Paraoxonase 1, quorum sensing, and P. aeruginosa infection: a novel model.

Pseudomonas aeruginosa is a Gram-negative bacterium which exacts a heavy burden on immunocompromised patients, but is non-pathogenic in a healthy host. Using small signaling molecules called acyl-homoserine lactones (AHLs), populations of P. aeruginosa can coordinate phenotypic changes, including biofilm formation and virulence factor secretion. This concentration-dependent process is called quorum sensing (QS). Interference with QS has been identified as a potential source of new treatments for P. aeruginosa infection. The human enzyme paraoxonase 1 (PON1) degrades AHL molecules, and is a promising candidate for QS interference therapy. Although paraoxonase orthologs exist in many species, genetic redundancy in humans and other mammals has made studying the specific effects of PON1 quite difficult. Arthropods, however, do not express any PON homologs. We generated a novel model to study the specific effects of PON1 by transgenically expressing human PON1 in Drosophila melanogaster. Using this model, we showed that P. aeruginosa infection lethality is QS-dependent, and that expression of PON1 has a protective effect. This work demonstrates the value of a D. melanogaster model for investigating the specific functions of members of the paraoxonase family in vivo, and suggests that PON1 plays a role in innate immunity.

Ankle fractures in patients with diabetes mellitus.

Diabetes mellitus is considered an indicator of poor prognosis for acute ankle fractures, but this risk may be specific to an identifiable subpopulation. We retrospectively reviewed 42 patients with both diabetes mellitus and an acute, closed, rotational ankle fracture. Patients were individually matched to controls by age, gender, fracture type, and surgical vs non-surgical treatment. Outcomes were major complications during the first six months of treatment. We contrasted secondarily 21 diabetic patients with and 21 without diabetic comorbidities. Diabetic patients and controls did not differ significantly in total complication rates. More diabetic patients required long-term bracing. Diabetic patients without comorbidities had complication rates equal to their controls. Diabetic patients with comorbidities had complications at a higher rate (ten patients; 47%) than matched controls (three patients; 14%, p = 0.034). A history of Charcot neuroarthropathy led to the highest rates of complication. An increased risk of complications in diabetic patients with closed rotational fractures of the ankle are specific to a subpopulation with identifiable related comorbidities.

Failure of standard criteria to diagnose nonemergency ectopic pregnancies in a noninfertility patient population.

Algorithms for the diagnosis of ectopic pregnancy are applied independent of the patient population. However, patients may require care at various times of gestation or for different reasons. To examine the utility of the same diagnostic criteria for identifying an ectopic pregnancy in different patient populations, we evaluated women from the infertility clinic and the residents' gynecology clinic at Yale-New Haven Hospital. Sixty women with nonemergency ectopic pregnancies were identified, 38 from the infertility clinic and 22 from the residents' clinic. Although the most common symptoms were the same in both groups (abdominal pain, spotting/bleeding >3 days, dizziness, shoulder pain), they were significantly more frequent in women form the residents' clinic. Despite care by the same attending physicians, ruptured ectopic pregnancies were more than 3 times as likely to occur in the noninfertility patients, and half as likely to be treated laparoscopically (p<0.01). Patients from the residents' clinic also were more likely to have postoperative complications (p<0.5), and had over a threefold higher risk of receiving a blood transfusion. We conclude that criteria for diagnosis and intervention in ectopic pregnancy may have to be modified on the basis of characteristics of the patient population.