Citations

AbstractBackgroundThe burden of disease, disability, and mortality that could be averted by surgery is growing. However, few low and middle income countries (LMICs) have the infrastructure or capacity to provide surgical services to meet this growing need. Equally, few of these countries have been assessed for key infrastructural capacity including surgical and anesthesia providers, equipment, and supplies. These assessments are critical to revealing magnitude of the evolving surgical and anesthesia workforce crisis, related morbidity and mortality, and necessary steps to mitigate the impact of the crisis.MethodsA pilot Internet‐based survey was conducted to estimate per‐capita anesthesia providers in LMICs. Information was obtained from e‐mail respondents at national health care addresses, and from individuals working in‐country on anesthesia‐related projects.ResultsWorkers from 6 of 98 countries responded to direct e‐mail inquiries, and an additional five responses came from individuals who were working or had worked in‐country at the time of the survey. The data collected revealed that the per‐capita anesthesia provider ratio in the countries surveyed was often 100 times lower than in developed countries.ConclusionsThis pilot study revealed that the number of anesthesia providers available per capita of population is markedly reduced in low and lower middle income countries compared to developed countries. As anesthesia providers are an integral part of the delivery of safe and effective surgical care, it is essential that more data is collected to fully understand the deficiencies in workforce and capacity in low and middle income countries.

ABSTRACTEosinophils are best known as the predominant cellular infiltrate associated with asthma and parasitic infections. Recently, numerous studies have documented the presence of Toll-like receptors (TLRs) on the surfaces of eosinophils, suggesting that these leukocytes may participate in the recognition and killing of viruses and bacteria. However, the significance of this role in the innate immune response to bacterial infection is largely unknown. Here we report a novel role for eosinophils as antibacterial defenders in the host response. Isolated mouse eosinophils possessed antipseudomonal properties in vitro. In vivo, interleukin-5 transgenic mice, which have profound eosinophilia, demonstrated improved clearance ofPseudomonas aeruginosaintroduced into the peritoneal cavity. The findings of improved bacterial clearance following adoptive transfer of eosinophils, and impaired bacterial clearance in mice with a congenital eosinophil deficiency, established that this effect was eosinophil specific. The data presented also demonstrate that eosinophils mediate this antibacterial effect in part through the release of cationic secondary granule proteins. Specifically, isolated eosinophil granules had antibacterial properties in vitro, and administration of eosinophil granule extracts significantly improved bacterial clearance in vivo. These data suggest a potent yet underappreciated antibacterial role for eosinophils in vivo, specifically for eosinophil granules. Moreover, the data suggest that the administration of eosinophil-derived products may represent a viable adjuvant therapy for septic or bacteremic patients in the intensive care unit.

Abstract Objective Emerging data demonstrate that a large fraction of the global burden of disease is amenable to surgical intervention. There is a paucity of data related to delivery of surgical care in low‐ and middle‐income countries, and no aggregate data describe the efforts of international organizations to provide surgical care in these settings. This study was designed to describe the roles and practices of international organizations delivering surgical care in developing nations with regard to surgical types and volume, outcomes tracking, and degree of integration with local health systems. Methods Between October 2008 and December 2008, an Internet‐based confidential questionnaire was distributed to 99 international organizations providing humanitarian surgical care to determine their size, scope, involvement in surgical data collection, and integration into local systems. Results Forty‐six international organizations responded (response rate 46%). Findings reveal that a majority of organizations that provide surgery track numbers of cases performed and immediate outcomes, such as mortality. In general, these groups have mechanisms in place to track volume and outcomes, provide for postintervention follow‐up, are committed to providing education, and work in conjunction with local health organizations and providers. Whereas most organizations surveyed provided fewer than 500 surgical procedures annually, more than half had the capacity to provide emergency services. In addition, a great diversity of specialized surgical care was provided, including obstetrics, orthopedic, plastic, and ophthalmologic surgery. Conclusions International organizations providing surgical services are diverse in size and breadth of surgical services provided yet, with consistency, provide rudimentary analysis, postoperative follow‐up care, and both education and integration of health services at the local level. The role of international organizations in the delivery of surgery is an important index, worthy of further evaluation.

Background The US Food and Drug Administration issued a black box warning regarding the use of droperidol and the potential for torsade de pointes (TdP). Methods The primary objective of this retrospective study was to determine whether low-dose droperidol administration increased the incidence of TdP in the general surgical population during a 3-yr time period before and after the Food and Drug Administration black box warning. A random sample of 150 surgical patients during each time interval was selected to estimate the droperidol use for each time period. Results During the time period before the black box warning (July 1, 1998 to June 30, 2001), 2,321/139,932 patients (1.66%) had QT prolongation, TdP, or death within 48 h after surgery. We could identify no patients who clearly developed TdP before the black box warning. There was one patient for whom the cause of death could not positively be ruled out as due to TdP. In the time period after the black box warning (July 1, 2002 to June 30, 2005), 2,207 patients (1.46%) had documented QT prolongation, TdP, or death within 48 h after surgery, including only two cases (<0.1%) of TdP. The incidence of droperidol exposure was approximately 12% (exact 95% confidence interval, 7.3-18.3%) before the black box warning and 0% after placement of the black box warning on droperidol. Therefore, we estimate that approximately 16,791 patients (95% confidence interval, 10,173-25,607) were exposed to droperidol, none of whom experienced documented TdP. Conclusions This indicates that the Food and Drug Administration black box warning for low dose droperidol is excessive and unnecessary.

Purpose Early clinical studies with gefitinib showed promising efficacy and mild toxicity in patients with advanced non–small-cell lung cancer (NSCLC). Thus, gefitinib was an ideal agent to evaluate in a maintenance setting in stage III disease. Patients and Methods Untreated patients with stage III NSCLC, a performance score of 0 to 1, and adequate organ function were eligible. All patients received cisplatin 50 mg/m 2 on days 1 and 8 plus etoposide 50 mg/m 2 on days 1 to 5, every 28 days for two cycles with concurrent thoracic radiation (1.8- to 2-Gy fractions per day; total dose, 61 Gy) followed by three cycles of docetaxel 75 mg/m 2 . Patients whose disease did not progress were randomly assigned to gefitinib 250 mg/d or placebo until disease progression, intolerable toxicity, or the end of 5 years. The planned sample size was 672 patients to confer power of 0.89 to detect a 33% increase over the expected median survival time of 21 months (one-sided P = .025, log-rank test). Random assignment was stratified by stage, histology, and measurable versus nonmeasurable disease. Results Enrollment began in July 2001. An unplanned interim analysis conducted in April 2005 rejected the alternative hypothesis of improved survival at the P = .0015 level for 243 randomly assigned patients. The study closed, and preliminary results were reported. Now, with a median follow-up time of 27 months, median survival time was 23 months for gefitinib (n = 118) and 35 months for placebo (n = 125; two-sided P = .013). The toxic death rate was 2% with gefitinib compared with 0% for placebo. Conclusion In this unselected population, gefitinib did not improve survival. Decreased survival was a result of tumor progression and not gefitinib toxicity.

Multiple myeloma is a radiosensitive malignancy that is currently incurable. Here, we generated a novel recombinant vesicular stomatitis virus [VSV(Δ51)-NIS] that has a deletion of methionine 51 in the matrix protein and expresses the human sodium iodide symporter (NIS) gene. VSV(Δ51)-NIS showed specific oncolytic activity against myeloma cell lines and primary myeloma cells and was able to replicate to high titers in myeloma cells in vitro. Iodide uptake assays showed accumulation of radioactive iodide in VSV(Δ51)-NIS–infected myeloma cells that was specific to the function of the NIS transgene. In bg/nd/xid mice with established subcutaneous myeloma tumors, administration of VSV(Δ51)-NIS resulted in high intratumoral virus replication and tumor regression. VSV-associated neurotoxicity was not observed. Intratumoral spread of the infection was monitored noninvasively by serial gamma camera imaging of 123I-iodide biodistribution. Dosimetry calculations based on these images pointed to the feasibility of combination radiovirotherapy with VSV(Δ51)-NIS plus 131I. Immunocompetent mice with syngeneic 5TGM1 myeloma tumors (either subcutaneous or orthotopic) showed significant enhancements of tumor regression and survival when VSV(Δ51)-NIS was combined with 131I. These results show that VSV(Δ51)-NIS is a safe oncolytic agent with significant therapeutic potential in multiple myeloma.

AbstractThe aim was to determine whether changes in enteric bacteriology, absorption, morphology, and emptying occur after ileal pouch–anal anastomosis for ulcerative colitis, and to relate any changes to the clinical result. Twenty patients were studied 26 ± 2 months (mean ± s.e.m.) after operation. Eight patients had a good result, six a poor result, and six a history of recurrent pouch ileitis. Anaerobic and aerobic overgrowth occurred in the jejunum of patients with a poor result, but not in those with a good result or with pouch ileitis. In contrast, ileal pouch bacterial overgrowth occurred in all patients regardless of the clinical result. Patients with jejunal overgrowth had increased 24 h stool volume and stool nitrogen, but other patients did not. The larger the stool volume, the greater the anaerobic overgrowth. Pouch biopsies showed chronic inflammation in all patients, while 45 per cent had colonic metaplasia. Neither the inflammation nor the metaplasia correlated with the clinical result, nor did the clinical result correlate with the efficiency of pouch emptying. In conclusion, jejunal bacterial overgrowth after ileal pouch–anal anastomosis was associated with an increased stool output, azotorrhoea, and a poor clinical result. A distinguishing bacterial, absorptive, morphological, or emptying abnormality was not found in patients with a history of recurrent pouch ileitis.

Summary In 4 dogs a 75-cm segment of jejunum was isolated from the intestinal stream. Stimulating electrodes were implanted at each end of the segment and recording electrodes at intervals between. The two ends of the segment were fashioned as stomas on the anterior abdominal wall. After recovery, the electrical activity of the segment was continuously recorded, whilst a solution of 100 mmol/l glucose and 90 mmol/l NaCl was infused into the proximal stoma at 2.9 ml/min. Effluent from the distal stoma was collected in 5-min aliquots for three consecutive 30-min periods. In the second period electrical stimuli were given via either the proximal or the distal bipolar electrodes to entrain pacesetter potentials. Both forward and backward electrical pacing decreased the output of water, glucose and sodium from the jejunal segment, but the decrease was significantly greater with backward pacing. We conclude that pacing a segment of jejunum backwards with electrical stimuli produces a greater increase in absorption from the segment than pacing it forwards, a finding which has therapeutic implications in patients with the short bowel syndrome.

Abstract Gastric emptying of solids and liquids was measured in 12 dogs with and without corporal or antral gastrojejunostomy. Both types of stoma hastened the onset but did not alter the time from onset to complete emptying of 40 small plastic spheres. Corporal gastrojejunostomy slowed the emptying of 400 ml. of 154 mM NaCl but not of 500 mM glucose, whereas antral gastrojejunostomy slowed the emptying of both.