Induction of immune tolerance in patients with hemophilia A and inhibitors treated with porcine VIIIC by home therapy

Home therapy with porcine factor VIIIC was safe and effective when administered to five hemophilic patients over periods of 8 1/2, 6, 4, 3 1/2, and 2 years. No significant transfusion reactions occurred. Before treatment with porcine factor VIIIC, all five had high-level, high- responding anti-human VIIIC inhibitors initially lacking anti-porcine factor VIIIC activity. Although specific anti-porcine VIIIC inhibitors arose in all patients, these were generally transient, and only one patient became refractory to treatment. We believe that porcine factor VIIIC is the treatment of choice in patients whose inhibitors do not cross-react. All five patients lost their original anti-human VIIIC inhibitors after starting treatment with porcine VIIIC, permitting the reintroduction of human VIIIC in three of them. There has been no recurrence of anti-human VIIIC inhibitor activity during 2 to 3 years of regular treatment with human VIIIC in these patients. This suggests that tolerance to human VIIIC has arisen as a result of treatment with porcine VIIIC. Porcine VIIIC may have a role in the desensitization of some factor VIIIC inhibitor patients.     

Locus assignment of two alpha-globin structural mutants from the Caribbean basin: alpha Fort de France (alpha 45 Arg) and alpha Spanish Town (alpha 27 Val)

Two alpha-globin structural mutants were mapped to their encoding loci by in vitro translation of hybrid-selected alpha 1- and alpha 2-globin mRNA. The more highly expressed mutant, alpha Spanish Town (alpha 27Val), is encoded at the alpha 2 locus and the less expressed mutant, alpha Fort de France (alpha 45Arg), is encoded at the alpha 1 locus. These results further define the distribution of alpha-globin structural mutations within the alpha-globin gene cluster and substantiate the dominant role of the alpha 2-globin locus in alpha- globin expression.     

Erythrocyte differentiation during the metamorphic hemoglobin switch of Rana catesbeiana.

Anurans (frogs and toads) switch from tadpole to adult hemoglobin synthesis during metamorphosis. A number of workers have attempted to determine whether tadpole and adult Hb types are expressed in the same or different erythroid cells during the switch. If the different Hb types are found in different cells during the transition, the switch in globin gene expression occurs at an early stage of cellular differentiation. Previous studies, in which immunocytochemical techniques were used to approach this question, are in conflict in regard to the metamorphic Hb switch of the North American bullfrog Rana catesbeiana. We have purified newly differentiating erythroid cells from the blood of metamorphosing tadpoles by using Percoll gradients. These new cells have an immature morphology, are very active in the synthesis of adult Hb, and contain no detectable tadpole Hb. The tadpole cells have no detectable adult Hb, are synthetically inactive, increase in density during the switch, and are then cleared from the circulation. Thus, only adult Hb expression is detected in newly differentiating erythroid cells during metamorphosis.     

Blood pressure reactivity to exercise: stability, determinants, family aggregation, and prediction

Previous studies have shown blood pressure reactivity to exercise predicts future resting blood pressure. Subjects in this study were 206 healthy Mexican-American and Anglo-American families with fifth or sixth grade children. A total of 539 children (mean age = 12 years) and parents (mean age = 37 years) had complete data at baseline, and 79% were remeasured 48 months later. Blood pressure was measured during a submaximal cycle ergometer fitness test. Reactivity measures included systolic blood pressure at 70% of maximal heart rate (SBP70) and slope of the blood pressure-heart rate association during exercise (SLOPE). Stability of reactivity measures over 24 months varied from .22 to .63 (all p less than 0.001). Correlates of blood pressure reactivity in parents included resting heart rate, gender, age, and sodium intake. Correlates of reactivity in children included resting heart rate, body mass index, and age. Modest but significant levels of family aggregation of blood pressure reactivity were observed. In stepwise multiple regression analyses, SBP70 at baseline predicted resting blood pressure 48 months later in parents but not in children. The present results confirm previous studies indicating systolic blood pressure reactivity to exercise is a significant predictor of later resting blood pressure.     

Equity concerns with the use of hospital services by the medically vulnerable

This study assessed distributional inequities in access to care among a representative sample of adults residing in Oklahoma. Inequities were identified by comparing the medically vulnerable to the less vulnerable with respect to their use or nonuse of hospital care and, among those admitted, the number of days of care consumed. The behavioral model was employed to guide the analysis and the development of hypotheses. Controlling for need, enabling, and predisposing factors, the results indicate that the use of service by the poor, the elderly who lack supplemental insurance, and the uninsured is incongruent with their health status and that current methods of financing care may contribute to distributional inequities. The implications of these findings are discussed in the context of options that may improve access to care by the medically vulnerable.     

The temporarily and chronically uninsured: does their use of primary care differ?

The purpose of this study is to examine differences in the use of preventive or early-detection services by the temporarily and chronically uninsured. The use of preventive care was measured by an index that depicts the use of nine preventive or early-detection services and the use or nonuse of each procedure on the index. Respondents whose lapse in insurance coverage was one year or more were identified as chronically uninsured, while those whose lapse in coverage was less than one year were identified as temporarily uninsured. The analysis indicates that the chronically uninsured and, to a lesser extent, the temporarily uninsured use significantly fewer preventive or early-detection services than their insured counterparts.     

Repair of full-thickness defects in alimentary tract wall with patches of expanded polytetrafluoroethylene

OBJECTIVES: To test the efficacy of patches of expanded polytetrafluoroethylene (ePTFE) for the repair of full-thickness defects in alimentary tract wall. SUMMARY BACKGROUND DATA: A recent report of successful replacement of duodenal wall with patches of ePTFE was met with skepticism and clearly warranted confirmation as well as evaluation in repair of other segments of the abdominal intestinal tract. METHODS: Defects of 4 cm2 were created in various segments of canine abdominal alimentary tract (stomach, duodenum, small bowel, and colon) as well as in bladder dome. For the duodenum in 13 dogs, three different ePTFE fabrications were used: CVX (cardiovascular), PDX (preclude dura membrane), and DLM (dual mesh plus). In repair of the other areas in six dogs, the PDX patch was used. When the animals were killed, both gross inspection of the parietes and tissue for histologic study became the basis for evaluation. Peritoneal and intraluminal cultures of the specific study viscera were also taken. RESULTS: There were no patch failures. Only six significant adhesions were noted in 3 of the 19 dogs. Serosal surface healing was complete without exception by 1 week in all animals. Patches of CVX and PDX had heaping mucosa at the margin of well-sealed patch edges in the study involving duodenum. However, the DLM patch had an undergrowth of mucosa with partial patch separation by 1 week, beginning patch extrusion into gut lumen at 3 weeks, and total separation of patch with complete mucosal repair at 6 weeks. The fate of the PDX patches at 6 weeks in stomach, small bowel, colon, and bladder was identical to what had been observed for the PDX patch in the duodenum. All peritoneal and bladder cultures had no growth, whereas the contents of the alimentary tract grew expected flora. CONCLUSIONS: These observations suggest that ePTFE may well be an acceptable membrane for at least temporary replacement of full-thickness hollow viscus defects, even in the face of heavy bacterial contamination, and that certain structural configurations of ePTFE may provide a base for increasing absorptive mucosal surface area.     

CDC international HIV prevention research activities among injection drug users in Thailand and Russia

The Centers for Disease Control and Prevention (CDC) has participated in collaborative HIV prevention research activities in injection drug users (IDUs) with the Bangkok Metropolitan Administration (BMA) in Bangkok, Thailand, from 1995 to the present and with the Orel AIDS Center in Orel Oblast, Russia, from 2001 to 2003. Studies in Bangkok have included an HIV prevention trial preparatory cohort from 1995 to 1998, a seroconverter cohort from 1998 to the present, a phase III trial of the AIDSVAX B/E gp 120 HIV vaccine from 1999 to 2003, and a phase II/III HIV prophylaxis trial with tenofovir scheduled to begin in 2005. Activities in Orel included a review of HIV surveillance data in 2001, focus group discussions and a case-control study with HIV-infected and-uninfected IDUs in 2001, a cross-sectional study with the female sex partners of male IDUs in 2002, and a community outreach intervention in 2002–2003. In Bangkok, 1,209 IDUs were enrolled in the preparatory cohort which revealed an HIV incidence of 5.8% per 100 person-years; 133 HIV-infected IDUs have been followed in the seroconverter cohort with >85% follow-up and HIV and tuberculosis care provided; 2,546 IDUs were enrolled in the HIV vaccine efficacy trial which was successfully completed with a followup rate of >95%, although the vaccine was not shown to be effective at reducing HIV incidence; and 1,600 IDUs will be enrolled in the daily tenofovir HIV prophylaxis trial in 2005. In Orel, initial focus group discussions and epidemiologic studies revealed low HIV knowledge and high rates of unsafe injecting and sexual practices among IDUs and their female sex partners; and educational campaigns and the community outreach intervention were developed and implemented. A steady decline in new HIV infections in IDUs was then observed in Orel in 2002–2003. CDC has participated in the conduct of successful collaborative HIV prevention research activities in Thailand and Russia over the past decade. The establishment of long-term relationships with in-country public health and community partners has been instrumental in the success of these efforts.