Liver involvement in the sulfone syndrome

A patient being treated with dapsone developed a hypersensitivity reaction with typical features of the "sulfone syndrome," including fever, malalse, and hepatitis. All abnormalities rapidly reversed with discontinuance of the dapsone regimen and institution of prednisone therapy. Hepatic involvement may be a prominent feature of the sulfone syndrome and may be of the hepatocellular or cholestatic type. Based on our review of the Food and Drug Administration reports, this syndrome appears to be relatively uncommon, but physicians need to recognize that expression of this syndrome may be incomplete. More clinical data are necessary to better define the incidence and pathogenesis of sulfone-induced liver disease.     

Type B hepatitis after needle-stick exposure: prevention with hepatitis B immune globulin. Final report of the Veterans Administration Cooperative Study.

Hepatitis B immune globulin (HBIG) and immune serum globulin (ISG) were examined in a randomized, double-blind trial to assess their relative efficacies in preventing type B hepatitis after needle-stick exposure to hepatitis B surface antigen (HBsAG)-positive donors. Clinical hepatitis developed in 1.4% of HBIG and in 5.9% of ISG recipients (P = 0.016), and seroconversion (anti-HBs) occurred in 5.6% and 20.7% of them respectively (P less than 0.001). Mild and transient side-effects were noted in 3.0% of ISG and in 3.2% of HBIG recipients. Available donor sera were examined for DNA polymerase (DNAP) and e antigen and antibody (HBeAg; anti-HBE). Both DNAP and HBeAg showed a highly statistically significant correlation with the infectivity of HBsAg-positive donors. Hepatitis B immune globulin remained significantly superior to ISG in preventing type B hepatitis even when the analysis was confined to these two high-risk subgroups. The efficacy of ISG in preventing type B hepatitis cannot be ascertained because a true placebo group was not included.     

Directional genomic hybridization for chromosomal inversion discovery and detection

Chromosomal rearrangements are a source of structural variation within the genome that figure prominently in human disease, where the importance of translocations and deletions is well recognized. In principle, inversions—reversals in the orientation of DNA sequences within a chromosome—should have similar detrimental potential. However, the study of inversions has been hampered by traditional approaches used for their detection, which are not particularly robust. Even with significant advances in whole genome approaches, changes in the absolute orientation of DNA remain difficult to detect routinely. Consequently, our understanding of inversions is still surprisingly limited, as is our appreciation for their frequency and involvement in human disease. Here, we introduce the directional genomic hybridization methodology of chromatid painting—a whole new way of looking at structural features of the genome—that can be employed with high resolution on a cell-by-cell basis, and demonstrate its basic capabilities for genome-wide discovery and targeted detection of inversions. Bioinformatics enabled development of sequence- and strand-specific directional probe sets, which when coupled with single-stranded hybridization, greatly improved the resolution and ease of inversion detection. We highlight examples of the far-ranging applicability of this cytogenomics-based approach, which include confirmation of the alignment of the human genome database and evidence that individuals themselves share similar sequence directionality, as well as use in comparative and evolutionary studies for any species whose genome has been sequenced. In addition to applications related to basic mechanistic studies, the information obtainable with strand-specific hybridization strategies may ultimately enable novel gene discovery, thereby benefitting the diagnosis and treatment of a variety of human disease states and disorders including cancer, autism, and idiopathic infertility.     

Spontaneous platelet aggregation in type IIB Tampa von Willebrand disease is inhibited by the 52/48-kDa fragment of normal von Willebrand factor, which contains the GPIb binding domain

The association of Type IIB von Willebrand disease (vWD) with chronic persistent thrombocytopenia and spontaneous platelet aggregation has recently been recognized. It has been shown that IIB von Willebrand factor (vWF) can initiate platelet aggregation by binding to the platelet glycoprotein (GP) lb receptor and inducing exposure of the GpIIb/IIIa fibrinogen receptor. In this study we demonstrate the increased binding of Type IIB Tampa vWF with normal platelets when compared with nonthrombocytopenic Type IIB vWF. Studies further demonstrate that spontaneous platelet aggregation initiated by IIB Tampa vWF can be blocked by a 52/48-kDa fragment of normal vWF, which contains the binding domain.     

Crohn''s Colitis Complicated by Superimposed Invasive Amebic Colitis

The clinical characteristics and endoscopic appearance of inflammatory bowel disease (IBD) may be very similar to those of amebic colitis. Physicians, especially in areas in which amebiasis is endemic, are familiar with this difficulty. Moreover, in individual cases, it may even be impossible to distinguish between the two conditions, since stool specimens, bowel biopsies, and serological studies may be negative for Entamoeba histolytica, even in the presence of invasive amebic colitis. Invasive amebiasis may rarely be superimposed on IBD, which further complicates the issue. We report here a young patient with a 7-yr history of Crohn's colitis proven histologically who developed invasive amebic colitis during steroid and 6-mercaptopurine treatment for active disease. Stool specimens, mucosal biopsies, and serological studies were negative for E. histolytica, and the diagnosis was established on pathological examination of a surgically resected bowel. Anti-amebic therapy should be considered in endemic areas in cases of persistent IBD.     

The diagnostic laboratory tests for histoplasmosis: analysis of experience in a large urban outbreak

Of 495 patients reported in a large urban histoplasmosis outbreak, we studied 276 whose serologic tests were done in a single laboratory. Serologic test results were positive in 96% of these patients (compared with less than 5% of controls from an endemic area), cultures were positive in 22%, and special stains in 19%. The immunodiffusion test results were negative in 13% of patients who had positive findings by complement fixation, and 1% had positive results only by immunodiffusion. The complement fixation test was almost twice as sensitive as the immunodiffusion test in patients with subclinical infection. The serologic response differed significantly among the clinical syndromes with higher titers in cavitary and lower titers in disseminated disease. Factors associated with titers of 1:64 or greater to both antigens were black race and immunocompetence. High mycelial titers were also associated with more intense exposure, and high yeast titers were associated with age less than 36 years. No prognostic significance could be proved for fourfold titer rises or falls or persistence of precipitins.     

Skin lesions treated with azathioprine and prednisone. Comparison of nontransplant patients and renal transplant recipients.

Cutaneous complications were studied in 120 patients who received azathioprine and prednisone for six months to ten years. Questionnaire, chart review, and physical examination were used to assess skin infections, rash, verrucae, herpes zoster, tumors, condylomata acuminata, hair loss, and color changes. One hundred patients with renal allografts were compared with 20 nontransplant patients with systemic disease. Dermatologic problems were more frequent in transplant recipients (P less than .02) than in nontransplant patients. Verrucae were more frequent in transplant recipients (P less than .001). There was no significant increase in the total number of skin manifestations with increasing length of therapy, although warts and herpes zoster increased with time. This study suggests that the increase in the total number of skin lesions noted in previous studies of renal transplant recipients is not as prevalent in nontransplant patients who receive azathioprine and prednisone, due primarily to fewer verrucae in nontransplant patients.     

Gender differences in recovery after coronary artery bypass graft surgery

This study examined the effect of gender on symptom evaluation, symptom response, and physical functioning following coronary artery bypass graft surgery. Symptom evaluation and symptom response were measured at baseline and 2, 4, and 6 weeks and 3 months following surgery, and physical functioning was measured at baseline, 6 weeks, and 3 months. The sample included 46 men and 19 women randomly assigned to the routine care group of a larger study examining symptom management intervention influence on recovery outcomes in elderly coronary artery bypass graft patients. No significant differences were found in symptom evaluation, symptom response, or physical functioning by gender over time. Women reported consistently higher symptom evaluation scores for shortness of breath, fatigue, depression, sleep disturbance, swelling, and anxiety and lower mean physical and vitality subscale scores than men at every time point. Gender-specific symptom management strategies should be developed and tested to address the differences in the reporting of symptoms by men and women.