Paneth cell α-defensin 6 (HD-6) is an antimicrobial peptide.

Defensins protect human barriers from commensal and pathogenic microorganisms. Human α-defensin 6 (HD-6) is produced exclusively by small intestinal Paneth cells but, in contrast to other antimicrobial peptides (AMPs) for HD-6, no direct antibacterial killing activity has been detected so far. Herein, we systematically tested how environmental factors, like pH and reducing conditions, affect antimicrobial activity of different defensins against anaerobic bacteria of the human intestinal microbiota. Remarkably, by mimicking the intestinal milieu we detected for the first time antibacterial activity of HD-6. Activity was observed against anaerobic gut commensals but not against some pathogenic strains. Antibiotic activity was attributable to the reduced peptide and independent of free cysteines or a conserved histidine residue. Furthermore, the oxidoreductase thioredoxin, which is also expressed in Paneth cells, is able to reduce a truncated physiological variant of HD-6. Ultrastructural analyses revealed that reduced HD-6 causes disintegration of cytoplasmic structures and alterations in the bacterial cell envelope, while maintaining extracellular net-like structures. We conclude that HD-6 is an antimicrobial peptide. Our data suggest two distinct antimicrobial mechanisms by one peptide: HD-6 kills specific microbes depending on the local environmental conditions, whereas known microbial trapping by extracellular net structures is independent of the reducing milieu.

Uterine retroversion for vaginoperineal reconstruction following resection of distal rectal tumors.

PURPOSE: Vaginal and perineal reconstruction following wide resection of locally invasive rectal cancer can be challenging. Various techniques have been reported, all of which contribute the additional morbidity inherent in tissue procurement. We present a technique applicable to nonhysterectomized patients who undergo posterior vaginal wall reconstruction with retroversion of the in situ uterus. METHODS: Four nonhysterectomized patients with recurrent rectal carcinoma and abdominoperineal resection with en bloc resection of the posterior vagina leaving a large defect necessitating reconstruction of the vagina, perineum, or both, have undergone posterior vaginal wall and perineal reconstruction with uterine retroversion into the posterior pelvis and fixation to the perineum. RESULTS: Satisfactory vaginoperineal reconstruction was achieved in all our patients at 3 months. In addition, patients are able to resume sexual activity after tissue re-epithelialization. CONCLUSION: Uterine retroversion is a viable option for vaginal and perineal reconstruction.

Cost-effectiveness of thrombolytic therapy for acute myocardial infarction.

OBJECTIVE: To estimate the cost-effectiveness of thrombolytic therapy versus no thrombolytic therapy for patients following acute myocardial infarction, focusing on the impact of time to treatment on outcome. METHODS: A decision model was developed to assess the benefits, risks, and costs associated with thrombolytic therapy for treatment of acute myocardial infarction compared with standard nonthrombolytic therapy. The model used pooled data from a recent study of nine large randomized, controlled clinical trials and 12-month outcome data from a recently published meta-analysis of thrombolytic therapy trial data. Outcomes were expressed in terms of survival to hospital discharge and survival to 1 year after discharge. The risks of treatment that led to death, morbidity, or added costs were estimated. The model determined excess and marginal costs per death averted to hospital discharge and at 1 year. Results were also estimated in terms of cost per year of life saved. Sensitivity analyses included variations in time to treatment and drug cost. RESULTS: The marginal cost of thrombolytic therapy per death averted at 1 year was $222,344, or $14,438 per year of life saved. For patients treated within 6 hours of acute myocardial infarction, the marginal cost per death averted was $181,536 at 1 year, or $11,788 per year of life saved. CONCLUSIONS: Thrombolytic therapy is significantly more cost-effective than many other cardiovascular interventions and compares favorably with other forms of medical therapy. Results suggest that shortening the time to treatment has a critical impact on the cost-effectiveness of thrombolytic therapy.

Emergency services use by elderly individuals.

Population predictions suggest that the proportion of elderly people will continue to rise until 1996, will remain constant until 2016, and will continue to rise again. If the current trends continue, the ED will become an increasingly important provider of primary health care for the elderly population. Practitioners, educators, and administrators in emergency medicine should prepare now to meet the growing needs of this population. The high cost and high rate of recidivism by aged ED patients suggest that attention should be paid to appropriateness, continuity, and effectiveness of care. Early social service intervention in the ED may prove beneficial to older patients. In addition, the basic principles of the care of elderly patients should be included in the training curriculum of ED physicians and primary care providers.