Objective 1. To examine relationships between 25-hydroxy vitamin D (25OHD) in women with type 1 diabetes (T1DM) during pregnancy, post-delivery and in cord blood. 2. To investigate interactions ...between maternal body mass index (BMI) and foetal vitamin D status. 3. To examine relationships between maternal 25OHD and glycosylated haemoglobin (HbA1c). Methodology An observational study of 52 pregnant controls without diabetes and 65 pregnant women with T1DM in a university teaching hospital. 25OHD was measured by liquid chromatography tandem mass spectrometry. Results Vitamin D deficiency (25OHD <25 nmol/L) was apparent in control and T1DM women in all 3 trimesters. All cord blood 25OHD were <50 nmol/L. Maternal 25OHD correlated positively with cord 25OHD at all 3 trimesters in the T1DM group ( p = 0.02; p < 0.001; p < 0.001). Cord 25OHD was significantly lower for T1D women classified as obese vs. normal weight at booking normal weight BMI <25 kg/m2 vs. obese BMI〉30 kg/m2 (nmol/L ± SD); 19.93 ± 11.15 vs. 13.73 ± 4.74, p = 0.026. In the T1DM group, HbA1c at booking was significantly negatively correlated with maternal 25OHD at all 3 trimesters ( p = 0.004; p = 0.001; p = 0.05). Conclusion In T1DM pregnancy, low vitamin D levels persist throughout gestation and post-delivery. Cord blood vitamin D levels correlate with those of the mother, and are significantly lower in obese vs normal weight women. Maternal vitamin D levels exhibit a significant negative relationship with HbA1c, supporting a potential role for this vitamin in maintaining glycaemic control.
Hyperglycemia and Adverse Pregnancy Outcomes Metzger, Boyd E; Lowe, Lynn P; Dyer, Alan R ...
The New England journal of medicine,
05/2008, Letnik:
358, Številka:
19
Journal Article
Recenzirano
Odprti dostop
In this large, multinational study, glucose levels that were increased during pregnancy but were below levels diagnostic of diabetes were significantly associated with increased risks of birth weight ...above the 90th percentile and C-peptide levels above the 90th percentile, as well as with other adverse pregnancy outcomes. These results indicate the need to reconsider current thresholds for diagnosing and treating hyperglycemia during pregnancy.
Glucose levels that were increased during pregnancy but were below levels diagnostic of diabetes were significantly associated with increased risks of birth weight above the 90th percentile and C-peptide levels above the 90th percentile, as well as with other adverse pregnancy outcomes.
Gestational diabetes mellitus, defined as “glucose intolerance with onset or first recognition during pregnancy,”
1
,
2
has been the subject of considerable controversy. Criteria for the diagnosis were initially established more than 40 years ago
3
and, with minor modifications, remain in use today. These criteria are not designed to identify pregnant women who are at increased risk for adverse perinatal outcomes but rather women who are at high risk for the development of diabetes after pregnancy,
3
,
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or they are the criteria used for the general population.
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Overt diabetes mellitus during pregnancy is associated with significantly increased risks of adverse perinatal . . .
Objective: The purpose of this study was to examine the relationships between maternal and cord leptin concentrations, maternal and neonatal outcomes, and measures of glycemic control in diabetic and ...nondiabetic pregnancy. Study Design: This was a prospective study of 60 type 1 diabetic and 50 nondiabetic pregnancies in a university teaching hospital. Serum leptin and hemoglobin A1c were measured serially throughout pregnancy; leptin, insulin, insulin-like growth factor-1, and C-peptide in venous cord blood were measured at delivery. Leptin was measured with the use of enzyme-linked immunosorbent assay. Data were analyzed with specific computer software. Results: Maternal leptin levels correlated with cord leptin levels in the nondiabetic group only. Cord leptin levels correlated with cord C-peptide, cord insulin-like growth factor-1, birth weight, birth weight corrected for gestational age, and neonatal anthropometry in both groups and with hemoglobin A1c in the diabetic group only. Cord leptin levels increased significantly with increasing birth weight corrected for gestational age but remained significantly higher at all birth weights in the diabetic group. Conclusion: There are strong associations between cord leptin levels and other measures of fetal growth in both groups and with glycemic control in the diabetic group. (Am J Obstet Gynecol 2003;188:1326-32.)
TNM8 staging for oropharyngeal squamous cell carcinomas (OPSCC) surrogates p16 immunohistochemistry for HPV testing. Patients with p16+ OPSCC may lack HPV aetiology. Here, we evaluate the suitability ...of TNM8 staging for guiding prognosis in such patients.
HPV status was ascertained using p16 immunohistochemistry and high-risk HPV RNA and DNA in situ hybridisation. Survival by stage in a cohort of OPSCC patients was evaluated using TNM7/TNM8 staging. Survival of p16+/HPV- patients was compared to p16 status.
TNM8 staging was found to improve on TNM7 (log rank p = 0·0190 for TNM8 compared with p = 0·0530 for TNM7) in p16+ patients. Patients who tested p16+ but were HPV- (n = 20) had significantly reduced five-year survival (33%) compared to p16+ patients (77%) but not p16- patients (35%). Cancer stage was reduced in 95% of p16+/HPV- patients despite having a mortality rate twice (HR 2.66 95% CI: 1.37-5.15) that of p16+/HPV+ patients under new TNM8 staging criteria.
Given the significantly poorer survival of p16+/HPV- OPSCCs, these data provide compelling evidence for use of an HPV-specific test for staging classification. This has particular relevance in light of potential treatment de-escalation that could expose these patients to inappropriately reduced treatment intensity as treatment algorithms evolve.
1. The body temperatures and resting oxygen consumptions of calorie-deficient and protein-deficient pigs have been measured at 12, 21, 26, 30, 36 and 40°. 2. A fall in the environmental temperature ...was followed by a rise of the same order in the oxygen consumptions of the two groups of animals, and past and present evidence indicates that the rise in normal animals of the same size is similar. 3. The rectal temperatures and oxygen consumptions of the protein-deficient pigs were higher at all the above temperatures than those of the calorie-deficient animals but not as high as those of normal animals. 4. The differences in rectal temperatures and oxygen consumptions were highly significant at 30°, which is probably within or near the zone of thermal neutrality of all the animals.
Four cases of asthma (one adult, three children) developing acute adrenal crisis after introduction of high-dose inhaled fluticasone proprionate are presented. The three children, aged 7-9 yrs, had ...been prescribed inhaled fluticasone, dosage 500-2,000 microg x day(-1) and duration 5 months-5 yrs. All presented with convulsions due to hypoglycaemia (blood glucose 1.3-1.8 mM). The fourth case was a male of 33 yrs with difficult-to-control asthma and had been taking fluticasone propionate 1,000-2,000 microg x day(-1) for 3 yrs. He presented with fatigue, lethargy, nausea and postural hypotension. Acute adrenal crisis in each case was confirmed by investigations which included measurement of acute phase cortisol levels, short and long Synacthen stimulation tests and glucagon stimulation tests. Other cases of hypthoalamic-pituitary-adrenal axis suppression were excluded.
The DIS diffractive cross section, , has been measured in the mass range GeV for c.m. energies GeV and photon virtualities to 140 GeV. For fixed and , the diffractive cross section rises rapidly with ..., with corresponding to a t-averaged pomeron trajectory of which is larger than observed in hadron-hadron scattering. The W dependence of the diffractive cross section is found to be the same as that of the total cross section for scattering of virtual photons on protons. The data are consistent with the assumption that the diffractive structure function factorizes according to . They are also consistent with QCD based models which incorporate factorization breaking. The rise of with decreasing and the weak dependence of on suggest a substantial contribution from partonic interactions.
To investigate the regulation of epithelial-to-mesenchymal transition (EMT) in head and neck squamous cell carcinoma (HNSCC) and its importance in tumor invasion.
We use a three-dimensional invasive ...organotypic raft culture model of human foreskin keratinocytes expressing the E6/E7 genes of the human papilloma virus-16, coupled with bioinformatic and IHC analysis of patient samples to investigate the role played by EMT in invasion and identify effectors and upstream regulatory pathways.
We identify SNAI2 (Slug) as a critical effector of EMT-activated downstream of TP63 overexpression in HNSCC. Splice-form-specific depletion and rescue experiments further identify the ΔNp63γ isoform as both necessary and sufficient to activate the SRC signaling axis and SNAI2-mediated EMT and invasion. Moreover, elevated SRC levels are associated with poor outcome in patients with HNSCC in The Cancer Genome Atlas dataset. Importantly, the effects on EMT and invasions and SNAI2 expression can be reversed by genetic or pharmacologic inhibition of SRC.
Overexpression of ΔNp63γ modulates cell invasion by inducing targetable SRC-Slug-evoked EMT in HNSCC, which can be reversed by inhibitors of the SRC signaling.
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In order to identify the individual contributions of the kringle (K) domains of human plasminogen (Pg) to the epsilon-aminocaproic acid (EACA) induced stimulation of Pg activation by ...low-molecular-weight urokinase-type plasminogen activator (LMW-uPA) and inhibition of this same activation by Cl-, we constructed the most conservative recombinant- (r-) Pg mutants possible that would greatly reduce the strength of the EACA binding site in the omega-amino acid binding kringles, K1Pg (D139-->Nr-Pg), K4Pg (D413-->Nr-Pg), and K5Pg (D515--Nr-Pg). In each case, this involved mutation of a critical Asp (to Asn) within these three kringle domains in intact Pg. The three r-mutants were expressed in r-baculovirus-infected lepidopteran insect (Trichoplusia ni) cells. In the presence of Cl-, the positive activation effector, EACA, first stimulated and then inhibited the LMW-uPA-catalyzed initial activation of wild-type (wt) r-Glu1Pg and, to a lesser extent, the K5Pg mutant, D518-->N/Glu1r-Pg. The concentration of EACA that produced 50% stimulation of activation (C50) occurred at 3.3 mM for wtr-Glu1Pg and at 0.7 mM for D518-->N/Glu1r-Pg. Subsequent inhibition by EACA occurred with a C50 of approximately 15 mM and is likely due to inhibition of the amidolytic activity of plasmin generated during the activation. Similar initial activation rates of both D139-->Nr-Pg and D413Nr-Pg did not display this initial EACA-mediated stimulatory phase but did undergo ultimate inhibition with a C50 for this process that was similar to wtr-Glu1Pg and D518-->N/Glu1r-Pg.
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