The effect of clomethiazole on plasma concentrations of interleukin-6, -8, -1beta,tumor necrosis factor-alpha,and neutrophil adhesion molecule expression during experimental extracorporeal circulation

Clomethiazole (CMZ), a neuroprotective drug, has antiinflammatory actions. We investigated the effects of CMZ administration on plasma concentrations of interleukin (IL)-6, IL-8, IL-1beta, tumor necrosis factor-alpha, and neutrophil adhesion molecule expression during experimental extracorporeal circulation. Five healthy volunteers each donated 500 mL of blood, which was subsequently divided into equal portions. Identical extracorporeal circuits were simultaneously primed with donated blood (250 mL) and circulated for 2 h at 37 degrees C. CMZ was added to 1 of the circuits of each pair to achieve a total plasma concentration of 40 micro mol/L. Blood samples were withdrawn at (i) donation, (ii) immediately after addition of CMZ, and at (iii) 30, 60, 90, and 120 min after commencing circulation. Plasma concentrations of IL-6, IL-8, and tumor necrosis factor-alpha were less in the CMZ group compared with control after 60 min of circulation (2.2 [0.3] versus 3.2 [0.4], 14.9 [4.8] versus 21.9 [18.4], 63.3 [43.5] versus 132.2 [118.9] pg/mL, respectively, P < 0.05). After 120 min of circulation, neutrophils from CMZ-treated circuits showed significantly less CD18 expression compared with control (237.5 [97.4] versus 280.5 [111.5], P = 0.03). The addition of CMZ to experimental extracorporeal circuits decreases the inflammatory response. This effect may be of clinical benefit by decreasing inflammatory-mediated neurological injury during cardiopulmonary bypass. IMPLICATIONS: Enhancement of gamma-aminobutyric acid(A)-mediated effects by clomethiazole (CMZ) and associated neuroprotection has been established in animal models of cerebral ischemia. In an ex vivo study, we demonstrated antiinflammatory activity of CMZ in experimental extracorporeal circulation. This represents a potential neuroprotective mechanism of CMZ in patients undergoing coronary artery bypass surgery.     

Roux-en-Y gastric bypass leak complications

HYPOTHESIS: Enteric leakage is a significant complication of the Roux-en-Y gastric bypass (RYGB) procedure that can be treated successfully. DESIGN: Retrospective study of 400 consecutive RYGB patients from 1999-2002. SETTING: Community hospital with a university surgical residency. PATIENTS: Hospital records of 400 morbidly obese patients who underwent gastric bypass surgery were reviewed. MAIN OUTCOME MEASURES: Time of discovery of leak, location of leak, treatment, hospital stay, and mortality. RESULTS: Twenty-one patients (5.25%) developed leaks. The mean body mass index (calculated as weight in kilograms divided by the square of height in meters) was 54.2. Thirteen patients were noted to develop a leak at the gastrojejunal anastomosis, with an average time to diagnosis of 7.0 days. Five of these patients underwent reexploration, and 8 were successfully treated with percutaneous drainage alone. Four patients developed leaks at the jejunojejunal anastomosis (mean time to diagnosis, 2.0 days). All of these patients required exploration, and 2 patients died. Four patients were noted to have leaks in other areas (average time to diagnosis, 3.5 days). Two patients were treated with drainage, and 2 underwent exploration. The average hospital stay of all patients was 33 days. CONCLUSIONS: Enteric leakage is a significant complication of the RYGB. Patients who are suspected of having an enteric leak because of signs of sepsis or hemodynamic instability require emergent exploration. Leaks that are more insidious may be treated successfully with percutaneous drainage. Aggressive exploration of patients who appear to be septic, and percutaneous drainage of insidiously developing leaks may decrease patients' morbidity and mortality.     

The effect of paramedic rapid sequence intubation on outcome in patients with severe traumatic brain injury

OBJECTIVE: To evaluate the effect of paramedic rapid sequence intubation (RSI) on outcome in patients with severe traumatic brain injury. METHODS: Adult major trauma victims were prospectively enrolled over two years using the following inclusion criteria: Glasgow Coma Scale (GCS) 3-8, suspected head injury by mechanism or physical examination, transport time > 10," and inability to intubate without RSI. Midazolam and succinylcholine were administered before laryngoscopy; rocuronium was given after tube placement was confirmed using physical examination, capnometry, syringe aspiration, and pulse oximetry. The Combitube was used as a salvage airway device. For this analysis, trial patients were excluded for absence of a head injury (Head/Neck AIS score < 2), failure to fulfill major trauma outcome study criteria, unsuccessful intubation or Combitube insertion, or death in the field or in the resuscitation suite within 30" of arrival. Each study patient was hand matched to three nonintubated historical controls from our trauma registry using the following parameters: age, sex, mechanism of injury, trauma center, and AIS score for each body system. Controls were excluded for Head/Neck AIS defined by a c-spine injury or death in the field or in the resuscitation suite within 30" of arrival. chi 2, odds ratios, and logistic regression were used to investigate the impact of RSI on the primary outcome measures of mortality and incidence of a "good outcome," defined as discharge to home, rehabilitation, psychiatric facility, jail, or signing out against medical advice. RESULTS: A total of 209 trial patients were hand matched to 627 controls. The groups were similar with regard to all matching parameters, admission vital signs, frequency of specific head injury diagnoses, and incidence of invasive procedures. Mortality was significantly increased in the trial cohort versus controls for all patients (33.0% versus 24.2%, p < 0.05) and in those with Head/Neck AIS scores of 3 or greater (41.1% versus 30.3%, p < 0.05). The incidence of a "good outcome" was lower in the trial cohort versus controls (45.5% versus 57.9%, p < 0.01). Factors that may have contributed to the increase in mortality include transient hypoxia, inadvertent hyperventilation, and longer scene times associated with the RSI procedure. CONCLUSION: Paramedic RSI protocols to facilitate intubation of head-injured patients were associated with an increase in mortality and decrease in good outcomes versus matched historical controls.     

Staged repair of tetralogy of Fallot and diminutive pulmonary arteries with a fenestrated ventricular septal defect patch

OBJECTIVES: Patients with tetralogy of Fallot and diminutive pulmonary arteries are at risk for suprasystemic right ventricular pressure and right ventricular failure after complete repair. We report the short-term outcome and medium-term follow-up after using a fenestrated ventricular septal defect patch as a component of staged repair in selected patients. METHODS: We reviewed 47 patients with tetralogy of Fallot and diminutive pulmonary arteries whose ventricular septal defect patch was fenestrated, either electively or as a rescue technique, at a single institution between 1984 and 2001. RESULTS: Early mortality was 10.6% and occurred only in patients who underwent rescue fenestration. Review of medium-term follow-up (median, 39 months) revealed 4 late deaths; an additional 4 patients experienced right ventricular failure despite fenestration. Most (7/8) of these late events occurred in patients who underwent planned fenestration. Excessive left-to-right shunt through the fenestration developed in only 2 patients. CONCLUSIONS: Fenestrated patch closure of the ventricular septal defect in patients with tetralogy of Fallot and diminutive pulmonary arteries resulted in 10.6% early mortality. Used preemptively in selected patients, this technique is associated with no surgical mortality and a low incidence of excessive left-to-right shunt (4%). Early survivors remain at risk for late death and right ventricular failure despite fenestration.     

Cytology of morcellated renal specimens: significance in diagnosis and dissemination

PURPOSE: Controversy surrounds the process of morcellation for retrieving laparoscopically removed specimens. The inability to assess tumor stage, increased difficulty in pathological examination and the potential for tumor spillage are cited as significant disadvantages of the technique. We examined cytological findings in bag washings after laparoscopic nephrectomy for benign and malignant diseases. MATERIALS AND METHODS: We prospectively obtained cytology washings from the retrieval bag after laparoscopic nephrectomy and manual morcellation. In 22 consecutive cases after specimen fragmentation in a LapSac (Cook Urological, Spencer, Indiana) the bag was thoroughly irrigated with 30 cc normal saline. This wash was then processed by ThinPrep (Cytyc Corp., Marlborough, Massachusetts) and stained with Papanicolaou stain. Standard pathological examination of the morcellated specimen was performed to determine renal histology. RESULTS: The histological diagnosis was clear cell renal carcinoma in 10 cases, multicystic renal carcinoma in 2, papillary renal cell carcinoma in 1, angiomyolipoma in 1, and oncocytoma in 1. Bag cytological results were accurate in 9 of 13 patients with carcinoma (69%), while in 3 cytological study provided additional information. In all 9 cases of benign histology, cytological findings were consistent with benign cellular features. Neoplastic cells were easily detected and classified into type and grade. CONCLUSIONS: Cytological examination of LapSac washings after specimen morcellation provided a pathological diagnosis in the majority of patients. This method may complement existing techniques and be useful for increasing the accuracy of pathological analysis of morcellated specimens. In addition, these data suggest that malignant cells are liberated during the morcellation process, which has significant implications for potential tumor dissemination.     

Physical activity determinants of military health care recipients

This study describes physical activity determinants (motivation, self-efficacy, benefits/barriers, and stage of change) of 71 healthy, military-affiliated volunteers, 28 men and 43 women (mean age, 31 +/- 7 years) from a military primary care setting. The physical activity determinants were measured with investigator-administered questionnaires at three time points over 8 months. The Kruskal-Wallis analysis of variance indicated that there were significant differences (p < 0.0001) among factors determining self-efficacy, motivation, and benefits/barriers. The subjects reported being most confident that they could be physically active even if they had to do it by themselves. The chief benefit reported was an improvement in physical performance, whereas the leading barrier to physical activity was the physical exertion involved. The biggest motivator was the positive health effect gained. Most subjects considered themselves to be in the "maintenance" stage of change. This study provides a platform for the development of an effective physical activity intervention in this population.     

Accuracy of image fusion of normal upper abdominal organs visualized with PET/CT

Although PET/CT scanners have the potential for precise fused registration of structures visualized on both PET and CT, physiological motion during the acquisition of both studies may alter the appearance of organ shape, size or location. The degree of possible mismatch in abdominal organ size and position between PET and CT has not been evaluated. The aim of this study was to assess the consistency in location and measured size of upper abdominal organs with PET and CT using a combined PET/CT system. Forty-six consecutive inpatients who underwent clinical PET/CT scans for suspected cancer were evaluated. CT and PET images attenuation corrected by both CT and germanium-68 transmission scans were obtained, and we separately determined the location of the top and bottom (height), anterior and posterior margins (thickness), and right and left margins (width) for each organ, including liver, spleen, and bilateral kidneys, using CT and both sets of PET images. Differences between the two modalities in terms of location and measured organ size were investigated. In the upper margin of the liver and lower margin of the spleen, more than 10% of the cases showed a larger discrepancy (>20 mm) between CT-based and Ge-corrected PET-based measurements, although the differences in the positions of the edges were less than 10 mm in most cases. The center of the liver tended to be located cephalad and to the right of the body, and that of the spleen tended to be cephalad and posterior on PET, as compared with CT. Moreover, the center of both kidneys tended to be seen cephalad, posterior, and to the right on PET. The liver appeared slightly larger on PET than CT in thickness (CT vs CT-corrected PET vs Ge-corrected PET = 156 mm vs 162 mm vs 162 mm) and width (186 mm vs 189 mm vs 188 mm). By contrast, the spleen appeared slightly smaller on PET than CT in height (84 mm vs 77 mm vs 80 mm) and width (85 mm vs 81 mm vs 80 mm). A similar tendency was observed in the left kidney (105 mm vs 100 mm vs 99 mm in height, and 64 mm vs 59 mm vs 58 mm in width) and the right kidney (99 mm vs 93 mm vs 93 mm in height, and 64 mm vs 59 mm vs 60 mm in width). These differences between the two modalities were statistically significant ( P<0.05). In conclusion, minor mismatches in location and organ size were found to exist between CT and PET images, in part due to physiological motion. Although these differences could potentially affect the quality of the image registrations, they were generally of a modest nature.     

Induction of tolerance in a rat model of laryngeal transplantation

BACKGROUND: The major limitation preventing expansion of laryngeal transplantation as a therapeutic modality is the necessity of lifelong immunosuppression. In this report, we describe an immunomodulatory strategy for tolerance induction in laryngeal allotransplantation that permits escape from chronic immunosuppression. MATERIALS AND METHODS: Larynges were transplanted from Lewis-Brown-Norway (RT1l/n, F1) donors to Lewis (RT1l) recipients. Recipients received 7 days of treatment with tacrolimus and mouse anti-rat alphabeta T-cell-receptor (TCR) monoclonal antibodies. Histology, mixed lymphocyte reaction (MLR), skin grafting, and flow cytometry assessed functional tolerance, efficacy of immunodepletion, and donor-specific chimerism. RESULTS: All 10 recipients survived until sacrifice at 100 days. Histology suggested functional allograft tolerance. Skin grafting, MLR, and flow cytometry revealed that tolerance is neither donor-specific nor related to systemic immunocompromise. CONCLUSIONS: In this rat laryngeal-transplantation model, functional tolerance was induced under combined tacrolimus and alphabeta TCR protocol. Mechanisms responsible for this tolerance induction require future elucidation.     

Airway anastomotic dehiscence associated with use of sirolimus immediately after lung transplantation

GOAL: The goal of this study was to assess the efficacy of sirolimus in lung-transplant recipients. METHODS: The study was designed as a single center, consecutive case study of lung-transplant recipients treated with sirolimus, tacrolimus, and prednisone. All study subjects also received an HMG-CoA reductase inhibitor, and prophylaxis for cytomegalovirus and Pneumocystis carinii. RESULTS: A total of 15 subjects were enrolled in the study. Within 6 months, significant airway complications occurred in four subjects, three of whom died. At that point, the investigators terminated enrollment in the study. The study population was compared retrospectively with a group of 83 consecutive lung recipients treated with cyclosporine (n=64) or tacrolimus (n=19), mycophenolate mofetil, and prednisone. This confirmed an increased incidence of airway dehiscence and reduced survival in the sirolimus-treated patients. Sirolimus-treated patients had a low incidence of acute rejection. No significant differences were noted in the incidence of bacterial or fungal bronchopulmonary infections. CONCLUSIONS: We observed an unexpectedly high incidence of postoperative airway dehiscence in lung-transplant recipients treated with sirolimus, in combination with tacrolimus, prednisone, and an HMG-CoA inhibitor. Further studies will be needed to determine the safety and efficacy of using sirolimus after complete airway healing has occurred.