PubMed Health⌕ Search

Biomedical subjects

Nicolas V Christou

Publications and source records attributed to Nicolas V Christou.

17 recordsLinked to original sources
PubMed2006

Weight gain after short- and long-limb gastric bypass in patients followed for longer than 10 years.

OBJECTIVE: To complete a long-term (>10 years) follow-up of patients undergoing isolated roux-en-Y gastric bypass for severe obesity. BACKGROUND: Long-term results of gastric bypass in patients followed for longer than 10 years is not reported in the literature. METHODS: Accurate weights were recorded on 228 of 272 (83.8%) of patients at a mean of 11.4 years (range, 4.7-14.9 years) after surgery. Results were documented on an individual basis for both long- and short-limb gastric bypass and compared with results at the nadir BMI and % excess weight loss (%EWL) at 5 years and >10 years post surgery. RESULTS: There was a significant (P < 0.0001) increase in BMI in both morbidly obese (BMI < 50 kg/m) and super obese patients (BMI > 50 kg/m) from the nadir to 5 years and from 5 to 10 years. The super obese lost more rapidly from time zero and gained more rapidly after reaching the lowest weight at approximately 2 years than the morbidly obese patients. There was no difference in results between the long- and short-limb operations. There was a significant increase in failures and decrease in excellent results at 10 years when compared with 5 years. The failure rate when all patients are followed for at least 10 years was 20.4% for morbidly obese patients and 34.9% for super obese patients. CONCLUSIONS: The gastric bypass limb length does not impact long-term weight loss. Significant weight gain occurs continuously in patients after reaching the nadir weight following gastric bypass. Despite this weight gain, the long-term mortality remains low at 3.1%.

Adult↗
PubMed2005

Pre- and post-prandial plasma ghrelin levels do not correlate with satiety or failure to achieve a successful outcome after Roux-en-Y gastric bypass.

BACKGROUND: We tested the hypothesis that the amount of weight lost after Roux-en-Y gastric bypass (RYGBP) correlates with plasma ghrelin levels. METHODS: 36 morbidly obese patients were studied 3 years after RYGBP (6 men, 30 women) with mean initial BMI 51 kg/m2 and 8 healthy controls (2 men, 6 women) with mean BMI 25 kg/m2. Subjects consumed a light breakfast, and the first blood sample was drawn at 1200 hrs immediately before lunch and the second sample at 1400 hrs. Satiety was assessed using a Visual Analog Scale (VAS). Patients were stratified as success (current BMI <35) or failures (current BMI > or =35). RESULTS: Plasma ghrelin levels were significantly lower in patients after RYGBP (269 +/- 66 pcg/ml) compared with lean controls (616 +/- 112 pcg/ml, P<0.001). Ghrelin levels pre or post meals were not different between patients who had a successful weight loss (preoperative BMI 47, current BMI 29, 72% EWL) or those who achieved a less then ideal weight loss (preoperative BMI 48, current BMI 41, 29% EWL). There was no correlation between any of the VAS scores and plasma ghrelin. There was a strong inverse correlation between pre-prandial ghrelin levels and the preoperative or current BMI. CONCLUSION: Failure to lose weight after RYGBP does not correlate with pre- or post-prandial ghrelin plasma levels. Ghrelin levels were inversely proportional to BMI and did not correlate with satiety. These data do not support a role for higher plasma ghrelin levels for inadequate weight loss after RYGBP.

Adult↗
PubMed2004

Intra-abdominal sepsis attenuates local inflammation-mediated increases in microvascular permeability at remote sites in mice in vivo.

BACKGROUND: Given that leukocyte delivery to remote sites is diminished in states of systemic inflammation, such as sepsis, and activated leukocytes may be responsible for endothelial injury leading to vascular leakage, we hypothesized that intra-abdominal sepsis would diminish microvascular leakage at remote sites by altering leukocyte-endothelial interactions. METHODS: Using a murine intravital microscopy model, we examined leukocyte-endothelial interactions and vascular leakage at a peripheral site in the presence of local and/or systemic inflammation. Forty mice were randomized to 1 of 4 study groups: local infection (orchitis), systemic infection (intra-abdominal sepsis by cecal ligation and puncture), local and systemic infection, and control. Postcapillary venules of the cremaster muscle were examined by bright light and fluorescence intravital microscopy. Microvascular leakage was determined after intravenous administration of fluorescent albumin. RESULTS: Systemic infection attenuated the increases in both leukocyte adherence and local infection-induced microvascular permeability. Neutrophil cell-surface expression of L-selectin, as determined by flow cytometry, diminished with both local and systemic infection, whereas expression of CD11b increased with systemic, but not local, infection. CONCLUSIONS: These data suggest that systemic (intra-abdominal) sepsis diminishes local inflammation-mediated vascular leakage by attenuating leukocyte adherence.

Abdomen↗
PubMed2004

Surgery decreases long-term mortality, morbidity, and health care use in morbidly obese patients.

OBJECTIVE: This study tested the hypothesis that weight-reduction (bariatric) surgery reduces long-term mortality in morbidly obese patients. BACKGROUND: Obesity is a significant cause of morbidity and mortality. The impact of surgically induced, long-term weight loss on this mortality is unknown. METHODS: We used an observational 2-cohort study. The treatment cohort (n = 1035) included patients having undergone bariatric surgery at the McGill University Health Centre between 1986 and 2002. The control group (n = 5746) included age- and gender-matched severely obese patients who had not undergone weight-reduction surgery identified from the Quebec provincial health insurance database. Subjects with medical conditions (other then morbid obesity) at cohort-inception into the study were excluded. The cohorts were followed for a maximum of 5 years from inception. RESULTS: The cohorts were well matched for age, gender, and duration of follow-up. Bariatric surgery resulted in significant reduction in mean percent excess weight loss (67.1%, P < 0.001). Bariatric surgery patients had significant risk reductions for developing cardiovascular, cancer, endocrine, infectious, psychiatric, and mental disorders compared with controls, with the exception of hematologic (no difference) and digestive diseases (increased rates in the bariatric cohort). The mortality rate in the bariatric surgery cohort was 0.68% compared with 6.17% in controls (relative risk 0.11, 95% confidence interval 0.04-0.27), which translates to a reduction in the relative risk of death by 89%. CONCLUSIONS: This study shows that weight-loss surgery significantly decreases overall mortality as well as the development of new health-related conditions in morbidly obese patients.

Adult↗
PubMed2004

The impact of weight reduction surgery on health-care costs in morbidly obese patients.

BACKGROUND: The treatment of obesity and related comorbidities are significant financial burdens and sources of resource expenditure. This study was conducted in order to assess the impact of weight-reduction surgery on health-related costs. METHODS: This was an observational two-cohort study. The treatment cohort included patients having undergone weight-reduction (bariatric) surgery at the McGill University Health Centre (MUHC) between 1986 and 2002. The control group included age and gender matched obese patients who had not undergone weight-reduction surgery from the Quebec provincial health insurance database (RAMQ). The cohorts were followed for a maximum of 5 years from inception. The primary outcome measure was overall direct healthcare costs. Secondary outcomes included cost analysis by diagnostic category for the treatment of new medical conditions following cohort inception. RESULTS: The cohorts were well-matched for age, gender and duration of follow-up. Patients having undergone bariatric surgery had significant reductions in mean percent initial excess weight loss (67.1%, P <0.001) and in percent change in initial body mass index (34.6%, P <0.001). Bariatric surgery patients had higher total costs for hospitalizations (per 1,000 patients) in the first year following cohort inception (surgery cohort = CDN 12,461,938 dollars; control cohort = CDN 3,609,680 dollars). At 5 years after cohort inception, average cumulative costs for operated patients were CDN 19,516,667 dollars versus CDN 25,264,608 dollars, for an absolute difference of almost CDN 6,000,000 dollars per 1,000 patients. CONCLUSION: Weight-reduction surgery in morbidly obese patients produces effective weight loss and decreases long-term direct health-care costs. The initial costs of surgery can be amortized over 3.5 years.

Body Mass Index↗
PubMed2004

Analysis of the incidence and risk factors for wound infections in open bariatric surgery.

BACKGROUND: Our clinical impression derived from >95% follow-up of patients was that our wound infection rate was higher than the 1-10% reported in the literature. The purpose of this study was to determine the incidence and risk factors for wound infection in open bariatric surgery. METHODS: We queried our prospectively acquired bariatric surgery outcomes database, and retrospectively audited the charts of patients operated from April 1 to March 31, 2003. Risk categories were obtained using the National Nosocomial Infection Surveillance (NNIS) definitions and stratification. Expected site-specific rates were adjusted for duration of operation, degree of wound contamination, and underlying disease condition. RESULTS: 269 patients undergoing a standardized open Roux-en-Y gastric bypass were studied. The mean age (SD) was 39.5 (10.5) years and the mean BMI was 54.3 (9.9). Operating time averaged 63 (17) minutes, and length of stay was 4.1 (1.3) days. Based on NNIS categories 10.9 wound infections were expected, but 54 were observed, for a rate of 20%. Bacterial isolates included S. aureus (39%), alpha-hemolytic strep (26%), Enterococcus (16%), P.mirabilis (9%), and multiple other bacteria at 10%. Epidural analgesia and delayed antibiotic prophylaxis administration (after the incision was made) increased the odds of developing a wound infection, whereas gender, age, BMI, duration of surgery, and incidence of diabetes had no effect. There was a high correlation between wound infection and subsequent incisional hernia formation. CONCLUSION: The incidence of wound infections following open bariatric surgery is high, and the current recommendations for antibiotic prophylaxis are ineffective. As these infections carry significant morbidity, effective methods to prevent them are needed.

Adult↗
PubMed2003

Science review: Cell membrane expression (connectivity) regulates neutrophil delivery, function and clearance.

As the principal cellular component of the inflammatory host defense and contributor to host injury after severe physiologic insult, the neutrophil is inherently coupled to patient outcome in both health and disease. Extensive research has focused on the mechanisms that regulate neutrophil delivery, function, and clearance from the inflammatory microenvironment. The neutrophil cell membrane mediates the interaction of the neutrophil with the extracellular environment; it expresses a complex array of adhesion molecules and receptors for various ligands, including mediators, cytokines, immunoglobulins, and membrane molecules on other cells. This article presents a review and analysis of the evidence that the neutrophil membrane plays a central role in regulating neutrophil delivery (production, rolling, adhesion, diapedesis, and chemotaxis), function (priming and activation, microbicidal activity, and neutrophil-mediated host injury), and clearance (apoptosis and necrosis). In addition, we review how change in neutrophil membrane expression is synonymous with change in neutrophil function in vivo. Employing a complementary analysis of the neutrophil as a complex system, neutrophil membrane expression may be regarded as a measure of neutrophil connectivity, with altered patterns of connectivity representing functionally distinct neutrophil states. Thus, not only does the neutrophil membrane mediate the processes that characterize the neutrophil lifecycle, but characterization of neutrophil membrane expression represents a technology with which to evaluate neutrophil function.

Antigens, CD↗
PubMed2003

Hypertonic saline resuscitation attenuates neutrophil lung sequestration and transmigration by diminishing leukocyte-endothelial interactions in a two-hit model of hemorrhagic shock and infection.

BACKGROUND: Hypertonic saline (HTS) attenuates polymorphonuclear neutrophil (PMN)-mediated tissue injury after hemorrhagic shock. We hypothesized that HTS resuscitation reduces early in vivo endothelial cell (EC)-PMN interactions and late lung PMN sequestration in a two-hit model of hemorrhagic shock followed by mimicked infection. METHODS: Thirty-two mice were hemorrhaged (40 mm Hg) for 60 minutes and then given intratracheal lipopolysaccharide (10 microg) 1 hour after resuscitation with shed blood and either HTS (4 mL/kg 7.5% NaCl) or Ringer's lactate (RL) (twice shed blood volume). Eleven controls were not manipulated. Cremaster intravital microscopy quantified 5-hour EC-PMN adherence, myeloperoxidase assay assessed lung PMN content (2 1/2 and 24 hours), and lung histology determined 24-hour PMN transmigration. RESULTS: Compared with RL, HTS animals displayed 55% less 5-hour EC-PMN adherence (p = 0.01), 61% lower 24-hour lung myeloperoxidase ( p= 0.007), and 57% lower mean 24-hour lung histologic score ( p= 0.027). CONCLUSION: Compared with RL, HTS resuscitation attenuates early EC-PMN adhesion and late lung PMN accumulation in hemorrhagic shock followed by inflammation. HTS resuscitation may attenuate PMN-mediated organ damage.

Animals↗
PubMed2003

Ertapenem versus piperacillin/tazobactam in the treatment of complicated intraabdominal infections: results of a double-blind, randomized comparative phase III trial.

OBJECTIVE: To examine the clinical efficacy and safety of ertapenem, a novel beta-lactam agent with wide activity against common pathogens encountered in intraabdominal infection. SUMMARY BACKGROUND DATA: Ertapenem has a pharmacokinetic profile and antimicrobial spectrum that support the potential for use as a once-a-day agent for the treatment of common mixed aerobic and anaerobic infections. METHODS This prospective, randomized, controlled, and double-blind trial was conducted to compare the safety and efficacy of ertapenem with piperacillin/tazobactam as therapy following adequate surgical management of complicated intraabdominal infections. RESULTS: Six hundred thirty-three patients were included in the modified intent-to-treat population, with 396 meeting all criteria for the evaluable population. Patients with a wide range of infections were enrolled; perforated or abscessed appendicitis was most common (approximately 60% in microbiologically evaluable population). A prospective, expert panel review was conducted to assess the adequacy of surgical source control in patients who were failures as a component of evaluability. For the modified intent-to-treat groups, 245 of 311 patients treated with ertapenem (79.3%) were cured, as were 232 of 304 (76.2) treated with piperacillin/tazobactam. One hundred seventy-six of 203 microbiologically evaluable patients treated with ertapenem (86.7%) were cured, as were 157 of the 193 (81.2%) treated with piperacillin/tazobactam. CONCLUSIONS: In this study, the efficacy of ertapenem 1 g once a day was equivalent to piperacillin/tazobactam 3.375 g every 6 hours in the treatment of a range of intraabdominal infections. Ertapenem was generally well tolerated and had a similar safety and tolerability profile to piperacillin/tazobactam. A formal process for review of adequacy of source control was found to be of benefit. The results of this trial suggest that ertapenem may be a useful option that could eliminate the need for combination and/or multidosed antibiotic regimens for the empiric treatment of intraabdominal infections.

Abdominal Abscess↗
PubMed2003

Hypertonic saline and the microcirculation.

The systemic inflammation that occurs in shock states is believed to promote overexuberant microcirculatory activation, the release of toxic proteases and oxygen radicals causing microvascular damage, and subsequent tissue and organ injury. Although shock-associated microvascular failure is often unresolved after standard resuscitation, hypertonic saline (HTS) appears to reduce microvascular collapse, restoring vital nutritional blood flow. In addition, hypertonic fluids tend to blunt the up-regulation of leukocyte and endothelial adhesion molecules that occurs with isotonic resuscitation of shock. Recently, direct evaluation by intravital microscopy has shown that HTS resuscitation dampens the interactions between leukocytes, platelets, and endothelium found with Ringer's lactate resuscitation. Furthermore, fewer cellular interactions have been correlated with attenuation in microvascular wall permeability after resuscitation with HTS. Better characterization of microcirculatory effects by hypertonic saline may provide mechanisms for improved morbidity and mortality associated with hypertonic resuscitation.

Fluid Therapy↗
PubMed2002

Alteration of chemoattractant receptor expression regulates human neutrophil chemotaxis in vivo.

OBJECTIVE: To elucidate the mechanisms that regulate human neutrophil delivery in vivo, as well as the mechanisms that lead to observed reduction in polymorphonuclear (PMN) delivery to remote sites in septic patients. METHODS: Alterations in human PMN chemoattractant receptor expression and chemotactic function in vivo were evaluated in two distinct experiments: exudate PMNs (PMNs that have undergone transmigration to skin window blisters in controls) and septic PMNs (circulating PMNs from septic patients in the intensive care unit) were both separately compared with control circulating PMNs. RESULTS: Exudate PMNs displayed increased C5a receptors and C5a chemotaxis, and reduced interleukin-8 receptors (both IL-8 RA and IL-8 RB) and IL-8 chemotaxis. Septic PMNs displayed reduced C5a and IL-8 receptors and decreased C5a chemotaxis but no change in IL-8 chemotaxis. IL-8 but not C5a receptor gene expression decreased in parallel to receptor alteration. CONCLUSIONS: These results suggest that change in PMN chemoattractant receptor expression serves to regulate PMN chemotaxis in vivo; that exudate PMN chemotaxis depends more on C5a than IL-8; and that diminished chemoattractant receptors and chemotaxis in septic PMNs may explain decreased PMN delivery in these patients.

Chemotaxis, Leukocyte↗
PubMed2002

Hypertonic saline resuscitation of hemorrhagic shock diminishes neutrophil rolling and adherence to endothelium and reduces in vivo vascular leakage.

OBJECTIVE: To evaluate the in vivo effects of hypertonic saline (HTS) resuscitation on the interactions of endothelial cells (ECs) and polymorphonuclear neutrophils (PMNs) and vascular permeability after hemorrhagic shock. SUMMARY BACKGROUND DATA: The PMN has been implicated in the pathogenesis of EC damage and organ injury following hemorrhagic shock. Compared to Ringer's lactate (RL), HTS resuscitation diminishes PMN and EC adhesion molecule expression and organ sequestration of PMNs. METHODS: In a murine model of hemorrhagic shock (50 mmHg for 45 minutes followed by resuscitation) using intravital microscopy on cremaster muscle, the authors studied PMN-EC interactions and vascular leakage (epifluorescence after 50 mg/kg fluorescent albumin) in three resuscitation groups: HTS (shed blood + 4 cc/kg 7.5% HTS, n = 12), RL (shed blood + RL [2x shed blood volume], n = 12), and sham (no hemorrhage or resuscitation, n = 9). EC ICAM-1 expression was evaluated by immunohistochemistry. Data, presented as mean +/- SEM, were evaluated by analysis of variance with Bonferroni correction. RESULTS: There were no differences between groups in flow mechanics. Compared to RL, HTS animals (t = 90 minutes) displayed diminished PMN rolling and PMN adhesion to EC at time intervals beyond t = 0. There were no differences between the sham and HTS groups. Vascular leakage was 45% lower in HTS than in RL-resuscitated animals. Cremaster EC ICAM-1 expression was similar in the two groups. CONCLUSIONS: Using HTS instead of RL to resuscitate hemorrhagic shock diminishes vascular permeability in vivo by altering PMN-EC interactions. HTS could serve as a novel means of immunomodulation in hemorrhagic shock victims, potentially reducing PMN-mediated tissue injury.

Animals↗
PubMed2002

Soluble L-selectin attenuates tumor necrosis factor-alpha-mediated leukocyte adherence and vascular permeability: a protective role for elevated soluble L-selectin in sepsis.

OBJECTIVE: We have previously demonstrated that leukocyte delivery to remote sites is decreased in sepsis and that increased concentrations of soluble L-selectin are, in part, responsible for this finding. Given that leukocytes have been implicated in the pathogenesis of vascular leakage, we hypothesized that the elevated soluble L-selectin concentrations in sepsis may translate into decreased inflammation-mediated leukocyte-endothelial cell interactions and vascular leakage at these sites. DESIGN: Prospective, controlled animal study. SETTING: Surgical research laboratory in a university hospital. SUBJECTS: Swiss white male mice weighing 25-35 g. INTERVENTIONS: Mice were randomized to one of three study groups: intracremaster tumor necrosis factor-alpha with subsequent intravenous bicarbonate buffered solution; intracremaster tumor necrosis factor-alpha with intravenous soluble L-selectin (10 microg/mL); and intracremaster bicarbonate buffered solution with intravenous bicarbonate buffered solution. The cremaster muscle was prepared for both light and fluorescence intravital microscopy 2 hrs after intracremaster injection, and fluorescein isothiocyanate-labeled albumin was injected intravenously. Leukocyte-endothelial interactions (rolling flux, rolling velocity, and adherence) were counted off-line. Postcapillary venule leakage was determined by the permeability index (perivenular/intravenular fluorescence) after intravenous injection of fluorescent albumin. MEASUREMENTS AND MAIN RESULTS: Soluble L-selectin significantly attenuated tumor necrosis factor-alpha-mediated increases in leukocyte adherence and vascular leakage. Leukocyte rolling velocity was restored to baseline with soluble L-selectin; however, rolling flux was not altered. Blood pressure, shear rate, and leukocyte counts did not differ between groups. CONCLUSIONS: Soluble L-selectin decreases local inflammation-mediated leukocyte adherence and vascular leakage in vivo. The increased concentrations of soluble L-selectin in sepsis may represent a protective mechanism by which the host attempts to diminish the deleterious systemic effects of activated leukocytes during sepsis.

Animals↗
PubMed2002

Pilot study examining the frequency of several gene polymorphisms in a morbidly obese population.

BACKGROUND: Obesity is a growing problem and is associated with numerous medical conditions. Several polymorphisms have been associated with lipid metabolism and obesity: PPAR-gamma2-Pro115Gln, PPARgamma2-Pro12Ala, beta3AR-Trp64Arg and SR-BI IVS5 C > T. We examined the frequency of these polymorphisms in patients with a BMI > 40 and compared them to individuals with a BMI < 30. Our hypothesis was that these polymorphisms would occur more frequently in the obese population. METHODS: This case-control study examined 126 individuals with a BMI > 40 in the McGill University Health Centre Bariatric Surgery Program and 102 individuals (controls) with a BMI < 30 attending a Lipid Clinic. DNA was extracted from whole blood by standard techniques. The polymorphisms were determined by polymerase chain reaction (PCR) and restriction genotyping. RESULTS: A significant difference between controls and the morbidly obese group was observed for 2 of 4 polymorphisms. The carrier frequency for PPARgamma2-Pro12Ala was 24.8% in the obese group and 12.9% in controls (odds ratio = 2.2; 95% CI = 1.1-4.4; P = 0.02). The carrier frequency for SR-BI IVS5 C > T was 22.8% in obese individuals versus 8.1% in controls (odds ratio = 3.5; 95% CI = 1.6-7.7; P = 0.002). There were no differences in frequency of diabetes in both obese (13/104) and control (9/126) groups (odds ratio = 1.86, 95% CI = 0.76 < O.R. < 4.54, P = 0.184). CONCLUSIONS: These results underscore the relationship between gene polymorphisms and obesity. Obese individuals may differ from non-obese individuals in the gene polymorphisms associated with metabolic control.

CD36 Antigens↗