bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in Renal Outcomes with ACE Inhibitors in Type 1 and Type 2 Diabetic Patients: Possible Explanations
Authors: Jerums George
Published: April 2003

In type 1 diabetic patients, ACE inhibitors exert a renoprotective effect which appears to be additional to, but not entirely independent of, changes in systemic blood pressure. This effect includes attenuation of albumin excretion rate (AER) as well as prevention or slowing of the rate of decline of the glomerular filtration rate (GFR). In type 2 diabetic patients, the results of ACE inhibition are more varied with some studies showing similar renoprotection to that observed in type 1 diabetes and others showing no additional effect to lowering of systemic blood pressure. This may be due to the diverse manifestations of the disease itself or to renal factors which may modify the response to ACE inhibitors. The major sytemic causes of diversity are variations in age, race and blood pressure. The major renal causes of diversity include changes in the relationship or ‘coupling’ of AER to onset of decline in GFR and a heterogeneity of renal ultrastructural changes in the glomeruli, tubules, interstitium and the renal vasculature. Factors that may be responsible for different renal responses to ACE inhibitors in type 2 diabetes include coexistence of coronary heart disease which may introduce survival bias in long-term studies, a lower specificity of microalbuminuria for diabetic nephropathy, early onset of a decline in GFR in hypertensive or normotensive patients at or prior to the onset of microalbuminuria, a greater contribution of arteriosclerotic changes in renal arteries to decline in renal function, a higher prevalence of nondiabetic renal disease, a higher prevalence of hypertension in the elderly and yet to be characterized genetic factors. These variants of type 2 diabetes may be expected to influence the response to ACE inhibitors either by altering the initial proteinuric response or by altering the hypotensive response. Future studies taking into account the above variables may help to determine the relative importance of the above factors in modifying the renal responses to ACE inhibitors and thereby leading to different renal outcomes in type 1 and type 2 diabetic patients. Such studies may also help to assess the relative importance of changes in systemic blood pressure and intrarenal effects as well as the role of hemodynamic versus structural factors in contributing to differences in renal outcome with ACE inhibitors in type 1 and type 2 diabetes.
Growth Hormone and the Heart
Authors: Cittadini Antonio , Longobardi Salvatore , Fazio Serafino , Saccà Luigi
Published: April 2003

Until a few years ago, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) were considered essential only to the control of linear growth, glucose homeostasis, and for the maintenance of skeletal muscle mass. A large body of evidence recently coming from animal and human studies has unequivocally proven that the heart is a target organ for the GH//IGF-1 axis. Specifically GH exerts both direct and indirect cardiovascular actions. Among the direct effects, the ability of GH to trigger cardiac tissue growth plays a pivotal role. Another direct effect is to augment cardiac contractility, independent of myocardial growth. Direct effects of GH also include the improvement of myocardial energetics and mechanical efficiency. Indirect effects of GH on the heart include decreased peripheral vascular resistance (PVR), expansion of blood volume, increased glomerular filtration rate, enhanced respiratory activity, increased skeletal muscle performance, and psychological well-being. Among them, the most consistently found is the decrease of PVR. GH may also raise preload through its sodium-retaining action and its interference with the hormonal system that regulates water and electrolyte metabolism. Particularly important is the effect of GH on skeletal muscle mass and performance. Taking into account that heart failure is characterized by left ventricular dilation, reduced cardiac contractility, and increase of wall stress and peripheral vascular resistance, GH may be beneficial for treatment of heart failure. Animal studies and preliminary human trials have confirmed the validity of the GH approach to the treatment of heart failure. Larger placebo-controlled human studies represent the main focus of future investigations.
Hypertension in Dialysis Patients
Authors: Bellinghieri Guido , Santoro Domenico , Mazzaglia Giampiero , Savica Vincenzo
Published: April 2003

Hypertension is a major risk for cardiovascular complications in dialysis patients. The pathogenesis of hypertension is multifactorial and is not completely understood. Hypervolemia has always been considered a major pathogenetic factor. In addition, a disturbed hormone profile with an activated renin angiotensin system, increased catecholamine, vasopressin and endothelin, and perhaps decreased nitrous oxide activity seem to play a role in the high incidence of hypertension in dialysis patients. The influence of autonomic dysfunction on blood pressure control in hemodialysis patients is not clear. The frequent use of erythropoietin during the last decade may have contributed to the increased incidence of hypertension in the dialysis population. Data from the First Report on Dialysis and Transplant in Sicily showed that hypertension is the cause of end-stage renal disease in 8% of dialysis patients and that the incidence of hypertension, as a cause of end-stage renal disease, increased with age.
Left Ventricular Hypertrophy in Daily Dialysis
Authors: Buoncristiani U. , Fagugli R. , Ciao G. , Ciucci A. , Carobi C. , Quintaliani G. , Pasini P.
Published: April 2003

Cardiac hypertrophy, a well-known independent risk factor for cardiovascular death, is a very frequent complication in ESRD patients. Its frequency tends to be even higher in dialyzed patients due to the fact that the current dialytic treatments are unable to keep under a satisfactory control the various responsible factors and particularly the blood pressure, which is largely the most important. Daily hemodialysis, a more frequent schedule consisting of 6–7 sessions/week lasting 2 or more hours, has definitely proved its superiority in controlling blood pressure and in improving anemia, and thus has the requisites for positively influencing cardiac hypertrophy. In fact, a series of studies, both retrospective and prospective, performed during the last years by our group, have confirmed that this new, more frequent and thus more physiological schedule, is able not only to stop the progression of the cardiac hypertrophy in uremic patients but also to revert toward the normality, in a relatively short time. This appears to be essentially a consequence of the excellent blood pressure control, which in turn derives from the easier control of the true dry weight, achievable with this type of dialytic treatment.
Anemia and Cardiovascular Complications: Iron and EPO Impact
Authors: Kurtzman Neil , Sabatini Sandra
Published: April 2003

Management of end-stage renal disease (ESRD) has been revolutionized by the advent of erythropoietin replacement. We briefly review its characteristics and clinical use. Also emphasized is the importance of iron deficiency in limiting the clinical response to erythropoietin therapy. Iron-replacement therapy in ESRD patients is briefly discussed.
Diagnosis, Pathogenesis, and Treatment of Dialysis-Related Amyloidosis
Authors: Kurokawa Kiyoshi , Miyata Toshio
Published: April 2003

Dialysis-related amyloidosis (DRA) is a major complication of chronic renal failure and long-term renal replacement therapy. β2-Microglobulin is a major constituent of amyloid fibrils in DRA. Amyloid deposition mainly involves bone and joint structures, presenting as carpal tunnel syndrome, destructive arthropathy, and subchondral bone erosions and cysts. While a definitive diagnosis of DRA can only be made by histological findings, various imaging techniques often support diagnosis. The molecular pathogenesis of this complication remains unknown. Recent studies, however, have suggested a pathogenic role of a new modification of β2-microglobulin in amyloid fibrils, i.e. the advanced glycation end products (AGEs). Increased carbonyl compounds derived from autoxidation of both carbohydrates and lipids modify proteins in uremia, leading to augment not only AGE production but also the advanced lipoxidation end product production. Thus, uremia might be a state of carbonyl overload with potentially damaging proteins (‘carbonyl stress’). Therapy of DRA is limited to symptomatic approaches and surgical removal of amyloid deposits. High-flux biocompatible dialysis membranes could be used to delay DRA development.
In vivo Morphologic Changes in the Rat Osteoclast Induced by Gallium Nitrate: The Result of Toxicity or Other Effects?
Authors: Gruber Helen E. , Norton H. James , Singer Frederick R.
Published: April 2003

Gallium nitrate, an approved antitumor drug, has found clinical application in the treatment of cancer-related hypercalcemia and of Paget’s disease; the exact mechanism of its action, however, remains unknown. The present study utilized rats in a 7-day exposure to gallium at doses similar to those used clinically. Quantitative histomorphometry and ultrastructural examination of osteoclast fine structure were carried out on specimens from animals with documented hypocalcemia. Gallium exposure produced striking changes in the osteoclast. The number of nuclei/osteoclast increased, and the ruffled borders of the osteoclasts were markedly decreased along the length of the Howship’s lacunar cavity. The absence of a decrease in osteoclast number and the types of changes seen in ultrastructure suggest that the mechanism of action of gallium seen here may differ from that of calcitonin, a nontoxic, reversible antiresorbing agent. Results underscore the difficulty in assessing the toxicity of agents such as gallium on the osteoclast, a mature differentiated cell which does not divide and which does not produce a characteristic extracellular matrix component.
Regulation of the Na/H Exchanger Regulatory Factor in OK Cells
Authors: Weinman Edward J. , Steplock Deborah , Lamprecht Georg , Yun C.H. Chris , Shenolikar Shirish
Published: April 2003

The Na/H exchanger regulatory factor (NHE-RE), a recently cloned renal protein, is a necessary cofactor in protein kinase A-mediated inhibition of the renal brush border membrane Na/H exchanger. No studies to date, however, have examined the regulation of NHE-RF itself. The rabbit NHE-RF cDNA and an antibody to rabbit NHE-RF were used to study the effects of serum and cyclic adenosine monophosphate (cAMP) on the steady-state levels of NHE-RF mRNA and on the abundance and intracellular distribution of the protein in OK cells. Incubation of quiescent cells with serum was associated with a significant decrease in steady-state NHE-RF mRNA and protein abundance in the cytosolic and membrane fractions. Incubation of cells with cAMP for 6 h was associated with no change in NHE-mRNA at 24 h. There was, however, a 46% increase in protein abundance in the cytosolic fraction of the cell and a 43% decrease in the membrane fraction. Despite the decrease in membrane-associated NHE-RF in quiescent cells treated with serum of cAMP, there were no differences in either the basal rate of Na/H exchange transport or the inhibitory effect of the acute addition of cAMP on the transporter between experimental and control cells. These studies provide the first description of the regulation of NHE-RF. The results indicate that serum is associated with a decrease in NHE-RF mRNA and protein, while chronic exposure to cAMP is associated with an altered distribution of NHE-RF between the cytosolic and membrane fractions of OK cells.
Association between Vitamin D Receptor Gene Polymorphism and Nephrolithiasis
Authors: Ruggiero Marco , Pacini Stefania , Amato Marcello , Aterini Stefano , Chiarugi Vincenzo
Published: April 2003

Aims: To study the distribution of vitamin D receptor (VDR) gene alleles in hypercalciuric and nonhypercalciuric nephrolithiasis patients, hypothesizing that distinct biochemical parameters would be associated with different VDR genotypes. Methods: 12 hypercalciuric, 15 normocalciuric nephrolithiasis patients, and 150 healthy subjects were recruited. The individual genetic pattern for VDR was evaluated by DNA extraction followed by polymerase chain reaction amplification of the VDR gene and digestion with the restriction enzyme BsmI. Results: In the hypercalciuric group, Bb patients represented 50% (6/12); bb patients 33% (4/12), and BB cases were 16% (2/12). The VDR frequency distribution was not statistically different in hypercalciuric patients and controls (Bb 72%; bb 16%; BB 12%). In the nonhypercalciuric group, the prevalence of the bb genotype (7/15; 47%) was thrice the percentage of control subjects, while the percentage of BB patients was similar to that of the control group (2/15; 13%). Patients with the bb haplotype exhibited a higher daily urinary calcium excretion. Among hypercalciuric patients, after a calcium-restricted diet, bb patients showed a 39% reduction in daily urinary calcium excretion in comparison with a nonsignificant 13% reduction observed in BB subjects (p = 0.004). Conclusions: The effects of VDR gene polymorphism on calcium metabolism contribute to the understanding of the pathogenesis of urinary calculi.
The Effect of EGF on Electrolyte Transport Is Mediated by Tyrosine Kinases in the Rabbit Cortical Collecting Duct
Authors: Ookawara Susumu , Tabei Kaoru , Furuya Hiroaki , Asano Yasushi
Published: April 2003

Epidermal growth factor (EGF) inhibits amiloride-sensitive Na+ conductance in the apical membrane of the isolated rabbit cortical collecting duct. However, there is no information on the relationship between electrolyte transport and tyrosine kinase. We examined the effect of EGF on transport of potassium and chloride as well as sodium and the roles of tyrosine kinases in the rabbit cortical collecting duct using in vitro isolated tubular microperfusion. Basolateral EGF depolarized the transepithelial voltage in a dose-dependent manner within a concentration range of 10−10 in 10−8 M. Basolateral ouabain and luminal amiloride completely abolished EGF-induced depolarization. However, luminal BaCl2 did not abolish its depolarization. To confirm the mechanism, sodium, potassium, and chloride fluxes were measured in the presence of 10−10M EGF. EGF significantly decreased the lumen-to-bath isotope flux of sodium and chloride from 93.6±12.5 to 61.1±9.6 pmol/mm/min (n = 5, p<0.05) and from 86.6±10.0 to 54.8±9.7 pmol/mm/min (n = 10, p<0.01), respectively. EGF also decreased net potassium secretion from −27.7±5.9 to –7.8±1.5 pmol/mm/min (n = 6, p<0.01). To examine whether EGF-induced depolarization is mediated by tyrosine kinase, tyrosine kinase inhibitors were applied from the basolateral side. Pretreatment with 1 µg/ml herbimycin A for 120 min completely abolished EGF-induced depolarization (90.9±5.4%, n = 4; NS). Herbimycin A itself also did not change the lumen-to-bath isotope flux of sodium and completely abolished the inhibition of Na+ absorption on EGF action (control 65.4±6.8, herbimycin A 61.8±6.3, EGF with herbimycin A 60.0±4.4 pmol/min/mm, n = 5; NS). In conclusion, EGF depolarizes transepithelial voltage by inhibiting sodium transport primarily and potassium and chloride transport secondarily. These effects were blocked by nonspecific tyrosine kinase inhibitors.
Mechanisms Causing Muscle Proteolysis in Uremia: The Influence of Insulin and Cytokines
Authors: Mitch William , Du Jie , Bailey James , Price S.R.
Published: April 2003

Decreased muscle mass in patients with chronic renal failure (CRF) can be caused by mechanisms that activate the ubiquitin-proteasome proteolytic system. This system accelerates the degradation of muscle protein. Concurrent with muscle protein breakdown, there is an increase in transcription of genes encoding components of this pathway, including ubiquitin and subunits of the proteasome. Potential activating signals include metabolic acidosis which stimulates proteolysis in CRF patients and in muscle of rats with CRF by a mechanism involving glucocorticoids. In CRF patients, there is insulin resistance and high circulating levels of tumor necrosis factor and other cytokines. As the ubiquitin-proteasome proteolytic system is activated in acute diabetes and in catabolic conditions associated with high levels of circulating cytokines, these factors could also activate this pathway. Consequently, we examined whether the transcription factor activated by certain cytokines, NF-ĸB, is involved in the transcriptional regulation of subunits of the 26S proteasome complex. The results suggest that cytokines may be involved in the regulation of muscle protein degradation in uremia.
The Potential of Intradialytic Parenteral Nutrition: A Review
Authors: Pupim Lara , Kent Pamela , Hakim Raymond
Published: April 2003

Malnutrition is common in chronic hemodialysis (CHD) patients and is strongly related to increased morbidity and mortality. Among the various approaches to treat malnutrition in this patient population, intradialytic parenteral nutrition (IDPN) is the treatment of choice for a small but important percentage of malnourished CHD patients. However, the new revised policies relating to IDPN reimbursement by Medicare in the US have made it very difficult to qualify patients for this potentially useful therapy. This restrictive policy was adopted mainly because there are no clear data that support IDPN use or efficacy. Studies to date in the literature do not provide clear documentation of the benefits of IDPN or their cost-effectiveness. The purpose of this review is to critically evaluate studies relating to the use of IDPN as a potential therapy to treat malnutrition in CHD patients and to discuss potential trials to prove its cost-effectiveness.
Nutrition Impact of Peritoneal Dialysis Solutions
Authors: Wolfson Marsha , Jones Michael
Published: April 2003

All peritoneal dialysis (PD) solutions are designed to remove toxins and water, normalize the blood electrolyte profile, and provide alkali to help maintain acid-base balance. Different formulations, however, may have different effects upon nutrition status. Solutions with 40, as opposed to 35, mEq/l of sodium lactate have been found to promote weight and muscle mass gain and reduce hospitalization in malnourished PD patients. Glucose is varied to produce solutions with different ultrafiltration potential. The glucose absorbed from the PD solution has a protein-sparing effect. The high glucose concentrations necessary for sustained ultrafiltration over a long dialysis dwell, however, often produce appetite suppression and metabolic abnormalities. Solutions formulated with glucose polymers, instead of hypertonic glucose, may provide sustained ultrafiltration over long dwells with lower carbohydrate absorption and perhaps fewer metabolic effects. Amino acids can also be substituted for glucose at relatively low concentrations. A number of studies have shown that amino acids absorbed from the dialysis solution can provide nutritional benefit to malnourished PD patients.
Vitamin D Analogs: Perspectives for Treatment
Authors: Brown Alex , Slatopolsky Eduardo
Published: April 2003

Vitamin D therapy is widely used for the treatment of secondary hyperparathyroidism associated with chronic renal failure. However, administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or its precursor 1α(OH)D3, especially in combination with calcium-based phosphate binders, often produces hypercalcemia. Several vitamin D analogs have been developed that retain the direct suppressive action of 1,25(OH)2D3 on the parathyroid glands but have less calcemic activity. These analogs offer a safer and more effective means of controlling secondary hyperparathyroidism. 22-Oxa-1,25(OH)2D3 (22-oxacalcitriol or OCT), 19-nor-1,25(OH)2D2 (19-norD2) and 1α(OH)D2 have been tested in animal models of uremia and in clinical trials. Intravenous 19-norD2 and oral 1α(OH)D2 have been approved for use in the United States; OCT is currently under review. The mechanisms by which these analogs exert their selective actions on the parathyroid glands are under investigation. The low calcemic activity of OCT has been attributed to its rapid clearance which prevents sustained effects on intestinal calcium absorption and bone resorption, but still allows a prolonged suppression of PTH gene expression. The selectivity of 19-norD2 and 1α(OH)D2 is achieved by a distinct mechanism(s). Knowledge of how these compounds exert their selective actions on the parathyroid glands may allow the design of more effective analogs in the future.
Nitric Oxide/L-Arginine in Uremia
Authors: Aiello Sistiana , Noris Marina , Remuzzi Giuseppe
Published: April 2003

Nitric oxide (NO), a gaseous free radical derived from L-arginine, is a potent modulator of vascular tone and platelet functions. A number of recent studies, both in the experimental model of renal mass reduction (RMR) in rats and in uremic patients, have raised the hypothesis that abnormalities of NO synthetic pathway could have a key role in mediating the complex hemodynamic and hemostatic disorders associated to the progression of renal disease. Thus, kidneys from rats with RMR produce less NO than normal rats and NO generation negatively correlates with markers of renal damage. The abnormality is due to a strong defect of inducible NO synthase (iNOS) content in the kidney. Recent in vitro and in vivo data have raised the possibility that excessive renal synthesis of the potent vasoconstrictor and promitogenic peptide endothelin-1 (ET-1) is a major determinant for progressive iNOS loss in the kidney of RMR rats. In contrast, uremia is associated with excessive systemic NO release, both in experimental model and in human beings. In the systemic circulation of uremic rats, as well as uremic patients, NO is formed in excessive amounts. Possible cause of the increased NO levels is higher release from systemic vessels due to the augmented expression of both iNOS and endothelial NOS. A putative cause for excessive NO production in uremia can be guanidinosuccinate, an uremic toxin that accumulates in the circulation of uremic patients and upregulates NO synthesis from cultured endothelial cells. Upregulation of systemic NO synthesis might be a defense mechanism against hypertension of uremia. On the other hand, more NO available to circulating cells may sustain the bleeding tendency, a well-known complication of uremia.
Challenges for Brain Repair: Insights from Adult Neurogenesis in Birds and Mammals
Authors: Doetsch Fiona , Scharff Constance
Published: April 2003

Adult neurogenesis is a widespread phenomenon occurring in many species, including humans. The functional and therapeutic implications of this form of brain plasticity are now beginning to be realized. Comparative approaches to adult neurogenesis will yield important clues about brain repair. Here, we compare adult neurogenesis in birds and mammals. We review recent studies on the glial identity of stem cells that generate new neurons, the different modes of migration used by the newly generated neurons to reach their destinations, and how these systems respond to experimentally induced cell death. We integrate these findings to address how comparative analysis at the molecular level might be used for brain repair.
Effects of Lobus parolfactorius Lesions on Repeated Acquisition of Spatial Discrimination in Pigeons
Authors: Watanabe Shigeru
Published: April 2003

The basal part of the avian telencephalon can be divided into the paleostriatum augmentatum, paleostriatum primitivum and lobus parolfactorius (LPO). In the present experiments, the cognitive functions of the LPO in pigeons were examined. Pigeons were trained on spatial discrimination with or without added color cues using a repeated acquisition procedure. The discrimination task was a choice of three keys in an operant chamber. Every time the subjects reached the criterion, they were trained on a different discrimination in which one of two previously incorrect keys became the correct key. In the task with added color each key had a unique color (i.e., color discrimination). The LPO lesions disrupted the acquisition of both the spatial discrimination and the discrimination with added color. Birds with LPO damage emitted many errors in the first trial indicating the preservation of a previously correct response. Thus, the LPO lesions caused cognitive rigidity. These results are consistent with clinical observations of patients with basal ganglia disorders.
Quantitative Analysis of the Retinal Ganglion Cell Layer in the Ostrich, Struthio camelus
Authors: Boire Denis , Dufour Jean-Sébastien , Théoret Hugo , Ptito Maurice
Published: April 2003

The total number, distribution and peak density of ganglion cells were evaluated in the Nissl-stained retina of the ostrich (Struthio camelus). The mean (n = 4) total number of retinal ganglion cells (RGC) was estimated at 2,274,128 (s.d. = 273, 152). The ostrich retina exhibited a prominent horizontal visual streak along which a central area located nasal to the pecten had a peak density of 9,500 cells/mm2. A high concentration of cells with a peak density of 2,646 cells/mm2 was also observed in the temporal retina, slightly dorsal to the visual streak. The results further showed that the ostrich eye has a 15-mm pupil entrance diameter, its mean axial length is 39.81 mm, the estimated retinal magnification factor is 0.4075 mm/deg and the maximum visual acuity along the well-defined visual streak was estimated to be 19.32 cycles/deg. The latter component of the retina might subserve vision along the horizon while the temporal region mediates binocular processing. The data also showed that the degree of retinal illumination in this bird could be comparable to that noted in some nocturnal species. The findings in this study suggest that the ostrich might not be restricted to diurnal activity.
Serum Cystatin C Reliably Detects Renal Dysfunction in Patients with Various Renal Diseases
Authors: Kazama Junichiro James , Kutsuwada Keiko , Ataka Ken , Maruyama Hiroki , Gejyo Fumitake
Published: April 2003

A clinical investigation was conducted to clarify the reliability and efficacy of serum cystatin C measurement for estimation of the glomerular filtration rate (GFR). Two hundred twelve patients with various renal diseases enrolled in the study. All patients were evaluated for 24-hour creatinine clearance (24 h CCr) and the standard sodium thiosulfate clearance test (CThio) within a week of blood sample collection. Serum cystatin C concentration was determined by a particle-enhanced immunonephelometry method. CThio and 1/cystatin C, 24 h CCr, 1/β2-microglobulin and 1/creatinine were well correlated. The correlation coefficients for CThio obtained by 24 h CCr and 1/cystatin C were comparable to each other (0.701 vs. 0.679). Receiver-operated characteristic (ROC) analysis revealed that 24 h CCr showed the highest area under the curve when CThio = 60 ml/min or CThio = 100 ml/min were applied as the discrimination point. However, the ROC value obtained by cystatin C was slightly greater than 24 h CCr when CThio = 80 ml/min was used as the discrimination point. Patient age, gender, glucose tolerance, presence of proteinuria, systemic inflammation, lupus, or systemic use of steroids did not interfere in the relationship between CThio and 1/cystatin C. In conclusion, serum cystatin C measurement is an excellent diagnostic test for detecting patients with subclinical renal dysfunction.
Repeated Pregnancies in Patients with Primary Membranous Glomerulonephritis
Authors: Malik Ghulam Hassan , Al-Harbi Ali Swaid , Al-Mohaya Suleiman , Al-Wakeel Jamal , Al-Hozaim Waleed , Kechrid Mohammad , Shetia Mohammad Sabry , Hammed Durdana
Published: April 2003

This retrospective study was carried out in patients with membranous glomerulonephritis (MGN) and repeated pregnancies, the aim being to see how one influences the other. Patients with two or more pregnancies after MGN were included in the study. Nine patients underwent 51 pregnancies (range 2–12, mean 5.6) and 30 were post-MGN (range 2–5, mean 3.2). Their ages were 27–44 (32 ± 5.7) years. The duration of follow-up was 2–10 (5.6 ± 2.5) years. The pregnancy outcome, i.e., number of full-term deliveries (FT), spontaneous abortion, preterm deliveries (PT), perinatal mortality (PM), low-birth-weight babies (LBW) and cesarean section (CS), was noted. In the pre-MGN group (n = 21), there were 20 (95.2%) live births and 1 (4.7%) abortion; none had PT, PM, LBW or CS. In the post-MGN group (n = 30), there were 27 (90%) live births, 2 (6.6%) PT, 1 (3.3%) abortion, 1 (3.3%) PM, 3 (10.0%) LBW baries and 3 (10.3%) CS. However, in comparison, there was no statistically significant difference in the pregnancy outcome between the two groups (p > 0.05 in all). Comparing the incidence of hypertension, proteinuria and serum creatinine levels between the first and the last post-MGN pregnancies, there was no statistically significant difference between the two groups. Only 1 patient developed renal insufficiency (serum creatinine 220 µmol/l) after undergoing 5 pregnancies and follow-up of 6 years. In conclusion, the outcome of repeated pregnancies in patients with MGN is good with 90% live births. Repeated pregnancies do not influence the course of MGN.
Blunted Nocturnal Blood Pressure Decrease and Left-Ventricular Mass in Hypertensive Hemodialysis Patients
Authors: Fagugli Riccardo M. , Quintaliani Giuseppe , Pasini Paolo , Ciao Giovanni , Cicconi Beatrice , Pasticci Franca , Buoncristiani Umberto
Published: April 2003

Left-ventricular hypertrophy (LVH) represents a frequent complication in hemodialysis (HD) patients. Hypertension is a well-known risk factor of cardiac morbidity which is present in 2 of 3 patients: among them about 60% have a blunted nocturnal decrease of blood pressure (BP). Although some large studies on essential hypertensives have documented that non-dipper patients have a higher number of cardiac events and a higher left ventricle (LV) mass than dipper ones, conflicting results have been reported for dialysis patients. Therefore, the aim of our study was to assess differences in LV mass between dipper and non-dipper hypertensive HD patients. We studied 66 patients with 24-hour ambulatory BP monitoring performed on HD and on inter-HD day. They were classified as dipper when a decrease of at least 10% of nocturnal systolic blood pressure on the inter-HD day was present. Echocardiography and bioimpedance were performed. 29% of the patients were classified as dippers and 71% as non-dippers. The 48-hour systolic and diastolic BP were not significantly different between the two groups (SBP: dipper = 144 ± 12.9 mm Hg, non-dipper = 149 ± 17.8 mm Hg; DBP: dipper = 80 ± 9.9 mm Hg, non-dipper = 81 ± 10.6 mm Hg). LV mass index (LVMi) did not differ between the two groups (dipper = 143.1 ± 40.7 g/m2; non-dipper = 159.4 ± 46.3 g/m2). No differences were reported between dipper and non-dipper patients regarding extracellular water distribution (ECW: 48.1 ± 7.7 vs. 49.8 ± 10.8%). SBP night/day ratio and 48-hour SBP were not correlated to LVMi. A strong correlation was reported between ECW% and LVMi (r = 0.53, p < 0.001). In conclusion, 2 of 3 hypertensive HD patients are non-dipper, and this condition does not seem to be associated with significant differences in 48-hour blood pressure and LV mass. Volume overload appears to be the main independent determinant of LVH in these patients.
Inhibition of c-Jun N-Terminal Kinase Ameliorates Apoptosis Induced by Hydrogen Peroxide in the Kidney Tubule Epithelial Cells (NRK-52E)
Authors: Wang LiMing , Matsushita Kazumichi , Araki Isao , Takeda Masayuki
Published: April 2003

Background: Hydrogen peroxide (H2O2)-induced apoptosis has been shown to be involved in ischemic and toxic tubular damage. Recent studies have revealed that oxidative stress can activate c-Jun N-terminal kinase (JNK), and the oxidative stress-JNK pathway is an important apoptotic pathway of cells exposed to various stresses. The present study was designed to investigate JNK activation and the effects of the JNK pathway inhibition during H2O2-induced apoptosis in kidney epithelial tubule cells (NRK-52E). Materials and Methods: NRK-52E cells were treated with 0–500 µM H2O2 and/or 100 µM quercetin (an inhibitor of the JNK pathway). Apoptosis was assessed by flow cytometry analysis and DNA ladder. JNK activity was assessed by the GST-c-Jun (1-169) binding/protein kinase assay. Results: H2O2 induced apoptosis in NRK-52E cells in a concentration-dependent manner, which was demonstrated by the reduced DNA PI staining, externalization of phosphatidylserine and DNA ladder. Apoptosis induced by H2O2 was accompanied by JNK activation and up-regulated JNK activity. Quercetin treatment suppressed the JNK activity and ameliorated apoptosis induced by H2O2. Conclusions: H2O2 induced apoptosis in NRK-52E cells, which was associated with activation and up-regulation of JNK. Quercetin treatment could decrease JNK activity and ameliorate H2O2-induced apoptosis.
Analyse und Religion als Übergangsphänomene1
Authors: Plaut Fred
Published: April 2003

Ich beziehe mich auf Winnicotts Beobachtungen von Kleinkindern und seinem späteren objektbeziehungstheoretischen Terminus «Übergangsphänomen», den ich mit Jungs Beobachtung der «aktiven Imagination» und seinem Terminus «vereinigendes Symbol» vergleiche. Unterstützt wird dieser Vergleich von einem gemeinsamen Nenner, nämlich dem Glauben, oder, ausserhalb der Religion, Vertrauen. Religion, Kunst und Philosophie sind für Freud unwissenschaftliche Gebiete, Analyse hingegen ist Wissenschaft. Aber meiner These nach ist die Analyse auch ein Übergangsphänomen. Hier teilen sich die Wege, dessen Extreme «Establishment» und «Mystiker» (Bion) genannt werden.
Comparative Pharmacokinetic and Pharmacodynamic Profile of Piperacillin/Tazobactam 3.375G Q4H and 4.5G Q6H
Authors: Mattoes Holly M. , Capitano Blair , Kim Myo-Kyoung , Xuan Dawei , Quintiliani Richard , Nightingale Charles H. , Nicolau David P.
Published: April 2003

When piperacillin/tazobactam has been used to treat hospitalized patients with serious infections, including nosocomial pneumonia caused by Pseudomonas aeruginosa, it has usually been dosed at 3.375 g q4h to provide serum concentrations above commonly encountered organisms’ MICs (T > MIC) for at least 40–50% of the dosing interval. Pharmacodynamic principles suggest that a similar efficacy can be realized with extended dosing intervals when a larger dose (e.g. 4.5 g q6h) is administered, which was the objective of this study. Twelve healthy volunteers, 29.4 ± 8.9 years of age, were enrolled in this multiple-dose, open-labeled, randomized, two-period crossover study. Blood samples were collected after the third dose and concentrations of piperacillin/tazobactam were determined with a validated HPLC method. Pharmacokinetic profiles were determined by noncompartment analysis. T > MIC of piperacillin was calculated for a range of MIC values. Piperacillin/tazobactam was well tolerated in 11 subjects who completed both regimens. The Cmax, T1/2, K, and AUC of P were significantly different according to a paired t test (p < 0.05) between two study regimens. Significant differences (p < 0.05) in tazobactam regimens were noted for Cmax, and AUC. The piperacillin/tazobactam regimen of 4.5 g q6h achieved a 44% T > MIC for MIC values of ≤16 µg/ml, while the 3.375-gram q4h regimen achieved 42% T > MIC, for MIC values of ≤32 µg/ml. Dosage regimens for treating serious infections can be extended safely and effectively to 4.5 g q6h and obtain at least 40–50% T > MIC in the coverage of pathogens implicated with serious infections, including P. aeruginosa.
Bactericidal Activities of Commonly Used Antiseptics against Multidrug-Resistant Mycobacterium tuberculosis
Authors: Rikimaru T. , Kondo M. , Kajimura K. , Hashimoto K. , Oyamada K. , Sagawa K. , Tanoue S. , Oizumi K.
Published: April 2003

Seventeen clinical isolates of Mycobacterium tuberculosis were selected in order to study the bactericidal activities against drug-resistant M. tuberculosis. The effects of different antiseptics against multidrug-resistant M. tuberculosis (MDR-TB) were examined. Each of the test strains was cultured on the surface of an agar slant containing Löwenstein-Jensen medium. 0.05 ml of the bacillary suspension was poured into a test tube, and 0.45 ml of various antiseptics was added. After the bacilli had been exposed to the antiseptic solution with 2% human serum for various periods of incubation time, the antiseptic was inactivated by addition of 0.45 ml neutralizer, a mixture containing 10% Tween 80, 3% soybean lecithin and 0.5% sodium thiosulfate. As the results, povidone-iodine (PVP-I) at a concentration of 0.2% killed 99.9% or more of all strains tested within 30 s. All of the strains tested with PVP-I were killed almost completely within 60 s. There was no difference in bactericidal activities of PVP-I between standard strain H37Rv and MDR-TB. 99.9% or more of all strains tested were killed after exposure to 1.0% cresol for 60 s. In the case of cresol however, the exposure time of 30 s was not enough to get satisfactory effects. 2.0% glutaraldehyde needed 5 min to kill 99.99% or more of the bacilli tested, and 0.2% alkyldiaminoethylglycine hydrochloride required 60 min to do so. The results of bactericidal activities of common antiseptics against MDR-TB were similar to those against H37Rv. We conclude that the commercially available PVP-I product is a useful antiseptic against MDR-TB similar to other M. tuberculosis.
Strategy of Control of Nosocomial Infections: Application of Disinfectants such as Povidone-Iodine
Authors: Kawana R.Rinji , Nagasawa Shigeru , Endo T.Tadaharu , Fukuroi Yumiko , Takahashi Yoshiko
Published: April 2003

At Morioka Yuai Hospital, the Infection Control Division was set up 5 years ago, and it has made efforts to actively control infections. In particular, the division succeeded in increasing the frequency of general round table discussions for patients with infections. We strongly recommend to frequently gargle with Isodine at operations. Recently, we have followed up patients with infections caused by MRSA, Pseudomonas aeruginosa and Serratia or carriers of these bacteria, and determined the drug sensitivities of clinical isolates. In addition, because of the current highly aged society, a high percentage of inpatients has various underlying diseases. In particular, there are quite a few cases in which pneumonia occurs as an opportunistic infection. From studies in these patients and patients of the dental department, it has been shown that oral microorganisms clearly decrease in count by careful tooth brushing and gargling with Isodine, with prevention of pneumonitis caused by oral microorganisms. As we consider that antisepsis with povidone-iodine is useful for the prevention of nosocomial and opportunistic infections, we would like to report the findings of our study currently under way.
Evaluation of the Bactericidal Activity of Povidone-Iodine and Commercially Available Gargle Preparations
Authors: Shiraishi Tadashi , Nakagawa Yoshito
Published: April 2003

Objective: Encouragement of gargling is important for the control of opportunistic and community-acquired infections. In hospitals, a povidone-iodine (PVP-I) gargle is used frequently. However, at pharmacies in the community a variety of gargles containing various ingredients are now available. In view of this, we conducted a study to compare the bactericidal activities of a PVP-I gargle with those of other commercially available gargles. In addition, we asked about the feeling after use by questionnaire. At middle schools in our city, we investigated whether the encouragement to use the PVP-I gargle had an effect on the absence rate from school due to common cold and influenza. Methods: In vitro, using 3 strains of gram-positive and 4 strains of gram-negative bacteria as the test strains, the bactericidal activities of the PVP-I, chlorhexidine gluconate (CHG) and cetylpiridium chloride gargles (CPC) were compared by the contact test method. In vivo, with subjects in groups of 6 each, the reduction rate in the oral bacterial count after gargling as compared to the baseline count before gargling was determined and compared among the 3 gargling agents used. In addition, a questionnaire study was conducted to compare the feeling after use of the 3 gargling agents. Whether the absence rate due to common cold and influenza changed by encouraging the use of the PVP-I gargle was determined by comparing a middle school where the PVP-I gargle was used and other middle schools where it was not. Results: (1) PVP-I killed all the test strains after 30 s of exposure. (2) The mean reduction rate in bacterial count immediately after gargling was 99.4% for PVP-I, 59.7% for CHG and 97.0% for CPC. (3) Findings of the questionnaire study revealed that the PVP-I gargle was evaluated highest in terms of taste, feeling after gargling and odor among all the gargles tested. (4) At the middle school where the use of the PVP-I gargle was encouraged, the absence rate due to common cold and influenza was significantly lower as compared to those at middle schools where another gargle was used. Conclusion: Of the 3 gargles tested, PVP-I showed the highest bactericidal rate and the highest reduction rate in oral bacterial count. Encouragement of the use of the PVP-I gargle contributed to the decrease in absence rates due to common cold and influenza, indicating that encouragement of gargling with PVP-I is useful for the prevention of common cold and influenza.
Experiences with the Use of Povidone-Iodine-Containing Local Therapeutics in Dermatological Surgery and in the Treatment of Burns: Testing for Allergic Sensitization in Postsurgery Patients
Authors: Juhász István
Published: April 2003

In dermatological surgery where the lesions to be removed are very often contaminated with bacteria, local use of antiseptics that are effective against a wide range of germs is often indicated. Polyvinylpyrrolidone (povidone = PVP)-bound iodine (in Hungary marketed as Betadine®) is used successfully in our department. After excision and suture in per primam healing wounds as well as after tissue destruction in per secundam healing wounds, a thin layer of Betadine ointment on the dressing right after surgery and at dressing changes may reduce the risk of wound infection. When the defect requires split-thickness skin grafting, a combination of tulle gras and a layer of gauze soaked with 1:10 dilution of Betadine solution is suggested. In the treatment of leg ulcers, Betadine is used for cleansing and for impregnating the gauze on top of the tulle gras layer both in the debridement and in the epithelization phases. PVP-I is beneficial on burn wounds due to its effect reducing bacterial colony counts. Its use is advised for superficial (grades 1 and 2a) burns as well as surgical debridement of deep burns or temporary xenograft or definitive autograft coverage of these wounds. After treating a large number of patients with Betadine, a statement can be made: despite its theoretical risk, no cytostatic effect is seen in the clinical setting. No allergy towards Betadine was observed among the author’s patients over several years of its use. Fifty patients previously treated with PVP-I were challenged with epicutaneous patch testing, and no sensitization was found. An account is made on the adverse effects attributed to Betadine found in the scientific literature, and its use with regard to the proper indications is suggested.
New Aspects of the Tolerance of the Antiseptic Povidone-Iodine in Different ex vivo Models
Authors: Kramer A. , Below H. , Behrens-Baumann W. , Müller G. , Rudolph P. , Reimer K.
Published: April 2003

Investigating new possibilities for the application of 1% (v/v) iodophors, povidone-iodine (PVP-I) was better tolerated in the HET-CAM or explant test than 1% (w/v) silver nitrate or tetracycline. After application to the eye, at least 2.6% of used iodine were adsorbed. Therefore PVP-I is more effective than silver nitrate or erythromycin, meaning a possible alternative for the prevention of ophthalmia neonatorum. PVP-I is more active against methicillin-resistant Staphylococcus aureus (MRSA) in a human ex vivo skin model, which results in a complete eradication of S. aureus in the nasal cavity of volunteers after 2 daily applications and will be better tolerated by human nasal cilial epithelium than chlorhexidine. Having the same clinical tolerance as mupirocin, PVP-I is a useful alternative for the antiseptic therapy of germ carriers of MRSA. The synthesis of proteoglycans in articular cartilage of bovine sesamoid bones was increased after application of 5% (v/v) PVP-I without any increase in catabolism revealing possibilities for the use as irrigation solution in the joint.
Ocular Applications of Povidone-Iodine
Authors: Isenberg S.J. , Apt L. , Campeas D.
Published: April 2003

Ocular infections can have devastating consequences and may lead to blindness. Povidone-iodine (PVP-I) has many potential advantages over the currently used drugs, including a broader antibacterial spectrum, it turns the surface of the eye brown for a few minutes, bacterial resistance has not been seen and it is cheaper than other agents. PVP-I has made a significant contribution to pre- and postoperative ocular surgical prophylaxis, ophthalmia neonatorum prophylaxis and treatment of bacterial conjunctivitis. Scientific support for these applications includes studies conducted over the past 17 years, which are reviewed.
In vitro Evaluation of Skin Sensitivity of Povidone-Iodine and Other Antiseptics Using a Three-Dimensional Human Skin Model
Authors: Nagasawa Mieko , Hayashi Hiroyuki , Nakayoshi Takemi
Published: April 2003

Povidone-iodine (PVP-I) is an antiseptic which has been widely used in various fields. It was reported to have a weaker skin irritancy than other antiseptics in the Draize skin irritation test using rabbits. Recent increased concern for animal welfare requires us to use skin models in the tests as an alternative to animal testing. Actually, there are some skin models already commercialized, which are available to evaluate skin irritancy caused by e.g. chemical reagents, cosmetics or medicines. In this study, we evaluated the potential of a PVP-I solution and other antiseptics to cause irritation using a cultured human skin model (three-dimensional skin model) under conditions similar to clinical use. This skin model has two layers like a real skin, such as the dermis and epidermis which includes the cornified layer. For the evaluation of skin irritancy in this model, cell viability was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay as an endpoint. Antiseptic formulations such as benzalkonium chloride (BAC), benzethonium chloride (BEC), chlorhexidine gluconate (CHG) and alkyldiaminoethylglycine hydrochloride (AEG) were used in this study. As a result, PVP-I showed a significantly weaker skin irritancy compared to the other antiseptics. The present in vitro study results revealed a correlation with the results of previously conducted in vivo skin irritancy tests using rabbits.
Pathology of Idiopathic Encephaloceles into the Middle Ear
Authors: Iurato Salvatore , Bux Giuseppe , Colucci Silvia , Dal Sasso Antonio , Mevoli Salvatore , Onofri Marina , Zambonin Alberta
Published: April 2003

Meningoencephalic herniations into the middle ear and mastoid are rare and histologic information has been supplied only in few reports. Sections from two idiopathic encephaloceles were compared with those from encephaloceles associated with previous trauma, infection or surgery described in the literature. In the idiopathic encephaloceles, the herniated tissue consisted of cortical neural tissue with degenerative changes and gliosis like that described in cases with a history of chronic infection, previous surgery or trauma, but no inflammatory cells were present.