Influence of verapamil and digoxin on the in vitro binding of doxorubicin to the rat heart

A study has been carried out to characterize the binding of doxorubicin to heart homogenates and subcellular fractions. The technique chosen to perform the study was equilibrium dialysis and the levels of anthracycline in the samples obtained from the dialysis were assessed using HPLC. Doxorubicin has high affinity to heart homogenates and subcellular fractions such as nuclear, mitochondrial and microsomal. The binding was saturable and dose-dependent. Doxorubicin binding is decreased in the presence of digoxin and especially verapamil.     

Identification and partial characterization of two steroid 5 alpha-reductase isozymes in the canine prostate

BACKGROUND AND OBJECTIVE: Intensive induction and post-remission therapies have improved the prognosis in adult acute lymphoblastic leukemia (ALL). However, different from children, the impact of late intensification therapy in the overall results of treatment has not been consistently evaluated. The objective of this study was to analyze the results of a multicenter prospective protocol, PETHEMA ALL-89, in which, after intensive induction and consolidation therapy, randomization to receive delayed intensification treatment was performed. DESIGN AND METHODS: One hundred and eight adults (age > or = 15 years) diagnosed with ALL (ALL L3 excluded) in 22 Spanish hospitals from 1989 to 1994 were treated with a five-drug induction therapy, followed by four cycles of early post-remission treatment during four months, and maintenance therapy for two years. Patients in remission at the end of the first year were randomized to receive one six-week cycle of late intensification therapy. Uni- and multivariate analyses of early response to treatment, complete remission (CR), leukemia-free survival (LFS) and overall survival (OS) were performed. RESULTS: The median (range) age of the series was 28 (15-74) years and leukocyte count 26 x 10(9)/L (1-600). ALL L1/L2 was present in 38/70 patients, early pre-B in 13, common in 53, pre-B in 12 and T in 30 cases. The CR rate was 86%, and refractory disease 9%. Median LFS was 34 months, with a 5-yr probability of 41% (95% CI, 29-53), whereas median OS was 51 months and 5-year probability 47% (34-59%). There were no differences in either LFS and OS between patients who did or did not receive delayed intensification therapy. Prognostic factors for CR attainment were advanced age and slow response to therapy. These two features were, in addition to high leukocyte counts, the parameters with negative influence in both LFS and OS. INTERPRETATION AND CONCLUSIONS: The results of PETHEMA ALL-89 are similar to those referred in other chemotherapy-based protocols in adult ALL. Delayed intensification has not improved the length of remission and survival. Efforts to improve the prognosis of adult ALL patients must be mainly focused in early intensification treatment.     

Reduction of renal uptake of monoclonal antibody fragments by amino acid infusion

The renal uptake of radiolabeled antibody fragments and peptides presents a problem in radioimmunodetection and therapy, compromising lesion sensitivity, especially with intracellularly-retained isotopes. Previously, we showed that cationic amino acids and their derivatives are capable of significantly reducing kidney uptake in animals. We report our initial clinical results of successful renal uptake reduction in five patients who underwent cancer radioimmunodetection with 99mTc-anti-CEA Fab' fragments. METHODS: The patients were infused with two liters of a commercially-available nutritive amino acid solution (containing approximately 2.25 g/liter lysine-glutamate and 2.50 g/liter arginine), whereas 75 control patients received the same volume of saline (quantification of organ and tumor kinetics from conjugate whole-body views by ROI technique). RESULTS: The renal uptake in the amino acid group was significantly lower (p<0.05) than in the control group (11.1 +/- 2.0% injected dose versus 17.7 +/- 7.0% injected dose at 24 hr postinjection), whereas the uptake of all other organs remained unaffected. Gel filtration chromatography of the urine taken from amino-acid-treated patients showed that a significantly higher amount of excreted activity was bound to intact Fab' (53% of excreted activity) in contrast to only less than 10% in the control group. CONCLUSION: The renal uptake of monoclonal antibody fragments in patients can be reduced significantly by amino acid infusion, even at considerably lower doses than those that were safe and effective in animals. As was found in animals, the mechanism seems to rely on an inhibition of the re-absorption of tubularly-filtered proteins by the proximal tubule cells. These results encourage further clinical trials to lower the renal uptake experienced in radioimmunodetection, as well as in therapeutic trials with antibody fragments and peptides.     

Modular PPM telemetry system with radio, infra-red and inductive loop transmission

Functional studies have shown that the murine macrophage resistance gene Lsh/Ity/Bcg (candidate Nramp) regulates macrophage priming/activation for antimicrobial activity via the tumour necrosis factor-alpha (TNF-alpha)-dependent production of reactive nitrogen intermediates. Since Toxoplasma gondii also parasitizes macrophages, is a stimulator of endogenous TNF-alpha release, and is sensitive to nitric oxide-mediated killing in activated macrophages, studies were carried out using chromosome 1 congenic mouse strains to determine whether Lsh influences T. gondii infection. Two interesting observations were made: (i) contrary to expectation, mice carrying the Lsh-resistant allele died earlier over the acute phase of infection than Lsh-susceptible mice; and (ii) Lsh-resistant mice which survived this acute phase of infection showed lower brain cyst numbers than the Lsh-susceptible mice. Whilst the latter occurred independently of route of inoculation (oral, intraperitoneal, or subcutaneous), the former was influenced both by the route of inoculation and the genetic background on which the Lsh-resistant allele had been isolated. Hence, following oral administration of 20 brain cysts of the RRA strain of T. gondii, mice carrying the Lsh-resistant allele on a B10 genetic background showed a significantly enhanced rate of mortality over the acute (first 8-12 days) phase of infection than B10 Lsh-susceptible mice. Although this acute phase of infection in B10 background mice was accompanied by an increase in serum TNF-alpha levels in both Lsh-resistant and -susceptible mouse strains, early mortality preceded the TNF-alpha peak, and administration of neutralizing rabbit anti-TNF-alpha did not significantly enhance survival. Hence, inflammatory mediators other than TNF-alpha appear to be responsible for the increased rate of acute mortality observed in resistant mice. Infection intraperitoneally led to delayed mortality in B10 mice, with the mean time to 50% mortality now being significantly longer in Lsh-resistant than in Lsh-susceptible mice. On a BALB genetic background, it was the i.p. route of infection which led to acute mortality and more rapid death in the Lsh-resistant strain. When a less virulent inoculum was used and mortality delayed, Lsh-susceptible mice died more rapidly, and i.p. administration of rabbit anti-TNF-alpha led to 100% mortality between days 8 and 10 of infection in both susceptible and resistant mouse strains, consistent with a crucial protective role for TNF-alpha during this phase of infection.(ABSTRACT TRUNCATED AT 400 WORDS)     

Escherichia coli and Lactobacillus plantarum responses to osmotic stress

Artificial insemination using cryopreserved semen is a common management tool of the contemporary livestock producer. However, cryopreservation is detrimental to sperm function and fertility, killing some 50% of the spermatozoa during the process. Prediction of cryopreservation damage from prefreeze samples remains elusive. Computer-automated sperm head morphometry was used in this study to determine the effects of cryopreservation on bovine sperm head morphometry. Semen was collected from 18 bulls and was divided. One portion was extended to 200 x 10(6) sperm/ml and a microscope slide was prepared, while the remaining portion was cryopreserved in a Triscitrate-yolk extender. After thawing, the cryopreserved samples were prepared on microscope slides. All slides were air dried and were stained with hematoxylin and rose bengal. The morphometric dimensions for length, width, width/length, area, and perimeter for a minimum of 200 sperm heads were analyzed from each slide by computer-aided sperm head morphometry analysis, and the mean measurements were recorded. Bull sperm heads were significantly (P < 0.01) smaller in cryopreserved spermatozoa than in the companion extended samples for length (8.56+/-0.07 vs. 8.63+/-0.08 microm), width (4.39+/-0.05 vs. 4.48+/-0.05 microm), area (28.42+/-0.07 vs. 29.14+/-0.08 microm), and perimeter (23.33+/-0.21 vs. 23.70+/-0.23 microm) for all bulls. Width/length was also different (0.513 vs. 0.519). In addition, differences (P < 0.05) were found within 14 of 18 bulls for at least four of the morphometric parameters. The percent change in measures after cryopreservation were correlated (P < or = 0.05) to the variability of the extended sample. Variations in sperm head measurements were lower (P < or = 0.05) in extended samples of the four bulls in which no changes occurred than in extended samples of the remaining 14 bulls. These data suggest that the variability in sperm head measurements of individual bulls, or ejaculates, may be an indicator of sperm cryosurvivability.     

The effects of perioperative blood salvage and autologous blood donation on transfusion requirements in scoliosis surgery

Fifty consecutive cases of surgical instrumentation and fusion for adolescent idiopathic scoliosis were prospectively studied to test the hypothesis that the use of predonated autologous blood combined with judicious perioperative blood salvage could decrease the amount of homologous blood needed. All cases had posterior instrumentation and fusion. Nineteen patients had their rib prominence resected with an average of 4.8 ribs per patient. Our protocol called for perioperative blood salvage with the cell saver and reinfusion of postoperative drained blood if more than 300 ml were drained in 4 hours. Two units of predonated autologous blood was made available. Hypotensive anesthesia and meticulous hemostasis kept the blood loss to a minimum. The average total blood loss was 1,055 ml. Blood loss per segment was 91 ml with an average of 11 segments fused per patient. Patients with rib resection had a blood loss of 1,105 ml, while those without had a blood loss of 955 ml. The cell saver blood returned per case was 391 ml with the hematocrit of the product averaging 46%. Twelve patients were reinfused an average of 300 ml of the postoperative drained blood. The predonated autologous blood was used as part of the intraoperative fluid management. In no patient was homologous blood needed. The average starting hematocrit was 35.6%, with the hematocrit at discharge (seventh day) being 32.4%. There were no complications or blood transfusion reactions. Our results suggest that judicious perioperative blood management may decrease the need for homologous blood transfusion in selected posterior idiopathic scoliosis surgery.     

A ten-year experience in the evaluation and management of patients with stress urinary incontinence

The surgical procedures used, the complications encountered and the results obtained in 549 patients with urinary stress incontinence with or without prolapse and 50 patients with prolapse without urinary stress incontinence are presented. Incontinence was cured in 347 patients, improved in 126, unchanged in 66 and worsened in ten. Seven patients operated on for uterine prolapse developed urinary incontinence after surgery. The overall recurrence of SUI was 12.75%. The introduction of suprapubic bladder drainage has practically eliminated postoperative urinary tract infections and reduced the length of hospitalization from 9.1 to 7.2 days. My experience in 214 patients with suprabpubic drainage demonstratedthe superiority of the Ansari method over the cystocath. The addition of Cantor's bladder neck plication improved the results (cured plus improved) from 80% to 100% in the Marshall-Marchetti-Krantz operation and from 81% to 86% when the Marshall-Marchetti-Krantz operation was associated with an abdominal hysterectomy.     

Experimental meningococcal septicemia. Effect of heparin therapy

The pathogenesis of experimental meningococcal septicemia and the efficacy of heparin sodium therapy were evaluated by inoculating rabbits intraperitoneally with type B meningococci in mucin. Half the rabbits died, and the respiratory distress and circulatory failure that occurred during the terminal phase of the disease were associated with diffuse pulmonary capillary and venular thrombosis and with renal glomerular fibrin deposition. Platelet and leukocyte counts and plasma fibrinogen levels decreased in all rabbits, and prothrombin and partial thromboplastin times were prolonged. Pretreatment with heparin sodium diminished intravascular fibrin deposition but failed to prevent the pulmonary microthrombi and did not either reduce the mortality or improve the survival time. We conclude that death in meningococcal septicemia is due to widespread thrombosis of the pulmonary microcirculation. The disease is complicated by diffuse intravascular coagulation, which can be controlled with heparin sodium but which is not immediately life-threatening.     

Cancer, emotions and mental illness: the present state of understanding

The authors review recent and current literature on the relationship between psychological factors and cancer. They discuss the roles of predisposing personality patterns and emotional stress in the development, site, and course of cancer; the influence of awareness of terminal illness on the behavior of cancer patients; and the management of psychiatric symptoms in these patients.     

Localization of intraorbital foreign bodies

A study was performed utilizing 3 mock eyes of different sizes to determine the precision and accuracy of 3 radiographic methods of localization of intraorbital foreign bodies. The Comberg method was found to be the most precise and accurate, next, the Sweet method, and then the modified spectacle frame method. However, the modified spectacle frame field expedient method of localization yielded a surprisingly high degree of accuracy in 2 of the 3 planes of reference, that is, mediolaterally and superointeriorly. A more accurate field expedient type of device which will permit greater accuracy in localization of intraorbital foreign bodies in the anteroposterior axis is currently under development.