Diversity of pituitary cells in primary cell culture. An immunocytochemical study

A bioassay system for rapid detection of carcinogenic agents has been developed using male Fischer 344 rats to bridge the gap between long-term carcinogenicity tests and short-term screening assays. The system, called the medium-term liver bioassay, is fundamentally based on the 2-stage hypothesis of tumor production, employing initiation by diethylnitrosamine (200 mg/kg, i.p.) in the first stage and test chemical administration during the second, in combination with two-thirds partial hepatectomy. It requires only 8 wk for animal experimentation and a further few weeks for quantitative analysis of immunohistochemically demonstrated glutathione S-transferase placental form positive hepatic foci. A total of 291 chemicals/substances have already been analyzed in our laboratory. Among 63 chemicals that were proved to be carcinogenic in the liver of rat and/or mouse, 57 (90%) gave positive results irrespective of their mutagenicity. Negative compounds include peroxisome proliferators and tamoxifen. Even nonhepatocarcinogens were positive at a rate of 24%. Eighty-six percent (12/14) of mouse liver carcinogens were also positive. On the other hand, only 2 out of 45 noncarcinogens showed very weak positivity. Thus, the efficacy of the system for hepatocarcinogens has been well established. This bioassay is increasingly regarded as an appropriate alternative test for carcinogenicity risk assessment and is practically used for a rapid evaluation of hepatocarcinogenicity of chemicals.     

Infrequent association: massive inguinoscrotal bladder hernia, multiple scrotal lithiasis, and bilateral obstructive uropathy]

BACKGROUND AND AIMS OF THE STUDY: Surgical treatment of functional tricuspid regurgitation associated with advanced valvular disease remains controversial, mainly due to the difficulty in choosing between valve replacement or reconstructive surgery. Failure to correct tricuspid regurgitation during valvular surgery carries a poor prognosis, as reoperation may represent a significant risk to the patient. Thus correct tricuspid valve surgery is vital to achieve improved early and long-term clinical results. METHODS: A total of 142 patients underwent concomitant tricuspid annuloplasty with mitral valve replacement and their clinical outcome was assessed. RESULTS: Overall hospital mortality rate was 11.3%. Seven patients died during follow up. The overall actuarial survival rate for 10 years was 74.1 +/- 14.2%. Postoperatively, 75.8% of the patients had no residual tricuspid insufficiency, while 24.2% had first- or second-degree tricuspid insufficiency and were treated medically. All patients were in NHYA functional class I or II postoperatively. CONCLUSION: Clinically, it is important to assess the severity of functional tricuspid insufficiency before and/or during the operation. Bicuspidalization annuloplasty for functional tricuspid insufficiency has provided good results, with a low incidence of reoperation and significant clinical improvement. The technique could be used in most patients with functional tricuspid regurgitation.     

An artificial intelligent diagnostic system on differential recognition of hematopoietic cells from microscopic images

The endothelium participates actively in homeostatic mechanisms such as the regulation of vascular tone and maintenance of a nonthrombotic environment, as well as directing biological responses such as leukocyte trafficking to inflammatory sites. Disruption of these processes leads to disease. In the antiphospholipid antibody syndrome autoantibodies provoke the endothelium to develop a prothrombotic surface. In systemic vasculitides associated with presence of antineutrophil cytoplasm antibodies, it is likely that the autoantibodies incite premature neutrophil activation, disrupted neutrophil-endothelium interactions and endothelial damage. This review considers how normal endothelial functions may be subverted in disease and how active endothelial responses may contribute to disease.     

A PMLRARalpha transgene initiates murine acute promyelocytic leukemia

The malignant cells of acute promyelocytic leukemia (APL) contain a reciprocal chromosomal translocation that fuses the promyelocytic leukemia gene (PML) with the retinoic acid receptor alpha gene (RAR alpha). To test the hypothesis that the chimera PMLRAR alpha plays a role in leukemogenesis, we expressed a PMLRAR alpha cDNA in myeloid cells of transgenic mice. PMLRAR alpha transgenic mice exhibited impaired neutrophil maturation early in life, which progressed at a low frequency over the course of several months to overt APL. Both the preleukemic state and the leukemia could be transplanted to nontransgenic mice, and the transplanted preleukemia could progress to APL. The APL recapitulated features of the human disease, including a response to retinoic acid. Retinoic acid caused the leukemic cells to differentiate in vitro and in vivo, eliciting remissions of both the preleukemic state and APL in mice. Our results demonstrate that PMLRAR alpha impairs neutrophil differentiation and initiates the development of APL. The transgenic mice described here provide an apparently accurate model for human APL that includes clear evidence of tumor progression. The model should be useful for exploring the molecular pathogenesis of APL and the mechanisms of the therapeutic response to retinoic acid, as well as for preclinical studies of therapeutic regimens.     

The in vivo metabolic pattern of low-grade brain gliomas: a positron emission tomographic study using 18F-fluorodeoxyglucose and 11C-L-methylmethionine

OBJECTIVE: The object of the present study was to identify metabolic differences between low-grade astrocytomas and oligodendrogliomas and to improve their diagnosis and noninvasive assessment, because both types of tumors look very similar from the point of view of clinical and radiological data (as assessed by computed tomography and magnetic resonance imaging). METHODS: Before any aggressive treatment, 22 patients with primary low-grade gliomas (astrocytomas in 12 patients and oligodendrogliomas in 10) were investigated with positron emission tomography for both glucose metabolism (18F-fluorodeoxyglucose) and amino acid uptake (11C-L-methylmethionine). An original software that allows a full metabolic analysis of the tumor region of interest (defined from the T1-weighted magnetic resonance image) and compares tumor tissue uptake tracer concentrations with average healthy tissue values has been implemented for data processing. Heterogeneity of each individual tumor has been taken into account and was expressed in histograms, which provided data about the mean and also extreme and intermediate values of tracer concentrations and the way these values are distributed among the full tumor mass. RESULTS: It has been shown that both tumor types exhibit a glucose hypometabolism (slightly more pronounced with astrocytomas), whereas they strongly differ in methionine uptake, which is high in all oligodendrogliomas and either decreased, normal, or moderately increased in astrocytomas. This latter metabolic difference between both tumor populations may be partially explained by their different cell densities. CONCLUSION: This study suggests that despite similar radiological and clinical presentations, these two kinds of low-grade gliomas are metabolically different and could therefore have specific responses to different therapies. Moreover, their in vivo metabolic follow-up with positron emission tomography should rely on different parameters, depending on their histological type; methionine uptake may be more relevant than glucose metabolism in the follow-up of oligodendrogliomas.     

Potency comparison of peptidomimetic inhibitors against HIV-1 and HIV-2 proteinases: design of equipotent lead compounds

The results of investigation of haptoglobin (Hp) types in 596 donor blood samples in some towns of Ukraine (Dnepropetrovsk, Kharkov, Odessa, Kiev, Uzhgorod, Zhitomir) are presented. Three normal Hp types (Hp1-1, Hp2-1 and Hp2-2) have been found. The reliable interpopulation differences in the Hp types frequency were not found. On the whole the Hp types frequency in the type Hp1-1 comprised 12.7%. In the type Hp2-1-48.1% and in the type Hp2-2-36.5%. The frequency of the gene Hp1 is 0.38. The frequency of the Hp types and of the gene Hpl in Ukraine is similar to that in population of Eastern Europe and European Part of Russia.     

Ability of pediatric residents to read critically research papers]

PURPOSE: To compare the response rates, toxicities and survival durations of elderly patients (70 years of age or more) with those of younger patients (less than 70 years of age) with non-small-cell lung cancer (NSCLC) treated with cisplatin-based chemotherapy. PATIENTS AND METHODS: We analyzed retrospectively the data of 203 assessable patients entered on a prospective randomized trial of cisplatin-based combination chemotherapy. Chemotherapy consisted of three dosage regimens: (1) vindesine and cisplatin (VP); (2) mitomycin, vindesine and cisplatin (MVP); or (3) etoposide and cisplatin alternating with vindesine and mitomycin (EP/VM). RESULTS: A greater proportion of elderly patients had localized disease and more squamous cell carcinoma than non-elderly patients. The overall response rates were 44% in the elderly group and 28% in the non-elderly group. In the EP/VM arm, the response rate was significantly better in the elderly group than in the non-elderly group. The frequency of grade 4 leukocytopenia in the MVP and EP/VM arms in the elderly group was significantly greater than in the non-elderly group (P < 0.05). No differences were found in nonhematological toxicities between the two groups. There was no difference in overall survival between the groups. CONCLUSION: Elderly patients treated with mitomycin-containing regimens have higher hematologic toxicities than younger patients. The results of this study are consistent with the previously reported pharmacologic data on mitomycin suggesting altered pharmacokinetics in elderly patients. The improved response rate in the elderly patients was probably because more elderly patients had earlier disease, squamous cell carcinoma and better performance status. Cisplatin-based chemotherapy was tolerable for most elderly NSCLC patients with good performance status.     

Low molecular weight heparins. Implications in anesthesia and resuscitation

Low molecular weight heparins are a group of drugs that have only recently been introduced in clinical practice. The are widely used for prophylaxis in thromboembolic disease and are being employed increasingly to treat established venous thrombosis. One way in which these drugs are often used is for prophylaxis in the perioperative period for patients at high risk of developing venous thromboembolism, and the anesthesiologist must therefore be familiar with the main aspects of this application. We review pharmacological characteristics of these drugs as well as the literature on low molecular weight heparins, stressing points of main interest to the anesthesiologist and intensive care recovery unit specialist, namely adverse effects (mainly bleeding) and the implications that use of low molecular weight heparin will have on choice of anesthetic (in particular the dilemma of whether to use local/regional anesthesia).