Sudden deafness: a randomized comparative study of 2 administration modalities of hyperbaric oxygenotherapy combined with naftidrofuryl

The pharmacokinetics of a single, oral dose of 750 mg of ciprofloxacin were studied in 35 subjects with various degrees of renal function (Group 1, Clcr > or = 80 ml/min; Group II, Clcr 50-79 ml/min; Group III, Clcr 10-49 ml/min) and on hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Blood, urine and CAPD dialysate samples were collected over a period of 48 hours after dosing. Data were fitted using non-linear, least squares regression. The mean Cmax was 3.4 +/- 1.0 mg/l and tmax was 2.3 +/- 0.9 hours. The mean AUC in Group I was 14.7 mg.h/l, Group II was 33.7 (p < 0.001), Group III 63.8 (p < 0.001), HD 57.9 (p < 0.0001) and CAPD 44.3 (p < 0.001). Half-life in Group I was 4.6 h, and was shorter than Group III (11.1 h, p < 0.001), HD (13.4 h, p < 0.001) and CAPD (8.9 h, p < 0.001). Total body clearance and renal clearance demonstrated significant differences also. The dialysis clearance in CAPD patients was 0.53 +/- 0.39 l/h. Peritoneal effluent concentrations varied from 0.6 mg/l during the first exchange, to a peak of 2.2 mg/l during the second, to 0.13 mg/l in the 48 hour (9th) exchange. Dosage adjustments of ciprofloxacin in the presence of renal insufficiency are indicated for subjects with a Clcr < 20 ml/min/1.73m2.     

A follow-up study on renal tubular dysfunction in women living in the cadmium-polluted Jinzu River basin in Toyama, Japan. Part 1. Changes in the level of exposure to cadmium after soil replacement of polluted paddy fields and the related effects on the prognosis of renal tubular dysfunction

A follow-up study on renal tubular dysfunction was carried out on 193 female inhabitants of the cadmium (Cd)-polluted Jinzu River basin and 40 reference subjects living in an adjacent area in 1994-95. They were 54 to 70 years old when the initial examination was conducted in 1983-84. In the Cd-polluted Jinzu River basin, extensive reclamation of polluted rice fields has been conducted since 1979; as a result, the average Cd concentrations in polished rice consumed by the subjects in the 1994-95 study (0.12 ppm in 1994, 0.14 ppm in 1995) were significantly lower than those in the 1983-84 study (0.26 ppm in 1983, 0.29 ppm in 1984). The average Cd levels in urine in the follow-up study (7.5 micrograms/g Cr. in 1994, 7.7 micrograms/g Cr. in 1995) were also significantly lower than those in the initial study (13.5 micrograms/g Cr. in 1983, 13.3 micrograms/g Cr. in 1984). However, the mean values for urinary excretion of beta 2-microglobulin (beta 2-m) (3.9 mg/g Cr. in 1994, 3.7 mg/g Cr. in 1995) and glucose (203 mg/g Cr. in 1994, 251 mg/g Cr. in 1995) in the follow-up study were significantly higher than those obtained at the initial examination (2.0 mg/g Cr. and 125 mg/g Cr. in 1983 and 1.1 mg/g Cr. and 78 mg/g Cr. in 1984 for beta 2-m and glucose excretion, respectively). The magnitude of increase in urinary excretion of beta 2-m and glucose in inhabitants of the Cd-polluted area was significantly higher than that of the inhabitants of the reference area. Moreover, an increase was observed in the prevalence of renal tubular dysfunction determined by urinary beta 2-m exceeding 10 mg/g creatinine and urinary glucose exceeding 150 mg/g creatinine only among inhabitants of the Cd-polluted area; it is noteworthy that 31 new cases of renal tubular dysfunction were observed in the follow-up study. These results indicate that renal tubular dysfunction among inhabitants of the Cd-polluted Jinzu River basin is irreversible and progressive, and many new cases of renal tubular dysfunction were also noted over a period of 11 years, despite the fact that Cd exposure had decreased over the past 11 years.     

Early diagnosis of impaired glomerular and renal tubule function in patients with acromegaly

BACKGROUND: Albuminuria (A), increased urinary excretion of glycosaminoglycans (GAG) and increased activity of N-acetyl-beta-glucosaminidase (NAG) in urine are early markers of glomerular and tubular changes in various pathological conditions at a time when renal functions do not yet display impaired function and when the changes are still reversible. The objective of the presented study was to assess to what extent these early changes may play a part in acromegaly. METHODS AND RESULTS: In a group of 24 acromegalic patients and in 18 healthy controls the authors examined the microalbuminuria (RIA Immunotech Prague), urinary excretion of glycosaminoglycans (spectrophotometrically by the carbazole method) and they assessed the NAG activity in urine (spectrophotometrically). In acromegalic patients before surgical and pharmacological treatment the authors found, as compared with healthy controls, increased urinary excretion of GAG [4.4 (0.9-22.7) g/mol creat. vs. 2.1 (0.8-5.5) g/mol creat, p < or = 0.001], elevated albuminuria [3.6 (0.3-37.4) g/mol creat. vs. 0.5 (0.1-2.2) g/mol creat, p < or = 0.001 and an enhanced NAG activity [1005 (345-2935) U/l vs. 470 (195-1135) U/l, p < or = 0.001]. The parameters of albuminuria and urinary GAG excretion characterize rather glomerular renal function, they correlate mutually (r = 0.64 p < or = 0.001), while the urinary NAG activity, depending on tubular function, does not correlate with them. No correlation of these parameters with the IGI concentration (for A: 0.3, for GAG: -0.04 and for NAG: -0.02 according to Pearson was found. CONCLUSIONS: In hormonally active acromegalic patients without apparent altered renal functions (normal serum creatinine, Albustix negative) the authors detected early changes of glomerular and tubular functions. They found a significant correction between albuminuria and GAG excretion.     

Cimetidine does not alter atorvastatin pharmacokinetics or LDL-cholesterol reduction

Renal involvement is common in homozygous sickle cell disease (HbSS), including glomerular hypertension and hypertrophy similar to that seen in rodent models of ablative nephrectomy and stage I diabetic nephropathy (DN). The proteinuria in the rodent models is attenuated by angiotensin converting enzyme inhibition (ACEI). Microalbuminuria (MA) is a sensitive marker for renal involvement in DN prior to the development of proteinuria, and is also attenuated with ACEI. Elevated urinary microalbumin/creatinine ratios (U Alb/Cr) >20 mg/g Cr are reported in 39%-43% of adults with HbSS, and studies are ongoing in this age group to assess the effect of attenuated proteinuria by ACEI on long-term renal function. The purpose of this study was to prospectively investigate the prevalence of MA in children with HbSS and determine factors which affect its expression. U Alb/Cr values were measured on spot urine samples in 102 children (aged 2-18 years, mean 9.47+/-4.62, M:F=53:49) by rate nephelometry. Children with prior known proteinuria, hypertension, or fever/pain episode in the last 15 days were excluded. MA was present in 26.5% of all children with HbSS. However, in children between the ages of 10 and 18 years, the prevalence was 46% (similar to the prevalence in adults). There was a strong correlation between patient age and prevalence of MA (P<0.0001) by both univariate and multivariate analysis. However, pain frequency, hospitalization, transfusion program, ferritin levels, and Cr clearance (C(Cr)) did not correlate with prevalence, although C(Cr) (as estimated by Schwartz formula) was elevated in all. We conclude that the prevalence of MA in the 2nd decade of life is similar to that in adults.     

In vivo determination of very-low-density lipoprotein-apolipoprotein B100 secretion rates in humans with a low dose of l-[1-13C]valine and isotope ratio mass spectrometry

Beta2-Microglobulin (beta2-m) is a polypeptide that is freely filtered and then mostly reabsorbed and degraded in the proximal renal tubule. Beta2-m is a marker of glomerular filtration (GFR) in renal failure, whereas urinary beta2-m is a marker of proximal renal tubular dysfunction. Preeclampsia (PE) (ie, de novo hypertension in pregnancy with accompanying renal, cerebral, or liver disease or thrombocytopenia) often has renal involvement characterized by proteinuria, decreasing glomerular filtration, or renal tubular dysfunction. The aim of this study was to determine whether serum beta2-m concentration or urinary beta2-m excretion were greater in women with PE than in women with gestational hypertension (GH) (ie, isolated de novo hypertension in the second half of pregnancy) and normal pregnant women. Seventy-five pregnant women (35 with PE, 22 with GH, and 18 normotensives) were studied prospectively. Serum creatinine and beta2-m concentrations, 24-hour proteinuria, and fractional excretion (FE) of beta2-m were measured. Preeclamptics had similar serum creatinine but higher serum beta2-m (3.26+/-0.99 mg/L) than gestational hypertensives (2.44+/-0.77 mg/L; P = 0.016), and both groups had higher serum beta2-m than controls (1.62+/-0.54 mg/L; P = 0.001). FE of beta2-m was similar amongst groups (PE: 0.27%; interquartile range [IQR]: 0.20-0.86; GH: 0.21%; IQR: 0.11-0.40; controls: 0.26%, IQR: 0.12-0.69). PE is characterized by higher serum beta2-m but similar serum creatinine to GH. Because FE beta2-m is similar in these groups, this implies reduced filtering of beta2-m in PE rather than altered tubular handling of beta2-m. Further studies are now necessary to assess whether measurement of serum beta2-m is helpful in the clinical management of the hypertensive disorders of pregnancy.     

Renal function in patients during and after hypotensive anesthesia with sevoflurane

STUDY OBJECTIVES: To evaluate renal function during and after hypotensive anesthesia with sevoflurane compared with isoflurane in the clinical setting. DESIGN: Randomized, prospective study. SETTING: Inpatient surgery at Rosai Hospital. PATIENTS: 26 ASA physical status I and II patients scheduled for orthopedic surgery. INTERVENTIONS: Patients received isoflurane, nitrous oxide (N2O), and fentanyl (Group I = isoflurane group; n = 13) or sevoflurane, N2O, and fentanyl (Group S = sevoflurane group; n = 13). Controlled hypotension was induced with either isoflurane or sevoflurane to maintain mean arterial pressure at 60 mmHg for 120 minutes. MEASUREMENTS AND MAIN RESULTS: Measurements included serum inorganic fluoride (previously speculated to influence renal function), creatinine clearance (CCr; to assess renal glomerular function), urinary N-acetyl-beta-D-glucosaminidase (NAG; to assess renal tubular function), blood urea nitrogen (BUN), and serum creatinine (as clinical renal function indices). Serum fluoride, CCr, and NAG were measured before hypotension, 60 minutes, and 120 minutes after the start of hypotension, 30 minutes after recovery of normotension, and on the first postoperative day. BUN and serum creatinine were measured preoperatively and on the third and seventh postoperative days. Minimum alveolar concentration times hour was 3.6 +/- 1.8 in Group I and 4.0 +/- 0.7 in Group S. In both groups, BUN and serum creatinine did not change, and CCr significantly decreased after the start of hypotension. In Group I, serum fluoride and NAG did not change. In Group S, serum fluoride significantly increased after the start of hypotension compared with prehypotension values and compared with Group I values. In addition, NAG significantly increased at 120 minutes after the start of hypotension and at 30 minutes after recovery of normotension, but returned to prehypotension values on the first postoperative day. CONCLUSIONS: Two hours of hypotensive anesthesia with sevoflurane under 5 L/min total gas flow in patients having no preoperative renal dysfunction transiently increased NAG, which is consistent with a temporary, reversible disturbance of renal tubular function.     

Effects of gemcitabine on renal function in patients with non-small cell lung cancer

Gemcitabine is a novel fluorine-substituted cytarabine (Ara-C) analogue with activity against a range of solid tumours. Besides dose-limiting haematological toxicity, renal side-effects were observed from phase I and II studies concerning elevations of serum creatinine, proteinuria and erythrocyturia. The aim of this study was to investigate the effect of gemcitabine on renal function in 11 untreated patients with non-small cell lung cancer (NSCLC). Gemcitabine was given as weekly infusions of 1250 mg/m2 for 3 weeks, followed by 1 week rest. This comprised one cycle (maximum of six cycles). The glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured simultaneously with a constant infusion of 125I-iothalamate and 131I-hippuran, respectively. Tubular damage was monitored by excretion of tubular enzymes (lactic dehydrogenase (LDH), alkaline phosphatase (ALP), gamma-glutamyltransferase (GT) and beta 2-microglobulin); glomerular damage was monitored by excretion of albumin in the urine. In 9 patients, the effect of the first infusion was evaluated. After the first infusion of gemcitabine, no change was observed in renal function. After two, three, and six cycles of treatment, no significant changes in GFR and ERPF were noticed in 9 evaluable patients. However, in 3 patients, a decrease in GFR of > 10% was observed after multiple cycles. In one of them this was accompanied with albuminuria (360 mg/24 h) and erythrocyturia. There were no significant changes in urinary excretion of tubular enzymes or albumin. In conclusion, we did not observe acute renal toxicity with gemcitabine. No significant cumulative effects of gemcitabine on renal function could be detected, although 3 patients, treated with multiple cycles of gemcitabine, showed a moderate decrease in renal function. Glomerular damage might play a role in the development of renal function loss.     

Activated T cells and genetic restriction in celiac disease

Studies in the last decade demonstrated that in children tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR) is identical to TP/GFR; TP indicating tubular phosphate reabsorption under basal conditions, without phosphate load. TP/GFR is calculated from the formula TP/GFR = SP-UP x SCr:UCr, based on simultaneous urine and blood creatinine and phosphate concentrations, and is applicable in both the fasting and non-fasting child. These studies also demonstrated that the use of Walton and Bijvoet nomogram in children may result in overestimation of TmP/GFR compared with TP/GFR calculated from the above formula. When using the formula, one should bear in mind that creatinine is used to express GFR and as a result a significant deviation from true GFR may occur in patients with renal failure. Therefore when employing TP/GFR for the investigation of the renal handling of phosphate in children, three factors should be taken into consideration: (1) the formula in reality expresses TP/CCr; (2) only data obtained by exactly the same methodology can be used as reference values; data obtained from studies in which the nomogram was utilized or in which methods other than CCr were used to measure GFR should not be used for reference; (3) in patients with renal failure, TP/CCr will significantly overestimate TP/Cinulin.     

Physiopathology of proteinuria and laboratory diagnostic strategy based on single protein analysis

A quantification of proteins of different molecular size has been shown to be useful in characterizing the mechanism and medical causes of proteinuria. By analyzing urine albumin, alpha1-microglobulin, immunoglobulin G and alpha2-macroglobulin together with total protein, prerenal, glomerular, tubular and postrenal causes of proteinuria can be detected and differentiated by their specific urine protein patterns. Using automated turbidimetric procedures, prerenal proteinurias are characterized by an albumin/total protein ratio below 0.4. Tubulo-interstitial diseases which are negative in the protein test strip procedure are detected and clearly differentiated from other causes of proteinuria by their high alpha1-microglobulin/albumin ratios. In post-renal proteinuria, alpha2-macroglobulin proved to be a useful marker, when albumin excretion exceeds 100 mg/l urine. This protein exhibits plasma-like ratios to albumin in postrenal causes, whereas it is much lower in renal proteinurias. The new strategy, which has been evaluated in more than 500 clinically and partly histologically proven cases of renal diseases, more sensitively detects glomerular and tubulo-interstitial diseases when applied in urine screening and allows us to distinguish all clinically important causes from analysis of a morning spot urine sample.     

A SPECT imaging study of MRI white matter hyperintensity in patients with degenerative dementia

Hydroxyethyl starch is commonly used in resuscitation, anaesthesia and intensive care medicine. Increasing creatinine values in patients treated with hydroxyethyl starch have been described in some case reports. These have also been some clinical signs such as pain in the renal region, and swelling of kidney parenchyma, but no differential and sensitive parameters of renal function have supported these possible side effects of hydroxyethyl starch. Twenty-five patients were randomly allocated to a control and a treatment group. In the treatment group, patients received 12 ml per kg body-weight hydroxyethyl starch 10% (200/0.5) daily. A non-invasive diagnostic spectrum of renal function was performed. Specific tubular proteins (alpha 1-microglobulin, Tamm-Horsfall protein), glomerular parameters (immunoglobulin G, albumin), and the brush border enzyme acetyl-beta-glucosaminidase, were examined. Additionally, renal blood flow and glomerular filtration rate, Apache-II-score, breathing therapy, infusions, transfusion, and all medical interventions were documented. Both groups were comparable with regard to drug therapy. Apache-II-score, and fluid management. There were differences in tubular function between the two groups. Patients undergoing HES therapy showed increased excretion of alpha 1-microglobulin. Tamm-Horsfall-protein and of brush border enzyme acetyl-beta-glucosaminidase. No significant differences were detectable in glomerular functions (glomerular filtration rate, renal blood flow), albumin, and IgG. Correlates of tubular damage after hydroxyethyl starch therapy were seen in intensive care patients. Many influences of intensive therapy act on renal function, and further studies with larger cohorts are necessary. With regard to the documented localisation of the tubular damage in the HES group, colloid therapy with hydroxyethyl starch in renal dysfunction should be monitored carefully by means of sensitive markers.     

Should benefit-risk ratio of the intramuscular vitamin K be reevaluated in newborn infants?

AIM: To compare the pharmacokinetics after po different doses of beta-carboxyethylgermanium sesquioxide (Ge-132). METHODS: An atomic absorption spectrophotometric system was used to measure germanium concentrations in plasma and urine samples after po Ge-132 1 (low dose, LD), 2.5 (medium dose, MD), and 4 (high dose, HD) g.m-2 in 24 healthy volunteers (one dose per 8 subjects). RESULTS: T1/2 alpha (LD, 1.2 +/- 0.7 h; MD, 1.1 +/- 0.6 h; HD, 1.2 +/- 0.5 h), T1/2 beta (LD, 5.2 +/- 1.2 h; MD, 5.8 +/- 2.5 h; HD, 5.5 +/- 1.4 h) and Cl/F (LD, 33 +/- 12 L.h-1; MD, 35 +/- 10 L.h-1; HD, 33 +/- 11 L.h-1) were not dose-related. Tmax was between 0.75 h and 2 h. Cmax (LD, 5.3 +/- 2.2 mg.L-1; MD, 13 +/- 5 mg.L-1; HD 18 +/- 8 mg.L-1, HD) and AUC (LD, 31 +/- 13 mg.h.L-1; MD, 60 +/- 16 mg.h.L-1; HD, 79 +/- 42 mg.h.L-1) were positive correlation to the dose of Ge-132. Urine-eliminated germanium within 24 h accounted for 11 +/- 3% of LD, 9 +/- 3% of MD, and 6 +/- 5% of HD (calculated from Ge/F) and showed a negative correlation to the dose. CONCLUSION: 1) Intracorporal process of Ge after po Ge-132 coincided with the first-order absorption and elimination with two-compartment kinetic model; 2) The amount of germanium eliminated in urine was below 11%.     

Clinicopathological significance of intratubular giant macrophages in progressive glomerulonephritis

Very large macrophages, which we have termed "giant macrophages" (G-M phi), have been found in renal tubules, some containing cytoplasmic vacuoles. To elucidate their pathophysiological roles, we examined renal biopsy tissues from various primary glomerulonephritis (GN) and tubulointerstitial nephritis (TIN) using immunohistochemistry with monoclonal antibodies against M phi and other cell surface markers. Giant macrophages were absent or rare in TIN, minimal change nephrotic syndrome, and minor glomerular abnormalities, but G-M phi was plentiful in progressive glomerulonephrides such as IgA nephropathy with crescents, membranoproliferative GN, focal segmental glomerulosclerosis, and especially in crescentic GN. These G-M phi were usually seen in the lumen of renal tubules, but occasionally were found in the Bowman's spaces and glomerular tufts, and similar cells were also found in urine. Moreover, they frequently made contact with tubular epithelial cells expressing intercellular adhesion molecule-1, and the tubular epithelial cells in such lesions often had degenerative changes. Giant M phi may damage tubular epithelial cells from the luminal side. Phenotypically, G-M phi showed activated (CD71+) and mature (25F9+) characteristics along with features of M phi (CD68+), and the cytoplasm contained a great deal of lipids. The numbers of G-M phi in renal tissues closely correlated with the degree of hematuria (rho = 0.5, P < 0.001), serum creatinine value (r = 0.63, P < 0.001) in GN patients (N = 96) and with proteinuria in IgA nephropathy patients (r = 0.89, P < 0.001, N = 27). These data suggest that G-M phi are M phi that were activated and matured in certain active inflammatory sites, which flowed into tubules and then into urine. Thus, the existence of G-M phi in biopsy tissue or urine reflect the activity of GN and may have a predictive value for the progression of GN.     

Role of CD59 in experimental glomerulonephritis in rats

CD59 is a molecule which is present on the host cell membranes and inhibits formation of membrane attack complex. A monoclonal antibody, 6D1, recognizes a rat analogue of human CD59. 6D1 inhibits function of rat CD59 and can enhance complement-mediated hemolysis in vitro. To assess the role of CD59 in complement-mediated glomerular injury, 6D1 was tested in a model of experimental glomerulonephritis induced by a lectin and its antibodies. The left kidney of a rat was perfused either with 200 micrograms of Lens culinaris hemagglutinin (LCH) plus 1 mg of 6D1 (IgG1 fraction) (Group I and III) or with LCH only (Group II) through a cannula placed in the left renal artery. All the perfusate was discarded from a cannula in the renal vein. The holes in the artery and vein were repaired by microsurgery and the blood circulation was re-established. Rats were injected either with 0.125 ml of rabbit anti-LCH serum (Group I and II), or with normal rabbit serum (Group III) via tail vein one minute after the recirculation. Fifteen minutes after injection, significant C9 deposition in the glomeruli was observed only in Group I, whereas C3 deposition in Group I and II were comparable. At Day 4, total glomerular cells, proliferating cells, glomerular expression of intercellular adhesion molecule-1 and fibrin deposition in Group I were all significantly increased when compared with Group II. At Day 7, number of total glomerular cells and leukocytes in the glomeruli of Group I were significantly higher than in Group II. The glomeruli in Group III appeared normal throughout experiments. These data indicate that the functional inhibition of a rat analogue of human CD59 worsens complement-mediated glomerular injury in vivo.     

Hemofiltration or hemodiafiltration with on-line production of substitution fluid: clinical observation of safety and effectiveness

OBJECTIVE: To observe the safety and cardiovascular stability of on-line hemofiltration (HF) or hemodiafiltration (HDF) and evaluate the clinical effectiveness of one HF or HDF session in addition to two hemodialysis (HD) sessions weekly. METHODS: Forty patients were randomly divided into four groups: group predilutional (PRD) HF (filtration rate: 259-333 ml/min) group predilutional HDF (filtration rate: 167 ml/min) group postdilutional (POD) HDF (filtration rate: 83 ml/min) and group bicarbonate HD. The reduction rate of parathyroid hormone (PTH), beta 2-microglobulin (beta 2MG), alpha 1-microglobulin (alpha 1MG) and KT/V in the initial treatment of every month was observed, and the incidence of hypotension and pyretic reaction during each treatment was evaluated. RESULTS: After 4-month observation, the KT/V for Group POD HDF is better than that for the other three groups, and for Group PRD HDF is better than that for Group HF and HD. Serum level of PTH and beta 2MG was not decreased after every treatment in Group HD, and so was serum level of alpha 1MG in all groups. Significant removal of PTH and beta 2MG was observed in Group HF, PRD HDF and POD HDF. The monthly serum level of beta 2MG and KT/V were stable in all groups, but the monthly serum level of PTH tended to be decreased in Group HF, PRD, HDF, and POD HDF. The incidence of pyretic reaction in HF or HDF was the same as in HD. Although the ultrafiltration volume was significantly higher during HF or PRD HDF than during HD, the incidence of hypotension in HF or PRD HDF was similar to that in HD. CONCLUSIONS: On-line HF or HDF proved to be a safe and reliable method. POD HDF mode seems to have the best KT/V, HF or PRD HDF offers a better choice for preventing intradialytic hypotension. One HF or HDF session in addition to two HD sessions weekly is similarly effective to decrease the serum level of PTH and the proof of the clinical effectiveness of such a therapy awaits a long-term observation.     

Duplex (thermotroph-psychrotroph) quadrant plates: convenient, error-avoiding tools for monitoring of HACCP-contained food lines and for epidemiological investigations under conditions of military or other constraints

The present study evaluated whether chronically administered low-dose (<5 mg/kg) ciclosporin A (CsA) affects renal haemodynamics and tubular function in renal transplant recipients (RTx) when studied at nadir CsA blood levels. The renal clearance of lithium was used as an index of proximal tubular outflow of sodium and water. Effective renal plasma flow, glomerular filtration rate, and renal clearance of lithium were studied in 67 stable non-diabetic RTx and 44 healthy controls. Forty-eight of the RTx were treated with CsA, prednisone, and azathioprine. Nineteen were treated exclusively with prednisone and azathioprine. In RTx with a good graft function (serum-creatinine <125 micromol/l), no specific CsA-induced renal haemodynamic and tubular dysfunctions were evident. In CsA-treated RTx with a slightly reduced renal function (serum creatinine 125-180 micromol/l) a decrease in fractional proximal tubular reabsorption was found. The renal clearances of urate and magnesium were comparable between RTx treated with or without CsA, and a significant correlation between glomerular filtration rate and renal clearance of urate was found. CsA-treated RTx had a significantly higher blood pressure, independent of glomerular filtration rate and segmental tubular function. In conclusion, at nadir CsA blood levels, no specific CsA-induced tubular dysfunction evaluated by the renal lithium clearance method could be demonstrated in RTx receiving chronically low-dose CsA. The hyperuricaemia commonly seen in RTx seems to be mainly caused by the reduced glomerular filtration rate.     

Interferon-gamma-inducing factor gene transfection into Lewis lung carcinoma cells reduces tumorigenicity in vivo

The operative mortality and morbidity in patients with severe left ventricular dysfunction who undergo coronary artery bypass grafting (CABG) remain high. The low ejection fraction is the major risk factor for operative mortality. However, ejection fraction (EF) alone may not necessarily be an accurate predictor of operative mortality. We studied the correlation between indices of left ventricular volume and operative mortality. One thousand patients undergoing isolated coronary bypass operations were divided into three groups according to their preoperative ejection fraction. Fifty patients (group I) had severe left ventricular dysfunction (EF < or = 0.3), 56 patients (group II) had moderately left ventricular dysfunction (0.3 < EF < or = 0.4) and 894 patients (group III) had good left ventricular function (EF > 0.4). We analyzed the relationship between hospital mortality and left ventricular volume in 106 patients with an EF < or = 0.4. RESULTS: Cardiac index was not significantly different among the three groups. The left ventricular end-diastolic pressure (LVEDP) and mean pulmonary artery pressure in groups I an II were higher than those in group III. The left ventricular end-diastolic volume (LVEDV) was 146 +/- 44 ml/m2 in Group I, 112 +/- 31 ml/m2 in Group II and 82 + 30 ml/m2 in Group III, respectively (Group I versus II, p < 0.05, Group I and II versus III, p < 0.01). The left ventricular end-systolic volume (LVESV) was 111 +/- 38 ml/m2 in Group I, 72 +/- 21 ml/m2 in Group II and 30 +/- 14 ml/m2 in Group III, respectively (Group I versus II, p < 0.05, Group I and II versus III, p < 0.01). The LVEDV and LVESV were higher in Group I than in Group II and both in Groups I and II were higher than in Group III. The hospital mortality of any cause before discharge was 8.0% (4/50) in Group I, 3.6% (2/56) in Group II, and 2.0% (18/894) in Group III. The mortality in Group I was higher than that in Group III, but the mortality between Groups I and II was not different. We assessed correlations between large left ventricle with left ventricular dysfunction and operative mortality in 106 patients with ejection fractions of < or = 0.4. The hospital mortality in patients with both under fraction 0.4 and an LVESV > or = 140 ml/m2 was 50% (4/8). This rate was higher than in patients with an LVESV between 80 and 140 ml/m2 (1.8%, 1/55) (p = 0.0006) and an LVESV less than 80 ml/m2 (2.3%, 1/43), (p = 0.0013). The hospital mortality in patients with an LVEDV > or = 200 ml/m2 was 67% (4/6). It was also higher than that in patients with an LVEDV between 200 and 120 ml/m2 (1.7%, 1/58), (p = 0.0001), and an LVEDV less than 120 ml/m2 (2.4%, 1/42), (p = 0.0004). We conclude that patients with a low ejection fraction and an elevated LVESV or LVEDV are at increased risk for hospital death following CABG.     

Renal handling of Zn-alpha2-glycoprotein as compared with that of albumin and the retinol-binding protein

An unusual electrophoretic pattern of the urine from a patient with malignant lymphoma was observed. One of the major proteins, identified Zn-alpha2-glycoprotein (Zn-alpha2), was isolated from the urine and partly characterized. The Stokes radius was found to be 3.24 nm and the molecular weight, determined by sodium dodecyl sulfate polyacrylamide electrophoresis, 42,000. The plasma level in healthy individuals was 39 +/- 7 (SD) mg/liter. In 12 of 25 healthy individuals, Zn-alpha2 was measurable in the urine and was found to be 1.0 +/- 1.1 mg/liter. In 23 patients with chronic glomerulonephritis (CGN), in 9 with proximal tubular dysfunction (PTD), in 23 with various renal diseases (VRD), and in 10 with malignant lymphoma, the plasma level and the urinary excretion were compared with those of albumin (mol wt 67,000) and of the retinol-binding protein (RBP, mol wt 21,000). A close correlation was found between the urine-to-plasma (U/P) ratios of Zn-alpha2 and albumin in the patients with CGN, whereas in the PTD patients the U/P ratios of Zn-alpha2 and RBP were correlated. No significant renal arteriovenous difference in Zn-alpha2 could be demonstrated. The Zn-alpha2 excretion was increased also in two patients with malignant lymphoma and proteinuria of a tubular pattern. The plasma Zn-alpha2 varied inversely with the glomerular filtration rate in the patients with renal disease, but was normal in those with malignant lymphoma. The results are consistent with the assumption of a sieving coefficient of Zn-alpha2, substantially exceeding that of albumin, but notably lower than that of smaller low-molecular-weight proteins. An increased excretion of Zn-alpha2 may be due to increased glomerular permeability as well as to defective proximal tubular reabsorption.     

Activity of cathepsin B and collagenase in urine and excretion of fibronectin and TGF-beta 1 in urine of patients with membranous glomerulonephritis

In 30% cases nephrotic syndrome is due to membranous glomerulonephritis (MG). Fifty percent of patients reveal end stage renal disease in 15 years follow-up. The another 50% gain persistent remission. The pathogenesis of disease is not known. Protein accumulation in glomeruli leads to progressive loss of kidney structure and function in MG. Also the role of tissue proteolytic systems and growth factors in this process is not known. We aimed to estimate urine cathepsin B, collagenase activity and urine excretion of TGF-beta 1 and fibronectin in MG. MG patients revealed increased urine cathepsin B activity (10.58 +/- 8.73 pmol AMC/mg creatinine/min. vs. control 7.11 +/- 2.05 pmol AMC/mg creatinine/min. [p < 0.05]), urine collagenase activity (8.59 +/- 4.26 pmol AMC/mg creatinine/min. vs. control 3.84 +/- 2.09 pmol AMC/mg creatinine/min. [p > 0.02]) and increased urine excretion of fibronectin (214 +/- 335 ng/mg creatinine vs. control 12.7 +/- 6.7 ng/mg creatinine [p < 0.05]) and increased urine excretion of TGF-beta 1 (283.55 +/- 248.13 pg/ml vs. control 36.11 +/- 48.01 pg/ml [p < 0.05]). The results indicates on glomerular overproduction of TGF-beta 1 and urinary leak of proteolytic enzymes which may exacerbate glomerular proteolytic activity in MG. This may lead to glomerular protein accumulation and progressive loss of kidney function and structure in MG. Increased urine fibronectin excretion in MG patients seems to confirm the hypothesis.     

Increased myocardial ultrasonic reflectivity is associated with extreme hypertensive left ventricular hypertrophy: a tissue characterization study in humans

We assessed myocardial reflectivity pattern in a large spectrum of left ventricular mass values, covering the extremes from absent to severe myocardial hypertensive hypertrophy. Quantitatively assessed ultrasonic backscatter is an index of ultrasonic tissue characterization directly related to the morphometrically evaluated collagen content in humans. We enrolled 88 essential hypertensives. With an echo prototype implemented in our Institute, integrated values of the radiofrequency signal of myocardial walls were obtained and normalized for those of the pericardium (Integrated Backscatter Index, IBI, %). Left ventricular mass index (LVMI) was measured by Devereux formula. There was a weak correlation between septal IBI and LVMI (r = 0.35; P < .001). On the basis of LVMI values, three groups of hypertensives were identified, with absent (Group I, n = 23; LVMI < 125 g/m2), mild to moderate (Group II, n = 44; LVMI from 125 to 174 g/m2), or severe (Group III, n = 21; LVMI > 175 g/m2) left ventricular hypertrophy. The Integrated Backscatter Index in the septum was lower in patients of Group I (IBI = 23.3% +/- 3.6%) and II (IBI = 26.5 +/- 7.6; P = NS v Group I), in comparison with patients of Group III (IBI = 31.1 +/- 5.9; P < .02 v II; P < .0001 v I). An increased myocardial wall reflectivity is detectable only in the presence of extreme forms of hypertensive left ventricular hypertrophy.     

Significance of the karyopyknotic index in the course control of hormone-treated prostatic carcinoma

Renal function was evaluated in 40 patients with fulminant hepatic failure, They were divided into two groups on the basis of glomerular filtration rates greater than 40 ml/min or less than 25 ml/min. A number of patients in group 1 had markedly abnormal renal retention of sodium together with a reduced free water clearance and low potassium excretion which could be explained by increased proximal tubular reabsorption of sodium. The patients in group 2 had evidence that renal tubular integrity was maintained when the glomerular filtration rate was greater than or equal ml/min (functional renal failure), but evidence of tubular damage was present when this was less than 3 ml/min (acute tubular necrosis).