The metabolic situation in ureterosigmoidostomy.

At reexamination 67 patients with ureterosigmoidostomies showed no significant alteration of their acid-base and electrolyte metabolism as compared to the preoperative situation and 39 patients with a colonic conduit. If required these patients had received an oral alkali substitution therapy; this proved to be necessary as a permanent measure only in cases with functional and morphological defects of the upper urinary tract. Spells of hyperchloremic acidosis had occurred in 13 patients during the follow-up period and always coincided with attacks of acute pyelonephritis and renal deterioration, often accompanied by irregularities in the substitution. Obviously metabolic problems arise only with a deteriorating urinary tract and timely discovery and treatment of these patients is the main task of the supervising doctor. Although the metabolic imbalances usually respond promptly to an adaptation of the substitution therapy, patients with a predamaged upper urinary tract should not be subjected to ureterosigmoidostomy.     

Is zinc protoporphyrin an indicator of iron-deficient erythropoiesis in maintenance haemodialysis patients?

BACKGROUND.: Zinc protoporphyrin (ZPP), a metabolic intermediate generatedin the red blood cell by incorporation of zinc instead of iron,has been suggested to be a sensitive and specific parameterof absolute iron deficiency in haemodialysis (HD) patients. METHODS.: We studied 62 HD patients, 29–86 years old, with ZPP levels>50 µmol/mol haeme (normal value of ZPP <40 µmol/molhaeme) assessing the value of ZPP as a marker of functionaliron deficiency at different cut-off points of ZPP. None ofthe patients had apparent inflammatory disease, infectious disease,or malignancy. ZPP, haemoglobin, iron and ferritin levels weredetermined before, and after a 24-week period of once-weeklyi.v. administration of 40 mg iron, to determine whether ZPPlevels return to normal during adequate iron supplementation(960 mg iron/patient). RESULTS.: There was no significant change in ZPP levels after iron supplementationin patients with a ZPP >50 µmol/mol haeme (96.7±49.8versus 88.4±43.5 µmol/mol haeme before and afteriron administration respectively, P=n.s.). However, in patientswith a ZPP >90 µmol/mol haeme, there was a significantreduction in ZPP levels (141.2±54.5 versus 108.0±48.8µmol/mol haeme, P<0.001). Serum ferritin increasedsignificantly in both groups. There was no correlation betweenZPP and serum ferritin at any time during the study. There wasalso no correlation between serum aluminium levels and ZPP andno significant difference in changes in ZPP in patients receivingdesferrioxamine therapy compared to those not receiving desferrioxaminetherapy. We did find a significant correlation between moderatelyelevated total blood lead concentrations and ZPP levels at theend of the study. The ZPP levels were not significantly differentin the range from 50–110 µmol/mol haeme before andafter i.v. iron supplementation in the responders (10% increaseof haemoglobin or 20% decrease of the recombinant human erythropoietindose) compared with the non-responders. CONCLUSIONS.: Our data indicate that ZPP cannot be used to predict the erythropoieticresponse to iron supplementation. However, ZPP levels may bean indicator of functional iron deficiency due to blockade ofthe reticuloendothelial iron release in haemodialysis patients.     

Die Tuberkulose des Ureters

Zusammenfassung An Hand des eigenen Krankengutes werden die 4 Arten von Ureterstrikturen im Rahmen einer Urogenitaltuberkulose diskutiert. Ausführliche Darstellung der m?glichen Infektionswege. Besprechung der zur Verfügung stehenden konservativen und operativen Behandlungsm?glichkeiten und Mitteilung der eigenen Resultate.

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Summary Four types of ureteral strictures are discussed. Possible ways of infection are demonstrated. Results of conservative and operative therapeutic regiments are compared to those of other autors.

     

Baseline neuropsychological profile and cognitive response to cerebrospinal fluid shunting for idiopathic normal pressure hydrocephalus

OBJECTIVE: To evaluate neurocognitive changes and predict neurocognitive outcome after ventriculoperitoneal shunting for idiopathic normal pressure hydrocephalus (INPH). BACKGROUND: Reports of neurocognitive response to shunting have been variable and studies that predict cognitive outcomes after shunting are limited. We reviewed our experience with cognitive outcomes for INPH patients who were selected for shunting based on abnormal cerebrospinal fluid (CSF) pressure monitoring and positive response in any of the NPH symptoms following large volume CSF drainage. METHODS: Forty-two INPH patients underwent neurocognitive testing and Folstein Mini-Mental State Examination (MMSE) prior to shunting. Neurocognitive testing or MMSEwere performed at least 3 months after shunt insertion. Significant improvement in a neurocognitive subtest was defined as improvement by one standard deviation (1 SD) for the patient's age, sex and education level. Significant improvement in overall neurocognitive outcome was defined as a 4-point improvement in MMSE or improvement by 1 SD in 50% of the administered neurocognitive subtests. Nonparametric tests were used to assess changes. Predictors of outcome were assessed via logistic regression analysis. RESULTS: Twenty-two patients (52.3%) showed overall neurocognitive improvement, and significant improvement was seen in tests of verbal memory and psychomotor speed. Predictive analysis showed that patients scoring more than 1 SD below mean at baseline on verbal memory immediate recall were fourfold less likely to show overall cognitive improvement, and sixfold less likely if also associated with visuoconstructional deficit or executive dysfunction. Verbal memory scores at baseline were higher in patients who showed overall cognitive improvement. CONCLUSIONS: Shunting INPH patients on the basis of CSF pressure monitoring and drainage response shows a significant rate of cognitive improvement, and baseline neurocognitive test scores may distinguish patients likely to respond to shunt surgery from those who will not.     

Skin permeation of polycyclic aromatic hydrocarbons: A solvent-based in vitro approach to assess dermal exposures against benzo[a]pyrene and dibenzopyrenes

Consumer products with high contents of polycyclic aromatic hydrocarbons (PAHs) were repeatedly identified by market surveillance authorities. Since several of the individual compounds have been identified as genotoxic carcinogens, there might be health risks associated with the usage of these items. It therefore becomes reasonable to argue to reduce PAH contents in consumer products to a level as low as possible. This study presents data on the migration of PAHs from consumer products into aqueous sweat simulant or aqueous ethanol and on its combined migration and penetration into human skin. Product specimens were either submerged in simulant, or placed directly on test skins in Franz cell chambers to simulate dermal contacts. Migration of hexacyclic dibenzopyrenes became detectable by using ethanolic simulant, but not in aqueous sweat simulant. Similarly, migration of the pentacyclic model carcinogen benzo[a]pyrene (B[a]P) into aqueous sweat simulant was significantly lower when compared with human skin or skin models. The results point to a gross underestimation (about two orders of magnitude) when using aqueous sweat simulant instead of human skin for assessing PAH migration. On the other side, the usage of 20% ethanol as simulant revealed good agreement to the actual exposure of human skin against B[a]P migrating out of contaminated products. Our results underline that aqueous sweat simulant is not suitable to study dermal migration of highly lipophilic compounds.     

Silencing S1P1 Receptors Regulates Collagen-V Reactive Lymphocyte-Mediated Immunobiology in the Transplanted Lung

Type V collagen (col[V])-reactive lymphocytes contribute to lung transplant rejection, but the mechanisms for emigration into the graft are unknown. Sphingosine-1-phosphate-1 receptors (S1P_1R) are believed to be required for lymphocyte emigration in other studies, but their role in col(V)-reactive lymphocyte rejection responses is not known. Utilizing small interfering RNA (siRNA) to reduce S1P_1R expression on col(V)-reactive lymphocytes, we examined the role of S1P_1R in the rejection response. Quantitative polymerase chain reaction (PCR) revealed strong expression of S1P_1R messenger RNA (mRNA) on col(V)-reactive lymphocytes isolated from immunized rats. S1P_1R-specific siRNA (S1P_1R siRNA) reduced expression of S1P_1R mRNA and protein, whereas scramble siRNA (SC siRNA) had no effect. Adoptive transfer of lymphocytes treated with S1P_1R siRNA to rat Wistar Kyoto (WKY) lung isograft recipients resulted in retention of cells within the liver with fewer cells in mediastinal lymph nodes when compared to cells exposed to SC siRNA. S1P_1R-deficient cells proliferated in response to alloantigens, but not in response to col(V), and produced less interferon (IFN)-γ in response to col(V) compared to controls. Downregulating S1P_1R did not affect production of interleukin (IL)-10 and tumor necrosis factor (TNF)-α, or expression of adhesion molecules critical for migration, but prevented rejection pathology and lowered local levels of IFN-γ post adoptive transfer. These data demonstrate novel roles of S1P_1R, which include regulating emigration and modulating lymphocyte activation.     

Metalloproteinase inhibition has differential effects on alloimmunity, autoimmunity, and histopathology in the transplanted lung

BACKGROUND: Upregulation of matrix metalloproteinases (MMPs) has been associated with chronic lung allograft rejection known as bronchiolitis obliterans syndrome. It has been suggested that MMP inhibition could prevent the rejection response. However, the effect of MMP inhibition on lung allograft rejection has not been reported. METHODS: Utilizing a rat model of lung transplantation, tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were overexpressed by gene therapy in F344 rat lung allografts prior to transplantation into WKY recipient rats. Separately, WKY rats that received F344 lung allografts were treated systemically with COL-3, a global MMP inhibitor. RESULTS: TIMP-1 and TIMP-2 had differential effects on delayed type hypersensitivity (DTH) responses to donor antigens and type V collagen, an autoantigen involved in the rejection response. Neither TIMP-1 or TIMP-2 affected the onset of rejection pathology. COL-3 suppressed DTH responses to donor antigens and type V collagen, abrogated local production of tumor necrosis factor-alpha, and interleukin-1beta. Although it did not prevent rejection pathology, COL-3 (30 mg/kg) induced intragraft B cell hyperplasia suggestive of posttransplant proliferative disorder (PTLD). CONCLUSIONS: These data identify a complex role for MMPs and TIMPs in the immunopathogenesis of lung allograft rejection, and indicate their effects are not limited to matrix remodeling.