Preserved antioxidative defense of lipoproteins in renal failure and during hemodialysis

Contact to artificial surfaces during hemodialysis activates leukocytes, which then form oxidized arachidonic acid products and free radicals. This might promote the oxidative modification of low-density lipoproteins (LDL) that play a key role in the initiation of atherosclerosis. Thus, leukocyte activation could specifically contribute to the high mortality from atherosclerotic complications on long-term hemodialysis. Therefore monitored LDL and high-density lipoprotein (HDL) resistance to copper-stimulated oxidation in patients with end-stage renal disease on maintenance hemodialysis with cellulose acetate or polysulfone membranes (n = 12), in patients with chronic renal failure (n = 13) and in healthy controls (n = 12). Six of the dialysis patients were restudied during a single cuprophane dialysis. Circulating leukocytes were reversibly reduced early in hemodialysis with cellulose acetate (minimum, 83.6% +/- 7.4% of baseline values at 30 minutes after dialysis start), polysulfone (minimum, 80.4% +/- 10.5% at 15 minutes; P < 0.05) and cuprophane (minimum, 24.5% +/- 8.5% at 60 minutes; P < 0.0001). Despite the leukocyte activation, LDL oxidation lag time was not shortened in comparison with healthy controls and was even prolonged at the end of cellulose acetate (P < 0.05) and cuprophane (P < 0.05) dialysis. HDL oxidation lag time increased (12.6% +/- 0.9%; P < 0.0001) 15 to 60 minutes after start of hemodialysis and returned to predialysis values thereafter. In patients with chronic renal failure, the lag time of HDL oxidation was significantly prolonged (13.34 minutes +/- 0.9) compared with healthy controls (10.91 +/- 2.0 minutes; P < 0.01) as well as compared with the dialysis patients at baseline (9.9 minutes +/- 1.4; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Reduced left ventricular hypertrophy in type 1 diabetic patients with end-stage renal failure. A comparison between groups investigated 1977-80 and 1991-93

BACKGROUND: During the last decade, control of hypertension, oedema, anaemia, uraemia, and blood glucose has improved in patients with diabetic nephropathy. We have investigated whether this has influenced cardiac function at the time of end-stage renal failure. STUDY DESIGN: Echocardiographic investigations were performed in 26 type 1 diabetic patients evaluated for kidney transplantation and the results compared with those obtained in healthy controls and in a similar group of patients investigated in 1977-1980. RESULTS: Blood pressure was 153 +/- 21/85 +/- 12 mmHg versus 174 +/- 17/91 +/- 9 (recent group versus early group). The left ventricular (LV) diameter index, a measure of volaemia, was increased in systole and diastole in the early but not in the recent group. Both groups had LV hypertrophy, but this was much less pronounced in the recent group; posterior wall thickness was 1.1 +/- 0.16 cm versus 1.3 +/- 0.26 cm (P = 0.0001) and LV mass index 132 +/- 43 g/m2 versus 166 +/- 44 g/m2 (P = 0.009). Blood pressure correlated significantly with indices of LV hypertrophy in the recent group. Systolic function was normal in both groups but diastolic function was disturbed in both and to the same extent, atrial systole contributing by 27 +/- 14% to ventricular filling. CONCLUSION: Better treatment of hypertension, fluid overload, and uraemia has led to less pronounced LV hypertrophy. The remaining correlation with blood pressure suggests that more could be gained by intensified antihypertensive treatment.     

Thiobarbituric acid reactive substances are increased in the subcutaneous fat tissue of patients with end-stage renal disease

BACKGROUND: Patients with end-stage renal disease are thought to be in a highly peroxidative state, based on studies showing decreased serum antioxidant activity and increased peroxidative products. In this study we confirm these findings by examining lipid peroxidation in subcutaneous fat tissue in uraemia. SUBJECTS AND METHODS: Twenty-seven subcutaneous fat samples were taken from patients with end-stage renal disease when they underwent intervention for arteriovenous fistula for haemodialyis or for catheter insertion for continuous ambulatory peritoneal dialysis. The control samples were taken from 11 patients with normal renal function and without any history of renal disease who had surgical interventions. Lipid peroxides were measured as thiobarbituric acid reactive substance. RESULTS: The concentration of thiobarbituric acid reactive substances in subcutaneous fat tissue in the patients with end-stage renal disease is 1.223 +/- 0.636 nmol/mg fat tissue (mean +/- SD) whereas the level in the control group is 0.097 +/- 0.054 nmol/mg fat tissue. A comparison of the two groups by Student's t test revealed a highly significant difference (P < 0.001). CONCLUSIONS: This study supports the finding of a severe peroxidative state in patients with end-stage renal disease.     

Similar rate of progression in the predialysis phase in type I and type II diabetes mellitus

Progression of diabetic nephropathy from the stage of macroproteinuria with near-normal renal function until start of dialysis was compared in 16 patients with type I and 16 patients with type II diabetes mellitus. The mean creatinine clearance at the beginning of the study was 89 +/- 13 ml/min/1.73 m2 in patients with type I and 81 +/- 6 ml/min/1.73 m2 in those with type II diabetes. Dialysis was started after a mean interval of 77 (44-133) months, when creatinine clearance had decreased to 8 +/- 2 ml/min/1.73 m2 in type I diabetic patients. The respective figures for type II diabetic patients were 81 (40-124) months and 7 +/- 2 ml/min/1.73 m2. The mean rate of decrease in creatinine clearance was 1.05 +/- 0.45 ml/min/month in type I and 0.91 +/- 0.41 ml/min/month in type II diabetes. The mean rate of decrease was 1.46 +/- 0.30 ml/min/month in type I diabetic patients with a systolic BP > 160 mmHg versus 0.80 +/- 0.42 ml/min/month with < 160 mmHg (P < 0.01). In the type II diabetics the respective figures were 1.38 +/- 0.40 ml/min/month versus 0.78 +/- 0.15 ml/min/month (P < 0.01). During the observation period the prevalence of coronary heart disease increased from 6 to 50% in type I and from 31 to 87% in type II diabetes. In conclusion, the rate of progression of diabetic nephropathy during the predialytic phase is similar in type I and type II diabetes; BP adversely affects the rate of progression to the same extent in both groups.     

Control of serum phosphate without any phosphate binders in patients treated with nocturnal hemodialysis

We compared the efficacy and the long-term effects of nocturnal hemodialysis (NHD) versus conventional hemodialysis (CHD) in controlling serum phosphate levels in patients with end-stage renal disease (ESRD). Patients underwent thrice weekly CHD and were subsequently switched to NHD six nights weekly. In the "acute" study serum and dialysate phosphate were measured during and after dialysis, and the total dialysate was collected to calculate mass solute removal. Although pre-dialysis (1.7 +/- 0.6 vs. 1.5 +/- 0.8 mM) serum phosphate levels were similar in CHD and NHD, respectively, post-dialysis levels were slightly lower with CHD (0.7 +/- 0.2 vs. 0.8 +/- 0.2 mM, P < 0.05). The measured phosphate removed per session of CHD or NHD was comparable, 25.3 +/- 7.5 versus 26.9 +/- 9.8 mumol/session, respectively. On the other hand, the cumulative weekly phosphate removal was significantly higher with NHD as compared to CHD, 75.8 +/- 22.5 versus 161.6 +/- 59.0 mumol/week (P < 0.01). In the "chronic" study serum phosphate levels were measured monthly for five months on CHD and for five months after the patients were switched to NHD. Dietary phosphate intake and the dosage of phosphate binders were tabulated. Serum phosphate levels fell during NHD: 2.1 +/- 0.5 mM at the beginning of the study and 1.3 +/- 0.2 mM five months after being switched to NHD (P < 0.001). At the same time dietary phosphate intake increased by 50%. By the fourth month of NHD therapy none of the patients was taking any phosphate binders. In conclusion, NHD is more effective in controlling serum phosphate levels than CHD, allowing patients to discontinue their phosphate binders completely and to ingest a more liberal diet.     

Reduced speed of sound in tibial bone of haemodialysed patients: association with serum PTH level

BACKGROUND: In end-stage renal disease, average bone mineral density has been reported to be normal or only modestly reduced, more so in the cortical bone. The purpose of the present study was to explore the potential use of quantitative ultrasound, a method reflecting both quantitative and qualitative properties of bone, in assessing bone status in patients on maintenance haemodialysis. METHODS: We studied 71 patients (age 17-81 years, time on dialysis 0-18 years). The speed of sound waves (tSOS; m/s) propagating along the cortical bone has been determined at the tibial shaft. tSOS results were expressed as Z scores, i.e. units of standard deviations from age- and sex-matched normal mean values, and correlated with relevant clinical and biochemical variables. RESULTS: SOS Z score averaged -2. 0 (range -6.8 to 0.6; P<0.001) and was negative in 93% of the patients. Significant inverse correlations were found between SOS Z score and both time on dialysis (r=-0.52; P<0.0001) and serum PTH (r=-0.39; P=0.0002). Markedly reduced SOS Z score, below -2, was found in 80% of the patients whose PTH levels exceeded 34 pmol/l (five times the upper normal limit), compared with 43% of the patients whose PTH levels were below 34 pmol/l(P=0.04). Compared to patients without bone pain (n=51), subjects with bone pain (n=20) had somewhat lower SOS Z scores -2.5+/-2.0 versus -1.8+/-1.4; P=0. 08), but this could be accounted for by longer time on dialysis. CONCLUSIONS: tSOS is substantially reduced in the majority of haemodialysed patients and is related to time on dialysis and serum PTH level. The clinical value of this novel method needs further exploration.     

Low dialysate [K+] decreases efficiency of hemodialysis and increases urea rebound

In a previous study, it was reported that hemodialysis with dialysate [K+] (KD) of 1.0 or 2.0 mmol/L caused an increase in BP shortly after completion of treatment due to arteriolar constriction. With this background, it was hypothesized that a low KD might decrease dialysis efficiency by a similar mechanism. To evaluate this hypothesis, paired observations of two consecutive 3-h treatments, with KD of 1.0 or 3.0 mmol/L, were performed in 14 stable end-stage renal disease patients. A KD of 1.0 mmol/L resulted in lower values for both urea reduction ratio and Kt/V evaluated at completion of dialysis and 1 h thereafter. Values at equilibrium were urea reduction ratio 42+/-1% versus 47+/-2% (P < 0.02), Kt/V 0.65+/-0.03 versus 0.73+/-0.03 (P < 0.02) for KD 1.0 or 3.0 mmol/L, respectively. The mechanisms responsible for the observed differences in dialysis efficiency were examined using a urea kinetics model that predicts urea sequestration caused by impaired blood flow to urea-rich tissues. For this purpose, urea rebound and its effect on Kt/V (by means of deltaKt/V, calculated as equilibrated minus single pool value) with KD 1.0 and 3.0 mmol/L were assessed. Greater urea rebound, 12.8+/-1.6% versus 8.6+/-1.4% (P < 0.001), and larger deltaKt/V, 0.12+/-0.01 versus 0.10+/-0.02 (P < 0.02), were observed with KD 1.0 mmol/L compared with 3.0 mmol/L. The theoretical model accurately predicted the deltaKt/V observed with KD 1.0 mmol/L. It is concluded that a low KD decreases dialysis efficiency. This effect is likely caused by reduced blood perfusion to nonvisceral organs, largely skeletal muscle. Conversely, hemodialysis with KD 3.0 mmol/L facilitates tissue perfusion, minimizes urea trapping in poorly perfused areas, and improves the efficiency of this treatment modality.     

Polymorphism in the microsatellite located in the promoters of the Tnfa and Tnfb genes of different mouse strains

BACKGROUND: Hyperparathyroidism is common in patients with renal disease. These patients may require operation for this disease if it cannot be controlled by medical therapy. Because these patients continue to have renal failure, the risk of recurrence and reoperation is high. METHODS: Sixty-nine patients with renal failure underwent operation for hyperparathyroidism. These patients were followed up on dialysis or after transplantation. RESULTS: Sixty-nine patients, aged 2 to 71 years old, with end-stage renal disease required parathyroidectomy for hyperparathyroidism 6.2 +/- 4.2 (standard deviation) years after beginning dialysis. Thirty-six patients had undergone renal transplantation (creatinine = 1.6 +/- 0.4 mg/dL). All patients had elevated parathyroid hormone (PTH) levels. Sixty-eight patients had hyperplasia; 1 patient had adenoma. Six patients required reoperation for recurrent hyperparathyroidism 30 to 123 months after their initial parathyroidectomy. CONCLUSION: Patients with end-stage renal disease are prone to abnormalities of calcium metabolism. They frequently develop parathyroid hyperplasia. Recurrence can occur following operation because of continuing renal failure.     

Modulation of renal kallikrein production by dietary protein in streptozotocin-induced diabetic rats

Renal kallikrein levels and excretion rates are increased in insulin-treated diabetic rats with hyperfiltration, and inhibition of kallikrein or blockade of kinin receptors reduces GFR and RPF. In contrast, insulin-deprived severely (SD) diabetic rats that display renal vasoconstriction show reduced levels and excretion rates of renal kallikrein. In these two models, dietary protein manipulation was utilized to study further the relationships between renal kallikrein and renal hemodynamic regulation. Insulin-deprived SD and insulin-treated moderately diabetic (MD) rats were fed a low (9%), normal (25%), and a high (50%) protein diet. In SD rats fed the 50% protein diet, GFR, RPF, and kallikrein excretion rate were increased compared with SD rats fed the 25% protein diet (GFR, 2.66 +/- 0.16 versus 1.74 +/- 0.30 mL/min; RPF, 7.78 +/- 0.58 versus 5.14 +/- 1.03 mL/min; total kallikrein, 248 +/- 24 versus 120 +/- 30 micrograms/24 h, SD 50% versus SD 25%, respectively; P < 0.005). In MD rats fed the 9% protein diet, GFR, RPF, and kallikrein excretion rate were significantly reduced compared with MD 25% protein-fed rats (GFR, 1.54 +/- 0.07 versus 1.95 +/- 0.09 mL/min; RPF, 5.58 +/- 0.35 versus 7.81 +/- 0.35 mL/min; total kallikrein, 119 +/- 8.3 versus 219 +/- 15 micrograms/24 h, MD 9% versus MD 25%, respectively; P < 0.005). Protein restriction in normal nondiabetic rats resulted in a twofold decrease in kallikrein mRNA levels. These findings suggest that the renal hemodynamic response to dietary protein manipulation in diabetic rats could be mediated via changes in renal kallikrein-kinin system activity.     

Renal osteodystrophy in diabetic patients

To assess the effects of diabetes mellitus on renal osteodystrophy, we examined the database of 256 patients (45% on hemodialysis and 55% on peritoneal dialysis) who were prospectively studied in three Toronto dialysis centers between October of 1987 and 1989. All patients had serial documentation of their clinical, laboratory and risk parameters of bone disease, and completed a series of investigations that included the deferoxamine test, measurement of intact 1-84 PTH levels, and an iliac crest bone biopsy. Twenty-five percent of these patients were diabetic. When compared to non-diabetic patients, they were on dialysis for a shorter duration (2.4 +/- 0.3 vs. 4.7 +/- 0.3 years; P < 0.0002), used calcium carbonate as the only phosphate binder more frequently (40 vs. 25%; P < 0.007), and had lower parathyroid hormone levels (12 +/- 1.4 vs. 24 +/- 2.3 pmol/liter; P < 0.002). High-turnover bone disorders (that is, osteitis fibrosa and mixed disorder) were distinctly uncommon (8 vs. 33%; P < 0.01 by Fisher's exact test), while the mild (19 vs. 9%; P = NS) and the aplastic disorders (with mean stainable bone surface aluminum of 6.5 +/- 0.7%) (46 vs. 31%; P = NS) tended to be more common in diabetic patients. The prevalence of aluminum bone disease was the same in both groups (27%). Diabetic patients ingested a smaller cumulative dose of aluminum gels (3.7 +/- 0.6 vs. 9.3 +/- 1.1 kg; P < 0.005), yet had a higher rate of aluminium accumulation on bone surfaces than non-diabetic patients (1.5 +/- 0.19 vs. 0.96 +/- 0.10% per month on dialysis; P < 0.015).(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment of pre-invasive conditions during opportunistic screening and its effectiveness on cervical cancer incidence in one Norwegian county

OBJECTIVE: To identify a correlation between dialysis treatment duration and severity of acquired cystic disease of the end-stage kidney measured by cyst sizes; and assess its effect on spontaneous improvement of anemia. MATERIALS AND METHODS: Ten patients, 6 males and 4 females were selected, who have been on hemodialytic treatment for more than 5 years. There was no patient selected with autosomal dominant polycystic kidney disease. The renal evaluation has been made through ultrasonographic studies. Acquired cystic disease of the end-stage kidney was characterized by finding four or more cysts in both kidneys. The largest cysts were measured for correlation effect. The diagnosis of anemia was established by hematocrit and hemoglobin serum values. It has also been analyzed serum urea, creatinine, albumin, iron, total iron-binding capacity and the per cent saturation of serum transferrin were tested. RESULTS: The patients were properly dialysed (serum urea and creatinine = 98.7 +/- 35 mg/dL e 9.7 +/- 2.7 mg/dL, respectively). There were in good nutritional shape (serum albumin = 4.5 +/- 0.5 g/dL) and had normal serum iron level (serum iron = 80 +/- 34 mg/dL). The prevalence of acquired renal cystic disease was 80%. No finding of malignancy has been detected in these cysts. There was a significant correlation between time on dialysis treatment and hematocrit values (R = 0.70; p < 0.05). Cyst sizes had a direct and significant correlation with hematocrit levels (R = 0.74; p < 0.05). CONCLUSION: These results show that spontaneous improvement on anemia seen in patients on chronic dialysis has a significant correlation with the severity of acquired cystic disease of the end-stage kidney. Our data suggest a functional role of acquired kidney cysts on endogenous erythropoietin production.     

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.     

Time of diagnosis of chronic renal failure and assessment of quality of life in haemodialysis patients

BACKGROUND: Time of diagnosis of chronic renal failure ani predialysis care may be important factors related to the quality of life of patients on dialysis treatment. METHODS: We evaluated the quality of life of 113 haemodialysis patients who had a late (< or = 1 month before starting dialysis, n = 53) or early (> or = 6 months, n = 60) diagnosis of chronic renal failure. At the time of the survey patients had been on dialysis for a median duration of 55 days (range 1-109). Quality of life was measured by the Kidney Disease Questionnaire (KDQ), including five dimensions with scales ranging from 1.0 to 7.0 (1.0 = more impairment): the health and life satisfaction indices (higher score = more dissatisfied), functional status (Karnofsky scale), and the time trade-off technique. RESULTS: Mean scores of quality of life measures were worse in the late- than in the early-diagnosis group. A significant difference (P < 0.05) was observed in the depression (4.46 +/- 1.45 vs 5.23 +/- 1.36), relationships with others (3.95 +/- 1.31 vs 4.53 +/- 1.31) and frustration (4.08 +/- 1.51 vs 5.21 +/- 1.34) dimensions of the KDQ. and in life satisfaction (4.11 +/- 1.92 vs 3.32 +/- 1.57). Functional status declined compared to 1 year before dialysis, particularly in the late-diagnosis group. Among the elderly patients, the magnitude of the difference was more pronounced, (including in the physical symptoms item of the KDQ). CONCLUSIONS: Our findings demonstrate that late diagnosis of chronic renal failure and the consequent lack of predialysis care adversely affect the quality of life of haemodialysis patients. Early diagnosis and regular predialysis care should be encouraged to improve the quality of life during dialysis treatment.     

Cloning and characterization of a novel membrane-associated antigenic protein of Helicobacter pylori

BACKGROUND: The aim of this study was to evaluate the effect of convective [hemodiafiltration (HDF) or hemofiltration (HF)] versus diffusive treatments [hemodialysis (HD)] on end-stage renal disease (ESRD) patient mortality and dialysis-related amyloidosis (DRA) using data from the Lombardy Registry. METHODS: For this purpose, 6, 444 patients (aged 56.4 +/- 15.6 years, females 39.5%, diabetics 10. 6%) who started renal replacement therapy (RRT) on HD, HDF, or HF between 1983 and 1995 were considered. A total of 1,082 patients were treated with HDF or HF (first choice in the case of 188), with a median follow-up of 29.7 months. The median follow-up of the 6,298 patients on HD (first choice in the case of 6256) was 22.4 months. The time of survival on dialysis to carpal tunnel syndrome (CTS) surgery was evaluated as a hard marker of DRA morbidity. Survival was compared by means of the Cox proportional regression hazards model, using CTS surgery and all deaths as events for morbidity and mortality, respectively. Explanatory covariates were age, gender, and comorbidities; dialysis modality was tested as a time-dependent covariate. RESULTS: The relative risk (RR) for CTS surgery was significantly higher in older patients [RR = 1.04 per year of age on admission to RRT, 95% confidence interval (CI) 1.02 to 1.06; P = 0. 0001], in diabetics (RR = 2.63, 95% CI 1.30 to 5.31; P = 0.0007), and in patients with heart disease (RR = 5.36, 95% CI 2.27 to 12.68 P = 0.0001). Adjusting for age and diabetic status, the RR for CTS surgery was 42% lower in the patients treated with HDF or HF (RR = 0. 58, 95% CI 0.35 to 0.95, P = 0.03). The RR for mortality, adjusted for age, gender, and comorbidities, was 10% lower in patients treated with HDF or HF (RR = 0.90, 95% CI 0.76 to 1.06; P = NS). CONCLUSION: These results support the hypothesis that convective treatments are associated with a nonsignificant trend toward better survival and significantly delay the need for CTS surgery. An older age and the presence of diabetes and heart disease are other important risk factors for CTS surgery. These results could have an important clinical impact given the relevance of DRA in dialysis patient morbidity.     

Immunoperoxidase staining in the differential diagnosis of parathyroid from thyroid origin in fine needle aspirates of suspected parathyroid lesions

Release of glucose by liver and kidney are both increased in diabetic animals. Although the overall release of glucose into the circulation is increased in humans with diabetes, excessive release of glucose by either their liver or kidney has not as yet been demonstrated. The present experiments were therefore undertaken to assess the relative contributions of hepatic and renal glucose release to the excessive glucose release found in type 2 diabetes. Using a combination of isotopic and balance techniques to determine total systemic glucose release and renal glucose release in postabsorptive type 2 diabetic subjects and age-weight-matched nondiabetic volunteers, their hepatic glucose release was then calculated as the difference between total systemic glucose release and renal glucose release. Renal glucose release was increased nearly 300% in diabetic subjects (321+/-36 vs. 125+/-15 micromol/min, P < 0.001). Hepatic glucose release was increased approximately 30% (P = 0.03), but increments in hepatic and renal glucose release were comparable (2.60+/-0.70 vs. 2.21+/-0.32, micromol.kg-1.min-1, respectively, P = 0.26). Renal glucose uptake was markedly increased in diabetic subjects (353+/-48 vs. 103+/-10 micromol/min, P < 0.001), resulting in net renal glucose uptake in the diabetic subjects (92+/-50 micromol/ min) versus a net output in the nondiabetic subjects (21+/-14 micromol/min, P = 0.043). Renal glucose uptake was inversely correlated with renal FFA uptake (r = -0.51, P < 0.01), which was reduced by approximately 60% in diabetic subjects (10. 9+/-2.7 vs. 27.0+/-3.3 micromol/min, P < 0.002). We conclude that in type 2 diabetes, both liver and kidney contribute to glucose overproduction and that renal glucose uptake is markedly increased. The latter may suppress renal FFA uptake via a glucose-fatty acid cycle and explain the accumulation of glycogen commonly found in the diabetic kidney.     

Tooth recontouring/reshaping a must in the preparation for removable partial denture

OBJECTIVE: To assess the extent of functional and vocational rehabilitation achieved by elderly inner-city patients sustained on maintenance hemodialysis. DESIGN: Inception cohort study of elderly patients who have end-stage renal disease using a modified Karnofsky rating system. The need for a wheelchair, participation in household activities, and effect of comorbid conditions were noted. Current status was compared with patient's recollection of functional activity level 2 years before commencing maintenance hemodialysis. SETTING: Seven outpatient, hospital-affiliated and private hemodialysis units in Brooklyn, NY. PATIENTS: One hundred four patients aged 65 years or older who were receiving maintenance hemodialysis for at least 6 months. MAIN OUTCOME MEASURES: A score of 76 or greater on a modified Karnofsky scale indicated independent function at a level that permitted participation in activities beyond those mandated by the hemodialysis regimen. A comorbidity score 6 or greater on a newly constructed index correlated with severe debility. Employment status was also recorded. RESULTS: Present functional activity had deteriorated to a modified Karnofsky score of 66 +/- 12.3 (+/- SD) compared with patients' recollection of a mean score of 84 +/- 14.3 (P < .001) 2 years before initiation of hemodialysis. Diabetic patients had a lower score than nondiabetic patients. The mean comorbidity index of the entire study group was 7.8 +/- 2.9 (mean +/- SD). Within the diabetic subset, severe debility constrained 71 patients (68%) to limit all activity to their residence with the exception of travel to and from their dialysis facility. By contrast, 2 years prior to commencing dialytic therapy, 81 diabetic patients (78%) had interests and activities that took them outside their homes (P < .001). Generalized weakness was the most common explanation given for the lack of outside activity by nine patients (9%) who were wheelchair bound. Erythropoietin, though regularly administered to 87 patients (84%) in the study group, was unsuccessful in raising mean hematocrit reading above 0.28 +/- 0.05 (mean +/- SD). CONCLUSIONS: Maintenance hemodialysis does not return inner-city elderly patients to their predialysis level of functioning. Few elderly, diabetic hemodialysis patients conduct any substantive portion of their lives outside their homes. For nondiabetic patients, the modified Karnofsky score of whites (70.4 +/- 11.9) and blacks (66.5 +/- 15.3), though low, was equivalent (P < .4).     

Serum ionic fluoride levels in haemodialysis and continuous ambulatory peritoneal dialysis patients

High serum fluoride (F-) in patients with chronic renal failure (CRF) and end-stage renal disease (ESRD) is associated with risk of renal osteodystrophy and other bone changes. This study was done to determine F- in normal healthy controls and patients with ESRD on haemodialysis (HD) or peritoneal dialysis (PD). Seventeen healthy controls (12 males, 5 females) and 39 ESRD patients on dialysis (17 males, 22 females) were recruited in the study in a community with 47.4 +/- 3.28 microM/l (range 44-51 microM/l) of F- content in drinking water. Control subjects showed a mean serum F- concentration of 1.08 +/- 0.350 microM/l. Males in control group showed slightly higher F- levels (1.15 +/- 0.334, range 0.55-1.9 microM/l) than females (0.92 +/- 0.370, range 0.6-1.5 microM/l). Mean serum F- concentration did not correlate significantly with age and sex among control subjects, whereas such correlation was observed in patients with ESRD on dialysis. Mean serum F- concentration was significantly higher in patients on dialysis (2.67 +/- 1.09, range 0.8-5.2 microM/l) than normal controls. When grouped according to sex, the mean serum F- concentration in males (3.05 +/- 1.04, range 1.8-5.2 microM/l) was significantly higher than females (2.38 +/- 1.08, range 0.8-5.2 microM/l). When patients were grouped according to age, it was observed that F- concentration was significantly higher in patients with age groups 21-70 (2.86 +/- 1.05) than those with age group 13-20 years (1.42 +/- 0.531). Thus F- concentration correlated with age and sex, being higher in males and above 20 years. Despite appreciable clearance of F- (39-90%) across the peritoneum, patients on CAPD showed higher serum F- concentration than those on HD (3.1 +/- 1.97 vs 2.5 +/- 1.137 microM/l). Of the total 39 patients on dialysis 39% had their serum F- concentration above 3.0 microM/l, posing the risk of renal osteodystrophy.     

Global alteration in perfusion response to increasing oxygen consumption in patients with single-vessel coronary artery disease

BACKGROUND: Recent evidence suggests that, in coronary artery disease (CAD), myocardial blood flow (MBF) regulation is abnormal in regions supplied by apparently normal coronary arteries. However, the relation between this alteration and MBF response to increasing metabolic demand has not been fully elucidated. METHODS AND RESULTS: MBF was assessed at baseline, during atrial pacing tachycardia, and after dipyridamole (0.56 mg/kg IV over 4 minutes) in 9 normal subjects and in 24 patients with ischemia on effort, no myocardial infarction, and isolated left anterior descending (n = 19) or left circumflex (n = 5) coronary artery stenosis (> or = 50% diameter narrowing). Perfusion of both poststenotic (S) and normally supplied (N) areas was measured off therapy by positron emission tomography and [13N]ammonia. Normal subjects and CAD patients showed similar rate-pressure products at baseline, during pacing, and after dipyridamole. In CAD patients, MBF was lower in S than in N territories at rest (0.68 +/- 0.14 versus 0.74 +/- 0.18 mL.min-1.g-1, respectively, P < .05), during pacing (0.92 +/- 0.29 versus 1.16 +/- 0.40 mL.min-1.g-1, respectively, P < .01), and after dipyridamole (1.18 +/- 0.34 versus 1.77 +/- 0.71 mL.min-1.g-1, respectively, P < .01). However, normal subjects showed significantly higher values of MBF both at rest (0.92 +/- 0.13 mL.min-1.g-1, P < .05 versus both S and N areas), during pacing tachycardia (1.95 +/- 0.64 mL.min-1.g-1, P < .01 versus both S and N areas), and after dipyridamole (3.59 +/- 0.71 mL.min-1.g-1, P < .01 versus both S and N areas). The percent change in flow was strictly correlated with the corresponding change in rate-pressure product in normal subjects (r = .85, P < .01) but not in either S (r = .04, P = NS) or N regions (r = .08, P = NS) of CAD patients. CONCLUSIONS: Besides epicardial stenosis, further factors may affect flow response to increasing metabolic demand and coronary reserve in patients with CAD.     

Effects of injection rates of contrast material on arterial phase hepatic CT

PURPOSE: The aim of our study was twofold: to determine the frequency and magnitude of perfusion defect in stroke patients who qualify for rtPA therapy within 3 hours of stroke onset and to determine the ability of rtPA to improve perfusion by 24 hours. SUBJECTS AND METHODS: Patients with suspected hemispheric stroke who fulfilled entry criteria into the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study and also had pretreatment injection of (99m)Tc-HMPAO, with single-photon emission computed tomography (SPECT) performed using a triple-head camera at baseline and 24 hours, were included. RESULTS: All 12 patients who qualified for rtPA therapy had perfusion defects on baseline SPECT (SPECT graded scale [SGS] score range, 16 to 79). Mean+/-SD perfusion defect was comparable in rtPA (n=4)versus placebo (n=5) groups (SGS score, 36+/-18 versus 39+/-12; NS) despite earlier injection time in the rtPA group (98+/-24 versus 141+/-21 minutes; P=.02). Total SPECT scanning time was 20 to 25 minutes. At 24 hours, reperfusion was greater in rtPA patients compared with the placebo group (SGS score, 7+/-9 versus 29+/-17; P=.05), with relative improvement in the region-of-interest scores of 87+/-16% after rtPA compared with 28+/-30% with placebo (P=.01). CONCLUSIONS: A substantial perfusion defect exists in stroke patients with larger hemispheric infarcts who meet NINDS criteria for rtPA therapy, and rtPA is better able than placebo to rectify this defect. SPECT is feasible for clinical trials and should be evaluated as a substituted end point in stroke therapeutic trials.     

Hyperinsulinism in patients with coronary artery disease

AIM: To assess the clinical impact of hyperinsulinism and major coronary risk factors in patients with angiographically documented or excluded coronary artery disease (CAD), a clinical study was carried out in 268 men admitted for left heart catheterization. METHODS: Fasting immunoreactive insulin (IRI) levels were correlated to all major cardiovascular risk factors and to the presence and degree of CAD. RESULTS: IRI levels were correlated significantly with the degree of CAD (one-vessel disease: mean IRI 9.45 microU/ml +/- 0.43 SEM; two-vessel disease: mean IRI 10.4 microU/ml +/- 0.71 SEM; three-vessel disease: mean IRI 11.88 microU/ml +/- 0.98 SEM) and inversely to the high-density lipoprotein level (P < 0.05). In patients with arterial hypertension, IRI levels were elevated, without a significant difference between those with and those without CAD, whereas the IRI levels of non-hypertensive men with CAD (n = 81; mean IRI 9.85 microU/ml +/- 0.51 SEM) differed significantly (P < 0.05) from those of non-hypertensive men without CAD (n = 59; mean IRI 7.76 microU/ml +/- 0.43 SEM). IRI levels were significantly higher (P < 0.05) in obese patients (n = 65; mean IRI 11.68 microU/ml +/- 0.70 SEM versus n = 203; mean IRI 9.32 microU/ml +/- 0.34 SEM), in patients with elevated triglycerides (n = 58 mean IRI 11.59 microU/ml +/- 0.81 SEM versus n = 210; mean IRI 9.42 microU/ml +/- 0.33 SEM), and in patients with lowered HDL cholesterol (n = 178; mean IRI 11.06 microU/ml +/- 0.63 SEM versus n = 90; mean IRI 9.29 microU/ml +/- 0.34 SEM). Diabetic patients on angiotensin converting enzyme inhibitor therapy (n = 11; mean IRI 7.91 microU/ml +/- 0.91 SEM) had significantly (P < 0.05) lower IRI levels than those not treated with ACE inhibitors (n = 25; mean IRI 12.96 microU/ml +/- 1.47 SEM). IRI levels exceeding 8 microU/ml were associated with a 1.98-fold risk for CAD compared with IRI levels below 8 microU/ml. Stepwise logistic regression showed that insulin was an independent determinant of CAD. CONCLUSION: Knowledge of the fasting insulin level is an important contribution to the identification of patients with, or at risk of, CAD.