Rituximab for primary chronic cold agglutinin disease: a prospective study of 37 courses of therapy in 27 patients

Conventional therapies for primary chronic cold agglutinin disease (CAD) are ineffective, but remissions after treatment with the anti-CD20 antibody rituximab have been described in a small, prospective trial and in some case reports. In this study we report on 37 courses of rituximab administered prospectively to 27 patients. Fourteen of 27 patients responded to their first course of rituximab, and 6 of 10 responded to re-treatment. In both groups combined, responses were achieved after 20 of 37 courses, giving an overall response rate of 54%. We observed 1 complete and 19 partial responses. Two nonresponders and 3 patients who experienced relapse received second-line therapy with interferon-alpha combined with a new course of rituximab, and 1 nonresponder and 2 patients who experienced relapse achieved partial responses. Responders achieved a median increase in hemoglobin levels of 40 g/L (4 g/dL). Median time to response was 1.5 months, and median observed response duration was 11 months. We conclude that rituximab is an effective and well-tolerated therapy for CAD. Histologic and flow cytometric findings suggest that some of the effect may be mediated by mechanisms other than the elimination of clonal lymphocytes. We were unable to predict responses from the hematologic, immunologic, or histologic parameters before therapy.     

Intrafamilial spread of hepatitis C virus

Summary We studied the prevalence of antibodies against hepatitis C virus (anti-HCV) among 530 household contacts of 225 anti-HCV- positive subjects (index cases). Twenty-six (4.9%) relatives had anti-HCV, a proportion higher than that found among blood donors (175 of 22,435; 0.78%) (p<0.001). We did not find any differences regarding the type of relation with the index case (sexual or nonsexual). The prevalence of anti- HCV increased with the age of the relatives, with the contact time with the index case, and with the time of exposure to HCV. On the other hand, the anti-HCV was associated mainly with the existence of cirrhosis or hepatocellular carcinoma in the patient. We concluded that intrafamilial transmission may be an important mechanism in the spread of HCV.

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Ausbreitung des Hepatitis-C-Virus in Familien

Zusammenfassung 530 Kontaktpersonen im häuslichen Bereich von 225 anti-HCV-positiven Personen (Indexfälle) wurden auf Antikörper gegen HCV untersucht. 26 Verwandte (4,9% der Untersuchten) waren anti-HCV-positiv. Dieser Prozentsatz übersteigt bei weitem den von Blutspendern (175 von 22.435 positiv; 0,78%); (p<0,001). Es fanden sich keine Unterschiede im Hinblick auf eine sexuelle oder nicht sexuelle Beziehung zwischen Indexfall und Kontaktperson. Die anti-HCV-Prävalenz nahm mit dem Alter der Verwandten und der Dauer des Kontaktes mit dem Indexfall und der Expositionszeit gegenüber HCV zu. Bei den Patienten bestand in der Mehrzahl der Fälle ein Zusammentreffen von anti-HCV-Positivität und Leberzirrhose oder hepatozellulärem Karzinom. Wir schließen aus unseren Beobachtungen, daß die übertragung in der Familie möglicherweise ein wichtiger Ausbreitungsweg für HCV ist.

     

High-definition optical magnification with digital chromoendoscopy detects gastric mucosal changes in dyspeptic-patients

BACKGROUND Accurate detection of gastric infection by Helicobacter pylori(H.pylori) and premalignant lesions are important for effective provision of treatment,preventing the development of gastric neoplasia.Optical enhancement systems with optical magnification improved the identification of mucosal superficial and vascular patterns in patients with dyspepsia.AIM To evaluate an optical enhancement system with high-definition magnification,for diagnosis of normal gastric mucosa,H.pylori-associated gastritis,and gastric atrophy.METHODS A cross-sectional,nonrandomized study from November 2015 to April 2016 performed in a single-tertiary academic center from Ecuador.Seventy-two consecutive patients with functional dyspepsia according to the Rome III criteria,were tested for H.pylori using a stool antigen test and were assigned to an Hp+group or an Hp-control group.Esophagogastroduodenoscopy with highdefinition optical magnification and digital chromoendoscopy was performed,and patients were classified into 4 groups,in accordance to the microvasculararchitecture pattern of the mucosa.Interobserver and intraobserver agreement among operators were calculated.RESULTS Of the 72 participants,35 were Hp+ and 37 were Hp-.Among 10 patients with normal mucosal histology in biopsy samples,90% had a Type I pattern of microvascular architecture by endoscopy.Among participants with type IIa and type IIb patterns,significantly more were Hp+ than Hp-(32 vs 8),and most(31 out of 40) had histological diagnoses of chronic active gastritis.Two of the three participants with a histological diagnosis of atrophy had a type III microvascular pattern.The type I pattern predicted normal mucosa,type IIa–IIb predicted H.pylori infection,and type III predicted atrophy with sensitivities of 90.0%,91.4%,and 66.7%,respectively.The intraobserver and interobserver agreements had kappa values of 0.91 and 0.89,respectively.CONCLUSION High-definition optical magnification with digital chromoendoscopy is useful for diagnosis of normal gastric mucosa and H.pylori-associated gastritis with high accuracy,but further studies are needed to determine whether endoscopic diagnosis of gastric atrophy is feasible.     

Knowledge and beliefs of breast cancer among elderly Puerto Rican women: validation process of scales

This paper presents the results of the validation process to determine the concepts for knowledge and beliefs about breast cancer early detection practices among Puerto Rican elderly women. An initial questionnaire was designed based on the scientific literature review and focus group experiences. To determine its reliability and validity, 50 elderly women, stratified by type of profession and place of residence, were interviewed twice. Consistency of the questionnaire was analyzed using binomial test, matched t-test, Pearson correlation coefficient, and Cronbach's coefficient effect. Factor analysis (FA) was the statistical technique used to analyze the grouping of the knowledge and beliefs statements. FA indicated that three scales for knowledge and one for beliefs can be constructed. The purpose of the scales was to identify differences among groups, according to breast cancer early detection practices. Construct validity was performed to determine the number of statistical associations between the scales and these practices. The results showed that beliefs scales was associated with practice of mammogram (p < 0.05), and visit to the gynecologist (p < 0.05) while the knowledge scale for early-detection was associated with the clinical breast examination (p < 0.05). The beliefs scale had better consistency than the knowledge scale. The Cronbach's alpha was 0.75 for the beliefs' scale and 0.30, 0.41 and 0.43 for each defined knowledge scale, respectively.     

Safety and immunogenicity of a combined hepatitis B virus-Haemophilus influenzae type B vaccine comprising a synthetic antigen in healthy adults

The combined HB-Hib vaccine candidate Hebervac HB-Hib (CIGB, La Habana), comprising recombinant HBsAg and tetanus toxoid conjugate synthetic PRP antigens has shown to be highly immunogenic in animal models. A phase I open, controlled, randomized clinical trial was carried out to assess the safety and immunogenicity profile of this bivalent vaccine in 25 healthy adults who were positive for antibody to HBsAg (anti-HBs). The trial was performed according to Good Clinical Practices and Guidelines. Volunteers were randomly allocated to receive the combined vaccine or simultaneous administration of HB vaccine Heberbiovac-HB and Hib vaccine QuimiHib (CIGB, La Habana). All individuals were intramuscularly immunized with a unique dose of 10 microg HBsAg plus 10 microg conjugated synthetic PRP. Adverse events were actively recorded after vaccine administration. Total anti-HBs and IgG anti-PRP antibody titers were evaluated using commercial ELISA kits at baseline and 30 days post-vaccination. The combined vaccine candidate was safe and well tolerated. The most common adverse reactions were local pain, febricula, fever and local erythema. These reactions were all mild in intensity and resolved without medical treatment. Adverse events were mostly reported during the first 6-72 hours post-vaccination. There were no serious adverse events during the study. No severe or unexpected events were either recorded during the trial. The combined vaccine elicited an anti-HBs and anti-PRP booster response in 100% of subjects at day 30 of the immunization schedule. Anti-HBs and anti-PRP antibody levels had at least a two-fold increase compared to baseline sera. Even more, anti-HBs antibody titer showed a four-fold increase in 100% of volunteers in the study group. The results indicate that the combined HB-Hib vaccine produces increased antibody levels in healthy adults who have previously been exposed to these two antigens. To our knowledge, this is the first demonstration of safety and immunogenicity for a combined vaccine comprising recombinant HBV and synthetic Hib antigens. The present results support phase I-II clinical trial in the target population, two months old healthy infants.     

DNA damage and prediction of radiation response in lymphocytes and epidermal skin human cells

The success of radiotherapy in eradicating tumours depends on the total radiation dose, but what limits this dose is the tolerance of the normal tissues within the treatment volume. Studies involving fibroblast survival have demonstrated the theoretical feasibility of a predictive assay of radiation sensitivity, but such an assay is still far from clinical application. Using pulsed-field gel electrophoresis (PFGE), we have quantified the initial “apparent” number of DNA double-strand breaks (dsb) induced by the radiation as an alternative measure of sensitivity in 2 different normal cell types from the same patients, epidermal skin cells and lymphocytes. We found significant inter-individual variation in the measured dsb (1–5 dsb/Gy/DNA unit). We also found a linear correlation between molecular damage in lymphocytes and skin samples from the same patient (slope = 0.83; r = 0.694; p = 0.0001). These results suggest that the initial number of dsb could be used as an indicator of the in vivo response to radiation. Int. J. Cancer 76:354–361, 1998.© 1998 Wiley-Liss, Inc.