Adrenal insufficiency is a contraindication for omalizumab therapy in mast cell activation disease: risk for serum sickness.

Omalizumab is an effective therapeutic humanized murine IgE antibody in many cases of primary systemic mast cell activation disease (MCAD). The present study should enable the clinician to recognize when treatment of MCAD with omalizumab is contraindicated because of the potential risk of severe serum sickness and to report our successful therapeutic strategy for such adverse event (AE). Our clinical observations, a review of the literature including the event reports in the FDA AE Reporting System, the European Medicines Agency Eudra-Vigilance databases (preferred search terms: omalizumab, Xolair®, and serum sickness) and information from the manufacturer's Novartis database were used. Omalizumab therapy may be more likely to cause serum sickness than previously thought. In patients with regular adrenal function, serum sickness can occur after 3 to 10 days which resolves after the antigen and circulating immune complexes are cleared. If the symptoms do not resolve within a week, injection of 20 to 40 mg of prednisolone on two consecutive days could be given. However, in MCAD patients whose adrenal cortical function is completely suppressed by exogenous glucocorticoid therapy, there is a high risk that serum sickness will be masked by the MCAD and evolve in a severe form with pronounced damage of organs and tissues, potentially leading to death. Therefore, before the application of the first omalizumab dose, it is important to ensure that the function of the adrenal cortex is not significantly limited so that any occurring type III allergy can be self-limiting.

Race, education, and knowledge of bone marrow registry: indicators of willingness to donate bone marrow among African Americans and Caucasians.

BACKGROUND: As bone marrow transplantation (BMT) increases, the availability of suitable donors becomes critical, especially for African Americans, who require a large donor pool to find a suitable match. Previous studies indicated willingness to donate marrow may be a barrier for achieving a large donor pool. METHODS: We conducted a random-sample, statewide telephone survey of 421 Caucasians and 408 African Americans in South Carolina to determine if racial differences in willingness to donate bone marrow exist. We assessed a general level of willingness, asking, "Will you be willing to be a marrow donor?" We assessed an additional level of willingness, asking, "Are you willing to be contacted about bone marrow donation?" RESULTS: We detected no racial differences in general willingness to donate (Caucasians 34%, African Americans 32%, P=.52), although there was a difference in willingness to be contacted to sign-up for the registry (Caucasians 18.3%, African Americans 11%, P=.003). African Americans were more aware that better matches occur within the same race (P <.0001). Caucasians were more knowledgeable about the registry (P <.0001). Younger, more highly educated respondents indicated a greater willingness to be donors. In both races, fear of pain was the most common reason for unwillingness to donate, and it was significantly higher in African Americans. CONCLUSION: Our study suggests reported lack of general willingness does not explain the racial disparities in BMT. Many who expressed willingness to donate were not willing to be contacted to sign up for the registry, especially African Americans. Education and adequate pain control may improve minority recruitment.

Medical therapy of prostate cancer: 1999.

Prostate cancer is the most commonly diagnosed male malignancy and the second most common cause of male cancer death in the U.S. The principles of management of newly diagnosed metastatic prostate cancer have changed little in the last 50 years. Medical therapy continues to have no standard role in the management of localized disease. The various hormonal monotherapy approaches targeting androgen deprivation yield comparable results in the treatment of advanced disease. Supplementing an LHRH agonist (but not orchiectomy) with an antiandrogen may improve survival in men with minimal disease, but the economic cost and the risk for significant impairment of quality of life are quite high. The benefit of combined androgen blockade for patients with more extensive disease remains unclear, with support for this approach waning in recent years. New chemotherapeutic agents and combinations of such, as well as agents with entirely new mechanisms of action, recently have shown encouraging results in the treatment of HRPC. Much additional research is needed to improve our armamentarium against this epidemic disease.

Electronic clinical trial protocol distribution via the World-Wide Web: a prototype for reducing costs and errors, improving accrual, and saving trees.

Clinical trials today typically are inefficient, paper-based operations. Poor community physician awareness of available trials and difficult referral mechanisms also contribute to poor accrual. The Physicians Research Network (PRN) web was developed for more efficient trial protocol distribution and eligibility inquiries. The Medical University of South Carolina's Hollings Cancer Center trials program and two community oncology practices served as a testbed. In 581 man-hours over 18 months, 147 protocols were loaded into PRN. The trials program eliminated all protocol hardcopies except the masters, reduced photocopier use 59%, and saved 1.0 full-time equivalents (FTE), but 1.0 FTE was needed to manage PRN. There were no known security breaches, downtime, or content-related problems. Therefore, PRN is a paperless, user-preferred, reliable, secure method for distributing protocols and reducing distribution errors and delays because only a single copy of each protocol is maintained. Furthermore, PRN is being extended to serve other aspects of trial operations.

Expression of oligohistidine-tagged ricin B chain in Spodoptera frugiperda.

DNA encoding ADPGH6G was fused to the 5'-end of RTB DNA and subcloned as a BamHI-EcoRI DNA cassette into the baculovirus transfer vector, pAcGP67A. Spodoptera frugiperda Sf9 cells were cotransfected with pAcGP67A-ADPGH6G-RTB DNA and BaculoGold AcNPV DNA, and recombinant baculovirus was isolated by two cycles of limiting dilution assay followed by dot blot analysis with 32P-dCTP random primer labeled RTB DNA. Recombinant virus was purified and amplified to obtain stocks at titers of 10(7) infectious particles/mL. Sf9 cells grown in serum-free medium were then infected at an moi of 3 in the presence of 25 mM alpha-lactose. After 5 days, supernatants and cell pellets were harvested and assayed by an asialofetuin ELISA for recombinant RTB protein. Fusion RTB protein was produced in the supernatant at 5 mg/L and in the cell pellet at 1 mg/L. Recombinant protein was purified to > 80% homogeneity using either a monoclonal antibody affinity matrix with alkaline elution or a Ni(2+)-NTA matrix with imidazole elution. The purified protein bound asialofetuin similarly to plant RTB. N-terminal sequencing confirmed the oligohistidine tag. SDS-PAGE confirmed the 1,000 Da increase in mass relative to "wild-type" recombinant RTB produced in Sf9 cells. Immunoblots confirmed reactivity with polyclonal and monoclonal antibodies to plant RTB. The fusion protein reassociated with plant RTA similarly to plant RTB.(ABSTRACT TRUNCATED AT 250 WORDS)

Medical therapy of prostate cancer.

Prostate cancer is now the most commonly diagnosed male malignancy and the second most common cause of male cancer death in the U.S. There is no standard role for medical therapy in the treatment of localized disease, although ongoing trials are investigating possible adjuvant and neoadjuvant roles. Subtotal androgen ablation by surgical or medical means is standard therapy for advanced disease, but such therapy does not exterminate the androgen-independent clone which is hypothesized to develop very early in the course of the disease. The current favored medical therapy for subtotal androgen ablation is the use of a depot formulation of an LHRH agonist accompanied initially by an antiandrogen. Once first-line hormonal therapy has failed, there is little to be gained by any other hormonal therapy, although withdrawal of the hormone(s) might itself be a therapeutic maneuver. Cytotoxic agents presently have no standard role in the management of prostate cancer. Future effective therapies for prostate cancer are being presaged by advances in prostate tumor biology.

The effect of physician personality on laboratory test ordering for hypertensive patients.

Laboratory tests are responsible for a large percentage of health care expenses in the United States. In a retrospective study of the outpatient test ordering by residents for hypertensive patients between the years 1980 and 1986 at the Department of Family Medicine at the Medical University of South Carolina, we found great variability in laboratory test ordering as well as an association between personality as measured by the Myers-Briggs Type Indicator (MBTI) and test ordering. Introverts ordered more than extroverts, and intuitives ordered more than sensors. This association was confirmed by a multiple regression analysis controlling for potential confounders of test ordering, such as severity of disease, the presence of coexisting diabetes mellitus, the demographic characteristics of the patient population, and the number of initial evaluations for hypertension. Elucidation of a relationship between resident personality and laboratory test ordering has important implications for planning intervention strategies to reduce excessive laboratory test ordering in ambulatory care.