Gastrointestinal involvement of dialysis-related amyloidosis

Beta-2 microglobulin-related amyloids were found in gastric biopsy specimens from 3 of 11 patients who had been on hemodialysis more than 10 years and examined. The deposits were found not only in arteriolar walls but also in lamina propria and muscle tissue. In another patient who was on hemodialysis for 8 years, beta 2-microglobulin-related amyloids were found in the muscle layer of operatively resected colon. These four patients also had the same substance deposited in the osteoarticular system. The results suggest the systemic involvement of beta 2-microglobulin-related amyloidosis in patients on long-term hemodialysis.     

Role of ve-cadherins, beta-1 integrins and endothelin-1 in endothelial dysfunction after cardiac transplantation

Introduction: Endothelial dysfunction is a major cause of chronic allograft vasculopathy in cardiac transplantation. The dysfunction of the endothelium in coronary vasculature can be due to the loss of endothelial contacts with the extracellular matrix, endothelial cell-to-cell contact. We investigated the expression of VE-cadherins, integrins and endothelin-1 in a heart transplant model in mice to determine if endothelial dysfunction is from the underexpression of these endothelial specific molecules. Methods: Nonvascularised neonatal heart allografts from C57 BL/6 (H-2b) were transplanted to ear pinna of Balb/c (H-2d) recipient mice. Isografts from C57 BL/6 (H-2b) mice were performed as control. Allo and isografts were harvested at P.O day 1,3,5,7 & immunostaining for endothelin-1, VE-cadherin and Beta-1 integrin was performed with monoclonal antibodies specific for each molecules. Results: In normal neonatal hearts, VE-cadherin and Beta-1 integrin were detected in endothelial cells only, while ET-1 was detected in both endothelial and myocardial cells. Following transplantation, VE-cadherin became undetectable until P.O day 7 in isografts and P.O.day 5 in allografts at which time it became detectable at low levels on endothelial cells. Beta-1 integrin showed a pattern similar to VE-cadherin, except that it became barely detectable in either iso or allografts after transplantation. ET-1 did not show any detectable changes in either allo or isografts after transplantation. Conclusion: VE-cadherin and Beta-1 integrin expression on endothelial cells is diminished after cardiac transplantation, while ET-1 expression continues after transplantation. These data provide molecular insights into the loss of vascular endothelial integrity in cardiac allografts.     

Beta-2 microglobulin in ESRD: an in-depth review

Beta-2 microglobulin is the most widely studied low-molecular-weight protein in end-stage renal disease. It is known to cause dialysis-related amyloidosis (DRA), by virtue of its retention when renal function fails, its deposition in tissues, its aggregation into fibrils, and its ability to become glycosylated. The onset of DRA may be protracted by the use of noncellulosic membranes, especially when high-volume hemodiafiltration is used in the treatment of renal failure. Adsorptive methods have been developed to improve the removal of beta-2 microglobulin. There seems to be a relative risk reduction in mortality when patients are treated with dialysis membranes that have a higher clearance of beta-2 microglobulin.     

Tension pneumocephalus: an unusual complication after lung resection.

On day 5, after right upper lobectomy, the patient developed headache, confusion and right hemiparesis and there was clear fluid drainage from the chest tube. Computed tomography (CT) scan of the head showed gas in the ventricles and subarachnoid space. The fluid from the drain was positive for Beta-2 transferrin signifying cerebrospinal fluid (CSF) fistula. Patient recovered completely with conservative management.     

Pathologic femoral neck fractures and para-articular beta 2 microglobulin amyloidosis in long-term dialysis patients: an increasingly frequent disease picture

Beta-2-microglobulin (beta 2-M)-amyloidosis is caused by retention of beta 2-M by dialyzing membranes and by deposition as an atypical amyloid in synovia, bone and tendons. Ten patients under long-term hemodialysis (13 +/- 2.7 years) were treated because of hip pain and cystiform skeletal alterations. First typical joint affections appeared nine years after start of hemodialysis. Five fractures of the hip neck due to large cystiform bone lesions occurred in four subjects. In all cases a total joint replacement was performed.     

Beta blockers and anesthesia

Beta-adrenoceptor antagonists (BB) demonstrate a competitive antagonism with endogenous catecholamines. Beta-1 receptor blockade mediates the depressive action on contractility, heart rate and atrio-ventricular conduction. Beta-2 receptor blockade mediates vascular, bronchial and uterine smooth muscle constriction. BB with beta-1 selective and intrinsec sympathomimetic activity do not increase systemic vascular resistance. BB are mostly used to treat ischaemic heart disease, hypertension and arrhythmias. Bradycardia, hypotension and bronchospasm are the main hazards in BB treated patients undergoing anaesthesia. However giving BB with premedication to patients taking usely this treatment allows better perioperative haemodynamic stability and avoids rebound effect. Experimentally, oxprenolol reverses regional dysfunction in ischaemic myocardium under halothane anaesthesia. During and after anaesthesia, intravenous (i.v.) BB must be used with caution to treat hypertension associated with tachycardia. In controlled hypotension, i.v. BB potentialise other agents. In phaechromocytoma surgery, alpha-blocking drugs are essential but additional BB can control tachycardia successfully. In coronary artery bypass surgery, giving BB prior to induction decreases cardiac enzymes serum levels. Esmolol, a new ultra-short-acting BB, would control perioperative tachycardia and hypertension without risk of prolonged cardiac depression.     

Cardioprotective effect of pretreatment with beta-glucan in coronary artery bypass grafting

BACKGROUND: Beta-glucan pretreatment has been shown to attenuate inflammatory response and to protect against ischemia-reperfusion injury in animal studies. The aims of the present study were to examine the safety of pretreatment with beta-1,3/1,6-glucan in patients scheduled for coronary artery bypass grafting (CABG), and to investigate whether beta-1,3/1,6-glucan pretreatment could suppress inflammatory response and protect against ischemia-reperfusion injury following CABG. METHODS: Twenty one patients scheduled for CABG were assigned to oral beta-1,3/1,6-glucan 700 mg (Group 1) or 1 400 mg (Group 2) five consecutive days before surgery and were compared with a control group (Group 3). Blood samples were drawn preoperatively and on the first, third and fifth postoperative day for analysis of acute-phase reactants, hematology, cytokines and myocardial enzymes. RESULTS: The study drug was well tolerated. Creatine kinase isoenzyme MB was significantly lower in Group 2 compared with controls on the first postoperative day (p = 0.028). Mean change in cardiac troponin T was lower in Group 2 compared with controls (p = 0.028). CONCLUSIONS: Beta-1,3/1,6-glucan pretreatment is safe in patients undergoing CABG and may protect against ischemia reperfusion injury following CABG.     

Serum beta-2-microglobulin levels in urological cancer.

Serum beta-2-microglobulin levels were measured in patients with renal, vesical and prostatic cancer. Measurements were made only on samples with a serum creatinine less than or equal to 105 mumol./l. to eliminate the possibility of elevated beta-2-microglobulin being a result of impaired renal function. This criterion eliminated 28 to 50 per cent of the patients with bladder cancer and 73 per cent of those who had undergone nephrectomy for renal carcinoma, which, obviously, limits the value of beta-2-microglobulin measurement for the surveillance in these cancers. Beta-2-microglobulin values in patients with prostatic cancer were seldom increased to more than 3.0 mg./l. In bladder cancer patients with normal serum creatinine the frequency of an elevated serum beta-2-microglobulin increased with the increase in tumor stage.     

Detection of plasma proteins during sequential ultrafiltration/dialysis

Elimination of low molecular weight proteins during sequential ultrafiltration/dialysis was studied in 29 uremic patients. Beta-2-microglobulin, retinol binding protein, free light chains lambda and kappa, Zn-alpha-2-glycoprotein, hemopexin, prealbumin, hemoglobin, albumin, acid alpha-1-glycoprotein, haptoglobin, alpha-1-antichymotrypsin, ribonuclease, lysozyme, amylase, non-specific esterase, and proteolytic activity were detected in all ultrafiltrates tested. The level of total protein and ribonuclease was determined in 36 crude ultrafiltrates from 23 patients. Concentrated ultrafiltrates were used to quantitate retinol binding protein, prealbumin, albumin, lysozyme, and amylase. Other proteins identified in the ultrafiltrates are present in trace amounts. The question was discussed whether ++inextensive but systematic loss of proteins during hemofiltration in chronic RDT might be the cause of patient homeostasis disturbances.     

No influence of chromosome Y haplogroup variation in acute graft-versus-host disease in sardinia

The donor-recipient sex-related mismatch has been reported as a risk factor for acute graft-versus-host disease (GVHD). However, the results obtained in previous studies appear to be contradictory. Here we evaluate the impact of donor-recipient sex-related mismatch in a series of 204 Sardinian individuals (92.1% of them affected by Beta- Thalassemia major) who underwent bone marrow transplantation (BMT) from human leukocyte antigen (HLA) identical siblings. In all, 78 of these patients had acute GVHD (aGVHD). We found that also in this homogenous group of patients from a homogenous population, the donor-female/recipient-male pair provided an increased risk for aGVHD when compared with a reference donor-male/recipient-male pair (POR=2.3, P=0.042). This data could be consistent with a role of variation in the male-specific portion of the Y chromosome in aGVHD. To assess this, we compared the distribution of the main Y-chromosome haplogroups in 28 male patients, who had aGVHD and underwent BMT from HLA-identical sisters, and 366 ethnically-matched controls. No significant differences were observed. These findings do not support the presence of Y chromosome founder variants contributing significantly to aGVHD in the Sardinian population.     

The use of a selective beta-adrenergic receptor blocker for the preoperative preparation of thyrotoxic patients.

Metoprolol, a cardioselective beta-blocker, was used in two asthmatic, thyrotoxic patients in preparation for thyroidectomy. Adequate reduction in resting heart rate was achieved in both individuals without inducing clinically significant airway obstruction. Beta-1-blockade can be selectively employed in this clinical setting, but patients should be hospitalized and closely monitored for adverse effects on pulmonary function. Metoprolol therapy in patients with reversible airway obstruction is discussed with reference to recent studies on relative cardioselectivity.     

Tubular marker excretion in children from families with Balkan nephropathy

Balkan nephropathy (BN) has not been described in children; however, some previous studies in children from families with BN have revealed abnormalities of the urinary tract. In this study, urinary excretion of β2-microglobulin, N-acetyl-β-D-glucosaminidase (NAG) and gamma-glutamyl transpeptidase (GGT) was studied three times a year: spring, autumn, and winter, during a 3-year period, in 703 healthy children, initial age 9–13, from endemic and nonendemic settlements around the South Morava River. Beta-2-microglobulin excretion in urine, in all three seasons, was highest in children from families with BN compared with the excretion in children from the city, nonendemic villages, and those from nonendemic families. Increased urinary GGT excretion in children from endemic villages in October was higher than in children from the city and control villages, being the same in both endemic and nonendemic families. However, in February, it was similar in children from the city, endemic, and control villages. In conclusion, children from families with BN excreted significantly more β2-microglobulin in all three seasons (spring, autumn, winter) of the study, in multivariate analysis significant for family status, gender, and the season (p < 0.001). NAG emerged as a potentially useful marker for seasonal exposure to an environmental nephrotoxin.     

Variation at the beta-1 adrenoceptor gene locus affects left ventricular mass in renal failure

OBJECTIVES: To examine the relationship between this variation in the beta1AR gene and the effect on LV mass. BACKGROUND: Left ventricular (LV) mass is an important cardiovascular risk factor. Beta-1 adrenoceptors (betaAR) are predominately located in the heart and their variation may, therefore, affect LV mass. A known polymorphism of the betaAR changes the amino acid at position 389 from glycine to arginine within an area critical for G-protein coupling and so cell signalling. The arginine-form of the receptor has been demonstrated to have increased GTP binding. METHODS: We studied 249 patients attending a renal clinic, 37% of whom were on renal replacement therapy (RRT). Raw LV mass was calculated by echocardiography. LV mass index (LVMI) and LV mass indexed to height2.7 were derived thereafter. Individuals were genotyped for the beta1AR variation and categorised CC if both alleles encoded for arginine at position 389, GG if both alleles encoded for glycine and CG if heterozygous. RESULTS: There was a highly significant difference in raw LV mass, LV mass index and LV mass indexed to height2.7 between the GG group when compared to both the CC and CG genotypes groups (p<0.05). The strength of the relationship was maintained when patients on RRT or taking beta-blockers were excluded (p<0.05). CONCLUSIONS: These data suggest that genetic variation at this locus is of importance in defining left ventricular mass.     

Effects of inhaled salbutamol in exercising non-asthmatic athletes

BACKGROUND: Beta-2 agonists such as salbutamol are used, not only by asthmatic athletes to prevent exercise induced asthma, but also by non-asthmatic athletes as a potentially ergogenic agent. We have investigated whether inhaled salbutamol enhances endurance performance in non-asthmatic athletes. METHODS: A prospective double blind, randomised, three way crossover design was used to study the effects of 200 microg and 800 microg inhaled salbutamol versus a placebo in 12 trained triathletes. The treatments were compared in three identical cycle ergometer sessions at 85% of the predetermined maximal oxygen uptake. Lung function, endurance time, metabolic parameters (glucose, potassium, lactate, free fatty acid, and glycerol), and psychomotor performance were evaluated. RESULTS: Neither endurance time nor post-exercise bronchodilation were significantly different between the treatments. Metabolic parameters were affected by exercise but not by treatment. CONCLUSIONS: Inhaled salbutamol, even in a high dose, did not have a significant effect on endurance performance in non-asthmatic athletes, although the bronchodilating effect of the drug at the beginning of exercise may have improved respiratory adaptation. Our results do not preclude an ergogenic effect of beta2 agonists given by other routes or for a longer period.     

Serum beta-2-microglobulin and angiotensin-converting enzyme activity in sarcoidosis

Angiotensin-converting enzyme activity in sarcoidosis is regarded both as a diagnostic feature and as an index of disease activity. Increased activity of this enzyme is thought to parallel macrophage and epithelioid cell activity. Beta-2-microglobulin, a low-molecular-weight protein associated with the histocompatibility antigens, is thought to reflect activation of immunocompetent cells, particularly lymphocytes. In 132 patients with known sarcoidosis no close association was found to exist between the results of the two assays (r = 0.53). Angiotensin-converting enzyme activity was raised in 33% and beta 2-microglobulin concentrations in 63% of patients with sarcoidosis. When analysed prospectively, the results of the two assays showed no correlation in 29 patients over periods of up to 19 months. Stage, duration of disease, and corticosteroid treatment showed no significant effect on levels of either angiotensin-converting enzyme or beta 2-microglobulin. The disparity between indices of macrophage and lymphocyte activation requires further study in sarcoidosis.     

Cardiovascular side effects of inhaled salbutamol in hypoxic asthmatic patients

BACKGROUND: Beta-2 adrenoceptor agonists have been associated with sudden death in asthma patients but the cause and underlying mechanism are unclear. Animal experiments indicate that the combination of hypoxia and beta2 agonists may result in detrimental cardiovascular effects. A study was undertaken to investigate the effect of hypoxia on the systemic vascular effects of salbutamol in patients with asthma who are hypoxic by assessing forearm blood flow (FBF) as a measure of peripheral vasodilatation. METHODS: Eight men with mild asthma underwent the following treatments: normoxia + placebo (NP), normoxia + salbutamol (NS), hypoxia + placebo (HP), and hypoxia + salbutamol (HS). The period of mask breathing started at t=0 minutes, lasted for 60 minutes, and at 30 minutes 800 microg salbutamol was inhaled. The experiment was completed 30 minutes after the inhalation (t=60 minutes). For the hypoxia treatment the SpO2 level was 82%. Differences between treatments were sought using factorial ANOVA on percentage change from the pretreatment value. RESULTS: There were no significant differences in blood pressure and potassium levels between the treatments. After 60 minutes the increase in FBF was 13% (95% CI -12 to 39) more for HP treatment than for NP, 21% (95% CI -5 to 46) more for NS than for NP, and 32% (95% CI 7 to 58) more for HS than for HP (p=0.016). The inhalation of salbutamol during hypoxia resulted in a significant increase in FBF of 45% (95% CI 20 to 71) compared with NP (p=0.001). CONCLUSION: Patients with asthma who are hypoxic and inhale beta2 agonists have serious systemic vascular side effects which may be an additional explanation for the association between asthma treatment and sudden death.     

Clinical Experience and Model Analysis on Beta-2-Microglobulin Kinetics in High-Flux Hemodialysis

Abstract: Beta-2-microglobulin (β₂M) is associated with amyloidosis. The study of β₂M kinetics can provide information on the elimination of this uremic toxin. A β₂M kinetic model modified from Gotch, considering the volume changes between intracellular, interstitial, and intravascular compartments and the generation stimulation and inhibition during hemodialysis is proposed. The clinical experiments on 8 stable hemodialysis patients treated with polysulfone (F80) and polymethyl methacrylate (PMMA, BK2.1p) 3 times a week were conducted. There was an 18% decrease of β₂M clearance in the period from 30 to 180 min with a time-averaged β₂M clearance of 48 ml/min using polysulfone dialyzers (F80). In PMMA dialyzers, there was a 64% decrease of β₂M clearance from 30 to 180 min with a time-averaged clearance of 56.3 ml/min. During hemodialysis, the generation rate was 0.379 mg/min in polysulfone and 0.828 mg/min in PMMA dialyzers. There was a stimulation generation of 0.309 mg/min in polysulfone and 0.749 mg/min in PMMA during hemodialysis. In conclusion, we provide a β₂M kinetic model including volume changes, polymerization, generation stimulation, and inhibition that is similar to the human physiological condition. This model can be used for further clinical study.     

Wilms' tumor

In the last 2 decades, important advances in the treatment of Wilms' tumor have been made. The remarkable improvement in survival in these patients has been the product of new surgical techniques, classification of the tumors into prognostic stages upon initial presentation and the tailoring of chemotherapy and radiation therapy thus permitted. A brief historical perspective is presented with a review of the current treatment and ongoing studies.     

Electrolitholysis--from basic research to the formulation of a new therapeutic method

OBJECTIVE: An electrochemical method, based on anodic oxidation and/or protolysis, has been developed with the aim of extending it to the dissolution of urinary stones. The method has been named electrolitholysis, or ELLYS. An ex vivo experimental trial has been performed to check the current intensity needed to obtain the dissolution of stones without lesions to tissues. A new therapeutic method has been conceived based on these preliminary findings. MATERIALS AND METHODS: An ex vivo experimental trial has been performed on twelve bladders surgically removed from pigs and placed in an experimental model resembling possible vital organs; the electrolytic dissolution of natural urinary stones was then performed in these bladders. RESULTS: The ex vivo trial showed that the method is safe and reliable if the current intensity is maintained at < or =30 mA. CONCLUSIONS: A new therapy based on a new concept has been conceived which can be delivered percutaneously through an electrified spiral stent implanted several days into renal cavities and connected with a power supplier (battery) attached to the patient's flank.     

电刺激器放置时间对周围神经再生影响的实验研究

目的：探索周围神经再生开始后,挪开电刺激器是否对神经再生有影响。方法：把Ｗｉｓｔａｒ鼠制成坐骨神经离断模型。Ａ、Ｂ组为电刺激器放置组;Ｃ组将医用硅胶管套在神经缝合处。Ａ、Ｃ组持续观察４周;Ｂ组２周时取出电刺激器,继续观察２周。结果：Ａ、Ｂ组在形态学、电生理学指标上均优于Ｃ组,Ａ、Ｂ组间差异无显著意义。结论：电刺激器对周围神经再生有促进作用,一旦神经再生开始去除电场对神经再生不产生影响。