Romantic, sexual, and sexual risk behaviours of adolescent females with severe obesity.

BACKGROUND: There is an increasing adolescent population with severe obesity with impairments in social and romantic relationships that are seeking clinical weight management, including weight loss surgery (WLS). OBJECTIVE: To document romantic, sexual and sexual risk behaviours in a clinical sample of adolescent females with severe obesity (BMI > 40 kg/m2 ) compared to those of healthy weight (HW). METHODS: This multi-site study-an ancillary to a prospective longitudinal observational study documenting health in adolescents having WLS-presents pre-operative/baseline data from 108 females undergoing WLS, 68 severely obese seeking lifestyle intervention and 118 of HW. Romantic and sexual risk behaviour and birth control information sources were assessed using the Sexual Activities and Attitudes Questionnaire (SAAQ). RESULTS: Severely obese females reported engaging in fewer romantic and sexual behaviours compared to HW. Similar to HW, a subgroup (25%) of severely females were engaging in higher rates of sexual risk behaviours and reported pregnancies and sexually transmitted infections (STIs). A considerable number (28-44%) reported receiving no birth control information from physicians. CONCLUSIONS: Discussion topics with the adolescent patient should extend beyond reproductive health needs (e.g. contraception, unintended pregnancies) to include guidance around navigating romantic and sexual health behaviours that are precursors to these outcomes.

Early metabolic improvement following bariatric surgery in morbidly obese adolescents.

Bariatric surgery results in durable weight loss and improved comorbidities. The objectives of this study were to examine the efficacy of gastric bypass in reducing comorbid burden and improving metabolic status among morbidly obese adolescents. The medical records of 15 gastric bypass patients were retrospectively reviewed. Changes in metabolic markers were determined at baseline, 1 and 2 years post-operatively. Comparative analysis demonstrated significant improvement in weight, BMI, insulin, HbA1C, C-peptide, %B, %S, IR, cholesterol, percentile cholesterol, TG, percentile TG, HDL, percentile HDL, LDL, percentile LDL, and VLDL. Results support bariatric surgery as a treatment for morbidly obese adolescents with comorbidities.

[Pheochromocytoma: diagnosis and treatment]. / Feochromocytom: diagnostika a lécba.

Pheochromocytoma (pheo) is adrenal or less frequently extraadrenal tumour of chromafine tissue. Pheos are rare, but cardiovascular and metabolic abnormalities are common. Unrecognised pheo may lead to fatal hypertensive crisis during anesthesia or other stresses. Proper diagnosis of pheo is thus of utmost importance. 24-h blood pressure (BP) monitoring may contribute to the diagnosis of pheo due to increased BP variability and absence of night BP decline. Pheo contains large amount of enzyme catechol-O-methyl transpherase (COMT) with subsequent excessive production of COMT metabolites like metanephrines. Measurement of plasma free metanephrines or urinary fraccionated metanephrines has usually higher sensivitivity and specificity compared with plasma or urinary catecholamines. Morphological diagnosis of adrenal/extraadrenal pheo is based on CT/MR visualisation and 123I-metaiodobenzylguanidin (MIBG) or PET 18F-fluorodeoxyglucose scan. Genetic analysis should be performed in all confirmed pheo cases, especially in younger subjects below 50 years of age in order to detect mutations of following genes: von Hippel-Lindau (VHL), RET- protooncogen, genes encoding B, C and D subunit of mitochondrial sukcinat dehydrogenaze (SDHB, SDHC, SDHD) and neurofibromatosis type I gene. Pharmacological treatment is based on alpha blockers with subsequent (after 24-48 hours) administration of beta-blockers/especially in patients with tendency to tachycardia/. Following this therapy normalisation of BP is common and laparoscopic excision of pheo tumour can be realised. Malignant pheos are difficult to treat due to early occurrence of metastasis and lack of response to chemotherapy or iradiation in most cases.

Streamlining the care of patients with hypertrophic pyloric stenosis: application of a clinical pathway.

PURPOSE: The purpose of this study was to evaluate the impact of a clinical pathway on infants admitted to a pediatric tertiary care center with the diagnosis of hypertrophic pyloric stenosis (HPS). METHODS: The records of 132 HPS patients were evaluated before and after implementation of a clinical pathway. Infants were excluded for prematurity, admission to nonsurgical services, or multiple diagnoses requiring prolonged hospitalization, resulting in 83 patients for analysis. Group I (prepathway, n = 40) and group II (postpathway, n = 43) infants were analyzed for time from admission to operation, operation to first feeding, operation to discharge, total length of stay, hospital charges, metabolic status at time of admission, and postoperative complications. The Mann-Whitney test was performed (statistical significance at P <.05). RESULTS: There was no significant difference between group I and group II patients in the length of preoperative hospitalization or metabolic status at the time of hospital admission. In comparison with group I patients, there was a significant reduction in time to resumption of oral feedings (4.6 +/- 1.9 hours v 7.5 +/- 3.2 hours; P <.001) for group II infants and a significantly earlier discharge (26.7 +/- 6.8 hours v 38.0 +/- 11.7 hours; P <.001). This resulted in a shortened length of stay (41.8 +/- 9.7 hours v 57.8 +/- 14.3 hours; P <.001) with an associated decrease in hospital charges ($4,555 +/- $464 v $5,400 +/- $1,017; P <.001). CONCLUSIONS: Elimination of practice variability by the use of a clinical pathway for HPS resulted in significant reduction of hospital stay and related charges. The impact of the pathway occurred in the postoperative period and is a consequence of a rapid and systematic return to oral feedings.

Heparin-binding EGF-like growth factor is present in human amniotic fluid and breast milk.

BACKGROUND/PURPOSE: Heparin-binding EGF-like growth factor (HB-EGF) is a member of the epidermal growth factor (EGF) family that has been implicated in the healing of various organ injuries. Endogenous HB-EGF production is upregulated in response to injury to the kidney, liver, brain, skin, and intestine. Exogenous administration of HB-EGF protects against intestinal epithelial cell apoptosis and necrosis and intestinal ischemia/reperfusion (I/R) injury. This study examines the presence of endogenous HB-EGF in human amniotic fluid and breast milk, fluids that are in intimate contact with the developing and neonatal gastrointestinal tract. METHODS: Breast milk samples were collected from lactating women and amniotic fluid was gathered from full-term uteri (cesarian sections) or preterm uteri (amniocentesis). Crude and partially purified breast milk and amniotic fluid samples were analyzed for HB-EGF levels using an HB-EGF-specific enzyme-linked immunosorbent assay (ELISA). RESULTS: Analysis results showed detectable HB-EGF levels in human amniotic fluid and breast milk, ranging from 0.2 to 230 pg/mL. Breast milk and amniotic fluid subjected to heparin affinity or HB-EGF-affinity column chromatography showed bioactivity eluting at positions consistent with those known for native HB-EGF. CONCLUSIONS: This study represents the first report of detectable HB-EGF in human amniotic fluid and breast milk. The presence of HB-EGF in these fluids may serve a role in the development of the gastrointestinal tract in utero, and in protection against gut mucosal injury after birth.

Heparin-binding EGF-like growth factor decreases apoptosis in intestinal epithelial cells in vitro.

BACKGROUND/PURPOSE: The production of heparin-binding EGF-like growth factor (HB-EGF) is upregulated during organ injury and has a cytoprotective effect during hypoxic stress in intestinal epithelial cells in vitro and intestinal ischemia-reperfusion injuries in vivo. The purpose of this study was to determine if HB-EGF-related cytoprotection is manifested through alterations in apoptosis. METHODS: Human intestinal epithelial cell monolayers (DLD-1 and Caco-2) were stimulated with interleukin (IL)-1 (20 ng/mL), tumor necrosis factor (TNF)-alpha (40 ng/mL), and interferon (IFN)-gamma (10 ng/mL) with or without HB-EGF (1, 10 or 100 ng/mL) and analyzed for rates of apoptosis utilizing a Cell Death Detection ELISA and flow cytometry. RESULTS: ELISA results showed a 3-fold increase in the level of apoptosis during stimulation with cytokines compared with nonstimulated cells (P <.05). Relative levels of cytokine induced apoptosis were reduced after 12 hours of HB-EGF exposure (P <.05) in a dose-dependent fashion. Results of flow cytometric analysis also showed a reduction in apoptosis at 6 hours when cell monolayers were stimulated with cytokines in conjunction with HB-EGF compared with cytokines alone (P <.05). CONCLUSIONS: HB-EGF downregulated apoptosis in intestinal epithelial cells exposed to proinflammatory cytokines in vitro. The results of this study suggest that alterations in apoptosis may represent a possible mechanism by which this growth factor exerts its cytoprotective effect at the mucosal level during the proinflammatory state.

Giant duodenal diverticulum: presentation by blunt trauma.

Most duodenal diverticula are asymptomatic, small (i.e., less than 5 cm in greatest dimension), acquired, extraluminal, and false. The only report of a massive or giant duodenal diverticulum (i.e., 10 cm or more), in the current literature, included severe nocturnal diarrhea. The present case report is the incidental finding of a massive duodenal diverticulum in a 34-year-old male trauma victim. The insidious nature of this case and the patient's age suggest a congenital etiology. We believe this is the first report of such a case.

Effect of acute-phase and heat-shock stress on apoptosis in intestinal epithelial cells (Caco-2).

OBJECTIVES: a) To determine if the sequence of exposure of intestinal epithelial cells to heat-shock or acute-phase stimuli would affect whether cellular protection or injury would occur; and b) to determine if the effects of a thermally induced heat-shock response can be mimicked by sodium arsenite, a nonthermal inducer of the heat-shock response. DESIGN: In vitro controlled study. SETTING: Institutional laboratories. SUBJECTS: Caco-2 human intestinal cell line. INTERVENTIONS: Human intestinal epithelial cells (Caco-2) were grown on 35-mm culture dishes, chamber slides, or in a bicameral culture system to confluence or until tight-junction integrity was established. The cells were examined for viability, apoptosis, and bacterial translocation after exposure to a series of insults. MEASUREMENTS AND MAIN RESULTS: Control Caco-2 cells (medium only) and cells exposed to arsenite or to LPS alone had an apoptotic cell rate of 5.7%, 7.9%, and 8.6%, respectively. However, Caco-2 cells exposed to the cytokines IL-1beta and IL-6 had a significantly higher rate of apoptosis (22.1%, p < .01 vs. other groups). Caco-2 cells exposed to arsenite followed by LPS had 6.7% apoptotic cells, while cells exposed to LPS followed by arsenite had a significantly greater number of apoptotic cells (19.7%, p < .05). In addition, cells exposed to cytokines followed by arsenite had a higher apoptotic rate than cells exposed to arsenite followed by cytokines (28.4% vs. 10.6%, p < .01). Similar results were seen when cell viability was quantitated. At 3 hrs after challenge with Escherichia coli, the cytokine-exposed Caco-2 monolayers had a significantly increased rate of bacterial passage across the Caco-2 monolayer than control monolayers (p < .05), while the Caco-2 monolayers exposed to arsenite followed by cytokines or arsenite alone had a decreased rate of bacterial passage (p < .05). Conversely, cells exposed to cytokines or LPS before arsenite had the highest number of bacteria crossing the monolayer (p < .05). CONCLUSIONS: These results indicate that preinduction of a heat-shock response (arsenite) can protect against cytokine or LPS-induced apoptosis and enterocyte dysfunction, as manifested by the passage of E. coli across an intact enterocyte monolayer. In contrast, the induction of a heat-shock response after exposure to acute-phase response inducers (cytokines and LPS) may result in decreased enterocyte viability, increased apoptosis, and cellular dysfunction.

[Comparison of the effectiveness of 17-beta-estradiol and calcitonin in women with postmenopausal bone loss]. / Porovnání úcinnosti lécby 17 beta-estradiolem a kalcitoninem u zen s úbytkem kostní hmoty po menopauze.

BACKGROUND: The objective of this study was to compare effects of 17 beta-estradiol and intranasal salmon calcitonin on bone mass and biochemical markers of bone turnover in postmenopausal women with an accelerated bone loss and osteopenia or osteoporosis. METHODS AND RESULTS: 72 women with significantly increased bone resorption were evaluated (urinary hydroxyproline/creatinine > or = 21.9 mmol/mol, mean age, 53.7 +/- 6.3 years, time since menopause 6.1 +/- 2.6 years). All patients received daily 500 mg Ca2+ and 400 IU vitamin D supplement. 48 patients with osteopenia and 24 patients with osteoporosis were randomly allocated to treatment with open-label 17 beta-estradiol (50 micrograms transdermally or 2 mg orally) or calcitonin (200 IU every other day). Bone mass was measured by dual-energy x-ray absorptiometry (DPX-L, Lunar, C.V., 1.10 +/- 0.55% and 1.41 +/- 0.55%, lumbar spine and femoral neck, respectively) every six month for 2.5 year, bone stiffness was measured by ultrasound (Achilles, Lunar, C.V., 3.88 +/- 1.95%). Biochemical markers of bone turnover (plasma osteocalcin and tartrate-resistant acid phosphatase, serum bone specific alkaline phosphatase and urinary hydroxyproline) were measured before and after 6, 12 and 24 month of treatment. Patients who received 17 beta-estradiol experienced significant increases (p < 0.05) in bone mass on the first and second year (by 2.6% and 2.1% at lumbar spine, 1.1% and 1.0%, at femoral neck, and 2.3% and 2% at the heel). A significant positive correlation was found between rates of bone mass change in all sites (p < 0.001). No statistically significant bone changes were found in calcitonin treated patients. In 17 beta-estradiol treated patients, biochemical markers of bone turnover decreased by 40-50% to the mean values in premenopausal women. In calcitonin treated patients, biochemical markers reached the upper normal limit. CONCLUSIONS: Estrogen replacement therapy increases bone mass in lumbar spine as well as in femoral neck. It is efficient for both prevention and treatment of postmenopausal osteoporosis. Salmon calcitonin effectively prevents bone loss. Efficacy of both the treatment can be assessed after 6 months using a biochemical marker of bone resorption and after 2 years using dual-energy x-ray densitometry.

Interleukin-6 and tumor necrosis factor production in an enterocyte cell model (Caco-2) during exposure to Escherichia coli.

Data linking interactions between bacteria and the intestine with elevated serum cytokine levels has led to the concept of the gut as a cytokine-producing organ. An in vitro cell culture model was used to investigate the potential role of intestinal mucosa within this paradigm. Polarized monolayers of human enterocytes (Caco-2) were grown in a two compartment system where the apical and basal aspects of the membrane could be studied. Supernatant was collected at 0, 1, 3, 6, and 24 h after the monolayer was exposed (apically or basally) to 10(2), 10(5), or 10(8) colony-forming units of Escherichia coli C25/mL and saved for interleukin (IL)-6 and tumor necrosis factor (TNF) bioassay analysis. Caco-2 cells (not bacterially challenged) secreted significant amounts of constitutive IL-6, but not TNF, into the apical and basal chambers. Both cytokines levels were increased in a dose-dependent fashion (p < .05) after the E. coli challenge. This stimulated cytokine response was polar, in that the highest cytokine levels were at the side of the bacterial challenge and were most notable at the highest dose (10(8) colony-forming units/mL) of E. coli C25 tested. Caco-2 cells produce IL-6 and TNF in a dose-dependent fashion in response to E. coli C25 and the magnitude of this response is maximal on the side of the bacterial challenge. This data supports the hypothesis that bacterially challenged human enterocytes may be important producers of cytokines.

Phenothiazines are potent inhibitors of osteoclastic bone resorption.

1. We have previously shown that promethazine inhibits osteoclastic bone resorption in the in vitro bone slice assay (IC50 = 0.8 microM), but the mechanism(s) involved are unclear. 2. We have now tested the effects on osteoclast activity of five other structurally related compounds. Phenothiazine, chlorpromazine, amitriptyline, phenazine, and phenoxazine had IC50 values of 0.8, 0.9, 6, 7, and > 10 microM, respectively, in the bone slice assay, indicating that the basic phenothiazine structural element itself is important for osteoclast inhibitory activity. 3. The results are discussed in terms of the known effects of phenothiazines on plasma membrane fluidity, blocking of ion channels, and inhibition of calmodulin.

Galactosyl hydroxylysine in assessment of Paget's bone disease.

Urinary galactosyl hydroxylysine/creatinine ratio (GHL) was used to assess rates of bone collagen degradation and the activity of the pagetic lesion as well as for monitoring the rate and degree of suppression of bone resorption over 1 year in patients treated with 30 mg of intravenous pamidronate for 3 consecutive days. The clinical utility of GHL was compared with that of urinary hydroxyproline/creatinine and deoxypyridinoline/creatinine and with bone isoenzyme of serum alkaline phosphatase. The results suggest that GHL is a quantitative marker of the activity of Paget's bone disease. GHL is less sensitive than hydroxyproline, deoxypyridinolone and bone alkaline phosphatase in monitoring treatment of Paget's disease. The assay of GHL is easier, faster and less costly than that of hydroxyproline or deoxypyridinoline and it can be easily standardized.

High-performance liquid chromatographic and mass spectrometric identification of phosphocitrate synthesized by human kidney homogenate.

Two high-performance liquid chromatographic techniques for the analysis of phosphocitrate, a metabolite synthesized by the cell that is thought to play a role in a number of physiological as well as pathological events, have been developed. The mass spectra of the isolated compound obtained under fast-atom bombardment and collisionally activated decomposition mass-analysed ion kinetic energy conditions are also reported.

Rat cortical and trabecular bone collagen glycosylation are differently influenced by ovariectomy.

This study sought to evaluate whether estrogen depletion influences the hydroxylysine glycosydes content of rat bone collagen. For this reason thirty 100 day old female rats were divided in 6 groups of 5 rats each. Three groups were ovariectomized and 3 groups were sham-operated. The animals were sacrificed at 115, 130 and 145 days of age (i.e., 15, 30 and 45 days after surgery). Cortical and trabecular bone was prepared from tibiae and femurs. Hydroxylysine glycosydes content was measured by HPLC. Ovariectomy is followed, in the rat, by an increased hydroxylysine glycosylation in trabecular bone but by a constant or slightly decreased hydroxylysine glycosylation in the cortical bone. In view of the different effects of estrogens on the two bone compartments previously reported, a possible functional explanation of these findings is proposed.

The glycosides of hydroxylysine are final products of collagen degradation in humans.

Glucosyl-galactosyl-hydroxylysine (GGHYL) and galactosyl-hydroxylysine (GHYL) are metabolites derived from collagen degradation. They are useful biochemical markers provided they are not further processed. Experiments were run to test the activity of alpha- and beta-glycosidases in human kidney cortex preparations. Results allow to exclude the presence of the specific enzymes, in contrast with what is reported for the rat kidney tissue.