Primary blast lung injury simulator: a new computerised model.

Mathematical modelling and computational simulation are becoming increasingly important tools in many fields of medicine where in vivo studies are expensive, difficult or impractical. This is particularly the case with primary blast lung injury, and in this paper, we give a brief overview of mathematical models before describing how we generated our blast lung injury simulator and describe some early results of its use.

Primary blast lung injury - a review.

Bomb or explosion-blast injuries are likely to be increasingly encountered as terrorist activity increases and pre-hospital medical care improves. We therefore reviewed the epidemiology, pathophysiology and treatment of primary blast lung injury. In addition to contemporary military publications and expert recommendation, an EMBASE and MEDLINE search of English speaking journals was undertaken using the medical subject headings (MeSHs) 'blast injury' and 'lung injury'. Review articles, retrospective case series, and controlled animal modelling studies published since 2000 were evaluated. 6-11% of military casualties in recent conflicts have suffered primary blast lung injury but the incidence increases to more than 90% in terrorist attacks occurring in enclosed spaces such as trains. The majority of victims require mechanical ventilation and intensive care management. Specific therapies do not exist and treatment is supportive utilizing current best practice. Understanding the consequences and supportive therapies available to treat primary blast lung injury are important for anaesthetists.

Prone position ventilation in the Role 2 Afloat environment.

Prone position ventilation is a life-saving technique for the management of hypoxic respiratory failure in ventilated patients. It has particular application in the isolated Role 2 Afloat (R2A) environment where both human and material resources are limited. It can be achieved with minimal training. This article describes the rationale behind prone position ventilation and equips the reader with the knowledge base that will allow the technique to be instigated.

Establishing and maintaining a robust Role 2 Afloat organisation within the Royal Naval Medical Services.

In 2009, the Royal Navy (RN) reconfigured the Role 2 maritime medical treatment capability, the Role 2 Afloat (R2A). This capability is now firmly established on a number of platforms in the fleet and was recently externally validated on RFA MOUNTS BAY prior to completion of an operational deployment supporting contingency operations in the Mediterranean. This article outlines the future challenges for R2A and offers suggestions on how to maintain a robust R2A organisation within the Royal Naval Medical Service (RNMS).

HLA-DR4 and pulmonary dysfunction in rheumatoid arthritis.

Rheumatoid arthritis is associated with an increased frequency of the B cell alloantigen HLA-DR4, and preliminary work has suggested an association between HLA-DR4 and obstructive lung disease in subjects with rheumatoid arthritis. To prospectively evaluate the influence of HLA-DR4 on pulmonary involvement in patients with rheumatoid arthritis, pulmonary function was measured in four groups of subjects with rheumatoid arthritis in whom HLA-DR4 and smoking status was known: 16 DR4-positive smokers (six current and 10 exsmokers), 16 DR4-negative smokers (six current and 10 exsmokers), eight DR4-positive nonsmokers, and eight DR4-negative nonsmokers. Significant reductions in one-second forced expiratory volume and forced vital capacity were observed in DR4-positive subjects compared with DR4-negative subjects irrespective of cigarette smoking status. In addition, patients with keratoconjunctivitis sicca (secondary Sjögren's syndrome) demonstrated significant reductions in one-second forced expiratory volume, forced vital capacity, and ratio of one-second forced expiratory volume to forced vital capacity compared with those patients without evidence of secondary Sjögren's syndrome. It is concluded that the presence of the HLA-DR4 antigen and secondary Sjögren's syndrome are associated with abnormal pulmonary function in patients with rheumatoid arthritis.

HLA-DQw alloantigens and pulmonary dysfunction in rheumatoid arthritis.

HLA-DR4 and keratoconjunctivitis sicca (secondary Sjögren's syndrome) are associated with abnormal pulmonary function in patients with rheumatoid arthritis. Since recent investigations have found that much of the genomic polymorphism of the HLA-DR4 haplotype comes from the closely linked DQw allele, we reanalyzed this set of data to evaluate the relationship between the DQw allotypes and pulmonary function in rheumatoid arthritis. Using a step-wise regression analysis, we found that the presence of DQw1 was a stronger predictor of an abnormal forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and carbon monoxide diffusing capacity (D) than the presence of DR4, keratoconjunctivitis sicca, smoking status, or any other clinical parameter. DQw1-positive patients had a mean (+/- SD) percent of predicted FEV1, FVC, and D of 84.2 (+/- 19.8), 88.0 (+/- 17.9) and 85.6 (+/- 20.9) percent, respectively, all significantly lower than DQw-1 negative patients (p = 0.02, 0.02, and 0.03). Smokers with the heterozygous phenotype, DQw1/DQw3, tended to have obstructive disease of the airways, with a mean (+/- SD) FEV1 of 80.1 +/- 24.4 percent of predicted, compared to 95.7 +/- 12.1 percent of predicted in DQw1/DQw3-negative individuals (p = 0.03). Patients who had a DQw2 allele were more likely to have normal pulmonary function. We conclude that the HLA-DQw1 allotype is a strong predictor of abnormal pulmonary function and that it may identify smoking subjects with rheumatoid arthritis subjects who are prone to develop obstruction of airflow.

Relationship of cardiovascular risk factors to racial differences in femoral bypass surgery and abdominal aortic aneurysmectomy in Massachusetts.

UNLABELLED: Atherosclerosis is more severe in blacks than in whites, but abdominal aortic aneurysms, which have traditionally been thought to have an atherosclerotic etiology, appear to be less common in blacks. Because of this incongruity, we compared risk factor profiles in patients undergoing abdominal aortic aneurysm repair and patients undergoing femoral bypass for atherosclerotic occlusive disease. A dual case-control study was conducted, first, comparing patients who had undergone aneurysmectomy to a control group of patients who had undergone appendectomy; and then comparing patients who had undergone femoral bypass surgery to the same appendectomy controls. We initially used hospital discharge data for the entire state of Massachusetts and, in a second phase, data obtained from a review of medical records from Boston University Medical Center Hospital and Boston City Hospital. The statewide database indicated that rates of femoral bypass surgery were higher in blacks than in whites, but after adjusting for differences in hypertension, diabetes, and low socioeconomic status, the black/white odds ratio for femoral bypass fell to 1.44 (95% confidence interval: 1.08, 1.92). A similar analysis based on the hospital chart review, provided better control of confounding and indicated that there was no racial difference in rates of femoral bypass after correcting for other risk factors (odds ratio = 0.94; 95% confidence interval: 0.40, 2.22; p = 0.90). In contrast, the statewide database found higher rates of abdominal aortic aneurysm surgery in whites, and particularly in white males. Smoking and hypertension were strong risk factors for aneurysmectomy, but diabetes mellitus and socioeconomic status were not. After adjusting for other variables, the black/white odds ratio for aneurysmectomy was 0.29 (95% confidence interval: 0.07, 1.23; p = 0.09). CONCLUSIONS: Substantial differences are found in the risk factor profiles for aneurysmal disease and femoral atherosclerotic occlusive disease. Diabetes is a particularly strong risk factor for femoral disease, but not for aneurysmal disease. In addition, blacks had higher rates of femoral bypass surgery in Massachusetts, but the apparent racial difference appeared to be due to a greater prevalence of hypertension, smoking, and diabetes in blacks. In contrast, abdominal aortic aneurysms occurred predominantly in white males, and adjustment for other risk factors further accentuated the greater risk in whites.

Increases in gallbladder prostaglandin synthesis before the formation of cholesterol gallstones.

Increased synthesis of prostaglandins in the wall of the gallbladder may play a role in the pathogenesis of cholesterol gallstones by mediating mucus hypersecretion and thereby accelerating nucleation and the precipitation of cholesterol-supersaturated bile. We induced gallstones in prairie dogs and guinea pigs by feeding a cholesterol-supplemented diet for periods as long as 6 weeks. Gallbladder prostaglandin synthesis was quantitated by specific radioimmunoassays that measured the amount of various prostanoids released from the gallbladder during in vitro incubation. The gallbladders of cholesterol-fed prairie dogs showed increased synthesis of prostaglandin E2, prostaglandin F2a, and thromboxane and increased concentrations of glycoprotein in gallbladder bile. These changes were evident as early as 2 weeks after institution of the cholesterol diet, although cholesterol gallstones did not form until 4 or more weeks. In contrast, cholesterol feeding of the guinea pig did not induce cholesterol supersaturation. In this species pigment gallstones formed, probably as a result of a cholesterol-induced hemolytic anemia, and gallbladder mucus hypersecretion did not occur. Pigment gallstone formation in the guinea pig was associated with an increase in prostacyclin synthesis, but the synthesis of prostaglandin F2a and thromboxane was decreased. Increased prostaglandin synthesis may contribute to the formation of cholesterol gallstones but does not appear to participate in pigment gallstone formation.

Risks of synchronous gastrointestinal or biliary surgery with splenectomy for hematologic disease.

BACKGROUND: The addition of splenectomy to a gastrointestinal (GI) operation may have an adverse effect on mortality, morbidity, and even survival. OBJECTIVE: To determine the risks of the converse: synchronous GI surgery appended to splenectomy for hematologic diseases. DESIGN: Retrospective cohort. SETTING: Multiple hospitals comprising an affiliated surgical training program. PATIENTS: Consecutive sample of 207 adults (mean age, 49 years) with splenectomies for hematologic diseases. INTERVENTION: Splenectomy and concomitant GI or biliary surgery (group 1, n=19) and splenectomy alone (group 2, n=188). MAIN OUTCOME MEASURES: Length of hospital or intensive care unit stay, later operations, postoperative infections, postoperative abdominal abscess, major complications, and death. RESULTS: Preoperative and intraoperative factors were similar in both groups. Operative mortality was 3 of 19 in group 1 and 8 of 188 in group 2 (p=.07). The mean number of major complications tended to be higher in group 1 (1.5 vs 0.5, P=07). Despite no difference between the incidences of overall postoperative infections, patients in group 1 were much more likely to develop an abdominal abscess (4 of 19 vs 3 of 188, P=.002). Logistic regression established that patients undergoing splenectomy and synchronous GI or biliary surgery were 25 times more likely to develop an intra-abdominal abscess than were patients with splenectomy alone, even controlling for confounding factors (odds ratio, 24.7; 95% confidence interval, 3.1 to 196; P=.002). CONCLUSIONS: Synchronous GI or biliary surgery with splenectomy for hematologic disease increases the risk of intra-abdominal abscess and should be avoided. Complication and mortality rates may also be increased.

Ileal pouch salvage following failed ileal pouch- anal anastomosis.

Attempts have been made to salvage failed ileal pouch-anal anastomoses (IPAA) performed for ulcerative colitis or familial polyposis coli. These can be categorized as total reconstruction of the IPAA, partial transabdominal approach, and partial transperineal approach. The aims of our study were to determine the overall success of pouch salvage; to examine the demographics, indications, and outcomes for each approach; and to assess anorectal physiology and patient satisfaction in those with successful salvage operations. We reviewed data, including results of anorectal manometry, from 29 patients undergoing salvage procedures for failed IPAA. Seventeen salvage attempts were successful, 11 attempts failed, and one patient was lost to follow-up. Success rates were 100% in the total reconstruction group, 25% in the partial transabdominal group, and 55% in the transperineal group. In those undergoing total reconstruction of the IPAA (n = 9), functional outcome, as measured by incontinence, improved with 50% reporting incontinence preoperatively compared to 0% postoperatively (P = 0.055). Mean 24-hour stool frequency and nighttime stool frequency declined. All patients reported satisfaction with their outcomes. Sixty percent of patients who underwent ileal pouch salvage following IPAA have been successful in avoiding permanent ileostomy. These results suggest that a continued effort to salvage failed IPAA, including the use of total reconstruction, is a viable alternative to permanent ileostomy.

Functional outcomes in limb salvage vascular surgery.

BACKGROUND: The crisis in health care brings a new focus to defining successful outcomes of medical treatments. The surgical literature has been criticized for not assessing functional outcomes in addition to technical success. METHODS: We evaluated the functional outcomes of limb salvage surgery over 3 years in 38 patients 65 years of age and older with limb-threatening ischemia. The RAND-36-Item Health Survey 1.0 was used as a health assessment tool. RESULTS: In spite of an 80% limb salvage rate, only 58% of patients survived 3 years and only 25% survived with the index limb and were able to walk. The RAND scores of patients whose limbs were amputated did not significantly differ from those of patients whose surgery was successful. CONCLUSION: Functional outcome goals need to be better defined for patients who need limb salvage vascular operations to enhance the quality of care given these patients and to be in concert with emerging health policy.

Is splenectomy more dangerous for massive spleens?

BACKGROUND: Reports vary about whether risks are greater for removal of massive (> or = 1500 g) spleens than for smaller (< 1500 g) spleens. We sought to determine the hazards of splenectomy. METHODS: We reviewed 223 consecutive adults with elective splenectomies for hematologic diseases. Morbidity and mortality rates were combined with published data to create a meta-analysis. RESULTS: Patients with massive spleens are more likely to have postoperative complications (relative risk [RR] 2.1, 95% confidence interval [CI] 1.3 to 3.4; P = 0.003) and death (RR 4.7, 95% CI, 1.5 to 15.1; P = 0.01). However, when the investigation is restricted to comparable diagnoses, patients with massive spleens do not differ from those with smaller spleens regarding complications (RR 1.4, 95% CI, 0.8 to 2.7; P = 0.3) or mortality (RR 2.1, 95% CI, 0.5 to 9.7; P = 0.4). These observations are confirmed by metaanalysis. Furthermore, multivariate analysis indicts age as a critical risk of complications and death. CONCLUSIONS: Increased age and underlying illness are the predominant factors associated with morbidity and mortality following splenectomy for hematologic disease. Adjusting for age and diagnosis, spleen size is not a hazard.

Intravenous glutamine fails to improve gut morphology after radiation injury.

Male Sprague-Dawley rats housed in individual metabolic cages received total parenteral nutrients via chronic indwelling internal jugular catheters to determine whether supplementing parenteral nutrition with glutamine would accelerate recovery of small-bowel morphology after abdominal radiation. After recovering from catheter insertion for 3 days they received either 1000 cGy gamma radiation to the abdomen only or no radiation and immediately thereafter received isonitrogenous and isocaloric intravenous solutions containing either 0% or 2% glutamine at 1.58 mL/h for the next 5 days. Intestinal segments were then assayed for whole-bowel deoxyribose nucleic acid content and villus height. Irradiation caused a 40% decrement in these parameters, which were not restored by glutamine supplementation. Therefore, intravenous glutamine supplementation failed to accelerate recovery of small-bowel morphology in this model of combined surgical and radiation injury.

Intestinal consumption of intravenously administered fuels.

Total parenteral nutrition has been extensively used to feed patients with a variety of gastrointestinal diseases, but little attention has focused on the nutritional requirements of the gut. To investigate intestinal consumption of intravenously administered nutrients, uptake of three principal fuels determined from in vitro studies was quantitated in seven awake, unrestrained dogs. Portal blood flow was measured by a dye dilution technique and, simultaneously, substrate samples were obtained from chronic indwelling arterial and portal venous catheters. Studies were performed during a postabsorptive basal period and during separate infusions of glutamine (0.10 mmol/kg X min), glucose (0.10 mmol/kg X min), and beta-hydroxybutyrate, (0.40 mmol/kg X min). During the basal period there was a significant arterial-portal vein gradient for glucose (144 +/- 26 mumol/liter) and glutamine (49 +/- 11 mumol/liter). These substances were taken up by the gut at rates of 4.11 +/- 1.23 and 1.43 +/- 0.19 mumol/kg X min, respectively. No significant uptake of beta-hydroxybutyrate was determined in the basal studies (0.27 +/- 0.10 mumol/kg X min). During substrate infusion, gut glucose uptake was unchanged (2.68 +/- 1.67 mumol/kg X min, NS), but consumption of glutamine (4.60 +/- 0.66 mumol/kg X min, p less than 0.001) and beta-hydroxybutyrate (4.33 +/- 0.71 mumol/kg X min, p less than 0.001) increased significantly. During parenteral feedings in patients with gastrointestinal disorders, circulating levels of beta-hydroxybutyrate and glutamine are often low, and glutamine is absent from standard amino acid solutions. Current parenteral formulation may not provide appropriate fuels for the gastrointestinal tract.

Gingival and bacterial plaque response to instrumentation, oral hygiene instruction and nutritional therapy.

Thirty-three male subjects participated in a study to examine the effect of supplements of multiple vitamins and minerals, local therapy (periodontal instrumentation and oral hygiene instruction) and a combination of both on gingival inflammation and bacterial plaque formation. Subjects were given either multivitamin and mineral supplements or placebos on a double-blind basis for 21 days. On Day 7, the mandibular incisors were instrumented, and each subject was instructed in brushing and flossing. Observations were taken at Days 0, 7 and 21. There was a significant (P = 0.004) effect from micronutrient supplementation at Day 7 on the gingival index but no significant effect on the plaque index. On Day 21 there was no statistical superiority noted for the supplemented group in respect to either the gingival or plaque index, although the gingival index approached significance (P = 0.062).

Effects of dietary fish oil on biliary phospholipids and prostaglandin synthesis in the cholesterol-fed prairie dog.

Cholesterol gallstone formation in the prairie dog is accompanied by an increase in the percentage of biliary phospholipids containing arachidonic acid, and an increase in gallbladder prostaglandin (PG) synthesis, but the pathogenetic significance of these changes is unclear. Dietary supplementation with eicosapentaenoic acid (EPA), an omega-3 fatty acid which is commonly found in fish oil, decreases prostaglandin synthesis in some tissues by replacing arachidonic acid, and by competitively inhibiting prostaglandin synthesis. We studied the effect of dietary fish oil on gallbladder PG synthesis, and the relative abundance of various molecular species of phosphatidylcholines and phosphatidylethanolamines in bile and gallbladder epithelium in the cholesterol-fed prairie dog. Prairie dogs were maintained for 4 weeks on one of four diets: i) control, ii) cholesterol-supplemented (0.34%), iii) menhaden oil (50 g/kg chow), or iv) cholesterol plus menhaden oil. Supplementation with menhaden oil resulted in a replacement of arachidonic and linoleic acids with EPA and docosahexaenoic acids in the phospholipids of bile and gallbladder mucosa. In cholesterol-fed animals, supplementation with menhaden oil prevented increased gallbladder PG synthesis. Menhaden oil also reduced the incidence of cholesterol monohydrate crystals among cholesterol-fed animals (9/20 with cholesterol plus menhaden oil vs 21/22 with cholesterol alone), but the improvement could not clearly be attributed to decreased PG synthesis since supplementation with menhaden oil also increased the total phospholipid concentration in bile, and decreased the degree of cholesterol saturation. These results demonstrate that dietary supplementation with omega-3 fatty acids significantly influences biliary phospholipids, and decreases the incidence of cholesterol monohydrate crystal formation in this animal model.

Clinical decision analysis as a means of technology assessment. The effectiveness of intraoperative cholangiography.

Three strategies for timely detection of common duct stones are examined by decision analysis: the use of intraoperative cholangiography (IOC) in ALL, NONE, or in SOME of the cases that are selected by the estimated probability of a common duct stone. Selective use of IOC is the most cost-effective option and offers a slightly lower mortality risk.