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)     

Validation of MCADD newborn screening

Medium‐chain acyl‐CoA dehydrogenase deficiency (MCADD) represents a potentially fatal fatty acid β‐oxidation disorder. Newborn screening (NBS) by tandem mass spectrometry (MS/MS) has been implemented worldwide, but is associated with unresolved questions regarding population heterogeneity, burden on healthy carriers, cut‐off policies, false‐positive and negative rates. In a retrospective case‐control study, 333 NBS samples showing borderline acylcarnitine patterns but not reaching recall criteria were genotyped for the two most common mutations (c.985A>G/c.199C>T) and compared with genotypes and acylcarnitines of 333 controls, 68 false‐positives, and 34 patients. c.985A>G was more frequently identified in the study group and false‐positives compared to controls (1:4.3/1:2.3 vs. 1:42), whereas c.199C>T was found more frequently only within the false‐positives (1:23). Biochemical criteria were devised to differentiate homozygous (c.985A>G), compound heterozygous (c.985A>G/c.199C>T), and heterozygous individuals. Four false‐negatives were identified because our initial algorithm required an elevation of octanoylcarnitine (C₈) and three secondary markers in the initial and follow‐up sample. The new approach allowed a reduction of false‐positives (by defining high cut‐offs: 1.4 μmol/l for C₈; 7 for C₈/C₁₂) and false‐negatives (by sequencing the ACADM gene of few suspicious samples). Our validation strategy is able to differentiate healthy carriers from patients doubling the positive predictive value (42→88%) and to target NBS to MCADD‐subsets with potentially higher risk of adverse outcome. It remains controversial, if NBS programs should aim at identifying all subsets of all diseases included. Because the natural course of milder variants cannot be assessed by observational studies, our strategy could serve as a general model for evaluation of MS/MS‐based NBS.     

Colorectal Cancer in the Family: Psychosocial Distress and Social Issues in the Years Following Genetic Counselling

Background

This study examined: (1) levels of cancer-specific distress more than one year after genetic counselling for hereditary nonpolyposis colorectal cancer (HNPCC); (2) associations between sociodemographic, clinical and psychosocial factors and levels of distress; (3) the impact of genetic counselling on family relationships, and (4) social consequences of genetic counselling.

Methods

In this cross-sectional study, individuals who had received genetic counselling for HNPCC during 1986–1998 completed a self-report questionnaire by mail.

Results

116 individuals (81% response rate) completed the questionnaire, on average 4 years after the last counselling session. Of all respondents, 6% had clinically significant levels of cancer-specific distress (Impact of Event Scale, IES). Having had contact with a professional psychosocial worker for cancer risk in the past 10 years was significantly associated with higher levels of current cancer specific distress. Only a minority of the counselees reported any adverse effects of genetic counselling on: communication about genetic counselling with their children (9%), family relationships (5%), obtaining life insurance (8%), choice or change of jobs (2%), and obtaining a mortgage (2%).

Conclusion

On average, four years after genetic counselling for HNPCC, only a small minority of counselled individuals reports clinically significant levels of distress, or significant family or social problems.

     

Primary infertility associated with schitosoma mansoni: a case report from the Jos plateau,north central Nigeria

Testicular schistosomiasis caused by Schistosoma mansoni is very rare and more so when associated with primary infertility. A 40 years old man from the Jos Plateau, North Central Nigeria presented with primary infertility after ten years of marriage. Sperm count revealed oligospermia and he also complained of inability to sustain erection. Testicular biopsy revealed several ova of Schistosoma mansoni in the connective tissue of the testes. Cases of infertility in endemic areas especially when there is no supply of potable water should raise suspicion of schistosomiasis among other pathologies and possible hormonal disturbances when the testes are involved.     

Antimicrobial technology in orthopedic and spinal implants

Infections can hinder orthopedic implant function and retention.Current implant-based antimicrobial strategies largely utilize coating-based approaches in order to reduce biofilm formation and bacterial adhesion.Several emerging antimicrobial technologies that integrate a multidisciplinary combination of drug delivery systems,material science,immunology,and polymer chemistry are in development and early clinical use.This review outlines orthopedic implant antimicrobial technology,its current applications and supporting evidence,and clinically promising future directions.     

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.