Lung disease severity in idiopathic pulmonary fibrosis is more strongly associated with impedance measures of bolus reflux than pH parameters of acid reflux alone.

BACKGROUND: Gastroesophageal reflux (GER) has been associated with idiopathic pulmonary fibrosis (IPF). Pathogenesis may be related to chronic micro-aspiration. We aimed to assess objective measures of GER on multichannel intraluminal impedance and pH study (MII-pH) and their relationship with pulmonary function testing (PFT) results, and to compare the performance of pH/acid reflux parameters vs corresponding MII/bolus parameters in predicting pulmonary dysfunction in IPF. METHODS: This was a retrospective cohort study of IPF patients undergoing prelung transplant evaluation with MII-pH off acid suppression, and having received PFT within 3 months. Patients with prior fundoplication were excluded. Severe pulmonary dysfunction was defined using diffusion capacity of the lung for carbon monoxide (DLCO) ≤40%. Six pH/acid reflux parameters with corresponding MII/bolus reflux measures were specified a priori. Multivariate analyses were applied using forward stepwise logistic regression. Predictive value of each parameter for severe pulmonary dysfunction was calculated by area-under-the-receiver-operating-characteristic-curve or c-statistic. KEY RESULTS: Forty-five subjects (67% M, age 59, 15 mild-moderate vs 30 severe) met criteria for inclusion. Patient demographics and clinical characteristics were similar between pulmonary dysfunction groups. Abnormal total reflux episodes and prolonged bolus clearance time were significantly associated with pulmonary dysfunction severity on univariate and multivariate analyses. No pH parameters were significant. The c-statistic of each pH parameter was lower than its MII counterpart in predicting pulmonary dysfunction. CONCLUSIONS & INFERENCES: MII/bolus reflux, but not pH/acid reflux, was associated with pulmonary dysfunction in prelung transplant patients with IPF. MII-pH may be more valuable than pH testing alone in characterizing GER in IPF.

Transmission of visceral leishmaniasis in dogs in a risk area of the metropolitan region of Belo Horizonte, Minas Gerais, Brazil / Transmissão da leishmaniose visceral em cães em área de risco da Região Metropolitana de Belo Horizonte, Minas Gerais, Brasil

Visceral leishmaniasis (VL) has spread rapidly across cities in the metropolitan region of Belo Horizonte. The aim of this study was to investigate VL dynamics in a prospective cohort study of dogs in Juatuba, between 2010 and 2011, to confirm the incidence of Leishmania infantum, and to assess possible risk factors associated with infection. An observational and prospective closed cohort study was performed using serology testing in dogs, randomly selected from the whole municipality. All seronegative dogs, or dogs with inconclusive results were monitored using indirect immunofluorescence (IIF) at 6-month intervals. The dog's owners completed a semi-structured questionnaire to assess possible causal factors of seroconversion, and the responses were assessed using logistic regression. The canine incidence coefficient was 206/1,000 dogs per year (CI: 178-238), and a cluster was identified in an area with a high concentration of seropositive dogs, but a low overall canine population. Large dogs were identified as a risk factor and the following variables were identified as protection factors: dogs aged over 4 years, daily peridomicile cleaning, and better socioeconomic conditions. VL is spreading over a large area in Juatuba in a short period of time.(AU)

A leishmaniose visceral (LV) expandiu-se de forma rápida e extensa pelos municípios da Região Metropolitana de Belo Horizonte. Objetivou-se estudar a dinâmica da LV em uma coorte prospectiva de cães em Juatuba, entre 2010 e 2011, para verificar a incidência e fatores de risco associados à infecção por Leishmania infantum. Foi feito um estudo observacional e prospectivo de coorte fechada por meio de análise sorológica em cães selecionados aleatoriamente em todo o município, com acompanhamento semestral dos resultados soronegativos e indeterminados na imunofluorescência indireta (IFI). Usou-se questionário semiestruturado junto aos proprietários de cães para avaliação da soroconversão e dos fatores determinantes a essa, por meio da regressão logística. O coeficiente de incidência canina foi de 206/1000 cães.ano (IC: 178 - 238), e foi identificado cluster em área com elevada concentração de cães soropositivos, mas com baixa densidade populacional canina. A variável cão de porte grande foi identificada como fator de risco, e as variáveis idade do cão superior a quatro anos, limpeza diária do peridomicílio e melhores condições socioeconômicas como fatores de proteção. A infecção por LV está ocorrendo em curto período de tempo e com ampla distribuição em Juatuba.(AU)

Effects of estradiol and progestins on follicular regression before, during, and after follicular deviation in postpartum beef cows.

The objective was to evaluate the effect of estradiol benzoate (EB), in association with three progestin protocols, on ovarian follicular regression of suckled beef cows treated at three stages of follicular development (pre-deviation, deviation, or post-deviation). Thirty-six suckled beef cows (60-90 d postpartum, given 125 microg cloprostenol on two occassions, 12h apart). Forty-eight hours after the first cloprostenol treatment, all follicles >5mm were ablated and transrectal ultrasound scanning (8 MHz) was performed every 24h until Day 7 (Day 0=treatment). When the largest follicle reached a designated diameter of 5-7, 8-10 or >10mm, cows were randomly allocated to receive 2mg of EB im in association with an intravaginal device containing 250 mg of medroxyprogesterone acetate (MPA) with or without 100mg of progesterone (P(4)) given im, or an intravaginal device containing P(4) (3 x 3 factorial design). Treatments induced follicular regression in all cows, independent of follicular stage or treatment. There was no interaction between progestin treatment and follicular stage, nor was there any difference in the time of follicular regression or new wave emergence among follicular stages. Treatment with MPA plus P(4) delayed follicular regression. In conclusion, EB in association with various progestins induced regression of growing follicles and emergence of a new follicular wave in postpartum beef cows, regardless of the stage of follicular development.

Simultaneous observation of collagen and elastin in normal and pathological tissues: analysis of Sirius-red-stained sections by fluorescence microscopy.

In order to observe collagen and elastic fibers simultaneously, sections of human aorta, skin, lung, liver, and bladder were stained by Sirius red and analyzed by fluorescence microscopy. In all cases, the fibers of collagen presented the characteristic fluorescent red-orange color that results from the interaction of this extracellular protein with the dye, whereas elastic fibers showed strong green fluorescence (intrinsic fluorescence). This method efficiently detects collagen and elastic fibers when these two structures are present and could have valuable applications in processes that involves both fibers.

Interação entre células do cumulus e atividade da proteína quinase C em diferentes fases da maturação nuclear de oócitos bovinos / Interaction between cumulus cells and the activity of protein kinase C at different stages of bovine oocyte nuclear maturation

Verificou-se a influência da proteína quinase C (PK-C) no reinício e na progressão da meiose em oócitos bovinos, determinando se as células do cumulus são mediadoras da PK-C na regulação da maturação dos oócitos. Complexos cumulus-oócitos (CCO) e oócitos desnudos (OD), distribuídos aleatoriamente em seis tratamentos (T) com base na presença de um ativador da PK-C (PMA) (T1 e T2), de um forbol éster incapaz de ativar a PK-C (4alfa-PDD-controle) (T3 e T4) ou de apenas o meio básico (TCM-199-controle) (T5 e T6), foram cultivados por 7, 9, 12, 18 e 22 horas. A percentagem de rompimento da vesícula germinativa no grupo cultivado com PMA foi maior do que nos dois grupos controle, com e sem células do cumulus. O cultivo de CCO e OD por 12 e 18 horas demonstrou que a PK-C influencia a progressão para os estádios de metáfase I (MI) e metáfase II (MII) de maneira dependente das células do cumulus. Nos períodos de 9 e 22 horas, não foi possível observar diferença entre os grupos quanto aos diferentes estádios de maturação. A ativação da PK-C acelera o reinício da meiose independentemente das células somáticas e acelera a progressão até os estádios de MI e MII na dependência das células do cumulus.

Effect of phenylalanine and p-chlorophenylalanine on Na+, K+-ATPase activity in the synaptic plasma membrane from the cerebral cortex of rats.

Na+, K+-ATPase activity was measured in synaptic plasma membrane from cerebral cortex of Wistar rats subjected to experimental phenylketonuria, i.e., chemical hyperphenylalaninemia induced by subcutaneous administration of 5.2 micromol phenylalanine / g body weight (twice a day) plus 0.9 micromol p-chlorophenylalanine / g body weight (once a day). The treatment was performed from the 6th to the 14th postpartum day and rats were killed 12 h after the last injection. Synaptic plasma membrane from cerebral cortex was prepared by a discontinuous density sucrose gradient for Na+, K+-ATPase activity determination. The results showed that the enzyme activity was decreased by 30% in animals subjected to experimental phenylketonuria when compared to control. The in vitro effects of the drugs on Na+, K+-ATPase activity were also investigated. Phenylalanine and p-chlorophenylalanine inhibited the enzyme activity and this inhibition was reversed by alanine. In addition, competition between phenylalanine and p-chlorophenylalanine for binding to the enzyme was observed, suggesting a common binding site for these substances. Our results suggest that reduction of Na+, K+-ATPase activity may be one of the mechanisms related to the brain dysfunction observed in human PKU.

Extramedullary hemangioblastoma of the conus medullaris.

BACKGROUND: We report the case of an extramedullary pathologically proven hemangioblastoma of the conus medullaris. As spinal dural arteriovenous fistulas most commonly present with a conus medullaris syndrome, our presentation of the MRI, myelographic, and angiographic findings of this unique lesion may be useful in differentiating these two entities. CLINICAL MATERIAL: We report the case of a 57 year old woman with a two year history of progressive low back and right lower extremity pain and weakness. Spinal MRI and myelography demonstrated serpiginous vasculature on the dorsum of the spinal cord consistent with either a vascular tumor or malformation. Selective spinal angiography was thus undertaken by the neuroendovascular team which revealed a tumor nodule consistent with vascular tumor. T12-L1 laminectomy was performed and a 6 mm vascularized tumor was found in the intradural extramedullary compartment adjacent to the conus medullaris. The tumor was completely removed and pathological analysis was consistent with hemangioblastoma. CONCLUSION: This report documents a unique location for extramedullary spinal hemangioblastomas. Although both MRI and myelography are helpful in studying these lesions, angiography remains the gold standard in differentiating between vascular tumor and malformation. We suggest that the angiography be performed by a neurointerventional team to facilitate embolization, should this be warranted.

Alanine prevents the decrease of Na+,K+-ATPase activity in experimental phenylketonuria.

Our objective was to investigate the effect of alanine administration on Na+,K+-ATPase activity in cerebral cortex of rats subjected to chemically-induced phenylketonuria. Wistar rats were treated from the 6th to the 28th day of life with subcutaneous injections of either 2.6 micromol alanine or 5.2 micromol phenylalanine plus 2.6 micromol alpha-methylphenylalanine per g body weight or phenylalanine plus alpha-methylphenylalanine plus alanine in the same doses or equivalent volumes of 0.15 M saline. The animals were killed on the 29th or 60th day of life. Synaptic plasma membrane from cerebral cortex was prepared for Na+,K+-ATPase activity determination. The results showed that alanine injection prevents the decrease of Na+,K+-ATPase activity in animals subjected to experimental phenylketonuria. Therefore, in case the same effects are achieved with ingested alanine, it is possible that alanine supplementation may be an important dietary adjuvant for phenylketonuric patients.

Renal cell carcinoma: a rare source of cauda equina metastasis. Case report.

The authors present the case of a patient in whom intradural metastasis from renal cell carcinoma spread to the cauda equina. To the authors' knowledge, this is only the second report of its kind. This male patient had undergone nephrectomy for the treatment of renal cell carcinoma for 5 years and was diagnosed as having metastatic lung disease 1 year prior to admission. The patient presented with lower back pain that radiated to both legs, but he exhibited no sensorimotor deficits. The majority of cauda equina tumors are primary tumors, and metastases are very rare. The literature is reviewed with reference to current molecular genetic paradigms of metastatic renal cell carcinoma.

Intrathecal administration of recombinant human superoxide dismutase 1 in amyotrophic lateral sclerosis: a preliminary safety and pharmacokinetic study.

We undertook a safety and pharmacokinetic study of intrathecal (i.t.) recombinant human superoxide dismutase (rhSOD1). We administered rhSOD1 as an acute bolus in three sheep and 16 human subjects with amyotrophic lateral sclerosis (ALS). Two sheep received chronic i.t. infusion of rhSOD1 (one at 17.7 mg per day, the second at 38.0 mg per day) for six months. Two of the 16 subjects had familial ALS and mutations in the gene for Cu/Zn SOD1. They both received i.t. infusion of rhSOD1 (5 to 10 mg per day) for 3 to 6 months. Intrathecal rhSOD1 administration was safe. Bolus i.t. administration of 0.25 mg rhSOD1 in sheep revealed a mean elimination half-life of 0.4 (SD +/- 0.06) hours, clearance of 12.2 +/- 3.2 ml per hour, and volume of distribution of 7.3 +/- 0.9 ml. After chronic i.t. infusion, the initial alpha-phase half-life was estimated as 1.2 hours and the extended beta-phase half-life was 15.0 hours. The mean clearance rate was 25.9 ml per hour and the steady-state volume of distribution was 920.6 ml. Bolus i.t. administration of 20 micrograms of rhSOD1 in ALS subjects revealed a mean elimination half-life of 2.2 +/- 0.8 hours, clearance of 1.2 +/- 0.6 ml per hour, and volume of distribution of 3.5 +/- 0.4 ml. With chronic i.t. infusion of 5 mg per day, cerebrospinal SOD1 levels increased approximately fortyfold. We detected no benefit of this treatment in the two patients with familial ALS.

Idiopathic spinal cord herniation: a treatable cause of the Brown-Sequard syndrome--case report.

Symptomatic herniation of the spinal cord through the dura is an uncommon clinical problem. Since 1989, we have encountered three patients who each presented with an unexplained, longstanding Brown-Sequard syndrome and were found to have idiopathic herniation of the thoracic spinal cord. This report describes the clinical, radiographic, and surgical findings in these three patients and reviews the five previously reported patients with this syndrome. Idiopathic herniation of the spinal cord is a treatable cause of the Brown-Sequard syndrome that may be more common than is currently recognized and should be known to all surgeons managing spinal disorders.

Central neurocytomas of the cervical spinal cord. Report of two cases.

Central neurocytoma is a neuronal neoplasm that occurs supratentorially in the lateral or third ventricles. The authors report the clinical, neuroradiological, and neuropathological features of two neurocytomas arising in the spinal cord of two men, aged 65 and 49 years. The patients presented with progressive neurological deficits referable to the cervical spinal cord. Magnetic resonance imaging revealed isodense intramedullary spinal cord tumors at the C3-4 level. Both tumors were initially misdiagnosed as gliomas. In Case 1 the correct diagnosis was made after electron microscopy revealed neuronal features. Immunostaining in Case 2 revealed that tumor cells were positive for synaptophysin and negative for glial fibrillary acidic protein, strongly indicating a neuronal tumor. It is suggested that this spinal cord neoplasm be included under the designation "central neurocytoma."

[Atriofascicular connection with slow conduction and longitudinal dissociation. Electrophysiologic evidence and clinical implications]. / Conexão átrio-fascicular com condução lenta e dissociação longitudinal. Comprovação eletrofisiológica e implicações clínicas.

We report on a patient with paroxysmal left bundle branch block-like tachycardia with electrophysiologic findings suggestive of nodoventricular pathway (ventricular pre-excitation dependent on slowing of AV conduction, and accessory pathway with exclusive anterograde conduction). There was no pre-excitation during sinus rhythm but it was brought on by intravenous verapamil. Atrioventricular node conduction curves showed no signs of duality. Diagnosis of an atriofascicular pathway with decremental properties was based on the following findings: 1) absence of AV dissociation during reciprocating tachycardia; 2) absence of fusion beats or narrowing QRS complexes during tachycardia; 3) advancement of right ventricular activation with late atrial extrastimuli delivered during antidromic tachycardia at a time of low right atrium refractoriness; 4) observation that earliest ventricular endocardial electrogram during tachycardia (activation mapping) was simultaneous with the right bundle potential; 5) surgical ablation of the accessory pathway by endocardial incision at the right anterior aspect of the tricuspid ring, far away from the AV node region. Evidences showing anterograde longitudinal dissociation of the accessory pathway included cycle length alternation during tachycardia and duality of accessory pathway conduction times and refractory periods. We hypothesize that reentry occurring in such AV node-like structure could give to a pre-excited tachycardia with AV dissociation mimicking antidromic tachycardia associated with nodoventricular pathway.

Infections in neurologic surgery. Host defenses.

Normal host defense mechanisms are effective in preventing central nervous system (CNS) infection. Opsonins and compliment levels are normally low in the CNS, however. The relationship of these factors to CNS infection, specifically surgical wound infection and shunt infection, is discussed.

Sprouting of corneal sensory fibers in rats treated at birth with capsaicin.

Normal structure and function of corneal epithelium is known to be related to proper innervation. To investigate possible trophic actions of sensory neurons on corneal epithelium, corneal innervation and various physical parameters were studied in normal rats and in rats treated as neonates with intraperitoneal injections of capsaicin. Corneal lesions were noted in treated rats which varied from multiple punctate areas of corneal opacity to deep stromal opacity with ulceration and neovascularization. These lesions waxed and waned throughout the animal's life. In addition, mechanical threshold of the corneal reflex was higher in capsaicin-treated rats. The tear rate in response to a provocative test was diminished in treated rats, presumably due to reduced afferent trigeminal input to the brain stem; blinking rates were more frequent in these animals. Using fluorescent retrograde tracing techniques, the number of cells innervating the cornea in capsaicin-treated rats was found to be significantly less compared with control animals. Innervation in the cornea (examined using a gold chloride technique) demonstrated a decrease in the number of corneal large axons in treated rats with neurite sprouting of these axons yielding a higher density of nerve fibers compared with controls. Thus, sprouting of residual sensory neurons occurs in response to the partial corneal denervation produced by capsaicin, and this sprouting does not functionally compensate to prevent the development of chronic keratitis.

Biologically inert synthetic dural substitutes. Appraisal of a medical-grade aliphatic polyurethane and a polysiloxane-carbonate block copolymer.

Two types of artificial membranes, a medical-grade aliphatic polyurethane and a polysiloxane-carbonate block copolymer, were tested as substitutes for dura in 24 and 12 rabbits, respectively. The films were placed either epidurally, subdurally, or as dural grafts in equal subgroups of animals. The postoperative course was uneventful with no manifestations of convulsive disorder or cerebrospinal fluid leak. The animals were sacrificed 3, 6, or 9 months after implantation of the artificial membranes. Both types of artificial membranes were easily removed from the underlying nervous and the other surrounding tissues. The histological examination failed to reveal adhesions, neomembrane formations, or any type of foreign body reactions to the polyurethane film. The implantation of the polysiloxane-carbonate film caused no reaction when it was applied epidurally. As a dural graft, the polysiloxane-carbonate copolymer induced the formation of a thin neomembrane of one to two layers of fibroblasts which formed a watertight seal of the dural defect. A similar thin neomembrane was found to encase this artificial membrane in the group of animals in which it was implanted subdurally. There was no foreign body reaction to the polysiloxane-carbonate film. The authors conclude that these materials hold promise as dural substitutes or in the prevention of spinal dural scarring, and should be evaluated clinically.

Changes in corneal innervation during postnatal development in normal rats and in rats treated at birth with capsaicin.

This study was undertaken to learn more about the keratitis that follows the neonatal administration of capsaicin to rats. In the first part of the study the density and pattern of corneal innervation were followed throughout postnatal development in litters of control rats and in rats that received capsaicin as neonates. In rats treated with capsaicin, the density of corneal innervation was lower than that of control rats until 28 days of age. Thereafter nerve fiber sprouting was observed within the corneas of capsaicin-treated rats. By 56 days of age the capsaicin-treated rats had a denser corneal innervation than did control rats. In the second part of the study the incidence and severity of the corneal trophic changes induced by capsaicin were studied in litters of rats treated with chronic tarsorrhaphy and in litters raised in the dark. Neither of these manipulations altered the incidence or severity of keratitis. These observations demonstrate that sprouting of the remaining corneal axons is related temporally to the previously observed decrease in keratitis. Furthermore the more severe keratitis observed in early postnatal life does not appear to be related to physical injury of the cornea.