Expression and cytokine regulation of glucocorticoid receptors in Kaposi's sarcoma.

Development of Kaposi's sarcoma (KS) after glucocorticoid therapy has been observed in a variety of clinical states including human immunodeficiency virus-1 infection and recent in vitro studies provided evidence for a direct stimulation effect of glucocorticoid hormones on KS cell proliferation. The importance of glucocorticoids in KS pathogenesis is further highlighted by the finding that glucocorticoids synergize with cytokines to promote acquired immune deficiency syndrome (AIDS)-associated KS (AIDS-KS) growth. Furthermore, cytokine effects were abrogated by the glucocorticoid antagonist RU-486. As glucocorticoid action is mediated through activation of their intracellular cognate receptors, we hypothesized that enhanced responsiveness of AIDS-KS cells to glucocorticoids may be due to elevated glucocorticoid receptor (GR) content. Indeed, high expression of GRs in AIDS-KS tumor biopsies was detected both at the level of mRNA and protein. Quantitative measurements of GRs in these specimens by a sensitive immunoassay showed that GR content was significantly elevated in the tumor tissue (4663 fmol/mg protein) compared with the uninvolved skin of the same patients (2777 fmol/mg protein), both of which were markedly above the normal skin of healthy donors (893 fmol/mg protein). Immunocytochemical analysis confirmed the presence of GRs in the cytoplasm and the nucleus of KS cells. Interestingly, four major KS cytokines, namely interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, and oncostatin M, all of which are known autocrine growth factors for AIDS-KS cells, significantly increased the expression of functional GRs in cultured AIDS-KS cells. The latter result may explain, at least in part, the synergistic effect of glucocorticoid and oncostatin M on AIDS-KS cell proliferation. Thus, the high levels of GR expression in AIDS-KS and the up-regulation of GRs by KS-growth-promoting factors may confer enhanced and sustained sensitivity to the stimulatory effects of glucocorticoids. The data presented also provide molecular bases for therapeutic interventions targeting GRs in this disease.     

Detection of hepatitis B virus DNA in the serum of Canadian hepatitis B surface antigen negative,anti-HBc positive individuals,using the polymerase chain reaction

Continuing hepatitis B virus (HBV) infection is normally associated with the presence of hepatitis B surface antigen (HBsAg) in the serum. In spite of sensitive screening assays for HBsAg, rare cases of post-transfusion HBV infection are still observed. Antibody to hepatitis B core antigen (anti-HBc) often indicates remote HBV infection but DNA hybridisation and more sensitive polymerase chain reaction (PCR) assays have demonstrated that some HBsAg negative individuals, positive for anti-HBc, have continuing HBV replication. To determine the incidence of ongoing HBV infection in a Canadian HBsAg negative, anti-HBc positive population we studied three groups with this combination of HBV markers: Group A, 36 patients referred for investigation of raised serum aminotransferases; Group B, 21 Canadian Red Cross blood donors; Group C, seven vaccinees in an Ottawa Health Care Student hepatitis B vaccination programme. The PCR was carried out using a nested PCR reaction with primers specific for the pre-core region of HBV. Seven of 36 (19%) patients in Group A had detectable HBV DNA whereas none of Group B or C were positive. This data indicates that in some HBsAg negative patients with ongoing hepatic inflammation, continuing HBV replication may persist. This was not observed in any healthy blood donors or health care students investigated. Larger studies are required, but this data would suggest that, in Canada, the addition of anti-HBc testing for all blood donors for detection of low level HBV replication would not be indicated. © 1994 Wiley-Liss, Inc.     

Simultaneous occurrence of Pneumocystis carinii pneumonia, cytomegalovirus infection, Kaposi's sarcoma, and B-immunoblastic sarcoma in a homosexual man

The most common manifestations of the acquired immunodeficiency syndrome include Pneumocystis carinii pneumonia and/or Kaposi's sarcoma. High-grade B-cell lymphomas have also been reported in homosexual men at risk for the acquired immunodeficiency syndrome. We herein present the case of a homosexual man, who presented simultaneously with Pneumocystis carinii pneumonia, acute cytomegalovirus infection, Kaposi's sarcoma, and B-cell immunoblastic sarcoma. Severe compromise of both the B- and T-cell arms of the immune system was documented. The patient had evidence of exposure to the human T-lymphotropic retrovirus III, evidence of reactivation of Epstein-Barr virus infection, and cytomegalovirus inclusions within Kaposi's sarcoma tissue. We conclude that exposure to these viral agents in the setting of severe immunocompromise may have led to the observed "opportunistic" neoplasms.     

Malignancies in the acquired immunodeficiency syndrome

Aside from opportunistic infections, several neoplasms have been identified as part of the spectrum of acquired immunodeficiency syndrome (AIDS) as defined by the Centers for Disease Control. Kaposi's sarcoma (KS) was the first such neoplasm to be recognized within the spectrum of AIDS. Although the classic form of Kaposi's sarcoma had been well recognized prior to the epidemic of AIDS, it was quite distinct from the illness that was seen in its "epidemic" form in young homosexual males. In this setting, Kaposi's sarcoma is an aggressive disease, with extensive involvement of skin and mucous membranes, early dissemination to lymph nodes, impressive development of extreme lymphedema, even in the absence of bulky adenopathy, and rapid spread to visceral organs, including lungs and gastrointestinal tract, among others. Although rapid clinical progression and short median survival have been the rule, a spectrum of disease has been seen such that some patients have survived for many years with disease limited to the skin. Certain clinical and laboratory features, such as presence of unexplained fever, night sweats, weight loss ("B" symptoms), or significant T-4-lymphocytopenia, have been identified as indicators of poor prognosis. Various therapeutic interventions have been employed in epidemic KS, and although partial and complete remissions have occurred, no regimen yet reported has significantly improved the survival of treated patients. High-dose recombinant alpha interferon has produced response rates in approximately 30% of treated patients, although toxicity has been observed in approximately 30% as well. Likewise, vinblastine has produced similar response rates with no evidence of long-term efficacy or "cure." Aside from Kaposi's sarcoma, lymphoma primary to the central nervous system was recognized early in the AIDS epidemic as a criterion for inclusion within AIDS in patients less than sixty years of age. Several years after the initial reports of disease, it became apparent that specific types of systemic lymphoma were also quite extraordinary, and the definition of AIDS was amended in June 1985 to include high-grade B-cell lymphomas in individuals who had positive serology or virology for the human immunodeficiency virus (HIV). The AIDS-related lymphomas are characteristic, both pathologically and clinically. The vast majority of these cases have been high-grade B-lymphoid tumors of either immunoblastic or small-non-cleaved type (also known as "undifferentiated," Burkitt, or Burkitt-like).(ABSTRACT TRUNCATED AT 400 WORDS)     

Estramustine phosphate compared with diethylstilbestrol. A randomized, double-blind, crossover trial for stage D prostate cancer

In a double-blind, crossover comparison, 236 patients with metastatic prostate cancer were randomized to receive estramustine phosphate (EMP) or diethylstilbestrol (DES). Previously castrated patients (66) were separately randomized. Patients kept taking their first drug until progression was proved by objective studies, at which time alternative treatment was begun. The primary determinant of efficacy was the duration between start of therapy and date of objective progression. Uncastrated patients treated with EMP had a significantly longer duration without progression than those treated with DES (p less than 0.01). The following subcategories of entry were further evaluated: little or no pain, moderate to severe pain, little reduction in activity, significant reduction in activity, presence or absence of cardiovascular disease, age above or below 70 years, and "good" or "bad" histology. For all but the last category, EMP was statistically superior to DES. Patients who underwent orchiectomy less than 3 months before randomization had nonprogression rates similar to those for noncastrated men in both groups. Secondary (crossover) therapy was less effective than first therapy in both groups: 46% of patients receiving EMP and 40% receiving DES had no progression at 6 months. Clinical and laboratory adverse experiences were similar for both drugs, except that gastrointestinal disturbances were more common in the EMP group.     

The floating knee. 40 cases of ipsilateral fractures of the femur and the tibia

Summary Floating knee is the term used to describe simultaneous fractures of the femur and tibia in the same limb. Thirty nine patients, with 40 such injuries, are presented with a follow up interval of six months to five years. The final functional result was poor if the femoral fracture was situated in the condylar flare and the results were comparatively better in those cases treated by cast bracing or when the fracture of the femur was stabilised internally. In all cases the fracture of the tibia was treated conservatively.

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Résumé Sous le terme de «genou flottant» les auteurs décrivent les fractures simultanées du fémur et du tibia au niveau du même membre. Ils présentent 40 lésions de ce type, chez 39 sujets, avec un recul compris entre six mois et cinq ans. Le résultat fonctionnel est médiocre lorsque le siège de la fracture du fémur est juxta-articulaire. Comparativement, les résultats sont meilleurs lorsque la fracture du fémur a été immobilisée dans une attelle plâtrée ou stabilisée par ostéosynthèse. Toutes les fractures du tibia ont été traitées orthopédiquement.

     

Quality of life profiles and their association with clinical and demographic characteristics and physical activity in people with a stoma: a latent profile analysis

Quality of Life Research - Quality of life can be negatively impacted by the formation of a stoma and is influenced by a number of factors. Research to date treats people with a stoma as a...     

Facilitators and Barriers in Cross-Country Transport of Evidence-based Preventive Interventions: a Case Study Using the Family Check-Up

Prevention Science - This study is a qualitative analysis of facilitators and barriers in the dissemination of Family Check-Up (FCU), a U.S.-developed preventive intervention in Sweden. The FCU is...