Stimulation of oxidant production in alveolar macrophages by pollutant and latex particles

Air pollutant dusts as well as chemically defined particles were examined for their activating effect on oxidant production (O₂^? and H₂O₂) in guinea pig alveolar macrophages (AM). Oxidant production was measured as chemiluminescence of albumin-bound luminol. All particles examined stimulated the AM in a dose-dependent manner to different maximal levels of oxidant production. Amphibole asbestos samples were the most active of all agents studied. Various immune reactants as well as silica, metal-oxide-coated fly ash, polymethyl methacrylate beads, and chrysotile asbestos had intermediate activity, while fugitive dusts, polybead carboxylate microspheres, glass and latex beads, uncoated fly ash, and fiberglass had the lowest activity. In addition to direct stimulatory action on AM, particles also lowered the subsequent responsiveness of the cells to the bacterial peptide stimulant, N-formylmethionyl phenylalanine. This effect was only partially due to the cytotoxicity of the particles. While some relationship appeared to exist between stimulatory activity and cytotoxicity of the particles, the exact role of O₂^? in mediating cytotoxic effects is still open to question. Oxidant production in AM is a parameter which may be important in determining the pathological effects of particles as well as of materials adsorbed to their surfaces.     

Augmentation of sulfate ion absorption from the rat lung by heavy metals.

In rats injected ip with 500 mg of cyclotrimethylenetrinitramine (RDX)/kg, the respective mean times to first seizure and to death were 23.8 and 171.0 min, and the mean plasma concentrations of RDX at seizure and death were 5.2 and 13.8 μg/ml. Following 100 mg/kg po, the plasma concentration was 2.1 μg/ml at 4 hr and 3.0 μg/ml at 24 hr, while the urine concentration was 5.5 μg/ml at 4 hr and 6.9 μg/ml at 24 hr. In the 6 days following 50 mg/kg po, 0.7% was excreted as RDX in the feces and 2.4% in the urine. Irrespective of dosage or route of administration, the concentration of RDX was greatest in kidney, most variable in liver, and did not accumulate in the brain. Twenty-four hours after po dosing with 50 mg of [¹⁴C]RDX/kg, the liver and urine contained large amounts of RDX metabolites, and, after the first 4 days, 90% of the total radioactivity was recovered: 34% in the urine, 43% as ¹⁴CO₂, 3% in the feces, and 10% in the carcass. In miniature swine dosed with 100 mg/kg po, the plasma concentration was 1.6 μg/ml at 2 hr and 4.7 μg/ml at 24 hr, while the urinary concentration was 2.0 μg/ml at 2 hr and 3.6 μg/ml at 24 hr. At 24 hr, the concentrations of RDX in brain, heart, liver, kidney cortex, kidney medulla, and fat were between 4.4 and 9.1 μg/g. Convulsions in pigs occurred 12–24 hr after dosing with RDX.     

Sentinel-Lymphonodektomie als Staging-Methode bei Kopf-Hals-Karzinomen

ZusammenfassungZiel Die Exzision von Sentinel-Lymphknoten (LK) bekommt eine zunehmende Bedeutung bei der Diagnostik von Mundhöhlen- und Oropharynxkarzinomen im Falle eines N0-Halses. Die Sentinel-Node-Biopsie (SNB) wurde in ihrer Wertigkeit als einzige chirurgische Staging-Maßnahme untersucht.Patienten und Methoden Im Rahmen eines multimodalen Behandlungskonzeptes wurde die SNB ohne elektive Neck-Dissection (ND) bei 70 Patienten im Rahmen der Operation des Primarius durchgeführt. Die Kontrolle der Genauigkeit erfolgte über die Manifestation von Hals-LK-Metastasen bei 45 Patienten, die keine postoperative Bestrahlung erhalten hatten.Ergebnisse Es konnten in 94% der Fälle Sentinel-LK exzidiert werden; 9 Patienten (13%) hatten positive LK und erhielten eine therapeutische ND. Es kam zu 2 Hals-LK-Metastasen im Zusammenhang mit Zweitkarzinomen, alle anderen Patienten blieben regionär unauffällig (mediane Beobachtungszeit: 26 Monate).Fazit Die SNB könnte als Staging-Maßnahme beim N0-Hals und T1- bis T3-Tumoren zu einer erheblichen Reduktion der Anzahl elektiver NDs führen. Sie kann gut in ein multimodales Behandlungsschema integriert werden.     

Current- and voltage-clamp recordings and computer simulations of Kenyon cells in the honeybee

The mushroom body of the insect brain is an important locus for olfactory information processing and associative learning. The present study investigated the biophysical properties of Kenyon cells, which form the mushroom body. Current- and voltage-clamp analyses were performed on cultured Kenyon cells from honeybees. Current-clamp analyses indicated that Kenyon cells did not spike spontaneously in vitro. However, spikes could be elicited by current injection in approximately 85% of the cells. Of the cells that produced spikes during a 1-s depolarizing current pulse, approximately 60% exhibited repetitive spiking, whereas the remaining approximately 40% fired a single spike. Cells that spiked repetitively showed little frequency adaptation. However, spikes consistently became broader and smaller during repetitive activity. Voltage-clamp analyses characterized a fast transient Na+ current (INa), a delayed rectifier K+ current (IK,V), and a fast transient K+ current (IK,A). Using the neurosimulator SNNAP, a Hodgkin-Huxley-type model was developed and used to investigate the roles of the different currents during spiking. The model led to the prediction of a slow transient outward current (IK,ST) that was subsequently identified by reevaluating the voltage-clamp data. Simulations indicated that the primary currents that underlie spiking are INa and IK,V, whereas IK,A and IK,ST primarily determined the responsiveness of the model to stimuli such as constant or oscillatory injections of current.     

The influence of thyroglobulin on functional imaging in differentiated thyroid cancer

AIM: Recombinant human thyroid stimulating hormone (rhTSH) for an exogenous stimulation of TSH and consequent thyroglobulin (hTG) synthesis has reinitiated a discussion about the usefulness of diagnostic procedures for the follow-up of differentiated thyroid cancer (DTC). METHOD: Fifty consecutive patients with DTC who received whole-body iodine scintigraphy (WBS) and positron emission tomography (PET) were evaluated. RESULTS: The work-up was normal in 18/50. In 32 patients, functional imaging detected DTC. In 44% exogenous TSH stimulation with rhTSH was used and thyroxin was withdrawn in the others. The hTG under stimulation ranged from 0.8 to 5.004 ng x ml(-1). It was below 2 ng x ml(-1) in four (12.5%) patients. In total, 91 tumour sites were identified by positron emission tomography (PET) and 47 sites by WBS. PET and WBS showed corresponding uptake in 38% of lymph node, 48% of parenchymal and 43% of bone metastases. PET detected additional 53% of lymph node (WBS 9%), 38% of parenchymal (WBS 14%) and 28.5% of bone metastases. CONCLUSION: It is concluded that PET is more sensitive than WBS for the detection of DTC. The follow-up of DTC patients with hTG levels alone misses a significant number of true positive cases. Its use should therefore be restricted to selected low risk patients only.     

Relationship between processes of care and coronary bypass operative mortality and morbidity

BACKGROUND: Information is limited regarding the effects of processes of care on cardiac surgical outcomes. Correspondingly, many recommended cardiac surgical processes of care are derived from animal experiments or clinical judgment. This report from the VA Cooperative Study in Health Services, "Processes, Structures, and Outcomes of Cardiac Surgery," focuses on the relationships between 3 process groups (preoperative evaluation, intraoperative care, and supervision by senior physicians) and a composite outcome, perioperative mortality and morbidity. METHODS: Data on 734 risk, process, and structure variables were collected prospectively on 3,988 patients who underwent coronary artery bypass grafting at 14 VA medical centers between 1992 and 1996. Data reduction was accomplished by examining data completeness and variation across sites and surgeon, using previously published data and clinical judgment. We then applied multivariable logistic regression to the 39 remaining processes of care to determine which were related to the composite outcome after adjusting for 17 patient-related risk factors and controlling for intraoperative complications. RESULTS: Our first analysis showed several measures of operative duration, the use of inotropic agents, transesophageal echo, lowest systemic temperature, and hemoconcentration/ultrafiltration, to be powerful predictors of the composite outcome. Because the use of inotropic agents and operative duration may be related to an intermediate outcome (eg, intraoperative complications), we performed a second analysis omitting these processes. The use of intraoperative transesophageal echo and hemoconcentration/ultrafiltration remained significantly associated with an increased risk of an event (odds ratios 1.60 and 1.36, respectively). CONCLUSIONS: Our results viewed in the context of past studies suggest the possibility that inotropic use, TEE, and hemoconcentration/ultrafiltration may have adverse effects on operative outcome. Further evaluation of these processes of care using observational data, as well as randomized trials when feasible, would be of interest.