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Biomedical subjects

M Pfister

Publications and source records attributed to M Pfister.

At least 37 records · Page 2Linked to original sources
PubMed2000

A polymorphism (80G->A) in the reduced folate carrier gene and its associations with folate status and homocysteinemia.

5-methyltetrahydrofolate is the predominant form of folate in plasma. It may be the preferred substrate for transport via the reduced-folate carrier (RFC). We isolated a cDNA for the reduced folate carrier (RFC-1) from human skin fibroblasts. A common polymorphism at position 80 in exon 2 of RFC-1 was identified. This polymorphism changes a guanine (G) to an adenine (A), abolishing a CfoI restriction site. Using genomic DNA samples from 169 healthy subjects, we identified 27.1% GG homozygotes, 21.9% AA homozygotes, and 50.9% GA heterozygotes. We explored the impact of this polymorphism, separately and in combination with the 677C->T polymorphism in the methylenetetrahydrofolate reductase gene, on folate status and total homocysteine levels. We found a moderate, but significant, increase in total homocysteine levels in doubly homozygous 80GG/677TT subjects as compared to 80GG/677CC (P = 0.01) or 80GG/677CT (P = 0.04) subjects. In addition, individuals who were 80AA/677CT had higher plasma folate levels than those who were 80GG/677CT (P = 0.02).

Base Sequence↗
PubMed2000

[Mutational analysis of the connexin26 gene in sporadic cases of moderate to profound deafness].

Non-syndromic neurosensory recessive deafness (NSRD) is one of the most common human sensory disorders. Mutations in the connexin 26 gene have been established as a major cause of inherited and sporadic non-syndromic deafness in different populations. The CX26 gene encodes the gap junction protein connexin 26 (beta-2, GJB2), whose expression was shown in several tissues and in the cochlea. The 30delG mutation is the most frequent mutation in the CX26 gene. It represents a deletion of guanosine (G) in a sequence of six Gs extending from position 30 to 35 of the CX26 cDNA. The deletion creates a frameshift resulting in a premature stop codon and a non-functional intracellular domain in the protein. The 30delG mutation can be detected at the molecular level using PCR followed by BsiYI digestion. We screened 164 mainly German patients with non-syndromic sporadic deafness for this mutation to determine its distribution in the German population. The frequency of the mutation in our analyzed patients was lower than in other studies and therefore indicates its dependency on geographically distinct populations.

Audiometry, Pure-Tone↗
PubMed2000

Novel dialysis cannulas: are they worth the higher price tag?

Accessory hemodialysis equipment, including dialysis cannulas, usually lack controlled and independent testing before being introduced onto the market. The aim of this study is a prospective comparison of a newly designed curved-tip dialysis cannula with a standard dialysis cannula of the same size from the same manufacturer. Fifteen chronic dialysis patients were enrolled onto a prospective 4-month crossover study. All patients had arteriovenous fistulas, except for two patients with polytetrafluoroethylene grafts. The routinely used standard cannulas were replaced by either a curved-tip 15G cannula or a new standard 15G cannula from the same manufacturer. The two cannulas were compared with respect to puncture-related pain and/or problems and bleeding complications, as well as blood-flow dynamics. Venous and arterial access pressures were recorded at blood-flow rates of 100 to 400 mL/min. Linear regression analyses of arterial and venous pressure profiles showed the same regression lines for the standard and curved-tip cannulas. Plasma haptoglobulin levels and occlusion times necessary to stop bleeding after removal of the cannulas did not differ between the two cannulas. Both patients and nurses independently reported equal puncture-related pain and/or problems for both cannulas on visual analogue scales. No correlation was found between puncture problems reported by nurses and puncture pain reported by patients. The curved-tip cannula does not offer an advantage compared with the less expensive standard cannula. Controlled testing of advertised advantages by manufacturers of accessory equipment should be a prerequisite before introduction into routine clinical treatment.

Adult↗
PubMed2000

The effect of 677C-->T and 1298A-->C mutations on plasma homocysteine and 5,10-methylenetetrahydrofolate reductase activity in healthy subjects.

We have studied the effect of common mutations (677C-->T and 1298A-->C) of the methylenetetrahydrofolate reductase (MTHFR) gene in sixty-six healthy French subjects, aged 27-47 years. Serum folate, vitamin B12, and plasma total homocysteine were measured as well as the specific activity of MTHFR in lymphocytes. The frequency of subjects homozygous for the 677TT genotype was 18%, and that of those homozygous for the 1298CC genotype was 12.5%. The frequency of individuals heterozygous for both mutations was 23.5%. The 1298A-->C mutation was associated with decreased MTHFR specific activity in subjects with both 677CC and 677CT genotypes. This activity was 60% for the 677CC/1298AC genotype and 52% for the 677CC/1298CC genotype when compared with the MTHFR specific activity of the 677CC/1298AA genotype. Heterozygotes for both mutations (677CT/1298AC genotype) had 36% of the reference specific activity. Although homocysteine levels in 677TT and 1298CC genotype subjects were higher than for other genotypes, no significant differences were observed among different genotypes. This may be due to high serum folate level in our samples, and suggests that folate therapy may be useful to prevent hyperhomocysteinaemia in homozygous mutant subjects.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed2000

5,10-methylenetetrahydrofolate reductase common mutations, folate status and plasma homocysteine in healthy French adults of the Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) cohort.

The 677cytosine mutation identified in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene has been frequently associated with an elevated plasma homocysteine concentration. The aim of the present study was to determine the impact of this MTHFR common mutation on plasma and erythrocyte folate (RCF) and plasma total homocysteine (tHcy) concentrations in healthy French adults. A cohort of 291 subjects living in the Paris area and participating in the Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) study were analysed to assess the impact of MTHFR polymorphism 677C-->T on folate status and plasma tHcy concentration. The frequency of the mutant homozygote for 677C-->T polymorphism (677TT genotype) in the present cohort was 16.8%. There were significant differences in plasma tHcy between 677CC, 677CT and 677TT genotype groups. The RCF concentrations were significantly different between each genotype, the lowest levels being associated with the 677TT genotype. When segregated by gender, no differences in tHcy between homozygous 677TT, heterozygous 677CT and wild-type 677CC genotype groups in women were observed. The fasting tHcy in women was unrelated to the 677C-->T mutation. However, tHcy was significantly increased in men with the homozygous 677TT genotype. We also analysed the possible implication of a second new MTHFR polymorphism (1298A-->C) in subjects with mild hyperhomocysteinaemia (4th quartile of homocysteinaemia; tHcy >11.1 micromol/l). The polymorphism 1298A-->C did not have a notable effect on tHcy or on the RCF levels. Our observations confirm a relatively high frequency of the 677TT genotype in the French population. Women with this genotype did not show the same increase in tHcy observed in men. In the present study dietary folate intake was not measured. Thus, the interaction of dietary folate with the MTHFR genotype in the French population needs further study.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed1999

Frequency of advanced neoplasia in the proximal colon without an index polyp in the rectosigmoid.

PURPOSE: Screening endoscopy has the potential to reduce colorectal cancer mortality. However, the efficacy of screening flexible sigmoidoscopy compared with colonoscopy strongly depends on the frequency of advanced proximal neoplasms without an index polyp in the rectosigmoid. We have therefore determined this frequency in our endoscopy population. METHODS: Endoscopic and histologic data were analyzed from all patients on whom integral colonoscopy was performed between 1980 and 1995. Advanced neoplasia was defined as cancer or adenomas >10 mm in diameter, adenomas with a villous component, or severe dysplasia. Patients with polyposis syndrome or inflammatory bowel disease were excluded. RESULTS: Colonoscopy was performed on 11,760 patients. 2,272 (19.3 percent) had at least one colorectal neoplasm, of which 39 percent had the neoplasm above the rectosigmoid. Twenty-two percent of all patients with neoplasia had no index polyp in the rectosigmoid and 16 percent of these had no index polyp, but at least one advanced proximal neoplasm. CONCLUSIONS: Although 39 percent of patients had neoplasms above the rectosigmoid, only 16 percent had an advanced proximal neoplasm without an index polyp in the rectosigmoid. This gives a figure on which to base the evaluation of screening sigmoidoscopy programs against those of screening colonoscopy.

Adenoma, Villous↗
PubMed1999

Comparative study of visual, auditory, and olfactory function in Usher syndrome.

BACKGROUND: Usher syndrome is a genotypically and phenotypically heterogeneous group of autosomal recessive diseases featuring retinitis pigmentosa (RP) and sensorineural hearing loss. A general ciliary dysfunction has been suspected following reports of a mutated cytoskeletal protein (myosin VIIA) in type IB, and preliminary data has suggested an olfactory deficit. The purpose of this study was to quantitatively assess olfactory function in Usher syndrome patients and to search for a correlation between the degree of impairment of the three sensory systems as indication of an underlying ciliary defect. METHODS: 39 patients with Usher syndrome (8 type I, 31 type II) were examined. The ophthalmologic protocol included patient history, visual acuity, eye morphology, Goldmann perimetry, and electroretinography. The ENT protocol included a thorough examination, speech-recognition test, pure-tone audiometry and an olfactory function test. RESULTS: In both groups, visual acuity was typically 20/40, the remaining visual field area was small, and the ERG responses were low to non-detectable. Average hearing loss was 100% in type I and 40% in type II. Olfactory thresholds were normal [median 9.7 (I) and 8.5 (II) vs. 8.5 in the control group]. There were multiple significant correlations between parameters of the same organ, but no relationship between parameters of different sensory systems. CONCLUSION: Almost all Usher syndrome patients in this study had an advanced form of RP. In contrast, auditory function differed considerably between type I and type II. An impairment of the olfactory system could not be detected, and there was no correlation between parameters representing visual function, hearing ability, and olfactory sense.

Adult↗
PubMed1999

Judgment analysis in clinical nephrology.

To ameliorate the clinical performance of nephrologists, improving their clinical judgment is crucial. No methodology for judgment analysis in nephrology is currently available. Therefore, we designed a trial to assess the intraphysician consistency of the judgment of typical non-end-stage renal disease (ESRD) patients by 24 board-certified nephrologists. The participants were asked to analyze cases to determine the interobserver variability with respect to diagnosis, therapy, prognosis, and strategy of follow-up. They were unaware that every patient was presented on 2 occasions separated by a period of 6 months. Of the 1,288 questionnaires that were completed, 28 cases belonged to 1 of the following 3 groups: (A) patients once with, once without renal histology, (B) patients twice without histology, and (C) patients twice with histology. Only cases of group (A) differed at the 2 occasions of assessment with respect to knowledge of histology. The results from the first and second assessment were compared and analyzed. The median (95% confidence interval) percentages of changed diagnoses were 64% (59% to 68%), 50% (44% to 62%), and 33% (26% to 47%) in groups A, B, and C, respectively, indicating large intraobserver variability. The frequency of changes in diagnoses declined with the degree of confidence in the first diagnosis in all 3 groups. The subjective desire to know the histology was without impact on the frequency of changes in diagnoses. However, a knowledge of the histology enhanced the degree of confidence in the diagnoses. Interestingly, the enormous variability in changing diagnoses from one analysis to the other was not reflected by corresponding changes in the judgment of prognosis, therapy to be prescribed, or strategy of follow-up. The individual judgment with respect to diagnosis of clinical cases is inconsistent and highly dependent on the subjective degree of confidence in the diagnosis. The practical relevant consequences traditionally derived from a diagnosis (therapy, prognosis, and strategy of follow-up) are only marginally, if at all, affected by changing the diagnosis. Thus, the utility of "diagnosis" for judgment analysis in clinical nephrology should be reconsidered.

Adult↗
PubMed1999

Pharmacokinetics and haemodynamics of candesartan cilexetil in hypertensive patients on regular haemodialysis.

AIMS: The pharmacokinetic profile of candesartan cilexetil might be altered in patients with end-stage renal disease (ESRD). No data are available about the pharmacokinetics and haemodynamics of the angiotensin II receptor antagonist candesartan cilexetil in ESRD patients on regular haemodialysis (HD). METHODS: We performed a repeated dose study (8 mg candesartan cilexetil once daily) in eight male HD patients over a treatment period of 5 days with an additional observation period of 3 days. RESULTS: Pharmacokinetic analysis with nonlinear mixed effects modeling (NONMEM) over the whole treatment period revealed a dependency of the volume of distribution on body weight and of the metabolic clearance on age and body weight in the studied population. No significant drug elimination by HD was observed. The estimated metabolic and intercompartmental clearances were 83 ml min-1 (CV 39%) and 9.9 ml min-1, respectively. The unexplained random variability of the final two compartment model was 30%. In one patient with adult polycystic kidney disease oral clearance decreased during the observation period, attributable to a significant increase in bioavailability. Maximum observed changes in blood pressure were -50/-27+/-14/8 mmHg on day 5 with haemodialysis therapy as compared with changes in blood pressure of -14/-12+/-14/8 mmHg on day 1 without haemodialysis treatment. The observed maximum decrease in systolic blood pressure correlated with the amount of ultrafiltration during the HD session on day 5 (r=0.70, P<0.05). In two patients, one of whom was binephrectomized, severe hypotensive episodes were observed during this HD session. CONCLUSIONS: HD does not influence the elimination kinetics of candesartan. The observed inter- and intraindividual variability of oral clearance and the pronounced influence of HD-induced volume contraction on the haemodynamic effects of candesartan makes it mandatory to carefully monitor HD patients treated with candesartan cilexetil.

Adult↗
PubMed1999

Five-year audit of ambulatory 24-hour esophageal pH-manometry in clinical practice.

BACKGROUND: Esophageal function testing was developed to aid diagnosis in patients with negative endoscopy. Although combined 24-h esophageal pH-manometry is now commercially available, its routine clinical effectiveness has not yet been studied. METHODS: From 1992 to 1996 we evaluated 303 consecutive patients who were first-time referrals to our unit for 24-h esophageal pH-manometry. The referral indications were gastroesophageal reflux disease, 47.2%; dysphagia, 18.5%; non-cardiac chest pain, 14.9%; connective tissue disease, 13.2%; and symptomatic patients after antireflux surgery, 6.3%. RESULTS: Overall, esophageal function testing altered the diagnosis of 44% of the patients, confirmed it in 38%, and specifically changed the management of 66%. The final clinical 'diagnosis' was reflux disease, 54% (32% with non-specific esophageal motility disorder); connective tissue disease, 9.9%; achalasia, 9.6%; other specific esophageal motility disorders, 3.3%; non-specific esophageal motility disorders, 6.9%; and normal, 16.2%. The cost per testing was estimated to be US$305 and per change in management US$465. CONCLUSION: Combined 24-h pH-manometry has been shown to be a useful and cost-effective test for the management of selected patients in whom the primary investigation was insufficient.

Adolescent↗
PubMed1999

Ambulatory nocturnal oximetry and sleep questionnaire-based findings in 38 patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal diseases (ESRD) have an increased risk of sleep-disordered breathing. With regard to this disorder, controversy persists about prevalence, cost-effective assessment and socio-economical relevance. METHODS: Therefore, we performed, for the first time, overnight ambulatory oximetry in combination with a sleep questionnaire in 38 unselected patients with ESRD and 37 healthy controls. An oxygen desaturation index (ODI) >15, defined as >15 falls in oxygen saturation of > or =4% per h, was observed more frequently in ESRD patients than in healthy controls (47 vs. 3%, P<0.001). RESULTS: In general, the results derived from the assessment of the Epworth Sleepiness Scale (ESS) as well as those from the visual analogue scale (VAS) did not reflect the ODI values of the respective patient population. Interestingly, 88% of ESRD patients with the questionnaire finding 'excessively loud snoring' had an ODI of >15 as compared with 13% without this complaint (P<0.05). Furthermore, 77% of ESRD patients with a systolic blood pressure >140 mm Hg and a body mass index (BMI) >25, had an ODI of >15. The percentage of ESRD patients with a professional activity was higher in the absence of sleep-disordered breathing (63 vs. 21%, P<0.05). CONCLUSION: 'Excessively loud snoring' and a BMI >25 combined with hypertension are risk factors for sleep-disordered breathing in ESRD patients. Nocturnal oxygen desaturations are assessed efficiently by ambulatory oximetry and correlate with relevant biological and socio-economical parameters in ESRD patients.

Adult↗
PubMed1999

Differential immunodiagnosis between cystic hydatid disease and other cross-reactive pathologies.

We assessed an Echinococcus granulosus hydatid fluid antigen-ELISA (EgHF-ELISA) as a serologic prescreening test for E. granulosus infections, supplemented by more specific confirmatory tests, including arc-5 immunoprecipitation and antigen B subunit 8-kD immunoblotting. The diagnostic sensitivity of the EgHF-ELISA was 91%. With regard to the test specificity of the EgHF-ELISA (overall = 82%), we observed relatively frequent cross-reactions in tumor patients (6%) and in patients with other parasitic diseases. Cestode-related cross-reactivity can be resolved by the complementary use of E. multilocularis-specific antigens or Taenia solium cysticercosis-specific immunoblotting. Immunoblotting based upon the detection of antibody reactivity to the 8-kD antigen of EgHF, or if appropriately detectable, to the 29-kD and 34-kD bands exhibited a 91% diagnostic sensitivity and an overall specificity of 97% or 94%, respectively. Thus, immunoblotting provided a 99% discrimination between seropositive pre-operative cystic hydatid disease cases and cross-reactive non-cestode parasitic infections or malignancies.

Agglutination Tests↗
PubMed1998

[Hereditary deafness in Turkey. Initial results].

The authors describe a study in progress to identify Turkish families with hereditary hearing loss and isolate possible responsible disease genes. Due to extreme genetic heterogeneity and limited audiological differentiation of hereditary hearing loss, it is necessary to identify large or small families from genetic isolates to locate loci responsible for hearing loss on a chromosome. To accomplish this goal, the medical records of 3800 children were examined at the ENT Clinic of Ege University between 1975 and 1994. All were suspected of having various hearing impairments. Additionally, students from two schools for the hearing impaired in Izmir and Eskisehir, Turkey were examined. To date, 16 families with syndromal deafness and 55 families with non-syndromal hereditary hearing loss involving two or more affected individuals have been identified and categorized according to the mode of inheritance. The majority (66%) of the non-syndromal families showed an autosomal recessive pattern, 29% an autosomal dominant inheritance and 5% an X-linked mode of inheritance. In the study presented there has been a predominance of affected males versus females and the consanguinity rate was 22%.

Child↗
PubMed1998

Nitrate induced coronary vasodilatation: differential effects of sublingual application by capsule or spray.

BACKGROUND: Sublingual nitroglycerin (glyceryltrinitrate, GTN) capsules or isosorbide dinitrate (ISDN) spray are routinely used to treat anginal attacks and to vasodilate maximally the epicardial coronary arteries during coronary angiography. OBJECTIVE: To compare the coronary vasodilatory effects of GTN capsules and ISDN spray with those induced by intracoronary GTN using quantitative coronary angiography. DESIGN: 96 patients (79 men and 17 women; median age 59 years) were randomised to four groups to receive either a sublingual capsule containing 0.8 mg GTN or two puffs of spray delivering 0.8 mg ISDN, followed or preceded by an intracoronary bolus of 0.2 mg GTN used as reference for maximal vasodilatation. RESULTS: There was a significant increase in the mean diameter of coronary arteries in angiographically normal segments in patients who received either intracoronary GTN (groups 1 and 2) or ISDN spray (group 4) as a first application (group 1, 0.46 mm, + 17%, (baseline vessel diameter 100%), p < 0.001; group 2, 0.45 mm, + 13%, p < 0.001; group 4, 0.47 mm, + 13%, p < 0.05). Patients who received a sublingual GTN capsule as the first application mode (group 3) had no significant change in epicardial vessel diameter (0.10 mm, + 5%, p = 0.3). CONCLUSIONS: Sublingual ISDN spray may be more efficacious than sublingual GTN capsules in certain patients with anginal attacks. ISDN spray should be preferred over capsules in coronary angiographic procedures.

Acute Disease↗