Cooling reverses pathological bifurcations to spontaneous firing caused by mild traumatic injury.

Mild traumatic injury can modify the key sodium (Na+) current underlying the excitability of neurons. It causes the activation and inactivation properties of this current to become shifted to more negative trans-membrane voltages. This so-called coupled left shift (CLS) leads to a chronic influx of Na+ into the cell that eventually causes spontaneous or "ectopic" firing along the axon, even in the absence of stimuli. The bifurcations underlying this enhanced excitability have been worked out in full ionic models of this effect. Here, we present computational evidence that increased temperature T can exacerbate this pathological state. Conversely, and perhaps of clinical relevance, mild cooling is shown to move the naturally quiescent cell further away from the threshold of ectopic behavior. The origin of this stabilization-by-cooling effect is analyzed by knocking in and knocking out, one at a time, various processes thought to be T-dependent. The T-dependence of the Na+ current, quantified by its Q 10-Na factor, has the biggest impact on the threshold, followed by Q 10-pump of the sodium-potassium exchanger. Below the ectopic boundary, the steady state for the gating variables and the resting potential are not modified by temperature, since our model separately tallies the Na+ and K+ ions including their separate leaks through the pump. When only the gating kinetics are considered, cooling is detrimental, but in the full T-dependent model, it is beneficial because the other processes dominate. Cooling decreases the pump's activity, and since the pump hyperpolarizes, less hyperpolarization should lead to more excitability and ectopic behavior. But actually the opposite happens in the full model because decreased pump activity leads to smaller gradients of Na+ and K+, which in turn decreases the driving force of the Na+ current.

Pharmacokinetics and pharmacodynamics of three formulations of firocoxib in healthy horses.

The objectives of this study were to compare the pharmacokinetics and COX selectivity of three commercially available formulations of firocoxib in the horse. Six healthy adult horses were administered a single dose of 57 mg intravenous, oral paste or oral tablet firocoxib in a three-way, randomized, crossover design. Blood was collected at predetermined times for PGE2 and TXB2 concentrations, as well as plasma drug concentrations. Similar to other reports, firocoxib exhibited a long elimination half-life (31.07 ± 10.64 h), a large volume of distribution (1.81 ± 0.59L/kg), and a slow clearance (42.61 ± 11.28 mL/h/kg). Comparison of the oral formulations revealed a higher Cmax , shorter Tmax , and greater AUC for the paste compared to the tablet. Bioavailability was 112% and 88% for the paste and tablet, respectively. Maximum inhibition of PGE2 was 83.76% for the I.V. formulation, 52.95% for the oral paste formulation, and 46.22% for the oral tablet formulation. Pharmacodynamic modeling suggests an IC50 of approximately 27 ng/mL and an IC80 of 108 ng/ mL for COX2 inhibition. Inhibition of TXB2 production was not detected. This study indicates a lack of bioequivalence between the oral formulations of firocoxib when administered as a single dose to healthy horses.

Pharmacokinetics of tobramycin following intravenous, intramuscular, and intra-articular administration in healthy horses.

The objectives of this study were to examine the pharmacokinetics of tobramycin in the horse following intravenous (IV), intramuscular (IM), and intra-articular (IA) administration. Six mares received 4 mg/kg tobramycin IV, IM, and IV with concurrent IA administration (IV+IA) in a randomized 3-way crossover design. A washout period of at least 7 days was allotted between experiments. After IV administration, the volume of distribution, clearance, and half-life were 0.18 ± 0.04 L/kg, 1.18 ± 0.32 mL·kg/min, and 4.61 ± 1.10 h, respectively. Concurrent IA administration could not be demonstrated to influence IV pharmacokinetics. The mean maximum plasma concentration (Cmax ) after IM administration was 18.24 ± 9.23 µg/mL at 1.0 h (range 1.0-2.0 h), with a mean bioavailability of 81.22 ± 44.05%. Intramuscular administration was well tolerated, despite the high volume of drug administered (50 mL per 500 kg horse). Trough concentrations at 24 h were below 2 µg/mL in all horses after all routes of administration. Specifically, trough concentrations at 24 h were 0.04 ± 0.01 µg/mL for the IV route, 0.04 ± 0.02 µg/mL for the IV/IA route, and 0.02 ± 0.02 for the IM route. An additional six mares received IA administration of 240 mg tobramycin. Synovial fluid concentrations were 3056.47 ± 1310.89 µg/mL at 30 min after administration, and they persisted for up to 48 h with concentrations of 14.80 ± 7.47 µg/mL. Tobramycin IA resulted in a mild chemical synovitis as evidenced by an increase in synovial fluid cell count and total protein, but appeared to be safe for administration. Monte Carlo simulations suggest that tobramycin would be effective against bacteria with a minimum inhibitory concentration (MIC) of 2 µg/mL for IV administration and 1 µg/mL for IM administration based on Cmax :MIC of 10.

Pharmacokinetics of intravenous and intramuscular buprenorphine in the horse.

The purpose of this study was to determine the pharmacokinetics of buprenorphine following intravenous (i.v.) and intramuscular (i.m.) administration in horses. Six horses received i.v. or i.m. buprenorphine (0.005 mg/kg) in a randomized, crossover design. Plasma samples were collected at predetermined times and horses were monitored for adverse reactions. Buprenorphine concentrations were measured using ultra-performance liquid chromatography with electrospray ionization mass spectrometry. Following i.v. administration, clearance was 7.97±5.16 mL/kg/min, and half-life (T(1/2)) was 3.58 h (harmonic mean). Volume of distribution was 3.01±1.69 L/kg. Following i.m. administration, maximum concentration (C(max)) was 1.74±0.09 ng/mL, which was significantly lower than the highest measured concentration (4.34±1.22 ng/mL) after i.v. administration (P<0.001). Time to C(max) was 0.9±0.69 h and T(1/2) was 4.24 h. Bioavailability was variable (51-88%). Several horses showed signs of excitement. Gut sounds were decreased 10±2.19 and 8.67±1.63 h in the i.v. and i.m. group, respectively. Buprenorphine has a moderate T(1/2) in the horse and was detected at concentrations expected to be therapeutic in other species after i.v. and i.m. administration of 0.005 mg/kg. Signs of excitement and gastrointestinal stasis may be noted.

Milk and plasma disposition of thymol following intramammary administration of a phytoceutical mastitis treatment.

Despite the recent growth of the organic dairy industry, organic producers and veterinarians have limited information when choosing mastitis treatments for animals in organic dairy production. Organic producers commonly administer homeopathic or other plant-based products without having research evaluating the efficacy of these products and using estimated or no withholding times to treat mastitis and other health problems in their herds. In this pilot study, we attempted to identify several active ingredients of Phyto-Mast (Penn Dutch Cow Care, Narvon, PA), a plant-based mastitis treatment used on organic dairy farms, and to quantify the product residue in milk and plasma after intramammary administration. We developed an assay to quantify thymol (one of the active ingredients in Phyto-Mast) in milk and plasma using gas chromatography and mass spectrometry (GC-MS). Thymol is a volatile aromatic compound with antiinflammatory properties. As a model for dairy cows, 5 healthy, lactating alpine dairy goats were given 5 mL of Phyto-Mast per udder half. For 10 d following treatment, we analyzed blood and milk samples for thymol residues using GC-MS. The GC-MS assay was very sensitive for thymol detection, to a concentration of 0.01 µg/mL in plasma. Using thymol as a marker, Phyto-Mast was detectable and quantifiable in plasma beginning with the 15-min posttreatment sample, but was no longer detectable in the 4-h posttreatment sample. Thymol residues were only detected in the 12-h posttreatment milk sample. An inflammatory response was not evident in the udder following phytoceutical administration. Although this study provides information about the elimination of thymol, the product contains several other active chemicals, which may have different pharmacokinetic behaviors. Further analysis and additional study animals will help to determine a milk withholding time for Phyto-Mast. Given the recent growth of the organic dairy industry, understanding the pharmacokinetics of therapeutics used in organic production and developing accurate withholding recommendations will help to ensure milk safety.

Permanent translocation heterozygosity and sex determination in East african mistletoes.

Viscum fischeri has 2n = 23 chromosomes in male plants. These fornm 7 bivalents and a translocation chain of 9 chromosomes during meiosis. Pollen with 11-and 12-chromosome genomes is thus produced. Female plants have 2n = 22 chromosomes and produce 11 bivalents during meiosis. Sex determination is technically a rare multiple X-multiple Y type, but more importantly it provides the mechanism whereby permanent translocation heterozygosity is maintained in the system. In a second species, Viscum engleri, male plants have 2n=28 chromosomes associating as 11 bivalents and a ring of 6 chomosomes at meiosis.

Intraoperative placement of total hip arthroplasty components with robotic-arm assisted technology correlates with postoperative implant position: a CT-based study.

AIMS: The aim of this study was to evaluate the accuracy of implant placement when using robotic assistance during total hip arthroplasty (THA). PATIENTS AND METHODS: A total of 20 patients underwent a planned THA using preoperative CT scans and robotic-assisted software. There were nine men and 11 women (n = 20 hips) with a mean age of 60.8 years (sd 6.0). Pelvic and femoral bone models were constructed by segmenting both preoperative and postoperative CT scan images. The preoperative anatomical landmarks using the robotic-assisted system were matched to the postoperative 3D reconstructions of the pelvis. Acetabular and femoral component positions as measured intraoperatively and postoperatively were evaluated and compared. RESULTS: The system reported accurate values for reconstruction of the hip when compared to those measured postoperatively using CT. The mean deviation from the executed overall hip length and offset were 1.6 mm (sd 2.9) and 0.5 mm (sd 3.0), respectively. Mean combined anteversion was similar and correlated between intraoperative measurements and postoperative CT measurements (32.5°, sd 5.9° versus 32.2°, sd 6.4°; respectively; R2 = 0.65; p < 0.001). There was a significant correlation between mean intraoperative (40.4°, sd 2.1°) acetabular component inclination and mean measured postoperative inclination (40.12°, sd 3.0°, R2 = 0.62; p < 0.001). There was a significant correlation between mean intraoperative version (23.2°, sd 2.3°), and postoperatively measured version (23.0°, sd 2.4°; R2 = 0.76; p < 0.001). Preoperative and postoperative femoral component anteversion were significantly correlated with one another (R2 = 0.64; p < 0.001). Three patients had CT scan measurements that differed substantially from the intraoperative robotic measurements when evaluating stem anteversion. CONCLUSION: This is the first study to evaluate the success of hip reconstruction overall using robotic-assisted THA. The overall hip reconstruction obtained in the operating theatre using robotic assistance accurately correlated with the postoperative component position assessed independently using CT based 3D modelling. Clinical correlation during surgery should continue to be practiced and compared with observed intraoperative robotic values. Cite this article: Bone Joint J 2018;100-B:1303-9.

The surgeon and emergency medical services for children.

A central focus of emergency medical services for children is the critically injured child, whose potential for recovery is great. Yet trauma remains the leading cause of mortality and morbidity among American children 1-14 years of age. Much unnecessary death and disability can be avoided through aggressive professional and public education in pediatric advanced life support and injury prevention. As the primary-care physician of the critically injured child, the surgeon plays a leading role in ensuring that trauma and emergency medical services systems are optimally prepared to meet the dual challenges of providing optimal pediatric trauma care and obviating the need for such treatment through all means possible.

Acute necrotizing enterocolitis in infancy: a review of 64 cases.

Sixty-four cases of necrotizing enterocolitis are reviewed. The diagnosis was based on tissue examination in 57 and on the clinical syndrome, including pneumatosis, in 7. Three factors are important in the development of the disease: injury to the intestinal mucosa, bacteria, and feedings. The indications for surgical intervention are pneumoperitoneum, signs of peritonitis, and intestinal obstruction. The importance of stress in the etiology of the disease is confirmed by the high incidence of perinatal complications, particularly hypoxia. The mortality was high, but results are improving with the institution of early aggressive treatment.

Investigation of alternative mechanisms of collagen-induced platelet activation by using monoclonal antibodies to glycoprotein IIb-IIIa and fibrinogen.

Anti-HuPl-ml (reactive with IIIa) and anti-C2G7 (reactive with the carboxyl terminal of the alpha chain of fibrinogen) were used to investigate platelet aggregation, fibrinogen binding and thromboxane synthesis induced by low dose collagen (LDC) or high dose collagen (HDC) in normal or aspirin treated platelets. Anti-HuPl-ml and anti-C2G7 inhibited LDC induced platelet aggregation almost completely whilst abolishing fibrinogen binding; thromboxane production although reduced, still occurred. Thus LDC activation was dependent on fibrinogen binding to Gp IIIa. Aggregation of platelets induced by HDC was inhibited with anti-C2G7 or anti-HuPl-ml by 15-35% in association with a modest reduction in thromboxane (TxB2) production (with anti-HuPl-ml) and total inhibition of fibrinogen binding. When anti-HuPl-ml was added to aspirin treated platelets, aggregation with HDC although substantially reduced was not totally abolished. Collagen appears to activate platelets in a dose related manner in which there are at least three possible mechanisms via: (i) GpIIb-IIIa and associated fibrinogen binding; (ii) prostaglandin pathway; (iii) an alternate pathway responsible for approximately 20%-30% of platelet aggregation.

Importance of multiple episodes of hypoxia or cold stress on the development of enterocolitis in an animal model.

Necrotizing enterocolitis, a highly lethal disease in the newborn infant characterized by ischemic necrosis of the gastrointestinal tract frequently leading to perforation, is seen primarily in low birth weight infants who have undergone stress, such as hypoxia. In an animal model it was demonstrated that cold stress was as effective as hypoxia in producing the disease in formula-fed newborn rats. Breast milk was completely protective in both cold- and hypoxic-stressed animals. Presumably cold stress produces the same selective circulatory ischemia as does hypoxia. The experiment further supports the concept that any insult or stress which decreases mesenteric blood flow may initiate the changes leading to necrotizing enterocolitis. It was shown also that the incidence of the disease in formula-fed rats was related directly to the number of episodes of either cold or hypoxic stress. These results suggest that a critical amount of ischemia is necessary to initiate these changes and may help to explain the fact that not all infants exposed to hypoxia or cold stress developthe disease.

The epidemiology of urban pediatric neurological trauma: evaluation of, and implications for, injury prevention programs.

OBJECTIVE: To describe the incidence and causes of pediatric head, spinal cord, and peripheral nerve injuries in an urban setting and to assess the implications of these data for injury prevention programs. METHODS: Pediatric deaths and hospital admissions secondary to neurological trauma included in the Northern Manhattan Injury Surveillance System from 1983 to 1992 were linked to census counts to compute incidence rates. Rates before the implementation of a nonspecific injury prevention program were compared with rates after the implementation, and rates for the target population were compared to rates for the control population. Rates were analyzed on the basis of the cause of injury as well as the age, gender, and neighborhood income level of the injured. RESULTS: The incidence of neurological injuries resulting in hospitalization or death was 155 incidents per 100,000 population per year; the mortality rate was 6 people per 100,000 population per year. Neurological injuries represented 18% of all pediatric injuries and accounted for 23% of all traumatic deaths. Spinal cord and peripheral nerve injuries were relatively rare (5%) compared to head injuries (95%). Minor head injuries, including isolated cranial fractures, minor concussions (<1 h loss of consciousness), and unspecified minor head injuries, accounted for the majority of neurological injuries (76%), whereas severe head injuries, including severe concussion (>1 h loss of consciousness), cerebral laceration/contusion, intracerebral hemorrhage, and unspecified major injuries, were less common (18% of all neurological injuries). Boys were more often affected than girls at every age, and this preference increased with age. Children younger than 1 year showed the highest incidence of both major and minor injuries. One- to 4-year olds showed the lowest rates, with steady increases thereafter. Traffic accidents and falls were the leading causes (38 and 34%, respectively), and assaults were the next leading causes (12%). Among children admitted to surveillance system hospitals, falls were most common in children younger than 4 years, pedestrian motor vehicle accidents were most common in late childhood, and assaults were most common in early adolescence. CASE: fatality rates were 5 to 7% for all age groups except 5- to 12-year-olds, for whom the case:fatality rate was 1.9%. Residence in a low-income neighborhood was associated with an increased risk of injury (rate ratio, 1.71; confidence interval, 95%, 1.54, 1.89). The average hospitalization cost per injury was $8502. Medicaid (54%) and other government sources (5%) covered the majority of expenses, including indirect reimbursement of usually uncollected self-pay billing (19%). Although injury incidence rates fell in both the control and intervention cohorts during implementation of a nonspecific injury prevention program, targeted age and population groups demonstrated greater relative reductions in injuries than nontargeted ones, suggesting a positive effect. CONCLUSIONS: Deaths and hospital admissions secondary to pediatric neurological trauma represent a significant public health problem, with the majority of the direct cost being born by government agencies. Future efforts to prevent neurological trauma in children who live in inner cities should focus on families with low incomes and provide novel education programs regarding infant abuse, infant neglect, and infant injury avoidance. Age-appropriate school-based programs should also be developed to address traffic safety and conflict resolution.

Stab wounds in children.

The Pediatric Surgical Service of Harlem Hospital Center admitted 75 children, 16-years-old and younger, with stab wounds since 1969. Rapid resuscitation and triage of children with major injuries directly to the operating room achieved 100% survival. Review of the circumstance of injury revealed that 75% of the stab wounds were inflicted by children and 66% were known to have been intentional. Social service and psychiatric intervention for troubled children and their families is essential and may decrease the risk of subsequent traumatic injury.

Fifteen years' experience with penetrating trauma to the head and neck in children.

To determine the extent and consequences of penetrating trauma to the head and neck in children, as well as the safety and efficacy of selective management of penetrating wounds of the face and neck, we reviewed our experience with these injuries since 1970. During this interval, 45 children aged 2 to 17 years were admitted for treatment of 37 missile wounds (MW) and eight stab wounds (SW). Most patients reached the hospital within 30 minutes of injury. The greatest single number of these injuries were due to accidents; violent crimes accounted for the remainder of injuries in which a motive for attack was known. Craniotomy was performed in neurologically viable patients only; neck exploration was reserved for those patients who presented with profuse hemorrhage, an expanding or pulsatile hematoma, respiratory distress, or violation of the esophagus, trachea, or great vessels seen on fluoroscopy, endoscopy, or angiography. Overall survival was 87% (MW 84%, SW 100%). Three of the nonsurvivors presented in extremis with gunshot (GSW) wounds to the head, and died shortly thereafter, while two who presented with similar injuries survived craniotomy but died subsequently from irreversible brain damage; one presented in shock due to massive hemorrhage (internal jugular vein transection flush with the base of the skull) and exsanguinated during attempted repair. Among the 39 survivors, 15 sustained multiple wounds, but only two presented in shock, due in both instances to tension pneumothorax. Soft tissue injuries of the scalp, face, and neck accounted for 36 of the 39 nonfatal wounds; five of these involved major cervical structures, but only four required immediate exploration.(ABSTRACT TRUNCATED AT 250 WORDS)

External silo reduction of the unruptured giant omphalocele.

Construction of an external silo dressing over the intact omphalocele membrane allows complete reduction of the giant omphalocele with enlargement of the abdominal cavity before surgical intervention, so that primary closure of the abdominal wall can be achieved. Three infants with giant omphalocele containing a central liver were successfully managed by this technique avoiding the complications associated with operative silo placement or simple membrane painting.

Indications and techniques of upper gastrointestinal endoscopy in infants and children.

Review of 98 endoscopies done over a 4-year period demonstrated that these procedures aided in the diagnosis and management of infants and children with upper gastrointestinal disorders. Endoscopic indications included evaluation of the esophagus in gastroesophageal reflux, achlasia, and lye ingestion; and evaluation of biliary and pancreatic diseases. Other indications included diagnosis of the site of upper gastrointestinal bleeding and treatment of esophageal varices with sclerotherapy, esophageal strictures with steroid injection and removal of foreign bodies. The majority of the procedures were done under sedation. There were no complications.

Angiographic diagnosis and treatment of bleeding by selective embolization following pelvic fracture in children.

Angiography has been used successfully in adults for evaluation following major trauma and to subsequently control hemorrhage associated with pelvic fracture by selective embolization. This report illustrates that the technique is applicable in the evaluation and treatment of children with similar injuries.

Mortality and truncal injury: the pediatric perspective.

To determine the extent and consequences of major truncal injury in children, we analyzed data collected prospectively by the National Pediatric Trauma Registry (NPTR) from 1985 to 1991. Of the 25,301 patients entered into the study, 1,553 (6%) had thoracic injuries (T); 2,047 (8%) had abdominal injuries (A). Blunt mechanisms predominated for both groups (86% T, 83% A), with the automobile being the most frequent blunt agent (74% T, 59% A); gunshot wounds were responsible for the majority of penetrating injuries (60% T, 56% A). Fifteen percent (195) of those with blunt thoracic injuries died; however, in only 14% of these cases (27) was thoracic injury the cause of death. Fourteen percent (33) of those with penetrating thoracic injuries died, with thoracic injury the cause of death in 97% of these cases (32). Only 9% (161) of those with blunt abdominal injuries died; in 22% (35) abdominal injury was the cause of death. Likewise, only 6% (15) of those with penetrating abdominal injuries died, but abdominal injury was the cause of death in 67% (10). The pleural space, lung, and ribs were the most frequently damaged thoracic organs; with the exception of lung contusion, injuries to these structures were associated with fatality rates in excess of 50%. The liver, spleen, kidneys, and gastrointestinal tract were the most frequently damaged abdominal organs; injuries to these structures were associated with fatality rates of 15% or less, except for injuries involving major blood vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Successful management of esophageal strictures without resection or replacement.

Esophageal resection or replacement has become the standard therapy for severe esophageal strictures chiefly because less aggressive methods generally have failed. We hereby report our experience with 12 consecutive infants and children who have been managed successfully by means of Stamm gastrostomy and string-guided esophageal dilatation, coupled with endoscopically guided four-quadrant intralesional steroid injection, protected by Nissen fundoplication when gastroesophageal reflux has been demonstrated. In six patients, the stricture(s) were caused by ingestion of lye. In five, they were associated with repair of esophageal atresia. In one, the etiology was never determined. The strictures averaged 3.5 cm in length (range, 1 to 10 cm); the severity of the lesions was indicated by the fact that, in all instances, patients were completely intolerant of solids, and was confirmed fluoroscopically by demonstration of significant luminal narrowing. A mean of 4.3 steroid injections (range, 1 to 8) was required to obtain complete remission of symptoms; there have been no complications except in one lye ingestion patient who developed a tiny perforation following the initial dilatation, which responded to antibiotics alone. All patients remain symptom-free; the mean length of follow-up is 6.2 years (range, 1 to 11 years). We conclude that string-guided esophageal dilatation, when coupled with endoscopically guided steroid injection, is a safe and reliable method for treatment of severe esophageal strictures, which should obviate the need for esophageal resection or replacement in most patients. Moreover, even if treatment should ultimately fail, a procedure of lesser magnitude than esophageal replacement will likely be possible.(ABSTRACT TRUNCATED AT 250 WORDS)