Use of the Complete Rockall Score and the Forrest Classification to Assess Outcome in Patients with Non-variceal Upper Gastrointestinal Bleeding Subject to After-hours Endoscopy: A Retrospective Cohort Study.

OBJECTIVES: To evaluate the usefulness of the Forrest classification and the complete Rockall score with customary cut-off values for assessing the risk of adverse events in patients with upper gastrointestinal bleeding (UGI-B) subject to after-hours emergency oesophago-gastro-duodenoscopy (E-EGD) within six hours after admission. METHODS: The medical records of patients with non-variceal UGI-B proven by after-hours endoscopy were analysed. For 'high risk' situations (Forrest stage Ia-IIb/complete Rockall score > 2), univariate analysis was conducted to evaluate odds ratio for reaching the study endpoints (30-day and one-year mortality, re-bleeding, hospital stay ≥ 3 days). RESULTS: During the study period (75 months), 86 cases (85 patients) met the inclusion criteria. Patients' age was 66.36 ± 14.38 years; 60.5% were male. Mean duration of hospital stay was 15.21 ± 19.24 days. Mortality rate was 16.7% (30 days) and 32.9% (one year); 14% of patients re-bled. Univariate analysis of post-endoscopic Rockall score ≥ 2 showed an odds ratio of 6.09 for death within 30 days (p = 0.04). No other significant correlations were found. CONCLUSION: In patients with UGI-B subject to after-hours endoscopy, a 'high-risk' Rockall score permits an estimation of the risk of death within 30 days but not of re-bleeding. A 'high-risk' Forrest score is not significantly associated with the study endpoints.

[Self-medication to treat pain in attacks of familial Mediterranean fever: aiming to find a new approach to pain management]. / Schmerztherapeutische Bedarfsmedikation bei Attacken von familiärem Mittelmeerfieber : Auf der Suche nach einem schmerztherapeutischen Ansatz.

BACKGROUND: Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by bouts of fever and serositis. Morbidity caused by bouts as well as self-medication were assessed among patients of Turkish ancestry living in Germany (D) or Turkey (T) in order to evaluate current analgetic concepts from a patient's perspective. MATERIAL AND METHODS: D and T were asked about the 3 months preceding the interview. RESULTS: A total of 40 D and 40 T were included; 35/40 D and 40/40 T were on colchicine. In the last 3 months, 61.3 % had ≥ 1 bout and suffered from peritonitis (87.8 %), fever (61.2 %), myalgia (45 %), pleuritis (42.8 %), arthralgia (36.7 %), and cephalgia (32.6 %). Of the patients, 65.3 % were bedridden during bouts, 61.2 % sought the attention of a physician, 53.1 % were unable to work or attend school, and 38.8 % were hospitalized. The following drugs were taken: NSAIDs (45.6 %), NSAIDs and paracetamol (42.6 %), and combinations of NSAIDs with other analgesics. NSAIDs (58.6 %) and paracetamol (20.7 %) were considered the most potent substances. CONCLUSION: FMF inflicts substantial morbidity. Patients most commonly rely on NSAIDs and paracetamol to relieve symptoms of FMF bouts.

Percutaneous transluminal angioplasty as first-line treatment of transplant renal artery stenosis.

BACKGROUND: Transplant renal artery stenosis (TRAS) is a frequent complication after renal transplantation, however long-term follow-up data after interventional treatment are rare. PATIENTS: In our transplant center 11 of 264 consecutive renal transplant recipients (4.17%) were diagnosed with TRAS. In addition, TRAS occurred in 2 renal transplant recipients that had been transplanted at other centers but who had their follow-up examinations in our center. Either a rise of the serum creatinine level and/or worsened systemic hypertension or routine examination with color Doppler sonography were indications for further diagnostic workup. METHODS: Direct angiography of the transplant renal artery was performed followed by percutaneous transluminal angioplasty (PTA) after the diagnosis of TRAS was confirmed in all of these patients. RESULTS: The immediate success rate for PTA was 92.3% (12/13). Only 1 patient with a severe kinking of the transplant renal artery had to undergo surgery to restore renal function. No complications occurred after the interventions. Thereafter the patients were monitored for a mean observation period of 33.15 months. Serum creatinine levels were significantly lower after the intervention, and estimated glomerular filtration rate (eGFR) increased accordingly. With regard to blood pressure there was only a trend for lower blood pressure levels and less antihypertensive use, whereas the dose of the prescribed drugs decreased significantly with time after interventional treatment of TRAS. In addition, a long-lasting rise of the hemoglobin levels could also be demonstrated. CONCLUSION: In summary, the beneficial effect of PTA of TRAS on renal function is long-lasting. Therefore, PTA, usually combined with stent placement, should be first-line treatment in TRAS in all patients. Surgical revascularization is only warranted, if PTA fails.

Dihydrotachysterol therapy for hypoparathyroidism: consequences of inadequate monitoring. Five cases and a review.

BACKGROUND: The half synthetic Vitamin D analogue dihydrotachysterol (DHT) is widely used for hypocalcaemic hypoparathyroidism following surgical removal of parathyroids. Such treatment generally initiated by surgeons right after surgery has to be continued in clinical practice. Unfortunately, the required careful monitoring of calcium metabolism is often lacking and as demonstrated may lead to life-threatening conditions. PATIENTS AND METHODS: Here we report on five patients referred to our nephrology unit because of unknown impairment of renal function during therapy with DHT. All patients had clinical signs of hypercalcaemia. Since most symptoms are nonspecific they were not perceived by primary care physicians. In fact DHT treatment was continued for 4 - 50 years. In all cases calcium levels were determined after inadequate long intervals ranging from 3.08 to 4.97 mmol/l. Creatinine levels ranged from 277 to 365 micromol/l. All patients suffered from symptoms of severe hypercalcaemia, three of them needing intensive care unit treatment. RESULTS: All patients were treated effectively with a regimen consisting of intravenous saline, a loop diuretic, and application of bisphosphonates. As confirmed by renal biopsy persisting alleviation of renal function was due to calcifications. After discontinuation of DHT therapy patients were safely switched to shorter acting vitamin D derivates maintaining a normal calcium level. CONCLUSIONS: In comparison to short acting vitamin-D derivates hypercalcaemic episodes with DHT appear to last longer and may therefore occur with higher incidence. A future option could be the use of synthetic parathyroid hormone (s-PTH) recently shown to be safe and effective. Nevertheless a customized therapy and careful monitoring is indispensable in any case to prevent irreversible organ damage.

[Homocysteine and its metabolites in chronic renal insufficiency and the effect of a vitamin replacement]. / Homocystein und seine Metaboliten bei chronischer Niereninsuffizienz und der Einfluss einer Vitaminsubstitution.

BACKGROUND: Hyperhomocysteinemia has been increasingly recognized as an important risk factor for elevated atherosclerotic vascular disease in chronic renal failure. We measured in patients with chronic renal failure homocysteine and metabolites of its 2 metabolic pathways, transulfuration (cystathionine, cysteine) and remethylation (methionine, methylmalonic acid, 2-methylcitric acid). PATIENTS AND METHODS: Eleven patients on conservative treatment (creatinine clearance 10 to 30 ml/min) and 50 chronic uremic subjects on regular hemodialysis were included in the study. Twenty-two of the dialysis patients received daily oral multivitamin supplementation containing 10 mg vitamin B6, 6 micrograms vitamin B12, and 1 mg folic acid during the last year before the study started. RESULTS: In the hemodialysis group homocysteine levels were higher compared with the patients on conservative treatment. Hemodialysis patients with additional vitamin supplementation showed significantly lower homocysteine levels than those without. The pattern of metabolites was different to these results: all metabolites were higher in hemodialysis patients, too (significant for cysteine and methionine), but vitamin supplementation failed to lower all metabolites. CONCLUSION: Analysis of metabolites additional to homocysteine levels may help to understand different results in evaluation of atherosclerotic risk of hyperhomocysteinemia in chronic renal failure.

[Pre-endoscopic assessment to predict outcome of acute upper gastrointestinal bleeding--a retrospective study in patients subject to emergency endoscopy outside regular working hours]. / Sind prä-endoskopische Scores als prognostische Instrumente bei oberen gastrointestinalen Blutungen geeignet? Retrospektive Untersuchung bei Patienten, die außerhalb der regulären Dienstzeiten notfallmäßig endoskopiert wurden.

BACKGROUND AND OBJECTIVES: To evaluate the predictive value of pre-endoscopic risk scores in patients with upper gastrointestinal bleeding (UGI-B). PATIENTS AND METHODS: The medical records of patients evaluated by emergency esophago-gastro-duodenoscopy (E-EGD) for suspected UGI-B outside regular working hours were retrospectively analysed. RESULTS: During the 75 months of the study period 112 E-EGDs met the inclusion criteria. Mean age was 65.5 ± 14.7 years. 38.4 % of patients were female. Endoscopy revealed 41 gastro-duodenal ulcers, 16 Mallory-Weiss, 13 varices, 4 neoplasia. 72 patients received transfusions, 39 had endoscopic interventions. 2 patients were surgically treated, 16 had recurrent bleeding. 16 of the 110 patients died during hospitalisation. The following sensitivities were found for the Blatchford score (cut-off > 1), the clinical Rockall score (cut-off > 0) and the Adamopoulos score (cut-off > 2) in predicting need for clinical intervention (endoscopic or surgical intervention or transfusion): 100/97.7/93%, recurrent bleeding: 100/100/93.8%, in-hospital mortality: 100/93.8/93.8%, respectively. CONCLUSIONS: The Blatchford score is a suitable tool in determining the need for clinical intervention and the risk of recurrent bleeding and death in patients with UGI-B. The clinical Rockall score and the Adamopoulos score (the latter had originally been developed to predict active UGI-B at endoscopy and was used with a lower cut-off in our study) are inferior alternatives.

[Demands for endoscopy service outside of regular hours: a retrospective study and literature analysis]. / Inanspruchnahme des Endoskopie-Hintergrunddienstes ausserhalb der regulären Dienstzeiten: Eine retrospektive Studie und Literaturanalyse.

BACKGROUND AND OBJECTIVE: Many acute care hospitals provide round-the-clock emergency endoscopy to guarantee immediate diagnosis and treatment of acute conditions of the gastrointestinal tract. This study is the first one to assess the demand for emergency endoscopy outside usual working hours. PATIENTS AND METHODS: This study evaluated retrospectively 315 consecutive emergency endoscopies done at an acute care hospital (575 beds; catchment population 100,000, in the Ruhr area of Germany) between 26.7.2003 and 01.11.2009 (6 years and 3 months) outside usual working hours (i.e. during the weekend and from 6 pm to 8 am during weekdays). This represents 50 emergency endoscopies outside working hours per 100,000 people per year. RESULTS: 56.8 % of the examinations took place during the weekend (Saturday or Sunday), 26.7 % during the night (10 pm - 8 am). The distribution of the different endoscopic modalities was: 228 EGD (72.4 %), 42 incomplete colonoscopies or recto-sigmoidoscopies (13.3 %), 28 retrograde cholangio- or cholangiopancreatographies (8.9 %), 16 complete colonoscopies (5.2 %) and one oral enteroscopy. 208 (66%) of endoscopic procedures were purely diagnostic without any therapeutic intervention. The indication for endoscopy was documented in 243 of the 315 procedures. In 76.5 % of those cases the suspicion of a gastrointestinal bleeding was the indication for endoscopy. CONCLUSION: In an acute care hospital in Germany 50 emergency endoscopies outside working hours were performed per 100,000 population per year. This rate exceeds that reported in other European countries (Great Britain: 26.7, Norway: 24). Further studies are needed to evaluate the impact of different emergency endoscopic strategies on patient outcome and treatment costs.

[Familial Mediterranean fever. Rare manifestation without fever and with inconspicuous family case history]. / Familiäres Mittelmeerfieber. Seltene Manifestation ohne Fieber und mit unauffälliger Familienanamnese.

HISTORY AND ADMISSION FINDINGS: A 33-year-old man of Turkish descent had suffered from recurrent diffuse abdominal pain and shoulder pain since 13 years. Repeatedly performed investigations in the past had produced numerous diagnoses. The symptoms had been recurring quarterly to weekly, lasted three days on average and resolved spontaneously. He never had fever and the family history was unremarkable. DIAGNOSIS, TREATMENT, AND COURSE: Blood tests demonstrated increased parameters for systemic inflammation and mild normochromic normocytic anemia. In addition to splemomegaly the abdominal computed tomography revealed signs of sacroiliitis. There was no arthritis of the shoulder radiologically. Despite lack of familial history and fever genetic analysis of the Mediterranean fever gene (MEFV) revealed two heterozygous mutations in this MEFV gene for M694 and V726A. The patient was treated with colchicine and has now remained free of symptoms for meanwhile 10 months. There had been no comparable symptom-free period during the last 10 years. CONCLUSION: Sometimes the name "Familial Mediterranean Fever" (FMF) is misleading because this disease may, although rarely, occur without both, fever and familial history. Because of the increasing number of immigrants FMF should be considered in the initial differential diagnosis of patients of Mediterranean origin presenting with abdominal pain. Genetic analysis of the MEFV-gene as well as a therapeutic trial with colchicine, may help to detect FMF.

[Ischemic colitis without atherosclerosis?]. / Ischämische Kolitis ohne Arteriosklerose?

HISTORY AND CLINICAL FINDINGS: A 69-year-old woman, who was being treated for a bipolar affective psychosis, was admitted because of abdominal pain, emesis and bloody stool. EXAMINATIONS: Blood tests showed increased inflammation parameters. Ultrasound revealed a swollen intestinal wall. Coloscopy correlated with the ultrasound findings and demonstrated an ischemic colitis. The histological report at first corroborated this as the possible diagnosis. But angiography of the mesenteric vessels and duplex ultrasound of the cervical vessels were normal. COURSE AND THERAPY: The symptoms persisted under therapy with acetylsalicylic acid (100 mg daily), no food intake and intravenous fluids. The coloscopic picture and the laboratory tests remained unchanged. The findings did not normalize until most of the antipsychotic drugs, especially perazine, were discontinued. The angiographic and duplexultrasound results spoke against the initially suspected diagnosis of an ischemic origin, but for necrotizing colitis as an adverse effect of perazine. A second biopsy confirmed this explanation. CONCLUSION: A necrotizing colitis as an adverse effect of drugs can simulate an ischemic colitis on endoscopy and in a biopsy. Even if the clinical pattern is present possible adverse reaction to the medication should be considered. The diagnosis of a necrotizing colitis was postulated only after the course of the disease had been taken into account and, in particular, atherosclerosis had been excluded as a possible cause, and an adverse reaction to the medication had been considered.

Results of a Phase I trial of sorafenib (BAY 43-9006) in combination with doxorubicin in patients with refractory solid tumors.

BACKGROUND: Sorafenib (BAY 43-9006), a novel, oral multi-kinase inhibitor, blocks serine/threonine and receptor tyrosine kinases in the tumor and vasculature. Sorafenib demonstrated single-agent activity in Phase I studies, and was tolerated and inhibited tumor growth in combination with doxorubicin in preclinical studies. This Phase I dose-escalation study determined the safety, pharmacokinetics and efficacy of sorafenib plus doxorubicin. PATIENTS AND METHODS: Thirty-four patients with refractory, solid tumors received doxorubicin 60 mg/m(2) on Day 1 of 3-week cycles, and oral sorafenib from Day 4 of Cycle 1 at 100, 200 or 400 mg bid. RESULTS: Common drug-related adverse events were neutropenia (56%), hand-foot skin reaction (44%), stomatitis (32%), and diarrhea (32%). The maximum tolerated dose was not reached. One patient with pleural mesothelioma achieved a partial response (modified WHO criteria) and remained on therapy for 39.7 weeks. Fifteen patients (48%) achieved stable disease for >/=12 weeks. Doxorubicin exposure increased moderately with sorafenib 400 mg bid. The pharmacokinetics of sorafenib and doxorubicinol were not affected. CONCLUSION: Sorafenib 400 mg bid plus doxorubicin 60 mg/m(2) was well tolerated. The increased doxorubicin exposure with sorafenib 400 mg bid did not result in significantly increased toxicity; low patient numbers make the clinical significance of this unclear. These promising efficacy results justify further clinical investigation.

[Antiphospholipid antibody syndrome as the cause of clinical rapidly progressing vasculopathy]. / Antiphospholipid-Antikörpersyndrom als Ursache einer klinisch rasch progredienten Vaskulopathie.

HISTORY AND ADMISSION FINDINGS: For 3 weeks a 54-year-old man had been unsuccessfully treated with antibiotics for ulcerating tonsillitis with fever, weight loss, occasional headaches, and hypertension. A year before he had suffered a transitory cerebral ischaemic attack. On admission he had a fever of 38.6 degrees C, blood pressure of 185/100 mmHg and a nonspecific 2/6 apical systolic murmur. INVESTIGATIONS: Erythrocyte sedimentation rate was 100/120 mm, C-reactive protein 1.5 mg/dl, serum creatinine 2.45 mg/dl, urinary protein 0.8 g/d. Tests for antinuclear antibodies (ANCA) against neutrophil granulocytes and for native DNA antibodies were negative, as were serological tests for Coxsackie virus, Cytomegalovirus and Epstein-Barr virus. Sonography and computed tomography revealed thrombosis along the entire aortic wall, renal artery stenosis and a contracted left kidney. Transoesophageal echocardiography demonstrated small thrombi on the aortic valve leaflets. Coloscopy showed ulcerative colitis. TREATMENT AND COURSE: The patient was anticoagulated. Local cold produced livedo reticularis. Tests for cardiolipin antibodies in serum and a skin biopsy provided the diagnosis of antiphospholipid antibody syndrome (APS). As the skin biopsy showed vasculitis, immunosuppressive treatment was started. This stabilized the condition and he was discharged to be followed by his general practitioner. CONCLUSION: APS can cause complex symptoms in many organs, but effective treatment (anticoagulation, corticosteroids, immunosuppressives) is available, as this case demonstrates.

Long-term effects of vitamin B(12), folate, and vitamin B(6) supplements in elderly people with normal serum vitamin B(12) concentrations.

BACKGROUND: In the elderly, deficiencies of folate, cobalamin (vitamin B(12)) and pyridoxal phosphate (vitamin B(6)) are common. The metabolites homocysteine, methylmalonic acid, 2-methylcitric acid and cystathionine have been reported to be sensitive markers of these vitamin deficiencies. OBJECTIVE: The long-term (269 days) effect of an intramuscular vitamin supplement containing 1 mg vitamin B(12), 1.1 mg folate, and 5 mg vitamin B(6) on serum concentrations of homocysteine (tHcy), methylmalonic acid (MMA), 2-methylcitric acid (2-MCA), and cystathionine (Cysta) was studied in 49 elderly subjects with normal levels of vitamin B(12). METHODS: Vitamin supplement was administered 8 times over a 21-day period, metabolite concentrations were measured until day 269 (e.g. 248 days after the end of vitamin supplementation). RESULTS: From day 0 to 21, the serum levels of the 3 vitamins increased significantly, after cessation of supplementation the levels returned to baseline within the follow-up period. The MMA, 2-MCA and tHcy levels decreased during the treatment period significantly and did not reach baseline values within the 248-day period. Cysta levels did not differ significantly from baseline, either during or after treatment. CONCLUSION: MMA and 2-MCA levels rather reflect the availability of vitamins, especially cobalamin, than the actual serum levels. Since deficiencies of folate, cobalamin and pyridoxal phosphate in the elderly may cause hyerhomocysteinemia and hence may have unfavorable effects on mental performance, determination of MMA and 2-MCA levels in elderly patients with mental disturbances may be a cost-effective measure to improve or maintain mental performance.

Vitamin supplementation during weight reduction--favourable effect on homocysteine metabolism.

Moderately elevated homocysteine concentrations, reflecting deficiency of some nutritional factors required for homocysteine metabolism (folate, vitamin B-6, vitamin B-12) and/or less severe genetic defects, are common in the general population. Several studies have indicated the role of homocysteine as an independent risk factor for vascular disease. A pilot study published recently suggested that plasma homocysteine levels increase during weight reduction in slightly overweight, otherwise healthy subjects (group A). We examined a comparable group of 13 overweight subjects (group B) using a standardised caloric intake and defined vitamin supplementation (Medyn: folate 0.2 mg/ vitamin B-68.0 mg/ vitamin B-120.010 mg three times the day orally) to determine the effect of weight reduction on serum homocysteine levels and to compare the results with those of the pilot study. Mean body weight declined from 87.0 +/- 20.2 to 84.2 +/- 20.1 kg (P < 0.05) in group A and 85.7 +/- 11.3 to 82.5 +/- 9.9 kg (P = 0.049) in group B. Serum homocysteine levels rose from 7.9 +/- 2.0 to 8.7 +/- 2.3 mumol/l (P < 0.0001) in group A and decreased from 8.19 +/- 1.73 to 7.35 +/- 0.88 mumol/l (P = 0.0022) in group B. No correlation was found between the changes in body weight and in homocysteine levels (r = 0.02 in group A, r = 0.18 in group B). Additionally, no correlation was found between serum folate levels and changes in homocysteine levels (r = 0.03 in group A, r = 0.09 in group B). The results suggest that an adequate oral vitamin-supplementation protects against increased homocysteine production during weight reduction.

Homocyst(e)ine metabolism in hemodialysis patients treated with vitamins B6, B12 and folate.

Hyperhomocyst(e)inemia is commonly accepted as an independent atherosclerotic risk factor. In most hemodialysis patients, serum homocyst(e)ine is markedly elevated and may contribute to premature atherosclerosis in these patients. Whereas the beneficial effect of folate supplementation on serum homocyst(e)ine has been extensively studied, there are less detailed studies on the effects of cobalamin and pyridoxal phosphate alone, or in combination with folate. We examined the effect of a four-week course of intravenous treatment with folate (1.1 mg), cobalamin (1.0 mg), and pyridoxal phosphate (5.0 mg), administered once (group 1), twice (group 2) or thrice (group 3) weekly in 33 hemodialysis patients divided in three groups of 11 patients. All patients were followed for a further four weeks after treatment was stopped. Serum homocyst(e)ine, cobalamin, folate and pyridoxal phosphate, as well as the metabolites of homocyst(e)ine, methylmalonate, 2-methylcitrate and cystathionine, were determined before, during and after treatment. Baseline serum homocyst(e)ine correlated significantly with serum folate (P=0.0149), cobalamin (P=0.0047) and pyridoxal phosphate (P=0.0408). Correlations independent from the other metabolites or vitamins were found for methylmalonate (P=0.003) and folate (P=0.029). All regimens increased serum cobalamin significantly (in group 1 from 444 +/- 215 to 17,303 +/- 11,989 pg/ml, P<0.01; in group 2 from 542 +/- 633 to 44,896 +/- 15,772 pg/ml, P<0.001; in group 3 from 548 +/- 394 to 77,961 +/- 31,546 pg/ml, P<0.001), but did not increase any of the other vitamin levels. Serum homocyst(e)ine was lowered significantly by 39.8% +/- 31.9% (P<0.05) with two and by 30.1% +/- 26.9% (P<0.05) with three vitamin dosages weekly, but not with one dosage weekly. Since methylmalonate is known to be a sensitive marker of cobalamin deficiency, the data support an important influence of cobalamin levels on baseline homocyst(e)ine levels. Increasing cobalamin levels and additional treatment with folate and pyridoxal phosphate 156 may decrease serum homocyst(e)ine in the same way as high doses of folate alone.

[Renal function in hypertensive patients with obstructive sleep apnea]. / Nierenfunktion bei hypertensiven Patienten mit obstruktiver Schlafapnoe.

BACKGROUND: Patients with hypertension often suffer from obstructive sleep apnea (OSA). In addition to hypertension several other risk factors (hypoxemia, hyperlipidemia, and increased sympathic nerve activity) may contribute to progressive renal dysfunction in OSA patients. The aim of this study was to compare renal function in OSA-patients with and without hypertension. METHODS: 81 consecutive patients (50 males, 31 females) were screened for sleep apnea. Parameters of renal function (serum creatinine, creatinine clearance, microalbuminuria), and of lipid and glucose metabolism were correlated to polysomnographic results. RESULTS: OSA (apnea/hypopnea index [AHI] > or = 5) was found in 57 of 81 patients. Mean AHI was 26.7 +/- 26.1. Hypertension (blood pressure > or = 140/90 mmHg or use of antihypertensive drugs) occurred in 63 of 81 patients. Serum creatinine in OSA patients was significantly higher than in patients without OSA (1.11 +/- 0.15 vs. 0.91 +/- 0.12 mg/dl, p < 0.001). Serum creatinine correlated significantly with AHI. Creatinine clearance was associated with age (r = -0.314; p = 0.014) and presence of OSA (r = 0.265; p = 0.093). No correlation was shown between hypertension and serum creatinine or creatinine clearance. Microalbuminuria was not associated with OSA. CONCLUSION: Our results suggest an independent association between OSA and impaired renal function. Further prospective studies will have to be done to elucidate the pathophysiological mechanisms.

Evidence of altered homocysteine metabolism in chronic renal failure.

The fasting serum concentrations of total homocysteine and metabolites of transsulfuration (cystathionine, cysteine, methylmalonic acid, 2-methylcitric acid) and remethylation (methionine) were determined by gas chromatography-mass spectrometry in 40 nondialyzed patients with chronic renal disease and in 50 patients with end-stage renal disease requiring chronic maintenance hemodialysis. The nondialyzed patients and 28 of the dialysis patients did not receive additional vitamin supplementations. Twenty-two of the dialysis patients received daily oral vitamin preparations containing 10 mg pyridoxine (vitamin B(6)), 6 microg cyanocobalamin (vitamin B(12)), and 1 mg folic acid. In the nondialyzed patients, linear regression analysis showed positive correlations between serum concentrations of creatinine and total homocysteine (r = 0.68, p < 0.0001), cystathionine (r = 0.73, p < 0. 0001), methylmalonic acid (r = 0.77, p < 0.0001), and 2-methylcitric acid (r = 0.81, p < 0.0001). Serum homocysteine was positively correlated with serum concentrations of cystathionine (r = 0.59, p < 0.0001), cysteine (r = 0.69, p = 0.004), methylmalonic acid (r = 0. 64, p = 0.0001), and 2-methylcitric acid (r = 0.64, p < 0.0001). There was no significant correlation between serum concentrations of homocysteine and methionine (r = -0.14, p = 0.63). In the hemodialysis patients receiving oral vitamin supplementation, serum homocysteine and cystathionine concentrations were significantly lower than in hemodialysis patients not receiving vitamins (homocysteine 21.8 +/- 1.1 vs. 33.2 +/- 3.7 micromol/l, p = 0.0004; cystathionine 2,075.9 +/- 387.1 vs. 3,171.3 +/- 680.2 nmol/l, p = 0. 02; mean +/- SEM). In summary, our results show increased intermediate products of the transsulfuration pathway, but no increase in remethylation of homocysteine in chronic renal disease, including end-stage renal disease requiring chronic maintenance dialysis.