one or more colic symptoms. CONCLUSION: Results of this study provide initial evidence that maternal intake of cruciferous vegetables, cow's milk, onion, or chocolate during exclusive breast-feeding is associated with colic symptoms in young infants.

Adult↗

A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis.

Hereditary haemochromatosis (HH), which affects some 1 in 400 and has an estimated carrier frequency of 1 in 10 individuals of Northern European descent, results in multi-organ dysfunction caused by increased iron deposition, and is treatable if detected early. Using linkage-disequilibrium and full haplotype analysis, we have identified a 250-kilobase region more than 3 megabases telomeric of the major histocompatibility complex (MHC) that is identical-by-descent in 85% of patient chromosomes. Within this region, we have identified a gene related to the MHC class I family, termed HLA-H, containing two missense alterations. One of these is predicted to inactivate this class of proteins and was found homozygous in 83% of 178 patients. A role of this gene in haemochromatosis is supported by the frequency and nature of the major mutation and prior studies implicating MHC class I-like proteins in iron metabolism.

Alleles↗

Maintaining compliance to ivermectin in communities in two West African countries.

We have investigated various aspects related to managing wide-scale ivermectin distribution schemes within randomized controlled trials in communities where onchocerciasis is endemic. Multiple logistic regression analysis of determinants of compliance to five doses of ivermectin in 589 people in Sierra Leone showed independent significant associations with leopard skin depigmentation, the severity of side effects of treatment, fulfilling the exclusion criteria for treatment, and long-term residence in the community. These results are useful for tailoring health promotion messages in Sierra Leone, but the associations may differ in other West African societies. In Nigeria 1847 people were interviewed about various subjective responses, including itching. None of these showed clear improvement after three years of ivermectin treatment. Positive comments about treatment were generally non-specific and similar in the placebo and ivermectin groups. Negative comments were usually related to adverse reactions, especially itching and rash, and were more common after ivermectin. The lack of any benefit attributable to ivermectin that is discernible to its recipients may make it difficult to maintain the high compliance rates needed for long periods if mass dosing programmes are to have a lasting impact on onchocerciasis. In addition, no consistent effects of ivermectin were found by measuring visual acuity, height, weight or haematocrit in comparison with placebo. This may indicate that evidence of clinical impact is very slow to develop and is hard to measure using simple objective methods after only three doses of treatment. At present it seems that parasitological, entomological and detailed ophthalmological or dermatological methods are required to demonstrate the impact of ivermectin treatment in the medium-term.

Adolescent↗

Necrotizing cerebritis in an allogeneic bone marrow transplant recipient due to Cladophialophora bantiana.

We describe a necrotizing cerebritis in an allogeneic bone marrow transplant recipient caused by the neurotropic, dematiaceous fungus Cladophialophora bantiana. The patient presented 7 months after bone marrow transplantation with fever and sudden onset of left-sided weakness, followed shortly by cranial nerve III and VI palsies. The patient had a lesion (3.0 by 2.0 by 2.0 cm) of the right midbrain with extension to the pons, the left brain stem, and the right superior and the middle cerebellar peduncles. The diagnosis was made by microscopic examination and culture of a brain biopsy.

Adult↗

[Neuropsychiatric performance of HIV-infected patients].

AIM: Can neuropsychic impairment which is clinically observed in the case of HIV-infected patients be objectivized, and what is the relationship to somatic features caused by the disease? PATIENTS AND METHOD: 65 HIV-infected men with no history of drug-addiction were examined by means of a test battery which monitored the functions memory/concentration and speed of response. The probands were then compared to a healthy control group which was parallelized with respect to age, sex and education. Immune status, HIV and AIDS associated symptoms as well as educational diseases were checked for their connection with neuropsychic impairment. RESULTS: Compared to healthy persons HIV patients presented significant deficits with respect to memory and concentration but showed no reduction of speed of response. Significant correlation could be determined with only one somatic feature: Half of the patients who had lost more than 10% of their body weight during the preceding three months suffered from clinically relevant memory and concentration disorders. CONCLUSIONS: 1. The massive memory and concentration disorders impair and isolate the patients and can have considerable job-related consequences. 2. Measures preventing loss of weight should be initiated as early as possible. 3. Training sessions, e.g. nutritional consultation, must take the patients' deficits with respect to concentration and memory into consideration. 4. Possible connections between loss of weight and changes in brain metabolism should be examined. 5. Future studies should determine whether measures weight increase coincide with an improvement of memory and concentration.

AIDS Dementia Complex↗

Longitudinal compliance with annual screening for fecal occult blood. Minnesota Colon Cancer Control Study.

In a randomized, controlled trial of fecal occult blood screening for colorectal cancer, the Minnesota Colon Cancer Control Study carried out 11 annual mail screens in two phases between 1976 and 1992. This long-term compliance record of 15,476 individuals is summarized and related to demographic characteristics as well as to the screening experience of the participants. There was a strong and consistent effect of age, with peak compliance among participants about 70 years old, and lower compliance among the youngest (< or = 55 years) and oldest (> or = 80 years) participants. There was a significantly higher rate of screen compliance among participants who lived with other participants, compared with households where only one individual participated in the study. Finally, participants who underwent a diagnostic colorectal examination with negative results had significantly lower odds of compliance.

Aged↗

[Incidence of insulin-dependent diabetes mellitus in Switzerland (1972-1993) in 19-year-old men].

There is current debate whether prevalence of insulin-dependent diabetes mellitus is increasing in western countries. In Switzerland every male at age 19 years is legally obligated to appear before the Military Conscript Board, where health status is determined by physicians. We analyzed prevalence data concerning the diagnosis of diabetes mellitus in four full surveys (1972, 1982, 1987, 1993). The study included data from 162,607 Swiss males at age 19 years. Case numbers of birth cohorts and prevalence rates per 1000 are the following: [table: see text] Although the number of years surveyed is limited, trend analysis showed no evidence of an increase in the diabetes rates (total chi 2 = 4.953, DF = 3, 0.1 < p 0.2; chi 2 due to linear regression = 3.013, DF = 1, 0.05 < p < 0.1; chi 2 due to departure from linear regression = 1.940, DF = 2, 0.3 < p < 0.5). Overall cumulative incidence of diabetes mellitus was 1.30/1000 conscripts (95% confidence interval: 1.13-1.48/1000). We conclude that, in contrast to reports from other European countries, the cumulative incidence of insulin dependent diabetes mellitus has not increased among cohorts of Swiss males at age 19 years.

Adult↗