Epicoccum allergy: skin reaction patterns and spore/mycelium disparities recognized by IgG and IgE ELISA inhibition

Comparable degrees of skin reactivity were observed towards spore and mycelium extracts from two isolates of Epicoccum and to one preparation of Alternaria in 35 rural and 120 university patients. The best experimental extracts detected Epicoccum sensitivity in 70% of the group tested while the commercial extract detected sensitivity in only 6%. Skin reaction correlations were greatest within isolates (eg, spore-A/mycelium-A), then for specific fungus parts (eg, spore-A/spore-B), then between isolates and parts (spore-A/mycelium-B). High correlations were found between individual IgG and IgE ELISA values for all antigens using serum from Epicoccum skin-reactive patients. ELISA inhibition results suggested that significant cross-reactivity exists between Epicoccum and Alternaria antigens recognized by IgG but not by IgE. ELISA inhibition cross-reaction patterns among Epicoccum antigens were comparable to skin reactions while IgG patterns showed little variability. Further characterization of spore/mycelium and interstrain recognition patterns among different immunoglobulin isotypes will be necessary before complete standardization of extracts from different parts of fungi will be possible. The use of spore material for skin testing and treatment of Epicoccum sensitivity appears to be both premature and unnecessary at this time.     

Immunization with cholinergic cell bodies induces histopathological changes in rat brains

We have previously shown that sera from patients with Alzheimer’s disease (AD) contain antibodies to the cell bodies (perikarya; PK) of purely cholinergicTorpedo neurons, and that repeated immunization of rats with this neuronal preparation for over a year induces learning and memory impairments. In the present study, we examined the brain morphology of cholinergic PK immunized rats relative to controls. Immunohistochemical studies of the brains of these rats revealed the accumulation of IgG in specific areas, such as, the hippocampus. Parallel histochemical studies demonstrated significant changes in the hippocampus, and in white matter areas. They included large vacuoles and necrotic nuclei in the granular layer of the dentate gyrus, tangle-like appearance in some pyramidal neurons of the hippocampus, and vacuolar degeneration accompanied by oligodendroglia hypertrophy in white matter tracts, such as, the corpus callosum and fimbria. In contrast, immunization withTorpedo cholinergic nerve terminals, that has no cognitive effects on the rat, also did not induce brain morphological changes. These findings suggest that the learning and memory deficits induced by immunizing rats with cholinergic PK are related to the observed brain morphological changes, and support the hypothesis that the antibodies to cholinergic neurons found in the sera of AD patients may play a role in neuronal degeneration in this disease.     

Challenges of leadership in an era of health care reform

Health care leadership has never been more difficult than in the past decade--and the next ten years promise to be even more demanding. As a new era for health care emerges, organizational leaders will be required to manage increased levels of risk, uncertainty, and rapid change. Successful chief executives will be those who recognize and nurture intangible leadership qualities including knowledge of self, commitment to service, and depth and breadth of vision. With the continued shift away from hospital inpatient care, health care leaders will be called on to develop multipurpose delivery systems that move from a market-based to a community-based focus and deliver high quality services in a cost-effective manner. Several leadership themes will unfold in the midst of health care reform, including: exploiting change for the good of the organization and community; serving as educator, communicator, and comforter to divergent constituencies; and reestablishing a balance between short-term goals and long-term vision.     

Low-dose sufentanil and lidocaine supplementation of general anaesthesia

This randomized double-blind study compared the effects of: (1) saline infusion (C); (2) sufentanil alone (1.0 micrograms.kg-1) (S); and (3) low-dose sufentanil (0.5 micrograms.kg-1) in combination with lidocaine (1.5 mg.kg-1) (LS): on the cardiovascular responses to tracheal intubation and on postoperative ventilation as monitored by respiratory inductive plethysmography in day-care surgical procedures of approximately 60 min duration. Thirty healthy, unpremedicated patients were studied. Thiopentone requirements were reduced by 40 and 28 per cent in the S and LS groups respectively compared with control (P less than 0.001). Both treatments suppressed HR and BP responses (P less than 0.005) to intubation. Postoperatively, PaCO2 was elevated (P less than 0.05) in group S. Dose-related respiratory depression was observed. The incidence of postoperative apnoea was significantly higher in both S and LS groups than compared with control (P less than 0.05). However, only patients in group S showed higher apnoea index and mean apnoea duration over the initial 10-20 min after surgery compared with control (P less than 0.005). In addition, group S showed slower respiratory frequency and prolonged expiratory time (P less than 0.005). In conclusion, an induction dose of sufentanil (1 microgram.kg-1) used in balanced anaesthesia of less than 70 min duration was associated with significant respiratory depression, particularly during the initial 10-20 min after surgery, whereas low-dose sufentanil (0.5 micrograms.kg-1) with lidocaine (1.5 mg.kg-1) had minimal postoperative respiratory depression and comparable attenuation of pressor responses to intubation.     

Epidural anesthesia in anin vitro fertilization and embryo transfer program

Objectives To investigate the potential advantages of epidural anesthesia in an in vitro fertilization and embryo transfer program.Study Design Between January 1991 and December 1992, 148 infertile patients underwent transvaginal ultrasound guided oocyte retrieval. A total of 44 patients (group A) had 50 retrievals under epidural anesthesia, and 104 patients (group B, control group) 112 retrievals under intravenous sedation (propofol) with mask-assisted ventilation (nitrous oxide).Results In group A satisfactory anesthesia was achieved in 49 of the 50 cases (98%); one patient required additional intravenous administration of propofol owing to extreme anxiety. No complications were observed. Adversely, in group B nausea was observed in 16 cases (14%) and nausea and vomiting in 7 cases (6%). In group A the fertilization, cleavage and pregnancy rates were 67.2%, 92% and 20% respectively, while in group B the rates were 69.3%, 93% and 19.6% respectively; the differences are not statistically significant.Conclusions Epidural anesthesia is an effective method for transvaginal oocyte retrieval but does not improve the treatment outcome as compared to an intravenous sedation with mask-assisted ventilation using propofol and nitrous oxide.     

The effect of a chemical phosphatase on single calcium channels and the inactivation of whole-cell calcium current from isolated guinea-pig ventricular myocytes

A chemical phosphatase, butanedione monoxime (BDM, at 12–20 mM), reduced open probability (P ₀) of single cardiac L-type Ca²⁺ channels in cellattached patches from guinea-pig ventricular myocytes, without effect on the amplitude of single-channel current, the mean open time or the mean shorter closed time, but it increased mean longer closed time and caused a fall in channel availability. A decrease in the mean time between first channel opening and last closing within a trace was principally due to an inhibition of the longer periods of activity. As a result, the time course of the mean currents, which resolved into an exponentially declining and a sustained component, was changed by an increase in the rate of the exponential phase and a profound reduction of the sustained current. Essentially similar results were obtained when studying whole-cell Ba²⁺ currents. The inactivation of the whole-cell Ca²⁺ currents was composed of two exponentially declining components with the slower showing a significantly greater sensitivity to BDM, an effect that was much more pronounced in myocytes exposed to isoprenaline with adenosine 5-O-(3-thiotriphosphate) (ATP[S]) in the pipette solution. The actions of BDM, which are the opposite of those produced by isoprenaline, suggest that the level of phosphorylation affects processes involved in the slow regulation of channel activity under basal conditions and that several sites (and probably several kinases) are involved. Channels with an inherently slow inactivation would seem to be converted into channels with a rapid inactivation by a dephosphorylation process.     

Pharmacokinetics and pharmacodynamics of prolonged oral etoposide in women with metastatic breast cancer

The pharmacokinetics and pharmacodynamics of prolonged oral etoposide chemotherapy were investigated in 15 women with metastatic breast cancer who received oral etoposide 100 mg as a single daily dose for up to 15 days. There was considerable interpatient variability in the day 1 pharmacokinetic parameters: area under the plasma concentration time curve (AUC) (0–24 h) 1.95±0.87 mg/ml per min (mean ± SD), apparent oral clearance 60.9±21.7 ml/min per 1.73 m², peak plasma concentration 5.6±2.5 g/ml, time to peak concentration 73±35 min and half-life 220±83 min. However, intrapatient variability in systemic exposure to etoposide was much less with repeated doses. The intrapatient coefficient of variation (CV) of AUC for day 8 relative to day 1 was 20% and for day 15 relative to day 1 was 15%, compared to the day 1 interpatient CV of 45%. Neutropenia was the principal toxicity. Day 1 pharmacokinetic parameters were related to the percentage decrease in absolute neutrophil count using the sigmoidal E_max equation. A good fit was found between day 1 AUC and neutrophil toxicity (R ²=0.77). All patients who had a day 1 AUC>2.0 mg/ml per min had WHO grade III or IV neutropenia. The predictive performance of the models for neutrophil toxicity was better for AUC (percentage mean predictive error 5%, percentage root mean square error 18.1%) than apparent oral clearance, peak plasma concentration, or daily dose (mg/m²). A limited sampling strategy was developed to predict AUC using a linear regression model incorporating a patient effect. Data sets were divided into training and test sets. The AUC could be estimated using a model utilizing plasma etoposide concentration at only two time points, 4 h and 6 h after oral dosing (R ²=98.9%). The equation AUC_pr=–0.376+0.631×C_4h+0.336×C_6h was validated on the test set with a relative mean predictive error of –0.88% and relative root mean square error of 6.4%. These results suggest monitoring of AUC to predict subsequent myelosuppression as a strategy for future trials with oral etoposide.Division of Haematology and Medical Oncology, Peter MacCallum Cancer Institute, Locked Bag 1, A'Beckett St, Melbourne 3000, Australia     

Degradation of Weathered Oil by Mixed Marine Bacteria and the Toxicity of Accumulated Water-Soluble Material to Two Marine Crustacea

Artificially weathered crude oil was degraded by four diverse cultures of mixed marine bacteria under optimized conditions for 7 and 14 days. Loss in total weight of starting oil (30 g) ranged from 6.8–17.3% in biologically active incubations compared with only 0.9–1.1% in sterile and nutrient-limited controls. In all incubations, both neutral and acidic water-soluble fractions (WSF) were accumulated. In biologically active systems, 50.9–249.0 mg neutral and 63.3–406.8 mg acidic WSF were accumulated whereas only 6.5–11.1 mg neutral and 1.7–2.2 mg acidic WSF were accumulated in control incubations. Analysis by gas chromatography demonstrated that accumulated WSF in biologically active systems contained compounds different from those washed from the starting crude oil. Exposure of grass shrimp (Palaemonetes pugio) embryos to neutral WSF from each of the biologically active cultures resulted in high embryo mortalities relative to sterile and nutrient-limited controls which exhibited >90% hatching success and larval survival. Toxicity of neutral WSF was also demonstrated on larvae of mysids (Mysidopsis bahia). In both cases, toxicity occurred only on exposure to neutral material accumulated by active, oil-degrading cultures and not with material washed from the weathered crude oil. These results imply that unique compounds were accumulated during degradation that may have been responsible for increased toxicity. Received: 23 December 1997/Accepted: 27 July 1998