Uveitis intermedia as the initial presentation of a primary lymphoma of the central nervous system.

Primary central nervous system lymphoma is one of the most infrequent brain tumours, accounting for 3% of primary central nervous system neoplasms. In addition to its low prevalence, clinical presentation is usually nonspecific, leading to diagnostic delay. Intraocular involvement occurs in 15% of cases, and disease onset in this location is even rarer. We present a case of a patient with intermediate uveitis as the first clinical manifestation of this neoplasm.

Uveítis intermedia como presentación inicial de un linfoma primario del sistema nervioso central / Uveitis intermedia as the initial presentation of a primary lymphoma of the central nervous system

El linfoma primario del sistema nervioso central (LPSNC) es una de las neoplasias cerebrales más infrecuentes, representando el 3% de los tumores primarios en dicha localización. Sumado a su baja prevalencia, las manifestaciones clínicas de esta patología son poco específicas, por lo que es común el retraso diagnóstico de esta entidad. El compromiso intraocular relacionado al LPSNC ocurre sólo en un 15% de los casos, siendo aún más inusual que dicha topografía se presente como debut en esta enfermedad. Presentamos el caso clínico de una paciente con uveítis intermedia como primera manifestación clínica de esta neoplasia (AU)

Primary central nervous system lymphoma is one of the most infrequent brain tumours, accounting for 3% of primary central nervous system neoplasms. In addition to its low prevalence, clinical presentation is usually nonspecific, leading to diagnostic delay. Intraocular involvement occurs in 15% of cases, and disease onset in this location is even rarer. We present a case of a patient with intermediate uveitis as the first clinical manifestation of this neoplasm (AU)

Uveitis intermedia as the initial presentation of a primary lymphoma of the central nervous system. / Uveítis intermedia como presentación inicial de un linfoma primario del sistema nervioso central.

Primary central nervous system lymphoma is one of the most infrequent brain tumours, accounting for 3% of primary central nervous system neoplasms. In addition to its low prevalence, clinical presentation is usually nonspecific, leading to diagnostic delay. Intraocular involvement occurs in 15% of cases, and disease onset in this location is even rarer. We present a case of a patient with intermediate uveitis as the first clinical manifestation of this neoplasm.

[Primary neurolymphomatosis in the cauda equina as the initial symptom of human immunodeficiency virus]. / Neurolinfomatosis primaria de cola de caballo como manifestacion inicial del virus de la inmunodeficiencia humana.

TITLE: Neurolinfomatosis primaria de cola de caballo como manifestacion inicial del virus de la inmunodeficiencia humana.

Nephron prorenin receptor deficiency alters renal medullary endothelin-1 and endothelin receptor expression.

The endothelin (ET) and prorenin/renin/prorenin receptor (PRR) systems have opposing physiological effects on collecting duct (CD) salt and water reabsorption. It is unknown if the CD ET and renin/PRR systems interact, hence we examined the effects of deleting CD renin or nephron PRR on CD ET system components. PRR knockout (KO) mice were polyuric and had markedly increased urinary ET-1 and inner medullary CD (IMCD) ET-1 mRNA. PRR KO mice had greatly increased IMCD ETA receptor mRNA and protein, while ETB mRNA and protein were decreased. Water loaded wild-type mice with similar polyuria as PRR KO mice had modestly increased urinary ET-1 excretion and inner medullary ET-1 mRNA, while inner medullary ETA and ETB mRNA or protein expression were unaffected. In contrast to PRR KO, CD prorenin/renin KO did not alter ET system components. Taken together, these results suggest that the nephron PRR is involved in regulating CD ET system expression, but this effect may be independent of CD-derived renin.

Targeting renal purinergic signalling for the treatment of lithium-induced nephrogenic diabetes insipidus.

Lithium still retains its critical position in the treatment of bipolar disorder by virtue of its ability to prevent suicidal tendencies. However, chronic use of lithium is often limited by the development of nephrogenic diabetes insipidus (NDI), a debilitating condition. Lithium-induced NDI is due to resistance of the kidney to arginine vasopressin (AVP), leading to polyuria, natriuresis and kaliuresis. Purinergic signalling mediated by extracellular nucleotides (ATP/UTP), acting via P2Y receptors, opposes the action of AVP on renal collecting duct (CD) by decreasing the cellular cAMP and thus AQP2 protein levels. Taking a cue from this phenomenon, we discovered the potential involvement of ATP/UTP-activated P2Y2 receptor in lithium-induced NDI in rats and showed that P2Y2 receptor knockout mice are significantly resistant to Li-induced polyuria, natriuresis and kaliuresis. Extension of these studies revealed that ADP-activated P2Y12 receptor is expressed in the kidney, and its irreversible blockade by the administration of clopidogrel bisulphate (Plavix(®)) ameliorates Li-induced NDI in rodents. Parallel in vitro studies showed that P2Y12 receptor blockade by the reversible antagonist PSB-0739 sensitizes CD to the action of AVP. Thus, our studies unravelled the potential beneficial effects of targeting P2Y2 or P2Y12 receptors to counter AVP resistance in lithium-induced NDI. If established in further studies, our findings may pave the way for the development of better and safer methods for the treatment of NDI by bringing a paradigm shift in the approach from the current therapies that predominantly counter the anti-AVP effects to those that enhance the sensitivity of the kidney to AVP action.

Bioimpedance spectroscopy for the estimation of body fluid volumes in mice.

Conventional indicator dilution techniques for measuring body fluid volume are laborious, expensive, and highly invasive. Bioimpedance spectroscopy (BIS) may be a useful alternative due to being rapid, minimally invasive, and allowing repeated measurements. BIS has not been reported in mice; hence we examined how well BIS estimates body fluid volume in mice. Using C57/Bl6 mice, the BIS system demonstrated <5% intermouse variation in total body water (TBW) and extracellular (ECFV) and intracellular fluid volume (ICFV) between animals of similar body weight. TBW, ECFV, and ICFV differed between heavier male and lighter female mice; however, the ratio of TBW, ECFV, and ICFV to body weight did not differ between mice and corresponded closely to values in the literature. Furthermore, repeat measurements over 1 wk demonstrated <5% intramouse variation. Default resistance coefficients used by the BIS system, defined for rats, produced body composition values for TBW that exceeded body weight in mice. Therefore, body composition was measured in mice using a range of resistance coefficients. Resistance values at 10% of those defined for rats provided TBW, ECFV, and ICFV ratios to body weight that were similar to those obtained by conventional isotope dilution. Further evaluation of the sensitivity of the BIS system was determined by its ability to detect volume changes after saline infusion; saline provided the predicted changes in compartmental fluid volumes. In summary, BIS is a noninvasive and accurate method for the estimation of body composition in mice. The ability to perform serial measurements will be a useful tool for future studies.

Effect of pioglitazone on survival and renal function in a mouse model of polycystic kidney disease.

BACKGROUND/AIMS: Cystic epithelia in polycystic kidney disease display features similar to malignant cells. Thiazolidinediones have been shown to have anti-neoplastic properties, therefore we tested the hypothesis that pioglitazone reduces cyst formation, improves renal function, and prolongs survival in a mouse model of polycystic kidney disease. METHODS: PC-Pkd1-KO mice, which have homozygous mutations of the Pkd1 gene in principal cells, were used. On the day after giving birth, mothers were fed standard mouse chow with or without pioglitazone (30 mg/kg chow). After weaning, the assigned diet was continued. At 1 month of age, blood pressure was measured and animals were sacrificed to determine kidney weight, body weight, and serum urea. Kidneys were evaluated for proliferation using Ki-67, apoptosis using TUNEL analysis, and cyst number using MRI. Survival was observed. RESULTS: Pioglitazone did not alter renal function, cell proliferation, apoptosis, or cyst formation in animals with polycystic kidney disease, however it did increase survival. Pioglitazone reduced blood pressure in PC-Pkd1-KO, but not in controls. CONCLUSION: These findings suggest that pioglitazone may have a unique antihypertensive effect in polycystic kidney disease, and that such an effect may promote improved survival.

Bone chemical structure response to mechanical stress studied by high pressure Raman spectroscopy.

While the biomechanical properties of bone are reasonably well understood at many levels of structural hierarchy, surprisingly little is known about the response of bone to loading at the ultrastructural and crystal lattice levels. In this study, our aim was to examine the response (i.e., rate of change of the vibrational frequency of mineral and matrix bands as a function of applied pressure) of murine cortical bone subjected to hydrostatic compression. We determined the relative response during loading and unloading of mineral vs. matrix, and within the mineral, phosphate vs. carbonate, as well as proteinated vs. deproteinated bone. For all mineral species, shifts to higher wave numbers were observed as pressure increased. However, the change in vibrational frequency with pressure for the more rigid carbonate was less than for phosphate, and caused primarily by movement of ions within the unit cell. Deformation of phosphate on the other hand, results from both ionic movement as well as distortion. Changes in vibrational frequencies of organic species with pressure are greater than for mineral species, and are consistent with changes in protein secondary structures such as alterations in interfibril cross-links and helix pitch. Changes in vibrational frequency with pressure are similar between loading and unloading, implying reversibility, as a result of the inability to permanently move water out of the lattice. The use of high pressure Raman microspectroscopy enables a deeper understanding of the response of tissue to mechanical stress and demonstrates that individual mineral and matrix constituents respond differently to pressure.

Effect of shigatoxin-1 on arachidonic acid release by human glomerular epithelial cells.

BACKGROUND: Altered arachidonic acid (AA) metabolism has been implicated in the pathogenesis of renal injury in the hemolytic uremic syndrome (HUS). However, there is very little information of the effect of shigatoxin (Stx; the putative mediator of renal damage in HUS) on AA release or metabolism by renal cells. Since recent studies have demonstrated that glomerular epithelial cells (GECs) may be important early targets of Stx, the current study was undertaken to examine the effects of Stx on AA release and metabolism by GECs. METHODS: Cultured human GECs were exposed to Stx1 +/- lipopolysaccharide (LPS) for 4 to 48 hours followed by determination of (3)H-arachidonate release, thromboxane A(2) (TxA(2)) and prostacyclin (PGI(2)) production, cyclooxygenase (COX) activity, and Western and Northern analyses for phospholipase A(2) (PLA(2)) and COX protein and mRNA levels, respectively. RESULTS: Stx1 increased arachidonate release by GECs. LPS alone had no such effect, but increased arachidonate release in response to Stx1. Stx1-stimulated arachidonate release correlated with elevations in cPLA(2) and sPLA(2) protein and cPLA(2) mRNA levels. Stx1 also increased both TxA(2) and PGI(2) production by GECs; LPS alone did not alter eicosanoid production, but augmented Stx1 effects. Both Stx1 and LPS stimulated COX activity; however, these effects were not additive. Although there was an accompanying elevation of COX-1 and COX-2 mRNA, Stx1 decreased and LPS did not change COX1 and COX2 protein levels. CONCLUSIONS: Stx1 alone or in conjunction with LPS increases arachidonate release and eicosanoid production by human GECs; this effect correlates with increased PLA(2) protein and mRNA levels. To our knowledge, this is the first study identifying the mechanisms of Stx1-stimulated AA release. These results raise the possibility that arachidonate release and metabolism by GECs, and conceivably other renal cell types, are involved in renal injury in HUS.

Shiga toxin-1 regulation of cytokine production by human glomerular epithelial cells.

BACKGROUND/AIMS: Inflammatory cytokines may enhance renal injury in post-diarrheal hemolytic uremic syndrome (Stx HUS) by enhancing the cytotoxic effect of Shiga toxins (Stx). The sources of inflammatory cytokines in Stx HUS are unclear. Since Stx-1 potently inhibits protein synthesis by glomerular epithelial cells (GEC) and increases cytokine release by renal epithelial cells, we examined Stx-1 regulation of cytokine production by human GEC. METHODS: Stx-1 (and cycloheximide (CHX), another protein synthesis inhibitor) cytotoxicity, protein synthesis inhibition, and effect on interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) release and mRNA levels were determined. RESULTS: Stx-1 alone had a modest stimulatory effect on inflammatory cytokine production by GEC that occurred at toxin concentrations ranging from minimal to 50% inhibition of protein synthesis. CHX, at concentrations that produced similar inhibition of protein synthesis, increased IL-1, IL-6, and TNF protein release and mRNA accumulation, but in a different time- and dose-dependent pattern than Stx. Lipopolysaccharide (LPS) did not change IL-1, but stimulated IL-6 and TNF production. LPS and Stx-1 combined stimulated production of all three cytokines to a greater extent than either toxin alone. CONCLUSION: These data indicate that: (1) Stx-1 alone modestly stimulates GEC inflammatory cytokine production; (2) LPS and Stx-1 combined can potently enhance GEC cytokine release, and (3) this action of Stx-1 may relate in part to inhibition of protein synthesis but cannot be fully attributed to this effect.

[Using interaction-intensive therapeutic nursing measures and "home remedies" in nursing care. An explorative study as a plea for integrated nursing practice]. / Der Einsatz von interaktionsintensiven pflegetherapeutischen Massnahmen und von "Hausmitteln" in der Pflege. Eine explorative Studie als Plädoyer für eine integrierte Pflegepraxis.

BACKGROUND: Until today there existed no major studies about the wide range of currently utilized methods or potential sociodemographic and institutional influences on utilization despite an immense interest among nurses in alternative nursing methods (in this study referred to as home remedies). METHODS: In this study, from standardized questionnaires with a convenience sample of three different settings of nursing practice, i.e. acute-care, nursing homes, and home health care were analyzed using the statistical program SPSS. RESULTS: Our analysis showed that a wide range of traditional home remedies is being utilized, e.g. application of heat and cold or herbal infusion (herbal teas). Furthermore, lay approaches such as aromatherapy were also commonly used. The statistical analysis revealed complex influences of age, duration of nursing practice and institutional setting in the utilization of home remedies. CONCLUSION: There is need for more systematic studies to further examine the alternative methods or home remedies so popular among nurses and their patients. Regarding a more consistent naming of the variety of different methods coming from naturopathy, folk and lay medicine, the authors suggest the term "integrative nursing care".

Pauci-immune necrotizing glomerulonephritis complicating rheumatoid arthritis.

Necrotizing glomerulonephritis associated with rheumatoid arthritis typically occurs in the setting of frankly apparent systemic vasculitic signs and symptoms. We report two recent cases that differed from this paradigm. Both patients had rheumatoid arthritis and deteriorating renal function due to P-ANCA positive pauci-immune necrotizing crescentic glomerulonephritis, but minimal systemic symptoms. Delay in diagnosis and institution of appropriate therapy may have contributed to the dialysis dependence of one of these patients. We suggest that heightened suspicion of an aggressive necrotizing glomerulonephritis should be maintained in all patients with rheumatoid arthritis who present with acute renal insufficiency even in the absence of frank vasculitis.

Cytotoxic effect of Shiga toxin-1 on human glomerular epithelial cells.

BACKGROUND: Shiga toxin-1 (Stx-1) has been implicated in the pathogenesis of postdiarrheal hemolytic-uremic syndrome (Stx HUS). Endothelial cells had been felt to be the primary renal target of Stx-1; however, recent studies suggest that renal epithelial cells may also be responsive. To further examine this issue, we evaluated the responsiveness of human glomerular epithelial cells (GECs) to the cytotoxic effects of Stx-1. METHODS: Cultured GECs were exposed to Stx-1 in the presence and absence of a variety of inflammatory factors likely to be elevated in the kidney or serum of patients with Stx HUS. Cell survival, protein synthesis, total cell Gb3 levels and synthesis, and Stx-1 binding were measured. RESULTS: GECs were sensitive to Stx-1, with an LD50 of approximately 10-7 g/L (1.4 pmol/L). Interleukin-1 (IL-1), lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), and butyrate increased Stx-1 cytotoxicity and total cell Gb3 levels. These agents, with the exception of TNF-alpha, also increased Stx-1 binding to GECs. IL-6 failed to alter Stx-1 toxicity, binding, or Gb3 content. CONCLUSIONS: These studies indicate that GECs are sensitive to the cytotoxic effects of Stx-1 and that inflammatory factors can increase toxin responsiveness. GECs may be a target of Stx-1 action in Stx HUS.

Aquaporin 2 is a vasopressin-independent, constitutive apical membrane protein in rat vas deferens.

Aquaporin 2 (AQP2), the vasopressin-regulated water channel, was originally identified in renal collecting duct principal cells. However, our recent description of AQP2 in the vas deferens indicated that this water channel may have extra-renal functions, possibly related to sperm concentration in the male reproductive tract. In this study, we have examined the regulation and membrane insertion pathway of AQP2 in the vas deferens. The amino acid sequence of vas deferens AQP2 showed 100% identity to the renal protein. AQP2 was highly expressed in the distal portion (ampulla) of the vas deferens, but not in the proximal portion nearest the epididymis. It was concentrated on the apical plasma membrane of vas deferens principal cells, and very little was detected on intracellular vesicles. Protein expression levels and cellular localization patterns were similar in normal rats and vasopressin-deficient Brattleboro homozygous rats, and were not changed after 36 h of dehydration, or after 3 days of vasopressin infusion into Brattleboro rats. AQP2 was not found in apical endosomes (labeled with Texas Red-dextran) in vas deferens principal cells, indicating that it is not rapidly recycling in this tissue. Finally, vasopressin receptors were not detectable on vas deferens epithelial cell membranes using a [(3)H]vasopressin binding assay. These data indicate that AQP2 is a constitutive apical membrane protein in the vas deferens, and that it is not vasopressin-regulated in this tissue. Thus AQP2 contains targeting information that can be interpreted in a cell-type-specific fashion in vivo.

Otologic surgery in patients with HIV-1 and AIDS.

Otologic disease in patients infected with HIV occurs frequently and usually represents rhinologic disease and associated eustachian tube dysfunction rather than manifestations of HIV infection. As in all patients, the decision to operate on an HIV-infected individual who would benefit from major otologic surgery is a balance between the risks of the procedure and the possible benefits to the patient. Many concerns regarding wound infection and healing have been raised. The objective of this study is to evaluate the outcome of otologic procedures in this population. The charts of 9 men and 4 women were reviewed. Seven patients (54%) met the Centers for Disease Control and Prevention criteria for AIDS. Patients with chronic otitis media (46%) underwent tympanomastoidectomies, and the cases of acute mastoiditis (31%) were managed with simple mastoidectomies. Other procedures included repair of cerebrospinal fluid leak (15%) and stapedectomy (8%). Two patients had early complications and died during their hospitalizations. Three patients had prolonged hospital courses requiring long-term antibiotics. These 5 patients underwent urgent procedures and were severely immunocompromised. Of the remaining 8 patients only 2 had AIDS, and all had an uncomplicated postoperative course. Six of these patients were followed up for more than 1 year, and only 2 developed subsequent otologic disease.

The Cre/loxP system and gene targeting in the kidney.

The Cre/loxP and Flp/FRT systems mediate site-specific DNA recombination and are being increasingly utilized to study gene function in vivo. These systems allow targeted gene disruption in a single cell type in vivo, thereby permitting study of the physiological and pathophysiological impact of a given gene product derived from a particular cell type. In the kidney, the Cre/loxP system has been employed to achieve gene deletion selectively within principal cells of the collecting duct. Disruption of target genes in the collecting duct, such as endothelin-1 or polycystic kidney disease-1 (PKD1), could lead to important insights into the biological roles of these gene products. With selection of the appropriate renal cell-specific promoters, these recombination systems could be used to target gene disruption to virtually any renal cell type. Although transgenic studies utilizing these recombination systems are promising, they are in their relative infancy and can be time consuming and expensive and yield unanticipated results. It is anticipated that continued experience with these systems will produce an important tool for analyzing gene function in renal health and disease.