ABSTRACT
AMD3100 given with G-CSF has been shown to mobilize CD34+ cells in non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), and Hodgkin's disease (HD) patients who could not collect sufficient cells for autologous transplant following other mobilization regimens. These poor mobilizers are usually excluded from company-sponsored trials, but have been included in an AMD3100 Single Patient Use protocol, referred to as a Compassionate Use Protocol (CUP). A cohort of 115 data-audited poor mobilizers in CUP was assessed, with the objective being to collect > or =2 x 10(6) CD34+ cells per kg following AMD3100 plus G-CSF mobilization. The rates of successful CD34+ cell collection were similar for patients who previously failed chemotherapy mobilization or cytokine-only mobilization: NHL -- 60.3%, MM -- 71.4% and HD -- 76.5%. Following transplant, median times to neutrophil and PLT engraftment were 11 days and 18 days, respectively. Engraftment was durable. There were no drug-related serious adverse events. Of the adverse events considered related to AMD3100, two (1.6%) were severe (one patient -- headache, one patient -- nightmares). Other AMD3100-related adverse events were mild (84.8%) or moderate (13.6%). The most common AMD3100-related adverse events were gastrointestinal reactions, injection site reactions and paresthesias. AMD3100 plus G-CSF offers a new treatment to collect CD34+ cells for autologous transplant from poor mobilizers, with a high success rate.
Subject(s)
Antigens, CD34 , Colony-Stimulating Factors/therapeutic use , Granulocyte Colony-Stimulating Factor/therapeutic use , Hematopoietic Stem Cell Mobilization/methods , Heterocyclic Compounds/therapeutic use , Lymphoproliferative Disorders/therapy , Salvage Therapy/methods , Adult , Aged , Benzylamines , Cyclams , Drug Synergism , Drug Therapy, Combination , Female , Graft Survival , Hematopoietic Stem Cell Transplantation/methods , Humans , Male , Middle Aged , Prospective Studies , Transplantation, Autologous/methodsABSTRACT
Disturbance is an important factor in structuring ecological communities, exerting its influence through changes to the physical environment and to the trajectories of successional processes. Marine environments are subject to a wide range of disturbances and while much is known about the effects of disturbance on macrobenthos in unconsolidated sediments, little is known about the responses of meiobenthos to disturbance in consolidated sediments, such as mangroves. Trampling was used to study the response of meiobenthos to disturbance in mangrove sediments. Even light trampling appeared to break up the mangrove root mat and increased the proportion of fine sediment. Densities of meiobenthos increased 2-3-fold in disturbed sediments, but there was no evidence of disproportionate abundance. Temporal variability was similar in all treatments, but spatial variability increased 4-5-fold in disturbed sediments. Effects persisted for at least 24 months, with little evidence of convergence of treatments. Meiobenthos may have exploited the increase in habitat resulting from loss of the root mat and possibly benefited from increased food from the decomposition of root material. These effects are likely to persist for several years because of the minimal recovery of the root mat.
Subject(s)
Avicennia/physiology , Biodiversity , Ecosystem , Geologic Sediments , Invertebrates/physiology , Animals , Time FactorsABSTRACT
Morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) are active metabolites of morphine. The effects of M3G and M6G on the opioid receptor transduction system has not yet been fully elucidated. Formation of cAMP after treatment with various doses of morphine, M3G, and M6G was studied. M6G and morphine, but not M3G, showed a dose dependent inhibition of cAMP accumulation. Naloxone blocked the inhibitory effect of M6G, M3G, and morphine. Pretreatment with M3G did not change the effects of morphine and M6G. The G-protein inhibitor PTX, prevented morphine, M3G, and M6G effects on cAMP. M3G and M6G vary in their ability to interact with the opioid receptor effector system. Inhibition of cAMP evoked by activation of opioid receptors and inhibitory G-proteins may play a role in the actions of M6G and M3G.
Subject(s)
Morphine Derivatives/pharmacology , Receptors, Opioid/drug effects , Alprostadil/pharmacology , Cyclic AMP/metabolism , Dose-Response Relationship, Drug , Humans , Naloxone/pharmacology , Receptors, Opioid/physiology , Tumor Cells, Cultured , Virulence Factors, Bordetella/pharmacologyABSTRACT
OBJECTIVE: To determine the effects of surgery, hypoxia, hypercapnia and flunixin administration on plasma ß-endorphin immunoreactivity (BEI) in anaesthetized horses. STUDY DESIGN: Prospective crossover study. ANIMALS: Six healthy adult Welsh Mountain ponies and seven healthy adult Thoroughbreds. METHODS: Ponies were anaesthetized with thiopentone and halothane or with pentobarbitone and the horses with guaiphenesin, thiopentone and halothane. Ponies were anaesthetized for 2 hours and on separate occasions underwent a period of hypoxia, hypercapnia, anaesthesia only, or were given flunixin at induction. The horses were anaesthetized for 2 hours and on separate occasions underwent surgery to relocate one carotid artery subcutaneously or anaesthesia only. Plasma samples were taken pre-anaesthesia, at 20 minute intervals during, and after anaesthesia for BEI assay using radio-immunoassay. Analysis of variance of the concentration-time curve was used for statistical analysis. RESULTS: Pre-anaesthetic ß-endorphin immunoreactivity (BEI) values ranged between 5.7 and 20.4 pmol L-1. Induction of anaesthesia caused a five to 10 fold increase in mean plasma BEI in all cases except the hypercapnia group. Halothane anaesthesia increased BEI in ponies and horses but there were no significant changes during pentobarbitone anaesthesia. The increase in BEI in the hypoxic group was greater (peak value 136.8 ± 32.2 pmol L-1) and sustained for a longer period compared with levels in those given halothane alone or in those which became hypercapnic. There was marked individual variation in the flunixin group and changes were not significant. Surgery in the horses resulted in the highest peak values in the study (182.5 ± 153.0 pmol L-1) but the AUC was not significantly higher than in the same animals without surgery, where the peak value was 102.9 ± 42.1 pmol L-1. CONCLUSIONS: Beta-endorphin appeared to be a sensitive marker of an endocrine stress response but its physiological role during equine anaesthesia is unknown. CLINICAL RELEVANCE: Unknown.
ABSTRACT
A urinary schistosomiasis survey undertaken in the Port St Johns district of the former Transkei showed the parasite to be endemic and noted an increase in overall infection rates in the region compared with previous studies. There was a general stability in infection over the sampling period 1987-1989. Prevalence rates were low to moderate with an overall prevalence of 42%. These ranged from approximately 10% in the low-prevalence settlement to 89.9% in the settlement with the highest prevalence. Infection rates were found to decrease nearer the coast, and settlements closest to the sea had the lowest prevalence rates. The intensity of infection was low, with the majority of patients having fewer than 200 eggs per 10 ml urine. Very few sufferers were treated with Ambilhar at clinics and hospitals.
Subject(s)
Schistosoma haematobium/isolation & purification , Schistosomiasis haematobia/epidemiology , Schistosomiasis haematobia/urine , Adolescent , Adult , Age Distribution , Aged , Animals , Child , Female , Humans , Male , Middle Aged , Niridazole/therapeutic use , Parasite Egg Count/methods , Prevalence , Schistosoma haematobium/pathogenicity , Schistosomiasis haematobia/drug therapy , Schistosomicides/therapeutic use , Seasons , South Africa/epidemiology , Urine/parasitologyABSTRACT
Sixty unpremedicated patients undergoing dilatation and curettage were allocated randomly to receive one of three inhalational agents (halothane, enflurane or isoflurane) to supplement 67% nitrous oxide in oxygen after induction of anaesthesia with methohexitone. Recovery was assessed by the time patients took to open their eyes, to give their correct date of birth, to regain their pre-operative level of manipulative skill with a children's postbox toy, and by comparing pre-operative and postoperative performance of a paper and pencil test (the p-deletion test). There was no difference in the time to open eyes or to regain their pre-operative score with the postbox whether the patients received halothane, enflurane or isoflurane. Patients in the isoflurane group took longer than patients in the enflurane group to give their correct date of birth, but they performed better in the p-deletion test postoperatively, completing more lines with the same number of errors. Patients receiving enflurane committed more errors postoperatively in the p-deletion test. The incidence of complications was low and was not influenced by the choice of inhalational agent.
Subject(s)
Ambulatory Surgical Procedures , Anesthesia, Inhalation , Adult , Consciousness , Enflurane/pharmacology , Female , Halothane/pharmacology , Humans , Isoflurane/pharmacology , Middle Aged , Postoperative Complications , Time FactorsABSTRACT
Arterial plasma concentrations of lignocaine were studied in fifteen adult patients following insertion of a tracheal tube whose cuff area was smeared with 5% lignocaine ointment. Twelve patients had 2 ml of ointment (114 mg) and samples were taken every 5 minutes until 30 minutes and in eight of the 12 patients at 40, 50 and 60 minutes after insertion and inflation of the tracheal tube and cuff. Three patients had 1 ml of ointment on the tube and were studied over 60 minutes. Plasma concentrations were determined using gas liquid chromatography. In the 2 ml lignocaine group mean plasma lignocaine levels were 1.9 (SD 0.9) micrograms/ml at 10 minutes, 2.3 (SD 0.8) micrograms/ml at 20 minutes, 2.3 (SD 0.8) micrograms/ml at 30 minutes and 1.7 (SD 1.0) micrograms/ml at 60 minutes. After 1 ml of lignocaine, levels were 1.2 (SD 0.1) micrograms/ml at 10 minutes, 1.1 (SD 0.7) micrograms/ml at 20 minutes, 0.8 (SD 0.3) micrograms/ml at 30 minutes and 0.75 (SD 0.1) micrograms/ml at 60 minutes.
Subject(s)
Intubation, Intratracheal/instrumentation , Lidocaine/blood , Absorption , Female , Humans , Lubrication , Male , Middle Aged , Time FactorsABSTRACT
Two groups of eight patients received infusions of either fentanyl at 3 micrograms kg-1 h-1 or alfentanil at 20 micrograms kg-1 h-1 as supplements to 66% N2O in oxygen anaesthesia, during and after body surface surgery. At the end of surgery, the N2O was reduced to 50% and after measurement of ventilatory frequency, minute ventilation, and the ventilatory response to carbon dioxide, N2O was discontinued. The opioid infusions were continued for a further hour and the ventilatory measurements repeated. Both sets of measurements were compared with preoperative values. Minute ventilation (P less than 0.01), frequency (P less than 0.01) and the response to carbon dioxide (P less than 0.01) were reduced during the infusion of fentanyl with N2O; with fentanyl alone, minute ventilation (P less than 0.05) and the response to carbon dioxide (P less than 0.01) were reduced but to a lesser degree. The elimination of nitrous oxide from the inspired gas mixture produced an increase in frequency (P less than 0.05) and increases in the slope (P less than 0.01) and ventilation at 7.3 kPa (P less than 0.025) of the carbon dioxide response curve. Minute ventilation (P less than 0.01) frequency (P less than 0.05) and response to carbon dioxide (P less than 0.01) were all reduced during the infusion of alfentanil with nitrous oxide; with alfentanil alone, minute ventilation (P less than 0.01), tidal volume (P less than 0.05), the slope (P less than 0.025) and the ventilation at 7.3 kPa (P less than 0.01) of the carbon-dioxide response curve were still reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Anesthesia, Inhalation , Fentanyl , Fentanyl/analogs & derivatives , Nitrous Oxide/pharmacology , Respiration/drug effects , Adjuvants, Anesthesia , Adult , Alfentanil , Analgesics, Opioid , Carbon Dioxide/pharmacology , Fentanyl/blood , Fentanyl/pharmacology , Humans , Middle Aged , Tidal VolumeABSTRACT
Twenty-four patients were allocated randomly into four groups for the study of the pharmacokinetics of, and effects on postoperative ventilation of, two doses of fentanyl (10 micrograms/kg or 25 micrograms/kg) administered at the start of general anesthesia in which ventilation was controlled at a fixed volume, but arterial PCO2 was adjusted to a range of either 38-42 torr, or 20-25 torr. During the first 2 hr after anesthesia, ventilatory depression (CO2 responsiveness decreased to less than 50% of awake values, PaCO2 greater than 48 torr) occurred only in patients who had received 25 micrograms/kg fentanyl, and was more marked in patients who were hyperventilated to a low PaCO2 during anesthesia. Plasma fentanyl concentrations associated with 50% depression of CO2 responsiveness were in the range 1.5-3.0 ng/ml, the lower values found in patients hyperventilated to a low PaCO2. Whole-body clearance of fentanyl was significantly decreased by hypocapnic hyperventilation.
Subject(s)
Anesthesia, General , Fentanyl/adverse effects , Respiration/drug effects , Adult , Aged , Carbon Dioxide/blood , Female , Fentanyl/blood , Humans , Kinetics , Male , Middle Aged , Postoperative Complications , Random AllocationABSTRACT
Three groups of patients received Althesin, minaxolone or di-isopropyl phenol to supplement 67% nitrous oxide in oxygen. A fourth group receiving halothane to supplement nitrous oxide in oxygen acted as a control. Hepatic function tests were measured before operation and on days 1, 3, 5 and 7 after major vascular reconstructive surgery. There were significant increases to a mean value above the upper limit of normal in aspartate amino-transferase activity by day 3 in all groups. Total lactic dehydrogenase activity increased in the patients receiving Althesin, minaxolone and halothane. No change was seen in the alkaline phosphatase in any of the study groups. Gamma glutamyl transpeptidase increased in all groups, but the mean value at day 7 was not greater than the upper limit of normal. The mean activity of ornithine carbamoyl transpeptidase showed no change in any group throughout the study period. Two of the patients receiving minaxolone suffered cholestatic jaundice during the first month. These results suggest that anaesthesia with Althesin or di-isopropyl phenol results in enzyme changes similar to those seen in a comparable group of patients receiving halothane to supplement nitrous oxide in oxygen anaesthesia.
Subject(s)
Anesthesia, General , Liver/physiology , Vascular Surgical Procedures , Aged , Alfaxalone Alfadolone Mixture , Aspartate Aminotransferases/blood , Bilirubin/blood , Halothane , Humans , L-Lactate Dehydrogenase/blood , Liver/metabolism , Middle Aged , Ornithine Carbamoyltransferase/blood , Phenols , Pregnanolone/analogs & derivatives , Propofol , gamma-Glutamyltransferase/bloodABSTRACT
The opioid drugs fentanyl and alfentanil were infused at a constant rate as supplements to nitrous oxide in oxygen anaesthesia throughout the period of surgery. These infusions were continued into the period after operation for 1 h after the discontinuation of anaesthesia. Continuous infusion of alfentanil 20 micrograms kg-1 h-1 and fentanyl 3 micrograms kg-1 h-1 resulted in depression of the carbon dioxide response curve with a lesser effect on frequency and minute ventilation. One hour after discontinuing the infusions the degree of ventilatory depression was only marginally less with fentanyl, but considerably less with alfentanil, reflecting the shorter terminal half-life of that drug.