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1.  Assessing gonadal function after childhood ovarian surgery 
Journal of pediatric surgery  2012;47(6):1272-1279.
Purpose
We aimed to assess the late effects of ovarian salvage or oophorectomy on gonadal function and fertility as measured by menstrual regularity.
Methods
We performed a 10-year retrospective review of females aged 20 years or younger who required surgery to treat an ovarian disorder. A mail survey was distributed to these patients to evaluate the effects of ovarian surgery on menarche, menstrual regularity, and pregnancy.
Results
A total of 180 females had surgery to treat an ovarian disorder. Eighty-six of these underwent unilateral oophorectomy (48%), whereas 94 (52%) had an ovary sparing procedure. Eighty-one patients (45%) returned completed surveys. Of the respondents, 44 had oophorectomy, and 37 had ovarian salvage. Ages of menarche were similar between surgical groups. Symptoms of menstrual irregularity differed most significantly according to painful menses (oophorectomy, 27.3%; salvage, 59.5%; P < .04). Interestingly, continuation of regular menses after surgery was higher in the oophorectomy group (oophorectomy, 70%; salvage, 15%; P = .013).
Conclusions
Unilateral oophorectomy does not appear to impair late gonadal function when compared with ovarian salvage. Surprisingly, oophorectomy appears to maintain more normal ovarian activity as estimated by menstrual regularity. Oophorectomy may be performed without apparent adverse effect on gonadal activity.
doi:10.1016/j.jpedsurg.2012.03.038
PMCID: PMC4148072  PMID: 22703805
Oophorectomy; Ovarian salvage; Fertility; Ovarian function; Menstrual irregularity; Children
2.  Dexamethasone reduces emesis after major gastrointestinal surgery (DREAMS) 
Trials  2013;14:249.
Background
Postoperative nausea and vomiting is one of the most common complications affecting patients after surgery and causes significant morbidity and increased length of hospital stay. It is accepted that patients undergoing surgery on the bowel are at a higher risk. In the current era of minimally invasive colorectal surgery combined with enhanced recovery, reducing the incidence and severity of postoperative nausea and vomiting is particularly important. Dexamethasone is widely, but not universally used. It is known to improve appetite and gastric emptying, thus reduce vomiting. However, this benefit is not established in patients undergoing bowel surgery, and dexamethasone has possible side effects such as increased risk of wound infection and anastomotic leak that could adversely affect recovery.
Design
DREAMS is a phase III, double-blind, multicenter, randomized controlled trial with the primary objective of determining if preoperative dexamethasone reduces postoperative nausea and vomiting in patients undergoing elective gastrointestinal resections. DREAMS aims to randomize 1,350 patients over 2.5 years.
Patients undergoing laparoscopic or open colorectal resections for malignant or benign pathology are randomized between 8 mg intravenous dexamethasone and control (no dexamethasone). All patients are given one additional antiemetic at the time of induction, prior to randomization. Both the patient and their surgeon are blinded as to the treatment arm.
Secondary objectives of the DREAMS trial are to determine whether there are other measurable benefits during recovery from surgery with the use of dexamethasone, including quicker return to oral diet and reduced length of stay. Health-related quality of life, fatigue and risks of infections will be investigated.
Trial registration
ISRCTN21973627
doi:10.1186/1745-6215-14-249
PMCID: PMC3765230  PMID: 23938028
Anti-emetics; Colorectal surgery; Dexamethasone; Enhanced recovery; Gastrointestinal/surgery; Post-operative nausea and vomiting
3.  Measuring thyroid peroxidase antibodies on the day nulliparous women present for management of miscarriage: a descriptive cohort study 
Background
There has been recent evidence suggesting the presence of anti-thyroid peroxidase antibodies (TPOAb) increases the risk of miscarriage, and levothyroxine can rescue miscarriages associated with TPOAb. We propose the most clinically pragmatic cohort to screen for TPOAb are women presenting for management of a missed miscarriage and have never birthed a liveborn. We measured serum TPOAb among nulliparous women presenting for management of miscarriage, and compared levels with women who have had 2 or more livebirths (and never miscarried). Given its potential role in immunomodulation, we also measured Vitamin D levels.
Methods
We performed a prospective descriptive cohort study at a tertiary hospital (Mercy Hospital for Women, Victoria, Australia). We measured TPOAb and Vitamin D levels in serum obtained from 118 nulliparous women presenting for management of miscarriage, and 162 controls with 2 or more livebirths (and no miscarriages). Controls were selected from a serum biobank prospectively collected in the first trimester at the same hospital.
Results
Nulliparous women with 1 or more miscarriages had higher thyroid peroxidase antibody (TPOAb) levels than those with 2 or more livebirths; TPOAb in miscarriage group was 0.3 mIU/L (interquartile range [IR]: 0.2-0.7) vs 0.2 mIU/L among controls (IR 0.0-0.5; p < 0.0001). We confirmed TPOAb levels were not correlated with serum human chorionic gonadotrophin (hCG) concentrations in either the miscarriage or control groups. In contrast, thyroid stimulating hormone, fT3 and fT4 levels (thyroid hormones) either trended towards a correlation, or were significantly correlated with serum hCG levels in the two groups. Of the entire cohort that was predominantly caucasian, only 12% were Vitamin D sufficient. Low Vitamin D levels were not associated with miscarriage.
Conclusions
We have confirmed the association between miscarriage and increased TPOAb levels. Furthermore, it appears TPOAb levels in maternal blood are not influenced by serum hCG levels. Therefore, we propose the day nulliparous women present for management for miscarriage is a clinically relevant, and pragmatic time to screen for TPOAb.
doi:10.1186/1477-7827-11-40
PMCID: PMC3655833  PMID: 23672306
Thyroid peroxidase antibodies; Miscarriage; Vitamin D; Thyroid autoimmunity
4.  Incidence and Predictors of Hospitalization for Bacterial Infection in Community-Based Patients with Type 2 Diabetes: The Fremantle Diabetes Study 
PLoS ONE  2013;8(3):e60502.
Background
The few studies that have examined the relationship between diabetes and bacterial infections have utilized administrative databases and/or have had limited/incomplete data including recognized infection risk factors. The aim of this study was to determine the incidence and associates of bacterial infection severe enough to require hospitalization in well-characterized community-based patients with type 2 diabetes.
Methods and Findings
We studied a cohort of 1,294 patients (mean±SD age 64.1±11.3 years) from the longitudinal observational Fremantle Diabetes Study Phase I (FDS1) and 5,156 age-, gender- and zip-code-matched non-diabetic controls. The main outcome measure was incident hospitalization for bacterial infection as principal diagnosis between 1993 and 2010. We also examined differences in statin use in 52 FDS1 pairs hospitalized with pneumonia (cases) or a contemporaneous non-infection-related cause (controls). During 12.0±5.4 years of follow-up, 251 (19.4%) patients were hospitalized on 368 occasions for infection (23.7/1,000 patient-years). This was more than double the rate in matched controls (incident rate ratio (IRR) (95% CI), 2.13 (1.88–2.42), P<0.001). IRRs for pneumonia, cellulitis, and septicemia/bacteremia were 1.86 (1.55–2.21), 2.45 (1.92–3.12), and 2.08 (1.41–3.04), respectively (P<0.001). Among the diabetic patients, older age, male sex, prior recent infection-related hospitalization, obesity, albuminuria, retinopathy and Aboriginal ethnicity were baseline variables independently associated with risk of first hospitalization with any infection (P≤0.005). After adjustment for these variables, baseline statin treatment was not significant (hazard ratio (95% CI), 0.70 (0.39–1.25), P = 0.22). Statin use at hospitalization for pneumonia among the case-control pairs was similar (23.1% vs. 13.5%, P = 0.27).
Conclusions
The risk of severe infection is increased among type 2 diabetic patients and is not reduced by statin therapy. There are a number of other easily-accessible sociodemographic and clinical variables that could be used to optimize infection-related education, prevention and management in type 2 diabetes.
doi:10.1371/journal.pone.0060502
PMCID: PMC3607595  PMID: 23536910
5.  Molecular Diagnosis of Subcutaneous Pythium insidiosum Infection by Use of PCR Screening and DNA Sequencing 
Journal of Clinical Microbiology  2012;50(4):1480-1483.
Pythium insidiosum is an emerging human pathogen classified among brown algae and diatoms that can cause significant morbidity and mortality in otherwise healthy individuals. Here we describe a pediatric patient with pythiosis acquired in the southern United States, diagnosed by molecular screening and DNA sequencing of internal transcribed spacer region 1.
doi:10.1128/JCM.06126-11
PMCID: PMC3318510  PMID: 22205808
6.  Proteomic and protein interaction network analysis of human T lymphocytes during cell-cycle entry 
Proteomic analysis of T cells emerging from quiescence identifies dynamic network-level changes in key cellular processes. Disruption of two such processes, ribosome biogenesis and RNA splicing, reveals that the programs controlling cell growth and cell-cycle entry are separable.
The authors conduct a proteomic and protein interaction network analysis of human T lymphocytes during entry into the first cell cycle.Inhibiting the induction of eIF6 (60S ribosome biogenesis) causes T cells to enter the cell cycle without growing in size.Inhibiting the induction of SF3B2/SF3B4 (U2/U12-dependent RNA splicing) allows an increase in cell size without entering the cell cycle.These results provide proof of principle that blastogenesis and proliferation programs are separable in primary human T cells.
Regulating the transition of cells such as T lymphocytes from quiescence (G0) into an activated, proliferating state involves initiation of cellular programs resulting in entry into the cell cycle (proliferation), the growth cycle (blastogenesis, cell size) and effector (functional) activation. We show the first proteomic analysis of protein interaction networks activated during entry into the first cell cycle from G0. We also provide proof of principle that blastogenesis and proliferation programs are separable in primary human T cells. We employed a proteomic profiling method to identify large-scale changes in chromatin/nuclear matrix-bound and unbound proteins in human T lymphocytes during the transition from G0 into the first cell cycle and mapped them to form functionally annotated, dynamic protein interaction networks. Inhibiting the induction of two proteins involved in two of the most significantly upregulated cellular processes, ribosome biogenesis (eIF6) and hnRNA splicing (SF3B2/SF3B4), showed, respectively, that human T cells can enter the cell cycle without growing in size, or increase in size without entering the cell cycle.
doi:10.1038/msb.2012.5
PMCID: PMC3321526  PMID: 22415777
cell cycle; cell size; mass spectrometry; proteomics; T cells
7.  Proteomic profiling of urine for the detection of colon cancer 
Proteome Science  2008;6:19.
Background
Colorectal cancer is the second most common cause of cancer related death in the developed world. To date, no blood or stool biomarkers with both high sensitivity and specificity for potentially curable early stage disease have been validated for clinical use. SELDI and MALDI profiling are being used increasingly to search for biomarkers in both blood and urine. Both techniques provide information predominantly on the low molecular weight proteome (<15 kDa). There have been several reports that colorectal cancer is associated with changes in the serum proteome that are detectable by SELDI and we hypothesised that proteomic changes would also be detectable in urine.
Results
We collected urine from 67 patients with colorectal cancer and 72 non-cancer control subjects, diluted to a constant protein concentration and generated MALDI and SELDI spectra. The intensities of 19 peaks differed significantly between cancer and non-cancer patients by both t-tests and after adjusting for confounders using multiple linear regressions. Logistic regression classifiers based on peak intensities identified colorectal cancer with up to 78% sensitivity at 87% specificity. We identified and independently quantified 3 of the discriminatory peaks using synthetic stable isotope peptides (an 1885 Da fragment of fibrinogen and hepcidin-20) or ELISA (β2-microglobulin).
Conclusion
Changes in the urine proteome may aid in the early detection of colorectal cancer.
doi:10.1186/1477-5956-6-19
PMCID: PMC2440369  PMID: 18558005

Results 1-7 (7)