Acute recognition and management of congestive heart failure

The acute recognition and management of CHF is challenging. A basic understanding of the determinants of cardiac performance and myocardial O2 consumption along with the pathophysiology of CHF is essential knowledge for the physician undertaking to treat this serious disorder. The basic value of the patient history and physical examination along with assessment of noninvasive tests remains unquestioned, but in addition much relevant and sophisticated information can be gained by invasive hemodynamic monitoring. The cardiopulmonary profile generated by such monitoring allows the physician to use specific hemodynamic and circulatory data for the purpose of manipulating these variables favorably for the heart and circulation. A wide array of therapeutic options is currently available, but, in general, respiratory support and pharmacotherapy are the mainstays of treatment. The traditional agents like digitalis and diuretics have assumed a lesser role during the last decade because of the availability of potent new vasodilator and inotropic agents. In addition, certain mechanical, procedural, and surgical options can be used if circumstances are urgent. In the final analysis, physicians who manage these patients must possess strong cognitive skills but also the clinical reflexes to carry them out: for every hemodynamic and circulatory action, they must be prepared to counter quickly and decisively with a clinical reaction which utilizes these principles to optimize cardiac function. It is hoped that the strategies presented in this article will allow them to perform in such a manner.     

Ingestion of immune bloodmeals and infection of Aedes fowleri, Aedes mcintoshi, and Culex pipiens with Rift Valley fever virus

Rift Valley fever (RVF) virus infection, dissemination, and transmission rates were determined for Aedes fowleri, Aedes mcintoshi and Culex pipiens 7 or 10 days after sequentially feeding to repletion on RVF virus immune hamsters and RVF viremic hamsters, or after feeding on a mixture of RVF virus immune sheep serum and RVF viremic hamster blood through a pledget. No significant differences in infection or dissemination rates were detected among Ae. fowleri and Cx. pipiens feeding to repletion on immune hamsters before or after feeding to repletion on a viremic hamster. Similarly, no significant differences in infection, dissemination, or transmission rates were observed among Ae. fowleri and Cx. pipiens feeding to repletion on immune hamsters or nonimmune (control) hamsters 0 or 24 hr after inoculation with RVF virus. Infection rates were significantly higher for Ae. fowleri (56/66, 85%) and Cx. pipiens (123/148, 83%) fed only on viremic hamsters than for those interrupted to complete feeding on an immune hamster (Ae. fowleri [24/49, 59%], Cx. pipiens [66/131, 50%]) or a nonimmune hamster (Ae. fowleri [32/51, 63%], Cx. pipiens [69/127, 54%]). However, no significant differences were detected in infection, dissemination, or transmission rates among Ae. fowleri, Ae. mcintoshi or Cx. pipiens fed on a viremic hamster and interrupted to complete feeding on an immune vs. a nonimmune hamster. Results from interrupted feeding experiments were significantly different from pledget feeding experiments.(ABSTRACT TRUNCATED AT 250 WORDS)     

Severe erythroblastopenia and hemolytic anemia during a hepatitis A infection

A 41-year-old woman had acute hepatitis A infection complicated with severe anemia due to selective erythroblastopenia and hemolysis. A mechanism involving a cellular immune reaction is suggested. The hematological complications resolved during steroid treatment. She later developed a transient seropositive arthritis.     

The predictive value of steroid hormone receptor analysis in breast, endometrial and ovarian cancer

The predictive value of female sex steroid, estrogen and progesterone, receptor (ER and PR, respectively) assays in breast, endometrial and ovarian cancer is reviewed with emphasis on comparative aspects of these malignant tumors in relation to their hormone dependency. The endocrine etiology of these three tumor types seems to be at least partly different, and so is the expression of these receptors in normal and malignant tissues of the breast, endometrium and ovary. There is a tendency for decreased receptor concentrations and disappearance of these receptors in association with advancement of these malignancies. There is also a decrease in the presence and concentrations of ER and PR in relation to loss of differentiation in breast and endometrial cancer. Receptor analyses have an established position in the selection of patients with advanced breast cancer for endocrine treatment, and they give promise of a similar application in endometrial cancer and in endometrioid cancer of the ovary. It is not clear whether the disease-free interval is related to the presence or concentrations of ER or PR as such in the tumor tissue. There is better survival in breast cancer patients with receptor-positive tumors, which might be due to a response to endocrine treatment. The same seems to be true for patients with endometrial cancer. Future progress in the application of female sex steroid receptor analyses in breast, endometrial and ovarian cancer needs additional controlled clinical trials and more highly developed receptor assays.     

Rapidly growing breast cancer: results of a retrospective analysis with a study of prognostic factors

Between January 1977 and December 1982, 66 consecutive patients have been treated for unilateral, rapidly progressing, non metastatic breast cancer. They were divided into three groups: Group A (n = 10): tumor whom volume had increased during the 2 months before diagnosis; Group B (n = 30): inflammatory signs (erythema, skin oedema, elevated local temperature) involving less than one half of the breast; Group C (n = 26): inflammatory signs involving more than one half of the breast. All patients where managed similarly: 3 to 4 courses of chemotherapy (CMF: n = 24; AVCF: n = 42), then loco regional irradiation therapy with cobalt 60, followed by maintenance chemotherapy, only if the first chemotherapy had proved effective (CMF: n = 13; AVCF: n = 27). Nine patients with residual tumor after radiotherapy underwent mastectomy with axillary dissection. The actuarial 5 years survival for the whole group is 29%, and respectively 49%, 38% and 9% for the groups A, B and C. The median disease free intervals are 43, 29 and 12 months respectively. Fifteen prognostic factors likely to influence overall survival or disease free survival were evaluated. With univariate analysis, 8 factors were found to be of individual prognostic value: extent of initial erythema, erythema present after initial chemotherapy, erythema present after radiotherapy, non menopaused status, tumor diameter greater than 10 cms, residual breast tumor (clinical or radiographic) after maintenance chemotherapy, supra clavicular adenopathy (N3). Age at the diagnosis, type of chemotherapy, or performance of a radical mastectomy did not influence the prognosis. Multivariate analysis using the Cox-model isolated 3 factors of bad prognosis: erythema involving the whole breast at initial diagnosis, erythema present at the end of initial chemotherapy, N3.     

Combining Vaccines with Conventional Therapies for Cancer

Preclinical and clinical investigations currently underway are employing novel strategies for combining vaccines with conventional and experimental anticancer therapies. To date, the FDA has not approved a therapeutic cancer vaccine. However, the results of recent investigations suggest an increasing role for vaccines in new models of combination therapy for many types of cancer. This article reviews and discusses therapeutic cancer strategies that employ vaccines in combination with local radiation, chemotherapy, hormone therapy, and anti-CTLA-4 mAb. Preclinical studies have shown that certain anticancer agents have immune modulatory effects that result in up-regulation of surface expression of MHC molecules, tumor-associated antigens, or Fas on malignant cells, rendering them more susceptible to immune destruction. Preliminary results of clinical studies using combination strategies have demonstrated a postvaccination antigen cascade, prolonged time to disease progression, and improved overall survival. Several larger randomized trials are ongoing, and more are required to support these findings.     

Synthesis of Indole-Containing 2-Thiobarbituric Acid Derivatives

The synthesis of barbituric acid derivatives containing α-phenylskatyl residues substituted at C(5) is described. The initial compound was α-phenylnorgramine, which had been previously successfully used for the alkylation of a series of CH-acids, in particular, for the synthesis of diethyl-1H-indol-3-yl(phenyl)methylmalonate. This compound has been used to obtain a series of 2-thiobarbituric acid derivatives, which are expected to possess antioxidant, membrane protector, and radioprotector properties.__________Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 1, pp. 29 – 33, January, 2005.     

Novel azapeptide inhibitors of cathepsins B and K. Structural background to increased specificity for cathepsin B

Abstract: We have designed and synthesized a new series of azapeptides which act as potential inhibitors of cathepsin B and/or cathepsin K. Their structures are based upon the inhibitory sites of natural cysteine protease inhibitors, cystatins. For the synthesized azapeptides, the equilibrium constants for dissociation of inhibitor–enzyme complex, K_i, were determined. Comparison of these values indicated that all of the azainhibitors act much stronger toward cathepsin B. Z‐Arg‐Leu‐His‐Agly‐Ile‐Val‐OMe ( 7 ) proved to be approximately 500 times more potent for cathepsin B than for cathepsin K. To be able to explain the obtained experimental values we used the molecular dynamics procedures to analyze the interactions between cathepsin B and compound 7 . We also determined the structure of the most potent and selective cathepsin B azainhibitor by means of NMR studies and theoretical calculations. In this report, we describe SAR studies of azapeptide inhibitors indicating the influence of the conformational flexibility of the examined compounds on inhibition of cathepsins B and K.     

Synthesis and anti-tuberculous activity of diesters based on isosteviol and dicarboxylic acids

Diesters based on isosteviol and dicarboxylic acids were synthesized and tested for antituberculous activity. Isosteviol and some of its derivatives exhibit appreciable tuberculostatic properties in vitro, the activity being dependent on the length of the polymethylene spacer connecting two ent-beyeran fragments. The mechanism of the antituberculous action of isosteviol derivatives are discussed. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 9, pp. 12–13, September, 2006.