[Acneiform skin eruption in patients with metastatic colorectal carcinoma].
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Antibodies, Monoclonal↗
Biomedical subjects
T Peters
Publications and source records attributed to T Peters.
Recurrent venous thromboembolism in patients with and without anticoagulation after inferior vena caval filter placement.
AIM: The aim of this study was to compare the rate of recurrent venothromboembolic (VTE) events and factors contributing to VTE events in patients with inferior vena caval (IVC) filters on chronic anticoagulation to those in whom anticoagulation was discontinued. METHODS: Retrospective cohort study of 353 patients who received IVC filters between 1986 and 2002. RESULTS: Anticoagulation status was available for 304 patients (132 on coumadin anticoagulation therapy and 172 who did not receive any anticoagulation therapy) whose IVC filters were placed within 30 days of their qualifying thromboembolic event. Two-year event-free survival for the anticoagulated group was 80.6% (95% confidence interval--CI--76.9, 84.3] and was 67.8% (95% CI 63.2, 72.3) for the non-anticoagulated group. Patients who had Greenfield filter had a higher, but not statistically significant different, rate of recurrence compared to those with other types of filters (hazard ratio 1.4; 95% CI 0.9, 2). The rate of recurrent VTE events was independent of age, gender, smoking status, or underlying medical condition. CONCLUSIONS: Among those with IVC filters, long-term anticoagulation therapy prolonged event-free survival for up to 2 years but did not prevent recurrent VTE events.
Adult↗
Efficient and fast targeted production of murine models based on ENU mutagenesis.
Mice with targeted genetic alterations are the most effective tools for deciphering organismal gene function. We generated an ENU-based parallel C3HeB/FeJ sperm and DNA archive characterized by a high probability to identify allelic variants of target genes as well as high efficiencies in allele retrieval and model revitalization. Our archive size of over 17,000 samples contains approximately 340,000 independent alleles (20 functional mutations per individual sample). Based on an estimated number of approximately 30,000 mouse genes, the parallel sperm/DNA archive should permit the identification and recovery of ten or more alleles per average target gene which translates to a calculated 99% success rate in the discovery of five allelic variants for any given average gene. The low rate of unrelated ENU-induced passenger mutations has no practical impact on the analysis of the allele-specific phenotype at the G3 generation because of dilution and free segregation of such unrelated passenger mutations. To date 39 mouse models representing 33 different genes have been recovered from our archive using in vitro fertilization techniques. The generation time for a murine model heterozygous for a mutation in a gene of interest is less than 2 months, i.e., three to four times faster compared with current embryonic stem-cell-based technologies. We conclude that ENU-based targeted mutagenesis is a powerful tool for the fast and high-throughput production of murine gene-specific models for biomedical research.
Alleles↗
Reduction in slippage with 11-cm Lap-Band and change of gastric banding technique.
BACKGROUND: Slippage occurs after 2-18% of gastric bandings performed by the perigastric technique (PGT). We investigated the slippage-rate before and after the introduction of the pars flaccida technique (PFT) and the 11-cm Lap-Band, and the long-term results of the re-operated patients. METHODS: Between Dec 1996 and Feb 2004, 360 patients with a mean BMI of 44 kg/m2 were operated. The PGT (n=168) and PFT9.75 (n=15) groups received the 9.75-cm Lap-Band, and the PFT11 group (n=177) received the new 11-cm Lap-Band. Follow-up rate was 99%. RESULTS: Slippage occurred in a total of 31 patients from all groups (PGT, n=28, or 17%; PFT9.75, n=1, or 7%; PFT11, n=2, or 1%). Average yearly re-operation rate for slippage in the first 3 years postoperatively was 3.8%, 2.2% and 0.9%, respectively. Laparoscopic re-banding was necessary for posterior (n=19) or lateral (n=12) slippage. The late postoperative course after re-banding was: uneventful 58%, weight regain 35% and/or esophageal motility disorder 23%, secondary band intolerance 20%, and one persistent posterior slippage. 8 patients (26%) needed biliopancreatic diversion. CONCLUSION: Since the introduction of the PFT and the 11-cm Lap-Band, we observed a significant reduction in slippage rate and no posterior slippage. Re-banding had a less favorable long-term result than did first-procedure banding.
Adolescent↗
Risk assessment model for venothromboembolism in post-hospitalized patients.
AIM: Venothromboembolism (VTE) is an important condition in hospitalized patients accounting for significant morbidity and mortality, and the risk of VTE often continues post-hospitalization. Although risk assessment models have been developed to predict the risk of deep venous thrombosis (DVT) in hospitalized patients, no models have been developed that determine the risk of DVT during the post-hospitalization period. The objective of this study was to create a risk profile using risk factor assessment that could be used to predict which patients are at highest risk of developing DVT within 60 days following hospital discharge. METHODS: The computerized medical records of 380 patients (190 with DVT and 190 without DVT) who received care from 1995-2002 and were subsequently re-hospitalized within 60 days of discharge were retrospectively reviewed. Univariate and multivariate logistic regression analyses were conducted to identify risk variables related to VTE. A novel risk assessment model was created using risk factors from the logistic regression analyses. RESULTS: The prevalence of VTE was found to be 93.2% (69/74) in the high-risk category, 52.9% (109/206) in the moderate-risk category, and 12% (12/100) in the low-risk category. CONCLUSIONS: Once validated, this risk assessment model may be applied to identify patients who may be at increased risk of developing VTE post-hospitalization. Those at high risk should be considered for anticoagulation therapy during the post-hospitalization period. Availability of a risk profile using risk factor assessment to guide decisions related to anticoagulation therapy will have important ramifications relative to patient outcomes including morbidity, mortality, and reductions in VTE-associated cost.
Hospitalization↗
[Autoantibodies against islet cell antigens and type 1 diabetes after treatment with interferon-alpha].
BACKGROUND AND OBJECTIVE: The aim of this study was to study the appearance of autoantibodies against islet cells and the development of type 1 diabetes in patients with chronic hepatitis C during interferon treatment. PATIENTS AND METHODS: 74 patients (24 women, 50 men, mean age: 46 years) with HCV infection were treated with interferon, ribavirin and amantadin versus placebo, after they had failed to previous interferon therapy in a prospective, randomised trial. At the end of treatment period anti-islet cell autoantibodies (anti-GAD, anti IA-2), anti-insulin antibodies, TSH, anti-thyroid autoantibodies (TPO, thyreoglobulin, TSH-receptor antibodies) were measured. RESULTS: In two patients, GAD autoantibodies were found, but both patients were negative for IA-2 and insulin antibodies. One of the patients developed type 1 diabetes five months after start of treatment. In this patient, the anti-GAD titer was initial 0 U/ml (normal: < 1.2). The titer raised to 52,2 U/ml after the interferon monotherapy. During the second interferon treatment (in combination) the titer raised from initial 41,1 U/ml to 59,6 U/ml. The anti-GAD titer of the second patient was 0 U/ml before treatment and raised to 1,7 U/ml. This patient did not develop a type 1 diabetes. CONCLUSION: Type 1 diabetes is a rare but serious complication of interferon therapy. Repetitive treatment seems to facilitate this complication. Screening for islet antibodies before a second therapy could be useful.
Amantadine↗
A mouse model for cystinuria type I.
Cystinuria, one of the most common inborn errors of metabolism in humans, accounts for 1-2% of all cases of renal lithiasis. It is caused by defects in the heterodimeric transporter system rBAT/b0,+AT, which lead to reduced reabsorption of cystine and dibasic amino acids through the epithelial cells of the renal tubules and the intestine. In an N-ethyl-N-nitrosourea mutagenesis screen for recessive mutations we identified a mutant mouse with elevated concentrations of lysine, arginine and ornithine in urine, displaying the clinical syndrome of urolithiasis and its complications. Positional cloning of the causative mutation identified a missense mutation in the solute carrier family 3 member 1 gene (Slc3a1) leading to an amino acid exchange D140G in the extracellular domain of the rBAT protein. The mouse model mimics the aetiology and clinical manifestations of human cystinuria type I, and is suitable for the study of its pathophysiology as well as the evaluation of therapeutic and metaphylactic approaches.
Amino Acid Sequence↗
Long-term growth arrest of PUVA-treated fibroblasts in G2/M in the absence of p16(INK4a) p21(CIP1) or p53.
Premature aging of the skin is a prominent side-effect of psoralen photoactivation, a therapy used for different skin disorders. Recently, we demonstrated that treatment of fibroblasts with 8-methoxypsoralen and ultraviolet A irradiation resulted in growth arrest with morphological and functional changes reminiscent of replicative senescence. To further elucidate the underlying molecular mechanisms, we analysed the cell-cycle phases of the growth-arrested fibroblasts. After PUVA treatment, fibroblasts arrested in G2/M, in contrast to spontaneously senesced fibroblasts arresting in a cell-cycle phase with many features similar to G1. To address the role of the cell-cycle controlling genes p16(INK4a), p21(CIP1) and p53, we analysed the expression of these genes. p16(INK4a), p21(CIP1) and p53 protein levels increased substantially with different time kinetics in growth-arrested fibroblasts. Because p16(INK4a), p21(CIP1) and p53 are involved in replicative senescence, we applied the PUVA regimen to fibroblasts deficient in either of these genes. p16(INK4a), p21(CIP1) and p53 null mutant fibroblast strains underwent growth arrest with a senescent phenotype similar to wild-type human fibroblasts. Based on these results, we propose that redundant or alternate pathways are involved in the response of dermal fibroblasts to PUVA treatment resulting in a phenocopy of replicative senescence in vitro.
Cell Division↗
Alopecia in a novel mouse model RCO3 is caused by mK6irs1 deficiency.
Reduced coat 3 (Rco3) is a new spontaneous autosomal recessive mutation with defects in hair structure and progressive alopecia. Here we describe chromosomal mapping and molecular identification of the Rco3 mutation. The murine Rco3 locus maps to a 2-Mb interval on chromosome 15 encompassing the keratin type II gene cluster. Recently, mK6irs1 was described as a type II keratin expressed in Henle's and Huxley's layer of the murine inner root sheath. Genomic sequencing revealed a 10-bp deletion in exon 1 of mK6irs1 resulting in a frameshift after 58 amino acid residues and, therefore, the absence of 422 carboxy-terminal amino acid residues containing the complete alpha-helical rod domain. Henle's and Huxley's layers show no immunoreactivity with mK6irs1-specific antibodies and the absence of intermediate filament formation in electron microscopic images. These results indicate that the expression of functional mK6irs1 is indispensable for intermediate filament formation in the inner root sheath and highlights the importance of the keratinization of the inner root sheath in the normal formation of the hair shaft.
Alopecia↗
Population requirement for primary knee replacement surgery: a cross-sectional study.
OBJECTIVES: To determine the population requirement for total knee replacement (TKR) in England. METHODS: Population-based study using an age/sex-stratified random sample of 28 080 individuals aged 35 yr and over. Incident disease was estimated from prevalence by statistical modelling. The New Zealand priority criteria for major joint replacement were used for case selection. RESULTS: Patients with knee disease were less likely than those with equally severe hip disease to have been referred to a specialist, to have consulted an orthopaedic surgeon or to be on a waiting list for joint replacement. The estimated annual requirement of TKRs in England, based on New Zealand Scores alone, was 55,800 (95% CI 40 700-70,900), contrasting sharply with an annual provision of 29,300 actually observed. However, in contrast to previously reported hip replacement data, when patient willingness to undergo surgery was considered, this estimate decreased considerably. CONCLUSIONS: There appears to be an underprovision of TKR in England. This may be due in part to differences in perception of disease severity and likely response to surgery between patients and general practitioners on one hand, and rheumatologists and orthopaedic surgeons on the other.
Adult↗
An investigation of child restraint/seatbelt usage in motor vehicles by Maori in Northland New Zealand.
OBJECTIVE: To investigate child restraint/seatbelt use by the indigenous (Maori) population in Northland New Zealand. METHOD: Observational surveys were conducted at the two main car parks (McDonald's and the largest supermarket) to determine the number of passengers restrained, the type of restraints, and correct use. Observations were restricted to those who were obviously Maori, based upon the local knowledge of the observer. In addition, face to face questionnaires were administered to Maori whanau/caregivers involved in the care of two or more children for more than three days a week. RESULTS: A total of 788 participants were observed. Babies were those most likely to have all occupants restrained correctly (97%), followed by toddlers (66%), adults (56%), and school age children (48%); 138 interviews were conducted. Females (86%) were significantly more likely to ensure that all passengers were restrained on short journeys compared to males (67%; p<0.05). Respondents under 45 (80%) were significantly less likely to restrain child passengers compared to people aged 45 or older (91%; p<0.05). DISCUSSION: This study highlights the problem that larger families in this study had in providing correct child restraints for all their children.
Adolescent↗
Prostate Testing for Cancer and Treatment (ProtecT) feasibility study.
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Aged↗
[Development and trial use of multistep diagnosis of musculoskeletal disorders during a routine physical examination at the workplace].
Musculoskeletal disorders represent the main cause for absenteeism. To determine the disorders exactly, a multistep inventory of examinations was developed. The method of diagnostics may be an indicator of the quality of occupational medical management. It may improve the availability of health data related to working conditions and may increase the chances of goal-oriented prevention in the field of working conditions as well as in the field of behavior. In addition, the standardized recording of data provides an opportunity for evaluation in epidemiological studies, which may be organized as longitudinal studies to look for the development of musculoskeletal disorders over time.
Humans↗
[Office workplace at a computer monitor from an occupational-orthopedic view].
Typical back problems as well as complaints in the shoulder-arm-hand system are increasing as the volume of sedentary office work at the computer screen rises. Various legal rules precisely define preventive measures. However, basic orthopedic-biomechanical principles are not being taken into consideration. Orthopedists as well as occupational physicians are equally challenged to enforce those legal guidelines by beginning to raise awareness of the principles and thus contributing towards improvement of working conditions.
Computer Terminals↗
Vascular endothelial growth factor causally contributes to the angiogenic response upon ultraviolet B irradiation in vivo.
BACKGROUND: Ultraviolet (UV)-B irradiation has been shown to be an inducer of vascular endothelial growth factor (VEGF) in primary keratinocytes and epidermal cell lines in vitro. OBJECTIVES: To determine the expression pattern and the causal role of VEGF in the UVB-mediated angiogenic response in vivo in human skin and in a mouse model. METHODS: Skin biopsies or epidermal lysates thereof were studied for VEGF expression following UVB irradiation at a dose of 50 or 60 mJ cm-2, respectively, using immunostaining and a VEGF-specific highly sensitive sandwich enzyme-linked immunosorbent assay. The VEGF-dependent increase in vessels upon repetitive UVB irradiation was studied in skh-1 hairless mice using immunostaining for factor VIII-related antigen (FVIII RAG) in the presence and absence of intraperitoneally injected neutralizing VEGF antibodies. RESULTS: VEGF was found to be induced in the epidermis following UVB irradiation of human and mouse skin. Repetitive UVB irradiation of skh-1 hairless mice resulted in an increase in FVIII RAG positive vessels in the skin. UVB-induced angiogenic response could be partly abrogated by neutralizing antibodies against VEGF, while isotype-matched IgG control antibodies did not reveal any suppressive effect. CONCLUSIONS: Our results support previous in vitro data and show the in vivo relevance of VEGF as a paracrine inducer of cutaneous vessels after UVB irradiation.
Animals↗
Beta 2 integrin-mediated adherence does not modulate superoxide anion release from neutrophils and subsequent lipid peroxidation of surrounding fibroblasts.
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Animals↗
Combination of pulsed-field gel electrophoresis (PFGE) and single-enzyme amplified fragment length polymorphism (SAFLP) for differentiation of multiresistant Salmonella enterica serotype typhimurium.
OBJECTIVE: To assess the combined application of plasmid profile typing, pulsed-field gel electrophoresis (PFGE) and PCR-based single-enzyme amplified fragment length polymorphism (SAFLP) for the differentiation of 18 multiresistant (MR) and one drug-sensitive strain of Salmonella enterica serotype typhimurium from humans and food animals. METHODS: Strains were phage typed and tested for resistance to a panel of antimicrobial agents. Strains were also tested for the ability to transfer resistance either directly or by mobilization to standard strains of Escherichia coli K12. Plasmid DNA was extracted from both drug-resistant donor strains and from drug-resistant exconjugants. Total genomic DNA was characterized by PFGE following digestion with the restriction endonuclease XbaI. The resultant patterns were categorized and analyzed by dendrogram analysis using the Dice coefficient and by data clustering using unweighted pair-group arithmetic averaging (UPGMA). Isolates were also characterized and categorized by SAFLP. The levels of discrimination achieved by each method were assessed individually and in combination. RESULTS: Plasmid DNA was detected in all of the 18 MR isolates but, not in the drug-sensitive isolate. Using PFGE, 19 different profiles were identified, falling into eight major categories. However, by SAFLP, only eight profiles were observed. Subsequent investigations have demonstrated epidemiologic relationships within at least one of these SAFLP profile groupings. CONCLUSIONS: These studies have demonstrated that PFGE and SAFLP can be used independently for the differentiation of MR S. Typhimurium from humans and food animals. However, when used in combination, SAFLP can provide a format for broad epidemiologic groupings. These groupings can be further subdivided by PFGE to provide detailed information on putative strain relationships at the genotypic level.
Animals↗
Autonomic failure mimicing dopamine agonist induced vertigo in a patient with macroprolactinoma.
A 68-year-old man presented with general fatigue, increasing adynamia, weakness, vertigo and recurrent syncope. Six weeks earlier the diagnosis of a macroprolactinoma had been established based on a greatly elevated prolactin concentration (161 170 micro U/l) and MR-evidence of a 3.5 cm measuring pituitary mass. The patient had been started on cabergoline (1.5 mg weekly). Orthostatic hypotension due to the dopamine agonist was considered very likely and carbergoline therapy was stopped. However, there was no relief of the symptoms and further syncopes followed. Testing of blood pressure and heart rate regulation, selective testing of postganglionic cardiac neurons with [ 123 J] metaiodobenzylguanidine scintigraphy provided evidence of grossly impaired neurogenic cardiovascular regulation due to failure of postganglionic efferent sympathetic activity. This is characteristic for pure autonomic failure. The patient was treated symptomatically with high fluid intake, compression stockings, fludrohydrocortisone (0.1 mg o.d.s.), piroxicam (20 mg o.d.s.) and etilephrin (10 mg q.d.s.), which enabled him to cope with daily activities without syncope. This case shows that vertigo in a patient with macroprolactinoma is not always related to drug therapy but may be related to other causes.
Adrenergic Agonists↗