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.

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.

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.

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.

Osmolar regulation of endothelin-1 production by rat inner medullary collecting duct.

Recent evidence has implicated endothelin-1 (ET-1) as an autocrine inhibitor of inner medullary collecting duct (IMCD) sodium and water transport. The regulators of IMCD ET-1 production are, however, largely unknown. Because of the unique hypertonic environment of the IMCD, the effect of varying extracellular tonicity on IMCD ET-1 production was evaluated. Increasing media osmolality from 300 to 450 mosmol with NaCl or mannitol but not urea caused a marked dose- and time-dependent reduction in ET-1 release by and ET-1 mRNA in cultured rat IMCD cells. In contrast, increasing osmolality had no effect on ET-1 production by rat endothelial or mesangial cells. To see if ET-1 varies in a similar manner in vivo, ET-1 production was assessed in volume expanded (lower medullary tonicity) or volume depleted (high medullary tonicity) rats. Urinary ET-1 excretion and inner medulla ET-1 mRNA were significantly reduced in volume depleted as compared to volume expanded animals. These results indicate that extracellular sodium concentration inhibits ET-1 production specifically in IMCD cells. We speculate that extracellular sodium concentration, via regulation of ET-1 production, provides a link between volume status and IMCD sodium and water reabsorption.

Identification of a contractile function for renal medullary interstitial cells.

Renomedullary interstitial cells (RMIC) are unique to the renal medulla. By virtue of their anatomic location and arrangement, RMIC may hinder axial dissipation of the concentration gradient, thereby aiding urinary concentration. A more active role in urinary concentration has been postulated on the basis of speculations about RMIC contractile potential, however, RMIC contraction has not been investigated. To determine if these cells are contractile, cultured rat RMIC were exposed to endothelin-1 (ET-1), a potent vasoconstrictor which binds to RMIC, and examined using video microscopy. ET-1 (as low as 10 pM) caused a slowly developing and dose-dependent reduction in RMIC surface area. ET-1 markedly increased the number and intensity of F-actin microfilament staining. ET-1-induced RMIC contraction was not altered by nifedipine, was partially reduced by nickel, and was completely inhibited by H7, indicating that ET-1 action is mediated by protein kinase C and is partially dependent upon receptor-operated calcium channels. The ET-1 effect does not involve nitric oxide since NG-monomethyl-L-arginine did not alter ET-1-induced RMIC contraction; in addition, ET-1 had only a minor effect on cGMP levels and no effect on nitrite production. PGE2 acts in an autocrine manner to dampen ET action since indomethacin potentiates, while PGE2 inhibits, ET-1-induced RMIC contraction. The contractile response is not unique to ET-1 since vasopressin also reduces RMIC surface area and increases F-actin microfiliment staining. These studies demonstrate that RMIC in culture are contractile. The possibility is raised that contraction of RMIC plays a role in modifying urinary concentration as well as regulation of other renal medullary functions.

Cytokine-induced expression of a nitric oxide synthase in rat renal tubule cells.

Nitric oxide (NO.) has been implicated in the regulation of renal vascular tone and tubular sodium transport. While the endothelial cell is a well known source of NO(.), recent studies suggest that tubular epithelial cells may constitutively generate NO(.). An inducible isoform of nitric oxide synthase which produces far greater quantities of NO. exists in some cell types. We sought to determine whether kidney epithelial cells exposed to cytokines could express an inducible nitric oxide synthase. Primary cultures of rat proximal tubule and inner medullary collecting duct cells generated NO. on exposure to TNF-alpha and IFN-gamma. NO. production by both cell types was inhibited by NG-monomethyl-L-arginine; this inhibition was partially reversed by the addition of excess L-arginine. Stimulation of kidney epithelial cells with TNF-alpha and IFN-gamma dramatically increased the level of inducible nitric oxide synthase mRNA. In summary, renal proximal tubule and inner medullary collecting duct cells can produce NO. via expression of an inducible isoform of nitric oxide synthase.

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.

Alterations in renal endothelin-1 production in the spontaneously hypertensive rat.

Endothelin-1 inhibits sodium and water transport systems in the inner medullary collecting duct. Endothelin-1 levels are reduced in the medulla of spontaneously hypertensive rats (SHR), raising the possibility that decreased inner medullary collecting duct production of endothelin-1 could contribute to inappropriate sodium and water retention. In the current study, immunoreactive endothelin-1 was measured in the urine, blood, and eluates from cortex and outer and inner medulla of SHR before (age 3-4 weeks) and after (age 8-9 weeks) the development of hypertension and in age-matched Wistar-Kyoto (WKY) controls. There was no difference in endothelin-1 levels between prehypertensive SHR and WKY rats. In contrast, 8-9-week-old SHR had significantly reduced endothelin-1 in the urine and outer and inner medulla, but not in the cortex or serum compared with those of WKY controls. Furthermore, inner medullary collecting duct cells from 8-9-week-old SHR, either acutely isolated or cultured, released less endothelin-1 than did those from WKY rats. Finally, the level of endothelin-1 messenger RNA was only reduced in the inner medulla and in inner medullary collecting duct cells from 8-9-week-old SHR. In summary, renal medullary, and in particular terminal collecting duct, endothelin-1 production is reduced in SHR only after the development of hypertension. Such decreases in inner medullary collecting duct endothelin-1 production may contribute to the hypertensive state in SHR.

Site-specific recombination using an epitope tagged bacteriophage P1 Cre recombinase.

Since the original description of Cre mediated site-specific recombination in bacteriophage P1 (Sternberg, N., Hamilton, D., 1981 J. Mol. Biol., 150, 467-487), the Cre-lox system of recombination has been widely used to manipulate prokaryotic and eukaryotic genomes. Unfortunately, there are few means available to measure Cre protein expression in vivo. We have constructed an expression vector wherein the Cre protein is tagged at the carboxy terminus with an 11-amino-acid epitope to the herpes simplex virus (HSV) glycoprotein D coat protein (Isola, V.J., Eisenberg, R.J., Siebert, G.R., Heilman, C.J., Wilcox, W.C., Cohan, G.H., 1989. J. Virol. 63, 2325-2334). The epitope tag facilitates detection of Cre expression in vitro and in vivo using immunofluorescent labeling with a commercially available antibody. The epitope tag does not interfere with Cre recombinase activity or alter recombination efficiency between loxP sites. We have shown in mice that a transgene expressing our tagged Cre is capable of excising a loxP flanked sequence contributed by another transgenic mouse. In summary, we have developed an epitope-tagged Cre recombinase that is fully active and readily detectable.

The effects of oral pentoxifylline on the cytokine release syndrome during inductive OKT3.

The cytokine release syndrome (CRS) accompanying OKT3 therapy is a major cause of posttransplant morbidity. The pathogenesis of this syndrome has been attributed to the synthesis of tumor necrosis factor, interleukin 2 (IL-2), interleukin 6 (IL-6), and gamma-interferon in response on T lymphocyte stimulation by OKT3. The hemorrheologic agent pentoxifylline (PTX) inhibits the synthesis of TNF alpha in vitro in response to a variety of stimuli, including OKT3. We performed a randomized, double-blinded trial of PTX during OKT3 induction in recipients of cadaveric renal allografts. Patients received either PTX 800 mg or placebo 2 hr before the initial dose of OKT3 and every 8 hr thereafter during the first 3 posttransplant days. Serum TNF alpha and IL-6 concentrations were measured pre-OKT3 and at 2 and 6 hr post-OKT3 on the first 3 posttransplant days. Despite the achievement of apparently adequate plasma levels of PTX and its active metabolites, no difference was observed in the incidence or severity of clinical manifestations of CRS. Serious manifestations of CRS--including acute pulmonary edema, encephalopathy, and aseptic meningitis--were not seen in either group. Serum TNF alpha and IL-6 concentrations were similar in PTX and control patients throughout the course of the study. Plasma levels of PTX and its active metabolites did not correlate with serum TNF alpha levels, serum IL-6 levels, or the incidence and severity of clinical manifestations of CRS.

Otologic disease in AIDS patients: CT correlation.

The contrast-enhanced computed tomographic (CT) scans of the temporal bone and brain in 18 patients with otologic disease and acquired immunodeficiency syndrome (AIDS) were retrospectively reviewed. Seven scans revealed middle ear and mastoid disease; three scans were consistent with central nervous system (CNS) pathology; and eight scans demonstrated no abnormalities. CT scanning was found useful in localizing otopathology and diagnosing CNS toxoplasmosis, aural polyps, osteomyelitis, mastoiditis, and middle ear effusion due to hypertrophic lymphoid tissue. The authors conclude that AIDS patients with sensorineural hearing loss should undergo contrast-enhanced brain CT scans to rule out CNS pathology; AIDS status does not alter criteria for CT scanning in patients with conductive hearing loss; and that images of the nasopharynx should be included on temporal bone CT scans of patients with conductive hearing loss in order to exclude eustachian tube obstruction by hypertrophic lymphoid tissue.

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.

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.

Rhinomanometric evaluation of two nasal steroid sprays in rhinitis.

A prospective, randomized study comparing the effectiveness of two nasal steroid sprays, flunisolide and beclomethasone dipropionate, in the treatment of nasal obstruction associated with allergic or vasomotor rhinitis has been conducted at New York University Medical Center-Bellevue Hospital. All patients underwent routine history and physical examinations and a modified radioallergosorbent test. Paranasal sinus films were used to exclude patients with sinusitis. The Rhinotest microprocessor rhinomanometer was used to quantify pretreatment and posttreatment total nasal air flow and resistance during a period of 2 months. These findings were assessed in conjunction with the patients' subjective complaints. Results demonstrated that anterior rhinomanometric assessment of the nasal airway during inhalant therapy correlated well with the patients' own subjective impressions of nasal air flow. Both steroid inhalants were effective; however, flunisolide provided for earlier and more substantial symptomatic relief. Beclomethasone dipropionate had milder side effects.

Otologic disease in patients with acquired immunodeficiency syndrome.

A 5-year retrospective study evaluating otologic disease in patients with acquired immunodeficiency syndrome (AIDS) was conducted at the New York University Medical Center-Bellevue Hospital Center. Twenty-six patients with documented otologic disease who met the Centers for Disease Control criteria for AIDS were identified and their charts were analyzed according to presenting complaints, physical examination, diagnostic modalities, pathologic condition, management, and outcome. A marked diversity of otologic diseases of varying severity was noted. The majority of patients complained of hearing loss and otalgia during their hospitalization for treatment of AIDS-related opportunistic infections. The most frequent diagnoses were otitis externa, acute otitis media, and otitis media with effusion. Sensorineural hearing loss frequently appeared to be related to ototoxic medications and neurologic infections.

Frontal bone reconstruction with split calvarial and cancellous iliac bone.

An autogenous split-thickness calvarial bone graft that was used to correct a marked depression in the frontal region of the forehead resulted in excellent cosmesis. Cancellous bone from the iliac crest, which was applied between the posterior wall of the frontal sinus and the anterior calvarial bone graft, eliminated the dead space and made infection less likely in an area prone to such infections.

[The practical realization of the hospice concept in health facilities]. / Die praktische Umsetzung des Hospizkonzepts in stationären Einrichtungen.

In a qualitative study the concept of hospices and their practical realization were reconstructed. Based on interviews with two nurses, each from a different hospice, and one nurse from a palliative ward, it is was found that fundamental differences in institutional structures exist between the hospices and the palliative ward. This has consequences for the care of a seriously ill patient and his family. These institutional differences are manifested in the two main points of the study "everyday life in the hospice" and "taking leave of the deceased".

[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".