Initial multicenter experience with double nucleoside therapy for human immunodeficiency virus infection during pregnancy.

OBJECTIVE: To study maternal and neonatal effects of combination nucleoside analog therapy administered to human immunodeficiency virus (HIV)-infected pregnant women for maternal indications. METHODS: A multicenter, prospective observational study was undertaken at six perinatal centers in the United States and Canada that supported regional referral programs for the treatment of HIV-infected pregnant women. Demographic, laboratory, and pregnancy outcome data were collected for 39 women whose antiretroviral treatment regimens were expanded to include more than one nucleoside analog for maternal indications. The 40 newborns were monitored at pediatric referral centers through at least three months of age to ascertain their HIV infection status. RESULTS: For all 39 women, zidovudine (ZDV) therapy was instituted at 13.4 +/- 8.2 weeks, with a second agent (lamivudine [3TC] in 85% of cases) being added at a mean gestational age of 17.6 weeks. Duration of therapy with two agents was 20.6 +/- 10.4 weeks overall, with no women stopping medications because of side effects or toxicity. No significant changes in maternal laboratory values were seen, except for an increase in mean corpuscular volume, over the course of pregnancy. No clinically significant adverse neonatal outcomes were noted, with all but the three preterm newborns leaving hospital with their mothers. Neonatal anemia (hematocrit < 50%) was seen in 62% of newborns, with no children needing transfusion; mild elevations of liver function tests, primarily aspartate aminotransferase, were noted in 58% of newborns tested, though none were clinically jaundiced. Overall rate of neonatal HIV infection was 2.5% (95% confidence interval: 0.1-13.2%). CONCLUSION: Combination antiretroviral therapy during pregnancy with two nucleoside analogs was well-tolerated by mothers and newborns, with no significant short-term toxicities or side effects noted. Surveillance of exposed newborns' hematologic and liver function appears warranted.     

Measuring clients' satisfaction with self-help agencies

OBJECTIVE: Clients' satisfaction with their involvement in treatment decisions has been largely overlooked in the formulation of satisfaction measures. The authors describe the development of a scale that assesses clients' satisfaction with services and with their involvement in treatment decisions. METHODS: Long-term users of four client-operated mental health self-help agencies were interviewed at baseline (N=310) and six months (N=248) using the 11-item Self-Help Agency Satisfaction Scale (SHASS). The scale was developed on the basis of consumers' input about their satisfaction with services and their involvement in treatment decisions. To explore the relationship between satisfaction as measured by the SHASS and outcomes, the six-month interview included four outcome measures-independent and assisted social functioning, symptom severity, and a sense of personal empowerment. Internal consistency, stability, and discriminant validity were evaluated. RESULTS: Factor analyses confirmed that the SHASS has two subscales, one assessing service satisfaction and the other assessing satisfaction with involvement in treatment decisions. The scale and its subscales showed high internal consistency, moderate stability, and discriminant validity. The SHASS subscales showed modest associations with two of four outcome measures-assisted and independent social functioning. CONCLUSIONS: The SHASS is a brief instrument that can be used to measure clients' satisfaction with their involvement in treatment in mental health self-help agencies.     

Patterns of III nerve synkinesis

PURPOSE Various patterns of synkinesis have been observed following both congenital and acquired III nerve palsies. Aberrant regeneration is the most widely accepted mechanism which explains this synkinesis. Two models of aberrant regeneration have been proposed, namely central collateral axon sprouting, and misdirection of regenerating neurones at the site of nerve injury. We have studied the clinical patterns of III nerve recovery and synkinesis following III nerve palsies and relate the findings to the proposed models of synkinesis. MATERIALS AND METHODS Twelve patients with acquired and two with early onset III nerve synkinesis were reviewed. The type, rate and pattern of recovery of III nerve palsy was established from case notes. Observations and measurements of ocular motility, pupil movements, eyelid position and intraocular pressure changes were performed on each patient. Signs of contralateral synkinetic movements were also sought. RESULTS Upper lid retraction on attempted down gaze and in adduction was the most frequent synkinetic movement recorded. Observation of pupil size revealed evidence of pupillary-extraocular muscle synkinesis in all gaze positions except abduction. Similarly, intraocular pressure changes and signs of globe retraction showed widespread extraocular muscle co-contraction. Synkinetic levator innervation of extraocular muscles [i.e., LPS to MR, IR, SR] was also observed, a finding not previously reported in III nerve palsy but predicted by our model of misdirection of regenerating neurones at the site of nerve injury. There was no evidence of contralateral aberrant innervation. CONCLUSION Evidence of III nerve synkinesis in patients with III nerve palsy is widespread and the patterns of synkinesis observed were broadly similar for all patients irrespective of the aetiology. Random aberrant III nerve regeneration at the site of nerve injury best explains the patterns of synkinesis observed. Central collateral axon sprouting does not seem to play a major part in the synkinetic movements observed in acquired III nerve lesions.     

EXPERIMENTAL ATTEMPTS TO INCREASE THE BLOOD SUPPLY TO THE DOG'S HEART BY MEANS OF CORONARY SINUS OCCLUSION

Sudden occlusion of the left anterior descending branch approximately 2 cm. below the ostium of the left circumflex coronary artery in the dog''s heart produces a mortality rate of approximately 50 per cent. In dogs weighing approximately 15 kilos surviving more than 24 hours (average 1 week), an infarction is produced which almost invariably measures 5 x 5 cm. on surface. Following coronary sinus obturation such secondary sudden occlusion of the left anterior descending branch is followed either by no infarction or by a reduction in the size of the infarct. The success of the procedure, quite apart from the mortality rate, depends upon the completeness of the coronary sinus obturation. On the other hand, sudden and complete coronary sinus obturation by itself is associated with a high operative mortality and apparently does not affect the mortality rate following subsequent sudden left anterior descending branch occlusion. Partial persistent obturation of the coronary sinus, however, is in itself associated with a low operative mortality. Furthermore, its experimental production in dogs appears to lower the mortality rate following subsequent sudden occlusion of the left anterior descending branch and to diminish the extent of the infarction. In the introduction to this report it was pointed out that there are three important desiderata to the problem of improving the coronary circulation in the human heart. The findings herein reported fulfill these requisites to an encouraging degree. It has been shown that following the outlined procedures, a functional increase in the blood supply to the heart can be produced in a significant proportion of experimental animals, this varying with the nature of the experimental procedure. The manipulation is simple, can be performed in the dog within approximately 20 minutes, and does not lead to appreciable pericardial adhesions. Increase in the nutrition of the myocardium is noted 1 week after the experimental procedure. Although no experiments employing sudden left anterior descending coronary branch occlusion were carried out sooner than 1 week, there is available anatomic evidence that within possibly 24 hours after coronary sinus occlusion a dilatation of the vascular bed occurs. In subsequent experiments attempts will be made to determine whether this early vascular dilatation is adequate to compensate for subsequent sudden left anterior descending branch occlusion. A discussion is given of the results following various coronary sinus occlusion procedures in which it is indicated that it is desirable to produce a partial or gradual occlusion in order to lower the mortality rate both of the initial procedure as well as of the subsequent sudden arterial occlusion. Experiments thus far reported on cardiopexy operations are lacking in evidence that they are associated with appreciable improvement in the vascular nutrition of the myocardium.     

FARVATX: Family‐Based Rare Variant Association Test for X‐Linked Genes

Although the X chromosome has many genes that are functionally related to human diseases, the complicated biological properties of the X chromosome have prevented efficient genetic association analyses, and only a few significantly associated X‐linked variants have been reported for complex traits. For instance, dosage compensation of X‐linked genes is often achieved via the inactivation of one allele in each X‐linked variant in females; however, some X‐linked variants can escape this X chromosome inactivation. Efficient genetic analyses cannot be conducted without prior knowledge about the gene expression process of X‐linked variants, and misspecified information can lead to power loss. In this report, we propose new statistical methods for rare X‐linked variant genetic association analysis of dichotomous phenotypes with family‐based samples. The proposed methods are computationally efficient and can complete X‐linked analyses within a few hours. Simulation studies demonstrate the statistical efficiency of the proposed methods, which were then applied to rare‐variant association analysis of the X chromosome in chronic obstructive pulmonary disease. Some promising significant X‐linked genes were identified, illustrating the practical importance of the proposed methods.     

Effects of Ambient Coarse,Fine, and Ultrafine Particles and Their Biological Constituents on Systemic Biomarkers: A Controlled Human Exposure Study

Background

Ambient coarse, fine, and ultrafine particles have been associated with mortality and morbidity. Few studies have compared how various particle size fractions affect systemic biomarkers.

Objectives

We examined changes of blood and urinary biomarkers following exposures to three particle sizes.

Methods

Fifty healthy nonsmoking volunteers, mean age of 28 years, were exposed to coarse (2.5–10 μm; mean, 213 μg/m³) and fine (0.15–2.5 μm; mean, 238 μg/m³) concentrated ambient particles (CAPs), and filtered ambient and/or medical air. Twenty-five participants were exposed to ultrafine CAP (< 0.3 μm; mean, 136 μg/m³) and filtered medical air. Exposures lasted 130 min, separated by ≥ 2 weeks. Blood/urine samples were collected preexposure and 1 hr and 21 hr postexposure to determine blood interleukin-6 and C-reactive protein (inflammation), endothelin-1 and vascular endothelial growth factor (VEGF; vascular mediators), and malondialdehyde (lipid peroxidation); as well as urinary VEGF, 8-hydroxy-deoxy-guanosine (DNA oxidation), and malondialdehyde. Mixed-model regressions assessed pre- and postexposure differences.

Results

One hour postexposure, for every 100-μg/m³ increase, coarse CAP was associated with increased blood VEGF (2.41 pg/mL; 95% CI: 0.41, 4.40) in models adjusted for O_3, fine CAP with increased urinary malondialdehyde in single- (0.31 nmol/mg creatinine; 95% CI: 0.02, 0.60) and two-pollutant models, and ultrafine CAP with increased urinary 8-hydroxydeoxyguanosine in single- (0.69 ng/mg creatinine; 95% CI: 0.09, 1.29) and two-pollutant models, lasting < 21 hr. Endotoxin was significantly associated with biomarker changes similar to those found with CAPs.

Conclusions

Ambient particles with various sizes/constituents may influence systemic biomarkers differently. Endotoxin in ambient particles may contribute to vascular mediator changes and oxidative stress.

Citation

Liu L, Urch B, Poon R, Szyszkowicz M, Speck M, Gold DR, Wheeler AJ, Scott JA, Brook JR, Thorne PS, Silverman FS. 2015. Effects of ambient coarse, fine, and ultrafine particles and their biological constituents on systemic biomarkers: a controlled human exposure study. Environ Health Perspect 123:534–540; http://dx.doi.org/10.1289/ehp.1408387