Non-invasive in-utero quantification of vascular reactivity in human placenta.

OBJECTIVE: Placental vascular reactivity (PlVR) indicates the ability of the placental vasculature to match blood supply to fetal demand. Many pregnancy disorders alter the characteristics of PlVR, resulting in suboptimal oxygen delivery, although current understanding is limited by the lack of non-invasive, repeatable methods to measure PlVR in utero. Our objective was to quantify PlVR by measuring the placental response to transient changes in maternal carbon dioxide (CO2) using blood-oxygen-level-dependent (BOLD) magnetic resonance imaging (MRI). We hypothesized that PlVR will increase with gestational age to meet the changing demands of a growing fetus, and that PlVR will be driven by a maternal response to changes in CO2 concentration. METHODS: This was a cross-sectional study of 35 women with a healthy singleton pregnancy, of whom 31 were included in the analysis. The median gestational age was 32.6 (range, 22.6-38.4) weeks. Pregnant women were instructed to follow audiovisual breathing cues during a MRI scan. Maternal end-tidal CO2 (EtCO2) was measured concurrently with resting placental BOLD MRI for a total of 7-8 min. Preprocessing of magnetic resonance images consisted of manual delineation of placental anatomy and motion correction. In each placental voxel, vascular reactivity was computed using a coherence-weighted general linear model between MRI signal and EtCO2 stimulus. Global PlVR was computed as the mean of voxel-wise PlVR values across the placenta. RESULTS: PlVR, quantified by the placental response to induced, transient changes in maternal CO2, was consistently measured in utero using BOLD MRI. PlVR increased non-linearly with advancing gestational age (P < 0.001) and was higher on the fetal side of the placenta. PlVR was associated positively with fetal brain volume after accounting for gestational age. PlVR did not show any significant associations with maternal characteristics. CONCLUSIONS: We present, for the first time, a non-invasive paradigm to quantify PlVR in ongoing human pregnancies without the use of exogenous gases or contrast agents. Our findings suggest that PlVR is driven by a fetal response to changes in maternal CO2. Ease of translation to the clinical setting makes PlVR a promising biomarker for the identification and management of high-risk pregnancies. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Olcegepant blocks neurogenic and non-neurogenic CGRPergic vasodepressor responses and facilitates noradrenergic vasopressor responses in pithed rats.

BACKGROUND AND PURPOSE: Olcegepant (BIBN4096BS) is a selective non-peptide CGRP receptor antagonist with acute antimigraine properties. Since systemic vascular tone is modulated by perivascular (primary sensory CGRPergic and sympathetic) nerves, this randomized study investigated in pithed rats the effect of acute i.v. treatment with olcegepant on the neurogenic and non-neurogenic: (i) CGRPergic vasodepressor responses; and (ii) noradrenergic vasopressor responses. The pithed rat is an experimental model predictive of systemic (cardio) vascular side effects. EXPERIMENTAL APPROACH: Seventy-five male Wistar rats (divided into 15 groups, n = 5 each) were pithed, artificially ventilated and prepared for: (i) spinal stimulation (T9 -T12 ; 0.56-5.6 Hz) of the sensory CGRPergic vasodepressor outflow or i.v. bolus injections (0.1-1 µg·kg-1 ) of α-CGRP, substance P or acetylcholine, which induced frequency-dependent or dose-dependent vasodepressor responses; or (ii) spinal stimulation (T7 -T9 ; 0.03-3 Hz) of the sympathetic vasopressor outflow or i.v. bolus injections (0.03-3 µg·kg-1 ) of noradrenaline, which produced frequency-dependent or dose-dependent vasopressor responses. KEY RESULTS: Olcegepant (1000 and 3000 µg·kg-1 , i.v.) dose-dependently blocked the vasodepressor responses to sensory nerve stimulation or i.v. α-CGRP, without affecting those to substance P or acetylcholine. Whereas it potentiated the vasopressor responses to sympathetic nerve stimulation or i.v. noradrenaline. CONCLUSIONS AND IMPLICATIONS: Olcegepant (i.v.) selectively blocked the neurogenic and non-neurogenic CGRPergic vasodepressor responses. This blockade by olcegepant potentiated the neurogenic and non-neurogenic noradrenergic vasopressor responses in pithed rats, an effect that might result in an increased vascular resistance and, consequently, in a prohypertensive action.

Knowledge of tuberculosis and vaccine trial preparedness in Lima, Peru.

SETTING: A safe, effective vaccine would improve tuberculosis (TB) control worldwide. Extensive community engagement will be essential to ensure the interest and participation of populations at highest risk. OBJECTIVE/METHOD: To inform the potential implementation of efficacy studies, we assessed TB knowledge, attitudes towards licensed vaccines and willingness to participate in future TB vaccine efficacy trials among 262 household contacts of 79 recently diagnosed pulmonary TB cases in Lima, Peru. RESULTS: Overall knowledge of TB was low. Only 41.6% of household contacts perceived themselves as being at high risk of acquiring TB. Slightly above half (54.2%) indicated willingness to participate in a TB vaccine trial. After clustered analysis adjusting for homogeneity among families, willingness to enroll was associated with belief that receiving all recommended vaccinations is important (adjusted OR [aOR] 3.28, P = 0.016), desire to know more about TB risk factors and clinical trials (aOR 2.60, P = 0.004), older age (aOR 1.02, P = 0.027) and TB knowledge (aOR 0.05, P = 0.039). CONCLUSION: Barriers to participation in TB vaccine trials exist among individuals at high risk for TB. Targeted education about TB risk factors, TB transmission and education about the clinical trial process will be critical for laying the groundwork for future vaccine trials.

Profile of the Health and Nutritional Status of Older Adults in Mexico. 2012 National Health and Nutrition Survey.

BACKGROUND: The health and nutritional conditions of older adults in Mexico are heterogeneous. The prevalence of chronic noncommunicable diseases is elevated with disparities in functionality and socioeconomic inequities. OBJECTIVES: To obtain updated information of the health and nutritional profile of older adults in Mexico in a national representative sample. METHODS: Information was obtained from 6,687 60 years and older adults from the 2012 National Health and Nutrition Survey (ENSANUT 2012). An index defining the status of «healthy adult¼ was constructed taking into account the variables of independence in performing activities of daily living (ADL), based on the development by Katz, instrumental ADL, no chronic diseases, nonsmoker and no active use of alcohol. Tables of frequencies and proportions were constructed and expanded to describe the general characteristics and nutritional status of the adult Mexican population. A logistic regression model was used to study changes in the probability of being classified as a healthy adult with respect to different variables of interest. Probabilities using the delta method were estimated to establish 95% confidence intervals. RESULTS: In this study 12.2% of the older adults, were classified as healthy. The logistic regression model adjusted for the variables included in the study shows that the interaction of age and gender is significant (P = 0.068), where the probability of healthy adult status decreases in women with ageing and remains stable for men. Also, living in the southern region of the country significantly decreases the probability of healthy adult status (P = 0.001). Gender of the older adult was not significant. CONCLUSIONS: In Mexico, the health conditions of older adults are deficient. Public policies need to be generated that are directed at this population group and will translate into self-care actions in the early stages of life so as to guarantee a healthy future.

[Transitory vision loss by orbital osteoma]. / Perte transitoire de la vision causée par un ostéome orbitaire.

The authors present a case of a 50-year-old woman with orbital osteoma complaining of gaze-evoked transitory vision loss of the right eye lasting for 6 months. The patient presented with normal visual acuity, pupils, eye movements, color vision, visual evoked potentials and visual fields. Orbital ultrasound showed a nasal intraorbitary neoformation, with low echogenicity and well-defined borders, suggesting an ethmoidal mucocele. Only a computed tomographic scan allowed the correct diagnosis, revealing a 2.7 cm x 2.2 cm calcified mass in the medial half of the right orbit, compatible with an osteoma. The x-ray view of the orbit confirmed the diagnosis. Although osteomas are slow-growing tumors, we decided to remove it because of the size, the complaints, and the patient's wishes. The tumor was approached and excised through an anterior medial orbitotomy. It was histopathologically shown to be a compact osteoma. The transitory vision loss resolved after surgery.

Prevalence of Toxoplasma gondii antibodies in rabbits (Oryctolagus cuniculus) from Mexico.

Antibodies to Toxoplasma gondii were determined by indirect enzyme-linked immunosorbent assay in serum samples from domestic rabbits from 3 rabbit farms in Mexico. Antibodies to T. gondii were found in 77 (26.9%) of 286 animals. On the farm with the higher rearing standards, the seroprevalence was 18.7%, whereas on the farm with medium standards and another managed by a family, seroprevalence was 39.7 and 33.3%, respectively. This report is the first report concerning the prevalence of antibodies to T. gondii in rabbits from Mexico. Although the prevalence found in the present study is within the range reported for other countries, 2 of the farms revealed a relatively high prevalence, which was probably associated with the presence of cats inside rabbit houses.

[Immediate reaction to latex: comparison between skin test and IgE determination with ELISA]. / Reacción inmediata al latex: comparación entre la prueba cutánea y la determinación de IgE por ELISA.

BACKGROUND: Development of latex hypersensitivity type 1 response mediated by IgE depends on exposition intensitivity and genetic predisposition. Clinical manifestations are urticaria, rhinoconjunctivitis, asthma and anaphylaxis. OBJECTIVE: The aim of the study was to determine the frequency of latex immediate skin reactivity on allergy patients from 1-15 yr old from Hospital Infantil de México. METHODS: A clinical, prospective trial was performed between november 1998 and april 1999. During the study we documented 629 patients with allergy. Of them 30 had positive skin prick test (SPT) to latex according to Aas classification and 30 with negative SPT were randomly chosen as control group. Both groups were similar with respect to diagnosis, age, and sex characteristics. RESULTS: 629 children's with SPT, 30 had positive skin princk test (4.76%), 15 men and 15 women, with an average age of 8.9 years. For groups 1-5 years of age. The group age 6-10 years 6.21% and that of age 11-15 8.9%. Atopia antecedent 73.3%. For rhinitis and asthma diagnostic 63%, rhinitis 13%, asthma 20%, conjunctivitis 20%, atopic dermatitis and anaphylaxis 3.3%, urticaria 6.6%. Surgery antecedent 30%. 100% used a sucking, 93% used a latex toy the relationship of symptoms with the use of latex was 6.6%. Statistica1 ana1ysis was performed using: Nonparametric correlations the Kendall's tau-b: 0.329 and Spearman's rho 0.348 correlation is significant. CONCLUSION: It does exist a correlation between SPT and test for latex-especific IgE antibodies, the older the patient, the higher frequency of latex reaction, history of atopy is the mayor risk factor.

RepA negatively autoregulates the transcription of the repABC operon of the Rhizobium etli symbiotic plasmid basic replicon.

The basic replicon of Rhizobium etli CE3, like other members of the repABC plasmid family, is constituted by the repABC operon. RepC is essential for replication, and RepA and RepB play a role in plasmid segregation. It has been shown that deletion derivatives lacking the repAB genes have an increased copy number, indicating that these genes participate in the control of plasmid copy number. RepA is also a trans-incompatibility factor. To understand the regulation of the repABC operon, in this paper: (i) the transcription start site of the repABC operon was determined; (ii) the promoter region was identified by site-directed mutagenesis of the putative -35 and -10 hexameric elements; and (iii) RepA was recognized as a negative regulator of the transcription of the repABC operon.

Lung transplantation and systemic sclerosis.

We performed lung transplantation in nine patients with Scleroderma related lung disease. Patient characteristics included: 7 (78%) females, 6 (67%) with limited and 3 (33%) with diffuse Scleroderma. Pulmonary fibrosis was present in 7 (78%) and pulmonary hypertension in 4 (44%). All patients were carefully screened by the Johns Hopkins and University of Maryland Scleroderma Center and only referred for transplantation when concomitant renal insufficiency (creatinine clearance < or = 50 ml/min), aspiration, and skin brakdown were excluded. When compared to a similar group of transplant patients with nonscleroderma lung disease (primary pulmonary fibrosis), there was no significant difference in post-transplant survival at four years (76.2 +/- 0.15% vs. 69.2% +/- 0.12%), mean annual incidence rate for acute rejection (0.14 +/- 0.14 vs. 0.47 +/- 0.13) and infection (viral 0.17 +/- 0.17 vs. 0.29 +/- 0.11) (bacterial 0.17 +/- 0.17 vs. 1.4 +/- 0.4) (fungal 0.99 +/- 0.69 vs. 0.36 +/- 0.16) or serum creatinine (1.55 +/- 0.34 mg/dl vs. 1.15 +/- 0.09 mg/dl). We conclude that lung transplantation is viable option for carefully selected patients with scleroderma related lung disease.

Evaluation of diabetic retinopathy by fluorophotometry. European concerted action on ocular fluorometry.

BACKGROUND: Fluorophotometric variables (permeability of the blood-retinal barrier (BRB) and blood-aqueous barrier (BAB), corneal autofluorescence, and lenticular light transmittance) are reported to correlate with the severity of diabetic retinopathy. This preliminary multicenter study was performed to measure these variables simultaneously in patients with type 2 diabetes mellitus and to assess which of these variables could be of help in evaluating diabetic retinopathy. METHODS: Eighty-two patients with type 2 diabetes and diabetic retinopathy were recruited in seven European university clinics. Each patient was investigated three times, at intervals of about one year. The investigations included fluorophotometric determination of corneal autofluorescence, lenticular light transmittance, and permeability of the BRB and BAB. Retinopathy was classified into four grades, using a simplified evaluation system based on the Modified Airlie House retinopathy classification and applied to color fundus slides of standard fields 1 and 2. RESULTS: Multiregression analyses revealed that only corneal autofluorescence and BRB permeability were correlated with the severity of diabetic retinopathy (P < 0.05). Corneal autofluorescence and BRB permeability as single variables were found to be indicative of severe nonproliferative retinopathy and proliferative retinopathy (sensitivity 100% and 86%, respectively, and specificity 65% and 85%, respectively). Combination of both variables increased specificity to 92%. CONCLUSIONS: This preliminary multicenter study shows that fluorophotometric variables can be measured simultaneously and reliably in patients with diabetes and that corneal autofluorescence and BRB permeability (individually or in combination) could be of help in detecting severe non-proliferative retinopathy and proliferative retinopathy.

Permeability of the blood-retinal barrier in healthy humans. European Concerted Action on Ocular Fluorometry.

BACKGROUND: The aim of this study was to compare the inward permeability of the blood-retinal barrier in healthy subjects from six European cities. METHODS: Seventy-two healthy subjects (age 20-70 years) were selected. At 30 min and 60 min after fluorescein injection, fluorescein mass in vitreous was calculated from the concentrations measured along the optical axis of the eye. Non-protein-bound fluorescein (NPBF) concentrations were measured in plasma prepared from blood samples taken 7, 15 and 55 min after injection. Blood-retinal barrier permeability (PBRB) was calculated from the vitreous fluorescein mass and the time integral of NPBF and was corrected for the autofluorescence of ocular tissue and for lenticular light transmittance. RESULTS: Mean PBRB values +/- SD (nm.s-1) were 2.07 +/- 0.54 (Coimbra), 2.01 +/- 0.43 (Frankfurt), 2.24 +/- 0.50 (Ghent), 2.37 +/- 0.56 (Herlev), 1.89 +/- 0.44 (Leiden) and 1.74 +/- 0.38 (Porto). Differences between centers were not significant (P > 0.35). Measurements were reproducible and independent of the time after fluorescein injection (P > 0.50). A PBRB higher than 3.16 nm.s-1 or a value which had increased by 32% was considered abnormal (P < 0.05). CONCLUSION: PBRB values were similar in all centers. The results demonstrate that this is a highly sensitive and reliable method for measuring the permeability of the blood-retinal barrier.

Retinal complications after bungee jumping.

Bungee jumping is becoming a popular sport in the Western world with some cases of ophthalmic complications being reported in recent literature. The authors reported a case of a 23-year-old healthy female who presented retinal complications following a bungee jumping. Her fundi showed superficial retinal hemorrhages in the right eye and a sub-internal limiting membrane hemorrhage affecting the left eye. A general examination, including a full neurological examination, was normal and laboratorial investigations were all within normal values. More studies are necessary to identify risk factors and the true incidence of related ocular lesions, but until then, we think this sport activity should be desencouraged, especially to those that are not psychological and physically fit.

Activities of four macrolides, including clarithromycin, against Mycobacterium fortuitum, Mycobacterium chelonae, and M. chelonae-like organisms.

Susceptibilities to erythromycin by broth microdilution were compared with those to the newer macrolide clarithromycin for 223 isolates of rapidly growing mycobacteria belonging to seven taxonomic groups. Seventy-nine random isolates were also tested against azithromycin and roxithromycin. The MIC of clarithromycin for 90% of strains tested (MIC90) was 0.25 microgram/ml for isolates of Mycobacterium chelonae subsp. chelonae and 0.5 microgram/ml for M. chelonae subsp. abscessus, with 100% of strains inhibited by less than or equal to 1 microgram/ml. Clarithromycin was 10 to 50 times more active than erythromycin and four- to eightfold more active than the other newer macrolides against M. chelonae. MICs of clarithromycin frequently increased with prolonged incubation with isolates of M. chelonae subsp. abscessus but not M. chelonae subsp. chelonae. MICs of clarithromycin were much higher for M. fortuitum bv. fortuitum (MIC50, 2.0 microgram/ml; MIC90, greater than 8.0 microgram/ml). The three newer macrolides had comparable activity against M. fortuitum bv. peregrinum (MIC90s of 0.5 to 2.0 microgram/ml compared with erythromycin MIC90s of greater than 8.0 microgram/ml). Overall, clarithromycin was the most active agent, inhibiting all isolates of M. chelonae subsp. chelonae, M. chelonae subsp. abscessus, M. fortuitum bv. peregrinum, and the M. chelonae-like organisms and 35% of M. fortuitum bv. fortuitum at less than or equal to 1 microgram/ml. Clinical trials of the newer macrolides, especially clarithromycin, against these environmental mycobacterial species appear to be warranted.

Long-term follow-up of central serous retinopathy in 150 patients.

To study the evolution of the retinal pigment epithelial lesions in the central serous retinopathy, the authors studied 150 patients with ages between 20 and 49 years at the first examination, during periods varying between 6 months and 14 years. It was found a greater incidence of the disease in the males (83.3%); bilaterality in 23.3%; only one point of leakage in 62.7%; 3 different types of diffusion (inkblot 71.4%; mushroom 23.8%; with serous pigment epithelial detachment 4.9%). The final visual acuity was < 20/40 in a quarter of the cases and the frequency of the recurrences was 30%. The laser treatment did not influence the recurrences. In 50 patients with a follow-up superior to 3 years, 8 (16%) developed lesions similar to those described as diffuse retinal pigment epitheliopathy with visual field defects and subnormal EOG. Actuarial calculus suggests that 50% of the patients may get the most severe and extensive form of the disease after 12 years of evolution. The results allow to conclude that the diffuse retinal pigment epitheliopathy is only the terminal state of the most severe cases of central serous retinopathy.