Filtration Markers, Cardiovascular Disease, Mortality, and Kidney Outcomes in Stable Kidney Transplant Recipients: The FAVORIT Trial.

Cystatin C and beta-2-microglobulin (B2M) are filtration markers associated with adverse outcomes in nontransplant populations, sometimes with stronger associations than for creatinine. We evaluated associations of estimated glomerular filtration rate from cystatin C (eGFRcys ), B2M (eGFRB2M ), and creatinine (eGFRcr ) with cardiovascular outcomes, mortality, and kidney failure in stable kidney transplant recipients using a case-cohort study nested within the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial. A random subcohort was selected (N = 508; mean age 51.6 years, median transplant vintage 4 years, 38% women, 23.6% nonwhite race) with enrichment for cardiovascular events (N = 306; 54 within the subcohort), mortality (N = 208; 68 within the subcohort), and kidney failure (N = 208; 52 within the subcohort). Mean eGFRcr , eGFRcys , and eGFRB2M were 46.0, 43.8, and 48.8 mL/min/1.73m2 , respectively. After multivariable adjustment, hazard ratios for eGFRcys and eGFRB2M <30 versus 60+ were 2.02 (95% confidence interval [CI] 1.09-3.76; p = 0.03) and 2.56 (1.35-4.88; p = 0.004) for cardiovascular events; 3.92 (2.11-7.31) and 4.09 (2.21-7.54; both p < 0.001) for mortality; and 9.49 (4.28-21.00) and 15.53 (6.99-34.51; both p < 0.001) for kidney failure. Associations persisted with additional adjustment for baseline eGFRcr . We conclude that cystatin C and B2M are strongly associated with cardiovascular events, mortality, and kidney failure in stable kidney transplant recipients.

Real-time phase-contrast flow MRI of haemodynamic changes in the ascending aorta and superior vena cava during Mueller manoeuvre.

AIM: To evaluate the potential of real-time phase-contrast flow magnetic resonance imaging (MRI) at 40 ms resolution for the simultaneous determination of blood flow in the ascending aorta (AA) and superior vena cava (SVC) in response to reduced intrathoracic pressure (Mueller manoeuvre). MATERIALS AND METHODS: Through-plane flow was assessed in 20 healthy young subjects using real-time phase-contrast MRI based on highly undersampled radial fast low-angle shot (FLASH) with image reconstruction by regularized non-linear inversion. Haemodynamic alterations (three repetitions per subject = 60 events) were evaluated during normal breathing (10 s), inhalation with nearly closed epiglottis (10 s), and recovery (20 s). RESULTS: Relative to normal breathing and despite interindividual differences, reduced intrathoracic pressure by at least 30 mmHg significantly decreased the initial peak mean velocity (averaged across the lumen) in the AA by -24 ± 9% and increased the velocity in the SVC by +28 ± 25% (p < 0.0001, n = 23 successful events). Respective changes in flow volume per heartbeat were -25 ± 9% in the AA and +49 ± 44% in the SVC (p < 0.0001, n = 23). Flow parameters returned to baseline during sustained pressure reduction, while the heart rate was elevated by 10% (p < 0.0001) after the start (n = 24) and end (n = 17) of the manoeuvre. CONCLUSIONS: Real-time flow MRI during low intrathoracic pressure non-invasively revealed quantitative haemodynamic adjustments in both the AA and SVC.

Effect of cryptosporidial and giardial diarrhoea on social maturity, intelligence and physical growth in children in a semi-urban slum in south India.

BACKGROUND: Early childhood diarrhoea is a major cause of infant morbidity and mortality in developing countries. Recurrent and persistent diarrhoea affect growth and cognition in children as young as 6 years. OBJECTIVES: To evaluate the effect of early childhood cryptosporidial and giardial diarrhoea on growth and development in children in a semi-urban slum in India. This is the first report of such assessment at 3 years of age. METHODS: This study was undertaken on 116 children who were part of an ongoing birth cohort study (n=452) of rotaviral and cryptosporidial diarrhoea between June and December 2005. Social quotients (SQ) assessed by the Vineland Social Maturity Scale, intelligence quotients (IQ) assessed by the Seguin Form Board Test, physical growth parameters and sociodemographic data in 84 children with a history of cryptosporidial or giardial diarrhoea were compared with those of 32 without diarrhoea. RESULTS: Children with a past history of giardial diarrhoea showed a trend towards lower SQ (p=0.09) and had significantly lower IQ (p=0.04) and increased wasting (p=0.04). Cryptosporidial diarrhoea was not associated with poor IQ, SQ or physical growth. CONCLUSION: This study demonstrates the long-term effect of protozoan diarrhoea, especially that caused by giardia, on both intelligence and physical growth in Indian children as early as 3 years of age and re-inforces the need for early detection and prevention of early childhood protozoan diarrhoea.

Training sensory signal-to-noise resolution in children with ADHD in a global mental health setting.

Children with attention deficit/hyperactivity disorder (ADHD) have impaired focus on goal-relevant signals and fail to suppress goal-irrelevant distractions. To address both these issues, we developed a novel neuroplasticity-based training program that adaptively trains the resolution of challenging sensory signals and the suppression of progressively more challenging distractions. We evaluated this sensory signal-to-noise resolution training in a small sample, global mental health study in Indian children with ADHD. The children trained for 30 h over 6 months in a double-blind, randomized controlled trial. Training completers showed steady and significant improvements in ADHD-associated behaviors from baseline to post training relative to controls, and benefits sustained in a 6-month follow-up. Post-training cognitive assessments showed significant positive results for response inhibition and Stroop interference tests in training completers vs controls, while measures of sustained attention and short-term memory showed nonsignificant improvement trends. Further, training-driven improvements in distractor suppression correlated with the improved ADHD symptoms. This initial study suggests utility of signal-to-noise resolution training for children with ADHD; it emphasizes the need for further research on this intervention and substantially informs the design of a larger trial.

Phenotype, genotype and gender identity in a large cohort of patients from India with 5α-reductase 2 deficiency.

Deficiency of the 5α-reductase 2 enzyme impairs the conversion of testosterone to dihydrotestosterone (DHT) and differentiation of external genitalia, seminal vesicles and prostate in males. The present study describes the phenotype, genotype and gender identity in a large cohort of patients with 5αRD2. All patients underwent detailed clinical evaluation, hormonal profile, karyotyping and molecular analysis of the SRD5A2 gene. The molecular analysis of the SRD5A2 gene showed the presence of mutant alleles in 24 patients. We found 6 novel mutations IVS(1-2) T>C, p.A52T, 188-189insTA, 904-905ins A, p.A12T and p.E57X in our patients. All patients had ambiguous genitalia and the degrees of under-virilization ranged from penoscrotal hypospadias and microphallus to clitoromegaly. The position of gonads was variable in patients with same mutation. All the patients with mutations in the SRD5A2 gene had male gender identity. Those reared as female had gender dysphoria and underwent gender reassignment. Though a specific genotype-phenotype correlation could not be established in our patient but confirming the diagnosis of 5αRD2 with assessment of the SRD5A2 gene may help in appropriate gender assignment.

Gender differences in disability: a comparison of married patients with schizophrenia.

Gender differences in disability constitute a fertile area of research, as disabilities need to be measured and evaluated in the social context which defines role expectations and consequently the role performance. This paper reports on the differences in disability in married patients with schizophrenia, as marital status is an important determinant of role expectation. The study sample constituted 30 married patients, of both sexes, who satisfied DSM-III criteria for schizophrenia, and were living with their spouse at the time of assessment. Disability was evaluated using the DAS (modified version). The findings indicated that women were more disabled than men on many of the evaluation parameters (p < 0.05); there was also a strong correlation between negative symptoms and disability variables in both the sexes. While a correlation between PSE syndromes and disability variables was seen in the case of males, the relationship was not seen in females. Stepwise regression also revealed that negative symptoms predominated among the factors associated with global disability in both sexes. Most of the reports in the literature reveal that women are less disabled than men. The findings of this study, that women are more disabled than men, is discussed in the context of the social conditions prevailing in India.

Sustained-release hormonal preparations XV: release of progesterone from cholesterol pellets in vivo.

Progesterone-sterol pellets were made that porvided a zero-order release of progesterone for 80 days. 4-(14)C-Progesterone was used to measure the release in vitro and in vivo. The dissolution rate in vitro (distilled water as the desorbing medium) for progesterone-cholesterol (59:41 w/w) and the progesterone-beta-sitosterol (47:53 w/w) pellets was 72 microng/100 mm2/24 hr. The average in vivo absorption from subcutaneously implanted pellets in rabbits was 2 +/- 0.1 microng/ml of plasma/cm2 of surface area. Of this amount, 20-25% was progesterone; the remainder was progesterone metabolites and conjugates. Zero-order release (plasma levels) was obtained for approximately 80 days or until about 70% of the available progesterone was exhausted. During this time, the level of excreted radioactivity in urine continuously decreased, indicating that monitoring only this parameter would lead to erroneous conclusions. A long-term effect and increased effectiveness were obtained with a 5-20-mg progesterone equivalent dose, using gel prepared from 2% methylcellulose as the suspending medium.

PIP: These experiments were designed to test the release and biological effectivenss of steroid-sterol pellets combined in the region of eutectic mixture. Details of preparation of pellets and of radioactive progesterone are given. Varying numbers of pellets were implanted in rabbits sc. Peripheral blood, urine, and feces of the rabbits were collected. Rats were ovariectomized on Day 5 following insemination and progesterone tablets were inserted. At autopsy on day 18 viable and resorbing fetuses were recorded. Some rats also received, on the day of ovariectomy and 1 week later, 1 mcg of estradiol benzoate. Dissolution rates of progesterone were high during the 1st few days of the test and then became more uniform. Dissolution of progesteorne from pellets of cholesterol 41% and beta-sitosterol 53% increased with decrease in pellet size. About 40% of total radioactivity in plasma was either extractable and 60% was in the aqueous phase. Radioactive progesterone metabolites were mostly excreted in urine. Pellets were recovered after the experiment. Amount of radioactivity left varied from 4 to 27%. Recovery of radioactive material in urine, feces, and from tissues near the implants averaged 85%. In the rabbits, ovulation was inhibited for the duration of the experiment, 45 days, with a dose of 121.5 mg (145 mcg/day). In ovariectomized rats, fetuses were rapidly absorbed. Progesterone pellets were an incomplete fetal support as only resorption sites were found at autopsy. Addition of 1 mcg of estradiol at weekly intervals inceased fetal salvage in rats. Measurement of plasma levels was more reliable than excretion rates. Progesterone in a lipid delivery system was estimated to be 20 times more active than daily injections dissolved in oil.

Real-time phase-contrast flow MRI of the ascending aorta and superior vena cava as a function of intrathoracic pressure (Valsalva manoeuvre).

OBJECTIVE: Real-time phase-contrast flow MRI at high spatiotemporal resolution was applied to simultaneously evaluate haemodynamic functions in the ascending aorta (AA) and superior vena cava (SVC) during elevated intrathoracic pressure (Valsalva manoeuvre). METHODS: Real-time phase-contrast flow MRI at 3 T was based on highly undersampled radial gradient-echo acquisitions and phase-sensitive image reconstructions by regularized non-linear inversion. Dynamic alterations of flow parameters were obtained for 19 subjects at 40-ms temporal resolution, 1.33-mm in-plane resolution and 6-mm section thickness. Real-time measurements were performed during normal breathing (10 s), increased intrathoracic pressure (10 s) and recovery (20 s). RESULTS: Real-time measurements were technically successful in all volunteers. During the Valsalva manoeuvre (late strain) and relative to values during normal breathing, the mean peak flow velocity and flow volume decreased significantly in both vessels (p < 0.001) followed by a return to normal parameters within the first 10 s of recovery in the AA. By contrast, flow in the SVC presented with a brief (1-2 heartbeats) but strong overshoot of both the peak velocity and blood volume immediately after pressure release followed by rapid normalization. CONCLUSION: Real-time phase-contrast flow MRI may assess cardiac haemodynamics non-invasively, in multiple vessels, across the entire luminal area and at high temporal and spatial resolution. ADVANCES IN KNOWLEDGE: Future clinical applications of this technique promise new insights into haemodynamic alterations associated with pre-clinical congestive heart failure or diastolic dysfunction, especially in cases where echocardiography is technically compromised.

Gender differnces in symptoms and course of schizophrenia.

This paper deals with gender differences in symptom pattern, course and (Usability in a cohort of 76 patients who were completely and prospectively followed up for a period often years. Both at inclusion and follow up, males had more of nuclear syndrome, but largely the differences were not statistically significant. Disability was more in the males, especially in the area of occupational functioning. The paper discusses gender based research in the Indian context.

A cephalometric comparative study of the soft tissue airway dimensions in persons with hyperdivergent and normodivergent facial patterns.

PURPOSE: This study was performed to compare the dimensions of the nasopharynx, oropharnynx, and hypopharynx of persons with hyperdivergent and normodivergent facial types, and to determine whether any variations exist. PATIENTS AND METHODS: Lateral cephalometric records of a population with a normodivergent facial pattern (n = 23) and a group with a hyperdivergent facial pattern (n = 27) as evidenced by increased mandibular plane angle were used to compare the soft tissue airway dimensions. Statistical analysis consisted of Student's t-tests, Wilcoxon rank sums, and chi2. Statistical significance was set .05. RESULTS: Overall the hyperdivergent group had a narrower anteroposterior pharyngeal dimension than the normodivergent control group. This narrowing was specifically noted in the nasopharynx at the level of the hard palate and in the oropharynx at the level of the tip of the soft palate and the mandible. In addition, the posterior pharyngeal wall had a thinning at the level of the inferior border of the third cervical vertebrae, and there was a more obtuse palatal angle. The tongue was also positioned more inferiorly and posteriorly in the hyperdivergent group, as evidenced by the increased distance between the hyoid bone and the mandibular plane and the increased distance between the soft palate tip and the epiglottis. The hyperdivergent group had more retruded maxillary and mandibular apical bases and a higher Class II skeletal discrepancy. CONCLUSIONS: The narrower anteroposterior dimension of the airway in hyperdivergent patients may be attributable to skeletal features common to such patients, that is, retrusion of the maxilla and the mandible and vertical maxillary excess. Other features, such as an obtuse soft palate and low-set hyoid, also may be contributory factors. The relatively thin posterior pharyngeal wall observed in hyperdivergent patients might be a compensatory mechanism.