Brentuximab vedotin followed by bendamustine supercharge for refractory or relapsed Hodgkin lymphoma.

We evaluated the impact on progression-free survival (PFS) of achieving a deep metabolic response at 2-deoxy-2[18F] fluoro-d-glucose positron emission tomography (FDG-PET) in patients with refractory or relapsed (R/R) classic Hodgkin lymphoma (cHL) following a new salvage regimen named Bv+Bs (brentuximab vedotin + bendamustine supercharge), from 2013 to 2017. In this real-life study, 20 consecutive patients (aged <60 years) with R/R cHL after failure of ≥1 salvage treatments received Bv+Bs regimen consisting of 3-days outpatient IV infusions of 1.8 mg/kg of Bv on day 1 of each 3-week cycle combined in sequence to bendamustine on days 2 and 3 of the treatment cycle at a fixed dose of 120 mg/m2 per day, for a total of 4 courses. A robust primary prophylaxis approach, including premedication, antimicrobials, stimulating factors, and cytomegalovirus monitoring, was systematically performed. The 20 patients (all evaluable) underwent 4 courses of Bv+Bs with a median dose intensity of 100% for both Bv and Bs. Ten patients (50%) experienced grade ≥3 treatment-related adverse events, without requiring hospitalization. At post-Bv+Bs reevaluation, 80% of patients had deep metabolic responses with Deauville 5-point scale scores ≤2. Thereafter, 14 patients (70%) received autologous hematopoietic stem cell transplantation (HSCT; peripheral blood stem cells previously harvested in 12 cases), and 4 patients (10%) received allogeneic HSCT. At a median follow-up of 27 months from Bv+Bs regimen initiation, the 2-year PFS of the entire population was 93.7% (95% confidence interval, 62.7% to 99.6%). Our data suggest that Bv+Bs regimen-driven strategy may be a promising salvage option to improve long-term control of high-risk Hodgkin lymphoma.

Coping with psychological aftermath of school violence: the teacher and the assaulted staff action program.

Violence in the United States has become a national public health epidemic. Increasingly, much of this violence has been committed by our young people. School settings have not been exempt from these aggressive acts, and principals, teachers, and support staff have been victims of murder, physical and sexual assaults, verbal threats, and the destruction of personal property. This present paper outlines a cost-effective, empirically-based, crisis intervention approach that was designed for health care providers, and that has immediate application to providers of school psychological services. Known as the Assaulted Staff Action Program (ASAP), ASAP has provided needed support to these employee victims of violence and has been associated with sharp reductions in facility violence. Since ASAP interventions are appropriate for all victims of violence, the implications of an ASAP approach for school faculty and staff victims are examined. The roles of school counselors in designing, fielding, and maintaining an ASAP program are presented.

Detection of nucleic acids in cells and tissues by in situ polymerase chain reaction.

The solution-based polymerase chain reaction (PCR) method for amplification of defined gene sequences has proved a valuable tool not only for basic researchers but also for clinical scientists. Using even a minute amount of DNA or RNA and choosing a thermostable enzyme from a large variety of sources, one can enlarge the amount of the gene of interest, which can be analyzed and sequenced. Therefore, genes, or segments of gene sequences present only in a small sample of cells or small fraction of mixed cellular populations can be examined. One of the major drawbacks of the solution-based PCR technique is that the procedure does not allow for the association of amplified signals of a specific gene segment with the histological cell type(s) (1-2). For example, it would be advantageous to determine what types of cells in the peripheral blood circulation or in pathological specimens carry HIV-1 gene sequences, a vector used for gene therapy, an aberrant gene in a leukemia patient, or to determine the percentage of leukemia cells present following antitumor therapy.

Localization of human herpesvirus type 8 (HHV-8) in the Kaposi's sarcoma tissues and the semen specimens of HIV-1 infected and uninfected individuals by utilizing in situ polymerase chain reaction.

Kaposi's sarcoma (KS) is a form of skin cancer, most commonly found in individuals suffering from acquired immunodeficiency syndrome, or AIDS. However, before the worldwide infection of human immunodeficiency virus (HIV), the rare occurrence of KS was confined to two distinct groups of individuals. In the Western world, the classical form of KS was often found in older men (60-70 years of age) from the Mediterranean area. Another form called endemic KS, was found in Equatorial Africa. Currently, the most common cases of KS are found in individuals suffering from AIDS. This is called AIDS-associated KS. Between 30 and 40% of male, homosexual AIDS patients suffer from AIDS-associated KS. KS is also occasionally diagnosed in transplant patients receiving immunosuppressive drugs (to keep their body from rejecting the foreign organ). As opposed to cases of classic and endemic KS, the KS in AIDS patients progresses very quickly, often with a fatal outcome. Human herpesvirus type 8 (HHV-8) has been implicated as the cause of Kaposi's sarcoma (KS), but the exact connection of the virus to the neoplasm is not known. The virus has been detected within the sarcoma skin lesions, but has additionally been seen in peripheral blood cells, semen samples, prostate tissue, and other types of soft tissue tumors. In this study, we evaluated HHV-8 within the skin lesion of KS as well as in semen specimens obtained from HIV-1 infected and uninfected specimens from HIV-1-seronegative individuals. Twenty-eight tissue samples representing AIDS-associated, endemic KS, and six non-KS patients were collected for observation from different centers throughout the world. The tissues were examined utilizing in situ polymerase chain reaction (ISPCR) and hybridization to identify and localize the herpesvirus within the KS lesions. With the use of the sensitive ISPCR technique, HHV-8 DNA was detected in the spindle cells within the nodular skin lesions, as well as in the microvascular endothelial cells which line small vessels within the lesions in all forms of KS. In addition, we analysed semen specimens from HIV-1 infected and uninfected men, our analyses revealed that HHV-8 was present in the significant proportions of the HIV-1-infected-individuals' sperm, as well as in the mononuclear cells of the semen specimens. HHV-8 DNA was demonstrated, by ISPCR, in KS lesions as well as in seminal mononuclear cells and sperm of significantly high proportion of HIV-1-infected men. What role the presence of HHV-8 in the sperm cells plays in the sexual transmission of this herpesvirus will require further study. However, the reports which demonstrate that KS lesions can develop in infants of only a few weeks of age, increases the possibility that this agent may be vertically transmitted. It can be suggested that HHV-8 is relatively ubiquitous and its frequency increases with the increasing immunosuppression.

[A review of clinical studies on the efficacy and tolerance of intravenous ciprofloxacin]. / Rassegna di studi clinici sull'efficacia e tollerabilità della ciprofloxacina endovenosa.

A review of the literature. Ciprofloxacin is a fluorinate quinolone with a broad spectrum of activity against gram-positive and gram-negative organisms. Orally administered ciprofloxacin has been successfully used in a variety of clinical settings, but reservations remain regarding the use of oral antibiotics in the treatment of serious infections. Furthermore, many seriously ill patients are unable to take drugs orally. An intravenous form of ciprofloxacin has undergone extensive clinical investigation for the treatment of a variety of infections in hospitalized patients. Reported here are the results of some clinical trials showing the effectiveness and safety of intravenous/sequential therapy with ciprofloxacin.

Rheumatoid factors and circulating immune complexes in HIV-infected individuals.

We studied serological aspects of autoimmunity in patients with AIDS, AIDS-related complex (ARC) and in individuals at risk for AIDS. Immunoglobulin (Ig) M, IgG and IgA rheumatoid factors (RF) were quantified by enzyme-linked immunosorbent assay (ELISA), Ig by radial immunodiffusion, and circulating immune complexes (CIC) by the CIC-conglutinin and CIC-complement 1q (C1q) assays. Mean IgM RF levels were normal in AIDS patients, but those of ARC patients were higher and more frequent than the levels defined by agglutination methods. Similar observations were made for intravenous drug users (IVDU) and for both HIV-seropositive and HIV-seronegative homosexual men. Mean IgG RF levels were normal in AIDS and ARC patients but high in homosexual men and, to a lesser degree, in IVDU. IgA RF levels were high in many AIDS and ARC patients, in homosexual men, and in haemophiliac and control groups. The selective increase of the IgA isotype in AIDS was confirmed by the Ig results, which also showed an IgG increase in all groups. IgM were mainly high in people with ARC. CIC were detected in 68% of ARC patients by both methods, and in 55% of AIDS patients by CIC-Clq. A high incidence of positive samples in all at-risk populations, but particularly in seronegative individuals, was observed using CIC-conglutinin. CIC-C1q also revealed larger amounts of CIC in HIV-seronegative individuals, mainly in homosexual men. The study of these humoral aspects of autoimmunity provides useful information on the impairment of B-cells in patients with AIDS and ARC.(ABSTRACT TRUNCATED AT 250 WORDS)

Meperidine in detoxification of hospitalized heroin addicts.

Forty-six heroin abusers were hospitalized and treated with meperidine either alone or in association with clonidine. Meperidine was given orally in rapidly decreasing doses according to three different schedules. The majority of patients (87%) successfully completed the detoxification program. The best meperidine starting posology was 200 mg four times daily, which allowed stoppage of the opioid treatment after gradual reduction of the daily dose in a mean time of 9.5 days. Association with clonidine was not proven to be useful. This study shows that meperidine can be effectively used in rapidly decreasing doses in the pharmacological detoxification treatment of hospitalized heroin addicts.

Expression of factor V on human umbilical vein endothelial cells is modulated by cell injury.

Since human endothelial cells synthesize Factor V but do not secrete it into the medium, we studied the effects of cell injury on the availability of Factor V at the surface of these cells. Human umbilical vein endothelial cells (HUVEC), grown to confluency and incubated with human 125I Factor Va, specifically bound 5000 to 7000 molecules per cell. In the absence of added Va, no antigen was detected on adherent HUVEC with either labeled anti-V(Va) monoclonal or polyclonal IgG. However, exogenous Va, not V, prebound to these cells allows binding of labeled 125I anti-V(Va). Immunodectectibility of bovine Factor V contributed by fetal calf serum in the concentration used in cultures is less than 0.1% of that detected in human plasma. HUVEC, suspended by scraping from dishes, specifically bound 4000 molecules/cell of 125/I monoclonal IgG against V(Va). Although undisturbed cells excluded trypan blue, dye uptake by many of the suspended HUVEC indicated cell injury. Quantitation of injury by 51Cr release after scraping followed by multiple passages through an 18 g needle showed that 51Cr release increased with number of manipulations up to 60% and was observed almost immediately after manipulation. We suggest that little Factor V(Va) is present on the surface of intact adherent HUVEC. However, mechanical injury to HUVEC released or exposed endogenous Factor V(Va), resulting in expression of V that might mediate Factor Xa binding as well as activation of protein C by thrombin. Thus, injured, but not intact, HUVEC could participate in both promoting and limiting blood coagulation.