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.     

Nerve growth factor modulates the activation status and fast axonal transport of ERK 1/2 in adult nociceptive neurones

Mature dorsal root ganglion cells respond to neurotrophins, and the intracellular signalling pathways activated by neurotrophins have been characterized in vitro. We have now used immunocytochemistry and Western blots to examine the expression and activation of extracellular signal-regulated protein kinase-1/2 (ERK) in rat dorsal root ganglion cells in vivo, using antisera to total (tERK) and phosphorylated (pERK) forms. This has revealed a number of novel findings. tERK immunoreactivity is present in most dorsal root ganglion cells but is expressed most strongly in small (nociceptive) cells and, surprisingly, is absent in a population of large cells that expressed trkB or trkC but mainly lack p75(NTR) immunoreactivity. In contrast pERK is prominent in a few trkA cells and in satellite glial cells, and is further increased by NGF treatment. tERK and pERK both undergo fast anterograde and retrograde axonal transport, indicated by accumulation at a sciatic nerve ligature, and NGF reduces the level of retrograde pERK transport.     

Expression of the 5-HT1B receptor by subtypes of rat trigeminal ganglion cells

The type of trigeminal ganglion cells that express 5-HT1B receptors has not been well characterized, despite the fact that these receptors are important targets for anti-migraine drugs. We have therefore used combined in situ hybridization and immunofluorescence to examine the expression of 5-HT1B receptor messenger RNA in identified subpopulations of rat trigeminal ganglion cells. 5-HT1B-expressing cells accounted for 15% of all trigeminal ganglion cells, were medium sized, and showed immunoreactivity for either 200,000 mol. wt neurofilament, calcitonin gene-related peptide, or nerve growth factor receptor (trkA). In contrast few 5-HT1B cells showed immunoreactivity for substance P or binding of the lectin Griffonia simplicifolia IB4. Our results are consistent with 5-HT1B receptors acting to control the release of calcitonin gene-related peptide from trigeminal neurons with finely myelinated axons. 5-HT1B receptor agonists may reduce neurogenic vasodilation by activating such receptors. However many nociceptive trigeminal neurons, including the substance P and IB4-binding populations, do not express the 5-HT1B receptor.     

Critical heart disease in the neonate: presentation and outcome at a tertiary care center.

OBJECTIVE: To define the modes of presentation, incidence of major organ dysfunction, predictors of hospital mortality, and adverse outcomes in neonates with critical heart disease admitted to a tertiary care center. DESIGN: Retrospective chart review. SETTING: A tertiary care pediatric cardiac intensive care unit and neonatal intensive care unit. PATIENTS: The medical records for all neonates (< or = 30 days of age) with heart disease admitted to the cardiac intensive care unit or neonatal intensive care unit between October 1, 2002, and September 30, 2003, were reviewed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 190 neonates met inclusion criteria during this 1-yr period, of which 146 (77%) had at least one surgical procedure. Single ventricle heart disease was present in 42%. The most common mode of presentation was following a prenatal diagnosis (53%), followed by diagnosis in the newborn nursery (38%) and diagnosis after newborn hospital discharge (8%). The most common presenting findings in the newborn nursery were isolated murmur (38%) or cyanosis (32%), while circulatory collapse (38%) was the most common presentation after discharge. For the entire study cohort, 13% had a known genetic syndrome, 23% had a major noncardiac congenital anomaly, and 16% weighed < 2.5 kg. The hospital mortality for the entire cohort was 7.4%. Risk factors associated with an increased risk of hospital mortality included younger age at admission, higher number of cardiopulmonary bypass runs, and need for postoperative cardiopulmonary resuscitation. Total hospital length of stay was > 1 month in 17% of neonates. CONCLUSIONS: In patients with complex congenital heart disease, including nearly half with single ventricle heart disease, neonatal hospital mortality was 7%. These patients have a high frequency of multiple congenital anomalies, genetic syndromes, low birth weight, and prolonged length of stay.     

Inherited disorders of 3-methylcrotonyl CoA carboxylation

The clinical course of 4 patients who had reduced activities of 3-methylcrotonyl CoA carboxylase (also called 3-methylcrotonylglycinuria) is described. Two children presented with a metabolic acidosis, one in the neonatal period and the other with episodes of acidosis that started in the second year of life. In the other 2 children neurological symptoms were prominent, one having infantile spasms and the other developmental regression with a skin rash and alopecia. Three of the children responded well to oral biotin and dietary protein restriction but the fourth, despite a biochemical response to biotin, has a severe neurological handicap. The clinical presentation of inborn errors of 3-methylcrotonyl CoA carboxylase is variable. Metabolic acidosis may not be conspicuous and instead neurological features may predominate.     

Hepatitis B vaccination in haemodialysis patients: A randomized clinical trial

Aim:   A short vaccination protocol against hepatitis B was compared to the standard approach in patients under haemodialysis who were primarily non-responsive to the vaccine.
Methods:   This randomized, controlled open trial included 51 chronic haemodialysis subjects previously vaccinated against hepatitis B and with anti-HBs levels of less than 10 IU/mol/L. Twenty-six patients received 20 µg i.m. once a week for 8 weeks (short protocol) and 25 subjects three doses of 40 µg i.m. at months 0, 1 and 6 (standard protocol). Clinical and laboratory data were compared between responders and non-responders. A logistic regression model included selected parameters to assess risk factors for non-seroconversion.
Results:   Seroconversion rates to vaccine at 2 months were 80% and 78% in the short and standard protocol groups, respectively ( P  = 0.99). Median of anti-HBs levels were similar up to 6 months of follow up, but patients in the standard protocol showed a trend to higher anti-HBs in month 3 and a more steady decline in antibody titres. Non-responders were older, had longer duration of dialysis and a higher prevalence of a prior renal transplant and hepatitis C. In multivariate analysis, only advanced age and hepatitis C remained independently associated with non-responsiveness to vaccination.
Conclusion:   In haemodialysis patients, a short vaccination protocol against hepatitis B did not provide any benefit compared to the standard approach with respect to peak anti-HBs titres or a higher rate of seroprotection at the end of follow up. Other strategies to increase seroconversion rates should be explored, especially in the elderly and in patients with hepatitis C.