Altered allelic distributions of the serotonin transporter gene in migraine without aura and migraine with aura

Allelic variation of the human serotonin transporter gene (HSERT), a highly plausible candidate gene for susceptibility to migraine, was investigated in 266 individuals with migraine, including 173 having migraine without aura (MO), 94 having migraine with aura (MA), 18 with co-occurrence of MO and MA, plus 133 unaffected controls. The distribution of a polymorphism with different forms of a variable tandem number repeat (VNTR) in intron 2 were compared. The MO group had an over-representation of genotypes with two twelve repeat alleles (STin2.12) and a reduction of genotypes containing one ten repeat (STin2.10) compared to controls. The MA group showed a similar pattern, but also a trend towards an increase in genotypes containing the nine repeat allele of the VNTR (STin2.9). Genotypes containing this allele were found in 6.4% of the MA group compared to 2.3% of controls. The group with co-occurrence of MO and MA had a significantly different pattern of overall allele frequency distribution from controls, reflecting a reduction in genotypes containing the STin2.10 allele and a shift both to STin2.9 carriers and to STin2.12 homozygosity. These results support the view that susceptibility to MO and MA has a genetic component, that these disorders are distinct, and that genetic susceptibility may in some cases be associated with a locus at or near the serotonin transporter gene.     

Incubation of platelet concentrates before transfusion does not improve posttransfusion recovery

Incubation of stored platelet concentrates (PCs) at 37 degrees C for 1 hour has been reported to result in a better morphology score and improved platelet recovery. A study was conducted in adult patients with leukemia to determine whether incubation of stored PCs results in an improved platelet recovery as measured by 10-minute posttransfusion corrected count increments (CCI). Eligible patients had platelet counts of less than 30,000 per microL and were clinically stable. Patients were transfused with 6 to 10 units of PC stored for 3 days (15 studies) or 4 days (5 studies). Platelets were pooled and then split in two equal volumes so that each patient received two sequential half-transfusions, one incubated at 37 degrees C for 1 hour and the other kept at 22 degrees C for 1 hour. Patients were randomized as to which half-transfusion was received first. The mean CCI of the incubated half-transfusions was 13.6 x 10(3) when they were given first and 14.5 x 10(3) when given second; this was not significantly different from the mean CCI of the nonincubated half-transfusions: 13.8 x 10(3) when they were given first and 13.8 x 10(3) when given second. In contrast to earlier reports, it can be concluded that incubation of pooled PCs does not improve platelet recovery.     

Platelet transfusions administered to patients with splenomegaly

It is generally felt that increments in platelet counts following platelet transfusions to patients with splenomegaly are severely reduced as a result of splenic sequestration. The results of 631 random-donor platelet transfusions administered to 66 thrombocytopenic patients with palpable splenomegaly were analyzed. Increasing splenomegaly had a significant effect on corrected count increments (CCIs), with the greatest deterioration occurring in patients whose spleens were palpable greater than 2.0 cm below the left costal margin. A similar trend was noted when the percentage of transfusions with satisfactory CCIs was compared, although it should be noted that 42 percent of the transfusions produced CCIs greater than 7500, and a large proportion produced clinically helpful absolute increments. Splenomegaly also had an effect on platelet survival: in patients with CCIs greater than 7500, the mean ratio of 24-hour CCIs to 1-hour CCIs was 0.29 to 0.47 in patients with various degrees of splenomegaly, as compared to an expected value of 0.6 to 0.7. Sixteen patients, most with spleens palpable less than 5.0 cm below the left costal margin, consistently had CCIs greater than 7500. A significant fraction of patients with splenomegaly can benefit from platelet transfusion, and thus splenomegaly should not preclude intensive therapeutic approaches.     

Survivors of acute myocardial infarction: who is at risk for sudden cardiac death?

Coronary artery disease is the leading cause of death in the United States. Approximately half of the deaths attributable to coronary artery disease are sudden cardiac deaths. A logical approach to prevention of sudden death is to identify those who are at risk and then to initiate effective therapy. Left ventricular dysfunction, frequent ventricular ectopic activity, nonsustained ventricular tachycardia, and late potentials have been identified as markers for increased risk of sudden cardiac death. The sensitivity and specificity of these risk factors vary, and the positive predictive power is less than satisfactory. The value of invasive electrophysiologic testing for risk stratification in the general postinfarction patient population remains unclear. In addition to these diagnostic difficulties, prevention of sudden death also has been limited by imperfect efficacy and potential lethal effects of the currently available antiarrhythmic agents. Automatic implantable defibrillators are effective for aborting sudden death; however, the potential for more general use of automatic defibrillators in asymptomatic but high-risk postinfarction patients has not been evaluated.     

Identification and characterization of an HIV-2 antibody-positive blood donor in the United States

BACKGROUND: As of June 1, 1992, the Food and Drug Administration recommended that all donated blood be screened for antibodies specific to HIV-2. Despite broad serologic surveillance, only two cases of HIV-2 infection had been detected among potential blood and plasma donors since the implementation of the test. CASE REPORT: The identification of a third HIV-2 antibody-positive blood donor is reported. The first- time donor was identified by routine screening procedures as anti-HIV- 1/HIV-2-reactive, and that status was confirmed by licensed HIV-1 Western blot. Concurrent whole-virus lysate enzyme immunoassay and Western blot for HIV-2 were strongly positive, but the possibility of HIV-1 cross-reactivity could not be eliminated. The donor was notified, counseled, and deferred from future donation. He subsequently enrolled in a Centers for Disease Control and Prevention-sponsored epidemiologic study of HIV-positive former donors. When it was revealed during the standardized interview that he was a native of an HIV-2-endemic region, follow-up samples were submitted to the Centers for Disease Control and Prevention. Investigational HIV-1 and HIV-2 peptide enzyme immunoassays indicated that this infection was due to HIV-2 only. CONCLUSION: Enzyme immunoassays for antibodies to synthetic peptides of HIV-1 and HIV-2 may be useful in differentiating the two viruses in individuals with ambiguous Western blot results and risk factors for HIV-2 infection.     

A southern analysis of Rh blood group genes: association between restriction fragment length polymorphism patterns and Rh serotypes

Polymorphisms within the Rh blood group system have been defined by serologic agglutination methods, but have not yet been defined at the DNA level. Two closely related genes associated with the Rh D antigen and with the Rh C/c and E/e antigens have been cloned. We used a Southern analysis incorporating probes to the 5' and 3' regions of the Rh C, E gene and D gene to identify polymorphisms associated with Rh C/c and E/e antigens, respectively. The D gene dosage could be determined by comparing the relative intensities of the D bands with bands from the 5' and 3' region of the Rh C, E gene. The concordance between restriction fragment length polymorphism (RFLP) patterns and serologic phenotypes for 102 randomly selected blood donors was 100% for C, e, and D, 94.8% for c, and 94.3% for E. The data are consistent with the sequences encoding the C/c epitopes residing on the 5' side of those for the E/e epitopes. All samples discordant for the 3' probe and E had the cE (r") serotype. These data show that the gene coding for the cE serotype is different in Rh-positive and -negative individuals. The study demonstrates that Rh DNA typing, including D gene dosage measurements and Rh gene haplotyping, may supplement traditional serotyping methods in transfusion medicine.     

Quantitation of ferritin iron in plasma, an explanation for non- transferrin iron

In 33 patients with thalassemia and idiopathic hemochromatosis, plasma ferritin protein levels ranged from 36 to 5,850 micrograms/L. The iron content of this ferritin as determined by immunoprecipitation ranged from undetectable amounts to 507 micrograms/L. The mean iron content of ferritin protein in those and other subjects with plasma ferritin concentrations of over 1,000 was 6.8% +/- 2.7%. Plasma transferrin was usually saturated with iron in patients with measurable ferritin iron, but exceptions occurred. In studies using electrophoretic separation, it was shown that some ferritin iron moved to transferrin during in vitro incubation, whereas exchange in the opposite direction was extremely limited. Because some plasma ferritin iron was measured by the standard colorimetric plasma iron determination, these observations (a) indicate that plasma ferritin contains a significant amount of iron (b) indicate that a significant proportion of nontransferrin iron in individuals with nontransferrin iron as detected by standard plasma iron and total iron-binding capacity measurements is due to the presence of ferritin, and (c) suggest that large amounts of ferritin iron may affect the saturation of plasma transferrin.     

Sudden death after radiofrequency ablation of the atrioventricular node in patients with atrial fibrillation

OBJECTIVES: We evaluated the incidence and predictors of sudden death after atrioventricular (AV) node ablation and pacemaker implantation. BACKGROUND: Sudden death may occur after radiofrequency catheter ablation of the AV node and pacemaker implantation in patients with atrial fibrillation (AF). Whether it is related to the procedure or to pre-existing heart disease remains unclear. METHODS: All patients who had radiofrequency catheter ablation of the AV node and pacemaker implantation for rate control of medically refractory AF were identified retrospectively and observed prospectively. All patients with sudden death after ablation were identified. The relationship between the procedure and sudden death was defined on the basis of the time between the two as "likely," "possibly" or "unlikely." RESULTS: Of 334 consecutive patients with AF who underwent AV node ablation, nine had sudden death after the ablation. Four patients (1.2%) had sudden death likely related to the procedure: in 3 patients, arrest occurred within 48 h after the procedure; in one patient, arrest occurred four days after the procedure. In three other patients (0.9%), sudden death was possibly related to the procedure because the event occurred within three months afterward. The remaining two deaths were unrelated to the procedure. Diabetes, New York Heart Association functional class (>or=II), preprocedure ventricular arrhythmia, mitral or aortic stenosis, aortic regurgitation and chronic obstructive pulmonary disease were independent predictors for sudden death. CONCLUSIONS: Sudden death likely or possibly related to catheter ablation occurred in 7 of 334 patients (2.1%). Risk of sudden death is highest within two days after the procedure.