Hypogammaglobulinemia is a common symptom in different immunodeficiencies. It is, however, not usually associated with Epstein-Barr virus (EBV) infections. The X-linked lymphoproliferative disease ...(XLP) on the other hand shows immunological changes in response to the EBV. Here we report three previously healthy boys, all of which developed persistent hypogammaglobulinemia following severe acute infectious mononucleosis. All three patients revealed T-cell abnormalities including inverted CD4/CD8 and increased CD8(+) T-cell numbers. The number of IFN-gamma-producing T cells were markedly increased in the two patients studied so far. In addition, patient 2 showed mainly T cells, instead of B cells, to be infected with the EBV. Apart from an uncle of patient 3, who died of malignant lymphoma, family history was unremarkable in all cases. All three patients exhibited mutations in the SH2D1A gene, establishing the diagnosis of XLP. Protein expression was found on immunoblot analysis in one patient with a missense mutation. Development of persistent hypogammaglobulinemia after severe primary EBV infection seems to be a specific diagnostic sign for XLP even in males with unremarkable family history.
IMPORTANCE: On the basis of observational studies, the use of thiazide diuretics for the treatment of hypertension is associated with reduced fracture risk compared with nonuse. Data from randomized ...clinical trials are lacking. OBJECTIVE: To examine whether the use of thiazide diuretics for the treatment of hypertension is associated with reduced fracture risk compared with nonuse. DESIGN, SETTING, AND PARTICIPANTS: Using Veterans Affairs and Medicare claims data, this study examined hip and pelvic fracture hospitalizations in Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial participants randomized to first-step therapy with a thiazide-type diuretic (chlorthalidone), a calcium channel blocker (amlodipine besylate), or an angiotensin-converting enzyme inhibitor (lisinopril). Recruitment was from February 1994 to January 1998; in-trial follow-up ended in March 2002. The mean follow-up was 4.9 years. Posttrial follow-up was conducted through the end of 2006, using passive surveillance via national databases. For this secondary analysis, which used an intention-to-treat approach, data were analyzed from February 1, 1994, through December 31, 2006. MAIN OUTCOMES AND MEASURES: Hip and pelvic fracture hospitalizations. RESULTS: A total of 22 180 participants (mean SD age, 70.4 6.7 years; 43.0% female; and 49.9% white non-Hispanic, 31.2% African American, and 19.1% other ethnic groups) were followed for up to 8 years (mean SD, 4.9 1.5 years) during masked therapy. After trial completion, 16 622 participants for whom claims data were available were followed for up to 5 additional years (mean SD total follow-up, 7.8 3.1 years). During the trial, 338 fractures occurred. Participants randomized to receive chlorthalidone vs amlodipine or lisinopril had a lower risk of fracture on adjusted analyses (hazards ratio HR, 0.79; 95% CI, 0.63-0.98; P = .04). Risk of fracture was significantly lower in participants randomized to receive chlorthalidone vs lisinopril (HR, 0.75; 95% CI, 0.58-0.98; P = .04) but not significantly different compared with those randomized to receive amlodipine (HR, 0.82; 95% CI, 0.63-1.08; P = .17). During the entire trial and posttrial period of follow-up, the cumulative incidence of fractures was nonsignificantly lower in participants randomized to receive chlorthalidone vs lisinopril or amlodipine (HR, 0.87; 95% CI, 0.74-1.03; P = .10) and vs each medication separately. In sensitivity analyses, when 1 year after randomization was used as the baseline (to allow for the effects of medications on bone to take effect), similar results were obtained for in-trial and in-trial plus posttrial follow-up. CONCLUSIONS AND RELEVANCE: These findings from a large randomized clinical trial provide evidence of a beneficial effect of thiazide-type diuretic therapy in reducing hip and pelvic fracture risk compared with treatment with other antihypertensive medications. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000542
Ligneous conjunctivitis is a rare form of chronic recurrent pseudomembranous disease and may be associated with systemic membranous pathological changes. Recently ligneous conjunctivitis has been ...linked to severe type I plasminogen deficiency. We report on a patient with plasminogen deficiency and severe bilateral ligneous conjunctivitis. A new treatment approach and its outcome in this patient are described.
We present the case of a 9-month-old Turkish girl with massive swelling of the eyelids and hard white pseudomembranes on both lids. The conjunctival smear was positive for Streptococcus pneumoniae. The clinical diagnosis was: ligneous conjunctivitis with superinfection. Histological investigation showed fibrin as major component of the pseudomembranes. The coagulation analyses revealed decreased plasminogen activity (<5%; normal 80-120%) and decreased plasminogen antigen (<0.4 mg/dl; normal 6-25 mg/dl). The failure of surgical therapy led to the attempt at treatment with intravenous lys-plasminogen. A significant improvement of the ocular symptoms occurred; stabilization with no recurrent pseudomembranes could be achieved for 6 months after treatment.
The initial amelioration of symptoms in our patient after systemic replacement therapy confirms the etiological importance of plasminogen deficiency in the development of ligneous conjunctivitis. Curative treatment of ligneous conjunctivitis is still not available. However, intravenous application of plasminogen offers new possibilities in therapy, although long-term treatment seems necessary.
Numerous previous studies have proposed a role for angiotensin II (AII) in the renal regulation of salt balance. At least one nephron site, the proximal convoluted segment, has been implicated in ...this role. We used in vitro microperfusion of rabbit proximal convoluted tubules to further examine this question. To insure use of appropriate in vivo concentrations as well as potency of the hormone in vitro, we measured plasma AII levels by radioimmunoassay in normal, sodium-depleted, and adrenalectomized rabbits, and measured AII activity by bioassay after incubation in various microperfusion baths. Plasma levels ranged from approximately 2 X 10(-11) to 5 X 10(-11) M. AII activity was stable in Ringer's solution plus albumin, but not in rabbit serum or Ringer's solution plus fetal calf serum. In Ringer's solution plus albumin, physiologic concentrations of AII stimulated volume reabsorption (Jv). 10(-11) M AII increased Jv by 16% (P less than 0.01). 10(-10) M AII produced a lesser increase, 7.5% (P less than 0.05). At a frequently studied, but probably pharmacologic dose, 10(-7) M AII inhibited Jv by 24% (P less than 0.001). AII at 10(-11) M did not stimulate Jv in the presence of 10(-7) M saralasin. Though previous studies have suggested agonistic effects of saralasin alone in epithelia, we found no significant effect of 10(-7) M saralasin on Jv. None of the AII doses measurably changed transepithelial voltage. We conclude that AII in physiologic doses directly stimulates Jv in proximal convoluted tubules and this effect is probably receptor mediated and, within the limits of detection, electroneutral.
Adolescents from different ethnic groups show different cigarette smoking prevalence rates, suggesting potential differences in receptivity to and influences from protobacco media. Understanding ...these differences will be helpful in tailoring smoking prevention and cessation programs for diverse adolescent populations in the United States. Data from cross-sectional surveys of 20,332 randomly sampled California boys and girls, 12-17 years of age, were analyzed. Results indicate that receptivity to protobacco media was lower among African Americans, Asian Americans, and Hispanics than among White youth. There was a consistent dose-response relationship between receptivity to protobacco media and 30-day cigarette smoking across ethnic groups. Having a cigarette brand preference was associated with the highest risk for cigarette smoking, having a favorite tobacco ad showed the lowest risk, while having received or being willing to use tobacco promotional items was associated with a moderate risk. After controlling for 13 covariates, the odds ratio for receptivity to protobacco media and 30-day cigarette smoking was significant for Whites (RR = 1.38, p < 0.01) and Hispanics (RR = 1.46, p < 0.01), but not for African American (RR = 1.05, p > 0.05) and Asian American (RR = 1.17, p > 0.05) youth. African American, Asian American, and Hispanic adolescents have a lower level of receptivity to protobacco media than do Whites. The association between media receptivity and 30-day cigarette smoking exists for all four ethnic groups without controlling for other smoking predictor variables, but only for Hispanics and Whites when other variables are controlled. Protecting adolescents from protobacco advertising influences is an important element in tobacco control among ethnic minority youth.
GI 87084B (3-4-methoxycarbonyl-4-(1-oxopropyl) phenylamino1-piperidinepropanoic acid, methyl ester, hydrochloride) was found to be a potent opioid agonist in the guinea pig ileum (EC50 = 2.4 +/- 0.6 ...nM), the rat vas deferens (EC50 = 387 +/- 44 nM) and the mouse vas deferens (EC50 = 39.5 +/- 7.4 nM). In the guinea pig ileum, GI 87084B, was roughly equivalent in potency to fentanyl (EC50 = 1.8 +/- 0.4 nM). GI 87084B was more potent in this tissue than alfentanil (EC50 = 20.1 +/- 1.2 nM) and less potent than sufentanil (EC50 = 0.3 +/- 0.09 nM). Schild analyses of antagonism of GI 87084B by naloxone yielded pKB values of 8.2 and slopes indistinguishable from unity in the guinea pig ileum and the mouse vas deferens. Insurmountable antagonism of GI 87084B by naloxone was observed in the rat vas deferens. However, an empirical measure of antagonist potency could be made: apparent pA2 = 8.1. The agonist dissociation constant (KA) for GI 87084B (220 +/- 90 nM) was determined by receptor alkylation with beta-chlornaltrexamine in the guinea pig ileum. Calculation of receptor occupancy suggested poor receptor-effector coupling and limited receptor reserve in the rat vas deferens, which could explain the insurmountable antagonism seen with higher concentrations of naloxone. These data suggest that GI 87084B acted through the mu class of opioid receptors to inhibit contraction induced by field stimulation in these tissues.
This study uses the Diffusion of Innovations Theory to examine the role of mass media–generated interpersonal communication in the adoption of antitobacco norms among opinion leaders in California. ...Data were collected from 503 key community opinion leaders within 18 California counties in 1997 as part of the Independent Evaluation of the California Tobacco Control Program. Results provide support for the proposition that tobacco control policies and behaviors of opinion leaders can be categorized according to stages in the innovation decision process. As hypothesized, the level of mass media–generated interpersonal communication was dependent upon an individual's stage of adoption such that the frequency of ad discussion increased with advancing stages on the continuum. Regression analyses also confirmed a strong positive associative trend between ad discussion and stage of adoption. Further analysis provided evidence that the impact of campaign exposure on adoption of antitobacco norms was mediated through discussion of the ads, highlighting the importance of social diffusion processes. This study provides evidence regarding the importance of using a stage‐based framework to understand the role of communication channels at distinct stages of innovation adoption and among various community opinion leaders.
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