Craniosynostosis and congenital heart anomalies associated with a maternal deletion of 15q15-22.1

We report an infant with multiple congenital anomalies, including craniosynostosis, tetralogy of Fallot variant, and limb anomalies associated with a maternal deletion of 15q15-22.1. Only two other patients have been reported with a similar deletion, but the deletion was paternal in both cases. We review our patient's findings and compare them to previously reported individuals with similar 15q abnormalities. Our patient allows an expansion of phenotype associated with mid-15q deletions to include severe craniosynostosis, congenital heart disease, and limb anomalies. This will assist in prenatal counseling and predicting postnatal outcome for other affected individuals. The specific breakpoints in our patient and the other patients with similar deletions may also assist in determining a critical region for suture formation.     

Cytopathic effect of in situ gene therapy in prostate cancer

This is a morphologic study of in situ gene therapy effects in patients with prostate cancer using the Herpes Simplex VirusThymidine Kinase gene (HSV-tk) followed by ganciclovir. Prostatectomy specimens from the first 4 patients showed the following morphologic changes: (1) various degrees of necrosis were seen in cancer foci; (2) cytopathic changes were seen across the whole spectrum of Gleason grades; (3) the normal prostate was rarely affected by necrosis, but contained an intense mononuclear infiltrate; (4) loss of nuclear detail was a common finding. Volumetric studies showed that only portions of the tumor show morphologic effects as well as an inverse relationship between percentage of affected tumor and prostate and tumor size. An inflammatory response was observed, with predominance of CD20-positive cells in normal prostate tissue, CD8 (cytotoxic T cells) in the tumor, and macrophages in all areas of the treated prostates. We believe that these changes represent the cytopathic effect of our in situ gene therapy on prostate cancer, and that they trigger a local immune response.     

Antigenic properties of polymers formed by beta-lactam antibiotics.

Purified polymers have been isolated from 6-aminopenicillanic acid and from semi-synthetic penicillins and cephalosporins. All the polymers were shown to react with rabbit antibody of penicillins and cephalosporins. All the polymers were shown to react with rabbit antibody of penicilloyl specificity, as demonstrated by passive cutaneous anaphylaxis in guinea pigs, and the reactions were shown to be penicilloyl-specific by hapten inhibition experiments. The cephalosporin-derived polymers in addition reacted with rabbit antibodies raised to the corresponding cephalosporin conjugates of bovine gamma-globulin. Using direct skin tests, passive cutaneous anaphylaxis and an in vitro assay, no evidence was obtained that the polymers induced the formation of specific antibodies in baboons, guinea pigs and rabbits, but in baboons the induction of cell-mediated immunity, demonstrable by delayed skin test reactions, was shown.     

Somatic von hippel-lindau mutation in clear cell papillary cystadenoma of the epididymis

Papillary cystadenoma of the epididymis is an uncommon benign lesion that may occur sporadically or as a manifestation of von Hippel—Lindau (VHL) disease. Neither immunohistochemical studies nor molecular genetic analyses of the VHL gene have been reported previously for this lesion. The authors describe two cases of clear cell papillary cystadenoma of the epididymis, both of which were initially confused with metastatic renal cell carcinoma. Both lesions showed positive immunohistochemical staining for low and intermediate molecular weight keratins (Cam 5.2 and AE1/AE3), EMA, vimentin, α₁-antitrypsin, and α₁-antichymotrypsin. Each was negative for CEA. Because clear cell papillary cystadenoma is similar to renal cell carcinoma histologically, and because both occur as components of the von Hippel—Lindau disease complex, the authors analyzed both cases for the presence of mutations in the VHL gene. A somatic VHL gene mutation was detected in one of the two tumors by polymerase chain reaction followed by single-strand conformation polymorphism analysis. Direct sequencing revealed a cytosine to thymine transition at nucleotide 694, resulting in the replacement of an arginine with a stop codon after the sixth amino acid of exon 3. As the VHL gene is believed to function as a tumor suppressor gene, VHL gene mutations may play a role in the initiation of tumorigenesis in sporadic cystadenomas of the epididymis.     

Immunogenicity in guinea pigs and tolerance in grass pollen-sensitive volunteers of enteric-coated grass pollen allergens

An acid-insoluble, methacrylic acid, methyl methacrylate copolymer (Eudragit L-100) was used to give an enteric coating to a grass pollen extract in order to protect it against gastric degradation. Substantial protection against the degradative effects of simulated gastric secretion was demonstrated using this preparation which was well tolerated by grass pollen-allergic volunteers. The enteric-coated allergen induced a greater secondary antibody response than did an aqueous presentation when administered orally to guinea pigs which had been primed previously by subcutaneous injection. This result indicates that an effective hyposensitisation regimen could consist of a short series of initial parenteral injections, followed by an oral course of the protected allergen.     

Adapting industry-style business model to academia in a system of Performance-based Incentive Compensation.

Performance-Based Incentive Compensation (PBIC) plans currently prevail throughout industry and have repeatedly demonstrated effectiveness as powerful motivational tools for attracting and retaining top talent, enhancing key indicators, increasing employee productivity, and, ultimately, enhancing mission-based parameters. The University of Arkansas for Medical Sciences (UAMS) College of Medicine introduced its PBIC plan to further the transition of the college to a high-performing academic and clinical enterprise. A forward-thinking compensation plan was progressively implemented during a three-year period.After the introduction of an aggressive five-year vision plan in 2002, the college introduced a PBIC plan designed to ensure the retention and recruitment of high-quality faculty through the use of uncapped salaries that reflect each faculty member's clinical, research, and education duties. The PBIC plan was introduced with broad, schoolwide principles adaptable to each department and purposely flexible to allow for tailor-made algorithms to fit the specific approaches required by individual departments.As of July 2006, the college had begun to reap a variety of short-term benefits from Phase I of its PBIC program, including increases in revenue and faculty salaries, and increased faculty morale and satisfaction.Successful implementation of a PBIC plan depends on a host of factors, including the development of a process for evaluating performance that is considered fair and reliable to the entire faculty. The college has become more efficient and effective by adopting such a program, which has helped it to increase overall productivity. The PBIC program continues to challenge our faculty members to attain their highest potential while rewarding them accordingly.     

Private cost containment. The effects of utilization review programs on health care use and expenditures

Utilization review has been regarded as one of the most promising approaches to the containment of health care costs. We analyzed insurance claims data on 222 groups of employees and dependents for 1984 and 1985 to evaluate the effects of utilization review programs instituted by a large private insurance carrier. The utilization review programs we studied were compulsory; patients who did not follow established utilization review procedures were subject to financial penalties. Controlling for employee characteristics, health care market area factors, and benefit-plan features, we found that utilization review reduced admissions by 12.3 percent, inpatient days by 8.0 percent, hospital expenditures by 11.9 percent, and total medical expenditures by 8.3 percent. When only groups that had relatively high admission rates before adopting utilization review were analyzed, it was found that they had a 34 percent reduction in patient days and a 30 percent reduction in hospital expenditures. The savings-to-cost ratio of utilization review for groups overall was highly favorable--approximately 8 to 1. Private utilization review programs of the type we studied appear to be effective in reducing hospital use and decreasing medical expenditures. This study did not address the possible effects of such programs on the health status of patients.     

Potentiation of in vitro synthesis of human IgE by cyclosporin A (CsA).

In this study, we investigated the modulatory effects of CsA on in vitro synthesis of IgE, IgG1 and IgG4 by human peripheral blood mononuclear cells (PBMC). In contrast to its known immunosuppressive effect, we have demonstrated that a low dose of CsA (10(-7) M, 120 ng/ml) potentiated IgE production by up to 40-fold (i.e. from 33 +/- 4.5 to 1346 +/- 290 ng/ml). This potentiation was specific for IgE since no such effect was demonstrable with IgG1 and IgG4. Potentiation of IgE synthesis by CsA in the PBMC cultures was partly due to CsA acting on T cells, as demonstrated by the addition of CsA-treated T cells to T cell-depleted cultures. However, potentiation was also demonstrable in a T cell-depleted, anti-CD40-stimulated culture (four-fold increase from 400 +/- 48 to 1606 +/- 127 ng/ml). Our data therefore suggest that there are at least two mechanisms for CsA-induced potentiation of IgE synthesis, one T cell-dependent and the other T cell-independent. The clinical implications of these findings are discussed with regard to the use of CsA in the treatment of Th2-mediated diseases.     

Immune response to soluble exoantigens of Plasmodium falciparum may contribute to both pathogenesis and protection in clinical malaria: evidence from a longitudinal, prospective study of semi-immune African children

Some soluble exoantigens of Plasmodium have lipopolysaccharide (LPS)-like properties and are believed to contribute to the pathogenesis of acute malaria. We have studied cellular and humoral immune responses to several purified exoantigens of Plasmodium falciparum in a cohort of children and compared these responses with their subsequent susceptibility to malaria infection and clinical disease. We found no evidence that either lymphoproliferative or interferon-gamma (IFN-gamma) responses to these antigens were associated with protective immunity. On the contrary, children whose cells produced IFN-gamma after in vitro activation with one of the soluble antigens (Ag7) were more likely to experience clinical manifestations of malaria infection (fever and malaise) than were children whose cells did not produce IFN-gamma. It is possible that exoantigen-induced IFN-gamma may exacerbate the LPS-like effects of these antigens. However, serum antibodies to another antigen (Ag2) were more prevalent in children with asymptomatic infections or low parasitemia than in children with fever and higher parasitemia (confirmed clinical malaria), suggesting that these antibodies may contribute to the development of protective immunity.     

Impedance plethysmography: the origin of electrical impedance changes measured in the human calf

Electrical impedance plethysmography of the lower leg is now a widely used test for detection of deep vein thrombosis. The origin of the impedance signal is difficult to evaluate in the living subject, and experimental animals have important anatomic differences. A controlled study on human cadavers was therefore undertaken. Conductive and nonconductive fluids were injected into the lower legs of cadavers, while electrical impedance changes were recorded utilising a 4-electrode technique. X-ray studies confirmed the localisation of the injections. Results from ten cadavers showed that significant impedance changes occurred only in response to injections of saline in the region between the electrodes. Injections of nonconductive silicone oil caused a small increase in the measured impedance. It is concluded that electrical impedance plethysmography reflects changes in conductivity confined to the region between the electrodes; and that the ratio of deep to superficial impedance sensitivity is a function of the electrode spacing.