Placental vascular resistance using umbilical velocimetry in patients undergoing cesarean section for fetal distress

Peak systolic (S) to lowest end-diastolic (D) ratios (S/D) of umbilical velocimetry have been used to assess downstream placental vascular resistance and predict adverse pregnancy outcome. The purpose of this study is to assess S/D ratios in patients undergoing cesarean section for clinical fetal distress. Fifty-six patients were identified who had umbilical velocimetry performed during antepartum fetal surveillance (nonstress testing and amniotic fluid index) within 7 days of undergoing cesarean section for fetal distress at Women's Hospital (Los Angeles, CA). The mean gestational age at delivery was 36.5 +/- 2.5 weeks. Thirty (53.6%) patients had elevated S/D ratios (greater than 3), 24 (42.9%) had abnormal amniotic fluid indices, and 20 (35.7%) had abnormal nonstress testing. Group 1 (N = 30) patients delivered small-for-gestational-age (SGA) fetuses and group 2 (N = 26) patients delivered appropriately grown (AGA) fetuses. In group 1, 24 (80%) patients had abnormal S/D ratios and 16 (53.3%) had abnormal amniotic fluid indices, compared to only 6 (23.1%) with abnormal S/D ratios and 8 (30.8%) with abnormal amniotic fluid indices in group 2 (p less than .05). In contrast, 14 (53.8%) of the 26 patients in group 2 had abnormal nonstress testing compared to only 6 (20%) of the 30 patients in group 1 (p less than .05). Eighteen (69.2%) of the 26 patients in group 2 were post-term pregnancies; 20 (66.7%) of the 30 patients in group 1 had chronic hypertension, pregnancy-induced hypertension, or superimposed preeclampsia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impact of hypercholesterolemia on toxicity of N-nitrosodiethylamine: biochemical and histopathological effects

N-nitrosodiethylamine (NDEA) is an important carcinogen frequently present in human environment and food chain. Nitrosamines such as NDEA produce oxidative stress due to generation of reactive oxygen species and alter the antioxidant defence system in the tissues. The present investigation was aimed at studying its toxicity under hypercholesterolemic conditions. NDEA administration brought about hepatic degeneration as evidenced by the significant decrease in liver weight index of both normal as well as hypercholesterolemic animals. Hypercholesterolemia did not affect the hemoglobin (Hb) content in experimental animals but resulted in an increase in the osmotic fragility of erythrocytes. The antioxygenic potential of experimental animals decreased in both, the NDEA-fed group as well as in the group that was also supplemented with a hypercholesterolemic diet. This was evident by increased in vitro lipid peroxidation (LPO) of erythrocytes. Administration of NDEA resulted in a substantial and significant increase in LPO in all the tissues under normal as well as hypercholesterolemic conditions. Addition of hypercholesterolemic diet in general, increased LPO in all the tissues to varying degrees but its effect was maximal in the liver. Effect of NDEA administration on antioxygenic enzymes under normal as well as hypercholesterolemic conditions was variable in different tissues. Histopathological analysis of different tissues (heart, liver, lungs, spleen and kidneys) showed mild to severe pathological changes among the control and experimental groups.     

Concomitant low-dose cisplatin and three-dimensional conformal radiotherapy for locally advanced squamous cell carcinoma of the head and neck: Analysis of survival and toxicity

BACKGROUND: Our center sought to implement a simple chemoradiotherapy schedule for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) with minimal toxicity to achieve rates of overall survival comparable to other schedules. METHODS: The chemoradiotherapy schedule consisted of daily radiation to 70 Gy over 7 weeks with concurrent cisplatin 20 mg/m(2) during days 1 to 4 of weeks 1 and 5. Acute and late toxicities were recorded according to the Radiation Therapy Oncology Group (RTOG) and common toxicity criteria (CTC) grading. The overall, disease-specific, and locoregional recurrence-free survival were calculated using the STATA statistics package. Possible factors influencing these endpoints were analyzed. RESULTS: Fifty-seven patients were treated, and 56 patients were evaluable for follow-up. Median follow-up of alive patients was 16.1 months. There was an 82% complete response rate to chemoradiotherapy. The 2-year Kaplan-Meier overall, disease-specific, and locoregional recurrence-free survival rates were 62%, 67%, and 63%. Acute grade 3 and 4 radiation toxicity was noted in 61% and 2%, respectively. Grade 3 or 4 hematologic toxicity was noted in 7% of patients. Factors influencing overall survival included: Karnofsky performance status, receiving more than 50% of planned chemotherapy, age, and initial hemoglobin level. CONCLUSION: This regimen is tolerable and achieves overall survival and locoregional control rates comparable to other chemoradiotherapy schedules.     

Sleep architecture and glucose and insulin homeostasis in obese adolescents

OBJECTIVE

Sleep deprivation is associated with increased risk of adult type 2 diabetes mellitus (T2DM). It is uncertain whether sleep deprivation and/or altered sleep architecture affects glycemic regulation or insulin sensitivity or secretion. We hypothesized that in obese adolescents, sleep disturbances would associate with altered glucose and insulin homeostasis.

RESEARCH DESIGN AND METHODS

This cross-sectional observational study of 62 obese adolescents took place at the Clinical and Translational Research Center and Sleep Laboratory in a tertiary care children’s hospital. Subjects underwent oral glucose tolerance test (OGTT), anthropometric measurements, overnight polysomnography, and frequently sampled intravenous glucose tolerance test (FSIGT). Hemoglobin A_1c (HbA_1c) and serial insulin and glucose levels were obtained, indices of insulin sensitivity and secretion were calculated, and sleep architecture was assessed. Correlation and regression analyses were performed to assess the association of total sleep and sleep stages with measures of insulin and glucose homeostasis, adjusted for confounding variables.

RESULTS

We found significant U-shaped (quadratic) associations between sleep duration and both HbA_1c and serial glucose levels on OGTT and positive associations between slow-wave sleep (N3) duration and insulin secretory measures, independent of degree of obesity, pubertal stage, sex, and obstructive sleep apnea measures.

CONCLUSIONS

Insufficient and excessive sleep was associated with short-term and long-term hyperglycemia in our obese adolescents. Decreased N3 was associated with decreased insulin secretion. These effects may be related, with reduced insulin secretory capacity leading to hyperglycemia. We speculate that optimizing sleep may stave off the development of T2DM in obese adolescents.Sleep deprivation is endemic; 9.3% of U.S. adults sleep <6 h per night (1), and 75% of high-school seniors report getting insufficient sleep (2). This cumulative societal sleep curtailment is significant, as sleep deprivation is associated with a number of metabolic consequences: increased predisposition to obesity (3) and insulin resistance (IR) (4) in both adults and children, increased risk of type 2 diabetes mellitus (T2DM) in adults (5), and higher fasting glucose in young adults with preexisting diabetes (6). The metabolic consequences of insufficient sleep may be the result of a lack of total sleep or insufficiency of a certain sleep component. The American Academy of Sleep Medicine recognizes four different sleep stages indicated as follows: stage 1 (N1), a brief transition between wake and sleep; stage 2 (N2); stage 3 (N3), “slow-wave” or “deep” sleep; and rapid eye movement (REM) (dream) sleep. In adult studies, cerebral glucose utilization declines (7) and plasma glucose rises (8) in N3 sleep. One pediatric study found a negative association between REM sleep duration and obesity (9), but there is little pediatric data on sleep architecture and glucose and insulin homeostasis. A potential confounding factor is obstructive sleep apnea (OSA), a syndrome more common in obesity in which upper airway obstruction leads to sleep fragmentation and desaturation (10). OSA has been associated with T2DM risk in adults (10) and with IR in children (11,12). We hypothesized that in obese adolescents (who are at risk for T2DM), altered sleep architecture is associated with abnormalities of insulin secretion and sensitivity and of glucose homeostasis independently of confounding factors (e.g., degree of obesity, presence of OSA, sex, and pubertal stage). Therefore, the aim of our study was to investigate the relationship between sleep architecture and insulin secretion and sensitivity and overall glycemia in this population.     

Protective role of dietary fibre on N-nitrosopyrrolidine-induced toxicity in hypercholesterolemic rats

N-nitrosopyrrolidine (NPYR) is an important carcinogen, frequently present in the environment and food chain. Oral administration of NPYR to experimental rats evoked severe biochemical and pathological changes. In the present investigation, the protective role of dietary fibre on NPYR-induced toxicity in hypercholesterolemic rats was studied. Supplementation of chickpea seed coat fibre in the diet reduced the hepato-toxic effects of NPYR, as evident from the decreased hepatic degeneration and improved liver weight index compared to control. Administration of NPYR resulted in an increase in the osmotic fragility of erythrocytes in the experimental animals. The antioxidant potential of experimental animals decreased in the NPYR-fed group, which was evident from the increased in vitro lipid peroxidation (LPO) of erythrocytes. However, chickpea seed coat fibre considerably reduced the peroxidative damage done by NPYR. Administration of NPYR resulted in a substantial and significant increase in LPO in all tissues, to a varying degree, though the effect was maximum in the case of the liver. Inclusion of chickpea seed coat fibre considerably reduced the peroxidative damage caused by NPYR in all tissues. The effect of NPYR administration on antioxidant potential was variable in different tissues, but the effect was reduced considerably on inclusion of chickpea seed coat fibre in the diet, providing reasonable protection against NPYR-induced oxidative stress, and, hence, its toxicity. Histopathological analysis of different tissues (heart, liver, lungs, spleen and kidneys) showed mild to severe pathological changes among the control and experimental groups. However, the pathological effects of NPYR administration were markedly reduced with the addition of chickpea seed coat fibre in the diet.     

Change in lipid profile in celiac disease: beneficial effect of gluten-free diet

Purpose

Celiac disease is associated with hypocholesterolemia, which is thought to contribute to a favorable cardiovascular risk profile. This led to suggestions that the diagnosis of celiac disease and its treatment with a gluten-free diet may result in elevation of the serum cholesterol level and worsen this risk profile. However, no study proves this in adults. We therefore examined the effect of a gluten-free diet on the lipid profile in patients with celiac disease.

Subjects and methods

We identified 132 patients with celiac disease who adhered to a gluten-free diet and had lipid profiles performed before and after a median of 20.5 months on the diet. The patients lacked diseases that may affect serum lipids.

Results

There were significant increases in total cholesterol and high-density lipoprotein (HDL) cholesterol (P < .0001) but not low-density lipoprotein (LDL) cholesterol (P = .06). The LDL/HDL ratio decreased by 0.36 ± 0.7 (P < .0001). Both men and women had a significant increase in total cholesterol and HDL and a significant decrease in the LDL/HDL ratio. Only men had increases in LDL (P = .02). The greatest increase in lipid values was seen in those with the lowest initial values. The largest increase in HDL was seen in subjects with more severe disease as indicated by low albumin level and presence of total villous atrophy.

Conclusions

Diagnosis of celiac disease and its treatment with a gluten-free diet resulted in improvement in the lipoprotein profile, which included an increase in HDL and a decrease in the LDL/HDL ratio.