On the Organization of Connexin36 Expression in Electrically Coupled Cholinergic V0c Neurons (Partition Cells) in the Spinal Cord and Their C-terminal Innervation of Motoneurons.

Large cholinergic neurons (V0c neurons; aka, partition cells) in the spinal cord project profusely to motoneurons on which they form C-terminal contacts distinguished by their specialized postsynaptic subsurface cisterns (SSCs). The V0c neurons are known to be rhythmically active during locomotion and release of acetylcholine (ACh) from their terminals is known to modulate the excitability of motoneurons in what appears to be a task-dependent manner. Here, we present evidence that a subpopulation of V0c neurons express the gap junction forming protein connexin36 (Cx36), indicating that they are coupled by electrical synapses. Based on immunofluorescence imaging and the use of Cx36BAC-enhanced green fluorescent protein (eGFP) mice in which C-terminals immunolabelled for their marker vesicular acetylcholine transporter (vAChT) are also labelled for eGFP, we found a heterogeneous distribution of eGFP+ C-terminals on motoneurons at cervical, thoracic and lumber spinal levels. The density of C-terminals on motoneurons varied as did the proportion of those that were eGFP+ vs. eGFP-. We present evidence that fast vs. slow motoneurons have a greater abundance of these terminals and fast motoneurons also have the highest density that were eGFP+. Thus, our results indicate that a subpopulation of V0c neurons projects preferentially to fast motoneurons, suggesting that the capacity for synchronous activity conferred by electrical synapses among networks of coupled V0c neurons enhances their dynamic capabilities for synchronous regulation of motoneuron excitability during high muscle force generation. The eGFP+ vs. eGFP- V0c neurons were more richly innervated by serotonergic terminals, suggesting their greater propensity for regulation by descending serotonergic systems.

Nonoperative treatment of biliary tract disease.

The rise of minimally invasive surgical techniques during the past 20 years has been one of the more dramatic developments in modern medicine. Minimally invasive procedures are now widely accepted for treatment of diseases involving many different organ systems. Minimally invasive procedures may be more common and more accepted in the treatment of diseases of the biliary tract than in any other area. The development of laparoscopic cholecystectomy serves as a benchmark for minimally invasive procedures, and it is now the standard of care for the treatment of cholelithiasis. Today, not only is laparoscopic cholecystectomy one of the most common operations performed in the United States, but many new techniques have been developed that allow minimally invasive treatment of a variety of biliary tract diseases. The development of nonoperative techniques for treatment of biliary tract disease has accompanied the rapid developments in minimally invasive surgical techniques. This article describes the nonoperative treatment of biliary tract disease.

PAF and CD18 mediate neutrophil infiltration in upper gastrointestinal tract during intra-abdominal sepsis.

Neutrophil infiltration is a critical event in the development of multiple organ failure during sepsis. We hypothesized that platelet-activating factor (PAF) release contributes to neutrophil infiltration in the gastrointestinal tract during sepsis. In the first experiments we administered exogenous PAF (1.56, 6.25, 25, and 100 ng . kg-1 . min-1 for 30 min) to urethan-anesthetized Sprague-Dawley rats. PAF was administered alone or in combination with either the PAF antagonist WEB-2086 (250 microg . kg-1 . min-1), a monoclonal antibody (MAb) to CD18, or a MAb to intercellular adhesion molecule 1 (ICAM-1). In separate groups of rats, cecal ligation and incision (CLI) was performed to create intra-abdominal sepsis, which we hypothesized would stimulate the release of endogenous PAF. CLI was performed in rats given either saline, WEB-2086, anti-CD18, or anti-ICAM-1 MAb. After these experiments, tissue myeloperoxidase (MPO) levels were determined as a marker of neutrophil infiltration. Both exogenous PAF and CLI induced significant increases in MPO activity in the stomach and duodenum. These increases were significantly attenuated by WEB-2086, anti-CD18 MAb, and anti-ICAM-1 MAb in both PAF- and CLI-treated rats. These results suggest that both the inflammatory mediator PAF and the CD18 integrins play a major role in neutrophil infiltration in the upper gastrointestinal tract during sepsis.

The role of gender in heart transplantation.

BACKGROUND: The effect of donor and recipient gender on the outcome of heart transplantation (HT) remains uncertain. METHODS: One hundred seventy-four patients who underwent HT were divided into four groups according to donor and recipient gender. Group A consisted of 81 men who received male donor hearts, group B of 18 women who received female donor hearts, group C of 21 women who received male donor hearts, and group D of 54 men who received female donor hearts. All patients were treated by the same group of surgeons according to standard HT protocols. Comparisons were made between groups with regard to short- and long-term outcomes. RESULTS: Donor gender and recipient gender did not affect outcomes significantly. Overall, donor-recipient gender mismatching significantly increased the number of rejection episodes and reduced creatinine clearance, survival, and censored survival in the first year after HT (p < 0.05). More specifically, among female recipients, donor-recipient gender mismatching significantly increased the number of rejection episodes and decreased creatinine clearance in the first year after HT (p < 0.05); among male recipients, donor-recipient gender mismatching significantly reduced 1-year survival and censored survival to date after HT (p < 0.05). CONCLUSIONS: Donor-recipient gender matching plays a significant role in determining HT outcomes.

Management of left ventricular assist device infection with heart transplantation.

BACKGROUND: Left ventricular assist devices (LVADs) are being used as bridges to heart transplantation (HT). Infection of the LVAD in this patient population represents a serious complication, as simple LVAD removal or delaying HT may result in death. To improve outcomes in this group of patients, we performed HT in the presence of LVAD infection. METHODS: Eighteen patients underwent LVAD implantation followed by HT. Ten underwent HT in the absence of LVAD infection (group 1); and 8, in the presence of LVAD infection (group 2). All patients were treated similarly except for modification of immunosuppression in group 2 patients. RESULTS: Infectious and noninfectious complications were equivalent between the two groups. There was no difference between groups in regard to intraoperative deaths (one versus none), long-term survival (8/10 versus 7/8), wound complications (three versus none), and mean length of hospital stay after HT (21 versus 26 days). CONCLUSIONS: Patients with LVAD infection are too seriously ill to allow LVAD removal or delay of HT. Transplantation in the face of infection is an effective treatment option.

Defining the role of aprotinin in heart transplantation.

BACKGROUND: Heart transplantation is associated with excessive bleeding due to recipient coagulopathy, frequent need for reoperative median sternotomy, and prolonged cardiopulmonary bypass. Aprotinin reduces bleeding and the inflammatory response after cardiopulmonary bypass, but there are concerns about efficacy and side effects. METHODS: To determine the role of aprotinin in primary and reoperative sternotomy heart transplantation, we studied 70 patients undergoing heart transplantation between August 1993 and October 1994. Thirty-eight undergoing primary sternotomy for heart transplantation and receiving no aprotinin were randomized to group A (n = 20); patients in group B (n = 18) received the full recommended dose. Similarly, 32 patients undergoing reoperative heart transplantation were randomized to group C (n = 16), receiving no aprotinin, and to group D (n = 16), receiving aprotinin at the full recommended dose. All patients received the same immunosuppression regimen. Similarities in the groups included recipient age, weight, preoperative hemodynamic indices, creatinine, creatinine clearance, platelet count, hemoglobin, percentage receiving warfarin, prothrombin time, partial thromboplastin time, cardiopulmonary bypass time, and creatinine level at 48 hours. RESULTS: There were no significant differences postoperatively between groups A and B. Differences (p < 0.05) 24 hours postoperatively between groups C and D, respectively, included: total blood product requirement (5.9 +/- 3.8 versus 3.6 +/- 2.0 U), total fluid balance (+752 +/- 300 versus -250 +/- 185 mL), chest tube drainage (894 +/- 120 versus 526 +/- 95 mL), alveolar-arterial O2 difference (120.4 +/- 45.9 versus 95.5 +/- 33.5), and pulmonary artery mean pressures (28.2 +/- 4.6 versus 21.1 +/- 3.5 mm Hg). CONCLUSIONS: Aprotinin decreases bleeding after reoperative heart transplantation without renal dysfunction. Decreased inflammation is manifested as reduced fluid requirement and improved pulmonary and right heart function, which benefit patients during the posttransplantation period. Aprotinin at recommended doses is effective and safe for patients undergoing reoperative heart transplantation.

Bladder pressure monitoring significantly enhances care of infants with abdominal wall defects: a prospective clinical study.

Increased intraabdominal pressure (IAP) has been demonstrated to cause intestinal and renal ischemia in both animals and humans. Neonates undergoing closure of anterior abdominal wall defects are at risk for these complications from markedly increased IAP, which are putatively responsible for a 13% to 20% mortality. In an effort to decrease morbidity and mortality we performed a 4-year prospective clinical study to determine if monitoring IAP using bladder pressure (BdP) measurements would significantly improve perioperative care in infants with abdominal wall defects. Forty-two consecutive infants with gastroschisis (28) and omphalocele (14) were prospectively studied. Intraoperative and serial postoperative measurements of BdP were obtained from an indwelling bladder catheter using a standard pressure transducer. Methods of initial closure, as well as manipulations in sedation, paralysis, and silo reduction, were selected to keep BdP < 20 mm Hg. Bladder pressure monitoring significantly altered the management of 64% of our patients, particularly those with gastroschisis (74%). Thirteen patients with gastroschisis underwent staged closure; in 7 (54%) this decision was based on high BdP even though bowel reduction was mechanically possible. Elevated BdP influenced the closure method and timing of silo reductions in 5 of 14 (42%) infants with omphalocele. There were no episodes of renal failure or refractory oliguria. There were three patients in a single cluster who developed uncomplicated, nonsurgical necrotizing enterocolitis late in their respective courses. One patient whose bowel was placed in a silo had severe hypotension associated with group B streptococcal sepsis and subsequently developed necrotic bowel despite low BdP.(ABSTRACT TRUNCATED AT 250 WORDS)

Nonphysician transport of intubated pediatric patients: a system evaluation.

OBJECTIVE: To evaluate the occurrence of complications and patient deteriorations during the air and ground transportation of intubated pediatric patients, performed by a nonphysician-based team under the direction of an intensive care attending physician or fellow. DESIGN: Retrospective chart review. SETTING: A 600-bed university hospital with a 16-bed neonatal ICU and a 12-bed pediatric ICU. PATIENTS: All intubated pediatric patients (422 of 614 patients transported during the study period) transported by the dedicated neonatal/pediatric transport team from April 1988 to April 1990. MEASUREMENTS AND MAIN RESULTS: The transport records of intubated pediatric patients were abstracted. Recorded data included age, weight, gestational age, vital signs, diagnosis, interventions received, and use of paralytic agents and sedatives/analgesics. Patients were analyzed in three groups: group 1 (n = 295) included neonates; group 2 (n = 66) included patients greater than 1 month and less than 1 yr of age; and group 3 patients (n = 61) were ages greater than 1 yr. Group 1 had nine (3.1%) complications or patient deteriorations; four (1.4%) were related to the endotracheal tube. Group 2 had one (1.5%) airway complication and one deterioration. Group 3 had no complications or deteriorations. All but one of the airway complications were effectively handled by the transport team. At the referring hospital, the transport nurse or respiratory therapist intubated 62 (19.8%) patients in group 1, five (7.5%) in group 2, and three (4.9%) patients in group 3. Sixty-seven (23%), 21 (32%), and 30 (49%) patients of groups 1, 2, and 3, respectively, were paralyzed for transport. No complications were secondary to the use of paralytic agents or sedatives. CONCLUSIONS: Under proper medical guidance, well-trained nonphysician personnel can provide low-risk transport of intubated pediatric patients. Use of sedatives and paralytic drugs did not increase the risk of complications or patient deterioration.

Factors improving survival in multisystem trauma patients.

This report analyzes the effect of air versus ground interhospital transport on survival following multisystem injury. There were 136 air-transported patients versus 194 ground-transported patients. The groups were similar in trauma scores, ages, mechanism of injury, and organ systems injured. There was a statistically significant survival advantage for air-transported patients with trauma scores between 10 and 5 (82.8% survival vs. 53.5%, p = less than 0.001). The time interval between accident and admission to the authors' institution was similar for both groups. Important therapeutic interventions contributing to better survival by the air-transported group included higher incidences of endotracheal intubation (50% vs. 25%), blood transfusions (32% vs. 10%), larger volumes of electrolyte fluid (3.3 L per patient vs. 2.1 L per patient) as well as the use of MAST trousers (60.3% vs. 34.9%). Transport charges for both ground and air services were similar. However, helicopter charges met only 15% of the operational budget of the aeromedical service. The remainder of the costs were generated from hospital patient revenues. Overall, total hospital charges were similar for both groups and were influenced by the variability of length of stay, particularly for orthopedic patients.