Effects of intravenous mu and kappa opioid receptor agonists on sensory responses of convergent neurones in the dorsal horn of spinalized rats.

1. Electrophysiological experiments have been performed to assess the effects of intravenously administered mu and kappa opioid agonists on the responses to noxious thermal and mechanical and non-noxious tactile stimuli of single convergent neurones in laminae III-VI of the dorsal horn of spinalized rats anaesthetized with alpha-chloralose. 2. The mu receptor agonists tested were fentanyl (1-16 micrograms kg-1) and morphine (0.5-16 mg kg-1) and the kappa-receptor agonists U-50,488 (1-16 mg kg-1) and tifluadom (0.1-1.6 mg kg-1). Multiple drug tests were made on each cell so that compounds could be compared under closely comparable conditions. 3. In one protocol, thermal and mechanical nociceptive responses of matched amplitudes were elicited alternately. Both mu and kappa agonists dose-dependently reduce the neuronal responses. Thermal nociceptive responses were as sensitive to the kappa agents as were the mechanical nociceptive responses; the mu agonists similarly reduced both types of response in parallel. 4. In another protocol, nociceptive and non-nociceptive responses were elicited alternately to permit the degree of selective antinociception to be assessed. The mu agonists were scarcely selective, fentanyl reducing nociceptive only slightly (but significantly at 4-16 micrograms kg-1) more than non-nociceptive responses. The kappa-opioid agonist U50,488 reduced tactile responses somewhat more than nociceptive responses. 5. The spontaneous discharge of these cells with ongoing activity was reduced to a significantly greater degree than the evoked responses; this is likely to have contributed to the non-selectivity of the reduction of the evoked responses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transesterification of peptide esters and peptidyl resins in methanol-containing calcium acetate

The following crude peptide derivatives obtained by thermolysin catalysis in the presence of calcium acetate, were dissolved in methanol and in methanol-containing calcium acetate to determine the possible occurrence of transesterification: Z-Asn-Leu-Gly-OEt, Boc-Asn-Leu-Gly-OEt, Moz-Asn-Leu-Gly-OBzl, Moz-Asn-Leu-Gly-OtBu, Moz-Gln-Leu-Gly-OEt, Moz-Asn-lle-Gly-OEt, and Moz-Asn-Leu-Ala-OEt. Only Z-Asn-Leu-Gly-OEt and Moz-Gln-Leu-Gly-OEt were transesterified in methanol, indicating the existence of a peptide derivative-Ca²⁺ catalytic complex that may favor the reaction. In the presence of calcium acetate, all protected peptide esters except the t-butyl esters were transesterified. The transesterification of several other di- and tripeptide derivatives of different structures in methanol-containing calcium acetate was detected by HPLC and confirmed by the isolation and characterization of some of the protected peptide methyl esters obtained. Boc-Leu-Gly- and Moz-Asn-Leu-Gly-Merrifield resin were also transesterified in these solutions.     

Effect of warfarin on survival in small cell carcinoma of the lung. Veterans Administration Study No. 75

In a controlled, randomized study, survival of patients with small cell carcinoma of the lung (SCCL) was prolonged on addition of warfarin sodium to combination chemotherapy plus radiation therapy. Median survival for 25 control patients was 24 weeks and for 25 warfarin-treated patients was 50 weeks. This difference could not be accounted for by differences between groups in performance status, extent of disease, age, or sex. The survival advantage associated with warfarin administration was observed both for patients with extensive disease and for those who failed to achieve complete or partial remission. The warfarin-treated group also demonstrated a significantly increased time to first evidence of disease progression. These results suggest that warfarin may be useful in the treatment of SCCL and also support the hypothesis that the blood coagulation mechanism may be involved in the growth and spread of cancer in man.     

Applications of ultraviolet light in the preparation of platelet concentrates

Passenger lymphocytes in platelet concentrates (PCs) may induce the formation of lymphocytotoxic antibodies (LCTAbs) and subsequent refractoriness to platelet transfusions. Ultraviolet (UV) irradiation can prevent lymphocytes' acting as stimulator or responder cells in mixed-lymphocyte reactions (MLRs) and could theoretically prevent LCTAb formation in vivo. A system has been devised for the delivery of UV irradiation to PCs; platelet storage characteristics and MLRs were evaluated in UV-irradiated PCs harvested from healthy donors with the Haemonetics V50 and PCS cell separators. MLR and response to phytohemagglutinin stimulation were abolished by a dose of 3000 joules per m2 at a mean wavelength of 310 nm. Platelet aggregatory responses to adenosine diphosphate (ADP), ristocetin, collagen and epinephrine, hypotonic shock response, and pH showed no important differences when control PCs and PCs irradiated as above were compared during 5 days of storage in Fenwal PL-1240 packs. Lactate production during storage was significantly higher in UV-treated PCs (p less than 0.001), but values did not exceed 20 mmol per L. UV transmission at 310 nm in standard blood product containers, including the Fenwal PL-146, PL-1240, and PL-732, was low (less than 30%), but it was acceptable in the Delmed Cryostorage and DuPont SteriCell packs (greater than 50%). UV irradiation may provide a simple and inexpensive means of producing nonimmunogenic PCs.     

Spermatological Investigations in Patients Treated with Etretinate and Isotretinoin

Possible side effects of the retinoids etretinate and isotretinoin on the germinal epithelium were examined. 15 men received etretinate and 13 isotretinoin. After 16 weeks of treatment at therapeutic doses, no changes were observed in fundamental spermatological parameters. On the basis of examinations and data in the literature, we hold the opinion that retinoid treatment is to be considered safe from the andrological viewpoint.     

Primary lung cancer: biodistribution and dosimetry of two In-111- labeled monoclonal antibodies

This study was undertaken to measure the biokinetics and organ dosimetry of indium-111-labeled monoclonal antibodies (MoAbs) with a whole-body gamma camera imaging technique. Twenty patients with primary lung cancer were studied with two different MoAb agents (anti-carcinoembryonic antigen ZCEO25 and antiadenocarcinoma LA20207). Imaging was performed at 1, 24, 72, and 144 hours after injection. Scintigraphic whole-body retention was verified by means of comparison with the results from in vitro counting of excreta. Organ retention was verified in an abdominal phantom. The MoAb cleared slowly from the heart and lungs, the brain and spleen showed no clearance, and the liver showed increased activity over the 6-day period. Dosimetry for ZCE025 showed a dose to the liver of 1.3 rad/mCi (0.36 mGy/MBq); heart, 1.5 rad/mCi (0.40 mGy/MBq); spleen, 1.1 rad/mCi (0.29 mGy/MBq); total body, 0.49 rad/mCi (0.13 mGy/MBq); and testes, 0.39 rad/mCi (0.11 mGy/MBq). The dosimetry for LA20207 was similar.     

Percutaneous cholecystolithotomy: preliminary experience and technical considerations

Surgical cholecystectomy is associated with a high morbidity and mortality in elderly patients with acute calculous cholecystitis and underlying cardiac or pulmonary disease. Currently there are few alternatives for treating these patients. The authors have used percutaneous cholecystolithotomy in 11 such high-risk patients for definitive treatment of gallbladder calculi. In all 11 patients all stones were successfully removed from the gallbladder and cystic duct. The entire procedure--from initial tube placement to final tube removal--lasted 17-40 days (mean, 21 days). There were two complications: one minor--local wound infection--and one major--bile peritonitis with eventual death. Percutaneous cholecystolithotomy is an effective alternative therapy for acute calculous cholecystitis in elderly, debilitated patients.