TB prevention cascade at a district hospital in rural Eastern Cape, South Africa.

SETTING: Rural Eastern Cape, South Africa. OBJECTIVE: To identify steps in the TB preventive care cascade from routinely collected data among TB patients at a district hospital prior to the implementation of a novel TB program. DESIGN: This was a retrospective study. We adapted the TB prevention cascade to measure indicators routinely collected at district hospitals for TB using a cascade framework to evaluate outcomes in the cohort of close contacts. RESULTS: A total of 1,722 charts of TB patients were reviewed. The majority of patients (87%) were newly diagnosed with no previous episodes of TB. A total of 1,548 (90%) patients identified at least one close contact. A total of 7,548 contacts were identified with a median of 4.9 (range 1-16) contacts per patient. Among all contacts identified, 2,913 (39%) were screened for TB. Only 15 (0.5%) started TB preventive therapy and 122 (4.4%) started TB treatment. Nearly 25% of all medical history and clinical information was left unanswered among the 1,722 TB charts reviewed. CONCLUSION: Few close contacts were screened or started on TB preventive therapy in this cohort. Primary care providers for TB care in district health facilities should be informed of best practices for screening and treating TB infection and disease.

CONTEXTE: Le Cap Est rural, le Cap, Afrique du Sud. OBJECTIF: Identifier les étapes de la cascade de soins préventifs de la TB à partir des données de routine recueillies parmi des patients dans un hôpital de district avant la mise en œuvre d'un nouveau programme TB. SCHÉMA: Ceci était une étude rétrospective. Nous avons adapté la cascade de prévention de la TB pour mesurer les indicateurs recueillis en routine dans les hôpitaux de district pour la TB en utilisant un cadre en cascade afin d'évaluer les résultats dans la cohorte des contacts étroits. RÉSULTATS: Un total de 1 722 dossiers de patients TB a été revu. La majorité des patients (87%) avait un diagnostic nouveau sans épisode de TB préalable. Un total de 1 548 (90%) patients ont identifié au moins un contact étroit ; 7 548 contacts ont été identifiés avec une médiane de 4,9 (fourchette 1­16) contacts par patient. Parmi tous les contacts identifiés, 2 913 (39%) ont eu une recherche de TB. Seulement 15 (0,5%) ont initié le traitement préventif et 122 (4,4%) ont mis en route le traitement de TB. Près de 25% de tous les antécédents et autres informations cliniques n'était pas remplis dans les 1 722 dossiers TB revus. CONCLUSION: Peu de contacts étroits ont été dépistés ou mis sous traitement préventif de TB dans cette cohorte. Les prestataires de soins de santé primaires pour la TB dans les structures de santé des districts doivent être informés des meilleures pratiques pour le dépistage et le traitement de la TB infection et maladie.

Central nervous system involvement in adults with epidemic hemolytic uremic syndrome.

Hemolytic uremic syndrome is a multisystem disorder that is caused by infection with Shiga-toxin-producing Escherichia coli. HUS affects mainly children and is rare among adults. This retrospective case series analyzes clinical signs and MR imaging findings of 11 adult patients with HUS associated nervous system involvement during the epidemic EHEC outbreak in northern Europe with its epicenter in Hamburg in May 2011. The most prevalent imaging finding was symmetric pointy vasogenic edema of the brain stem in the acute and subacute phases of the disease (n = 5). One patient exhibited additional symmetric mesiotemporal signal changes mimicking limbic encephalitis. Two patients developed subcortical patchy lesions, and 4 subjects did not present with any signal changes. Remarkably, territorial ischemia, signs of hemorrhage, or blood-brain barrier disruption have not been detected. While brain stem lesions were transient and normalized with clinical recovery, supratentorial lesions did not resolve completely at 2-month follow-up examination.

[Clinical symptoms, treatment and outcome of EHEC and EHEC-HUS patients treated as in-patients]. / Klinische Symptomatik, Therapie und Verlauf Stationär Behandelter EHEC/EHEC-HUS Patienten.

BACKGROUND AND OBJECTIVE: From May to June 2011 an outbreak of Shiga-toxin-producing Escherichia coli (EHEC) infections occurred in northern Germany leading to a great number of patients with hemolytic-uremic syndrome (HUS). A monocentric case series from Hamburg is described. MATERIAL AND METHODS: All patients at that time presenting with acute diarrhoea at the Asklepios Clinic Barmbek in Hamburg were proved for EHEC infections. Clinical data of EHEC and EHEC-HUS patients treated as in-patients as well as stool analysis and laboratory results were documented. RESULTS: In total, 117 patients suspicious to have EHEC infection were treated as in-patients. In 68 patients an EHEC infection (n = 36) or HUS (n = 32) could be confirmed. Additional infections with other diarrhoea-causative organism could be revealed in 23 of these 68 patients (34 %). The median age of the HUS patients was 44 years being significantly lower compared to the age of EHEC patients without HUS (51 years, p = 0,04). In the group of HUS patients there were significantly more women (26/32 vs. 21/36, p = 0.03). 19 patients with HUS dialysis was necessary. In total, a number of 248 plasma separations were required. 18 patients developed severe neuro-psychiatric symptoms. One patient died. CONCLUSION: This monocentric case series describes one of the so far largest published series of mostly young and female patients with EHEC and EHEC-HUS.

A new role for the neuronal ubiquitin C-terminal hydrolase-L1 (UCH-L1) in podocyte process formation and podocyte injury in human glomerulopathies.

Glomerular epithelial cell (podocyte) injury is characterized by foot process retraction, slit diaphragm reorganization, and degradation of podocyte-specific proteins. However, the mechanisms underlying podocyte injury are largely unknown. The ubiquitin C-terminal hydrolase-L1 (UCH-L1) is a key modulator of ubiquitin modification in neurons. Like neurons, UCH-L1 expression was associated with an undifferentiated status in cultured human podocytes, whereas differentiation and arborization decreased UCH-L1 and monoUb expression. Inhibition of UCH-L1 induced time and concentration-dependent process formation with alpha-actinin-4 distribution to the cell membrane and processes. An immunohistochemical approach was used to evaluate whether UCH-L1 expression was associated with podocyte injury in 15 different human glomerular diseases. Whereas normal kidneys expressed no UCH-L1 and little ubiquitin, a subset of human glomerulopathies associated with podocyte foot process effacement (membranous nephropathy, SLE class V, FSGS) de novo expressed UCH-L1 in podocyte cell bodies, nuclei, and processes. Interestingly, UCH-L1 expression correlated with podocyte ubiquitin content and internalization of the podocyte-specific proteins nephrin and alpha-actinin-4. In contrast, minimal change glomerulonephritis, a reversible disease, demonstrated minimal UCH-L1 and ubiquitin expression with intact alpha-actinin-4 but internalized nephrin. Glomerular kidney diseases typically not associated with foot process effacement (SLE class IV, ANCA+ necrotizing GN, amyloidosis, IgA nephritis) expressed intermediate to no UCH-L1 and ubiquitin. These studies show a role for UCH-L1 and ubiquitin modification in podocyte differentiation and injury.

A new mouse model of immune-mediated podocyte injury.

Podocytes play a major role in the initiation and progression of glomerular diseases and are a target of both immune-mediated and non-immune-mediated injury. To establish a mouse model of such injury, we preimmunized mice with Freunds adjuvant 5 days before intravenous injection of a rabbit polyclonal antibody directed against a murine podocyte cell line. For the next 7 weeks, we collected urine, serum, and kidney samples. Nephritic animals developed severe albuminuria, which was maximal on day 10. Histochemistry revealed diffuse mesangial matrix expansion. Mouse immunoglobulin G and complement were detected in a linear pattern along the glomerular filtration barrier and in the mesangial hinge region. Complement depletion, however, did not prevent proteinuria. Glomerular T cells were increased, whereas podocytes were significantly reduced. Glomerular foot processes were flattened in regions with mesangial matrix deposition as viewed by electron microscopy. Immunohistochemistry detected the injected anti-podocyte antibody exclusively at the glomerular tuft on all days examined. Immunoelectron microscopy localized the antibody to podocyte foot processes and the glomerular basement membrane, which was morphologically intact. This suggests that the podocyte was the main target of the antiserum. Our study establishes a new mouse model of immune-mediated podocyte injury.

Reassembly of the tight junction after oxidative stress depends on tyrosine kinase activity.

Oxidative stress compromises the tight junction, but the mechanisms underlying its recovery remain unclear. We developed a model in which oxidative stress reversibly disrupts the tight junction. Exposure of Madin-Darby canine kidney cells to hydrogen peroxide markedly reduced transepithelial resistance and disrupted the staining patterns of the tight junction proteins ZO-1 and occludin. These changes were reversed by catalase. The short-term reassembly of tight junctions was not dependent on new protein synthesis, suggesting that recovery occurs through re-utilization of existing proteins. Although ATP levels were reduced, the reduction was insufficient to explain the observed changes, since a comparable reduction of ATP levels (with 2-deoxy-D-glucose) did not induce these changes. The intracellular hydrogen peroxide scavenger pyruvate protected Madin-Darby canine kidney cells from loss of transepithelial resistance as did the heavy metal scavenger N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine. Of a wide variety of agents examined, only tyrosine kinase inhibitors and protein kinase C inhibitors markedly inhibited tight junction reassembly. During reassembly, tyrosine phosphorylation in or near the lateral membrane, was detected by immunofluorescence. The tyrosine kinase inhibitors genistein and PP-2 inhibited the recovery of transepithelial resistance and perturbed the relocalization of ZO-1 and occludin to the tight junction, indicating that tyrosine kinases, possibly members of the Src family, are critical for reassembly after oxidative stress.

Intrachoroidal neovascularization in transgenic mice overexpressing vascular endothelial growth factor in the retinal pigment epithelium.

Choroidal neovascularization in age-related macular degeneration is a frequent and poorly treatable cause of vision loss in elderly Caucasians. This choroidal neovascularization has been associated with the expression of vascular endothelial growth factor (VEGF). In current animal models choroidal neovascularization is induced by subretinal injection of growth factors or vectors encoding growth factors such as VEGF, or by disruption of the Bruch's membrane/retinal pigment epithelium complex with laser treatment. We wished to establish a transgenic murine model of age-related macular degeneration, in which the overexpression of VEGF by the retinal pigment epithelium induces choroidal neovascularization. A construct consisting of a tissue-specific murine retinal pigment epithelium promoter (RPE(65) promoter) coupled to murine VEGF(164) cDNA with a rabbit beta-globin-3' UTR was introduced into the genome of albino mice. Transgene mRNA was expressed in the retinal pigment epithelium at all ages peaking at 4 months. The expression of VEGF protein was increased in both the retinal pigment epithelium and choroid. An increase of intravascular adherent leukocytes and vessel leakage was observed. Histopathology revealed intrachoroidal neovascularization that did not penetrate through an intact Bruch's membrane. These results support the hypothesis that additional insults to the integrity of Bruch's membrane are required to induce growth of choroidal vessels into the subretinal space as seen in age-related macular degeneration. This model may be useful to screen for inhibitors of choroidal vessel growth.

Heat shock response reduces mortality after severe experimental burns.

The heat shock response has imparted protective effects in animal models of septic shock and endotoxemia. This study has tested the hypothesis that it could be protective in experimental burns. One hundred and fifteen adult male Fischer rats were randomly divided into four groups. Rats in the first group (n = 12) were anesthetized and shaved. In the second group (n = 15) rats were anesthetized and heated in a 45 degrees C water bath. In the third group (n = 44), rats were anesthetized, shaved and submitted to 26-30% body surface third-degree burns using a brass bar. In the fourth group (n = 44), rats were anesthetized, heated and, 1 day after, they were burnt. Mortality rates were measured at 3, 7, 15 and 25 days. Liver and lung samples were collected from all groups for heat-shock protein 70 detection. Heat-shock protein 70 was positive in heated animals. No animals died in the first or second group. Heated and burnt animals showed significantly decreased mortality at days 3 (p < 0.05, Fischer's exact test) and at days 7, 15 and 25 (p < 0.01) after burns, when compared to unheated burnt animals. In conclusion, eliciting the heat-shock response significantly reduced mortality rates in this model of experimental burns.

Hydrogen peroxide activates ion currents in rat mesangial cells.

BACKGROUND: Hydrogen peroxide (H2O2) is an important mediator of glomerular injury, which induces proliferation and cell contraction in mesangial cells. The aim of this study was to investigate whether and which ion currents are activated during the early cellular responses to H2O2, and to study possible mechanisms of their activation. METHODS: The effect of H2O2 on membrane voltage of mesangial cells in short-term culture was investigated with the patch clamp technique in the fast whole cell configuration. RESULTS: H2O2 contracted mesangial cells and induced a concentration-dependent biphasic membrane voltage response. One hundred micromol/liter H2O2 led to a hyperpolarization of mesangial cells from -45 +/- 1 to -55 +/- 1 mV, which was followed by a sustained depolarization to -20 +/- 3 mV. The hyperpolarization induced by H2O2 was completely blocked by the K+ channel blocker Ba2+. In the presence of a low extracellular Cl- concentration (32 mmol/liter), the depolarization induced by H2O2 was significantly increased. The H2O2-induced depolarization was inhibited by 100 micromol/liter of the disulfide-reducing agent dithiothreitol, whereas higher concentrations of dithiothreitol (1 mmol/liter) were required to partially inhibit the hyperpolarization. Protein kinase C inhibitors blocked the H2O2-induced depolarization, but not the hyperpolarization. CONCLUSIONS: The data indicate that H2O2 leads to a biphasic membrane voltage response in mesangial cells: an initial transient hyperpolarization, which is due to the activation of a K+ conductance, and a subsequent depolarization, which is, at least in part, due to the activation of a Cl- conductance. The oxidation of thiol groups by H2O2 is involved in the membrane voltage response, and the depolarization may be regulated by protein kinase C.

Tratamiento quirúrgico para la úlcera péptica a la luz de una estudio radiológico retrospectivo del tono y motilidad del estómago / A surgical alternative peptic ulcer based on a retrospective radiological study of gastric tonus and motility

Los autores hacen un análisis retrospectivo de 1085 estudios radiológicos de estómago y duodeno para estudiar la relación entre la úlcera péptica y los disturbios de tonicidad y motilidad ganstricas.Fueran observados alteraciones del tono y de la motilidad en mayor número de pacientes con úlcera péptica,en comparación con los pacientes sin úlcera .Fué verificado disminución significativa de la tonicidad del estómgo en la úlcera gástrica, sin predominio de hiper o hipomotilidad en las úlceras duodenales y gástricas.Luego del análisis ,presentan sugestiones acerca de la etiopatogenia de la enfermedad,proponiendo la técnica de vagotomía,antrectomía y anastomosis gastroduodenal a nivel de la curvatura menor,como una cirugía eficaz para la corrección de la úlcera,hoy principalmente,en la obstrucción del píloro,llevando en consideración la preservación del tono y de la motilidad gástrica

Tratamiento quirúrgico para la úlcera péptica a la luz de una estudio radiológico retrospectivo del tono y motilidad del estómago / A surgical alternative peptic ulcer based on a retrospective radiological study of gastric tonus and motility

Los autores hacen un análisis retrospectivo de 1085 estudios radiológicos de estómago y duodeno para estudiar la relación entre la úlcera péptica y los disturbios de tonicidad y motilidad ganstricas.Fueran observados alteraciones del tono y de la motilidad en mayor número de pacientes con úlcera péptica,en comparación con los pacientes sin úlcera .Fué verificado disminución significativa de la tonicidad del estómgo en la úlcera gástrica, sin predominio de hiper o hipomotilidad en las úlceras duodenales y gástricas.Luego del análisis ,presentan sugestiones acerca de la etiopatogenia de la enfermedad,proponiendo la técnica de vagotomía,antrectomía y anastomosis gastroduodenal a nivel de la curvatura menor,como una cirugía eficaz para la corrección de la úlcera,hoy principalmente,en la obstrucción del píloro,llevando en consideración la preservación del tono y de la motilidad gástrica

Tensile and tear properties of dental dam.

The tensile and tear properties of highly extensible latex are sensitive to specimen shape. Three specimen shapes (ASTM D412 Die C dumbbell tensile specimen, rectangular tensile specimen with 1.74 mm hole, and ASTM D624 Die C tear specimen) were evaluated for proposed ANSI/ADA specification #90 for dental dams. Fresh and aged dental dams from two manufacturers (Aseptico and Hygenic) in three weights (thin, medium, and heavy) and from two other manufacturers (Ivory and Ivoclar) in one weight (medium) were tested. Means and standard deviations of 10 specimens for tensile strength (MPa), elongation (%), and tear strength (kN/m) are included herein. Data were analyzed by analysis of variance. Means were compared by a Tukey-Kramer interval calculated at the 0.05 significance level. The use of the dumbbell and tear specimens for the evaluation of dental dam should be reconsidered. The rectangular specimen with a hole is recommended for use in the proposed specification because of its sensitivity to condition (fresh versus aged) and manufacturer.

Hydrogen peroxide increases the intracellular calcium activity in rat mesangial cells in primary culture.

Oxygen radicals are known to be mediators of renal injury under several pathophysiological conditions. We have examined the effect of hydrogen peroxide (H2O2) on intracellular calcium activity ([Ca2+]i) in mesangial cells in primary culture. Mesangial cells were loaded with 1 mumol/liter fura-2, and kept in a Ringer-like solution. Fura-2 fluorescence was measured in an inverted microscope at 37 degrees C. Angiotensin II (0.1 nmol/liter) and ATP (0.1 mumol/liter) induced a rapid transient increase of [Ca2+]i, which was followed by a sustained plateau (N = 37 and N = 24). In contrast, the addition of H2O2 (0.01 to 10 mmol/liter, N = 157) caused a time- and concentration-dependent slow increase of [Ca2+]i, which reached a stable [Ca2+]i plateau after 3 to 10 minutes (ED50: 100 mumol/liter). After the removal of H2O2 [Ca2+]i decreased partially and reached a stable value approximately 90% above the resting [Ca2+]i value. Addition of 100 mumol/liter H2O2 to an extracellular Ca(2+)-free solution resulted either in no rise of [Ca2+]i in some experiments (N = 7), or [Ca2+]i oscillations in others (N = 10). In the presence of H2O2 (> 25 mumol/liter), the angiotensin II or ATP mediated increases in [Ca2+]i were almost completely inhibited (N = 15 and N = 10). The cations Ni2+ and La3+ and the Ca(2+)-antagonist verapamil (10 mumol/liter) did not inhibit the H2O2 mediated increase of -Ca2+-i (N = 6 to 9). Flufenamate (100 mumol/liter), an inhibitor of non-selective cation channels inhibited the H2O2 induced increase of [Ca2+]i by 63 +/- 11% (N = 7). Preincubation of the cells with a disulphide reducing agent (dithiothreitol, 500 mumol/liter, N = 5) or an iron-chelator (deferoxamine, 100 mumol/liter, N = 5) attenuated the H2O2 mediated effect by 95 +/- 15% and 74 +/- 6%, respectively. The H2O2 mediated [Ca2+]i increase was completely inhibited when mesangial cells were preincubated with 1 mumol/liter U-83836E, an inhibitor of lipid peroxidation (N = 7), and inhibited by 84 +/- 6% when the cells were pretreated with 1 mmol/liter pyruvate (N = 5). The data indicate that H2O2: (i) increases [Ca2+]i in mesangial cells by a mechanism distinct from angiotensin II or ATP and (ii) that it inhibits the [Ca2+]i response to both agonists.