Familial neuromyelitis optica

Background: Detection of aquaporin-4-specific immunoglobulin G (IgG) has expanded the spectrum of neuromyelitis optica (NMO). Rare reports of familial aggregation have suggested a component of genetic susceptibility but these reports mostly antedated the discovery of the NMO-IgG biomarker and recently updated diagnostic criteria. Methods: We report a case series describing the demographic, clinical, neuroimaging, and NMO-IgG serologic status of 12 multiplex NMO pedigrees with a total of 25 affected individuals. Results: Twenty-one patients (84%) were women. Families were Asian (n = 5), Latino (n = 4), white (n = 1), or African (n = 2). Apparent transmission was either maternal (n = 5) or paternal (n = 2). In 1 family, 3 individuals had NMO; in the others, 2 individuals were affected. Sibling pairs (n = 6), parent-child (n = 4), and aunt-niece (n = 3) pairs were observed. Nineteen patients (76%) were NMO-IgG positive. Twelve (48%) had clinical or serologic evidence of another autoimmune disease. Familial occurrence of NMO occurs in approximately 3% of patients with well-established diagnosis of NMO. Conclusions: A small proportion of patients with NMO have relatives with this condition, but familial occurrence is more common than would be expected from its frequency in the general population. Familial NMO is indistinguishable from sporadic NMO based on clinical symptoms, age at onset, sex distribution, and frequency of NMO-IgG detection. One or 2 generations were affected and affected individuals represented a small fraction of family members. Taken together, these data suggest complex genetic susceptibility in NMO. Neurology (R) 2010;75:310-315

Forefoot Deformity in Diabetic Neuropathic Individuals and its Role in Pressure Distribution and Gait

Background. Foot deformities have been related to diabetic neuropathy progression but their influence on plantar distribution during dynamic tasks is not completely understood. The purpose of the present study was to investigate the influence of metatarsal head prominence and claw toes on regional plantar pressures during gait in patients with diabetic neuropathy Methods Seventy-one adults participated in this study categorized into three groups: a control group (CG, n = 32), patients with diabetic neuropathy without any foot deformities (DG, n = 20), and patients with diabetic neuropathy with metatarsal head prominence and/or claw toes (DMHG, n = 19). Plantar pressure variables (contact area, peak pressure, and maximum mean pressure) were evaluated during gait on rearfoot, midfoot, and forefoot using capacitive insoles (Pedar-X System, Novel Inc., Munich, Germany). A general linear model was applied to repeatedly measure and analyze variance relationships between groups and areas. Results. DMHG. presented larger contact areas at the forefoot and midfoot along with higher peak pressure at the rearfoot compared to the other two groups The DG showed higher mean pressure at the midfoot compared to:the other two groups. Conclusion. The coexistence of diabetic neuropathy and metatarsal head prominence in addition to claw toes, resulted in overloading the rearfoot and enhancing the contact area of forefoot and midfoot while walking. This plantar pressure distribution is a result of a different coordination pattern adopted in order to reduce plantar loads at the anterior parts of the foot that were structurally altered. Patients with diabetic neuropathy without any forefoot deformities presented a different plantar pressure distribution than patients with deformities suggesting that both neuropathy and structural foot alterations can influence foot rollover mechanisms.

Study of the discovery potential of light custodians in a clean decay channel at the LHC

Models of warped extra dimensions with custodial symmetry usually predict the existence of a light Kaluza-Klein fermion arising as a partner of the right-handed top quark, sometimes called light custodians which we will denote (b) over tilde (R). The production of these particles at the LHC can give rise to multi-W events which could be observed in same-sign dilepton channels, but its mass reconstruction is challenging. In this paper we study the possibility of finding a signal for the pair production of this new particle at the LHC focusing on a rarer, but cleaner decay mode of a light custodian into a Z boson and a b-quark. In this mode it would be possible to reconstruct the light custodian mass. In addition to the dominant standard model QCD production processes, we include the contribution of a Kaluza-Klein gluon first mode. We find that (b) over tilde (R) stands out from the background as a peak in the bZ invariant mass. However, when taking into account only the electronic and muonic decay modes of the Z boson and b-tagging efficiencies, the LHC will have access only to the very light range of masses, m((b) over tilde) = O(500) GeV.

Initial hepatosplanchnic blood flow distribution and oxygen metabolism in experimental model of hypotensive brain death

Background: Organs from the so-called marginal donors have been used with a significant higher risk of primary non function than organs retrieved from the optimal donors. We investigated the early metabolic changes and blood flow redistribution in splanchnic territory in an experimental model that mimics marginal brain-dead (BD) donor. Material/Methods: Ten dogs (21.3 +/- 0.9 kg), were subjected to a brain death protocol induced by subdural balloon inflation and observed for 30 min thereafter without ally additional interventions. Mean arterial and intracranial pressures, heart rate, cardiac output (CO), portal vein and hepatic artery blood flows (PVBF and HABF, ultrasonic flowprobe), and O(2)-derived variables were evaluated. Results: An increase in arterial pressure, CO, PVBF and HABF was observed after BD induction. At the end, an intense hypotension with normalization in CO (3.0 +/- 0.2 VS. 2.8 +/- 2.8 L/min) and PVBF (687 +/- 114 vs. 623 +/- 130 ml/min) was observed, whereas HABF (277 33 vs. 134 28 ml/min, p<0.005) remained lower than baseline values. Conclusions: Despite severe hypotension induced by sudden increase of intracranial pressure, the systemic and splanchnic blood flows were partially preserved without signs of severe hypoperfusion (i.e. hyperlactatemia). Additionally, the HABF was mostly negatively affected in this model of marginal BD donor. Our data suggest that not only the cardiac output, but the intrinsic hepatic microcirculatory mechanism plays a role in the hepatic blood flow control after BD.

Calcium channel blockers are independently associated with short sleep duration in hypertensive patients with obstructive sleep apnea

Objective Obstructive sleep apnea (OSA) and hypertension (HYP) frequently coexist and have additive harmful effects on the cardiovascular system. There is also growing evidence that short sleep duration may contribute independently to poor cardiovascular outcome. The aim of this study was to evaluate the potential influence of antihypertensive medication on sleep parameters objectively measured by standard polysomnography in hypertensive patients with OSA. Methods We evaluated consecutive patients with a recent diagnosis of OSA by full polysomnography (apnea hypopnea index >= 5 events/h) and HYP. Smokers, patients with diabetes mellitus, heart failure, or using hypnotics and benzodiazepines were excluded. Results We evaluated 186 hypertensive patients with OSA, 64% men. All patients were on at least one antihypertensive medication, including angiotensin-converting enzyme inhibitors (37%), beta-blockers (35%), angiotensin receptor blockers (32%), diuretics (29%) and calcium channel blockers (21%). Backward multiple regression analysis showed that age (P <= 0.001) and the use of calcium channel blockers (P=0.037) were the only factors inversely associated with lower total sleep time. Sleep efficiency was inversely associated only with age (P <= 0.001), whereas the use of calcium channel blockers had a nonsignificant trend (P=0.092). Use of calcium channel blockers was associated with significant reduction in total sleep time (-41 min, P=0.005) and 8% lower sleep efficiency (P=0.004). No other antihypertensive medication, including diuretics and beta-blockers, was associated with sleep impairment. Conclusion Calcium channel blockers may impact negatively on sleep duration in hypertensive patients with OSA. The mechanisms and significance of this novel finding warrants further investigation. J Hypertens 29: 1236-1241 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Capnography reflects ventilation/perfusion distribution in a model of acute lung injury

Background Changes in the shape of the capnogram may reflect changes in lung physiology. We studied the effect of different ventilation/perfusion ratios (V/Q) induced by positive end-expiratory pressures (PEEP) and lung recruitment on phase III slope (S(III)) of volumetric capnograms. Methods Seven lung-lavaged pigs received volume control ventilation at tidal volumes of 6 ml/kg. After a lung recruitment maneuver, open-lung PEEP (OL-PEEP) was defined at 2 cmH(2)O above the PEEP at the onset of lung collapse as identified by the maximum respiratory compliance during a decremental PEEP trial. Thereafter, six distinct PEEP levels either at OL-PEEP, 4 cmH(2)O above or below this level were applied in a random order, either with or without a prior lung recruitment maneuver. Ventilation-perfusion distribution (using multiple inert gas elimination technique), hemodynamics, blood gases and volumetric capnography data were recorded at the end of each condition (minute 40). Results S(III) showed the lowest value whenever lung recruitment and OL-PEEP were jointly applied and was associated with the lowest dispersion of ventilation and perfusion (Disp(R-E)), the lowest ratio of alveolar dead space to alveolar tidal volume (VD(alv)/VT(alv)) and the lowest difference between arterial and end-tidal pCO(2) (Pa-ETCO(2)). Spearman`s rank correlations between S(III) and Disp(R-E) showed a =0.85 with 95% CI for (Fisher`s Z-transformation) of 0.74-0.91, P < 0.0001. Conclusion In this experimental model of lung injury, changes in the phase III slope of the capnograms were directly correlated with the degree of ventilation/perfusion dispersion.

Immediate and lasting improvements in weight distribution seen in baropodometry following a high-velocity, low-amplitude thrust manipulation of the sacroiliac joint

The biomechanics of the sacroiliac joint makes the pelvic segment responsible for proper weight distribution between lower extremities; however, it is known to be susceptible to altered mobility. The objective of this study was to analyze baropodometric responses following thrust manipulation on subjects with sacroiliac joint restrictions. Twenty asymptomatic subjects were submitted to computerized baropodometric analysis before, after, and seven days following sacroiliac manipulation. The variables peak pressure and contact area were obtained at each of these periods as the average of absolute values of the difference between the right and left foot based on three trials. Data revealed significant reduction only in peak pressure immediately after manipulation and at follow-up when compared to pre-manipulative values (p < 0.05). Strong correlation was found between the dominant foot and the foot with greater contact area (r - 0.978), as well as between the side of joint restriction and the foot with greater contact area (r = 0.884). Weak correlation was observed between the dominant foot and the foot with greater peak pressure (r = 0.501), as well as between the side of joint restriction and the foot with greater peak pressure (r = 0.694). The results suggest that sacroiliac joint manipulation can influence peak pressure distribution between feet, but contact area does not seem to be related to the biomechanical aspects addressed in this study. (C) 2011 Elsevier Ltd. All rights reserved.

Genotype and mating type distribution within clinical Cryptococcus neoformans and Cryptococcus gattii isolates from patients with cryptococcal meningitis in Uberaba, Minas Gerais, Brazil

We molecularly characterized 81 cryptococcal isolates recovered from cerebrospinal fluid samples of 77 patients diagnosed between 1998 and 2007 as having cryptococcal meningitis in Uberaba Minas Gerais, Brazil. Fifty-seven (74%) were male with a mean age 35.6 years. Seventy-two (88.9%) of the isolates were from 68 AIDS patients and cryptococcosis was the first AIDS-defining condition in 38 (55.9%) patients. Cryptococcosis and AIDS were simultaneously diagnosed in 25 (65.8%) of these 38 patients. Genotypes were characterized through the use of URA5 restriction fragment length polymorphisms analysis, the genetic variability was determined using PCR-fingerprinting with the minisatellite-specific primer M13, and the mating type and serotypes were established by PCR. Seventy-six of the 81 isolates were Cryptococcus neoformans (93.8%), while the remaining five were C. gattii (6.1%), but all were mating type a. C. neoformans isolates were genotype VNI (serotype A), while C. gattii isolates were VGII. Four of the latter isolates were identical, but only two were from AIDS patients. Six of the nine isolates from non-AIDS patients were VNI. PCR fingerprints of the isolates from two of the three AIDS patients with clinical relapse were 100% identical. The predominance of VNI and mating type a is in accordance with data from other parts of the world. The occurrence of VGII in Minas Gerais indicates a geographical expansion within Brazil.

Sildenafil inhibits duodenal contractility via activation of the NO-K+ channel pathway

Phosphodiesterase type-5 (PDE5) specifically cleaves cyclic guanosine monophosphate (cGMP), a key intracellular secondary messenger. The PDE5 inhibitor sildenafil is a well-known vasodilator that also has gastrointestinal myorelaxant properties. In the present study, we further investigated sildenafil-induced myorelaxation in rat isolated duodenum, assessing its interaction with nitric oxide (NO) synthase and K+ channel opening. The spontaneous contractions of duodenal strips were reversibly inhibited by sildenafil (0.1-300 mu M) in a concentration-dependent manner [mean (95% confidence interval); EC50 = 6.8 (2.7-17.3) mu M]. The sildenafil-induced myorelaxation was significantly decreased by the NO synthase inhibitor N-nitro-L-arginine methyl ester [increasing the EC50 value to 41.9 (26.1-67.3) mu M]. Sodium nitroprusside or forskolin pretreatments enhanced the sildenafil-induced myorelaxation. In isolated strips pretreated with BaCl2 (0.2 mM), 4-aminopyridine (4-AP, 3 mM), or glybenclamide (1 mu M), the sildenafil-induced EC50 value was significantly increased to 32.8 (19.1-56.4), 27.1 (15.2-48.3) and 20.1 (16.4-24.7) mu M, respectively. Minoxidil (50 mu M) or diazoxide (100 mu M) also significantly attenuated the sildenafil-induced potency. In conclusion, the NO synthase/cyclic nucleotide pathway activation is involved in sildenafil-induced inhibition of spontaneous duodenal contractions. Its pharmacological action seems to be influenced by K+ channel opening, especially the voltage-sensitive ones, being inhibited by 4-AP and K-ATP channels, sensitive to glybenclamide.

Study of the spatial distribution of the absorbed dose in blood volumes irradiated using a teletherapy unit

Blood irradiation can be performed using a dedicated blood irradiator or a teletherapy unit. A thermal device providing appropriate storage conditions during blood components irradiation with a teletherapy unit has been recently proposed. However, the most appropriated volume of the thermal device was not indicated. The goal of this study was to indicate the most appropriated blood volume for irradiation using a teletherapy unit in order to minimize both the dose heterogeneity in the volume and the blood irradiation time using these equipments. Theoretical and experimental methods were used to study the dose distribution in the blood volume irradiated using a linear accelerator and a cobalt-60 therapy machine. The calculation of absorbed doses in the middle plane of cylindrical acrylic volumes was accomplished by a treatment planning system. Experimentally, we also used cylindrical acrylic phantoms and thermoluminescent dosimeters to confirm the calculated doses. The data obtained were represented by isodose curves. We observed that an irradiation volume should have a height of 28 cm and a diameter of 28 cm and a height of 35 cm and a diameter of 35 cm, when the irradiation is to be performed by a linear accelerator and a cobalt-60 teletherapy unit, respectively. Calculated values of relative doses varied from 93% to 100% in the smaller volume, and from 66% to 100% in the largest one. A difference of 5.0%, approximately, was observed between calculated and experimental data. The size of these volumes permits the irradiation of blood bags in only one bath without compromising the homogeneity of the absorbed dose over the irradiated volume. Thus, these irradiation volumes can be recommend to minimize the irradiation time when a teletherapy unit is used to irradiate blood. (C) 2010 Elsevier Ltd. All rights reserved.

Frequency distribution of XbaIG > T and HaeIIIT > C GLUT1 polymorphisms among different Brazilian ethnic groups

GLUT is the major glucose transporter in mammalian cells. Single nucleotide polymorphisms (SNP) at GLUT1 promoter and regulatory regions have been associated to the risk of developing nephropathy in different type 1 and type 2 diabetic populations. It has been demonstrated that differences in allelic and genotypic frequencies of GLUT1 gene (SLC2A1) polymorphisms occur among different populations. Therefore, ethnic differences in distribution of GLUT1 gene polymorphisms may be an important factor in determining gene-disease association. In this study, we investigated the XbaIG > T and HaeIIIT > C polymorphisms in six different Brazilian populations: 102 individuals from Salvador population (Northern Brazil), 56 European descendants from Joinville (South Brazil), 85 Indians from Tiryi tribe (North Brazil) and 127 samples from Southern Brazil: 44 from European descendants, 42 from African descendants and 41 from Japanese descendants. Genotype frequencies from both sites did not differ significantly from those expected under the Hardy-Weinberg equilibrium. We verified that the allele frequencies of both polymorphisms were heterogeneous in these six Brazilian ethnic groups.