Gastric emptying: a contributory factor in gastro-oesophageal reflux activity?

AIMS: To evaluate the impact of total and proximal stomach emptying on 24 hour and postprandial reflux as well as the number of reflux episodes per hour in relation to the impact of lower oesophageal sphincter (LOS) pressure, and oesophageal contractile and clearance function. METHODS: Seventy one outpatients (37 female, 34 male; age 23-82 years) with symptoms suggestive of both delayed gastric emptying and reflux referred for further investigations participated in the study. Gastric emptying of a semisolid 1168 kJ meal and oesophageal clearance of a water bolus (supine) were recorded scintigraphically, reflux by 24 hour pH monitoring, and oesophageal motility manometrically. RESULTS: Slow proximal but not slow distal or total stomach emptying correlated with increased 24 hour and postprandial acid exposure and increased number of reflux episodes/hour. No relationship was found between total or proximal emptying and LOS resting pressure, oesophageal contraction amplitude, percentage of failed contractions, or clearance. Multiple linear regression analyses showed that slow proximal emptying and low LOS pressure contributed significantly to both 24 hour (p=0.0007 and p=0. 0001) and two hour postprandial acid exposure (p=0.007 and p=0.0001). In contrast, the rate of total emptying contributed to neither 24 hour nor postprandial acid exposure. CONCLUSION: Our data suggest that in contrast with total stomach emptying, the rate of proximal stomach emptying contributes to the extent of 24 hour as well as postprandial acid exposure and the number of reflux episodes/hour.

The gender gap in depression reconsidered: the influence of marital and employment status on the female/male ratio of treated incidence rates.

BACKGROUND: The consistently observed predominance of female over male rates in depression - in treated as well as in untreated populations - has never been satisfactorily explained. Among the many possible biological and psychosocial explanations, marital and employment status have not been extensively studied and virtually nothing is known about the combined effect of these variables on sex differences in depression. A main reason for this lack of knowledge is the limited number of cases available in epidemiological studies. METHODS: The present paper examines the combined effects of marital and employment status on sex differences in depression rates by analysing in-patient admission rates of all depressed patients aged 18-67 admitted for the first ever time to the Department of Psychiatry of the University of Vienna from a strictly defined catchment area over a period of 42 months. Stepwise Poisson regression analyses were carried out in order to identify the relative contribution of these variables to the variance of first ever in-patient admission rates for depression. RESULTS: A total of 2599 depressed patients fulfilled the inclusion criteria. When analysed separately, sex, marital status and employment status were shown to have distinct influences, with the "not married" carrying a two-fold higher risk than the married (2:1), and female sex (1.7:1) as well as not being employed (1.7:1) showing similar but smaller effects. In the detailed combined analysis, marriage was significantly less advantageous for women than for men, while sex differences disappeared completely in the widowed group. Also, there was no sex difference in the employed divorced; in the employed widowed there was even a slight preponderance in men. The highest rates were found in not employed divorced women, the lowest in employed married men. CONCLUSION: While in-patient admissions are certainly selective in relation to epidemiological data, the large sample made it possible to perform combined analyses of sex, marital status and employment status. It was shown that the statement of a female preponderance in depression, which was found for the total sample, is a gross oversimplification. If marital and employment status are considered simultaneously, the sex differences disappear in some subgroups and in some are even reversed. We suggest that the combined influence of marital and employment status should be studied in epidemiological studies as well before conclusions about the influence of sex on depression rates are drawn.

Evaluation of a multicentre study of synchronous application of narrowband ultraviolet B phototherapy (TL-01) and bathing in Dead Sea salt solution for psoriasis vulgaris.

The synchronous application of narrowband UVB phototherapy with 311 nm lamps (Philips TL-01) and bathing in Dead Sea salt solution was evaluated in a multicentre trial (n = 60) in outpatients suffering from psoriasis vulgaris. The study design consisted of an initial therapy phase of up to 35 treatments (three to five times a week) followed by maintenance therapy with up to 35 further applications (once or twice a week). Evaluation was performed separately for patients in according-to-protocol (ATP) (n = 280) and intention-to-treat (ITT) (n = 692) groups. An overall significant improvement of the Psoriasis Area and Severity Index (PASI) score (P < 0.05) could be shown for both groups during initial therapy with 71.4% improvement for ATP and 61% for ITT patients. The mean PASI for ATP (values for ITT in parentheses) was 17.7 (18.6) at baseline, 9.5 (10.7) after 20 applications and 5.2 (7.4) at the end of initial therapy. On average, ATP patients received 3.9 (3.5) applications per week with a cumulative irradiation dose of 19.5 J cm-2 (16.2 J cm-2). The most frequent side-effect was erythema, observed in 8.7% of the patients. Subjective evaluation of the therapy by the patients (n = 168) was excellent. Seventy-nine per cent of patients preferred the new treatment strategy in comparison with other previous therapies and 88% regarded this therapy as pleasant and comfortable. In conclusion, we could demonstrate a significant effect of therapy in both the ATP and the ITT groups for this new treatment system which imitates, as far as possible, the Dead Sea climatic conditions, with no severe side-effects and a high acceptance by the patients.

High prevalence of hyperhomocysteinemia in critically ill patients.

OBJECTIVE: To test the hypothesis that the prevalence of hyperhomocysteinemia is increased in critically ill patients and correlates with disease severity and mortality in these patients. DESIGN: A prospective study. SETTING: Three medical intensive care units at the University of vienna Medical School serving both medical and surgical patients. PATIENTS: All consecutive admissions (n = 56) during a period of 4 wks. A total of 112 age- and gender-matched healthy individuals constituted the control group. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood samples were drawn within 24 hrs after admission for analysis of total homocysteine (tHcy), folate, vitamin B6 levels, and vitamin B12 levels as well as to identify the 677C-->T polymorphism in the gene coding for the enzyme 5,10-methylenetetrahydrofolate reductase. Acute Physiology and Chronic Health Evaluation III scores at admission and 24 hrs after admission as well as 30-day survival were documented in all patients. Hyperhomocysteinemia was more prevalent in critically ill patients (16.1%; 95% confidence interval, 7.6% to 28.3%) compared with age- and gender-matched healthy individuals (5.4%; 95% confidence interval, 2.0% to 11.3%; chi-square test; p = .022). There was no difference in tHcy plasma concentrations in the first 24 hrs after admission to an intensive care unit between survivors and nonsurvivors. The 5,10-methylenetetrahydrofolate reductase 677C-->T polymorphism had no influence on tHcy levels and survival of intensive care unit patients. CONCLUSIONS: The prevalence of hyperhomocysteinemia is increased in critically ill patients compared to age- and gender-matched healthy individuals. The clinical significance of this finding remains to be determined.

Recombinant tissue plasminogen activator is a useful alternative to heparin in priming quinton permcath.

Soft, cuffed, implantable central venous catheters such as the Quinton Permcath (Quinton Instrument Co, Seattle, WA) are increasingly used as permanent access in patients with end-stage renal disease. Their major limitations, besides infection, are thrombosis and inadequate blood flow. To prevent those complications, heparin is conventionally used for priming the Quinton Permcath between dialysis sessions. In this study, we compared recombinant tissue plasminogen activator (rTPA) with heparin for priming the Quinton Permcath in a prospective, randomized, crossover design. Twelve patients were randomly assigned to receive 2,000 IU of heparin or 2 mg of rTPA injected into each catheter lumen at the end of each dialysis session over a period of 4 months, followed by a switch to the other substance. Blood flow rate (flow), venous pressure (VP), and arterial pressure (AP) were monitored at each dialysis session hourly. Flow was significantly greater (P = 0.0001) with rTPA (mean +/- SD, 237.7 +/- 18.1 and 231.6 +/- 12.4 mL/min for the first and second 2 months, respectively) compared with heparin (208.5 +/- 10.1 and 206.9 +/- 14.2 mL/min for the first and second 2 months, respectively). VP was significantly less (P = 0.0001) with rTPA (135.4 +/- 8.2 and 140 +/- 15.2 mm Hg for the first and second 2 months, respectively) compared with heparin (160.5 +/- 16.1 and 159.2 +/- 20.7 mm Hg for the first and second 2 months, respectively). AP was significantly greater (P = 0.0002) with rTPA (-113.5 +/- 11.8 and -115.9 +/- 12.7 mm Hg for the first and second 2 months, respectively) compared with heparin (-136.5 +/- 23.3 and -134.7 +/- 25.8 mm Hg for the first and second 2 months, respectively). In addition, fewer complications (flow problems, clotting, and need for fibrinolysis) occurred in the rTPA period. These results show that rTPA is superior to heparin for priming the Quinton Permcath between hemodialysis sessions and can be used as a valuable alternative to conventional heparin in selected patients.

Comparison of migration in modular sockets with ceramic and polyethylene inlays.

This study compared migration in 73 cementless total hip arthroplasties (THAs) with either alumina ceramic (n = 23) or polyethylene (n = 50) inlays; prosthesis sockets and stems were identical except for the inlays. After 7 years of follow-up, 5 sockets (4 with ceramic and 1 with polyethylene inlays) had been revised an average of 63.3 months (range: 49-81 months) after implantation, and survival analysis showed a significantly higher revision rate for sockets with ceramic inlays (89 +/- 6%) versus polyethylene inlays (98.2 +/- 1.7%) (P = .032). Migration analysis of the first three postoperative years revealed significantly higher vertical migration in sockets with ceramic inlays (P = .047), in patients aged <60 years (P = .02), and in osteoporotic type C bone (A versus C, P = .0071 and B versus C, P = .0004).

Effects of tibolone on auditory brainstem responses in postmenopausal women--a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To investigate the influence of tibolone, a synthetic steroid, in modifying auditory brainstem response (ABR) in postmenopausal women. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: Outpatient menopausal clinic in a university hospital. PATIENT(S): Twenty-four healthy postmenopausal women. INTERVENTION(S): Administration of either tibolone or placebo for 12 weeks; evaluation of ABR and hormone levels before and after treatment. MAIN OUTCOME MEASURE(S): Changes in auditory brainstem response latencies. RESULT(S): Comparison of the ABR latency data from the two treatment groups showed a significant decrease in wave II, III, and V peak latencies in women receiving tibolone. No significant differences in pretreatment and posttreatment circulating hormone concentrations were observed between the tibolone and placebo group. Furthermore, there was no significant increase in hormone levels in either of the groups at 12 weeks. CONCLUSION(S): Our findings show an improvement in auditory function via brainstem auditory neural pathways sensitive to tibolone in postmenopausal women. Tibolone may offer new therapeutic strategies in otologic disorders.

Loss of correction after lateral closing wedge high tibial osteotomy--a human cadaver study.

In 12 human cadaver tibiae, osteotomies were carried out at two levels (2 and 3 cm from the distal joint line) with three different wedges (5 degrees, 10 degrees, 15 degrees) to evaluate the influence of displacement of the osteotomy fragments on areas of cortical contact. In undisplaced osteotomies (medical cortical edges superposed) cortical contact areas formed 28% (level 2 cm) and 40.5% (level 3 cm) of the cortical circumference of the proximal fragments (NS). Wedge angles and levels of osteotomy displayed no statistical differences. In displaced osteotomies cortical contact decreased significantly (P < 0.05). Displacing the distal fragment laterally, medial cortical contact is lost, and weight-bearing leads to revarisation as cancellous bone sustains only 3 MPa, and the measured compressive stresses at the medial edge amounted to 6 MPa on average. Displacing the distal fragment medially leads to a decrease of total cortical contact, too, but at the medial edge of the osteotomy cortical contact areas are still present. As a result of the study, postoperative weight-bearing without additional plaster cast fixation is recommended only in cases with undisplaced fragments.

Toxicity of a particulate formulation for the intraperitoneal application of mitoxantrone.

Mitoxantrone (MXN) has demonstrated therapeutic efficacy in the intraperitoneal treatment of malignancies. However, severe local toxicity is dose limiting. Therefore, a particulate formulation of MXN, the drug incorporated in albumin microspheres, was evaluated concerning tolerability. Survival rates as well as alterations in body weight, food intake, water intake, urine volume, urine specific gravity, urine protein content, and complete blood count were observed following single or multiple intraperitoneal injections of MXN solution, dispersions containing MXN-loaded microspheres or unloaded microspheres, and the injection vehicle to female and male Sprague-Dawley rats. Applied MXN dosage was equivalent to 30 mg/m2 body surface area. Unloaded microspheres were well tolerated without signs of toxicity. Application of MXN solution or MXN-loaded microspheres resulted in similar survival rates (56% 9 weeks after single injection) and in a comparable bone marrow toxicity (mainly leucopenia). Body weight, food and water intake as well as urine volume were decreased following application of MXN solution, whereas a progressive gain in weight and no remarkable alterations in nutrition and urine excretion were noted after administration of MXN-loaded and unloaded microspheres, or of the injection vehicle. In conclusion, intraperitoneal injection of MXN incorporated in albumin microspheres exhibits in part less toxicity than conventional treatment.

Cross-cultural adaptation of the Roland-Morris questionnaire for German-speaking patients with low back pain.

STUDY DESIGN: Cross-cultural adaptation and cross-sectional psychometric testing. OBJECTIVES: To develop and validate a cross-cultural version of the Roland-Morris Questionnaire for use in German-speaking patients with low back pain. SUMMARY OF THE BACKGROUND DATA: Clinical research related to the management of back pain would be facilitated enormously if a small number of patient-oriented questionnaires became widely used. If the transposition of a questionnaire from its original cultural context is done by simple translation, it is unlikely to be successful because of language and cultural differences. Therefore, a simple direct translation of a questionnaire from one language to another does not permit its use in clinical trials. METHODS: The instrument was translated and back-translated, pretested, and reviewed by a committee. The German version of the Roland-Morris Questionnaire was tested in 125 patients with low back pain. The study was conducted at the spa resort at Senftenberg, Austria, which is visited by patients from all countries of German-speaking Europe. Reliability and concurrent construct validity were assessed with Pearson's correlation coefficient on the Roland-Morris Questionnaire scores compared with the scales of the Medical Outcome Study Short Form-36 questionnaire. RESULTS: Pearson's correlation coefficient for test-retest reliability of the German version was r = 0.82 (P = 0.0001), and Cronbach's alpha was 0.81. The concurrent validity was r = 0.81 (Roland-Morris Questionnaire/pain rating; P = 0.0001), r = 0.48 (Roland-Morris Questionnaire/forward bending; P = 0.0001), and r = -0.47 (Roland-Morris Questionnaire/lateral bending; P = 0.0001). Correlation between the functional scales of the Medical Outcome Study Short Form-36 questionnaire and the Roland-Morris Questionnaire sum scores ranged from r = -0.29 (emotional limitations; P = 0.0011) to r = -0.71 (physical limitations; P = 0.0001). CONCLUSION: Because the German version of the Roland-Morris Questionnaire seems to be reliable and valid for the assessment of the functional status in German-speaking patients with low back pain, the use of this translated instrument can be recommended in future clinical trials.

Peritoneal elimination of homocysteine moieties in continuous ambulatory peritoneal dialysis patients.

BACKGROUND: The amount of total homocysteine eliminated by peritoneal dialysis and its relationship to peritoneal transport characteristics in continuous ambulatory peritoneal dialysis (CAPD) patients are unknown. METHODS: The influence of total homocysteine, folate, and vitamin B12 plasma concentrations, serum albumin levels, age, sex, dialysate to plasma ratio (D/P) creatinine, D/D0 glucose, D/P albumin, dialysate effluent volume, and effluent albumin on the daily peritoneal excretion of total homocysteine was investigated in 39 CAPD patients. The relationship of D/P creatinine to D/P total homocysteine, D/P free homocysteine, and D/P protein-bound homocysteine was analyzed additionally in a subgroup of 25 patients. RESULTS: We observed a significant influence of plasma total homocysteine concentrations (P = 0.0001) of the daily dialysate effluent volume (P = 0.0221) and of the D/P creatinine (P = 0.0132) on peritoneal elimination of total homocysteine. The daily peritoneal excretion of total homocysteine was 38.94 +/- 20.82 mumol (5.27 +/- 2.81 mg). There was a positive linear association of the daily total homocysteine elimination with plasma total homocysteine concentrations (P = 0.0001). A significant linear correlation was observed between D/P creatinine and D/P total homocysteine (P = 0.0001), D/P free homocysteine (P = 0.0001), as well as D/P protein-bound homocysteine (P = 0.0001). CONCLUSIONS: The peritoneal elimination of total homocysteine primarily depends on the plasma total homocysteine concentration. Elevated total homocysteine plasma levels cannot be reduced efficiently by peritoneal dialysis.

Effect of MTHFR 677C>T on plasma total homocysteine levels in renal graft recipients.

BACKGROUND: Hyperhomocysteinemia is an established, independent risk factor for vascular disease morbidity and mortality. The 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism C677T has been shown to result in increased total homocysteine concentrations on the basis of low folate levels caused by a decreased enzyme activity. The effect of this polymorphism on total homocysteine and folate plasma levels in renal transplant patients is unknown. METHODS: We screened 636 kidney graft recipients for the presence of the MTHFR C677T gene polymorphism. The major determinants of total homocysteine and folate plasma concentrations of 63 patients, who were identified to be homozygous for this gene polymorphism compared with heterozygotes (N = 63), and patients with wild-type alleles (N = 63), who were matched for sex, age, glomerular filtration rate (GFR), and body mass index, were identified by analysis of covariance. The variables included sex, age, GFR, body mass index, time since transplantation, folate and vitamin B12 levels, the use of azathioprine, and the MTHFR genotype. To investigate the impact of the kidney donor MTHFR genotype on total homocysteine and folate plasma concentrations, a similar model was applied in 111 kidney graft recipients with stable graft function, in whom the kidney donor C677T MTHFR gene polymorphism was determined. RESULTS: The allele frequency of the C677T polymorphism in the MTHFR gene was 0.313 in the whole study population [wild-type (CC), 301; heterozygous (CT), 272; and homozygous mutant (TT), 63 patients, respectively] and showed no difference in the patient subgroups with various renal diseases. The MTHFR C677T gene polymorphism significantly influenced total homocysteine and folate plasma concentrations in renal transplant recipients (P = 0.0009 and P = 0.0002, respectively). Furthermore, a significant influence of the GFR (P = 0.0001), folate levels (P = 0.0001), age (P = 0.0001), body mass index (P = 0.0001), gender (P = 0.0005), and vitamin B12 levels (P = 0.004) on total homocysteine concentrations was observed. The donor MTHFR gene polymorphism had no influence on total homocysteine and folate levels. Geometric mean total homocysteine levels in patients homozygous for the mutant MTHFR allele were 18.6 micromol/liter compared with 14.6 micromol/liter and 14.9 micromol/liter in patients heterozygous for the MTHFR gene polymorphism and those with wild-type alleles (P < 0.05 for TT vs. CT and CC). Geometric mean folate levels were lower in CT and TT patients (11.2 and 10.2 nmol/liter) compared with CC patients (13.6 nmol/liter, P < 0.05 vs. CT and TT). CONCLUSIONS: This study demonstrates that homozygosity for the C677T polymorphism in the MTHFR gene significantly increases total homocysteine concentrations and lowers folate levels in kidney graft recipients, even in patients with excellent renal function (GFR more than median). These findings have important implications for risk evaluation and vitamin intervention therapy in these patients who carry an increased risk for the development of cardiovascular disease.

Different cup migration in rheumatoid arthritis and arthrosis: a radiographic analysis of 127 uncemented acetabular cups.

We compared retrospectively the radiographic migration profiles of 82 acetabular components in 61 patients having rheumatoid arthritis with those of 45 hips having arthrosis who underwent a standardized technique of cementless arthroplasty with the Zweymüller prosthesis (Alloclassic). We used a modification of Dickob's technique of digital migration analysis that corrects for magnification errors and horizontal pelvic tilt. The rheumatoid patients were stratified as having oligoarticular, polyarticular, or mutilating arthritis. The overall rate of acetabular loosening in rheumatoid hips after mean 88 (26-117) months was 4%. Loosening was seen only in cases with mutilating arthritis and acetabular protrusion, where the direction of cup migration was also clearly different from that detected in the other types of rheumatoid arthritis and in arthrosis. The different patterns of cup migration in cementless hip replacement for rheumatoid arthritis, depending on disease severity, is of importance when comparing outcome of total hip arthroplasty in rheumatoid patients.

Monitoring of median nerve somatosensory evoked potentials in carotid surgery.

The purpose of this study was to compare median somatosensory evoked potentials (SEP) in patients undergoing carotid endarterectomy (CEA) with routine shunting and nonshunting (excluding the option of selective shunting) and to evaluate the significance of a decrease in the amplitude of the cortically generated waveforms of the SEP and/or an increase in the central conduction time (CCT) on the one hand, and that of a loss of the cortical SEP, on the other. Somatosensory evoked potentials were recorded in 32 patients before, during, and after CEA with routine shunting or nonshunting. The N13 and N20 latency, the CCT, and the N20/P25 amplitude were evaluated. In addition, a meta-analysis of 15 previous studies was performed comprising a total of 3,136 patients. The intraoperative cortical SEP showed no differences between shunted and nonshunted patients, apart from the preclamping value of the N20/P25 amplitude which was lower in the nonshunted subjects. The number of patients with decreased and/or delayed cortical SEP (findings frequently used as criterion for selective shunting) was similar in the two study groups. A loss of the cortical SEP occurred in one patient operated on without an indwelling shunt. None of these patients had a new neurologic deficit after surgery. In the meta-analysis, the positive predictive value of decreased and/or delayed cortical SEP was extremely poor, that of absent cortical SEP was poor to moderate and the prevalence of new neurologic deficits was similar in patients undergoing CEA with routine shunting-nonshunting and those with selective shunting-nonshunting. Our study suggests that decreased and/or delayed cortical SEP are unreliable predictors of the neurological outcome of CEA patients and consequently an unsuitable criterion for selective shunting. The meta-analysis confirms this finding and shows that the neurologic outcome is not improved by using an indwelling shunt selectively based on SEP monitoring.

Major determinants of hyperhomocysteinemia in peritoneal dialysis patients.

The mechanisms leading to elevated total homocysteine concentrations in peritoneal dialysis patients are only partially understood. We show that a common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (C677T transition) results in increased total homocysteine levels in peritoneal dialysis patients compared to age- and sex-matched healthy individuals. The allelic frequency of the C677T transition in the MTHFR gene in peritoneal dialysis patients (0.29) was comparable to the frequency in healthy individuals (0.34). Separate comparison of the total homocysteine plasma levels between non-carriers of the MTHFR polymorphism (C/C), heterozygous (C/T) and homozygous (T/T) subjects was performed by analysis of covariance in the patient and the control group. In the patient group the mean total homocysteine level was 61.7 +/- 40.1 mumol/liter in individuals with the (T/T) genotype, which was significantly higher than the total homocysteine concentration of 23.1 +/- 15.8 mumol/liter in (C/T) patients and 22.2 +/- 11.1 mumol/liter for non-carriers (P = 0.0001). Vitamin B12 (P = 0.0001), folate (P = 0.0005), serum creatinine (P = 0.016), albumin (P = 0.0157) and dialysis center (P = 0.0173) significantly influenced total homocysteine plasma levels in peritoneal dialysis patients, whereas this was not the case for age, gender, weekly Kt/V, weekly creatinine clearance, residual renal function, duration of dialysis, mode of peritoneal dialysis and vitamin intake. Folate levels in peritoneal dialysis patients were significantly affected by the MTHFR genotype (P = 0.016). Elevated total homocysteine levels in diabetic patients with cardiovascular disease were associated with increased cardiovascular morbidity. In summary, the present study provides evidence that homozygosity for the C677T transition in the MTHFR gene, low vitamin B12 and low folate levels result in elevated total homocysteine levels in peritoneal dialysis patients.

Mutation (677 C to T) in the methylenetetrahydrofolate reductase gene aggravates hyperhomocysteinemia in hemodialysis patients.

Hyperhomocysteinemia is frequent in hemodialysis patients and represents an independent risk factor for vascular disease in these patients. Elevated total homocysteine (tHcy) plasma levels can results from defective remethylation of Hcy to methionine due to decreased activity of the enzyme methylenetetrahydrofolate reductase (MTHFR). A genetic aberration in the MTHFR gene (677 C to T substitution) has been shown to result in reduced MTHFR activity. We tested the hypothesis that elevation of tHcy plasma levels in hemodialysis patients is influenced by the 677 C to T mutation of the MTHFR gene and examined the relation of the genotype with tHcy, folate and vitamin B12 plasma levels in these patients. The allelic frequency of the MTHFR mutation was evaluated in 203 patients maintained on chronic hemodialysis treatment. Total Hcy, folate, vitamin B12 levels and the MTHFR mutation were analyzed in 69 of the 203 patients and in 69 age- and sex-matched healthy control subjects. The allelic frequency of the 677 C to T transition in the MTHFR gene in hemodialysis patients was 34.7% versus 35.5% in healthy controls. Of 203 patients 26 (12.8%) were homozygous for the mutation (+/+) versus 10.2% in healthy subjects. The heterozygous (+/-) genotype was identified in 43.8% of patients versus 50.7% in controls. The mean tHcy level in hemodialysis patients was 28.7 +/- 11.0 mumol/liter versus 10.0 +/- 3.0 mumol/liter in control subjects. The mean tHcy levels were 36.4 +/- 13.4 mumol/liter in (+/+) patients and 12.2 +/- 4.5 mumol/liter in (+/+) controls, 28.7 +/- 10.8 mumol/liter in (+/-) patients and 9.9 +/- 2.7 mumol/liter in (+/-) controls and 25.4 +/- 8.5 mumol/liter in (-/-) hemodialysis patients versus 9.7 +/- 2.8 mumol/liter in (-/-) controls: There was no significant difference of folate and vitamin B12 concentrations in patients and controls with different MTHFR genotypes. Analysis of covariance including age, gender, folate concentrations, vitamin B12 levels, albumin and creatinine as covariables revealed a significant influence of the (+/+) genotype, albumin and folate status on tHcy levels in hemodialysis patients. Together, our data demonstrate that the extent of hyperhomocysteinemia in hemodialysis patients is not only the result of uremia or folate status, but is also genetically determined by the (+/+) MTHFR genotype. The presence of the 677 C to T mutation in the MTHFR gene does not appear to represent a risk factor for development of end-stage renal disease.