Enhancing human islet transplantation by localized release of trophic factors from PLG scaffolds.

Islet transplantation represents a potential cure for type 1 diabetes, yet the clinical approach of intrahepatic delivery is limited by the microenvironment. Microporous scaffolds enable extrahepatic transplantation, and the microenvironment can be designed to enhance islet engraftment and function. We investigated localized trophic factor delivery in a xenogeneic human islet to mouse model of islet transplantation. Double emulsion microspheres containing exendin-4 (Ex4) or insulin-like growth factor-1 (IGF-1) were incorporated into a layered scaffold design consisting of porous outer layers for islet transplantation and a center layer for sustained factor release. Protein encapsulation and release were dependent on both the polymer concentration and the identity of the protein. Proteins retained bioactivity upon release from scaffolds in vitro. A minimal human islet mass transplanted on Ex4-releasing scaffolds demonstrated significant improvement and prolongation of graft function relative to blank scaffolds carrying no protein, and the release profile significantly impacted the duration over which the graft functioned. Ex4-releasing scaffolds enabled better glycemic control in animals subjected to an intraperitoneal glucose tolerance test. Scaffolds releasing IGF-1 lowered blood glucose levels, yet the reduction was insufficient to achieve euglycemia. Ex4-delivering scaffolds provide an extrahepatic transplantation site for modulating the islet microenvironment to enhance islet function posttransplant.

Seroepidemiology of infections due to spotted fever group rickettsiae and Ehrlichia species in military personnel exposed in areas of the United States where such infections are endemic.

A prospective, seroepidemiologic study of spotted fever group rickettsiae (SFGR) and Ehrlichia infections was done among 1194 US military personnel exposed in a heavily tick-infested area of Arkansas in 1990. Seroconversion (4-fold) and seroprevalence rates were determined by indirect immunofluorescent antibody assays. Seroconversions to SFGR occurred in 30 persons (2.5%), whereas seroconversion to Ehrlichia species occurred in 15 (1.3%). The majority of seroconverters did not report symptoms (22/30 [73%] of SFGR seroconverters; 10/15 [67%] of Ehrlichia species seroconverters). History of tick attachment was associated with seroconversion to SFGR (relative risk [RR] = 4.3, P < .001) and Ehrlichia species (RR = 3.6, P < .05). Use of permethrin-impregnated uniforms significantly decreased risk of infection (P < .01); use of bed nets increased risk by 4-fold. Tickborne infections represent a significant threat to military personnel training in areas in which these infections are endemic.

Rickettsialpox in a New York City hospital, 1980 to 1989.

BACKGROUND: Rickettsialpox is caused by Rickettsia akari, which is transmitted from rodents to humans by bloodsucking mites. The initial skin lesion forms an eschar and is followed by the development of fever, malaise, myalgia, and 5 to 40 maculopapules and papulovesicles. The disease, which responds to tetracycline, can be mistaken for chickenpox. The diagnosis has been based on an increase in serum antibody titers against R. akari over a period of three to eight weeks. We discuss a more rapid technique that uses direct immunofluorescence to identify R. akari in paraffin-embedded tissue, and we describe the histopathological findings of lesional skin. METHODS: We studied 13 patients (age, 11 months to 58 years) who were seen at Lincoln Hospital in New York City from 1980 to 1989 and were suspected of having rickettsialpox. In nine patients serum samples were obtained during the acute and convalescent phases of the illness for indirect fluorescent-antibody testing. Punch-biopsy specimens of skin lesions were examined by microscopy and by direct fluorescent-antibody testing with an anti-R. rickettsii globulin conjugated with fluorescein isothiocyanate. RESULTS: The diagnosis was confirmed in all 13 patients by indirect or direct fluorescent-antibody techniques. Direct fluorescent-antibody testing of eschars from seven patients was positive in five patients, but negative in two patients who had serologically confirmed rickettsialpox. In contrast, direct fluorescent-antibody testing of papulovesicles from nine patients was positive in only one patient. Histopathological analysis of the eschars revealed extensive necrosis and inflammation. In biopsy specimens of papulovesicles, dermal edema, subepidermal vesicles, and vascular changes were present. CONCLUSIONS: The combination of direct fluorescent-antibody testing of an eschar from the presumed site of inoculation and histopathological examination of papulovesicles for distinctive features represents an improved method of diagnosing rickettsialpox.

Evaluation of specificity of indirect enzyme-linked immunosorbent assay for diagnosis of human Q fever.

Ninety-five acute- and convalescent-phase serum specimens from 48 patients suspected of having rickettsial or Legionella infections were assayed for antibodies to Coxiella burnetii, the causative agent of Q fever. To evaluate the specificity of the indirect enzyme-linked immunosorbent assay (ELISA) for human Q fever, we compared the ELISA results with those of the indirect immunofluorescence antibody (IFA) test. The ELISA data were analyzed by two different criteria for a positive test. The first criterion for positive results by ELISA was based upon diagnostic titers established in a study of 150 subjects who had no demonstrable cellular or humoral immune responses to C. burnetii phase I or phase II whole cells or phase I lipopolysaccharide. The second criterion was based upon diagnostic antibody titers in a study of 51 subjects who had been diagnosed as having clinical Q fever and had fourfold or greater rises in humoral immune responses to C. burnetii phase I and phase II whole-cell antigens. A comparison of the ELISA and IFA test results of the 95 serum specimens indicated excellent agreement between the tests (Kappa = 92.9%; P < 0.05). None of the 38 patients whose etiologies were confirmed serologically as Legionnaires' disease or rickettsial diseases other than Q fever were classified as positive for C. burnetii by the ELISA. Only one patient identified by the IFA test as having Q fever was not scored positive by the ELISA. These results suggest that the ELISA is useful for epidemiologic screening and as a diagnostic test for human Q fever.

Alcohol use patterns of first-year medical students: I. Development of shared norms.

Freshman medical students (96% of one class; n = 116) completed questionnaires on alcohol use at orientation, and again in April (n = 106) of that same year. Quantity/frequency and self-label ratings of alcohol use were employed to define normative ranges (in ethanol oz/wk). The confidentiality of student participants was protected. Males consumed five drinks per week over the summer and dropped to four per week during school; females consumed two drinks per week over both periods. Summertime and school year consumption rates were strongly correlated. Normative ranges of drinking converged from September to April, suggesting the emerging norms were the product of social experience with classmates. Class norms described a "cutpoint" separating acceptable range from excessive drinking (more than two drinks per day). The authors conclude that reliable "community norms" for medical students could be identified, the norms evolve over time, and they can be employed to determine the boundaries of acceptable drinking for research and screening purposes.

Tumor pediculado de pezón. Presentación de un caso / Pediculate nipple tumor. A case report

Se presenta el caso de una paciente con tumor del pezón de larga evolución, gran tamaño y naturaleza benigna. Se destacan las particularidades morfológicas de este poco frecuente tumor, así como la buena evolución posoperatoria después de 3 años (AU)