Creutzfeldt--Jakob Disease in Recipients of Human Growth Hormone in the United Kingdom: A Clinical and Radiographic Study

In the past 3 years there have been five further cases, in additionto one case reported in 1985, of Creutzfeldt-Jakob disease inrecipients of human growth hormone in the United Kingdom. Theclinical findings of two of these cases are described, demonstratinga typical presentation with a predominantly cerebellar syndromeat onset which is not commonly a presenting feature of sporadicCreutzfeldt-Jakob disease. In one case a ^99mTc hexamethylpropylenaminesingle photon emission tomographic scan showed marked impairmentof tracer uptake in the basal ganglia and cerebral cortex ata time when the clinical picture was predominantly cerebellar.This technique may be useful in early diagnosis. In the othercase post mortem examination of the brain showed prominent amyloiddeposition in the cerebellum, which has not been described previouslyin pituitary-hormone related Creutzfeldt-Jakob disease. Thepreviously published cases of growth hormone-related Creutzfeldt-Jakobdisease are reviewed and reasons for the particular clinicalpattern seen are discussed.     

Effect of amphotericin B and fluconazole on platelet membrane glycoproteins

BACKGROUND : Fever, chills, and reduced platelet recovery may result when platelets are transfused simultaneously with amphotericin B. Amphotericin B reportedly increases the pitting of membranes in stored platelets. STUDY DESIGN AND METHODS : The effects of amphotericin B and another antifungal agent, fluconazole, on platelet membrane glycoproteins (GP) were examined by the incubation of split aliquots of fresh and stored platelet concentrates (PCs) with these drugs for 3 days in storage bags. To determine the effect of storage, PCs were stored for 5 days, and aliquots removed on Days 1 through 5 were placed in platelet storage bags with 4 micrograms per mL of amphotericin B for 2 to 6 hours. Membrane glycoprotein expression was assessed by flow cytometry with fluorescein isothiocyanate-labeled monoclonal antibodies (MoAbs) directed against the following antigens: GPIb (CD42b), CD63 (an activation protein), P-selectin (CD62), and GPIIb/IIIa (CD41a). RESULTS : Amphotericin B produced a concentration-dependent decrease in the surface binding of CD42b MoAb with no consistent changes in the binding of CD41a, CD63, or CD62 MoAbs after a 3-day exposure. Stored but not fresh PCs showed decreased binding of MoAb CD42b after a 6-hour exposure to amphotericin B (4 micrograms/mL). Fluconazole produced no changes. When the binding of MoAb CD42b to permeabilized platelets was used to measure total platelet content, amphotericin B (4 micrograms/mL) decreased MoAb CD42b binding to a similar degree in fresh and stored platelets. Inhibition of aggregation to ADP and collagen and ADP and epinephrine was seen in stored but not fresh PCs. CONCLUSION : Therapeutic levels of amphotericin B resulted in partial loss of total platelet GPIb in fresh and stored PCs, but decreased surface expression of platelet membrane GPIb only in stored platelets. This difference between fresh and stored platelets may be related to the limited reservoir of GPIb available for redistribution to the membrane in the previously stored PCs and may account for the decreased recovery of transfused platelets observed in some patients receiving amphotericin B.     

Serologic test for syphilis as a surrogate marker for human immunodeficiency virus infection among United States blood donors

BACKGROUND: This study evaluated the usefulness of the serologic test for syphilis (STS) in preventing the transmission of human immunodeficiency virus (HIV), hepatitis B and C viruses, and human T- lymphotropic virus via the transfusion of seronegative, infectious window-period blood. STUDY DESIGN AND METHODS: Demographic and laboratory information on blood donations made between January 1992 and June 1994 in 18 American Red Cross regions was analyzed. It was assumed that the same proportion of HIV-positive and HIV-infectious window- period donations reacted on STS and were negative on other screening tests (hepatitis B and C viruses and human T-lymphotropic virus). This proportion multiplied by the estimated number of HIV-infectious window- period donations is the number of post-screening HIV-infectious donations removed by STS. RESULTS: Of 4,468,570 donations, 12,145 (0.27%) were STS positive and 377 (0.008%) were HIV positive. Among donations that were negative on other screening tests, STS-reactive donations were 12 times more likely to be HIV positive (odds ratio = 11.9; 95% CI = 5,26). However, of an estimated 13 infectious window- period donations, 0.2 would have been removed because of a reactive STS, at a cost of over $16 million. CONCLUSION: STS is a poor marker and a costly strategy for preventing post-screening HIV infections and other blood-borne diseases.     

Effect of white cells on platelets during storage

White cells (WBCs) present in stored platelet concentrates have adverse effects on platelet function and on posttransfusion recovery. Although these effects have been attributed to the fall in pH that results from active WBC metabolism, platelets stored in gas-permeable storage bags still exhibit abnormalities, despite maintenance of a stable pH of greater than 6.0. The changes in platelet proteins and function brought about by storage with a controlled number of WBCs were studied. Twelve platelet-pheresis specimens were centrifuged at 180 x g to achieve a WBC count of less than 2 x 10(5) per mL (which contained less than 10% granulocytes). These specimens were split into two aliquots and placed in platelet bags for storage at 22 degrees C with constant horizontal agitation. Neutrophils, obtained from the same donor by centrifugation of 50 mL of whole blood through a discontinuous ficoll gradient, were added to one of the two platelet storage bags to achieve a final neutrophil count of 1 x 10(6) per mL. Platelet aliquots were removed and studied on Days 3 and 5. In platelets stored without neutrophils, the average response to ristocetin, using the mean slope as an index of platelet responsiveness, was 10.3 (n = 9, SD = 11) on Day 3, whereas for the platelets stored with neutrophils, it was 1.25 (n = 12, SD = 0.9, p less than 0.01). Significant differences were also seen on Day 5 (slope = 4.5 for platelets stored without neutrophils, slope = 0.3 for platelets stored with neutrophils, p less than 0.01). Platelet aggregation with 8 microM ADP and 1.5 mg per mL of collagen did not differ significantly.(ABSTRACT TRUNCATED AT 250 WORDS)     

Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin

Background

Despite the efficacy of statins in lowering low-density lipoprotein cholesterol (LDL-C) levels, many patients who are at high risk for heart disease with hypercholesterolemia require additional LDL-C level reduction. The cholesterol absorption inhibitor, ezetimibe, has been shown to provide significant incremental reductions in LDL-C levels when co-administered with statins. This study was performed to compare the efficacy and safety of ezetimibe (10 mg) plus response-based atorvastatin titration versus response-based atorvastatin titration alone in the attainment of LDL-C goals in subjects who are at high risk for coronary heart disease (CHD) and are not at their LDL-C goal on the starting dose of atorvastatin.

Methods

This was a 14-week, multicenter, randomized, double-blind, active-controlled study conducted in 113 clinical research centers in 21 countries. Participants were adults with heterozygous familial hypercholesterolemia (HeFH), CHD, or multiple (≥2) cardiovascular risk factors, and a LDL-C level ≥130 mg/dL after a 6- to10-week dietary stabilization and atorvastatin (10 mg/day) open-label run-in period. Eligible subjects continued to receive atorvastatin (10 mg) and were randomized to receive blinded treatment with ezetimibe (10 mg/day; n = 305) or an additional 10 mg/day of atorvastatin (n = 316). The atorvastatin dose in both groups was doubled after 4 weeks, 9 weeks, or both when the LDL-C level was not at its goal (≤100 mg/dL), so that patients receiving combined therapy could reach 40 mg/day and patients receiving atorvastatin alone could reach 80 mg/day. The primary end point was the proportion of subjects achieving their LDL-C level goal at week 14. A secondary end point was the change in LDL-C level and other lipid parameters at 4 weeks after ezetimibe co-administration with 10 mg/day of atorvastatin versus 20 mg/day of atorvastatin monotherapy.

Results

The proportion of subjects reaching their target LDL-C level goal of ≤100 mg/dL was significantly higher in the co-administration group than in the atorvastatin monotherapy group (22% vs 7%; P <.01). At 4 weeks, levels of LDL-C, triglycerides, and non-high-density lipoprotein cholesterol were reduced significantly more by combination therapy than by doubling the dose of atorvastatin (LDL-C −22.8% versus −8.6%; P <.01). The combination regimen had a safety and tolerability profile similar to that of atorvastatin alone.

Conclusions

The addition of ezetimibe to the starting dose of 10 mg/day of atorvastatin followed by response-based atorvastatin dose titration to a maximum of 40 mg/day provides a more effective means for reducing LDL-C levels in patients at high risk for CHD than continued doubling of atorvastatin as high as 80 mg/day alone.     

Surgical therapies for pulmonary arterial hypertension

Surgical therapies for the treatment of pulmonary arterial hypertension typically are reserved for patients who are deemed to be refractory to medical therapy and have evidence of progressive right-sided heart failure. Atrial septostomy, a primarily palliative procedure, may stave off hemodynamic collapse from right-sided heart failure long enough to permit a more definitive surgical treatment such as lung or combined heart-lung transplantation. This article discusses indications for and results of atrial septostomy and lung and heart-lung transplantation in patients who have pulmonary arterial hypertension.     

Compensation in Academic Medicine: Progress Toward Gender Equity

Background Studies have documented substantial salary disparities between women and men in academic medicine. While various strategies have been proposed to increase equity, to our knowledge, no interventions have been evaluated. Objective This paper aims to assess the effect of an identity-conscious intervention on salary equity. Design This study shows comparison of adjusted annual salaries for women and men before and after an intervention. Participants/Setting We studied full time faculty employed in FY00 (n = 393) and FY04 (n = 462) in one College of Medicine. Intervention Compensation data were obtained from personnel databases for women and men, and adjusted for predictors. After verification of data accuracy by departments, comparable individuals within the same department who had different salaries were identified. The Dean discussed apparent disparities with department heads, and salaries were adjusted. Measurements Total adjusted annualized salaries were compared for men and women for the year the project began and the year after the intervention using multivariate models. Female faculty members’ salaries were also considered as a percent of male faculty members’ salaries. Results Twenty-one potential salary disparities were identified. Eight women received equity adjustments to their salaries, with the average increase being $17,323. Adjusted salaries for women as a percent of salary for men increased from 89.4% before the intervention to 93.5% after the intervention. Disparities in compensation were no longer significant in FY2004 in basic science departments, where women were paid 97.6% of what men were paid. Conclusions This study shows that gender disparities in compensation can be reduced through careful documentation, identification of comparable individuals paid different salaries, and commitment from leadership to hold the appropriate person accountable.     

PET/CT findings in a multicentric form of Castleman's disease

We report a case of a multicentric form of Castleman's disease (CD). A thoracic computerized tomography (CT) scan showed multiple mediastinal and bilateral axillary lymph nodes. Fluoro-18 fluoro deoxyglucose ((18)F-FDG) positron emission tomography-PET/CT scan demonstrated increased (18)F-FDG accumulation in multiple lymphatic regions and in bilateral pleural areas. The histopathological sampling of an excised left axillary lymph node revealed a multicentric form of CD, of an intermediate (mixed) cell type. The disease, its differential diagnosis and the diagnostic contribution of nuclear medicine imaging, are described.