The antitumor immune response in HER-2 positive,metastatic breast cancer patients

The aim of this study was to determine the basis for anti-tumor immune reactivity observed in patients with human epidermal growth factor receptor-2 (HER-2) (3+) breast carcinoma using an in vitro model in which the role of the HER-2-specific monoclonal antibody Herceptin was also investigated. Patients with metastatic breast cancer who had their primary tumor resected were included in this study. Peripheral blood mononuclear cell (PBMC)-dependent cytotoxicity in the presence or absence of Herceptin were assessed using the survival of target breast adenocarcinoma MDA-MB-361 cells as a parameter in a (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) test. We observed a significant increase in PBMC-dependent cytotoxicity when autologous serum was introduced in the assay. Furthermore, the addition of Herceptin significantly increases their cytotoxicity. These data suggest that autologous serum constitutively contains factors that might affect PBMC-dependent cytotoxic activity against HER-2 positive cancer cells.     

Transfer of cadmium through the rat's intestinal wall

The transfer of ^115mCd through the wall of the duodenum, jejunum, and ileum in 6-week-old male albino rats was studied by the in vitro method of the “everted gut sac.” Cadmium transport through the duodenal and jejunal wall was practically the same, but it was significantly lower through the ileum. Although being highest in the duodenal wall, cadmium retention did not depend significantly on any particular intestinal segment. No cadmium transport against a chemical gradient seems to have taken place through the wall of any segment.     

Metabolic alkalosis with hypoelectrolytemia in infants with cystic fibrosis

BACKGROUND: Infants with cystic fibrosis (CF) can develop episodes of hyponatremic hypochloremic dehydration with metabolic alkalosis when they sweat excessively, which is not caused by sweating in normal infants. We investigated the incidence of the metabolic alkalosis with hypoelectrolytemia in CF infants, the possible risk factors for its occurrence and the importance of the manifestation in the diagnosis of CF. METHODS: In order to evaluate the incidence and the risk factors for the development of this sweat-related metabolic disorder in CF, we reviewed the records of all children diagnosed as having CF before the age of 12 months in a 10-year period. Data analysis included medical history data, clinical features, biochemical parameters (blood pH, serum bicarbonate, sodium, chloride and potassium levels), sweat chloride test values, as well as genetic analysis data. RESULTS: The prevalence of metabolic alkalosis in association with low serum electrolyte concentrations (hyponatremia, hypochloremia, and hypokalemia) in infant CF population in our region was 16.5%. We found no season predilection in its occurrence. Early infant age, breast-feeding, delayed CF diagnosis, heat exhaustion and the presence of severe CF transmembrane conductance regulator mutations are predisposed factors for the development of metabolic alkalosis with hypoelectrolytemia. CONCLUSIONS: The results from our study suggest that metabolic alkalosis with hypoelectrolytemia is a relatively common manifestation of CF in infancy. The possibility of CF should be seriously considered in any infant with this metabolic disorder.     

New alternative scheme for human blood coagulation

Shortening of the prothrombin time (PT) of normal 0.025 M sodium oxalate stored plasma, non-glass contact dependent, was confirmed. Shortening of PT of haemophilias A and B 0.025 M sodium oxalate stored plasma was observed. Normal kaolin partial thromboplastin time (K-PTT) of haemophilia A 0.020 M sodium oxalate plasma, maintained in 16 × 100 mm glass tube, was observed. Very prolonged K-PTT of the haemophilia B 0.020 M sodium oxalate plasma, maintained in 16 × 100 mm glass tubes, was observed. Based on the outlined results, a new alternative pathway in blood coagulation is discussed.     

Evaluation of cytogenetic damage in nuclear medicine personnel occupationally exposed to low-level ionising radiation

The aim of this study was to provide data on genetic hazards associated with occupational exposure to low doses of ionising radiation in nuclear medicine departments. The DNA damage in peripheral blood lymphocytes of medical staff was assessed using the chromosome aberration test. Altogether 120 subjects (60 exposed and 60 controls) participated in the study. The exposed subjects showed significantly higher frequencies of chromosome aberrations than controls. Significant inter-individual differences in DNA damage within the exposed population indicate different genome sensitivity. Age and sex were not confounding factors, while smoking increased DNA damage only in control subjects. This study suggests that chronic exposure to low doses of ionising radiation in nuclear medicine departments causes cytogenetic damage. For this reason, exposed medical personnel should minimise radiation exposure wherever possible. Our results also point to the significance of biological indicators, which provide information about the actual risk for the radiation-exposed individuals.     

Acute cytogenetic effects of antineoplastic drugs on peripheral blood lymphocytes in cancer patients chromosome aberrations and micronuclei

AIMS AND BACKGROUND: The aim of the present study was to evaluate the individual sensitivity of cancer patients to different antineoplastic drugs administered in standard protocols by assessing their acute cytogenetic effects on peripheral blood lymphocytes. METHODS AND STUDY DESIGN: In 12 patients undergoing cancer chemotherapy, acute cytogenetic effects on peripheral blood lymphocytes were evaluated by analysis of structural chromosome aberrations and micronuclei. All patients were given antineoplastic drugs, mainly as polychemotherapy. The frequencies of both cytogenetic biomarkers determined after the first chemotherapy cycle were compared with their pre-treatment (baseline) values. RESULTS: All chemotherapy protocols employed induced clear cytogenetic effects in both tests studied. The results obtained indicate interindividual variations between cytogenetic damage in peripheral blood lymphocytes among cancer patients. Statistically significant increases in the total number of structural chromosome aberrations and micronuclei in lymphocytes analyzed after chemotherapy compared to pre-therapy samples were observed in almost all patients studied. The highest level of chromosome damage as well as the highest incidence of micronuclei was observed following administration of the ACOP protocol (adriamycin, cyclophosphamide and vincristine). The proportions of signal-positive and signal-negative micronuclei were evaluated using DAPI staining, while silver staining revealed Ag-NOR+ and Ag-NOR- micronuclei. In some patients the incidence of signal-positive and Ag-NOR+ micronuclei after treatment was increased, indicating a more pronounced susceptibility of particular chromosomes to damage caused by antineoplastic drugs. CONCLUSIONS: With regard to the results obtained we may conclude that both parameters used in the present study on peripheral lymphocytes are sensitive biomarkers and can be successfully employed for biomonitoring of acute cytogenetic effects induced by antineoplastic drugs in standard clinical protocols for cancer treatment.     

In vitro biological efficiency of tenocyclidine – TCP and its adamantane derivative TAMORF

Tenocyclidine – TCP showing a broad spectrum of pharmacological activity including antidotal effect in organophosphorus compounds poisoning, radioprotective and anticancer effects. We investigated in vitro interactions of TCP and its adamantane derivative – TAMORF with human erythrocyte acetylcholinesterase (AChE). Moreover, their genotoxicity and radioprotective activity on human white blood cells were studied using the alkaline comet assay, viability testing and the analysis of the structural chromosome aberrations. The tested compounds were found to be weak inhibitors of AChE, for TCP IC₅₀ = 1 × 10⁻⁵ M and for TAMORF IC₅₀ > 1 × 10⁻³ M, without reactivating and protective effects on AChE inhibited by soman. Results suggest that TCP modified by the replacement of the cyclohexyl ring with an adamantly ring and piperidine with morpholine group (TAMORF) have lower toxicity. Both compounds possess low cytotoxicity and radioprotective activity, but TAMORF also shows cell growth inhibitory effects. To clarify differences in their biological efficiency observed in vitro and in vivo, additional analyses are necessary. Since TAMORF was found to significantly inhibit cell growth and proliferation in vitro, it is reasonably to consider it as a source molecule promising for further modifications and development of more potent substances with antitumor properties rather then radioprotector or antidote in organophosphorus poisoning.     

Thrombendvenectomy for Organized Portal Vein Thrombosis at the Time of Liver Transplantation

OBJECTIVE: To determine the efficacy of portal thrombendvenectomy in cases of portal vein thrombosis at the time of orthotopic liver transplantation. SUMMARY BACKGROUND DATA: Portal vein thrombosis (PVT) has been reported to have an incidence of 2% to 39% in end-stage liver disease. Multiple techniques have been suggested to treat this finding. Several reports have suggested suboptimal results after liver transplantation in recipients with PVT. METHODS: The authors prospectively collected data on 1,546 patients who underwent an initial orthotopic liver transplant at the authors' institution between December 1984 and October 1999. There were 820 male patients and 726 female patients. All recipients received either cyclosporine or tacrolimus immunosuppression. Intraoperative flows of the portal vein and hepatic artery were routinely measured. Duplex sonography was routinely performed on the first postoperative day and routinely 1, 2, 5, and 10 years after transplantation. Eighty-five patients underwent thrombendvenectomy for organized thrombus partially or completely occluding the portal vein. Postoperative treatment included low-molecular-weight dextran for 48 hours and daily aspirin for 3 months. There were 53 male patients and 32 female patients. The PVT group was compared with a control group consisting of transplant recipients without PVT. RESULTS: When compared with the control group, PVT patients were older at the time of transplantation and had a higher incidence of liver disease secondary to cryptogenic cirrhosis and Laennec's cirrhosis. There were no significant differences among both groups for 1-, 3-, and 6-year patient and graft survival rates. CONCLUSIONS: Thrombendvenectomy provides a rapid resolution of an otherwise complex problem. It is the authors' procedure of choice in cases of organized PVT at the time of transplantation. Operative time and length of stay in the intensive care unit are not prolonged, and patient and graft survival rates are not compromised.     

Importance of anticoagulant concentration for the activation of some human blood clotting factors

The effects of varying concentrations of decalcifying salts and of type of surfaces on clotting tests of plasma were studied. The results indicated that plasma obtained with 0.025 M sodium oxalate, 1 part to 9 parts of blood stored either at 3 °C or at room temperature, no matter if in glass or in siliconed tubes, always shortened its prothrombin time. Similar results in samples drawn with 0.125 M sodium citrate, and stored either in glass or in siliconed tubes were obtained, but with a very weak effect. No activation either of prothrombin or of Factor V or of Factor X was observed.

Activation of Factor VII would explain the shortening of the prothombin time.

A reacting system that uses a very small amount of calcium, and that activates Factor VII appeared responsible for that effect.