Use of Gonadotropin-Releasing Hormone Analogs in Children: Update by an International Consortium.

This update, written by authors designated by multiple pediatric endocrinology societies (see List of Participating Societies) from around the globe, concisely addresses topics related to changes in GnRHa usage in children and adolescents over the last decade. Topics related to the use of GnRHa in precocious puberty include diagnostic criteria, globally available formulations, considerations of benefit of treatment, monitoring of therapy, adverse events, and long-term outcome data. Additional sections review use in transgender individuals and other pediatric endocrine related conditions. Although there have been many significant changes in GnRHa usage, there is a definite paucity of evidence-based publications to support them. Therefore, this paper is explicitly not intended to evaluate what is recommended in terms of the best use of GnRHa, based on evidence and expert opinion, but rather to describe how these drugs are used, irrespective of any qualitative evaluation. Thus, this paper should be considered a narrative review on GnRHa utilization in precocious puberty and other clinical situations. These changes are reviewed not only to point out deficiencies in the literature but also to stimulate future studies and publications in this area.

Carbon isotope fractionation studies of bacterial strain Rhodococcus rhodochrous MTCC 291.

Carbon isotope fractionation associated with the aerobic consumption of propane (C3) were determined using Rhodococcus rhodochrous MTCC 291 bacterial strain to estimate the amount of hydrocarbon oxidized using GC, fractionation of delta13C carbon isotopes of propane and CO2 using GC-C-IRMS and growth of bacteria by UV-Visible Spectrophotometer. The initial delta13C isotopic value of propane was -34 per thousand and after incubation the changes of the isotopic values have been determined on 6th, 10th, 14th, and 17th days. The propane isotopic fractionation value was found to be maximum of -38.0 per thousand with an average value of -36.5 per thousand and a standard deviation of -1.22 per thousand. The initial delta13C isotopic value of CO2 was -19.601 per thousand. The CO2 isotopic fractionation value was found to be maximum of -29.153 per thousand with an average value of -26.859 per thousand and a standard deviation of -28.338 per thousand. The consumption of propane gas was estimated using Gas Chromatograph. The initial concentration of propane in control was found to be 53 ppm. On incubation, the consumption of the propane gas was observed to be of 26 ppm. The carbon isotope fractionation presented here may be applied to estimate the extent of C1-C4 oxidation in natural gas samples, and should prove useful in further studying the microbial oxidation of these compounds in the natural environment.

Characterization of light gaseous hydrocarbons of the surface soils of Krishna-Godavari basin, India.

Several techniques are used for the exploration of hydrocarbons, of which; the geochemical techniques involving the microbiological technique use the principle of detecting the light hydrocarbon seepage activities for indication of sub-surface petroleum accumulations. Asurvey was carried out to characterize the light gaseous hydrocarbons seeping in oil and gas fields of Krishna-Godavari basin ofAndhra Pradesh. Aset of 50 sub-soil samples were collected at depths of about 3 m for geochemical analyses and 1m for microbiological analysis. The microbial prospecting studies showed the presence of high bacterial population for methane 2.5 x 10(2) to 6.0 x 10(6) cfu g(-1), propane 1x10(2) to 8.0 x 10(6) cfu g(-1) in soil samples. The adsorbed soil gas analysis showed the presence of moderate to low concentrations of methane (26 to 139 ppb), ethane (0 to 17 ppb), propane (0 to 8 ppb), butane (0 to 5 ppb) and pentane (0 to 2 ppb) in the soil samples of the study area. Carbon isotope analysis for methane ('13C1) ranging from -36.6 to -22.7 per hundred Pee Dee Belemnite (PDB) suggests these gases are of thermogenic origin. Geo-microbial prospecting method coupled with adsorbed soil gas and carbon isotope ratio analysis have thus shown good correlation with existing oil/gas fields of Krishna-Godavari basin.

Assessment of drinking water quality using ICP-MS and microbiological methods in the Bholakpur area, Hyderabad, India.

A total of 16 people died and over 500 people were hospitalized due to diarrhoeal illness in the Bholakpur area of Hyderabad, India on 6th May 2009. A study was conducted with immediate effect to evaluate the quality of municipal tap water of the Bholakpur locality. The study consists of the determination of physico-chemical properties, trace metals, heavy metals, rare earth elements and microbiological quality of drinking water. The data showed the variation of the investigated parameters in samples as follows: pH 7.14 to 8.72, EC 455 to 769 µS/cm, TDS 303.51 to 515.23 ppm and DO 1.01 to 6.83 mg/L which are within WHO guidelines for drinking water quality. The water samples were analyzed for 27 elements (Li, Be, B, Na, Mg, Al, Si, K, Ca, V, Cr, Mn, Fe, Ni, Co, Cu, Zn, As, Se, Rb, Sr, Mo, Ag, Cd, Sb, Ba and Pb) using inductively coupled plasma-mass spectrometry (ICP-MS). The concentrations of Fe (0.12 to 1.13 mg/L), Pb (0.01 to 0.07 mg/L), Cu (0.01 to 0.19 mg/L), Ni (0.01 to 0.15 mg/L), Al (0.16 to 0.49 mg/L), and Na (38.36 to 68.69 mg/L) were obtained, which exceed the permissible limits of the World Health Organization (WHO) for drinking water quality guidelines. The remaining elements were within the permissible limits. The microbiological quality of water was tested using standard plate count, membrane filtration technique, thermotolerant coliform (TTC), and most probable number (MPN) methods. The total heterotrophic bacteria ranged from 1.0 × 10(5) to 18 × 10(7 )cfu/ml. Total viable bacteria in all the water samples were found to be too numerable to count and total number of coliform bacteria in all water samples were found to be of order of 1,100 to >2,400 MPN index/100 ml. TTC tested positive for coliform bacteria at 44.2°C. All the water samples of the study area exceeded the permissible counts of WHO and that (zero and minimal counts) of the control site (National Geophysical Research Institute) water samples. Excessively high colony numbers indicate that the water is highly contaminated with microorganisms and is hazardous for drinking purposes. Bacteriological pollution of drinking water supplies caused diarrhoeal illness in Bholakpur, which is due to the infiltration of contaminated water (sewage) through cross connection, leakage points, and back siphoning.

Evaluation of potable groundwater quality in some villages of Adilabad in Andhra Pradesh, India.

Reconnaissance hydrochemical survey was conducted in some villages of Adilabad district, Andhra Pradesh to assess the quality of groundwater, which is mainly used for drinking purpose. The study consists of the determination of physico-chemical properties, trace metals, heavy metals and rare earth elements in water samples. The data showed the variation of the investigated parameters in samples as follows: pH 6.92 to 8.32, EC 192 to 2706 microS cm(-1), TDS 129.18 to 1813.02 ppm. The pH of the waters was within the permissible limits whereas EC and TDS were above the permissible limits of World Health Organization (WHO). Total 27 elements (Li, Be, B, Na, Mg, Al, Si, K, Ca, V, Cr, Mn, Fe, Ni, Co, Cu, Zn, As, Se, Rb, Sr, Mo, Ag, Cd, Sb, Ba and Pb) were analyzed using Inductively Coupled Plasma-Mass Spectrometer (ICP-MS). The concentration of elements in water samples ranged between 0.063 to 0.611 mg l(-1) for B, 11.273 to 392 mg l(-)1 for Na, 5.871 to 77.475 mg l(-1) for Mg, 0.035 to 1.905 mg l(-1) for Al, 0.752 to 227.893 mg l(-1) for K, 11.556 to 121.655 mg l(-1) for Ca and 0.076 to 0.669 mg l(-1) for Fe respectively. The concentrations of Na, Mg, Al, K, Ca, and Fe exceeded the permissible limits of WHO and BIS guidelines for drinking water quality. In the present study, Bhimavaram, Kazipalli, Kannepalli and Chennur areas of the Adilabad are especially prone to geogenic contamination. Overall water quality was found unsatisfactory for drinking purposes.

The need for better data about counterfeit drugs in developing countries: a proposed standard research methodology tested in Chennai, India.

WHAT IS KNOWN AND OBJECTIVE: There is still surprisingly little basic research data to support widely repeated claims about the prevalence of drug counterfeiting. To meet the need for more reliable drug quality data, we designed a study framework that includes clear definitions of measured end points, sampling methods and assay technique. Our objective was to test this research design in Chennai (formerly Madras), India, using a joint Indian and Canadian team. METHODS: The city was divided into ten areas along municipal lines. From each area, ten stores and pharmacies selling drugs were selected. At each of these 100 outlets, three study drugs (artesunate, ciprofloxacin and rifampicin) were purchased. The 300 samples were tested by Liquid Chromatography-Mass Spectrometry. Assay content was expressed as a percentage of stated tablet content. Based on assay results and their distribution, we developed drug quality definitions for normal manufacturing standards, counterfeiting, decomposition, poor quality control and adulteration. RESULTS: The group mean for ciprofloxacin was close to normal manufacturing limits (99·2 ± 7·1%) but rifampicin (91·6 ± 5·7%), and artesunate (80·1 ± 9·1%), were both below normal pharmaceutical standards. Overall, 43% of all samples fell below the widely accepted manufacturing range of 90-110% of stated content. No tablet from any sample contained less than 50% of the stated dose. WHAT IS NEW AND CONCLUSION: The quality of at least some anti-infective drugs in Chennai is below commonly accepted standards but we found no evidence of criminal counterfeiting. Poor drug quality was most likely due to decomposition during storage or poor manufacturing standards. Our research methodology worked well under practical conditions and should hopefully be of value to others working in this area.

Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Women with a sonographic short cervix in the mid-trimester are at increased risk for preterm delivery. This study was undertaken to determine the efficacy and safety of using micronized vaginal progesterone gel to reduce the risk of preterm birth and associated neonatal complications in women with a sonographic short cervix. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled asymptomatic women with a singleton pregnancy and a sonographic short cervix (10-20 mm) at 19 + 0 to 23 + 6 weeks of gestation. Women were allocated randomly to receive vaginal progesterone gel or placebo daily starting from 20 to 23 + 6 weeks until 36 + 6 weeks, rupture of membranes or delivery, whichever occurred first. Randomization sequence was stratified by center and history of a previous preterm birth. The primary endpoint was preterm birth before 33 weeks of gestation. Analysis was by intention to treat. RESULTS: Of 465 women randomized, seven were lost to follow-up and 458 (vaginal progesterone gel, n=235; placebo, n=223) were included in the analysis. Women allocated to receive vaginal progesterone had a lower rate of preterm birth before 33 weeks than did those allocated to placebo (8.9% (n=21) vs 16.1% (n=36); relative risk (RR), 0.55; 95% CI, 0.33-0.92; P=0.02). The effect remained significant after adjustment for covariables (adjusted RR, 0.52; 95% CI, 0.31-0.91; P=0.02). Vaginal progesterone was also associated with a significant reduction in the rate of preterm birth before 28 weeks (5.1% vs 10.3%; RR, 0.50; 95% CI, 0.25-0.97; P=0.04) and 35 weeks (14.5% vs 23.3%; RR, 0.62; 95% CI, 0.42-0.92; P=0.02), respiratory distress syndrome (3.0% vs 7.6%; RR, 0.39; 95% CI, 0.17-0.92; P=0.03), any neonatal morbidity or mortality event (7.7% vs 13.5%; RR, 0.57; 95% CI, 0.33-0.99; P=0.04) and birth weight < 1500 g (6.4% (15/234) vs 13.6% (30/220); RR, 0.47; 95% CI, 0.26-0.85; P=0.01). There were no differences in the incidence of treatment-related adverse events between the groups. CONCLUSIONS: The administration of vaginal progesterone gel to women with a sonographic short cervix in the mid-trimester is associated with a 45% reduction in the rate of preterm birth before 33 weeks of gestation and with improved neonatal outcome.

Anaesthetic management of a child with "cor-triatriatum" and multiple ventricular septal defects - A rare congenital anomaly.

Cor-triatriatum is a rare congenital cardiac anomaly. It accounts for 0.1% of congenital heart diseases. Its association with multiple ventricular septal defects (VSD) is even rarer. A five-month-old baby was admitted with respiratory distress and failure to thrive. Clinical examination revealed diastolic murmur over mitral area. Chest X-ray showed cardiomegaly. Haematological and biochemical investigations were within normal limits. Electrocardiogram showed left atrial enlargement. 2D echo showed double-chambered left atrium (cor-triatriatum), atrial septal defect (ASD) and muscular VSD with moderate pulmonary arterial hypertension. The child was treated with 100% oxygen, diuretics and digoxin and was stabilized medically. We used balanced anaesthetic technique using oxygen, air, isoflurane, fentanyl, midazolam and vecuronium. Patient was operated under cardiopulmonary bypass (CPB) with moderate hypothermia. Through right atriotomy abnormal membrane in the left atrium was excised to make one chamber. VSD were closed with Dacron patches and ASD was closed with autologous pericardial patch. Patient tolerated the whole procedure well and was ventilated electively for 12h in the intensive care unit. He was discharged on the 10(th) postoperative day.

Latent tuberculosis infection: risks to health care students at a hospital in Lima, Peru.

SETTING: University hospital and university campus in Lima, Peru. OBJECTIVE: To demonstrate the risk of latent tuberculosis infection (LTBI) in the hospital relative to the community. DESIGN: Prospective cohort study of university students measuring prevalence, boosting, and conversion of tuberculin skin tests (TSTs) among health care students (HCS) and non-health care students (NHCS). RESULTS: Among the HCS relative to NHCS, prevalence of initial positive TST was 20.9% vs. 12.2% (P < 0.001), and conversion rate was 1.1% vs. 0% (P = 0.423) at the 10 mm cut-off and 11.8% vs. 0% at the 6 mm cut-off (P = 0.00005). Multivariate analysis showed that the HCS group had a higher risk of baseline positive TST compared with the NHCS group after controlling for confounding factors (OR 1.7, 95% CI 1.1-2.6). CONCLUSION: HCS are at greater risk than NHCS for having positive baseline TSTs and for TST conversion at the 6 mm cut-off. We conclude that the hospital we studied in Lima, Peru, poses a greater risk than the surrounding community for tuberculosis infection, and greater attention to hospital infection control measures is warranted. A higher rate of skin test boosting among the HCS cohort suggests the possibility of transient, non-progressive LTBI, which merits further study.

Fetal death after normal biophysical profile score: An eighteen-year experience.

OBJECTIVE: It was our goal to determine the false-negative rate of the biophysical profile, characterize an 18-year variation in the false-negative rate, examine the relationship between the last normal biophysical profile score and death, and compare the false-negative rate of 2 disparate populations. STUDY DESIGN: Biophysical profile scores of 86,955 patients at 2 medical centers were collected and recorded prospectively. All perinatal deaths occurring within 1 week of a normal score were similarly recorded. The annual false-negative rate, the cumulative false-negative rate, and the ratio of false-negative results in cases of subsequent fetal death to the perinatal mortality rate were calculated. RESULTS: There were 65 fetal deaths among 86,955 fetuses. Over an 18-year study period at one institution, the false-negative rate varied but not significantly. The cumulative false-negative rate was 0.708 per 1000 at one medical center studied and 2.289 per 1000 at the other center. The average interval between last normal score and fetal death was 3.62 days and did not vary significantly between the medical centers. CONCLUSIONS: False-negative results in cases of subsequent fetal death reflect events that are subsequent to the last normal test result. Fetomaternal hemorrhage was the single most identifiable fetal cause of false-negative results in cases of subsequent fetal death. The ratio of the false-negative rate in cases of subsequent fetal death to the perinatal mortality rate should be used as a more objective approach to reporting this value, because the false-negative rate likely reflects the underlying perinatal mortality.

Acute oligohydramnios and deteriorating fetal biophysical profile associated with severe preeclampsia.

Acute changes in fetal biophysical profile (BPP) status usually include rapid cessation of all nonessential acute biophysical activities, yet not necessarily an acute decrease in the amniotic fluid volume, or oligohydramnios. A 36-year-old para 3 with early third-trimester severe preeclampsia, mild placental abruption, and fetal growth restriction, with a reassuring BPP of 8/8, was managed expectantly with intravenous magnesium sulfate, hydralazine, and intramuscular corticosteroids. Within 20 h of admission a marked change in the BPP was noted, with a score of 0/8. Amniotic fluid index (AFI), which on admission had been 20.1, progressively became 0, despite a stable normovolemic maternal status. At immediate cesarean, a mildly acidotic and hypoxic fetus was delivered which subsequently did well. This case supports the concept that acute oligohydramnios may develop rapidly in the presence of acute fetal hypoxemia.

Extensive spontaneous retroperitoneal hemorrhage: an unusual complication of heparin anticoagulation during pregnancy.

A 27-year-old patient at 13 weeks' gestation maintained on subcutaneous heparinization due to hemoglobin S and hemoglobin C (SC) sickle cell disease and previous splenic vein thrombosis presented with spontaneous acute onset of severe left lower abdominal and groin pain. The pain, which radiated to the anterior aspect of the thigh, was associated with nausea and vomiting and was exacerbated by extension of the left lower extremity. The patient was hemodynamically stable, yet during the first 24 h of hospitalization a marked decrease in hematocrit from 29% to 22% occurred. Contrast computed tomography (CT) revealed an extensive abdominal-pelvic, retroperitoneal hematoma extending approximately 15 cm in length from above L5 cephalad to below the greater trochanter of the left femur caudally. The retroperitoneal hemorrhage self-tamponaded and did not require surgical management. The dosage of heparin was decreased and maintained with appropriate activated partial prothrombin (aPTT) levels. To our knowledge, this is the first report of a spontaneous retroperitoneal hemorrhage complicating heparin anticoagulation in pregnancy. Unusual hemorrhagic complications of anticoagulation therapy are discussed.

Cytokine secretion by deltagamma and alphabeta T cells in monophasic experimental autoimmune encephalomyelitis.

Mononuclear cells were isolated from the central nervous system (CNS), lymph nodes (LN), spleen and blood, over the course of murine monophasic experimental autoimmune encephalomyelitis (EAE). Individual cytokine secreting T cells were enumerated. IL-2-secreting alphabeta T cells were numerous at all sites at disease onset. By disease peak their numbers had fallen profoundly; they remained low thereafter. IL-2 secreting gammadelta T cells were rare throughout. IFN-gamma-secreting cells were plentiful at all sites at disease onset. gammadelta T cells comprised 7% of total and 20% of IFN-gamma-secreting CNS-derived cells at disease onset; values at disease peak were 12 and 40% respectively. IL-4-secreting alphabeta T cells were rare in the CNS and LN throughout and did not increase in the spleen from baseline values. In contrast, splenic IL-4-secreting gammadelta T cells had increased to four-fold baseline values at disease onset and seven-fold at disease peak. Recovery from EAE is associated with a global inhibition of IL-2-secreting alphabeta T cells and to a lesser extent with IFN-gamma-secreting alphabeta and gammadelta T cells, whereas IL-4-secreting gammadelta T cells increase in the spleen as disease evolves.

All-trans retinoic acid potentiates the ability of interferon beta-1b to augment suppressor cell function in multiple sclerosis.

OBJECTIVE: To determine the effects of combination all-trans retinoic acid (RA) and interferon beta-1b therapy on immune system functions potentially relevant to multiple sclerosis (MS). DESIGN: Interferon gamma-secreting cells, T suppressor cell function, and lymphocyte proliferative responses were assayed using peripheral blood mononuclear cells from patients with MS and control subjects under control conditions and in the presence of interferon beta-1b, RA, and the 2 combined. SETTING: A university hospital MS clinic. PARTICIPANTS: Seventeen patients with secondarily progressive MS and 25 control subjects. RESULTS: Interferon beta-1b use increased interferon gamma-secreting cell counts, augmented T suppressor cell function, and inhibited T-cell proliferation. Therapy with RA decreased interferon gamma-secreting cell counts, had a minimal positive effect on T suppressor cell function, and had no effect on T-cell proliferation. When RA and interferon beta-1b were combined, the inhibitory effect of RA on interferon gamma-secreting cells predominated, T suppressor cell function increased synergistically over the increment observed with interferon beta-1b use alone, and the inhibitory effect of interferon beta-1b alone on T-cell proliferation remained unchanged. CONCLUSIONS: Treatment with interferon beta-1b partially restores defective T suppressor cell function in patients with MS. This potentially beneficial action is synergistically potentiated by RA. Interferon beta-1b increases the number of interferon gamma-secreting cells in the circulation when treatment is initiated. A similar increment in interferon gamma-secreting cells is observed when interferon beta-1b is added to cultural peripheral blood mononuclear cells in vitro. This potentially deleterious action of interferon beta-1b is reversed by RA. Interferon beta-1b inhibits lymphocyte proliferation modestly but reproducibly. This action of interferon beta-1b is unaltered by RA. These data provide a rationale for a trial of combination treatment with interferon beta-1b and RA in patients with MS.

Role of interferons in demyelinating diseases.

IFN beta-1b reduces the frequency of major multiple sclerosis attacks by 50 percent. Serial MRI scanning over the course of the clinical trial that led to approval of the agent revealed a significant lessening both in disease activity and in accumulating burden of disease in IFN beta-1b-treated patients compared to placebo-treated controls. The mechanism by which IFN beta-1b exerts its beneficial effect in multiple sclerosis is unknown. T suppressor cell function fails during MS attacks and is persistently subnormal in multiple sclerosis patients with progressive disease. IFN beta-1b partially restores suppressor function in multiple sclerosis patients. IFN beta-1b also inhibits release of lymphotoxin, tumor necrosis factor, and interferon gamma, at least in vitro. All three cytokines are toxic to oligodendrocytes. In contrast; production of transforming growth factor beta-1 (TGF beta 1) is increased by IFN beta-1b. TGF beta 1 is an immunosuppressive cytokine. All of the above listed actions of IFN beta-1b could contribute to its beneficial effect. Perhaps all do.

Earth-Based Observations of the Galileo Probe Entry Site

Earth-based observations of Jupiter indicate that the Galileo probe probably entered Jupiter's atmosphere just inside a region that has less cloud cover and drier conditions than more than 99 percent of the rest of the planet. The visual appearance of the clouds at the site was generally dark at longer wavelengths. The tropospheric and stratospheric temperature fields have a strong longitudinal wave structure that is expected to manifest itself in the vertical temperature profile.

Interferon-gamma-secreting cells in multiple sclerosis patients treated with interferon beta-1b.

Fifteen percent of multiple sclerosis patients about to be treated with interferon beta-1b exhibited elevated numbers of circulating interferon-gamma-secreting cells, defined as a value that exceeded the mean value for healthy controls by more than two standard deviations. Sixty percent of patients receiving the drug exhibited elevated interferon-gamma-secreting cell numbers during their first 2 months of treatment. Values normalized after 3 months. Prednisone treatment during the first month on the drug prevented the interferon-gamma-secreting cell surge.

Use of levamisole in maintaining remission in steroid-sensitive nephrotic syndrome in children.

A randomized, controlled trial was conducted in a pediatric unit in a teaching hospital in India to assess the efficacy of levamisole in maintaining remission in children with steroid-sensitive nephrotic syndrome. Sixty-one children with steroid-sensitive nephrotic syndrome, who had achieved remission with corticosteroids, were allocated to a treatment group (33 patients) receiving levamisole (2-3 mg/kg/day) twice a week for 12 months or to a control group (28 patients) receiving no treatment. The main outcome measure was duration of remission. Thirty months later, in the levamisole group, 21 of 33 patients were in remission as against 12 of 28 patients in the control group (chi 2 = 2.54, p = 0.11, NS). The median duration of remission maintenance was 12 months in the levamisole group as compared with 10.5 months in the control group. On survival analysis, the difference in duration of remission maintenance between the two groups was not significant (p = 0.10), though there was a trend in favor of the treatment group. On stratified survival analysis, multiple relapsers in the levamisole group had longer remission maintenance than the control group though this did not reach statistical significance (p = 0.08). The clinically significant trend towards increased duration of remission maintenance in steroid-sensitive nephrotic syndrome observed with levamisole therapy, especially in patients with multiple relapses, may require a larger study with a longer follow-up for definitive confirmation.