Adrenomedullin and Its Possible Role in Improved Survival in Female Patients with Sepsis: A Study in the South East Asian Region.

AIMS AND OBJECTIVES: Serum adrenomedullin (ADM) as a prognostic biomarker to study the gender-related differences in mortality pattern and its correlation with the sequential organ failure assessment (SOFA) and acute physiologic assessment and chronic health evaluation II (APACHE II) scores in patients of sepsis. MEASUREMENTS AND MAIN RESULTS: Eighty patients of sepsis of which 36 were males and 44 were females, were taken in the study as per sepsis III guidelines. They were followed up for a period of 28 days. Serum ADM was measured on day 1 and day 5. The endpoint was mortality or survival at day 28 after admission. The death rate among males was higher, with 23 of the total 36 (63.89%) patients having died when compared with females in which 25 patients out of 44 (56.82%) had died. The observed mortality rates correlated well with average APACHE II scores. The average APACHE II score was slightly higher in males (29 ± 8.97) when compared with females (27.02 ± 8.69). Similarly, day 1 SOFA and mean SOFA values were higher in males (10.22 ± 5.36) and (10.73 ± 6.01) when compared with females (8.27 ± 4.79) and (8.89 ± 5.6), respectively. Males despite having higher mortality rates, higher APACHE II, SOFA, and mean SOFA values were still having less mean levels of serum ADM (454.40 ± 81.13 pg/mL) when compared with females (479.62 ± 126.97 pg/mL). CONCLUSION: Adrenomedullin is a protective neurohormone with antibacterial and anti-inflammatory properties. It is elevated in all patients with sepsis but the rise is more so in the female when compared with males. Higher ADM levels in females may suggest the protective effect of ADM as a part of the general protective neurohormonal stress response, which may explain the low death rate in females in sepsis. HOW TO CITE THIS ARTICLE: Daga MK, Kumar L, Mawari G, Kumar N, Singh S, Mishra TK. Adrenomedullin and Its Possible Role in Improved Survival in Female Patients with Sepsis: A Study in the South East Asian Region. Indian J Crit Care Med 2020;24(12):1180-1184.

Children with isolated hypospadias have different hormonal profile compared to those with associated anomalies.

AIM: The objective of this study is to compare the hormonal profile of children with isolated hypospadias to controls and hypospadiacs with associated anomalies. STUDY DESIGN: Prospective observation at a tertiary referral hospital. STUDY SUBJECTS: One hundred consecutive children (0-12 years) with isolated hypospadias (H), 23 with hypospadias and associated anomalies (HO). CONTROLS: One hundred children (0-12 years) without any genitourinary/endocrine abnormalities (C). PROCEDURE: Prehuman chorionic gonadotropin (HCG) and post-HCG fasting blood samples were drawn for estimation of serum gonadotropins, dehydroepiandrosterone sulfate (DHEA-S), estrogen (E), progesterone (P), and testosterone (T) and dihydrotestosterone (DHT). STATISTICAL ANALYSIS: Differences in hormonal levels between controls and subjects were computed with p < or = 0.05 as significant. RESULTS: Compared with controls, "H" had significantly higher follicular stimulating hormone (FSH) (1.37 vs. 1.29 mIU/mL p=0.01), lower estrogen (8.08 vs. 13.78 pg/mL, p=0.00), and lower DHEA-S (27.34 vs. 40.24 microg/dL, p=0.03) levels; HO had higher FSH, lower basal T (0.13 vs. 0.46 ng/mL, p=0.01), and lower peak testosterone (1.53 vs. 2.32 ng/mL, p=0.01). "HO" had lower androgens (basal T, 0.13 vs. 0.29 ng/mL, p=0.03; peak T, 1.53 vs. 2.36 ng/mL, p=0.01), and higher estrogen (12.56 vs. 8.08 pg/mL, p=0.001) and progesterone (0.46 vs. 0.31 ng/mL, p=0.04) levels in comparison with H. CONCLUSION: Consistently lower output of androgens among HO explains the association of other anomalies (generally undescended testes) in them. High FSH among hypospadiacs hints at the possibility of Sertoli cell dysfunction and may have long-lasting sequelae for reproductive functions during adulthood. However, Leydig cell functions are affected more among HO.

Pyrazinamide blood concentrations in children suffering from tuberculosis: a comparative study at two doses.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Pyrazinamide is recommended in doses varying from 15 to 40 mg kg(-1). The most commonly used average daily dose is 25 mg kg(-1). Its use is associated with dose dependent hepatotoxicity. Lower doses are not used because of lack of pharmacokinetic data especially in children. There is only one detailed study of pyrazinamide in children at a dose of 35 mg kg(-1). WHAT THIS STUDY ADDS: This is the first study evaluating serum concentrations of pyrazinamide in children at a dose of 15 mg kg(-1) which is on the lower side of the recommended dose. The study also compared the serum concentrations and pharmacokinetics achieved with this dose with the widely used dose of 25 mg kg(-1) in children suffering from tuberculosis. The pharmacokinetics and pharmacodynamic indices of pyrazinamide were comparable with the 25 and 15 mg kg(-1) doses. AIMS: To evaluate the pharmacokinetics and pharmacodynamic indices of pyrazinamide at doses of 15 and 25 mg kg(-1) in children suffering from tuberculosis. METHODS: Twenty children with tuberculosis received pyrazinamide at a single dose of 25 mg kg(-1) (group I) and 15 mg kg(-1) (group II). Serial blood samples were collected and the drug concentrations were analyzed spectrophotometrically. The pharmacokinetic parameters were calculated and the duration of time for which pyrazinamide concentrations in serum remained above the pyrazinamide inhibitory concentrations of 20 microg ml(-1) and 25 microg ml(-1) was studied. RESULTS: The mean peak serum concentration was 42.4 +/- 3.3 microg ml(-1) (95% CI +/- 6.5) and 38.6 +/- 3.9 microg ml(-1) (95% CI +/- 7.7) in groups I and II, respectively. The elimination half-life was 9.3 +/- 1.3 h and 10.5 +/- 2.3 h (P = 0.6) and clearance was 0.06 +/- 0.01 l h(-1) kg(-1) and 0.04 +/- 0.01 l h(-1) kg(-1) (P = 0.08) in groups I and II, respectively. Pharmacokinetic parameters and PKPD indices were comparable with both the doses. CONCLUSIONS: The study indicates that comparable serum concentrations of pyrazinamide are attained with 25 mg kg(-1) and 15 mg kg(-1) doses in children. The elimination half-life was longer and volume of distribution greater in children than in the adult population.

Interaction of low-frequency axisymmetric ultrasonic guided waves with bends in pipes of arbitrary bend angle and general bend radius.

The use of ultrasonic guided waves for the inspection of pipes with elbow and U-type bends has received much attention in recent years, but studies for more general bend angles which may also occur commonly, for example in cross-country pipes, are limited. Here, we address this topic considering a general bend angle φ, a more general mean bend radius R in terms of the wavelength of the mode studied and pipe thickness b. We use 3D Finite Element (FE) simulation to understand the propagation of fundamental axisymmetric L(0,2) mode across bends of different angles φ. The effect of the ratio of the mean bend radius to the wavelength of the mode studied, on the transmission and reflection of incident wave is also considered. The studies show that as the bend angle is reduced, a progressively larger extent of mode-conversion affects the transmission and velocity characteristics of the L(0,2) mode. However the overall message on the potential of guided waves for inspection and monitoring of bent pipes remains positive, as bends seem to impact mode transmission only to the extent of 20% even at low bend angles. The conclusions seem to be valid for different typical pipe thicknesses b and bend radii. The modeling approach is validated by experiments and discussed in light of physics of guided waves.

Hormonal profile in children with isolated hypospadias associates better with comprehensive score of local anatomical factors as compared to meatal location or degree of chordee.

BACKGROUND: To evaluate if hormonal profile of children with isolated hypospadias (IH) associates better with comprehensive local anatomical factor score (LAFS) than with clinically adjudged urethral meatus location or severity of chordee/k.j. MATERIAL AND METHODS: Ninety-nine children with IH were enrolled, as per inclusion criteria. Meatal location was recorded at first clinical examination in OPD; while LAFS was computed per-operatively using indigenously devised scale, except for neonates. Hypospadiacs were first classified into three standard meatal based groups and subsequently into LAFS based two groups (≤19, >19). For all participants, pre HCG and post HCG (96 hour post- injection) estimation of serum gonadotropins, DHEA-S, estrogen (E), progesterone (P), testosterone (T) and Dihydrotestosterone (DHT) was done. Statistical tests were applied to assess significance of hormonal levels with respect to meatal location, chordee and LAFS. RESULTS: Only FSH levels differed significantly among meatal based groups; while among LAFS groups, multiple hormonal differences were noted; with poor LAFS associated significantly with higher FSH, LH and lower E, T/DHT. Children with severe degree of chordee had poorer T output and a significantly lower LAFS as compared to those with moderate/mild chordee. CONCLUSION: Serotoli cell dysfunction, indirectly indicated by high FSH was found among midpenile hypospadiacs and those with poorer LAFS. Since groups based on LAFS revealed multiple intergroup hormonal differences than what was seen for meatal/chordee based groups; LAFS should be considered a better guide for prognostication and for deciding about hormonal supplementation. Lower androgenic output was particularly noted in children with severe chordee.

Breast cancer: interaction between oxidant-antioxidant dynamics and inflammation in Indian females.

OBJECTIVES: Oxidative stress and pro-inflammatory mediators have been implicated in breast carcinogenesis. We attempted to evaluate the markers of oxidative stress, antioxidant mechanism and the inflammatory pathway in patients with breast cancer. METHODS: This study was carried out in departments of Biochemistry and Surgery, Maulana Azad Medical College and associated Hospitals, New Delhi, India. A total of 60 cases of carcinoma of the breast and 60 healthy controls were included in the study. The parameters that were assayed include markers of oxidative stress-conjugated dienes, thiobarbitone reactive substances (TBARS), antioxidants-superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH) and markers of inflammation-interleukin-6(IL-6) and ferritin. RESULTS: There was a significant decline in the antioxidant levels and a significant rise in oxidant levels in patients with carcinoma of the breast, compared to controls. The inflammatory markers-IL-6 and ferritin-were also significantly higher in patients with breast cancer. A significantly positive correlation was observed between the IL-6 levels and conjugated dienes with the stage of breast carcinoma; whilst a significantly negative correlation was observed between the levels of conjugated dienes and superoxide dismutase and superoxide dismutase levels with the disease staging. CONCLUSIONS: This study underlines the interplay between inflammatory pathways and oxidative stress in the pathogenesis of breast cancer. MINI ABSTRACT: An intense research is underway to identify the possible risk factors and the molecular mechanisms involved in pathogenesis of breast cancer. Inflammation and oxidative stress are two such etiologies investigated in our study.