Vincristine potentiates cytochalasin B-induced DNA fragmentation in vitro

Summary The cytochalasins are fungal metabolites that have previously been shown to have some chemotherapeutic potential. When various cell types are treated in vitro with both cytochalasin B and vincristine, the resultant DNA fragmentation is greater than the sum of that caused by each agent alone. The levels necessary to achieve this potentiation are obtainable in vivo. DNA fragmentation induced by cytochalasin E, an actin-specific agent, is potentiated by vincristine. Pretreatment of the mastocytoma line P815 with vincristine results in an enhancement of the ability of cytochalasin B to fragment DNA. These results inducate that cytochalasin B might be effective as a chemotherapeutic agent in the presence of vincristine.This work was supported in part by the Women's Cancer Association and by the Sylvester Comprehensive Cancer Center     

A prospective comparison of laparoscopic versus open cholecystectomy.

In one surgical unit, 115 patients undergoing cholecystectomy were studied to compare patient recovery, subjective and objective pain experienced and complications after laparoscopic and open cholecystectomy. The data were collected prospectively where allocation to open or laparoscopic cholecystectomy was by consecutive attendance. Laparoscopic cholecystectomy was feasible in 90% of patients presenting with symptomatic gallstones. Compared with the open operation, laparoscopic cholecystectomy was safe with less peroperative and postoperative morbidity, was more cost-effective and was associated with faster patient recovery as documented by less postoperative pain, earlier return to diet, earlier full mobilisation and discharge home. Laparoscopic cholecystectomy is superior to open cholecystectomy and should be available to all patients requiring elective cholecystectomy.     

Autologous Fat Injection for Vocal Cord Medialization in the Canine Larynx

This study examined the use of autologous fat as an alternative to Teflon® and collagen as the implantable material in vocal cord medialization. Five animals underwent left recurrent laryngeal nerve sections with subsequent fat harvest and implantation into the left true vocal cords. Three animals were killed after 48 hours and 2 after 3 weeks; their larynges were examined with light microscopy. The results of the 48-hour samples show moderate acute inflammation and few areas of focal necrosis. The 3-week samples show no necrotic foci, minimal foreign-body reaction, and maintenance of structure and volume of the injected fat. Autologous fat may prove to be a valuable alternative to nonautologous injectable material in vocal cord augmentation.     

Antagonism of central and peripheral anorectic effects of caerulein by L-364,718

The reduction in food intake induced by i.p. injections of the cholecystokinin (CCK) analogue caerulein was antagonised by a low dose (0.25 mumol/kg s.c.) of the selective CCK antagonist L-364,718. To block the anorectic effect of centrally administered caerulein a dose of 25 mumol/kg of L-364,718 was required, demonstrating that central CCK receptors can be blocked effectively in the rat by choosing appropriate doses of L-364,718.     

Effects of single and repeated electroconvulsive therapy sessions on plasma ACTH, prolactin, growth hormone and cortisol concentrations.

To study the effects of electroconvulsive therapy (ECT) on hormone release, we measured circulating concentrations of adrenocorticotropic hormone (ACTH), prolactin (PRL), growth hormone (GH) and cortisol (CORT) immediately before and at 2 min, 5 min, 15 min, and 30 min following ECT. Compared to pre-ECT concentrations, there were significant increases in post-ECT plasma ACTH, PRL and CORT. GH did not change consistently. No significant difference between unilateral and bilateral ECT was observed. Compared to the first ECT, repeated treatments were associated with a significant decrease in the magnitude of hormone surge. These hormonal changes induced by ECT may reflect changes at the neurotransmitter level.     

Permeability of human brain tumor to 99mTc-gluco-heptonate and 99mTc-albumin. Implications for monoclonal antibody therapy

The variable penetration of chemotherapeutic drugs into brain and tumor is more dependent upon lipid solubility than upon size. In contrast, the molecular weight of virus- and tumor-specific monoclonal antibodies appears to limit uptake. The authors have studied eight patients with malignant brain tumors in order to compare tumor uptake of an iodinated contrast agent evaluated by computerized tomography scanning with uptake of the low and high molecular weight imaging agents technetium-99m (99mTc)-glucoheptonate and 99mTc-albumin, respectively, measured by radionuclide brain scanning. The agent 99mTc-labeled albumin was chosen for evaluation because its molecular weight (68,000) is similar to that of the most clinically promising monoclonal antibody fragment, the immunoglobulin (Ig) G Fab monomeric fragment. The radionuclide brain scans in the eight patients showed highly variable permeability of brain tumor to these markers, with uptake of the high molecular weight marker in the tumor being much less than that of the low molecular weight radionuclide. A clinical implication of these studies is that the success of monoclonal antibody therapy in the treatment of malignant brain tumors may require techniques to increase permeability of the blood-brain barrier and blood-tumor barrier to protein.     

Novel antiepileptic drug levetiracetam decreases dyskinesia elicited by L-dopa and ropinirole in the MPTP-lesioned marmoset.

Long-term dopamine replacement therapy of Parkinson's disease leads to the occurrence of dyskinesias. Altered firing patterns of neurons of the internal globus pallidus, involving a pathological synchronization/desynchronization process, may contribute significantly to the genesis of dyskinesia. Levetiracetam, an antiepileptic drug that counteracts neuronal (hyper)synchronization in animal models of epilepsy, was assessed in the MPTP-lesioned marmoset model of Parkinson's disease, after coadministration with (1) levodopa (L-dopa) or (2) ropinirole/L-dopa combination. Oral administration of levetiracetam (13-60 mg/kg) in combination with either L-dopa (12 mg/kg) alone or L-dopa (8 mg/kg)/ropinirole (1.25 mg/kg) treatments was associated with significantly less dyskinesia, in comparison to L-dopa monotherapy during the first hour after administration. Thus, new nondopaminergic treatment strategies targeting normalization of abnormal firing patterns in basal ganglia structures may prove useful as an adjunct to reduce dyskinesia induced by dopamine replacement therapy without affecting its antiparkinsonian action.     

Laparoscopically assisted hysterectomy.

OBJECTIVE: To determine the feasibility and effectiveness of laparoscopically assisted hysterectomy. DESIGN: A prospective study of the planned surgical procedure was carried out by two teams, each with two gynaecologists, who were experienced in operative laparoscopy. SETTING: The operations were carried out in a private hospital, where advanced operative laparoscopy equipment was available. PATIENTS: Seventeen patients were selected for the procedure, all of whom required hysterectomy for symptoms of pain or menorrhagia in association with uterine or other pelvic disease. Patients with carcinoma or uterine enlargement beyond 12 cm were excluded. PROCEDURE: Laparoscopically assisted hysterectomy was carried out by means of a video monitor, uterine manipulation by vaginal instrumentation, three or four abdominal punctures of less than 1 cm, and bipolar diathermy to secure vascular pedicles. The uterus was removed from the vagina by cutting vaginal skin and the cardinal ligaments. RESULTS: The operating time was 90-220 min, the blood loss was 30-200 mL, and the hospital stay lasted two to five days and convalescence two to four weeks. No serious complications occurred. CONCLUSIONS: Laparoscopically assisted hysterectomy may be valuable when adnexal or uterine abnormalities are present and vaginal hysterectomy is either contraindicated or more difficult. The procedure requires special equipment and may only be carried out by experienced gynaecological operative laparoscopists. Its acceptance will depend upon reducing the operating time to less than 90 min. It has the advantage of reducing the duration of hospital stay and the duration of convalescence when compared with abdominal hysterectomy.