Effects of exercise during the holiday season on changes in body weight, body composition and blood pressure.

BACKGROUND/OBJECTIVES: Identifying critical periods of greater weight gain could provide useful information to combat the obesity epidemic. We tested whether body weight (BW), body fat percentage (BF%) and blood pressure (BP) changed during the holiday season (thanksgiving to new year's day) and the impact of regular exercise on these parameters. SUBJECTS/METHODS: A total of 48 males and 100 females (age 18-65 years) with a mean body mass index of 25.1±0.5 kg/m(2) were evaluated in mid-November (visit 1) and early January (visit 2; across 57±0.5 days). Anthropometric data, BF%, BP and self-reported exercise were recorded. RESULTS: Participants showed significant increases in BW (0.78±0.1 kg, P<0.001, 95% confidence interval (CI): 0.57-0.99), BF% (0.5±0.2%, P=0.007, 95% CI: 0.12-0.77), systolic blood pressure (SBP; 2.3±1.2 mm Hg, P=0.048, 95% CI: 0.01-4.63) and diastolic blood pressure (1.8±0.8 mm Hg, P=0.028, 95% CI: 0.20-3.49). Obese participants (35.2±0.8 kg/m(2)) showed a greater increase in BF% compared with normal weight participants (21.7±0.2 kg/m(2), P<0.05, 95% CI: 0.53-2.37) and a trend vs overweight participants (26.8±0.3 kg/m(2), P=0.07, 95% CI: -0.18-1.65). Exercise (4.8±0.6 h per week) did not protect against holiday weight gain and was not a significant predictor for changes in BW or BF%. Data are reported as means±s.e. CONCLUSION: Our participants gained an average of 0.78 kg, which indicates the majority of average annual weight gain (1 kg/y) reported by others may occur during the holiday season. Obese participants are most at risk as they showed the greatest increases in BF%. Initial BW, not exercise, significantly predicted BF% and BW gain.

Physician handwashing: what do parents want?

Transmission of micro-organisms from the hands of healthcare workers to patients is a major cause of healthcare-acquired infections. In 2002, the US Centers for Disease Control and Prevention (CDC) published guidelines for healthcare workers that included the recommendation for alcohol-based hand rub for hand hygiene during patient visits. In this prospective study we surveyed parental and healthcare workers' preferences for the hand hygiene practices of emergency physicians. The study comprised 99 parents of ill or injured children presenting to our emergency department and 100 healthcare providers (64 nurses, 29 physicians and seven nurse practitioners) within the department. There was a clear and similar preference by parents and healthcare workers for hand hygiene using soap and water over alcohol cleansing rubs. Furthermore, both groups preferred hand hygiene before and after the examination and wanted to observe the physician perform this procedure. In conclusion, families and healthcare worker preferences for hand hygiene are not in keeping with recommendations published by the CDC. Educational interventions are needed to disseminate the CDC's guidelines and to promote compliance with evidence-based recommendations for hand hygiene.

Stapled versus sutured gastrointestinal anastomoses in the trauma patient: a multicenter trial.

BACKGROUND: Construction of gastrointestinal anastomoses utilizing stapling devices has become a familiar procedure. In elective surgery, studies have shown no significant differences in complications between stapled and sutured anastomoses. Controversy has recently arisen regarding the accurate incidence of complications associated with anastomoses in the trauma patient. The objective of this multi-institutional study was to determine whether the incidence of postoperative complications differs between stapled and sutured anastomoses following the emergent repair of traumatic bowel injuries. METHODS: Using a retrospective cohort design, all trauma registry records from five Level I trauma centers over a period of 4 years were reviewed. RESULTS: A total of 199 patients with 289 anastomoses were identified. A surgical stapling device was used to create 175 separate anastomoses, while a hand-sutured method was employed in 114 anastomoses. A complication was defined as an anastomotic leak verified at reoperation, an intra-abdominal abscess, or an enterocutaneous fistula. The mean abdominal Abbreviated Injury Scale score and Injury Severity Score were similar in the two cohort groups. Stapling and suturing techniques were evenly distributed in both small and large bowel repairs. Seven of the total 175 stapled anastomoses and none of the 114 hand-sewn anastomoses resulted in a clinically significant leak requiring reoperation (RR = undefined, 95% CI 1.08-infinity, p = 0.04). Each anastomotic leak occurred in a separate individual. Nineteen stapled anastomoses and four sutured anastomoses were associated with an intra-abdominal abscess (RR = 2.7, 95% CI 0.96-7.57, p = 0.04). Enterocutaneous fistula formation was not statistically associated with either type of anastomoses (stapled cohort = 3 of 175 and sutured cohort = 2 of 114). Overall, 22 (13%) stapled anastomoses and 6 (5%) sutured anastomoses were associated with an intra-abdominal complication (RR = 2.08, 95% CI 0.89-4.86, p = 0.076). CONCLUSION: Anastomotic leaks and intra-abdominal abscesses appear to be more likely with stapled bowel repairs compared with sutured anastomoses in the injured patient. Caution should be exercised in deciding to staple a bowel anastomosis in the trauma patient.

Differential activation of wild-type and variant forms of estrogen receptor alpha by synthetic and natural estrogenic compounds using a promoter containing three estrogen-responsive elements.

Structure-dependent estrogen receptor alpha (ER alpha) agonist and antagonist activities of synthetic and natural estrogenic compounds were investigated in human HepG2, MDA-MB-231 and U2 cancer cell lines. Compounds used in this study include 4'-hydroxytamoxifen, ICI 182,780, bisphenol-A (BPA), 2',4',6'-trichloro-4-biphenylol (3Cl-PCB-OH), 2',3',4',5'-tetrachloro-4-biphenylol (4Cl-PCB-OH), p-t-octylphenol, p-nonylphenol, naringenin, kepone, resveratrol, and 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE). Cells were transfected with a construct (pERE(3)) containing three tandem estrogen responsive elements (EREs) and either wild-type estrogen receptor alpha (ER-wt) or variants expressing activation function-1 (ER-AF1) or AF-2 (ER-AF2). The ER agonist activities of the synthetic mono and dihydroxy aromatic compounds are comparable in all three-cell lines, whereas the activities of naringenin, kepone and resveratrol are dependent on cell context and expression of wild-type or variant forms of ER alpha. In contrast, the ER antagonist activities for these compounds were highly complex and, with the exception of 3Cl-PCB-OH, all compounds inhibited E2-induced wild-type or variant ER action. Results of this in vitro study suggest that the estrogenic and antiestrogenic activity of structurally diverse synthetic and natural estrogenic compounds is complex, and this is consistent with published data that often give contradictory results for these compounds.

Both serotonin and a nitric-oxide donor cause chloride secretion in rat colonocytes by stimulating cGMP.

BACKGROUND: Previous studies have demonstrated that an antagonist of nitric oxide synthase inhibits neurally mediated chloride secretion in response to serotonin (5-HT). The purpose of this study was to demonstrate that chloride secretion in rat colonocytes that were caused by stimulation of neural 5-HT receptors is mediated by way of a nitrergic pathway that involves the activation of guanylate cyclase. METHODS: The nitric oxide (NO) donor, diethylenetriamine/NO (DNO), was added to an enriched suspension of rat colonocytes that were preloaded with (36)Cl(-). In parallel experiments, DNO (1 micromol/L) was added to cells that were pretreated with the specific inhibitor of soluble guanylate cyclase, NS2028 (2 micromol/L). In additional studies, the neural 5-HT(3) receptor agonist, 2-methyl-5-HT (10 micromol/L), was added to the serosal surface of muscle-stripped sheets of rat colonic mucosa that were mounted in Ussing chambers under voltage clamp conditions, both in the absence and presence of NS2028 (20 mircro). RESULTS: DNO induced 18.0% +/- 8.0% greater (36)Cl(-) efflux than controls (P <.05; n = 14 animals). This efflux was abolished by previous treatment with NS2028. In the chamber experiments, 2-methyl-5-HT induced electrogenic chloride secretion that was significantly inhibited by previous treatment with NS2028 (2.2 +/- 0.5 microA/cm(2) vs 13.1 +/- 2.1 microA/cm(2); P <.001; n = 9 animals). CONCLUSIONS: The predominant secretomotor neurotransmitter that mediates the chloride secretory effects of 5-HT in vitro is nitric oxide. Both the secretory effect initiated at the 5-HT(3) receptor on enteric neurons and at the NO(-) receptor on the rat colonocytes are mediated through the activation of intracellular guanylate cyclase and the production of cyclic guanosine monophosphate.

Melanocyte repopulation in full-thickness wounds using a cell spray apparatus.

Melanocyte restoration is critical in reconstituting skin color. We developed a spotted (piebald) pig wound model to study methods of restoring melanocytes to the epidermis. Paired, full-thickness, porcine wounds were covered with nonpigmented, fully expanded, 3:1 meshed, split-thickness skin grafts and were sprayed with an epidermal cell suspension. The suspensions were highly pigmented skin (HPS) cell isolates for half of the wounds (n = 16) and nonpigmented skin (NPS) cell isolates for the remaining wounds (n = 16). Histologic sections showed 6.0 +/- 3.0 and 15 +/- 4.0 pigmented melanocytes per high-power field on days 8 and 20 in HPS-treated wounds and no pigmented melanocytes in NPS-treated wounds. Melanin pigment was dispersed in all layers of the epithelium for the HPS group on day 20 compared with a lack of melanin pigment observed in the NPS group. Cell spraying may provide a clinical method to restore color to skin; further work is needed to control the expression of melanin.

Penetrating esophageal injuries: multicenter study of the American Association for the Surgery of Trauma.

OBJECTIVE: The purpose of this study was to define the period of time after which delays in management incurred by investigations cause increased morbidity and mortality. The outcome study is intended to correlate time with death from esophageal causes, overall complications, esophageal related complications, and surgical intensive care unit length of stay. METHODS: This was a retrospective multicenter study involving 34 trauma centers in the United States, under the auspices of the American Association for the Surgery of Trauma Multi-institutional Trials Committee over a span of 10.5 years. Patients surviving to reach the operating room (OR) were divided into two groups: those that underwent diagnostic studies to identify their injuries (preoperative evaluation group) and those that went immediately to the OR (no preoperative evaluation group). Statistical methods included Fisher's exact test, Student's T test, and logistic regression analysis. RESULTS: The study involved 405 patients: 355 male patients (86.5%) and 50 female patients (13.5%). The mean Revised Trauma Score was 6.3, the mean Injury Severity Score was 28, and the mean time interval to the OR was 6.5 hours. There were associated injuries in 356 patients (88%), and an overall complication rate of 53.5%. Overall mortality was 78 of 405 (19%). Three hundred forty-six patients survived to reach the OR: 171 in the preoperative evaluation group and 175 in the no preoperative evaluation group. No statistically significant differences were noted in the two groups in the following parameters: number of patients, age, Injury Severity Score, admission blood pressure, anatomic location of injury (cervical or thoracic), surgical management (primary repair, resection and anastomosis, resection and diversion, flaps), number of associated injuries, and mortality. Average length of time to the OR was 13 hours in the preoperative evaluation group versus 1 hour in the no preoperative evaluation group (p < 0.001). Overall complications occurred in 134 in the preoperative evaluation group versus 87 in the no preoperative evaluation group (p < 0.001), and 74 (41%) esophageal related complications occurred in the preoperative evaluation group versus 32 (19%) in the no preoperative evaluation group (p = 0.003). Mean surgical intensive care unit length of stay was 11 days in the preoperative evaluation group versus 7 days in the no preoperative evaluation group (p = 0.012). Logistic regression analysis identified as independent risk factors for the development of esophageal related complications included time delays in preoperative evaluation (odds ratio, 3.13), American Association for the Surgery of Trauma Organ Injury Scale grade >2 (odds ratio, 2.62), and resection and diversion (odds ratio, 4.47). CONCLUSION: Esophageal injuries carry a high morbidity and mortality. Increased esophageal related morbidity occurs with the diagnostic workup and its inherent delay in operative repair of these injuries. For centers practicing selective management of penetrating neck injuries and transmediastinal gunshot wounds, rapid diagnosis and definitive repair should be made a high priority.

Transcriptional activation of deoxyribonucleic acid polymerase alpha gene expression in MCF-7 cells by 17 beta-estradiol.

Treatment of MCF-7 human breast cancer cells with 17beta-estradiol (E(2)) results in increased DNA synthesis and cell proliferation and enhanced enzyme activities associated with purine/pyrimidine biosynthesis. The mechanism of enhanced DNA polymerase alpha activity was investigated by analysis of the promoter region of this gene. E(2) induced luciferase (reporter gene) activity in MCF-7 cells transfected with pDNAP1, pDNAP2, and pDNAP3 containing -1515 to +45, -248 to +45 and -116 to +45 inserts from the DNA polymerase alpha gene promoter, whereas no induction was observed with pDNAP4 (-65 to +45 insert). The induction response was dependent on cotransfection with estrogen receptor alpha (ER(alpha)), and transactivation was also observed with a mutant ER(alpha) that did not express the DNA-binding domain. Subsequent functional, DNA binding, and DNA footprinting studies showed that a GC-rich region at -106 to -100 was required for E(2)-mediated transactivation, and Sp1 protein, but not ER(alpha), bound this sequence. Transcriptional activation of DNA polymerase alpha by E(2) is associated with ER(alpha)/Sp1 action at a proximal GC-rich promoter sequence, and this gene is among a growing list of E(2)-responsive genes that are induced via ER(alpha)/Sp1 protein interactions that do not require direct binding of the hormone receptor to DNA.

Assessment of adhesion assays for use with keratinocytes.

Cell attachment, as a biological process, is an important aspect with respect to graft survival and "take". With the ever-increasing use of cultured epithelial autografts for coverage and re-epithelialization of wounds, the assessment of keratinocyte adhesion in vitro has become a more common requirement in studies involving extracellular matrix proteins and their receptor molecules. Cell adhesion has been well-documented in immunological research, however keratinocyte adhesion has been investigated by manual counting (using methylene blue) or other less sensitive colorimetric methods. With the increase in number of fluorogenic probes available, their use as a sensitive alternative to radioactive labelling has been promoted in the literature. This study was carried out to investigate the possibility of using fluorescent probe 5,6-carboxyfluorescein diacetate succidimyl ester to achieve a more standardized assay in the assessment of keratinocyte adhesion. Adhesion was assessed on extracellular matrix proteins such as fibronectin, collagen types I & IV and laminin. We concluded that the fluorescent probe might provide greater sensitivity in measuring adhesion, however it may be cytotoxic to keratinocytes. Pre-labelling of keratinocytes may affect cellular functions such as adhesion and even proliferation and consequently the probe must be chosen with care.

Health tips for computer users.

Computers have changed everything about our world. Any change of this magnitude brings new challenges and new concerns for the long-term effects of exposure to the product. Computers especially pose specific risks to home care workers. This article reviews health and safety practices related to desktop and hand-held computers.

Crosstalk between estrogen receptor alpha and the aryl hydrocarbon receptor in breast cancer cells involves unidirectional activation of proteasomes.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxin that activates the aryl hydrocarbon receptor (AhR) and disrupts multiple endocrine signaling pathways. T47D human breast cancer cells express a functional estrogen receptor alpha (ERalpha) and AhR, and treatment of these cells with 17beta-estradiol (E2) or TCDD resulted in a rapid proteasome-dependent decrease in immunoreactive ERalpha and AhR proteins (>60-80%), respectively. E2 did not affect the AhR, whereas TCDD induced proteasome-dependent degradation of both the AhR and ERalpha in T47D and MCF-7 human breast cancer cells, and these responses were specifically blocked by proteasome inhibitors. Thus, TCDD-induced degradation of ERalpha may contribute to the antiestrogenic activity of AhR agonists and this pathway may be involved in AhR-mediated disruption of other endocrine responses.

Nitric oxide is a neurotransmitter in the chloride secretory response to serotonin in rat colon.

BACKGROUND: Serotonin (5-hydroxytryptamine [5-HT]) has been shown to induce chloride secretion through a nonadrenergic/noncholinergic neural pathway, mediated by a 5-HT(3) receptor. We hypothesized that 5-HT(3)-induced Cl(-) secretion is ultimately mediated by nitric oxide (NO). METHODS: Unstripped sheets of rat distal colon were mounted in Ussing chambers and short-circuited. The 5-HT(3) receptor agonist, 2-methyl-5-HT, was added in the absence and presence of the NO synthase inhibitor, L-NAME. Companion studies involved the addition of sodium nitroprusside to tissue that was incubated with or without tetrodotoxin. RESULTS: L-NAME caused a significant reduction in the 2-methyl-5-HT-induced change in circuit current, in a concentration-dependent manner. Sodium nitroprusside caused a change in circuit current over baseline in 5 minutes. The addition of tetrodotoxin did not significantly alter the change in circuit current; however, the apical Cl(-) channel blocker, anthracene-9-carboxylic acid, abolished this response. CONCLUSIONS: Neurally mediated Cl(-) secretion in response to 2-methyl-5-HT is inhibited by an NO synthase inhibitor. Exogenous NO mimics this response, which is unaffected by tetrodotoxin. These data suggest that neurally mediated serotoninergic Cl(-) secretion is, in part, mediated by NO. The ability of exogenous NO to induce a change in circuit current in the presence of tetrodotoxin suggests that NO is a final neurotransmitter in this neural-mucosal reflex and therefore acts directly on the enterocyte to induce secretion.

Vasoactive intestinal peptide is a neuropeptide mediator of the secretory response to serotonin in rat.

BACKGROUND: The chloride secretory response to serotonin (5-HT) has nonneural and neural mechanisms, the latter mediated through a 5-HT(3) receptor. We hypothesized that 5-HT(3)-induced C1(-) secretion is partially mediated by VIP as a neurosecretory transmitter. Therefore it should be inhibited by a VIP receptor antagonist, VIP 6-28. Furthermore, exogenous VIP should induce secretion in the presence of tetrodotoxin (TTX). METHODS: Unstripped sheets of rat colon (n = 6) were mounted in Ussing chambers. The 5-HT(3) receptor agonist 2-Me-5-HT (10 microM) was added in the absence and presence of VIP 6-28 (30 microM). In companion studies VIP (1 microM) was added to tissue with or without TTX. Changes in short-circuit current (DeltaI(SC)) were recorded and repeat-measure ANOVA was used to analyze data. RESULTS: Addition of 2-Me-5-HT induced a rise in DeltaI(SC) seen in controls at 1 to 5 min (3.2 +/- 1.5 to 12.3 +/- 3.7 microA/cm(2), P < 0.02). VIP 6-28 blunted DeltaI(SC) (1.2 +/- 0.4 to 3.7 +/- 1.3 microA/cm(2), P < 0.01). VIP caused DeltaI(SC) to increase above baseline in 15 min (4.7 +/- 2.6 to 10.4 +/- 3.0 microA/cm(2), P < 0.01). The addition of TTX prior to VIP did not alter DeltaI(SC). CONCLUSION: Activation of the neural 5-HT(3) receptor by 2-Me-5-HT induces a secretory response in rat colon that is inhibited by a VIP receptor antagonist. Exogenous VIP mimics this response and is unaffected by TTX. VIP is a likely nonadrenergic, noncholinergic neurotransmitter in this pathway.

Inhibition of vascular endothelial growth factor expression in HEC1A endometrial cancer cells through interactions of estrogen receptor alpha and Sp3 proteins.

Treatment of HEC1A endometrial cancer cells with 10 nm 17beta-estradiol (E2) resulted in decreased vascular endothelial growth factor (VEGF) mRNA expression, and a similar response was observed using a construct, pVEGF1, containing a VEGF gene promoter insert from -2018 to +50. In HEC1A cells transiently transfected with pVEGF1 and a series of deletion plasmids, it was shown that E2-dependent down-regulation was dependent on wild-type estrogen receptor alpha (ERalpha) and reversed by the anti-estrogen ICI 182, 780, and this response was not affected by progestins. Deletion analysis of the VEGF gene promoter identified an overlapping G/GC-rich site between -66 to -47 that was required for decreased transactivation by E2. Protein-DNA binding studies using electrophoretic mobility shift and DNA footprinting assays showed that both Sp1 and Sp3 proteins bound this region of the VEGF promoter. Coimmunoprecipitation and pull-down assays demonstrated that Sp3 and ERalpha proteins physically interact, and the interacting domains of both proteins are different from those previously observed for interactions between Sp1 and ERalpha proteins. Using a dominant negative form of Sp3 and transcriptional activation assays in Schneider SL-2 insect cells, it was confirmed that ERalpha-Sp3 interactions define a pathway for E2-mediated inhibition of gene expression, and this represents a new mechanism for decreased gene expression by E2.

Intestinal perforation secondary to Salmonella typhi: case report and review of the literature.

The case of a young woman presenting with fever, abdominal distention, and diarrhea is presented. While hospitalized, she developed peritonitis, and a laparotomy was performed emergently. Intraoperative and pathologic examinations are highly suggestive of Salmonella typhi as an etiology for her symptoms and eventual perforation. Salmonella enteritis can be a difficult diagnosis to make, but in most cases it is a self-limited disease process. In a minority of cases, multidrug antibiotic therapy may be required secondary to an increasing prevalence of resistant strains. Patients who perforate require prompt operation to limit morbidity and mortality. Outcome is significantly improved in those patients by directed resection of the affected segment of bowel and by aggressive perioperative care.

The treatment of hypopigmented lesions with cultured epithelial autograft.

Hypopigmentation may be a significant problem after burn injury. It is often difficult to predictably repair with conventional surgical techniques. It has been our experience that epidermal cells cultured from patients with dark skin produce pigment within the epidermal cell sheets, which indicates the presence of melanocytes. The presence of melanocytes and melanin in these cell sheets was demonstrated with the use of histochemical techniques. The results indicate that repigmentation with cultured epithelial autograft is possible. We describe a novel technique of dermabrasion and a co-culture of epidermal cells and melanocytes.

Sprayed keratinocyte suspensions accelerate epidermal coverage in a porcine microwound model.

Keratinocyte suspensions can potentially treat a variety of epidermal defects, but the mechanism of action has not been fully determined. We developed a porcine model to study the effect of sprayed cell suspensions delivered on small wounds within a meshed autograft. Paired full-thickness surgically excised wounds were covered with a fully expanded 3:1 meshed split-thickness autograft. A keratinocyte cell suspension was sprayed onto half of the wounds at a seeding density of 2.8 x 10(3) cells/cm2; the remaining wounds were sprayed with cell culture medium alone. Histologic analysis at days 5 and 8 showed an increase in average epidermal thickness, confluence, keratin cysts, and blood vessels in the keratinocyte cell suspension group compared with the cell culture medium control group. Wounds sprayed with the cell suspension showed faster and better quality of epithelialization than wounds sprayed with cell culture medium alone.