Effect of histamine H3 receptor blockade on venous return and splanchnic hemodynamics in experimental bacteremia

OBJECTIVE: In the heart, histamine H3 receptors may function as inhibitory presynaptic receptors that decrease adrenergic neural norepinephrine release in conditions of enhanced sympathetic tone. In a previous study, we found that H3 receptor blockade improved cardiac contractility and systemic hemodynamics in experimental bacteremia in dogs. Because histamine H3 receptors have been found in the splanchnic circulation in other animal models, it was not clear the extent to which H3 receptor blockade may have altered splanchnic hemodynamics, and variables of venous return, that in turn contributed to the overall improvement in systemic hemodynamics observed in the previous experiment. In the present study, we examined splanchnic hemodynamics in the presence of H3 receptor blockade in a canine model of Escherichia coli bacteremia. DESIGN: Bacteremia was produced by intravenous infusion of live E. coli administered throughout the experiment. Variables of venous return included mean systemic pressure, resistance to venous return, and mean right atrial pressure. Splanchnic measurements included hepatic and portal pressures and flows. Measurements were obtained before and after H3 receptor blockade with thioperamide maleate. The animals were studied while ventilated and anesthetized. RESULTS: H3 receptor blockade caused a decrease in mean right atrial pressure from 5.9 mm Hg pretreatment to 3.5 mm Hg posttreatment (p < .05), although it did not affect mean systemic pressure or resistance to venous return. There were no changes in portal or hepatic flows after H3 receptor blockade. The cardiac function curve after H3 receptor blockade was shifted upward and to the left compared with the pretreatment curve. CONCLUSIONS: The results showed that the primary effect of H3 receptor blockade in experimental bacteremia was attributable to an increase in inotropy. There was no evidence to indicate that H3 receptor activation contributed to altered splanchnic hemodynamics in this model.     

Paediatric trainees and the transportation of critically ill neonates: experience, training and confidence

AIM: To study the experience of, training in, and confidence in the transportation of critically ill neonates amongst paediatric trainees in one UK region. DESIGN: An anonymized questionnaire was sent to all middle grades with paediatrics National Training Numbers from the Trent region. RESULTS: The response rate was 78%. Less than half (45%) of the respondents reported receiving any training in the transportation of neonates, either in the UK or abroad; 45% (30/66) of the trainees reported having performed 10 or fewer neonatal transfers. The self-perceived confidence for transporting neonates was scored on a 10-point scale, to produce a "confidence score", the median score being 7 (IQ range 5, 8). Both as a group and individually, the trainee paediatricians were more confident in transporting neonates than older infants or children (p < 0.0001). Using multiple analysis of covariance, it was found that the most important and significant variables affecting the "confidence scores" for the inter-hospital transportation of critically ill neonates were receipt of any relevant transport training, and the current frequency of transports performed. CONCLUSIONS: Many training-grade paediatricians lack both the experience and training in transporting critically ill neonates, factors that were found to affect their confidence in transferring sick neonates. As the overwhelming majority of neonatal transports in the UK are still arranged by individual units and performed by training-grade paediatricians, concerns regarding both the safety and effectiveness of the current service provision for the inter-hospital transfer of critically ill neonates remain valid.     

Ventral hernia repair: a study of current practice

Ventral wall hernias are common; despite this, there are no guidelines on the best surgical management. The aim of this study was to examine the types of repair in use for abdominal wall hernias in the West of Scotland over a 3-month period. Data were gathered on 120 patients. There were 60 incisional, 32 umbilical, and 28 epigastric hernias. The main indication for repair was pain (78%), while 12 patients (10%), presented acutely with incarceration or strangulation. The most common method of repair was sutured (55%), followed by mesh (29%) and Mayo repair (16%). There was no correlation between use of mesh and hernia size or whether repair was for a recurrent hernia. Surgical practice varies widely in the repair of ventral wall hernias. Clinical trials are required to establish the best method of repair for this common condition. Electronic Publication     

D2 lymphadenectomy in the management of gastric cancer

Background Gastric carcinoma is a significant cause of death in Ireland. Surgery offers the best option of cure, but the five-year survival following resection remains dismal at 10–15%. Experience from Japan and from some Western units suggest that an extended (D2) lymphadenectomy in association with gastrectomy increases the prospect of cure, but concern about the morbidity and mortality of this operation and lack of evidence from randomised studies has limited its acceptance. Aims This study reports the experience of a specialist upper gastrointestinal unit with D2 gastrectomy in a four-year audit. Methods Sixty-two resections were performed for gastric cancer. Results Nineteen patients were deemed unsuitable for the D2 procedure and underwent a more limited lymphadenectomy (DO or D1). Forty-three patients underwent D2 resection, 12 with an oesophagogastrectomy, 22 with total gastrectomy and nine with a sub-total distal resection. Eight patients undergoing D2 resection had extended resections, five with splenectomy and three with a distal pancreatectomy. Post-operative complications occurred in 31% of patients. Thirty-day and 90-day mortality were zero. Median survival was 822 days in the D2 group (range 120–1,320). Conclusions These results show that a D2 gastrectomy can be performed with a low morbidity and mortality and a median survival of greater than two years.     

Effect of tumour and chemoradiotherapy on oesophageal motility

Background The contribution of dysmotility to dysphagia in oesophageal cancer is unclear. Aim To examine oesophageal motility in patients with oesophageal carcinoma and to assess the effect of chemoradiotherapy on motility. Methods Stationary manometry and 24-hour pH-metry were performed in 12 patients with oesophageal carcinoma and one week following completion of chemoradiotherapy using 5-fluorouracil (5-FU), cisplatin and 40Gy radiotherapy. Results All patients had abnormal motility prior to treatment. Peristalsis was impaired in 11 patients with a mean (SD) of 25% (9) of waves normally propagated. Eight patients had 20% or more simultaneous waves. Following chemoradiotherapy, the percentage of waves normally propagated increased from 25% (9) to 52% (10) (p < 0.03) and normal peristalsis was restored in four patients. The percentage of simultaneous waves decreased from 38% (11) to 21.6% (10) (p=0.129) while the percentage of dropped or increased waves decreased from 20% (11) to 8.3% (4) (p=0.264). Conclusions Oesophageal motility is disturbed in oesophageal cancer. Dysphagia in oesophageal cancer may be partly explained by oesophageal dysmotility. This is improved by chemotherapy.     

Basal ganglia dysfunction in Tourette's syndrome: a new hypothesis

Tourette's syndrome is a neuropsychiatric syndrome with onset in childhood that is characterized by chronic multiple tics. The cause of Tourette's syndrome is unknown, but the pathophysiology most likely involves basal ganglia and frontocortical circuits. A useful scheme of basal ganglia dysfunction should be able to account for the features that make Tourette's syndrome unique, in addition to the features that Tourette's syndrome shares with other disorders. Recent advances in knowledge of basal ganglia functional anatomy and physiology make it possible to hypothesize how specific neural mechanisms relate to specific clinical manifestations of Tourette's syndrome. A model of selection and suppression of competing behaviors by the basal ganglia is presented. The functional anatomy of basal ganglia circuits and new information on dopamine modulation of those circuits provide the basis for hypotheses of basal ganglia dysfunction in Tourette's syndrome.     

Heilungsprozess des Knorpels in Verbindung mit PDS-Folie

Background and objective. To correct severe septal deformities, it is often necessary to perform an extracorporal septoplasty with temporary removal of the deviated septal cartilage, followed by straightening and reimplantation into the nose as free graft. The utilization of a compound graft, which sutures the cartilage fragments to a resorbable polydioxanon (PDS) foil, facilitates this technique immediately while simultaneously ensuring support of the nasal dorsum. Patients/Methods. On account of the good clinical experiences (during the past 3 years 71 patients have been treated using this method), we investigated the biological properties of the foil and its degradation products in connection with cartilage in an animal model from a histological point of view. In five rabbits, a 0.15-mm-thick PDS foil was implanted in combination with the cartilage into the outer ear. The follow-up period was between 2 and 25 weeks. Results. The results showed the following: (1) Up to the tenth week, the foil maintains the original structure; (2) The foil will be completely resorbed after 25 weeks; (3) The cartilage underneath the foil is protected from necrosis; (4) The degradation products of the polydioxanon do not interfere with the healing process; (5) Concerning the regeneration of cartilage, the foil acts as a guarding splint; (6) After resorption, almost no scar tissue remains. Conclusions. Due to the fact that the PDS foil endonasal implant means no additional risk to the patient, we can recommend the compound graft for simplification of extracorporal septoplasty.     

Elevation of brain natriuretic peptide levels in children with septic shock

OBJECTIVES: 1) To compare brain natriuretic peptide levels in pediatric patients with septic shock with both children admitted to the pediatric intensive care unit without infection and with healthy subjects; and 2) to evaluate the correlation between brain natriuretic peptide with severity of illness and with myocardial dysfunction in children with septic shock. DESIGN:: Prospective, observational study. SETTING: Children's Hospital pediatric intensive care unit. PATIENTS: Children from age 2 wks to 18 yrs. Thirteen children with septic shock requiring inotropic support, 12 healthy controls, and five critically ill patients without infection or heart disease were evaluated. INTERVENTIONS: For patients with septic shock, brain natriuretic peptide was measured within 6 hrs of admission and throughout the pediatric intensive care unit course. Echocardiograms were performed within 12 hrs of admission and then repeated if the patient continued to require inotropic support. For controls, one measurement was performed. MEASUREMENTS AND MAIN RESULTS: Children with septic shock had an elevated (p < 0.0001) brain natriuretic peptide on admission (median 115 pg/mL [range 26-2960]) when compared with healthy (9 pg/mL [5-30]) and pediatric intensive care unit controls (10 pg/mL [5-30]). In patients with septic shock, brain natriuretic peptide at 12 hrs correlated directly with Pediatric Risk of Mortality III score (rs = .80, p = 0.002) and inversely with fractional shortening (rs = -.66, p = 0.014). In children with cold shock, brain natriuretic peptide at 12 hrs (718 pg/mL) [63-1530] was higher (p = 0.007) than in those with warm shock (208 pg/mL [20-366]). There was no pattern (p > 0.05) observed for brain natriuretic peptide over time. CONCLUSIONS: Brain natriuretic peptide measured early after admission is increased in children with septic shock, especially in those with cold shock. In addition, the level at 12 hrs correlates with both severity of illness and myocardial dysfunction. Brain natriuretic peptide may be useful in assessing myocardial dysfunction from septic shock, particularly in identifying children with cold shock. Further studies are warranted to determine whether this measurement will be helpful in guiding therapy in pediatric septic shock.     

Progestational agents and blood coagulation. VII. Thromboembolic and other complications of oral contraceptive therapy in relationship to pretreatment levels of blood coagulation factors: summary report of a ten-year study.

During a ten-year period, 348 women were studied for a total of 5,877 patient months in four separate studies relating oral contraceptives to changes in hematologic parameters. Significant increases in certain factors of the blood coagulation and fibrinolysin systems (factors I,II,VII,VIII,IX, and X and plasminogen) were observed in the treated groups. Severe complications developed in four patients. All four had an abnormal blood coagulation profile, suggesting "hypercoagulability" before initiation of therapy. Some of these findings represented the most extreme abnormalities seen in the entire group of patients; some increased further during therapy. One of these patients developed a myocardial infarction before receiving any medication, shortly after the base-line values were obtained. One patient developed retinopathy 19 months after she began therapy, and another developed thrombophlebitis after 27 months of therapy. The fourth patient developed thrombophlebitis 14 days after initiation of contraceptive therapy. All four patients were of the A or AB blood group. Previous studies suggested the possiblility of increased propensity for thromboembolic episodes in patients possessing the A antigen. It appears from these data that hematologic work-ups may be useful in women who are about to start long-term oral contraceptive therapy.