Localization of ionotropic glutamate receptors in peripheral axons of human skin

Recent observations suggest that glutamate is important in sensory transduction in the periphery, contributing to peripheral sensitization of nociceptors and the hyperalgesia that accompanies inflammation. This study examined the presence of ionotropic glutamate receptors N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazolone-4-propionic acid (AMPA) and kainate (KA) in normal human hairy skin (n=6) using immunohistochemistry at the electron microscopic level. Analysis of labeled axons at the dermal-epidermal junction demonstrated that 26. 9+/-2, 19.5+/-3 and 18.5+/-1% of the axons analyzed were labeled for subunits of the NMDA, AMPA or KA receptors, respectively. An occasional Schwann cell process was labeled for either NMDA or KA receptors. The findings support the hypothesis that glutamate and its ionotropic receptors may play a role in the periphery in sensory processing in humans.     

Morphologic and biochemical changes in articular cartilages of immature beagle dogs dosed with difloxacin.

Quinolones are efficacious antibacterial compounds, but they have been associated with arthralgia in human patients; experimentally, they have caused lesions in articular cartilages of immature animals. The earliest morphologic and biochemical changes induced in articular-epiphyseal cartilage complexes by difloxacin, a fluoroquinolone, were investigated in 27 3-month-old Beagle dogs that were dosed orally with the drug at 300 mg/kg body weight per day. Paraffin-embedded sections of humeral and femoral heads that were stained with either hematoxylin and eosin or toluidine blue and fast green were evaluated histologically, and lesions were scored according to established criteria. Although morphologic changes were not observed in cartilages of the control dogs or of the treated dogs in the 24-hr group, the severity of lesions, as represented by mean scores for lesions, increased during the 36-48 hr after dosing. The initial morphologic change, observed in cartilages from the treated dogs of the 36- and the 48-hr groups, was necrosis of chondrocytes that was rapidly followed by disruption of extracellular matrix and formation of fissures. Although glycosaminoglycan was aggregated along the margins of fissures, its concentration was not reduced in cartilages of any group of treated dogs. Collagen, however, was depleted from the cartilages of the dogs that were euthanized 36 or 48 hr after the first dose of difloxacin. Because degenerative changes were observed ultrastructurally in chondrocytes by 24 hr in a previous study, it was concluded that collagen was lost from affected cartilages as an early sequel to the degeneration of chondrocytes.     

Comparative Carcinogenicity of 5,5-Diphenylhydantoin with or without Perinatal Exposure in Rats and Mice

Volume 21, Number 2 (1993), in the article "Comparative Carcinogenicityof 5,5-Diphenyihydantoin with or without Perinatal Exposurein Rats and Mice," by R. S. Chhabra, J. R. Bucher, J. K. Haseman,M. R. Elwell, P. J. Kurtz, and B. D. Canton, pages 174–186:Since the publication of the above article, the authors havefound that the feed and estimated DPH consumption data reportedin Tables 2 and 6 were incorrect. The following Tables 2 and6 contain revised feed and DPH consumption data:     

Modeling breathing-zone concentrations of airborne contaminants generated during compressed air spray painting

This paper presents a mathematical model to predict breathing-zone concentrations of airborne contaminants generated during compressed air spray painting in cross-flow ventilated booths. The model focuses on characterizing the generation and transport of overspray mist. It extends previous work on conventional spray guns to include exposures generated by HVLP guns. Dimensional analysis and scale model wind-tunnel studies are employed using non-volatile oils, instead of paint, to produce empirical equations for estimating exposure to total mass. Results indicate that a dimensionless breathing zone concentration is a nonlinear function of the ratio of momentum flux of air from the spray gun to the momentum flux of air passing through the projected area of the worker's body. The orientation of the spraying operation within the booth is also very significant. The exposure model requires an estimate of the contaminant generation rate, which is approximated by a simple impactor model. The results represent an initial step in the construction of more realistic models capable of predicting exposure as a mathematical function of the governing parameters.     

Application of evaporative light scattering detection to the characterization of combinatorial and parallel synthesis libraries for pharmaceutical drug discovery

The advent of combinatorial and parallel synthesis methodologies in drug discovery have necessitated the development of analytical techniques which permit high throughput quantitative analysis of mixtures of small organic molecules. High pressure liquid chromatography with evaporative light scattering detection has become the major tool for this task. In this article we briefly review the theory of evaporative light scattering detection and the design of commercial instruments, as well as discuss the operational constraints imposed by the exigency of analyzing en masse the product libraries generated by these new drug discovery methods. The application of evaporative light scattering detection to library analysis is illustrated using examples from our library synthesis program. Complemented by ultraviolet absorbance detection for purity assessment and mass spectrometry for product identification, evaporative light scattering detection is the only technique affording sufficient accuracy and sensitivity for high throughput library analysis.     

The use of chemical restraint in helicopter transport

Introduction: Helicopter transport of the combative patient is a major safety hazard facing air medical teams. Although physical restraints alone are helpful, the addition of chemical restraint (CR) often is necessary to control these patients while in flight.

Methods: A survey was conducted to determine the current practices of using nonparalyzing CR in air medical transport programs nationwide. The survey consisted of 24 questions on the use of CR during transport. Each U.S. program belonging to the Association of Air Medical Services was contacted by telephone, and a flight nurse or paramedic provided answers based on personal experience and statistics compiled by his or her individual program.

Results: Of the 100 programs responding, benzodiazepines were used most commonly to control agitation with 51% using midazolam. Patients with a head injury required CR more frequently than any other condition (73%). Crews flying larger aircraft reported less need for CR. A physician order was required by only 30% of the programs, but delays infrequently endangered the patient (2%). Only 7% of the responding programs had a patient whose condition deteriorated because of CR.

Conclusion: CR is necessary in air medical transport. Most programs use short-acting benzodiazepines. Crews in smaller aircraft use CR more frequently, and head injury is the most common condition requiring such restraint.     

Inflammation-induced changes in peripheral glutamate receptor populations

The ionotropic glutamate receptors N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) have been localized on subpopulations of unmyelinated and myelinated sensory axons in normal skin. Behavioral studies indicate that activation of these receptors results in nociceptive behaviors and contributes to inflammatory pain. The goal of the present study was to determine if these glutamate receptors might contribute to the peripheral hypersensitivity observed in inflammation. The major findings were that 48 h following complete Freund's adjuvant (CFA)-induced inflammation, the proportions of unmyelinated axons labeled for NMDA, AMPA or KA receptors were 61%, 43% and 48%, respectively, in cutaneous nerves in the inflamed paw compared to 48%, 22% and 27%, respectively, in the non-inflamed paw. The proportions of myelinated axons labeled for NMDA, AMPA or KA receptors were 61%, 61% and 43%, respectively, compared to 43%, 42% and 28%, respectively, in the non-inflamed hindpaw. These increases were all significant. These data indicate that the number of sensory axons containing ionotropic glutamate receptors increases during inflammation, and this may be a contributing factor to peripheral sensitization in inflammation.     

Transfer of Bacillus thuringiensis plasmids coding for delta-endotoxin among strains of B. thuringiensis and B. cereus.

The recently discovered high-frequency transfer of plasmids between strains of Bacillus thuringiensis was used to study the genetic relationship between plasmids and production of the insecticidal delta-endotoxin crystal. Three strains of B. thuringiensis transmitted the Cry+ (crystal-producing) phenotype to Cry- (acrystalliferous) B. thuringiensis recipients. Agarose gel electrophoresis showed that one specific plasmid from each donor strain was always present in Cry+ "transcipients." The size of the transmissible crystal-coding plasmid varied with the donor strain, being 75 MDal (megadaltons) in size in HD-2, 50 MDal in HD-73, and 44 MDal in HD-263. Immunological analysis showed the Cry+ transcipients to be hybrid strains, having flagella of the recipient serotype and crystals of the donor serotype. These results demonstrate that the structural genes for the delta-endotoxin are plasmid borne. Crystal-coding plasmids also transferred into two strains of the related species Bacillus cereus and yielded transcipients that produced crystals of the same antigenicity as the donor strain.     

Financial impact of tertiary care in an academic medical center

OBJECTIVE: To analyze the financial impact of three complex vascular surgical procedures to both an academic hospital and a department of surgery and to examine the potential impact of decreased reimbursements. SUMMARY BACKGROUND DATA: The cost of providing tertiary care has been implicated as one potential cause of the financial difficulties affecting academic medical centers. METHODS: Patients undergoing revascularization for chronic mesenteric ischemia, elective thoracoabdominal aortic aneurysm repair, and treatment of infected aortic grafts at the University of Florida were compared with those undergoing elective infrarenal aortic reconstruction and carotid endarterectomy. Hospital costs and profit summaries were obtained from the Clinical Resource Management Office. Departmental costs and profit summary were estimated based on the procedural relative value units (RVUs), the average clinical cost per RVU ($33.12), surgeon charges, and the collection rate for the vascular surgery division (30.2%) obtained from the Faculty Group Practice. Surgeon work effort was analyzed using the procedural work RVUs and the estimated total care time. The analyses were performed for all payors and the subset of Medicare patients, and the potential impact of a 15% reduction in hospital and physician reimbursement was analyzed. RESULTS: Net hospital income was positive for all but one of the tertiary care procedures, but net losses were sustained by the hospital for the mesenteric ischemia and infected aortic graft groups among the Medicare patients. In contrast, the estimated reimbursement to the department of surgery for all payors was insufficient to offset the clinical cost of providing the RVUs for all procedures, and the estimated losses were greater for the Medicare patients alone. The surgeon work effort was dramatically higher for the tertiary care procedures, whereas the reimbursement per work effort was lower. A 15% reduction in reimbursement would result in an estimated net loss to the hospital for each of the tertiary care procedures and would exacerbate the estimated losses to the department. CONCLUSIONS: Caring for complex surgical problems is currently profitable to an academic hospital but is associated with marginal losses for a department of surgery. Economic forces resulting from further decreases in hospital and physician reimbursement may limit access to academic medical centers and surgeons for patients with complex surgical problems and may compromise the overall academic mission.     

Major complications arising from 1265 operative laparoscopic cases: a prospective review from a single center

STUDY OBJECTIVE: To identify the volume and type of laparoscopic surgery being performed. To review the incidence, nature of associated complications, and reasons for conversion to laparotomy. DESIGN: A multicenter, prospective case load analysis and chart review, identifying operations performed by 6 advanced laparoscopic surgeons over a 12-month period (1/1/05 to 12/31/05). SETTING: Surgical cases were performed in 5 hospitals in Sydney, New South Wales. PATIENTS: One thousand two hundred sixty-five women underwent a variety of major and advanced operative procedures. MEASUREMENTS AND MAIN RESULTS: A total of 1265 major and advanced laparoscopic procedures were performed. Laparoscopic hysterectomy accounted for 364 cases (28.8%), pelvic floor repair and Burch colposuspension 280 cases (22.2%), excisional endometriosis surgery 354 cases (28%), adnexal surgery 177 cases (13.9%), adhesiolysis 75 cases (5.9%), and miscellaneous cases 15 (1.2%). Overall major complications in terms of bowel, urologic, or major vessel injuries accounted for 8 cases (0.6%). There were 4 injuries of the bowel, 2 injuries to the bladder, and 2 injuries to ureters. There were no major vessel injuries. There were no injuries associated with primary trocar or Veres needle insertion. The most common perioperative morbidity reported was the requirement for blood transfusion (11 cases [0.9%]), and the second most common was venous thromboembolism (4 patients [0.3%]). Six (0.5%) cases were converted to laparotomy, 2 as a result of a complication and 4 for technical reasons. Six of the 8 complications were managed laparoscopically, and a multidisciplinary input was sought only in 4 of the 8 complications. CONCLUSIONS: Despite the advanced nature of laparoscopic procedures performed by our group, the complication rate and conversion to laparotomy remain low. There is an increasing feasibility to perform traditional open operations laparoscopically. An increasing number of these complications are now being managed laparoscopically by the gynecologist.