Evaluation of surgical outcomes of retro-rectus versus intraperitoneal reinforcement with bio-prosthetic mesh in the repair of contaminated ventral hernias.

INTRODUCTION: Hernia repairs in contaminated fields are often reinforced with a bioprosthetic mesh. When choosing which of the multiple musculofascial abdominal wall planes provides the most durable repair, there is little guidance. We hypothesized that the retro-rectus plane would reduce recurrence rates versus intraperitoneal placement due to greater surface area contact of mesh with well-vascularized tissue. METHODS: Forty-nine of the 80 patients in an ongoing, prospective, multicenter study of contaminated ventral hernia repairs (RICH study, NCT00617357) achieved fascial closure after musculofascial centralization and reinforcement with non-crosslinked porcine acellular dermal matrix (Strattice™, LifeCell, Branchburg, NJ) and were retrospectively analyzed. The Strattice was placed in the retro-rectus position in 23 patients and in the intraperitoneal position in 26. RESULTS: Subjects were comparable in age, obesity, prior wound infection, presence of a stoma, and infected mesh removal (p > 0.05). More smokers were present in the intraperitoneal group (p = 0.02). Retro-rectus defects were significantly wider and had larger area than the intraperitoneal repairs. At the 1-year follow-up, 44 (90%) of patients were available for review. There was no difference in wound infections, seromas, or hematomas. Recurrent hernias were identified in 10% of retro-rectus repairs and 30% of intraperitoneal repairs (p = 0.14). CONCLUSIONS: In this retrospective analysis of a prospective multicenter study of large, contaminated ventral hernias, despite a larger hernia defect in the retro-rectus group, placement of the mesh in the retro-rectus compartment resulted in a similar recurrence rate to intraperitoneal mesh placement. Ongoing evaluation is important to establish longer-term outcomes and the validity of these findings.

Abbreviated thoracotomy and temporary chest closure: an application of damage control after thoracic trauma.

HYPOTHESIS: Abbreviated thoracotomy, a damage-control strategy, improves survival in patients with metabolic exhaustion. DESIGN: Case series report. SETTING: University-based, level I trauma center. PATIENTS: All patients admitted to our trauma center with severe chest trauma in whom an abbreviated thoracotomy was performed between January 1, 1994, and January 1, 1998. INTERVENTIONS: Patients in whom an abbreviated thoracotomy was performed had their life-threatening thoracic injuries treated and had temporary closure of the incision. They were then resuscitated in the intensive care unit (ICU). Definitive care of injuries and formal chest closure were performed when physiological characteristics were normalized. MAIN OUTCOME MEASURES: Survival to discharge and postoperative complications. RESULTS: Of 10 787 patients admitted to the trauma center, 196 required thoracic operations. Eleven of these 196 patients underwent abbreviated thoracotomy; all patients survived to reach the ICU. Four died in the ICU within 24 hours of injury; the remaining 7 patients survived and were discharged. Based on their Trauma and Injury Severity Score, predicted mortality for our 11 patients was 59%; our mortality was 36%. Complications after abbreviated thoracotomy were similar to those seen after standard thoracotomy. CONCLUSIONS: Abbreviated thoracotomy is a useful strategy in the treatment of severe chest trauma. Its use in situations of metabolic exhaustion or planned reexploration may increase patient survival rates by expediting transfer of the patient from the operating room to the ICU, where homeostasis can be restored.

Comparison of zafirlukast (Accolate) absorption after oral and colonic administration in humans.

PURPOSE: This study characterized the gastrointestinal (GI) absorption of zafirlukast after oral and colonic administration in humans. METHODS: Five healthy subjects received zafirlukast solution (40 mg) orally and via an oroenteric tube into the colon in a randomized, crossover fashion. Two additional subjects were dosed into the distal ileum. Serial blood samples were obtained and plasma concentrations were quantitated by HPLC. RESULTS: Mean +/- SD pharmacokinetic parameters after oral vs. colonic administration were: AUC infinity of 2076 +/- 548 vs. 602 +/- 373 ng x h/mL, respectively, and Cmax of 697 +/- 314 vs. 194 +/- 316 ng/mL, respectively. Mean colon:oral AUCalpha and Cmax were 0.29 and 0.30, respectively. Median tmax values were 2.0 and 1.35 hr after oral and colonic administration. First-order absorption rate constants (Ka and Kac) were estimated from a two-compartment model with first-order elimination. Kac:Ka was <0.5 in 4 of the 5 subjects dosed in the colon. CONCLUSIONS: Zafirlukast was absorbed at multiple sites in the GI tract. The rate and extent of zafirlukast absorption was less after colonic than oral administration. Zafirlukast was significantly absorbed in the distal ileum. This study demonstrated that gamma scintigraphy, digital radiography, and fluoroscopy can be used to track the movement and confirm the location of the oroenteric tube in the GI tract.

Expression of naked plasmid DNA injected into the afferent and efferent vessels of rodent and dog livers.

A variety of reporter genes within plasmid constructs were injected into the afferent and efferent vessels of the liver in mice, rats, and dogs. Efficient plasmid expression was obtained following delivery via the portal vein, the hepatic vein, and the bile duct. The use of hyperosmotic injection solutions and occlusion of the blood outflow from the liver substantially increased the expression levels. Combining these surgical approaches with improved plasmid vectors enabled uncommonly high levels of foreign gene expression in which over 15 microg of luciferase protein/liver was produced in mice and over 50 microg in rats. Equally high levels of beta-galactosidase (beta-Gal) expression were obtained, in that over 5% of the hepatocytes had intense blue staining. Expression of luciferase or beta-Gal was evenly distributed in hepatocytes throughout the entire liver when either of the three routes were injected. Peri-acinar hepatocytes were preferentially transfected when the portal vein was injected in rats. These levels of foreign gene expression are among the highest levels obtained with nonviral vectors. Repetitive plasmid administration through the bile duct led to successive events of foreign gene expression. The integration of these findings into laboratory and clinical protocols is discussed.

Split tolerance induced by immunotoxin in a rhesus kidney allograft model.

BACKGROUND: Renal allografts were performed in rhesus monkeys using FN18-CRM9, a potent immunotoxin capable of depleting T cells to less than 1% of baseline levels in blood and lymph nodes, as a preparative agent. We have recently reported that animals pretreated with FN18-CRM9 1 week before transplantation without further immunosuppression had prolonged graft survival time compared with control animals, and frequently became tolerant. METHODS: This report examines the alloimmune responses of recipient monkeys to the donor, including cytotoxic T lymphocyte precursor (CTLp) frequency, mixed lymphocyte response, and antidonor IgG response. RESULTS: CTLp frequencies declined significantly (P<0.01) after FN18-CRM9 treatment and renal transplantation. This decline in CTLp was initially nonspecific, as CTLp frequencies against third-party animals also declined (P<0.01). The decrease in CTLp was maintained in five of five animals tested 6 months after transplant. However, unresponsiveness was limited to the CTL arm of the immune response as antidonor IgG was detected in four of four animals tested, and the 5-day mixed lymphocyte response stimulation index and relative response were not significantly different before and after transplant. In long-term survivors (>150 days), an increase in anti-third-party CTLp was detected 1 month after grafting with third-party skin. No change was seen in the antidonor CTLp frequency after donor skin grafting, indicating that a specific defect in the antidonor CTL response had developed. CONCLUSIONS: These data suggest that FN18-CRM9 treatment of rhesus monkeys allows the development of specific down-regulation of antidonor CTL activity in renal allograft recipients.

FN18-CRM9 immunotoxin promotes tolerance in primate renal allografts.

BACKGROUND: Transplant tolerance, rather than immunity, may be favored in the setting of a lower mature lymphoid mass in the recipient induced by anti-T cell agents. A novel immunosuppressive agent, FN18-CRM9, known to specifically kill T cells with great potency, was evaluated in a transplant model. METHODS: In order to ablate recipient T cells, the immunotoxin FN18-CRM9 was administered to rhesus monkey recipients of MHC-mismatched renal allografts. Donor lymphocytes were injected intrathymically into some animals. RESULTS: All monkeys with T-cell depletion by immunotoxin had prolonged allograft survival, and tolerance confirmed by skin grafting has been confirmed in five of six long-surviving recipients. CONCLUSIONS: In this clinically relevant model, profound but transient T-cell depletion by a single agent substantially promotes tolerance.

Dopamine does not enhance furosemide-induced natriuresis in patients with congestive heart failure.

The objective of this study was to determine whether the addition of low-dose (renal-dose) dopamine to furosemide therapy enhances natriuresis in patients with compensated congestive heart failure, New York Heart Association Class II or III. We performed a randomized, controlled, open-label, crossover study wherein urinary sodium, creatinine, and furosemide excretion rates and GFR determined by inulin clearance rates were measured during each of three treatment interventions: furosemide infusion alone, dopamine infusion alone, and furosemide and dopamine infusions administered concurrently. Six of eight recruited subjects (4 male, 2 female) were able to complete the study. The baseline sodium excretion rate after equilibration on a metabolic diet was 6.7 +/- 0.7 mEq (mean +/- SE) over 3 h. Infusion of dopamine alone caused a slight nonsignificant increase in natriuresis to 36.7 +/- 8.5 mEq/3 h. Furosemide alone markedly increased sodium excretion to 276.6 +/- 47.2 mEq/3 h. No significant additional increment in natriuresis occurred when dopamine and furosemide were administered concurrently (253.8 +/- 73.6 mEq/3 h). Neither dopamine, furosemide, or their coadministration affected GFR. In conclusion, infusion of low-dose dopamine does not enhance furosemide-induced urinary sodium excretion rates in patients with compensated congestive heart failure, New York Heart Association Class II or III.

Using electronic medical records to predict mortality in primary care patients with heart disease: prognostic power and pathophysiologic implications.

OBJECTIVE: To identify high-risk patients with heart disease by using data stored in an electronic medical record system to predict six-year mortality. DESIGN: Retrospective cohort study. SETTING: Academic primary care general internal medicine practice affiliated with an urban teaching hospital with a state-of-the-art electronic medical record system. PATIENTS: Of 2,434 patients with evidence of ischemic heart disease or heart failure or both who visited an urban primary care practice in 1986, half were used to derive a proportional hazards model, and half were used to validate it. MEASUREMENTS: Mortality from any cause within six years of inception date. Model discrimination was assessed with the C statistic, and goodness-of-fit was measured with a calibration curve and Hosmer-Lemeshow statistic. MAIN RESULTS: Of these patients 82% had evidence of ischemic heart disease, 53% heart failure, and 35% both conditions. Mean survival among the 653 (27%) who died was 2.8 years; mean follow-up among survivors was 5.0 years. Those with both heart conditions had the highest mortality rate (45% at 6 years), followed by isolated heart failure (39%) and ischemic heart disease (18%). Of 300 potential predictive characteristics, 100 passed a univariate screen and were submitted to maltivariable proportional hazards regression. Twelve variables contributed independent predictive information: age, weight, more than one previous hospitalization for heart failure, and nine conditions indicated on diagnostic tests and problem lists. No drug treatment variables were independent predictors. The model C statistic was 0.76 in the derivation sample of patients and 0.74 in a randomly selected validation sample, and it was well calibrated. Patients in the lowest and highest quartiles of risk differed more than five-fold in their average risk. CONCLUSIONS: Routine clinical data stored in patients electronic medical records are capable of predicting mortality among patients with heart disease. This could allow increasingly scarce health care resources to be focused on those at highest mortality risk.

Computerizing guidelines to improve care and patient outcomes: the example of heart failure.

Increasing amounts of medical knowledge, clinical data, and patient expectations have created a fertile environment for developing and using clinical practice guidelines. Electronic medical records have provided an opportunity to invoke guidelines during the everyday practice of clinical medicine to improve health care quality and control costs. In this paper, efforts to incorporate complex guidelines [those for heart failure from the Agency for Health Care Policy and Research (AHCPR)] into a network of physicians' interactive microcomputer workstations are reported. The task proved difficult because the guidelines often lack explicit definitions (e.g., for symptom severity and adverse events) that are necessary to navigate the AHCPR algorithm. They also focus more on errors of omission (not doing the right thing) than on errors of commission (doing the wrong thing) and do not account for comorbid conditions, concurrent drug therapy, or the timing of most interventions and follow-up. As they stand, the heart failure guidelines give good general guidance to individual practitioners, but cannot be used to assess quality or care without extensive "translation" into the local environment. Specific recommendations are made so that future guidelines will prove useful to a wide range of prospective users.

Bioavailability, pharmacokinetics, and pharmacodynamics of torsemide and furosemide in patients with congestive heart failure.

The bioavailability, pharmacokinetics, and pharmacodynamics of torsemide (10 mg orally and intravenously) and furosemide (40 mg orally and 20 mg intravenously) were determined in a randomized crossover clinical trial in 16 patients with compensated congestive heart failure. Torsemide (time to reach maximum concentration [tmax], 1.1 +/- 0.9 hour) was more rapidly absorbed than furosemide (tmax, 2.4 +/- 2.5 hours), the absorption of which was delayed compared with that in healthy volunteers. Bioavailability of torsemide was also greater and less variable than that of furosemide. All four treatments yielded comparable changes from baseline in 24-hour electrolyte excretion. Based on the relationships between sodium excretion rate and fractional sodium and urinary drug excretion rate, response to both diuretic agents at the level of the nephron was decreased compared with previous studies with healthy subjects. Assessment of the clinical relevance, if any, of the difference in the variability of absorption warrants further study.

Free-tissue transfer with the aid of loupe magnification: experience with 251 procedures.

Eight years ago, the principal author (Shenaq) began employing high-power ocular loupes for microvascular anastomoses. Subsequently, 251 free-tissue transfers were performed with loupes as the sole means of magnification. Procedures included free flaps, toe-to-hand transfers, and digital replantations, with the external diameter of the vascular pedicles averaging 1.5 mm. Analysis of the series revealed a 97.2 percent overall success rate, a 1.2 percent partial flap necrosis rate, and an 8.3 percent revision rate for anastomoses (during the initial operative procedure), which compare favorably with the success rates frequently cited for microscope-assisted procedures. The most favorable results were achieved with free flaps and toe-to-hand transfers with 98.5 and 96.4 percent success rates, respectively. The 79.2 percent survival rate achieved with digital replantation falls within the range (74.0 to 94.2 percent) reported in the literature. This experience indicates that in practiced hands, high-power ocular loupes provide an alternative to the operating microscope for microvascular anastomosis of vessels 1.0 mm or greater in diameter. Loupe use is advocated on the grounds of cost-effectiveness, portability, and operator freedom.

How to help diabetic patients avoid amputation. Prevention and management of foot ulcers.

Foot ulcers are a weighty complication of diabetes whose significance is often underestimated. They are associated with a high degree of morbidity and mortality, and treatment is laborious and costly. The problem of susceptibility to foot ulceration is best addressed through a prevention program emphasizing patient education, pedal hygiene, regular follow-up visits, and lifestyle modification. Such programs are most efficiently administered by a healthcare team. When ulcers do occur, it is important to take a systematic approach to management, stressing infection control, metabolic stabilization, thorough debridement, and meticulous wound care.

The pharmacodynamics of torsemide in patients with congestive heart failure.

The pharmacodynamics of torsemide (a new loop diuretic of the pyridine sulfonylurea class) was studied in 16 subjects who had compensated congestive heart failure and had been receiving stable diuretic therapy. Oral doses of 50, 100, and 200 mg were studied by use of a randomized crossover design. The results of this study show that the pharmacokinetics of torsemide is linear up to at least a dose of 200 mg in patients with congestive heart failure. Approximately 20% of each of the three doses was excreted unchanged, consistent with previous findings in healthy volunteers. A hyperbolic relationship between diuretic effect and drug excretion rate was defined. The maximum urinary sodium excretion rate attained was about 0.6 mEq/min, which is about 20% of that in healthy subjects, indicating diuretic resistance in these patients. Although there was no saturation of the urinary excretory pathway with doses as high as 200 mg, the upper plateau of the dose-response curve was reached with doses of 50 mg, indicating that this dose represents a ceiling dose in patients with New York Heart Association class II and III congestive heart failure.

Colonic bacterial flora and serum cholesterol: alterations induced by dietary citrus pectin.

The influence of dietary pectin on blood lipids and stool bacterial flora, enzyme activity, and physical properties was investigated. Fifteen grams of citrus pectin were added to the normal diets of 10 subjects. A decrease in serum cholesterol was observed after 2 wk of dietary supplementation, but was not statistically significant after the 3rd wk. Fecal bacterial flora was modified by pectin; anaerobic bacteria increased and aerobic bacteria increased. No change in stool bacterial 7 alpha dehydroxylase or cholesterol dehydrogenase activity was observed. The daily stool output, pH, and water content were not influenced by the addition of pectin to the diet.

Reaction of enzyme-bound 5-deazaflavin with peroxides. Pyrimidine ring contraction via an epoxide intermediate.

Reaction of peroxides with 5-deazaflavin bound to glucose oxidase, lactate oxidase, or D-amino acid oxidase results in the formation of 5-deazaflavin 4a, 5-epoxide. The reaction of D-amino acid oxidase with m-chloroperoxybenzoate is an exception since the reagent reacts rapidly with the protein moiety to form m-chlorobenzoate which then binds noncovalently near the unmodified coenzyme. Epoxide bound to glucose oxidase is converted to deazaFAD X X in a reaction similar to that observed previously with oxynitrilase and glycolate oxidase. With lactate oxidase the epoxide is quite stable in the absence of light. With D-amino acid oxidase, denaturation of the protein is accompanied by the release of the epoxide into solution where it decomposes in a manner similar to that observed with model epoxide compounds at neutral pH. Reaction of deazaFAD X X with phosphodiesterase and alkaline phosphatase yields deazariboflavin X X. The same compound has been formed in model studies by exposing 5-deazariboflavin 4a,5-epoxide to alkaline conditions. Structural studies indicate that this reaction involves contraction of the pyrimidine ring to yield 4-ribityl-6,7-dimethyloxazolo[ 4,5-b ]quinolin-2(4H)-one. Model reaction studies are consistent with a mechanism initiated by alkaline hydrolysis of the pyrimidine ring at position 4 followed by two additional steps which proceed at neutral pH. A similar mechanism for the enzyme reactions appears likely since analogous intermediates are detected in the glycolate oxidase and the model reactions. The results suggest that position 4 of the coenzyme in oxynitrilase, glycolate oxidase, and glucose oxidase must be accessible to solvent and that the protein moiety must facilitate the initial hydrolysis of the pyrimidine ring since the enzyme reactions occur at neutral pH. Failure to observe formation of deazaFMN X X with lactate oxidase is attributed, at least in part, to the inaccessibility of the pyrimidine ring to solvent.