MRI biomarker of muscle composition is associated with severity of pelvic organ prolapse.

BACKGROUND: The pathophysiology of pelvic organ prolapse is largely unknown. We hypothesized that reduced muscle mass on magnetic resonance defecography (MRD) is associated with increased pelvic floor laxity. The aim of this study was to compare the psoas and puborectalis muscle mass composition and cross-sectional area among patients with or without pelvic laxity. METHODS: An observational retrospective study was conducted on women > age 18 years old who had undergone MRD for pelvic floor complaints from January 2020 to December 2020 at Stanford Pelvic Health Center. Pelvic floor laxity, pelvic organ descent, and rectal prolapse were characterized by standard measurements on MRD and compared to the psoas (L4 level) and puborectalis muscle index (cross-sectional area adjusted by height) and relative fat fraction, quantified by utilizing a 2-point Dixon technique. Regression analysis was used to quantify the association between muscle characteristics and pelvic organ measurements. RESULTS: The psoas fat fraction was significantly elevated in patients with abnormally increased resting and strain H and M lines (p < 0.05) and increased with rising grades of Oxford rectal prolapse (p = 0.0001), uterovaginal descent (p = 0.001) and bladder descent (p = 0.0005). In multivariate regression analysis, adjusted for age and body mass index, the psoas fat fraction (not muscle index) was an independent risk factor for abnormal strain H and M line; odds ratio (95% confidence interval) of 17.8 (2-155.4) and 18.5 (1.3-258.3) respectively, and rising Oxford grade of rectal prolapse 153.9 (4.4-5383) and bladder descent 12.4 (1.5-106). Puborectalis fat fraction was increased by rising grades of Oxford rectal prolapse (p = 0.0002). CONCLUSIONS: Severity of pelvic organ prolapse appears to be associated with increasing psoas muscle fat fraction, a biomarker for reduced skeletal muscle mass. Future prospective research is needed to determine if sarcopenia may predict postsurgical outcomes after pelvic organ prolapse repair.

Pegfilgrastim: More Cost Effective and Equally Efficacious Option as Compared to Filgrastim in Autologous Stem Cell Transplant.

Use of growth factor after high-dose chemotherapy (HDC) and autologous peripheral blood stem cell (PBSC) support is current standard in reducing days of neutropenia. This retrospective study aims to compare the efficacy of two standard growth factors, pegfilgrastim (PEG) and filgrastim (FIL) after HDC. We collected data on 195 consecutive adult patients who received an autotransplant (myeloma, lymphoma and others) between January 2004 and December 2014 at two tertiary care centres. The primary end point was the duration of neutropenia in terms of days to reach an ANC > 0.5 × 109/L. Filgrastim was given to 110 patients and PEG was given to 85 patients. Time to engraftment, defined as the time to reach an ANC of 0.5 × 109/L on 2 consecutive days after the day of auto-SCT, was 12.6 days with FIL compared with 12.1 days with PEG group (p = 0.126). When comparing the total days of severe neutropenia (WBC < 0.1 × 109/L), there were 5.5 days of severe neutropenia with FIL compared with 5.8 days with PEG group (p = 0.7). The duration of febrile neutropenia was an average of 5.3 days with FIL and 4.6 days with PEG (p = 0.029). The total number of antibiotic days was shorter for the patients who received PEG, being 11.08 days with PEG and 12.1 days with FIL (p = 0.184).The average cost savings per person in terms of number of days of hospitalization and number of days of total parental nutrition was 582 Rs (p = 0.512) and 6003 Rs (p = 0.018) respectively in favour of PEG arm. PEG is similar to FIL in hematological reconstitution, however it is more cost effective alternative after HDC and PBSC.

Engraftment Syndrome: Clinical Features and Predictive Factors in Autologous Stem Cell Transplant.

Engraftment Syndrome (ES) maybe observed in patients who undergo autologous stem cell transplant (SCT). To investigate clinical criteria for ES diagnosis and analyse the risk factors for this complication, we reviewed all auto-SCT cases (Lymphoma and Myeloma) performed during the past 9 years at two tertiary care centres. We analysed all patients with a non-infectious fever, developed within 7 days of engraftment (first day of ANC of 500 on two consecutive days) in 178 patients undergoing autologous stem cell transplant. A total of 46/178 (25.8%) patients developed non-infectious fever and one or more clinical signs of ES within 7 days of engraftment. In all, 29 (61%) fulfilled the Maiolino and 12 (26%) the Spitzer criteria. The incidence of engraftment syndrome using the Maiolino criteria in our study was 29 (15%), which compares well with Spanish study (13% using same criteria) and the original Maiolino study (20%). All patients with ES satisfactorily recovered and discharged with a median of 20 days from hospital. There was no significant difference in number of days of hospitalisation and days of antibiotics between the ES and non ES arms. All patients recovered without any morbidity and only 1 (2%) patient required readmission for fungal pneumonitis. 8 (17%) patients required ICU admission due to delay in initiation of steroids. None of the factors including number of chemotherapy cycles, conditioning regime, disease status, CD34 collection, growth factors and day of WBC engraftment except female (p = 0.064) were statistically significant (in univariate or multivariate analysis). Our study shows that engraftment syndrome is common in autologous transplant setting. Maiolino criteria to diagnose ES is more sensitive in our setting. If detected and treated early there is not much morbidity or mortality related to ES.

Low-pass genome-wide sequencing and variant inference using identity-by-descent in an isolated human population.

Whole-genome sequencing in an isolated population with few founders directly ascertains variants from the population bottleneck that may be rare elsewhere. In such populations, shared haplotypes allow imputation of variants in unsequenced samples without resorting to complex statistical methods as in studies of outbred cohorts. We focus on an isolated population cohort from the Pacific Island of Kosrae, Micronesia, where we previously collected SNP array and rich phenotype data for the majority of the population. We report identification of long regions with haplotypes co-inherited between pairs of individuals and methodology to leverage such shared genetic content for imputation. Our estimates show that sequencing as few as 40 personal genomes allows for inference in up to 60% of the 3000-person cohort at the average locus. We ascertained a pilot data set of whole-genome sequences from seven Kosraean individuals, with average 5× coverage. This assay identified 5,735,306 unique sites of which 1,212,831 were previously unknown. Additionally, these variants are unusually enriched for alleles that are rare in other populations when compared to geographic neighbors (published Korean genome SJK). We used the presence of shared haplotypes between the seven Kosraen individuals to estimate expected imputation accuracy of known and novel homozygous variants at 99.6% and 97.3%, respectively. This study presents whole-genome analysis of a homogenous isolate population with emphasis on optimal rare variant inference.

The role of glucocorticoid pulse therapy in pulmonary involvement in leptospirosis.

OBJECTIVES: This study discusses incidence and clinical profile of pulmonary involvement in leptospirosis in South Gujarat. It also tries to evaluate the effect of high dose glucocorticoid pulse therapy (GPT) on it. METHOD: A study was carried out on hundred and two patients of suspected leptospirosis, referred to Government Medical College, New Civil Hospital, Surat between June 99 to September 99. The incidence, clinical profile, and specific investigations were studied in patients having pulmonary involvement. Some of the patients were given high dose glucocorticoid pulse therapy. Their outcomes were compared with those who had not been given glucocorticoid pulse therapy. RESULTS: Out of seventy seven seropositive patients 13 (16.8%) developed pulmonary involvement. Mortality was two out of eight patients in the group that received GPT and four out of five patients in the group that did not receive GPT. Two patients who died in the steroid treated group received the drug after 12 hours of onset of dyspnea. CONCLUSIONS: High dose GPT should be given as early as possible after the onset of dyspnea to all the patients with pulmonary involvement in leptospirosis. Further studies are required to establish the GPT as a standard regimen in treatment of pulmonary involvement in leptospirosis.

Preliminary experience with use of a selective 5HT3 receptor antagonist (ondansetron) to prevent high dose chemotherapy induced emesis.

Ondansetron was used as an antiemetic along with dexamethasone during 16 cycles of highly or moderately ematogenic chemotherapy. There was major control in two cycles and complete control in the remaining 14. Side effects were minor and did not require discontinuation of the drug. This combination, therefore, appears to be safe and effective in preventing chemotherapy induced emesis.

Prevalence of microalbuminuria in diabetic subjects.

Total 193 diabetic patients were investigated to assess the prevalence of microalbuminuria. Urinary albumin excretion rate (UAER) was measured by radioimmunoassay (RIA) on 3 hours urine samples. The prevalence of microalbuminuria (UAER) > 15 micrograms/min was 41%. Microalbuminuria was commonly observed in patients having diabetes for more than 5 years. A significant correlation was found between duration of diabetes and microalbuminuria (p < 0.01). Glycemic control (fasting and postprandial blood sugar) did not show any correlation with UAER, whereas blood urea (r.39, p < 0.01), creatinine (r.26, p < 0.05) and chloride (r.24, p < 0.05) were positively correlated. A significant correlation was found between raised blood pressure and UAER (p < 0.01).

Ranitidine-induced acute interstitial nephritis with epithelial cell foot process fusion.

Although acute interstitial nephritis has been well described with the histamine H2-receptor antagonist cimetidine, we found only one previous case report of ranitidine-induced interstitial nephritis in the literature. We describe an additional patient who developed acute interstitial nephritis after taking ranitidine. Electron microscopy showed focal fusion of the epithelial cell foot processes that was not described in the previous report of ranitidine-induced interstitial nephritis.

Isolation and identification of Pseudomonas spp. from Schirmacher Oasis, Antarctica.

Ten cultures of Pseudomonas spp. were established from soil samples collected in and around a lake in Antarctica. Based on their morphology, biochemical and physiological characteristics, and moles percent G + C of their DNA, they were identified as P. fluorescens, P. putida, and P. syringae. This is the first report on the identification of Pseudomonas spp. from continental Antarctica.

The solubility of 17 beta-oestradiol in aqueous polyethylene glycol 400.

The solubility of 17 beta-oestradiol (E2) in aqueous solutions of polyethylene glycol (PEG) 400 has been measured at 35 degrees C. Up to 80% w/w PEG the solubility data conform to a log linear equation ln S = ln Sw + f sigma where S is the E2 concentration in the water/cosolvent mixture, Sw is E2 solubility in water, f is the weight fraction of PEG 400 and sigma is a parameter representing the solubilizing power of the cosolvent for the drug. Above 80% PEG the relationship becomes less convincing, with significant deviation from anticipated values. Reasons for these aberrations are discussed. It is suggested that conformational changes may be induced in the PEG by the addition of small quantities of water. Deviations noted for the melting point, viscosity and density data of PEG 400-water solutions may also confirm this suggestion.

Secretion and adenylate cyclase in thyroid nodules.

Thyrotropin (TSH)- and sodium fluoride (NaF)-sensitive adenylate cyclase (AC) activity was measured in ten cases of "cold" thyroid nodules and compared with perinodular tissue. Findings were correlated with the ultrastructure of the nodular and perinodular tissue. Comparisons of the results of assay studies revealed an increase of basal and NaF- and TSH-stimulated AC activity in cold lesions. There was no dissociation of NaF- and TSH-sensitive AC. Ultrastructural findings disclosed a lack of correlation between elevated AC activity and the expected organelle profile indicative of stimulation. Since organelle modulations that are associated with increased protein synthesis were not observed in the face of increased AC activity, an unknown intracellular defect may exist in the expression of the AC-cyclic AMP (adenosine 3':5'-cyclic phosphate) system in cold thyroid nodules.