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A survey was used to gather information regarding airway management patterns in thermally injured children. North American pediatric burn centers listed by the American Burn Association were sent a survey designed to examine patterns of pediatric airway management in children with acute respiratory failure. The sample population means for the number of patients ventilated more than 48 hours and the number of patients ventilated more than 48 hours with inhalation injury were used to separate centers into large and small pediatric burn centers. Small pediatric burn centers had less than 50 patients who were intubated during a 5-year period. A five-point nominal scale was used to facilitate statistical analysis. Twenty-five pediatric burn centers included in the analysis estimated that 11,494 children were admitted during the 5-year period. There was no statistically dominant ventilator mode being used in the setting of acute respiratory failure identified by this survey. Large pediatric burn centers reported more frequent use of cuffed endotracheal tubes and more frequent change from an uncuffed to a cuffed endotracheal tube in patients who were difficult to ventilate because of an excess leak. Large pediatric burn centers reported a higher prevalence of tracheomalacia then small pediatric burn centers. Steroids were used by most centers before extubation in patients with persistent airway edema. No centers reported complications from steroid use. There is lack of clear consensus regarding the application of various ventilator modes in the setting of acute respiratory failure irrespective of center volume. There were divergent of practice patterns between large and small pediatric burn centers regarding the use of cuffed endotracheal tubes and the timing of tracheostomy. There was agreement between large and small pediatric burn centers in tracheostomy use in children older the age of 7 and the use of steroids as an adjunct to extubation in patients with lingering airway edema. Pediatric burn patients may benefit from clinical trials that clarify the advantages and disadvantages of various ventilator modes, the use of cuffed tubes, and the timing of tracheostomy. [ABSTRACT FROM AUTHOR]

Stroke is the fifth leading cause of death in the United States, and is the leading cause of serious, long-term disability worldwide. There are at least 795,000 new or recurrent strokes each year, and approximately 85% of all stroke occurrences are ischemic. Unfortunately, companion animals are also at risk for ischemic stroke. Although the exact incidence of ischemic stroke in companion animals is unknown, some studies, and the veterinary information network (VIN), report that approximately 3% of neurological case referrals are due to a stroke. There is a long list of predisposing factors associated with the risk of ischemic stroke in both humans and canines; however, these factors do not explain why a stroke happens at a particular time on a particular day. Our understanding of these potential stroke "triggers" is limited, and the effect of transient environmental exposures may be one such "trigger". The present study investigated the extent to which the natural occurrence of canine ischemic stroke was related to the weather conditions in the time-period immediately preceding the onset of stroke. The results of the present study demonstrated that the change in weather conditions could be a potential stroke trigger, with the strokes evaluated occurring after periods of rapid, large fluctuations in weather conditions. There are currently no epidemiological data on the seasonal variability of ischemic stroke in dogs, and determining whether canine stroke parallels human stroke would further validate the use of companion dogs as an appropriate naturally occurring model., Competing Interests: The authors declare no conflict of interest.

Objective: To report the clinical signs, imaging findings and surgical treatment of a meningoencephalocele in a cat., Study Design: Case report., Animal: Domestic shorthaired cat, 4 months old., Methods: A parietal meningoencephalocele was identified and characterized by magnetic resonance and computed tomography (CT) imaging. The abnormal tissue was excised and submitted for histopathology, and the meningeal and skull defects were reconstructed., Results: The cat made a full recovery and the episodes of aggression, restlessness and apparent discomfort that occurred before surgery ceased after surgical treatment. The cat was clinically normal 1 year postoperatively., Conclusion: Surgical management of meningoencephalocele in cats may be a viable treatment option., (© Copyright 2011 by The American College of Veterinary Surgeons.)

Time-course microarray experiments are capable of capturing dynamic gene expression profiles. It is important to study how these dynamic profiles depend on the multiple factors that characterize the experimental condition under which the time course is observed. Analytic methods are needed to simultaneously handle the time course and factorial structure in the data. We developed a method to evaluate factor effects by pooling information across the time course while accounting for multiple testing and nonnormality of the microarray data. The method effectively extracts gene-specific response features and models their dependency on the experimental factors. Both longitudinal and cross-sectional time-course data can be handled by our approach. The method was used to analyze the impact of age on the temporal gene response to burn injury in a large-scale clinical study. Our analysis reveals that 21% of the genes responsive to burn are age-specific, among which expressions of mitochondria and immunoglobulin genes are differentially perturbed in pediatric and adult patients by burn injury. These new findings in the body's response to burn injury between children and adults support further investigations of therapeutic options targeting specific age groups. The methodology proposed here has been implemented in R package "TANOVA" and submitted to the Comprehensive R Archive Network at http://www.r-project.org/. It is also available for download at http://gluegrant1.stanford.edu/TANOVA/.

Objective: To assess tolerability and short-term efficacy of oral administration of pregabalin as an adjunct to phenobarbital, potassium bromide, or a combination of phenobarbital and potassium bromide for treatment of dogs with poorly controlled suspected idiopathic epilepsy., Design: Open-label, noncomparative clinical trial., Animals: 11 client-owned dogs suspected of having idiopathic epilepsy that was inadequately controlled with phenobarbital, potassium bromide, or a combination of these 2 drugs., Procedures: Dogs were treated with pregabalin (3 to 4 mg/kg [1.4 to 1.8 mg/lb], PO, q 8 h) for 3 months. Number of generalized seizures in the 3 months before and after initiation of pregabalin treatment was recorded. Number of responders (>or= 50% reduction in seizure frequency) was recorded, and seizure frequency before and after initiation of pregabalin treatment was compared by use of a nonparametric Wilcoxon signed rank test., Results: Seizures were significantly reduced (mean, 57%; median, 50%) after pregabalin administration in the 9 dogs that completed the study; 7 were considered responders with mean and median seizure reductions of 64% and 58%, respectively. Adverse effects for pregabalin were reported in 10 dogs. Mean and median plasma pregabalin concentrations for all dogs were 6.4 and 7.3 microg/mL, respectively., Conclusions and Clinical Relevance: Pregabalin may hold promise as a safe and effective adjunct anticonvulsant drug for epileptic dogs poorly controlled with the standard drugs phenobarbital or potassium bromide. Adverse effects of pregabalin appeared to be mild. Additional studies with larger numbers of dogs and longer follow-up intervals are warranted.

Pharmacologic modulation of hypermetabolism clearly benefits children with major burns, however, its role in adult burns remains to be defined. Oxandrolone appears to be a promising anabolic agent although few outcome data are as yet available. We examined whether early oxandrolone treatment in severely burned adults was associated with improved outcomes during acute hospitalization. We evaluated for potential associations between oxandrolone treatment and outcomes in a large cohort of severely burned adults in the context of a multicenter observational study. Patients were dichotomized with respect to oxandrolone treatment, defined as administration within 7 days after admission, with duration of at least 7 days. Acute hospitalization outcomes were compared with univariate and multivariate analyses. One hundred seventeen patients were included in this analysis. Mean patient age was 42.6 years (range, 18-86); 77% were male, with an average TBSA of 44.1%. Baseline and injury characteristics were similar among treatment and nontreatment cohorts. Oxandrolone treatment (N = 59) did not impact length of stay but was associated with a lower mortality rate (P = .01) by univariate analysis. Oxandrolone treatment was independently associated with higher survival by adjusted analyses (P = .02). Examination of early oxandrolone treatment in this cohort of severely burned adults suggests that this therapy is safe and may be associated with improved survival. Further studies are necessary to define the exact mechanisms by which oxandrolone is beneficial during inpatient treatment.

A number of fluorinated 1-aryl-tetrahydrocyclopentapyrazoles were synthesized and their insecticidal activity was evaluated. Some of the fluorinated compounds had significant insecticidal properties.

A convenient synthetic route to novel 4-arylpyrazoles is described. The potential for insecticidal activity through GABA channel blockage by this series of compounds, as well as their selectivity for insect versus mammalian receptors, are explored through in vitro and in vivo assays.

The potential for controlling blood-feeding by the cattle pest, Haematobia irritans irritans (horn fly), was tested by vaccination against thrombostasin (TS), an inhibitor of mammalian thrombin that is released into skin during horn fly blood-feeding. The increase in blood meal size that occurred for flies feeding on sensitized non-vaccinated hosts was blocked and egg development in female flies was delayed when horn flies fed on rabbits and cattle immunized with recombinant TS. This demonstration of the impact of disrupting TS action by vaccination provides a novel approach toward control of this veterinary pest and offers a paradigm for limiting blood-feeding in other medically-important insect species.

Clinical outcomes and complications of a technique used for atlantoaxial stabilization were evaluated in a group of 12 dogs. At surgery, the atlantoaxial joint was realigned and rigidly fixated using cortical bone screws, K-wire, and polymethyl methacrylate. Results in nine dogs were graded as excellent. Results in two dogs were judged as good. One dog was euthanized 17 months after surgery for recurrent cervical pain. Eight dogs had no postoperative complications. The surgical technique described provided an adaptable method for the correction of atlantoaxial instability.

Several clones encoding serine protease inhibitors were isolated from larval and adult flea cDNA expression libraries by immunoscreening and PCR amplification. Each cDNA contained an open reading frame encoding a protein of approximately 45 kDa, which had significant sequence similarity with the serpin family of serine protease inhibitors. The thirteen cDNA clones isolated to date encode serpin proteins, which share a primary structure that includes a nearly identical constant region of about 360 amino acids, followed by a C-terminal variable region of about 40-60 amino acids. The variable C-terminal sequences encode most of the reactive site loop (RSL) and are generated by mutually exclusive alternative exon splicing, which may confer unique protease selectivity to each serpin. Utilization of an alternative exon splicing mechanism has been verified by sequence analysis of a flea serpin genomic clone and adjacent genomic sequences. RNA expression patterns of the cloned genes have been examined by Northern blot analysis using variable region-specific probes. Several putative serpins have been overexpressed using the cDNA clones in Escherichia coli and baculovirus expression systems. Two purified baculovirus-expressed recombinant proteins have N-terminal amino acid sequences identical to the respective purified native mature flea serpins indicating that appropriate N-terminal processing occurred in the virus-infected insect cells., (Copyright 2004 Wiley-Liss, Inc.)

Experimental evidence implicates Fas ligand-mediated keratinocyte apoptosis as an underlying mechanism of toxic epidermal necrolysis syndrome (TEN). In vitro studies indicate a potential role for immunoglobulin (Ig) therapy in blocking Fas ligand signaling, thus reducing the severity of TEN. Anecdotal reports have described successful treatment of TEN patients with Ig; however, no study to date has analyzed outcome data in a large series of patients treated with Ig using institutional controls. The SCORTEN severity-of-illness score ranks severity and predicts prognosis in TEN patients using age, heart rate, TBSA slough, history of malignancy, and admission blood urea nitrogen, serum bicarbonate, and glucose levels. A retrospective chart review was performed that included all patients treated for TEN at our burn center since 1997. Ig therapy was instituted for all patients with biopsy-proven TEN beginning in January 2000. Twenty-one TEN patients were treated before Ig (no-Ig group), and 24 patients have been treated with Ig. SCORTEN data were collected, as well as length of stay (LOS) and status upon discharge. Each patient was given a SCORTEN of 0 to 6, with 1 point each for age greater than 40, TBSA slough greater than 10%, history of malignancy, admission BUN greater than 28 mg/dl, HCO3 less than 20 mg/dl, and glucose greater then 252 mg/dl. Outcome was compared between patients treated with Ig and without Ig. Overall mortality for patients treated before Ig was 28.6% (6/21), and with Ig, mortality was 41.7%% (10/24). There was no significant difference in age or TBSA slough. The average SCORTEN between the groups was equivalent (2.2 in no-Ig group vs 2.7 in Ig group, P = 0.3), and no group of patients with any SCORTEN score showed a significant benefit from Ig therapy. Overall LOS as well as LOS for survivors was longer in the Ig group. This series represents the largest single-institution analysis of TEN patient outcome after institution of Ig therapy. Our data do not show a significant improvement in mortality for TEN patients treated with Ig at any level of severity and may indicate a potential detriment in using Ig. Ig should not be given to TEN patients outside of a clinical trial. A multicenter, prospective, double-blinded randomized trial is necessary and urgently indicated to determine whether Ig therapy is beneficial or harmful in the care of TEN patients.

Open surgical repair of retrohepatic inferior vena cava (IVC) injuries can be technically difficult, usually requiring extensive hepatic mobilization and associated with significant morbidity. We report a case of uncontrolled hemorrhage from the retrohepatic inferior vena cava (IVC), which occurred during attempted resection of a large retroperitoneal leiomyosarcoma, and was successfully managed using an endoluminal stent-graft. This case demonstrates that endoluminal grafts can be successfully applied to control life-threatening hemorrhage arising from lesions in the retrohepatic IVC that are otherwise extremely difficult or inaccessible to direct surgical repair.

Pyrazole 2a is a novel, potent ligand for insect GABA receptors obtained from housefly head membrane preparations (K(i)=8 nM). It is 500-fold selective against the mammalian receptor (mouse brain preparations). Its specifically tritiated version (2b) was synthesized by reduction of disulfide 10 with NaBH(4) followed by alkylation with [3H(3)]-CH(3)I.

Background: Trauma care demands constant physician availability, resulting in rotational coverage systems. Third-party payors consider separate trauma surgeon bills as originating from the same individual. Trauma surgeons may be unaware of their colleagues' billing history on jointly managed patients. Not all postoperative procedures and evaluation and management services are denied by global surgical package rules. We investigated whether a networked billing program designed to crosscheck for global package coding concerns would reduce payment denials., Methods: A networked relational database was created for trauma surgeons to enter billable encounters, displaying global periods and operative diagnoses while prompting for postoperative modifiers. Denials were compared for equivalent time periods before and after program initiation., Results: Payment denials fell from 361 to 16 for "bundled" evaluation and management services and from 55 to 13 for bundled postoperative procedures. Time spent on billing decreased and legibility improved. Overall savings totaled $183,404., Conclusion: Collaborative billing can improve payments for professional trauma care.

The degradation of cat immunoglobulin G (IgG) in blood-fed adult C. felis midguts was examined. SDS-PAGE analysis of dissected midgut extracts obtained from C. felis that had been blood fed for various times between 0 to 44 h revealed that by 24 h most of the high molecular weight proteins, including the heavy chain of IgG, were digested. A 31-kDa serine protease with IgG degrading activity was purified from fed C. felis midguts by benzamidine affinity chromatography, hydrophobic interaction chromatography, and cation exchange chromatography. Three primary cleavage products between 30- and 40-kDa were observed when the purified protease was incubated with protein A purified cat IgG. N-terminal amino acid sequence analysis of the products revealed that the IgG degrading protease cleaves after specific cysteine and lysine residues within the hinge region of IgG. The enzyme is also capable of degrading other immunoglobulins, serum albumin, and hemoglobin, suggesting that it may have roles in both combating the host's immune system and providing nutrients for the flea. A cDNA clone encoding the 265 amino acid IgG degrading protease proenzyme was isolated. When expressed in a baculovirus/insect cell expression system, the recombinant protein had the same N-terminus as the processed 237 amino acid mature native protein and possessed IgG degrading activity indistinguishable from the native protein. Arch. Insect Biochem., (Copyright 2002 Wiley-Liss, Inc.)

cDNAs encoding two different epoxide hydrolases (nCfEH1 and nCfEH2) were cloned from a cDNA library prepared from the wandering larval stage of the cat flea, Ctenocephalides felis. Predicted translations of the open reading frames indicated the clones encoded proteins of 464 (CfEH1) and 465 (CfEH2) amino acids. These proteins have a predicted molecular weight of 53 kDa and a putative 22 amino acid N-terminal hydrophobic membrane anchor. The amino acid sequences are 77% identical, and both are homologous to previously isolated epoxide hydrolases from Manduca sexta, Trichoplusia ni, and Rattus norvegicus. Purification of native juvenile hormone epoxide hydrolase (JHEH) from unfed adult cat fleas generated a partially pure protein that hydrolyzed juvenile hormone III to juvenile hormone III-diol. The amino terminal sequence of this;50-kDa protein is identical to the deduced amino terminus of the protein encoded by the nCfEH1 clone. Affinity-purified rabbit polyclonal antibodies raised against Escherichia coli-expressed HisCfEH1 recognized a approximately 50-kDa protein present in the partially purified fraction containing JHEH activity. Immunohistochemistry experiments using the same affinity-purified rabbit polyclonal antibodies localized the epoxide hydrolase in developing oocytes, fat body, and midgut epithelium of the adult flea. The presence of JHEH in various flea life stages and tissues was assessed by Northern blot and enzymatic activity assays. JHEH mRNA expression remained relatively constant throughout the different flea larval stages and was slightly elevated in the unfed adult flea. JHEH enzymatic activity was highest in the late larval, pupal, and adult stages. In all stages and tissues examined, JHEH activity was significantly lower than juvenile hormone esterase (JHE) activity, the other enzyme responsible for JH catalysis., (Copyright 2002 Wiley-Liss, Inc.)

Objective: To determine factors associated with the occurrence of pneumonia after intracranial surgery in dogs., Study Design: Retrospective cohort study. Animals-Forty-nine client-owned dogs., Methods: The medical records of 49 dogs with space-occupying intracranial disease that underwent craniotomy were reviewed. Development of pneumonia after surgery was considered highly likely in 12 dogs (affected dogs) based on clinical signs, including acute dyspnea or coughing in association with typical radiographic findings or abnormal transtracheal wash results. Pneumonia was confirmed in 6 dogs based on necropsy findings. Affected dogs were compared with 37 dogs that did not develop pneumonia (unaffected dogs) subsequent to intracranial surgery. Based on the medical records of affected dogs, determinations were made regarding time between development of pneumonia and surgery, surgical procedure, intracranial lesion type, and intracranial lesion location. Risk factors examined for both affected and unaffected dogs included level of consciousness, body position during the postoperative recovery period, duration of anesthesia, occurrence of vomiting or regurgitation, presence of seizures, cranial nerve deficiencies, and the presence of megaesophagus before and after surgery. We also compared the feeding protocol after surgery for each group., Results: Pneumonia typically occurred within the first week after surgery (median, 6.5 days); however, this was variable (range, 1-96 days). Of the factors that were present within 24 hours before the clinical signs of pneumonia, vomiting or regurgitation and megaesophagus were found to be significant risk factors. Dogs that vomited or regurgitated were 2.71 times more likely to develop pneumonia than dogs that did not. Vomiting or regurgitation occurred in 63% of the dogs that developed pneumonia in this cohort. Dogs with megaesophagus were 9.25 times more likely to develop pneumonia than dogs without megaesophagus. Seven dogs with pneumonia died. Five of these 7 dogs appeared to have died as a direct sequel to pneumonia., Conclusion: Dogs undergoing craniectomies for space-occupying intracranial disease may be at higher risk for development of pneumonia due to several factors, including vomiting, regurgitation, and megaesophagus., (Copyright 2001 by The American College of Veterinary Surgeons)

A 6 month-old dog was examined for progressive paraparesis. On physical examination bony malformations were palpated over the cranial lumbar vertebral bodies and on the left metatarsal bone. Neuroanatomic lesion localization for the paraparesis was a T3-L3 spinal cord lesion. Radiographs confirmed bony masses at L1-L2 and on the left 3rd metatarsal bone. Magnetic resonance imaging was performed from T3-L3. Severe spinal cord compression was identified at L1-L2. Surgical decompression and biopsy confirmed the mass to be cartilaginous exostoses. This paper is an example of cartilaginous exostoses imaged with MR.

Objective: To determine the minimal ultrasonic aspirator pressure necessary to damage the cerebral cortex of healthy dogs., Animals: 9 mixed-breed dogs., Procedure: The study comprised 2 parts. In part A, 6 dogs were euthanatized immediately prior to the experiment. In part B, 3 dogs were anesthetized for recording of physiologic variables. In both parts, craniectomy and durotomy were performed to bilaterally expose the lateral aspect of the cerebral cortex. An ultrasonic aspirator was placed in contact with various areas of the cerebral cortex, and aspirator power was altered (10, 20, 30, and 40%). Duration of contact at each power was 5 and 10 seconds. Subsequently, gross morphologic and histologic damage was assessed in the cortex., Results: Gross observations for all dogs were similar. At 10% power, visible or histologic damage was not evident in the cortex. At 20% power, the cortex was slightly indented from contact with the hand piece; however, cortical disruption was not evident. Cortical disruption was initially detectable at 30% power in some dogs and was consistently evident at 40% power in both sets of dogs., Conclusions and Clinical Relevance: Ultrasonic aspirator power of < 20% created minimal acute morphologic damage to the cortex. Power settings between 20 and 30% may superficially damage the cerebral cortex in healthy dogs, whereas 40% power consistently damages the cerebral cortex. Knowledge of the degree of damage to cerebral cortex caused by various amounts of power for ultrasonic aspirators will allow surgeons to avoid damaging normal brain tissues during surgery.

Twenty-one dogs with confirmed tumors of the spinal cord or paraspinal tissues were imaged with magnetic resonance (MR) imaging. Anatomical location, location in relation to the dura and the medulla (spinal cord), and bone infiltration were assessed on the MR images and compared to findings at surgery or necropsy. Localization of tumors in the intradural-extramedullary compartment was not always possible. Bone infiltration was correctly assessed in all but one dog, and the anatomical locations involved were accurately determined in all dogs. Sagittal T2-weighted images were helpful to determine the anatomical location. Transverse T1-weighted images pre and post Gd-DTPA administration were helpful for additional localization and definition of tumor extension.

Objective: To determine the prevalence of various clinical signs in dogs with brain tumors., Design: Retrospective study., Animals: 97 dogs with brain tumors., Procedure: Medical records were reviewed for signalment, tumor type and location, and clinical signs., Results: 33 breeds were represented; Golden Retrievers were most commonly affected. Most dogs were older (median age, 9 years); 95% of dogs were > or = 5 years old. Seventy-six percent of dogs had tumors in the supratentorial region. Seizures were the most common clinical sign at initial examination, with lower prevalence for circling, ataxia, and head tilt. Meningioma was the most common tumor., Conclusions and Clinical Relevance: Brain tumors develop most often in dogs > or = 5 years old and are uncommon in dogs < 5 years old. Seizures are a common clinical sign, and a brain tumor should be considered in dogs that have their first seizure after they are 4 years old.

Passage of ingested cat immunoglobulin G (IgG) into the hemocoel of cat fleas, Ctenocephalides felis (Bouché), was examined using antibody capture enzyme-linked immunosorbent assays (ELISA) and Western blotting. Fleas were fed heparinized cat blood via membrane feeders. Cat IgG was present in the hemolymph of engorged female fleas 1 h after ingestion at an estimated quantity of 35 +/- 14 micrograms/ml. The prevalence of fleas with demonstrable cat IgG in their hemolymph 1 h after feeding was 100% for both female and male fleas. Following a single blood meal, cat IgG was present in the hemolymph of all 15 fleas tested 1 h after ingestion but dissipated below detectable levels in 10 of 20 fleas examined 3 h after ingestion, and was detectable in only 1 of 10 fleas examined 18 h after ingestion. However, when fleas were provided with continual access to blood over a 72-h period, IgG content in hemolymph, as measured in excised, triturated legs of individual fleas, remained fairly constant (3-16 pg IgG per sample). Flea feeding studies using specific antisera indicated that IgG in flea hemolymph retained its binding activity, and that at least a portion of the IgG was intact. Passage of ingested host antibody from gut into hemocoel is a prerequisite for the possible development of antiflea vaccines that target antigens outside of the flea midgut lumen (e.g., key components of the flea endocrine system controlling oogenesis).

Priming of polymorphonuclear neutrophils (PMN) in whole blood (by tumor necrosis factor alpha and interleukin-8 for enhancement of luminol-dependent chemiluminescence induced by human complement-opsonized zymosan) was stable for 120 min. In contrast, priming of isolated PMN in plasma-free suspension for responses to opsonized zymosan, formyl-methionyl-leucyl-phenylalanine, and phorbol myristate acetate was markedly less stable. Decay of priming was not due to irreversible inactivation of the terminal CL production machinery because PMN could be reprimed by platelet-activating factor or leukotriene B4. The tumor necrosis factor-alpha-primed state of isolated PMN was stabilized by host plasma in a concentration-dependent fashion. We conclude that PMN priming results in a dynamic state that is reversible. Our findings suggest the existence of blood-borne components that may act to stabilize or modify PMN priming.

A 7-month-old female Mastiff was admitted for weakness in the hind limbs and an abnormal gait. There was an obvious scoliosis in the midlumbar region. Using electromyography, fibrillation potentials and positive sharp waves were found in the epaxial musculature of the vertebral column lateral to the spinous processes of Tl3-L4 on the right (convex) side of the body. On myelographic evaluation, contrast medium irregularly filled the subdural and epidural space of Tl1-L3. On surgical examination, the dog had a cystic lesion of the spinal cord that correlated with myelographic findings. This lesion was incised and drained. The scoliotic defect was surgically straightened, and the affected vertebrae were fused. Six months after surgery, the vertebral column continued to be straight and the paraparesis had resolved.

Isoprene (2-methyl-1,3-butadiene) is a volatile hydrocarbon emitted from many plant species to the atmosphere, where it plays an important role in atmospheric chemistry. An enzyme extracted from aspen (Populus tremuloides) leaves was previously found to catalyze the Mg(2+)-dependent elimination of pyrophosphate from dimethylallyl diphosphate (DMAPP) to form isoprene (Silver, G. M., and Fall, R. (1991) Plant Physiol. 97, 1588-1591). This enzyme, isoprene synthase, has now been purified 4000-fold to near homogeneity. The enzyme had a native molecular mass of 98-137 kDa and isoelectric point of 4.7 and contained 58- and 62-kDa subunits, implying that it is a heterodimer. Partial amino acid sequences of the two subunits indicated they are closely related to each other and that they do not share a strong homology with any other reported proteins. The isoprene synthase reaction was dependent on Mg2+ or Mn2+, and the reaction products were shown to be isoprene and pyrophosphate with a stoichiometry close to 1:1. The Km for DMAPP was high at 8 mM, and the kcat of 1.7 s-1 was low, but similar to those of other allylic diphosphate-utilizing enzymes. It is argued that the isoprene synthase reaction may be much more efficient in vivo, where it is under light-dependent control. It seems probable that this unique enzyme, rather than non-enzymatic reactions, can account for the emission of hundreds of millions of metric tons of isoprene from plants to the global atmosphere each year.

While screening aerobic, heterotrophic marine bacteria for production of volatile organic compounds, we found that a group of isolates produced substantial amounts of acetone. Acetone production was confirmed by gas chromatography, gas chromatography-mass spectrometry, and high-performance liquid chromatography. The major acetone producers were identified as nonclinical Vibrio species. Acetone production was maximal in the stationary phase of growth and was stimulated by addition of l-leucine but not the other common amino acids, suggesting that leucine degradation leads to acetone formation. Acetone production by marine vibrios may contribute to the dissolved organic carbon associated with phytoplankton, and some of the acetone produced may be volatilized to the atmosphere.

In the past few years we have greatly improved our understanding of the pathophysiologic mechanisms underlying the clinical syndrome of sepsis. As of this writing, however, this improved understanding has failed to result in the development of a single pharmacologic agent with clearly documented efficacy for improving outcome in septic patients. Research in this field, however, is yielding new insights on almost a daily basis, and it seems probable that the pharmacotherapy of sepsis and septic shock will undergo dramatic changes in the near future.

Infections remain a serious problem following injury. Immune modulation offers an additional strategy for the treatment of infections. We evaluated the ability of a multilineage hematopoietic growth factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), to improve survival following burn injury with a superimposed burn wound infection. Groups of 12 BDF1 mice received a 15% total body surface area (TBSA) thermal injury by immersion in 100 degrees C water; 6 x 10(3) Pseudomonas was then applied to the burn wound. The GM-CSF was injected subcutaneously B.I.D. for 7 days. Mice receiving the 10-ng dose of GM-CSF had significantly improved survival compared with the controls; other doses had no significant effect on survival. Clinical trials to assess the ability of GM-CSF to reduce infectious complications following burn injury are underway and these data suggest selecting a specific dose may be critical in achieving maximal benefit.

Polymicrobial infection is a significant cause of mortality in critically ill patients. Antibiotics and surgical intervention are useful but limited in their effectiveness for combating mixed infections. New prophylactic and therapeutic approaches are required to improve survival in critically ill patients. Neutrophils are a known primary host defense mechanism against bacterial infection. We evaluated the use of a neutrophil growth factor, recombinant human granulocyte colony-stimulating factor (G-CSF), to improve survival in a well-established sepsis model, cecal ligation and puncture (CLP). When administered beginning 4 days before CLP with injections continuing for 14 days after CLP, mice that received 10, 100, or 1000 ng of G-CSF had significantly improved survival compared with the control group. When treatment began at the time of CLP and continued for 7 days after CLP, G-CSF treatment resulted in a dose-dependent improvement in survival in groups that received 100, 500, or 1000 ng. The interaction of G-CSF and conventional antimicrobial therapy was evaluated by administration of G-CSF plus gentamicin. Mice received 100 ng of G-CSF beginning on day 1 before CLP with injections continuing for 3 days after CLP. Gentamicin-treated mice received a single 15 mg/kg injection of gentamicin at the time of CLP. Mice that received G-CSF alone or gentamicin alone had significantly improved survival compared with controls. Mice that received G-CSF plus gentamicin had improved survival compared with control mice and compared with mice that received G-CSF alone but not compared with mice that received gentamicin alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Despite antibiotic therapy intra-abdominal sepsis following major surgery is a significant cause of mortality. We sought to determine if interleukin-1 beta (IL-1) could improve survival in a murine model of intra-abdominal infection. Groups of 10 BDF1 mice received a single subcutaneous (sc) injection of recombinant human IL-1 beta 24 hr prior to cecal ligation and puncture (CLP) and were assessed twice daily for survival. Mice that received a single injection of IL-1 beta 24 hr prior to CLP had a dose-dependent improval in survival compared to controls. The beneficial effect of IL-1 treatment may have been related to its ability to stimulate myelopiesis. The addition of indomethacin, in an effort to limit possible toxicity of IL-1, did not further improve survival. Appropriate timing of specific immunomodulators may provide an additional strategy for the treatment of infections.

Isoprene emissions from the leaves of velvet bean (Mucuna pruriens L. var utilis) plants exhibited temperature response patterns that were dependent on the plant's growth temperature. Plants grown in a warm regimen (34/28 degrees C, day/night) exhibited a temperature optimum for emissions of 45 degrees C, whereas those grown in a cooler regimen (26/20 degrees C, day/night) exhibited an optimum of 40 degrees C. Several previous studies have provided evidence of a linkage between isoprene emissions and photosynthesis, and more recent studies have demonstrated that isoprene emissions are linked to the activity of isoprene synthase in plant leaves. To further explore this linkage within the context of the temperature dependence of isoprene emissions, we determined the relative temperature dependencies of photosynthetic electron transport, CO(2) assimilation, and isoprene synthase activity. When measured over a broad range of temperatures, the temperature dependence of isoprene emission rate was not closely correlated with either the electron transport rate or the CO(2) assimilation rate. The temperature optima for electron transport rate and CO(2) assimilation rate were 5 to 10 degrees C lower than that for the isoprene emission rate. The dependence of isoprene emissions on photon flux density was also affected by measurement temperature in a pattern independent of those exhibited for electron transport rate and CO(2) assimilation rate. Thus, despite no change in the electron transport rate or CO(2) assimilation rate at 26 and 34 degrees C, the isoprene emission rate changed markedly. The quantum yield of isoprene emissions was stimulated by a temperature increase from 26 to 34 degrees C, whereas the quantum yield for CO(2) assimilation was inhibited. In greenhouse-grown aspen leaves (Populus tremuloides Michaux.), the high temperature threshold for inhibition of isoprene emissions was closely correlated with the high temperature-induced decrease in the in vitro activity of isoprene synthase. When taken together, the results indicate that although there may be a linkage between isoprene emission rate and photosynthesis, the temperature dependence of isoprene emission is not determined solely by the rates of CO(2) assimilation or electron transport. Rather, we propose that regulation is accomplished primarily through the enzyme isoprene synthase.

Aspen (Populus tremuloides Michx.) leaf extracts contain a newly discovered enzyme activity that catalyzes the magnesium ion-dependent elimination of diphosphate from dimethylallyl diphosphate with rearrangement to form isoprene (2-methyl, 1-3-butadiene). This isoprene synthase activity has been partially purified. The nonenzymatic reaction of dimethylallyl diphosphate to isoprene, known to be acid catalyzed, may be insignificant at physiological pH. In contrast, the enzymatic reaction may be responsible for the majority of light-dependent isoprene production by isoprene-emitting plants.

Severe thermal injury results in impairment of granulocyte production and function. The ability to improve the functional capacity of neutrophils could contribute to a reduced morbidity and mortality from sepsis following thermal injury. Previous studies from this laboratory have shown that rhG-CSF increases the number of femoral marrow granulocyte progenitor cells and circulating neutrophils as well as the survival rate following burn wound infection. The studies reported here examine the effect of in-vivo administration of rhG-CSF on neutrophil chemotaxis following a burn injury and also following superimposed Pseudomonas burn wound sepsis in mice. Casein-elicited peritoneal neutrophils were harvested 72 hours after burn injury and 24 hours after infection. Chemotaxis was assessed using microchemotaxis chambers and 10(-5) M fMet-Phe as a chemoattractant. The number of neutrophils that migrated into the filter was used as an index of directed chemotaxis. Burn injury resulted in depressed chemotaxis compared with sham or sham/G-CSF-treated animals (p less than 0.05). Administration of rhG-CSF to burned animals resulted in a level of neutrophil chemotaxis comparable with that in control animals. The presence of a burn wound infection caused no further impairment of chemotaxis. Administration of rhG-CSF to animals with a burn wound infection resulted in improved chemotaxis compared with sham, burned, and burned/infected animals. The beneficial effect of G-CSF following burn wound infections from this and previous studies appears to be a combination of expanded numbers of myeloid elements and preservation of their function.

We examined the effects of human recombinant interleukin 1 alpha (IL-1 alpha) in a murine model of burn wound sepsis. The BDF1 male mice received a 15% burn injury, followed by burn wound inoculation with Pseudomonas aeruginosa. Improvement in survival was noted in the mice that received a single injection of 100 or 1000 ng of IL-1 alpha in comparison with the control animals (IL-1 alpha, 100 ng vs control, 60% vs 13%; IL-1 alpha, 1000 ng vs control, 40% vs 0%). The animals that received 1 ng twice daily for 7 days had improved survival in comparison with the controls (IL-1 alpha vs control, 70.8% vs 20.8%). The animals that received a single injection of 1000 ng after a bacterial challenge with 10(4) P aeruginosa of IL-1 alpha had fewer positive blood cultures at 48 hours compared with the controls (57% vs 89%). In addition, the animals that received 100 ng of IL-1 alpha had significantly increased absolute neutrophil counts at 6, 24, and 48 hours after thermal injury and bacterial challenge with 10(3) colony-forming units of P aeruginosa. The use of cytokines to modulate the host response to injury or infection may lead to additional strategies to improve the outcome following burn injury.

Porcine bioprostheses implanted in both the mitral and aortic valve positions simultaneously in 5 patients aged 20 to 61 years (mean 45) were reexamined 18 to 107 months (mean 51) later. In 4 patients, the degenerative changes were distinctly more severe in the bioprostheses in the mitral than in the aortic valve position.

Inadequate granulopoiesis and decreased granulocyte function are thought to play a significant role in the burned victim's susceptibility to infection. In an attempt to determine whether the regulatory granulopoietic growth factor G-CSF could favorably affect survival when used in combination with antibiotics, we examined survival in a murine model of Pseudomonas aeruginosa burn wound infection. One hundred twenty male BDF1 mice received a 15% total body surface area burn and were randomized to one of five treatment groups: (1) burn only, (2) burn + infection, (3) burn + infection + G-CSF, (4) burn + infection + gentamicin, and (5) burn + infection + G-CSF + gentamicin. Infected mice received a 10(3) colony-forming units topical inoculum of Pseudomonas to the wound immediately postburn. Gentamicin animals received 6.0 mg/kg intraperitoneal gentamicin as a single dose immediately postburn. G-CSF was administered as 100 ng twice daily for 7 days. All treatment groups showed improved survival compared with the burn + infection group, which showed 100% mortality by day 9 (p less than 0.001 all groups; Cox-Mantel statistic). Group 5 (burn + infection + G-CSF + gentamicin) exhibited improved survival as compared with either group 3 (burn + infection + G-CSF, p = 0.054) or group 4 (burn + infection + gentamicin, p = 0.007). The use of hematopoietic growth stimulants in combination with antibiotic therapy may result in improved outcome after burn injury, and it suggests new treatment options in the management of postburn infectious complications.