Model-Predicted Performance of Second-Trimester Down Syndrome Screening With Sonographic Prenasal Thickness

Objective. The purpose of this study was to estimate the Down syndrome detection and false-positive rates for second-trimester sonographic prenasal thickness (PT) measurement alone and in combination with other markers. Methods. Multivariate log Gaussian modeling was performed using numerical integration. Parameters for the PT distribution, in multiples of the normal gestation-specific median (MoM), were derived from 105 Down syndrome and 1385 unaffected pregnancies scanned at 14 to 27 weeks. The data included a new series of 25 cases and 535 controls combined with 4 previously published series. The means were estimated by the median and the SDs by the 10th to 90th range divided by 2.563. Parameters for other markers were obtained from the literature. Results. A log Gaussian model fitted the distribution of PT values well in Down syndrome and unaffected pregnancies. The distribution parameters were as follows: Down syndrome, mean, 1.334 MoM; log(10) SD, 0.0772; unaffected pregnancies, 0.995 and 0.0752, respectively. The model-predicted detection rates for 1%, 3%, and 5% false-positive rates for PT alone were 35%, 51%, and 60%, respectively. The addition of PT to a 4 serum marker protocol increased detection by 14% to 18% compared with serum alone. The simultaneous sonographic measurement of PT and nasal bone length increased detection by 19% to 26%, and with a third sonographic marker, nuchal skin fold, performance was comparable with first-trimester protocols. Conclusions. Second-trimester screening with sonographic PT and serum markers is predicted to have a high detection rate, and further sonographic markers could perform comparably with first-trimester screening protocols.

Vascular density and distribution of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 (Flk-1) are significantly higher in patients with deeply infiltrating endometriosis affecting the rectum

Objective: To analyze vascular density and immunolocalization of angiogenic vascular endothelial growth factor (VEGF) and its receptor Flk-1 in the proliferative and secretory eutopic human endometrium. and in three different sites of endometriosis: the ovary, bladder, and rectum. Design: Prospective study. Setting: University hospital. Patient(s): Thirty women with endometriosis (10 ovarian, 1.0 bladder, 10 rectal) and 32 control women (10 proliferative endometrium, 10 secretory endometrium, 4 normal ovary, 4 normal bladder, 4 normal rectum). Intervention(s): Normal endometrial samples were obtained from women during laparoscopic ablation of subserous myoma, and biopsy specimens of endometriosis were obtained from patients undergoing surgery for the diagnosis and treatment of endometriosis. Normal tissues of ovary, bladder, and rectum were obtained from these organs beside the lesions of endometriosis. Main Outcome Measure(S): Blood vessels were quantified according to the number of von Willebrand factor-positive endothelial cells. The VEGF and Flk-1 distribution were evaluated semiquantitatively by immunohistochemical staining. Result(s): More blood vessels were found in cases of endometriosis, particularly rectal endometriosis, compared with the respective control samples and with the eutopic endometrium, and they were localized in endometrial stroma around the glands. The VEGF and Flk-1 expression levels were also higher in cases of endometriosis, especially rectal endometriosis. Conclusion(s): Vascularization and VEGF and Flk-1 expression are significantly higher in deeply infiltrating endometriosis affecting the rectum, reinforcing the hypothesis that antiangiogenesis therapy may constitute a new modality of treatment, especially in cases of deep endometriosis involving the rectum.

Seroprevalence of Human Papillomavirus 6, 11, 16, and 18 in Young Primiparous Women in Sao Paulo, Brazil

Introduction: Data on epidemiology of HPV infection are needed for the development of human papillomavirus (HPV) vaccine recommendations, especially in countries where HPV vaccination is not yet included in public vaccination programs. The aim of this study was to determine the prevalence of serum antibodies to HPV types 6, 11, 16, and 18 and associated factors among young women after birth of the first child. Methods: This cross-sectional study was carried out in a large public maternity hospital in Sao Paulo, Brazil. Three hundred one women aged 15 to 24 years who gave birth to their first child were recruited between 43 and 60 days after delivery. Seroprevalence was performed using a type-specific enzyme-linked immunosorbent assay based on HPV Late protein 1 viruslike particles. The association of seroreactivity with these 4 HPV types with selected demographic and behavioral factors was assessed by Generalized Linear Model analysis. Results: Fifty-eight (19.3%) women (95% confidence interval, 15.0%-24.2%) had antibodies to any of the 4 viruslike particles tested. The overall seroprevalence rates of the HPV types were: HPV16, 9.0%; HPV18, 7.0%; and HPV 6+11, 7.7%, which are targeted by the HPV prophylactic vaccines. In the multivariate analysis, only age (inversely, P = 0.044 for trend) and previous sexually transmitted disease (P = 0.008) were 2 factors independently associated with HPV seropositivity. Conclusions: These data offer additional information on the epidemiology of HPV in a group of young Brazilian women after first delivery and contribute to establish a baseline of HPV seroprevalence against which post-HPV vaccine era seroprevalence can be compared.

Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report

Animal and human studies indicate that cannabidiol (CBD), a major constituent of cannabis, has anxiolytic properties. However, no study to date has investigated the effects of this compound on human pathological anxiety and its underlying brain mechanisms. The aim of the present study was to investigate this in patients with generalized social anxiety disorder (SAD) using functional neuroimaging. Regional cerebral blood flow (rCBF) at rest was measured twice using (99m)Tc-ECD SPECT in 10 treatment-naive patients with SAD. In the first session, subjects were given an oral dose of CBD (400 mg) or placebo, in a double-blind procedure. In the second session, the same procedure was performed using the drug that had not been administered in the previous session. Within-subject between-condition rCBF comparisons were performed using statistical parametric mapping. Relative to placebo, CBD was associated with significantly decreased subjective anxiety (p < 0.001), reduced ECD uptake in the left parahippocampal gyrus, hippocampus, and inferior temporal gyrus (p < 0.001, uncorrected), and increased ECD uptake in the right posterior cingulate gyrus (p < 0.001, uncorrected). These results suggest that CBD reduces anxiety in SAD and that this is related to its effects on activity in limbic and paralimbic brain areas.

Collagen Fiber and Versican Distribution Within the Lamina Propria of Fetal Vocal Folds

Objectives: To analyze the presence and distribution of collagen fibers and versican in human vocal fold lamina propria of fetal larynges. Study Design: Cross sectional analysis of cadaveric vocal folds of human fetuses. Methods: Seven fetal larynges obtained from 28- to 36-week-old fetuses were analyzed with the Picrosirius-polarization method, immunohistochemistry, and image analysis. Results: Collagen fibers within the lamina propria exhibited a monolaminar distribution pattern and spatial arrangement in ""wicker basket."" Versican distribution was larger in the superficial and intermediate layers when compared to the deep layer. Conclusion: Our findings suggest that collagen and versican distribution and arrangement within the lamina propria in the developing fetus are important for vocalization at birth.

Prevalence and distribution of the GBV-C/HGV among HIV-1-infected patients under anti-retroviral therapy

Infection with GB virus C (GBV-C) or hepatitis G virus (HGV) is highly prevalent among HIV/AIDS patients. GBV-C/HGV viremia has not been associated with liver disease and seems to slow HIV disease progression. To study the GBV-C/HGV genotypes prevalence among HIV/AIDS patients and its association with HIV viral load (VL) and CD4+ lymphocyte counts. From February 2003 to February 2004, we analyzed 210 HIV-1-infected subjects who were on anti-retroviral therapy (ART). For 63 of them a PCR-nested to the non-coding 5` (5`NCR) region of the GBV-C/HGV was done, and for 49 a DNA direct sequencing was done. A phylogenetic analysis was performed by PHYLIP program. 63(30%) of the HIV-1-infected patients were co-infected with GBV-C/HGV. The phylogenetic analysis revealed the following genotypes (and respective relative frequencies): 1(10%), 2a (41%), 2b (43%), and 3 (6%). Co-infected patients presented lower HIV-1 VL and higher T CD4+ lymphocyte cells counts as compared with patients negative for GBV-C/HGV sequences (log = 4.52 vs. 4.71, p = 0.036), and T CD4+ lymphocyte counts (cells/mm(3) = 322.6 vs. 273.5, p = 0.081, respectively). T CD4+ cells counts equal to, or higher than, 200/mm(3) were significantly more common among co-infected patients than among HIV-infected-only patients (p = 0.042). The lowest T CD4+ cells counts were associated with genotype 1 and the highest with genotype 2b (p = 0.05). The GBV-C/HGV infection prevalence was 30% among HIV-1-infected subjects, and was associated with lower VL and higher CD4+ lymphocyte counts. GBV-C/HGV genotype 2b may be associated with better immunological response. Published by Elsevier B.V.

Ventilation Distribution Studies Comparing Technegas and ""Gallgas"" Using (68)GaCl(3) as the Label

Ventilation distribution can be assessed by SPECT with Technegas. This study was undertaken in piglets with different degrees of ventilation inhomogeneity to compare PET using (68)Ga-labeled pseudogas or ""Gallgas"" with Technegas. Methods: Twelve piglets were studied in 3 groups: control, lobar obstruction, and diffuse airway obstruction. Two more piglets were assessed for lung volume (functional residual capacity). Results: In controls, SPECT and PET images showed an even distribution of radioactivity. With lobar obstruction, the absence of ventilation of the obstructed lobe was visible with both techniques. In diffuse airway obstruction, SPECT images showed an even distribution of radioactivity, and PET images showed more varied radioactivity over the lung. Conclusion: PET provides detailed ventilation distribution images and a better appreciation of ventilation heterogeneity. Gallgas with PET is a promising new diagnostic tool for the assessment of ventilation distribution.

POISSON DISTRIBUTION TO ANALYZE NEAR-THRESHOLD MOTOR EVOKED POTENTIALS

Motor unit action potentials (MUAPs) evoked by repetitive, low-intensity transcranial magnetic stimulation can be modeled as a Poisson process. A mathematical consequence of such a model is that the ratio of the variance to the mean of the amplitudes of motor evoked potentials (MEPs) should provide an estimate of the mean size of the individual MUAPs that summate to generate each MEP. We found that this is, in fact, the case. Our finding thus supports the use of the Poisson distribution to model MEP generation and indicates that this model enables characterization of the motor unit population that contributes to near-threshold MEPs. Muscle Nerve 42: 825-828, 2010

Generalized Pustular Psoriasis in Childhood

Generalized pustular psoriasis is a rare form of psoriasis consisting of a generalized eruption of sudden onset with erythema and sterile pustules. In children, generalized pustular psoriasis is even more uncommon and may present as a severe and potentially life-threatening disorder. In this study, we present demographics, clinical aspects, treatment response, and follow-up of seven children with generalized pustular psoriasis. Retrospective study reviewing the records of seven children with generalized pustular psoriasis including age, gender, age of onset, presence of scalp and nail involvement, family history, concomitant diseases, precipitating factors, treatment modalities, and outcome. Age of first symptoms ranged from 1 month to 11 years. All patients received systemic retinoids at one time of the follow-up period. Other treatment modalities included immunosuppressive drugs, biologics, phototherapy, and sulfasalazine. Two patients presented with severe constitutional illness, secondary infection and septic shock, including one fatal outcome. All further cases have remained free of recurrences for a mean period of up to 3 years. In our study, generalized pustular psoriasis presented a wide clinical spectrum in children ranging from mild, asymptomatic outbreaks to more severe, life-threatening episodes. One fatality was observed. Children generally responded well to systemic retinoids. Further studies and long-term follow-up periods are needed to define potential trigger factors, efficacy and safety of different treatment modalities in children with generalized pustular psoriasis.

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.

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.

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.

Some results on holomorphic generalized functions

In this note, we present three independent results within generalized complex analysis (in the Colombeau sense). The first of them deals with non-removable singularities; we construct a generalized function u on an open subset Omega of C(n), which is not a holomorphic generalized function on Omega but it is a holomorphic generalized function on Omega\S, where S is a hypersurface contained in Omega. The second result shows the existence of a holomorphic generalized function with prescribed values in the zero-set of a classical holomorphic function. The last result states the existence of a compactly supported solution to the (partial derivative) over bar operator.