Human herpesvirus 6: infection and disease following autologous and allogeneic bone marrow transplantation

Human herpesvirus 6 activity (HHV-6) was studied in 15 allogeneic and 11 autologous marrow transplantation patients. After transplantation, HHV-6 was isolated from the peripheral blood mononuclear cells of 12 of 26 patients (6 allogeneic and 6 autologous). All isolates were variant B. Eleven of 26 and 12 of 19 patients showed salivary shedding of HHV-6 DNA before and after transplantation, respectively. The antibody titer increased in 7 of 26 patients. Thus, 23 of 26 patients showed evidence of active HHV-6 infection either by virus isolation, salivary shedding, or increases in antibody titers. The fraction of saliva specimens positive in 19 patients was negatively associated with their antibody titers (P= .005). The proportion of cultures positive increased after transplantation (P = .007). Sinusitis was associated with HHV-6 isolation in autologous recipients (P= .002). In allogeneic patients, active human cytomegalovirus infection was associated with HHV-6 isolation (P = .04). No association was observed between HHV-6 infection and GVHD, pneumonia, delay in engraftment, or marrow suppression. Of the 120 clinical events analyzed in 26 patients, HHV-6 was defined as a probable cause of 16 events in 9 patients based on the propinquity of HHV-6 activity and the clinical event plus the absence of other identified causes of the event.     

Selective induction of a glycoprotein IIIa ligand-induced binding site by fibrinogen and von Willebrand factor

Ligand-induced binding sites (LIBS) are neoantigenic regions of glycoprotein (GP)IIb-IIIa that are exposed upon interaction of the receptor with the ligand fibrinogen or the ligand recognition sequence (RGDS). LIBS have been suggested to contribute to postreceptor occupancy events such as full-scale platelet aggregation, adhesion to collagen, and clot retraction. This study examined the induction requirements of a GPIIIa LIBS with regard to ligand specificity. Through the use of the anti-LIBS D3, we report that this complex- activating antibody induces fibrinogen- and von Willebrand factor- binding to GPIIb-IIIa on intact platelets. Bound ligand was detected by flow cytometric analysis and platelet aggregation assays. These bound ligands increased the number of D3-binding sites and altered the affinity of D3 for GPIIb-IIIa on platelets. In contrast, activation of platelet GPIIb-IIIa by D3 did not increase the binding of another RGD- containing ligand, vitronectin. Furthermore, bound vitronectin on thrombin-stimulated platelets did not cause the expression of the D3 LIBS epitope. We conclude direct activation of GPIIb-IIIa in the absence of platelet activation results in selective ligand interaction and that D3 LIBS induction requires the binding of the multivalent ligands, fibrinogen or von Willebrand factor. Thus, the region of GPIIIa recognized by D3 may be an important regulatory domain in ligand- receptor interactions that directly mediate platelet aggregation.     

Age-bridging among young, urban, heterosexual males with asymptomatic Chlamydia trachomatis

OBJECTIVES: To determine the prevalence of age-bridgers among urban males aged 14-24 years, asymptomatically infected with chlamydia and to determine factors that distinguish age-bridgers from non age-bridgers. An index was defined as an age-bridger if within 2 months, he had had at least two sexual partners who differed from him in age by > or =2 years. METHODS: Infected males provided data about themselves and up to four sexual partners in the past 2 months. Bivariate and multivariable logistic regression was used in the analysis. RESULTS: The prevalence of age bridging was 21% in Baltimore and 26% in Denver. In both cities, in bivariate analysis, age-bridgers and their partners engaged in significantly more risky sexual behaviours. In adjusted multivariable analysis after controlling for number of sexual partners, age bridging was associated with having a sexual partner in the past 2 months, who, at time of last sexual intercourse, was drinking. CONCLUSION: Age-bridgers represented major proportions of the study populations and, along with their sexual partners, were more likely to engage in risky sexual behaviours. Male age-bridgers may be key players in the transmission of sexually transmitted infections among youth linking age-disparate sexual networks.     

Cardiac Cycle Time Effects on Performance, Phasic Cardiac Responses, and Their Intercorrelation in Choice Reaction Time

Temporal relationships between phasic cardiac responses and choice reaction time (RT) performance were studied in 8 human volunteers using a speed-accuracy tradeoff design. “Cardiac cycle time” was varied by presenting stimuli at either the R wave of the electrocardiogram or 350 msec afterward. The speed and accuracy of choice RT performance were systematically manipulated by rewarding subjects for responding as close as possible to five different RT targets (150, 200, 250, 300, and 350 msec). The magnitude of both the cardiac deceleration which preceded stimulus onset and the cardiac acceleration which followed the response varied systematically with RT; both anticipatory deceleration and accelerative recovery were larger for faster RTs. More importantly, the timing of the shift from anticipatory deceleration to accelerative recovery varied systematically as a function of both cardiac cycle time and RT. Correlations between performance and cardiac interbeat intervals (IBIs) before, during, and after the RT were uniformly low, but showed consistent variation as a function of temporal proximity of the IBI to the stimulus. An hypothesis which relates timing of task completion, timing of vagal inhibition, and phasic cardiac responses was proposed to account for the timing of the shift from anticipatory deceleration to accelerative recovery.     

Determinants of the response to beclomethasone aerosol at various dosage levels: A multiple regression analysis to identify clinically useful predictors

In a dose-response study of beclomethasone aerosol (BA) therapy we noted considerable variation in responsiveness of the 34 participating asthma patients. The data were analyzed by stepwise multiple regression to identify factors which favored or inhibited the response to the drug. Among the 33 variables tested, the significant determinant variables differed depending on the BA dosage. The range studied was 200, 400, 800, and 1,600 μg/day. The reliability of several sets of these criteria for predicting the results of a therapeutic trial of BA in a given patient were checked by a cross-validation method. This demonstrated 79.4% prognostic accuracy for a set of 4 clinical variables and 88.2% for a set of 6 clinical and laboratory variables. Those patients whose symptom improvement was poor, despite receiving 1,600 μg BA per day, differed from the responsive patients mainly in the greater degree of chronic obstructive lung disease (COLD) associated with asthma. On the other hand, the symptom response to this dosage of BA in this group tended to be more favorable in nonsmoking, female asthmatic patients with frequent asthma attacks but relatively little associated COLD and no recurrent mucopurulent bronchitis. We did not demonstrate important correlations for some variables reported in other studies to significantly influence BA responsiveness, e.g., associated chronic bronchitis, prednisone daily dosage or duration, the pretreatment values for air flow indices, or allergic skin test reactivity. These data indicate that a therapeutic trial of BA is likely to benefit patients with long-term asthma regardless of its pathogenetic classification or chronicity. They further suggest that a trial with high-dose BA rather than low dosage can give more accurately predictable results.     

Endocardial fibroelastosis, neurologic dysfunction and unusual facial appearance in two brothers, coincidentally associated with dominantly inherited macrocephaly

We describe two brothers with endocardial fibroelastosis, unusual facial appearance, and cryptorchidism. The surviving brother has mental retardation, seizures and possible hypothalamic dysfunction. Both brothers have a head size greater than two standard deviations above normal; this appears to be related to superimposed presence of coincidental autosomal dominant macrocephaly in this family.     

Immunodeterminant specificity of human immunity to type III group B streptococcus

The type III polysaccharides of group B Streptococcus in its native state chemically consists of glucose, galactose, glucosamine, and sialic acid. The core of this polysaccharide lacks sialic acid and precipitates with type III antiserum to give a partial identity with the precipitate between the native antigen and this serum. The core determinant is immunochemically similar to the capsular polysaccharide of type XIV Streptococcus pneumoniae, while the native type III group B streptococcal polysaccharide does not cross-react with type XIV pneumococcal antiserum. In human sera, it is antibody directed to the native antigen which correlates very highly with opsonic immunity (r = 0.94) while a poorer correlation exists between antibody to the core antigen and opsonins (r = 0.51 P less than 0.001). In natural infections, as association exists between low levels of maternal antibody to the native antigen and risk of disease in the infant. This association is not true for antibody to the core structure, where both infected infants and their mothers have much higher levels of antibody to the core than the native antigens. Infected infants are also more likely to respond to infection by developing antibody to the native antigen. Immunization of 12 adults with multivalent pneumococcal polysaccharide induced significantly better antibody response to the core antigen than to the native, and this vaccine induced opsonic activity in only one recipient. Immunization of adults with type III group B streptococcal antigens induced antibody to the native determinant which correlated with opsonic activity. Therefore, it would appear that native group B streptococcal polysaccharides will provide the best candidate antigens for immunization.     

Vitamin D uptake and metabolism by perfused rat liver: influences of carrier proteins

Several blood proteins have been associated with the transport of vitamin D sterols. Vitamin D is synthesized in the skin or absorbed from the intestine, and there is evidence for different rates of transfer to the liver from these sources. To evaluate the influences of various plasma proteins on the hepatic accumulation of vitamin D3, human plasma albumin, D-binding protein, chylomicrons, chylomicron remnants, low density lipoprotein (LDL) and high density lipoprotein were isolated and incubated with [3H]vitamin D3 before single-pass perfusions of the isolated, vitamin D-deficient rat liver. Hepatic uptake of sterol was greatest when vitamin D3 was presented on LDL or chylomicron remnants, whereas D-binding protein permitted the least uptake. Silicic acid chromatography revealed greater amounts of 25-hydroxyvitamin D3 when substrate was presented on carriers known to have hepatic receptors. After iv administration of tracer amounts of vitamin D3 to fasting rats, gradient gel electrophoretic analyses of plasma revealed most of the [3H] associated with the vitamin D-binding protein, and smaller amounts associated with LDL and high density lipoprotein. Our results suggest a major role for chylomicron remnants in the hepatic presentation of ingested vitamin D3 and support the possibility that hepatic delivery from cutaneous sites may involve lipoprotein carriers.     

Near fatal puerperal thrombosis on Björk-Shiley mitral valve prosthesis.

A 22-year-old woman required emergency mitral valve replacement three weeks post partum because of thrombotic obstruction of her prosthetic mitral valve. Low dose subcutaneous heparin was administered from the 17th week of pregnancy. Though there was a successful fetal outcome, heparin did not prevent thrombosis on the prosthesis and its continuation into the puerperium proved nearly fatal.