Reversible increase of the apo CII/apo CIII-1 ratio in the very low density lipoproteins after procetofen treatment in hypertriglyceridemic patients

Procetofen, a new hypolipidemic drug with a powerful cholesterol and triglyceride lowering activity, was administered to hypertriglyceridemic patients, in an effort to determine the major lipoprotein and apoprotein changes, thus providing an insight of the drug's mechanism of action. The twenty-six selected patients (13 type IIB and 13 type IV) were given 100 mg tid of the compound for 9 weeks. Procetofen lowered triglycerides in plasma (-50%) and in all lipoprotein classes (-30-50%) in both patient groups; an 18% reduction of low density lipoprotein cholesterol levels also occurred in type IIB patients. High density lipoprotein cholesterol generally increased significantly, with a maximum of 11% in type IV patients. Plasma apolipoproteins showed a pattern of changes, characteristic of each hyperlipoproteinemia phenotype, reversible after the end of drug treatment. Apoprotein B decreased 16% in type IIB patients, but was not modified in type IV. Conversely, apoprotein CII increased significantly in the very low density lipoproteins of both groups of treated subjects, with a reduction of CIII-1. These findings support the hypothesis that procetofen may act primarily as a stimulator of the catabolism of triglyceride rich lipoproteins. On the other hand, the significant reduction of total and low density lipoprotein cholesterol levels in type IIB, also indicates that other mechanisms, possibly related to changes in the direct liver secretion of apoprotein B or to remnant removal, may be operative with this new drug.     

Imatinib-associated neutropenia may not be overcome by filgrastim treatment in patients with blastic phase of chronic myeloid leukaemia

Imatinib mesylate is a very effective treatment in patients with Philadelphia (Ph)-positive chronic myeloid leukaemia (CML). However, in patients with advanced phase CML, it is still unclear whether, in the presence of myelosuppression, therapy with imatinib should be continued. It has been reported that intermittent filgrastim treatment may overcome imatinib-associated neutropenia and allow improved delivery of imatinib. Such combined sequential treatment is theoretically attractive as it may lead to better disease response. Here, we report a patient with blastic phase CML who developed severe and prolonged myelosuppression during imatinib treatment. Despite cessation of imatinib and 2 months of filgrastim therapy neither recurrence of Ph-positive or Ph-negative cells occurred. We conclude that filgrastim treatment may not always reverse imatinib-associated neutropenia therefore the decision of continued imatinib therapy in patients with advanced CML should be taken with caution.     

Crohn's disease-associated genetic marker is seen in medically unresponsive ulcerative colitis patients and may be associated with pouch-specific complications

PURPOSE: Genetic markers have been used to define subgroups of patients within the broad categories of Crohn's disease and ulcerative colitis that may differ in clinical course and response to medical therapy. The tumor necrosis factor microsatellite haplotype a2b1c2d4e1 has been found previously to be present in 24 percent of patients with Crohn's disease and only 5 percent of patients with ulcerative colitis. This study examined associations between this microsatellite haplotype and the postoperative clinical course of patients with ulcerative colitis undergoing ileal pouch-anal anastomosis. METHODS: As part of a large, controlled, prospective study to correlate genetic markers with clinical phenotypes, tumor necrosis factor microsatellite alleles at five loci (a, b, c, d, and e) were determined from genomic DNA by polymerase chain reaction in 32 patients with a clinical and histopathologic diagnosis of ulcerative colitis who underwent ileal pouch-anal anastomosis for medically unresponsive disease. All patients with ileal pouch-anal anastomosis were also studied prospectively for pouch-specific complications. RESULTS: The tumor necrosis factor haplotype a2b1c2d4e1 was present in 11 patients. Median follow-up was 19 months. Thirteen patients had a pouch-specific complication (12 pouchitis and 1 pouch-perineal fistula). Six of 11 patients (55 percent) with the haplotype had a pouch-specific complication compared with 7 of the 21 patients (33 percent) who did not possess this haplotype (P=0.22). Median time from surgery to pouch-specific complication was eight months. Patients with the haplotype had a median time to pouch-specific complication of three months, whereas patients without the haplotype had a median time of 11 months (P=0.04). In addition, 36 percent of patients with the haplotype had chronic pouch complicationsvs. only 10 percent of patients without the haplotype (P=0.05). CONCLUSION: The Crohn's disease-associated tumor necrosis factor haplotype a2b1c2d4e1 may define a subgroup of medically unresponsive patients with ulcerative colitis who are predisposed to a higher incidence of pouch-specific complications after ileal pouch-anal anastomosis.Read at the meeting of The American Society of Colon and Rectal Surgeons, Philadelphia, Pennsylvania, June 22 to 26, 1997.     

Treatment of depression and effect of antidepression treatment on nutritional status in chronic hemodialysis patients

BACKGROUND: Depression, which is the most common psychological complication in patients with end-stage renal disease (ESRD), has an impact on the clinical outcome and is associated with malnutrition in chronic hemodialysis patients. This study evaluated the effect of antidepression treatment on nutritional status in depressed chronic hemodialysis patients. METHODS: Sixty-two ESRD patients who underwent dialysis for more than 6 months were interviewed and completed a Beck Depression Inventory assessment. Thirty-four patients who had scores greater than 18 on the Beck Depression Inventory score and met Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria for major depressive disorder were selected to receive paroxetine 10 mg/day and psychotherapy for 8 weeks. The remaining 28 patients were assigned to the control group. Change in the severity of depressive symptoms was ascertained by administering the Hamilton Depression Rating Scale. Nutritional status was evaluated by normalized protein catabolic rate, serum albumin and blood urea nitrogen level. RESULTS: All patients successfully completed 8 weeks of antidepression treatment. Antidepression treatment decreased the severity of depressive symptoms (Hamilton Depression Rating Scale score: 16.6 +/- 7.0 versus 15.1 +/- 6.6, P < 0.01) and increased normalized protein catabolic rate (1.04 +/- 0.24 versus 1.17 +/- 0.29 g/kg/day, P < 0.05), serum albumin (37.3 +/- 2.0 versus 38.7 +/- 3.2 g/l, P < 0.005), and prehemodialysis blood urea nitrogen level (24.3 +/- 5.6 versus 30.2 +/- 7.9 mmol/L, P < 0.001). In the control group, no change was noted during the study period. CONCLUSION: This study suggests that antidepressant medication with supportive psychotherapy can successfully treat depression and improve nutritional status in chronic hemodialysis patients with depression.     

Intravenous methylcobalamin treatment for uremic and diabetic neuropathy in chronic hemodialysis patients.

OBJECT: To study the effects of the intravenous administration of methylcobalamin, an analogue of vitamin B12, for uremic or uremic-diabetic polyneuropathy in patients who are receiving maintenance hemodialysis. An ultra-high dose of vitamin B12 has been reported to promote peripheral nerve regeneration in experimental neuropathy. METHODS: Nine patients received a 500 microg methylcobalamin injection 3 times a week for 6 months. The effects were evaluated using neuropathic pain grading and a nerve conduction study. RESULTS: Serum concentrations of vitamin B12 were ultra-high during treatment due to the lack of urinary excretion. After 6 months of treatment, the patients' pain or paresthesia had lessened, and the ulnar motor and median sensory nerve conduction velocities showed significant improvement. There were no side effects. CONCLUSION: Intravenous methycobalamin treatment is a safe and potentially beneficial therapy for neuropathy in chronic hemodialysis patients.     

Poor compliance with guidelines on anemia treatment in a cohort of chronic hemodialysis patients

Background/Aims: Guidelines for the management of anemia and iron deficiency in chronic hemodialysis (HD) patients have been developed to standardize therapy and improve clinical outcome. The present study evaluated compliance with anemia guidelines and investigated whether differences between centers were present. Methods: Data on anemia management from patients in the baseline cohort of the CONTRAST study (NCT00205556) were analyzed. 598 chronic HD patients (62% male, age 63.6 ± 14.0 years) from 26 Dutch dialysis centers were included. Results: Mean hemoglobin (Hb) level was 11.9 ± 1.3 g/dl and Hb was ≥11.0 g/dl in 81% of the patients. Compliance with all anemia targets (Hb 11.0-12.0 g/dl, transferrin saturation ratio ≥20%, ferritin 100-500 ng/ml) was reached in 11.6% (95% CI 7.8-17.0) of the patients, with a wide range among centers (4-26%, adjusted for case mix, treatment-related factors and center-specific characteristics). Conclusion: Compliance with anemia targets in stable HD patients was poor and showed a wide variation between treatment facilities.     

Glucose metabolism and insulin sensitivity in patients on chronic hemodialysis

In order to evaluate the potential role of parathyroid hormone on glucose metabolism in patients on chronic hemodialysis hyperglycemic clamp studies were performed in 7 parathyroidectomized and 11 nonparathyroidectomized patients on chronic hemodialysis and in healthy controls. There were no significant differences in the peripheral glucose uptake of the 3 groups. The beta cell response to hyperglycemia during the early phase as well as during the steady state was almost identical in controls and in nonparathyroidectomized uremics, whereas in the parathyroidectomized group a markedly enhanced insulin secretion was found. Calculated tissue sensitivity to insulin therefore was equal in controls and in nonparathyroidectomized uremics, whereas patients after parathyroidectomy had peripheral insulin resistance. Our results demonstrate that patients on chronic hemodialysis apparently have normal peripheral glucose uptake. The subgroup of patients who have undergone parathyroidectomy, however, show an enhanced insulin response to hyperglycemia suggesting peripheral insulin resistance. We conclude that longstanding and severe secondary hyperparathyroidism--the usual cause for parathyroidectomy in these patients--results in irreversible insulin resistance with a compensatory increase of insulin secretion.     

Serum carnitine concentration and the acyl to free carnitine ratio in nondialysis chronic kidney disease and hemodialysis patients

Mechanisms of impaired fatty acid metabolism may not be the same in nondialysis and hemodialysis patients. Correlations between the serum-free carnitine concentration (FC), acylcarnitine concentration (AC), acyl to free carnitine ratio (AC/FC), and estimated glomerular filtration rate (eGFR) in the nondialysis population and the duration of hemodialysis in hemodialysis patients were investigated. As the eGFR decreased, the FC and AC increased, and as the duration of hemodialysis became longer, the FC and AC decreased. The AC/FC increased consistently as the eGFR decreased and the duration of hemodialysis increased. As an exception, the AC/FC decreased in the patients with a hemodialysis duration less than 90 days, which was not explained by carnitine removal by hemodialysis. In nondialysis patients, a functional, rather than an absolute, carnitine deficiency is a main cause of impaired fatty acid metabolism. Long-term hemodialysis exacerbates absolute carnitine deficiency, whereas hemodialysis treatment may improve impaired fatty acid metabolism.     

Imatinib‐associated neutropenia may not be overcome by filgrastim treatment in patients with blastic phase of chronic myeloid leukaemia

Imatinib mesylate is a very effective treatment in patients with Philadelphia (Ph)‐positive chronic myeloid leukaemia (CML). However, in patients with advanced phase CML, it is still unclear whether, in the presence of myelosuppression, therapy with imatinib should be continued. It has been reported that intermittent filgrastim treatment may overcome imatinib‐associated neutropenia and allow improved delivery of imatinib. Such combined sequential treatment is theoretically attractive as it may lead to better disease response. Here, we report a patient with blastic phase CML who developed severe and prolonged myelosuppression during imatinib treatment. Despite cessation of imatinib and 2 months of filgrastim therapy neither recurrence of Ph‐positive or Ph‐negative cells occurred. We conclude that filgrastim treatment may not always reverse imatinib‐associated neutropenia therefore the decision of continued imatinib therapy in patients with advanced CML should be taken with caution.     

Lower th-1/th-2 ratio before interferon therapy may favor long-term virological responses in patients with chronic hepatitis C

It is still controversial whether alterations in helper-T cell subpopulations contribute to the pathogenesis and clinical characteristics of chronic hepatitis C. The aim of this study was to clarify this issue, particularly in relation to interferon therapy. Thirty-one patients with histologically proven chronic hepatitis C were treated by conventional interferon (IFN) monotherapy for 6 months, and virological responses were evaluated by polymerase chain reaction 6 months later. Helper-T cell subpopulations, Th-1 and Th-2, were determined in peripheral blood by intracellular cytokine assay using flow cytometry. In chronic hepatitis C, the percentage of Th-1 and Th-2 subpopulations in peripheral blood were significantly increased, by 1.4-fold as compared with normal controls. Serum levels of ALT were inversely proportional to the percentage of Th-1 subpopulations, while directly proportional to that of Th-2 subpopulations. In nonresponders (N = 16) to interferon therapy, the percentage of Th-1 subpopulations and Th-1/Th-2 ratio were significantly higher than those in complete responders (N = 15). By multivariate logistic regression analysis, HCV genotype non-1b, HCV viral load less than 500 kilocopies/ml, and the lower Th-1/Th-2 ratio could independently merit favorable long-term virological responses. Helper-T cell subpopulations, Th-1 and Th-2, seem to contribute to progression of chronic hepatitis C in a reciprocal fashion. The imbalance between the two subpopulations may determine the final outcome of interferon therapy as one of the host factors.     

Incidence and features of liver disease in patients on chronic hemodialysis

We examined the incidence and features of liver disease and the presence of serologic markers of hepatitis B virus (HBV) infection in 134 patients on hemodialysis for 2 to 14 years. Twenty-three patients (17%) had had a single episode of acute hepatitis while on dialysis and two patients had had two episodes, which were attributed to infection by hepatitis B virus in 7 instances and by hepatitis non-A, non-B virus in 20. Chronicity supervened in 4 cases of hepatitis B (57%) and in 14 cases of hepatitis non-A, non-B (70%). A prolonged rise of serum aminotransferases, which was not preceded by acute hepatitis, was detected in 23 additional patients (17%). Acute hepatitis and prolonged hypertransaminasemia were more frequent in patients dialyzed at a hospital unit than in patients dialyzed outside the hospital or at home. These observations indicate that development of acute and chronic liver disease, mainly hepatitis non-A, non-B, is frequent in patients on chronic hemodialysis, particularly in those dialyzed in hospital. Serologic evidence of current or past infection by HBV was detected in 57 patients (42%) with sustained positivity of HBV serum markers. Transient positivity for anti-HBc, anti-HBs, or both, possibly related to passive transmission of antibodies by blood transfusion, was observed in 20 patients (15%). These findings indicate that periodic, repeated testing for HBV serum markers is necessary only in a minority of patients on long-term hemodialysis.     

Pathogenesis and therapy for vascular calcification in patients on chronic hemodialysis

Vascular calcification is a common complication of end-stage renal disease (ESRD) and is likely related to the high incidence of cardiovascular disease in patients with ESRD. Vascular calcification occurs both in the vascular intima and in the tunica media. Intimal calcification is disseminated and is associated with damaged endothelium and macrophage. On the contrary, medial calcification occurs in patchy distribution and the most frequent cells types found in its vicinity are smooth muscle cells (SMC). The uremic state is associated with numerous metabolic abnormalities and endocrine disturbances primarily involving calcium and phosphorus metabolism. In addition, ESRD is considered state of active inflammatory response. These dysfunctions likely contribute to the development and progression of vascular calcification. Recent reports have shown that this is a highly regulated process governed by factors that closely resemble calcium deposition in bone tissue. Vascular calcification requires changes in the phenotype of SMC and the expression of several bone-associated proteins normally involved in bone metabolism. This review is focused on the role of phosphorus in the pathogenesis of vascular calcification and the therapeutic approaches currently available to slow its progression in patients with ESRD.     

Prevalence,treatment, and control of hypertension in chronic hemodialysis patients in the United States

BACKGROUND: Hypertension is common in chronic hemodialysis patients, yet there are limited data on the epidemiology of hypertension in these patients in the United States. METHODS: We assessed the prevalence, treatment, and control of hypertension in a cohort of 2535 clinically stable, adult hemodialysis patients who participated in a multicenter study of the safety and tolerability of an intravenous iron preparation. Hypertension was defined as an average predialysis systolic blood pressure >150 mm Hg or diastolic blood pressure >85 mm Hg, or the use of antihypertensive medications. RESULTS: Hypertension was documented in 86% (n = 2173) of patients. The prevalence of hypertension, in contrast to that observed in the general population, did not increase linearly with age and was not affected by sex or ethnicity. Hypertension was controlled adequately in only 30% (n = 659) of the hypertensive patients. In the remaining patients, hypertension was either untreated (12% [252/2173]) or treated inadequately (58% [1262/2173]). CONCLUSION: Control of hypertension, particularly systolic hypertension, in chronic hemodialysis patients in the United States is inadequate, despite recognition of its prevalence and the frequent use of antihypertensive drugs. Optimizing the use of medications and closer attention to nonpharmacologic interventions, such as adjustment of dry weight, a low-sodium diet, and exercise, may improve control.     

Decreased ratio of CD4/CD8 lymphocytes might be predictive for successful interferon alpha and lamivudine combined therapy in childhood chronic hepatitis B infection: A preliminary study

BACKGROUND: In the development of chronic hepatitis with hepatitis B virus infection and in response to therapy, the immune status of the infected host plays a critical role. In this study, immunological variables were assessed in patients before interferon alpha and lamivudine therapy to determine if any pretreatment immunological parameter could be an indicator of response to therapy in childhood chronic hepatitis B infection. METHODS: Forty-four patients with chronic hepatitis B virus infection, aged 9.0 +/- 3.9 years, were enrolled in the study. The pretreatment clinical features, biochemical test results, histological activity indexes and immunological parameters were evaluated. All patients received interferon alpha for 6 months and lamivudine for 52 weeks. Four patients who could not be followed up were excluded from the study. The other 40 patients have been followed for a mean period of 27.5 +/- 9.7 months after therapy discontinuation. RESULTS: Seventeen patients showed loss of hepatitis B early antigen (HBeAg) with appearance of anti-HBe (42.5%) and six of those who responded also showed loss of hepatitis B surface antigen (HBsAg) with the presence of anti-HBs (15%). Except elevated aspartate aminotransferase levels, there was no significantly correlation between response and sex, age, pretreatment duration of disease and histological activity indexes. Pretreatment immunoglobulins (Ig), IgG subclasses, complement C3, C4 and secretory IgA levels were also not found to be significantly related to response. The evaluation of lymphocyte subsets showed that therapy responders had significantly reduced pretreatment ratios of CD4/CD8+ lymphocytes due to prominent increased percentages of CD8+ cells. The other cellular immunity parameters and some cell surface adhesion molecules were similar in both groups. CONCLUSION: This study emphasizes the importance of increased pretreatment CD8+ lymphocyte percentages leading to a significant decrease in CD4/CD8 ratio in chronic hepatitis B virus infection of childhood as an immunological factor predicting response to treatment.     

Cardiac surgery in patients on chronic hemodialysis: short and long-term survival

OBJECTIVE: Open-heart surgery carries a high risk for hemodialysis patients. This study focuses on the short and long-term outcomes of hemodialysis patients undergoing heart surgery. DESIGN: The study was carried out as a retrospective analysis in the Department of Cardiothoracic Surgery in a large university-affiliated hospital. PATIENTS: 115 hemodialysis patients underwent cardiac surgery in our department between 1 July 1996 and 31 July 2006. 67.5 % (77 patients) underwent isolated coronary artery bypass grafting (CABG), 13.2 % (15 patients) underwent isolated aortic valve replacement (AVR) and 20.2 % (23 patients) underwent mitral valve surgery or combined valve and coronary artery bypass grafting or multiple valve surgery. METHODS: The relationship between several variables (age, sex, hypertension, diabetes, and previous myocardial infarction, type of disease, preoperative ejection fraction, and congestive heart failure) and operative (30 days) mortality and late survival was analyzed. RESULTS: The overall 30-day mortality was 18.3 % (21 patients). It was 13 % (10/77 patients) for the isolated CABG group and 13.3 % (2/15) for the isolated AVR group. Patients undergoing combined valve and coronary surgery or multiple valve surgery had a higher perioperative mortality of 39.1 % (9/23) compared to the isolated CABG and isolated AVR patients. Perioperative death was also higher in patients with moderate and severe LV dysfunction, and in patients with diabetes. The duration of dialysis periods was not related to perioperative death. Mean follow-up was 26.4 +/- 29.7 months (0.1 to 104 months). Actuarial survival at 1 year and 5 years was 76 % and 55 % for isolated CABG, 59 % and 21 % for isolated AVR, and 44 % and 33 % for all other cases, respectively (log rank P = 0.001). CONCLUSION: Patients on dialysis have a high risk of perioperative mortality and poor long-term survival rates. Mortality is higher and survival is worse after combined CABG and valve-related procedures or multiple valve surgery than after isolated CABG and AVR.     

维持血液透析的尿毒症病人乙型丙型肝炎病毒感染情况研究

目的　了解北京地区 (东城、宣武、朝阳区 )接受规律性血液透析患者 ,乙型肝炎病毒 (HBV)和丙型肝炎病毒 (HCV)的感染情况及其相关因素。方法　 1998年 3～ 12月在北京协和医院、朝阳医院等 4家医院血液净化中心 ,长期维持血液透析的尿毒症患者 2 2 5例 ,血透中心工作人员及健康献血者 5 0例为对照组。分别用PCR法和高敏PCR法检测HBVDNA、HCVRNA ,ELISA法检测乙肝两对半及丙肝抗体 ,并分析其与透析时间、输血、肝功能损害的关系。结果　 2 2 5例血液透析病人中 ,HCVRNA阳性 37例 (16 4 %) ;HBVDNA阳性 3例(1 33%)。多元回归分析表明 :输血和透析时间是丙型肝炎感染的危险因素。共有 3 0 %(3/ 99)的病人同时感染乙肝和丙肝 ,均有肝功能的损害和临床症状 ,8 1%(8/ 99)HBcAb阳性患者同时合并HCV感染。结论　血液透析病人乙肝和丙肝感染远高于对照组 ,透析时间和输血次数是丙肝感染的危险因素 ,HBV和HCV同时感染问题值得重视。     

ECG changes and cardiac arrhythmias in chronic renal failure patients on hemodialysis

Serial 12-lead electrocardiogram (ECG) recordings and 24-hour Holter monitoring were carried out in 39 patients with chronic renal failure, starting just before a routine dialysis session. In an attempt to identify risk factors for cardiac arrhythmias, the results obtained from each patient were correlated with a variety of clinical, hematological, and biochemical data. All patients exhibited ECG changes, which were most pronounced during the first 2 hours of dialysis. The most frequent of these changes were a decrease in T wave amplitude and increase in Tmax time (all patients), an increase of QRS amplitude (61% of patients), shortened or prolonged QTc interval (61%) and ischemic-like ST-T changes (22% and 39%, respectively). Potentially clinically significant arrhythmias occurred in 12 patients (31%) of which 8 were supraventricular, 3 were combined ventricular and supraventricular, and 1 was pure ventricular. The only clinically identified risk factor for complex ventricular and supraventricular arrhythmia was advanced age. The arrhythmia and nonarrhythmia groups differed significantly in their predialysis hematocrit, O2 content, serum urea, and osmolarity, and in their postdialysis serum phosphorus and osmolarity. The results indicate that patients with chronic renal failure frequently exhibit ECG changes and a high incidence of ventricular and supraventricular arrhythmias, which may be prognostically significant, during and after hemodialysis.