Factors affecting peritoneal dialysis selection in Taiwanese patients with chronic kidney disease.

BACKGROUND: Taiwan has the highest incidence and prevalence of end-stage renal disease (ESRD) in the world with 55,499 ESRD patients on long-term dialysis. Nevertheless, 90.96% of these patients are managed on maintenance haemodialysis (HD), with only 9.03% enrolled in a peritoneal dialysis (PD) programme. AIM: The study aim was to identify the factors affecting Taiwanese patient's selection of PD in preference to HD for chronic kidney disease. METHODS: A cross-sectional research design was utilized with 130 chronic renal failure (CRF) patients purposively selected from outpatient nephrology clinics at four separate Taiwan hospitals. Logistic regression was used to identify the main factors affecting the patient's choice of dialysis type. RESULTS: Single-factor logistic regression found significant differences in opinion related to age, education level, occupation type, disease characteristics, lifestyle modifications, self-care ability, know-how of dialysis modality, security considerations and findings related to the decisions made by medical personnel (P < 0.05). Moreover, multinomial logistic regression after adjustment for interfering variables found that self-care ability and dialysis modality know-how were the two main factors affecting the person's selection of dialysis type. CONCLUSIONS: Self-care ability and the person's knowledge of the different types of dialysis modality and how they function were the major determinants for selection of dialysis type in Taiwan based on the results from this study. The results indicate that the education of CRF patients about the types of dialysis available is essential to enable them to understand the benefits or limitations of both types of dialysis.

Growth of multiple metal/semiconductor nanoheterostructures through point and line contact reactions.

Forming functional circuit components in future nanotechnology requires systematic studies of solid-state chemical reactions in the nanoscale. Here, we report efficient and unique methods, point and line contact reactions on Si nanowires, fabricating high quality and quantity of multiple nanoheterostructures of NiSi/Si and investigation of NiSi formation in nanoscale. By using the point contact reaction between several Ni nanodots and a Si nanowire carried out in situ in an ultrahigh vacuum transmission electron microscopy, multiple sections of single-crystal NiSi and Si with very sharp interfaces were produced in a Si nanowire. Owing to the supply limited point contact reaction, we propose that the nucleation and growth of the sugar cane-type NiSi grains start at the middle of the point contacts between two Ni nanodots and a Si nanowire. The reaction happens by the dissolution of Ni into the Si nanowire at the point contacts and by interstitial diffusion of Ni atoms within a Si nanowire. The growth of NiSi stops as the amount of Ni in the Ni nanodots is consumed. Additionally, without lithography, utilizing the line contact reaction between PS nanosphere-mediated Ni nanopatterns and a nanowire of Si, we have fabricated periodic multi-NiSi/Si/NiSi heterostructure nanonowires that may enhance the development of circuit elements in nanoscale electronic devices. Unlike the point contact reaction, silicide growth starts at the contact area in the line contact reaction; the different silicide formation modes resulting from point and line contact reactions are compared and analyzed. A mechanism on the basis of flux divergence is proposed for controlling the growth of the nano-multiheterostructures.

Suppressive effect of COX2 inhibitor on the progression of adipose inflammation in high-fat-induced obese rats.

BACKGROUND: The aim was to examine whether the inhibition of selective cyclooxygenase (COX) 2 activation could suppress the development of inflammatory reaction in visceral and subcutaneous abdominal fats of high-fat-induced obese rats. MATERIALS AND METHODS: The rats were fed separately regular diet (CONT), high-fat diet ad libitum or energy-restrictedly (HFr) for 12 weeks. Rats fed high-fat diet ad libitum were further divided into those co-treated with vehicle (HFa), a selective COX2 inhibitor-celecoxib (HFa-Cel) or nimesulide (HFa-Nim). Oral glucose tolerance test (OGTT) was performed at the end of weeks 4, 8, 12. Another set of rats with similar grouping was divided into those with a 4-, 8- or 12-week intervention for tissue sampling. RESULTS: Body and epididymal fat weights were increased similarly in HFa, HFa-Cel and HFa-Nim. Time-dependent increases in plasma insulin, triglyceride, impaired OGTT shown in HFa were significantly reversed in HFa-Cel and HFa-Nim. The obese-linked increases in gene expressions of COX-2, monocyte chemoattractant protein-1 (MCP-1) and tumour necrosis factor-alpha (TNF-alpha) in epididymal and subcutaneous fats (especially in the former) were significantly suppressed in HFa-Cel and HFa-Nim. The protein contents of MCP-1 and TNF-alpha in epididymal fats were changed consistently with their gene expressions. Plasma MCP-1 was increased time-dependently in HFa and suppressed in HFa-Cel and HFa-Nim. The increased CD68 positive cells showed in both epididymal and subcutaneous fats of HFa were significantly attenuated in HFa-Cel and HFa-Nim. CONCLUSIONS: Our findings suggest that COX2 activation is crucially involved in the development of inflammatory response in adipose tissues of high-fat-induced obese rats.

Angiostatin K1-3 induces E-selectin via AP1 and Ets1: a mediator for anti-angiogenic action of K1-3.

BACKGROUND: Angiostatin, a circulating angiogenic inhibitor, is an internal fragment of plasminogen and consists of several isoforms, K1-3 included. We previously showed that K1-3 was the most potent angiostatin to induce E-selectin mRNA expression. The purpose of this study was to identify the mechanism responsible for K1-3-induced E-selectin expression and investigate the role of E-selectin in the anti-angiogenic action of K1-3. METHODS AND RESULTS: Quantitative real time RT-PCR and Western blotting analyses confirmed a time-dependent increase of E-selectin mRNA and protein induced by K1-3. Subcellular fractionation and immunofluorescence microscopy showed the co-localization of K1-3-induced E-selectin with caveolin 1 (Cav1) in lipid rafts in which E-selectin may behave as a signaling receptor. Promoter-driven reporter assays and site-directed mutagenesis showed that K1-3 induced E-selectin expression via promoter activation and AP1 and Ets-1 binding sites in the proximal E-selectin promoter were required for E-selectin induction. The in vivo binding of both protein complexes to the proximal promoter was confirmed by chromatin immunoprecipitation (ChIP). Although K1-3 induced the activation of ERK1/2 and JNK, only repression of JNK activation attenuated the induction of E-selectin by K1-3. A modulatory role of E-selectin in the anti-angiogenic action of K1-3 was manifested by both overexpression and knockdown of E-selectin followed by cell proliferation assay. CONCLUSIONS: We show that K1-3 induced E-selectin expression via AP1 and Ets-1 binding to the proximal E-selectin promoter (-356/+1), which was positively mediated by JNK activation. Our findings also demonstrate E-selectin as a novel target for the anti-angiogenic therapy.

Incidence and factors predictive of acute renal failure in patients with advanced liver cirrhosis.

BACKGROUND: Acute renal failure (ARF) is a life-threatening entity that frequently complicates advanced liver disease. This study documents a number of factors that may predispose to or precipitate ARF and influence outcomes in patients with advanced liver disease. Comparisons are also made between subgroups of patients with viral and alcohol-induced liver cirrhosis in those with ARF. PATIENTS AND METHODS: We conducted a retrospective chart review over one year of 127 consecutive hospital admissions in 82 patients who were diagnosed with advanced liver cirrhosis (Child-Pugh Class C) in a tertiary care center. A diagnosis of ARF was made in 29 admissions and another 98 admissions not complicated by ARF served as controls. This study evaluated different etiologies of ARF and developed a database which included clinical features, biochemical parameters, the etiology of cirrhosis, possible predisposing factors, and precipitating events. Version II of the Acute Physiology and Chronic Health Physiology Scoring system (APACHE II) was applied to predict short-term hospital mortality rates. RESULTS: ARF occurred in 29 admissions over the one-year study period (23%). The mean age of these patients was 56.8 +/- 12.0 years, and 73% were men. The patients with ARF had significant hyponatremia and higher levels of serum bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and white cell counts on admission than the controls. Patients who developed ARF were more likely to have had infection, especially septicemia, and gastrointestinal (GI) bleeding. Mortality rate in the patients with ARF was much higher than in those patients without ARF (72% vs. 13%, p < 0.001). The patients with viral cirrhosis and ARF were found to have higher leukocyte counts, serum bilirubin levels, and more frequent incidence of infection, septicemia and GI bleeding compared to the patients with alcoholic liver cirrhosis and ARF. Those with viral hepatitis were also significantly older and had more frequent incidence of ascites, but had lower levels of gamma-glutamyl transpeptidase and less frequent incidence of encephalopathy. CONCLUSIONS: The risk of ARF is significantly increased in patients with advanced liver cirrhosis presenting with marked hyperbilirubinemia, hyponatremia, elevated liver enzymes, infection, and GI bleeding. The presence of ARF leads to higher mortality rates in both viral and alcohol-induced liver cirrhosis.

Apoptotic markers on lymphocytes and monocytes are unchanged during single hemodialysis sessions using either regenerated cellulose or polysulfone membranes.

BACKGROUND: There is an increased rate of apoptosis of peripheral blood mononuclear cells (PBMCs) in patients undergoing hemodialysis (HD), but little is known about how different dialysis membranes may contribute to the process. We, therefore, studied the influence of two different dialysis membranes on apoptotic markers during HD. METHODS: 8 healthy controls and 8 patients on regular HD 3 times per week were enrolled in this cross-controlled study. Patients received HD using polysulfone and then regenerated cellulose dialysis membranes for one week each, sequentially. Serum was collected for C-reactive protein (CRP) detection; flow cytometry with dual antibody staining was used to measure the apoptotic markers Fas (CD95), FasL (CD 178) and TNF-R2 (CD120b) in T cells (CD3+), B cells (CD19+), and monocytes (CD14+) at 0, 15, 120 and 240 min after starting HD. We also measured total leukocyte numbers and differential white cell counts. RESULTS: Hemodialysis patients revealed lymphocytopenia, monocytopenia, higher CRP levels and higher Fas and TNF-R2 expression on lymphocytes and monocytes at baseline when compared with normal controls. Leukocyte numbers, including neutrophils, lymphocytes and monocytes, dropped significantly after 15 min of dialysis. There were no significant differences in Fas levels during hemodialysis on T and B lymphocytes or on monocytes. T lymphocyte FasL (CD 178) levels remained unchanged throughout the process. There was a significantly lower overall level of CD120b at 15 min of HD, whereas this marker was higher on monocytes after dialysis. There were no significant differences in the levels of apoptotic markers between the two membranes. CONCLUSION: Our results suggest that uremia itself contributes to PBMC apoptosis. The two different dialysis membranes used in this study did not influence apoptotic markers on PBMCs significantly, but increased TNF-R2 expression on monocytes during a single dialysis session.

Prevention of obliterative airway disease in HLA-A2-transgenic tracheal allografts by neutralization of tumor necrosis factor.

BACKGROUND: Inflammatory cytokines play an important role in the development of experimental obliterative airway disease (OAD) after transplantation. To further determine the immunologic mechanisms associated with OAD development, we used a murine tracheal transplant model in which a single mismatched HLA-A2-transgenic molecule is indirectly recognized by the recipient CD4+ T cells and then determined whether neutralization of several inflammatory cytokines affected the development of OAD. METHODS: Tracheas from HLA-A2+ C57BL/6 mice were heterotopically transplanted into C57BL/6 mice. Recipients were treated with neutralizing antibodies against tumor necrosis factor (TNF), interferon-gamma (IFN-gamma), or interleukin-1 (IL-1). Allograft histology as well as anti-HLA-A2 antibody development and T cell proliferative responses were determined at days +5, +15, +28, and +60. RESULTS: Allografts in untreated and anti-IFN-gamma-treated recipients demonstrated full development of OAD by day +28. Allografts in anti-TNF-treated recipients showed no evidence of OAD, even at day +60. Allografts in anti-IL-1-treated recipients showed airway epithelium changes by day +28 but minimal evidence of OAD by day +60. Spleen cells from untreated and anti-IFN-gamma-treated recipients showed significantly higher proliferative responses to HLA-A2+ cells, compared with syngeneic recipients (negative controls). In contrast, anti-TNF and anti-IL-1-treated recipients showed significantly lower proliferative responses to HLA-A2+ cells, compared with untreated recipients. Development of anti-HLA-A2 antibodies was detected in all recipients by day +15, with the exception of those treated with anti-TNF. CONCLUSION: Among the inflammatory cytokines, TNF seems to play a crucial role in the immunopathology of OAD developed after transplantation.

Western and Chinese antirheumatic drug-induced T cell apoptotic DNA damage uses different caspase cascades and is independent of Fas/Fas ligand interaction.

Spontaneous or therapeutic induction of T cell apoptosis plays a critical role in establishing transplantation tolerance and maintaining remission of autoimmune diseases. We investigated the mechanisms of apoptosis induced by Chinese and Western antirheumatic drugs (ARDs) in human T cells. We found that hydroxychloroquine, Tripterygium wilfordii hook F, and tetrandrine (Tet), but not methotrexate, at therapeutic concentrations can cause T cell death. In addition, Tet selectively killed T cells, especially activated T cells. Although ARD-induced cytotoxicity was mediated through apoptotic mechanisms, Fas/Fas ligand interaction was not required. We further demonstrated that the processes of phosphatidylserine externalization and DNA damage along the ARD-induced T cell apoptotic pathway could operate independently, and that selective inhibition of DNA damage by caspase inhibitors did not prevent T cells from undergoing cell death. Moreover, we found that Tet- and Tripterygium wilfordii hook F-induced T cell DNA damage required caspase-3 activity, and hydroxychloroquine-induced T cell DNA damage was mediated through a caspase-3- and caspase-8-independent, but Z-Asp-Glu-Val-Asp-fluomethyl ketone-sensitive, signaling pathway. Finally, the observation that ARD-induced activation of caspase-3 in both Fas-sensitive and Fas-resistant Jurkat T cells indicates that Fas/Fas ligand interaction plays no role in ARD-induced T cell apoptosis. Our observations provide new information about the complex apoptotic mechanisms of ARDs, and have implications for combining Western and Chinese ARDs that have different immunomodulatory mechanisms in the therapy of autoimmune diseases and transplantation rejection.

Acute correction of metabolic acidosis increases serum procollagen type I carboxyterminal propeptide in patients with chronic renal failure.

BACKGROUND AND PURPOSE: Previous in vitro study has shown that an acidic medium increases osteoclastic and inhibits osteoblastic activity. The present study sought to determine the role of alkali therapy in osteoblast function in patients with chronic renal failure by assessing the serum concentration of procollagen type I carboxyterminal propeptide (PICP), a marker of bone formation, before and after bicarbonate infusion. PATIENTS AND METHODS: Eighteen patients with chronic renal failure (creatinine clearance 12 +/- 6.6 mL/min) associated with mild to moderate metabolic acidosis were enrolled in this study. None had undergone dialysis. Metabolic acidosis was corrected by continuous bicarbonate infusion while plasma ionized calcium was clamped at the preinfusion level by calcium gluconate infusion throughout the procedure. RESULTS: After bicarbonate infusion, there were significant increases in plasma pH (7.31 +/- 0.04 to 7.40 +/- 0.03, p < 0.001), bicarbonate concentration (18.46 +/- 2.49 to 23.66 +/- 2.72, p < 0.001), serum total calcium concentration (2.01 +/- 0.24 to 2.12 +/- 0.24 mmol/L, p < 0.001), and PICP concentration (137.3 +/- 56.25 to 159.6 +/- 57.30 micrograms/L, p < 0.05), whereas serum parathyroid hormone concentrations assessed by radioimmunoassay decreased significantly (153.7 +/- 88.6 to 111.5 +/- 78.7, p < 0.001). Serum ionized calcium concentrations showed no significant difference before and after bicarbonate infusion. CONCLUSION: These results suggest that acute correction of metabolic acidosis improves osteoblast function and appear to underline the importance of maintaining normal acid-base homeostasis in chronic renal failure.

Energy metabolism in exertional heat stroke with acute renal failure.

BACKGROUND: Heat stroke is the clinical syndrome produced when the body overheats. It can develop in the army and in healthy civilian populations who physically exert themselves in a hot and humid environment during the summer, and may result in a significant number of heat-related deaths. Since strenuous exercise is one of the major exacerbating and precipitating factors, the incidence of exertional heat stroke (ExHS) is high among military personnel undergoing military training. Furthermore, acute renal failure (ARF) may occur in 25% of patients with ExHS and it can cause metabolic alterations that affect amino acid, carbohydrate, and lipid metabolism. Adequate nutritional support is essential for the treatment of ARF. The most important determinant of nutrient requirement in ARF is the degree of hypercatabolism caused by disease associated with renal function impairment. Indirect calorimetry (IDCM) is the method by which metabolic rate is estimated from measurements of oxygen consumption and carbon dioxide production. It can also provide information about the type and rate of substrate utilization in vivo (protein, carbohydrate, and fat). METHOD: The present clinical study is a comprehensive analysis of metabolic changes which includes energy expenditure (EE) and substrate utilization in 10 patients with ExHS with ARF and 10 patients with exertional heat exhaustion (ExHE) by the use of IDCM. RESULTS: Serum urea nitrogen, creatinine, peak creatine phosphokinase levels and heart rate were significantly increased in ExHS patients during ARF stage. Serum albumin levels were significantly decreased in ExHS patients with ARF. Resting energy expenditure (REE) was increased in patients with ExHS induced ARF and was not correlated with body temperature (r = 0.421). The average increase in EE during ARF stage was about 24%. The respiratory quotient in patients with ExHS induced ARF was lower than that in normal subjects and also in patients with ExHE. Urea nitrogen appearance rate increased in patients with ExHS induced ARF and in patients with ExHE without ARF. The percentage of total REE derived from fat in ExHS induced ARF and ExHE increased, while in patients with ExHS induced ARF and ExHE, the percentages of total REE derived from carbohydrate and protein were lower than those in control subjects. CONCLUSIONS: The present results suggest that patients with exertional heat injury (both ExHS and ExHE) have hypermetabolism during the acute stage. Furthermore, patients with exertional heat-induced rhabdomyolysis and ARF have a moderately higher hypermetabolism than those without ARF during the acute stage. We believe that this mainly reflects a more pronounced reduction of the vital cell mass (muscle) in relation to body weight, and/or a compromised substrate oxidation in ExHS with ARF. Whether or not this subgroup of patients will require a higher energy/caloric support merits further investigation.

Infective endocarditis complicated with rapidly progressive glomerulonephritis: a case report.

A 26-year-old man who had suffered from intermittent chills and fever over a two month period was quite clear of heart or kidney involved developed acute deterioration of renal function. A new pansystolic murmur over the apex of the heart was heard on auscultation, and echocardiography clearly showed a vegetation about 0.7-0.9 cm in size on the atrial site of the mitral value. Laboratory investigation displayed normochromic anemia with negative Coombs' test. Immunological studies were positive for rheumatoid factor and circulating immune complex. High serum levels of erythrocyte sedimentation rate and C-reactive protein, nephritic sediment of urinalysis and negative blood cultures for bacteria, tuberculosis or fungus were also noted. Abdominal sonography showed normal kidney size, bilaterally. Renal biopsy revealed typical crescentic glomerulonephritis. After intravenous penicillin therapy for two weeks, the serum creatinine level recovered from 6.7 mg/dl to 2.0 mg/dl and circulating immune complex disappeared. In consideration of cardiac insufficiency and the potential risk for complications of the vegetation, the patient underwent mitral valve replacement. Four weeks after operation, all the abnormal data had resolved completely. These data suggested that infective endocarditis with rapidly progressive glomerulonephritis is curable by antibiotic therapy and surgical intervention.

Cytokine production during hemodialysis: effects of dialytic membrane and complement activation.

Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are closely associated with acute and chronic inflammatory processes in hemodialytic patients. However, the mechanisms concerning cytokine production by monocytes during hemodialysis are still conflicting. With the use of the more specific monoclonal antibody ELISA method, contamination detection and crossover protocol of complement-activating and noncomplement-activating hollow fibers, we were able to confirm augmented II-1 beta production by zymosan-stimulated monocytes with complement-activating hollow fiber as compared to noncomplement-activating hollow fiber before (1,411.9 +/- 865.7 +/- 149.9 pg/ ml/2 x 10(6) monocytes, p < 0.01). at the 15th minute (530.6 +/- 89.1 vs. 247.3 +/- 45.2 pg/ml/2 x 10(6) monocytes, p < 0.01) and at the end of dialysis (1,201.8 +/- 135.1 vs. 707.4 +/- 109.3 pg/ml/2 x 10(6) monocytes, p < 0.01). Similar results were observed with TNF-alpha production. IL-1 beta as well as TNF-alpha production decreased significantly at the 15th min of dialysis, thereafter they increased and approached the baseline levels towards the end of hemodialysis with both hollow fibers. Plasma C3a at the 15th minute correlated positively with postdialysis IL-1 beta and TNF-alpha production, while plasma C3a did not change in patients dialyzed with noncomplement-activating hollow fiber. Complement activation with complement-activating hollow fiber as well as monocyte-membrane interaction with complement-activating and noncomplement-activating hollow fiber might be involved in the pathogenesis of cytokine production during hemodialysis. Uremic toxin removal as well as stimulation of cytokine production inhibitor might contribute to the decreased cytokine production at the 15th minute of hemodialysis and monocyte-membrane interaction with or without complement activation resulted in augmented cytokine production toward the end of hemodialysis with both hollow fibers. We thus concluded that hollow fiber of bioincompatibility triggered much more cytokine production throughout the dialysis procedure.

Effect of calcitriol treatment on psoriasis in hemodialysis patient: a case report.

The case of a 67-year-old man who has had psoriasis with multiple joints involvement for 30 years and renal failure for 1 year is described. He was admitted because of uremic symptoms and exacerbation of psoriasis. Hypocalcemia and low serum active 1.25(OH)2D3 were also observed. Hemodialysis, oral 1.25(OH)2D3 and CaCO3 supplement were employed. Interestingly, the psoriasis strikingly improved. The relationships among psoriasis, renal failure, 1.25(OH)2D3, serum calcium level and dialysis are discussed.

Influence of metabolic acidosis on serum 1,25(OH)2D3 levels in chronic renal failure.

Metabolic acidosis has been shown to alter vitamin D metabolism. There is also evidence that calcium may modulate 1,25(OH)2D3 by a parathyroid hormone (PTH)-independent mechanism. To investigate the effect of rapid correction of chronic metabolic acidosis on serum 1,25(OH)2D3 levels by free calcium clamp in chronic renal failure, 20 patients with mild to moderate metabolic acidosis (mean pH 7.31 +/- 0.04) and secondary hyperparathyroidism (mean intact PTH 156.47 +/- 84.20 ng/l) were enrolled in this study. None had yet received any dialysis therapy. Metabolic acidosis was corrected by continuous bicarbonate infusion for 3-4 h until plasma pH was around 7.4, while plasma ionized calcium was held at the preinfusion level by calcium solution infusion during the entire procedure. The plasma pH, bicarbonate, total CO2, sodium, and serum total calcium levels were significantly increased while serum concentrations of alkaline phosphatase and albumin were significantly decreased after bicarbonate infusion. The plasma ionized calcium, potassium, serum magnesium, inorganic phosphorus, and 25(OH)D levels showed no significant change before and after bicarbonate infusion. The serum 1,25(OH)2D3 levels were significantly increased (38.66 +/- 11.77 vs. 47.04 +/- 16.56 pmol/l, p < 0.05) after correction of metabolic acidosis. These results demonstrate that rapid correction of metabolic acidosis raises serum 1,25(OH)2D3 levels in vitamin D-deficient chronic renal failure patients, and may underline the importance of maintaining normal acid-base homeostasis in the presence of secondary hyperparathyroidism in chronic renal failure.

A prospective study of calcium metabolism in exertional heat stroke with rhabdomyolysis and acute renal failure.

Intensive training in a humid and warm environment can cause exertional heat stroke (ExHS) and rhabdomolysis (RBD) in military recruits. To investigate the role of vitamin D and monomeric calcitonin (CT) on the calcium metabolism in ExHS with RBD and acute renal failure (ARF), we studied 21 recruits with ExHS (mean age 21.4 years), 7 of which had ARF. Another 11 age-matched recruits with heat exhaustion (HE) and 11 healthy subjects were selected as controls. Our results showed that in 14 ExHS patients without ARF, mean serum creatinine (Cr) levels were significantly higher (151.16 vs. 106.08 mumol/l, p < 0.01), whereas serum osteocalcin (OC) levels were significantly lower (2.22 vs. 4.65 micrograms/l, p < 0.01) than in healthy controls. In 7 patients with ExHS and ARF, the mean serum Cr (774.38 vs. 105.20 mumol/l, p < 0.01), phosphorus (P) (2.26 vs. 1.26 mmol/l, p < 0.05), creatine phosphokinase (CPK) 274,143.97 vs. 85.78 IU/l, p < 0.05), intact parathyroid hormone (I-PTH) (299.81 vs. 18.66 ng/l, p < 0.05) and CT (13.58 vs. 6.63 ng/l, p < 0.01) levels on admission were significantly higher while the mean ionized calcium (iCa) levels were significantly lower than the healthy controls (0.9 vs. 1.18 mmol/l, p < 0.01). The mean serum 25-hydroxyvitamin D [25(OH)D] levels were not significantly different from healthy controls. However, mean serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels and the ratio of 1,25(OH)2D to 25(OH)D were significantly lower than healthy controls throughout the whole course of ARF. None of the 7 patients with ExHS and ARF developed hypercalcemia during the diuretic phase. Their mean serum I-PTH levels decreased significantly from 299 to 18 ng/l during the recovery phase (p < 0.05). Our study seems to suggest that the abnormal calcium metabolism in this unique patient group is in part caused by persistently decreased renal production of 1,25(OH)2D, although increased monomeric CT levels were associated with hypocalcemia. However, whether or not a causal relationship exists merits further investigation.

Effects of intravenous calcitriol on lipid profiles and glucose tolerance in uraemic patients with secondary hyperparathyroidism.

1. Secondary hyperparathyroidism in chronic renal failure may contribute to abnormalities of lipid metabolism and glucose tolerance. Amelioration of secondary hyperparathyroidism has been reported to mitigate the hyperlipidaemia and improve glucose tolerance experimentally. 2. The effect of the partial suppression of hyperparathyroidism by intravenous calcitriol on lipid levels and glucose tolerance was studied in 15 haemodialysis patients with secondary hyperparathyroidism. All received intravenous calcitriol 1 microgram at the end of haemodialysis thrice weekly for eight weeks. Oral glucose tolerance test and plasma lipid profiles including triglyceride, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apoprotein A-I and apoprotein B were determined simultaneously before and after eight weeks of therapy. 3. Before calcitriol treatment, uraemic patients with secondary hyperparathyroidism displayed a significant higher triglyceride and a significant lower HDL-C and apoprotein A-I as well as marked glucose intolerance with an increment of the area below the glucose curve when compared with healthy control subjects. 4. After eight weeks of calcitriol treatment, there was a significant decrement in serum intact parathyroid hormone (476.45 +/- 48.33 versus 191.37 +/- 30.17 ng/l, P < 0.001) and plasma triglyceride (2.24 +/- 0.34 versus 1.80 +/- 0.29 mmol/l, P < 0.05) as well as a significant increment of plasma apoprotein A-I (38.13 +/- 2.14 versus 44.19 +/- 2.18 mumol/l, P < 0.05), whereas there was no significant change in serum total cholesterol, LDL-C, HDL-C, and apoprotein B.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of intravenous calcitriol on platelet intracellular calcium in uremic hemodialysis patients with secondary hyperparathyroidism.

BACKGROUND: To investigate the effect of the reversal of hyperparathyroidism on platelet intracellular free calcium ([Ca2+]i) by pharmacological parathyroidectomy with intravenous calcitriol in uremic patients with secondary hyperparathyroidism (2 degrees HPT). METHODS: Serum concentrations of intact parathyroid hormone (I-PTH) were measured by two-site immunometric assay, and platelet [Ca2+]i was assessed using the fluorescent indicator fura-2. Fifteen hemodialysis patients with 2 degrees HPT and serum I-PTH 4 times greater than the normal upper limits, were selected for treatment with intravenous calcitriol 1 microgram thrice weekly for one month. RESULTS: An increase of serum I-PTH (449.17 +/- 52.35 vs 32.52 +/- 1.95 pg/ml) and elevated platelet [Ca2+]i (139.49 +/- 8.78 vs 74.70 +/- 6.48 nM/L) was observed in uremic patients with 2 degrees HPT. Serum I-PTH levels were significantly correlated with platelet [Ca2+]i in uremic patients with 2 degrees HPT (r = 0.736, p = 0.002). The serum I-PTH levels decreased from 449.17 +/- 52.35 to 221.27 +/- 35.66 pg/ml (p < 0.001) and platelet [Ca2+]i fell from 139.49 +/- 8.78 to 97.86 +/- 7.25 nM/L (p < 0.001) after treatment. Fall in platelet [Ca2+]i was related to concomitant reduction in PTH levels (r = 0.572, p = 0.026). CONCLUSIONS: It was concluded that an increase in cytosolic calcium in uremia may be at least in part induced by PTH. Besides, intravenous calcitriol can provide an effective way to suppress elevated serum I-PTH and attenuate platelet free calcium in uremia with 2 degrees HPT.

Imerslund-Grasbeck syndrome in a Chinese family with distinct skin lesions refractory to vitamin B12.

Two brothers in a Chinese family with selective malabsorption of vitamin B12 associated with proteinuria (Imerslund-Grasbeck syndrome) presented with widespread mottled skin pigmentation, termed poikiloderma. In contrast to anaemia, this pigmentary disturbance remained unresponsive to vitamin B12 replacement. This is different from the reported hyperpigmentation sometimes seen in vitamin B12 deficiency which is reversible following treatment. As far as is known, an irreversible and persistent skin disorder has not been reported in this syndrome before.