Studies on cardiac distribution and function of neuropeptide Y

High concentrations of a novel peptide, neuropeptide Y, have been demonstrated in the guinea-pig and canine heart and in the latter, a particularly high concentration was found in the region of the coronary vasculature (126 +/- 31 pmol g-1). Intra-arterial infusion of neuropeptide Y for 30 s into the coronary artery of the intact, innervated dog heart resulted in a rapid and short-lasting reduction of blood flow from 38 +/- 4 to 31 +/- 3 ml min-1 (P less than 0.05) to resume control level, 39 +/- 5 ml min-1, within 5 min. These injections were unaccompanied by changes in heart rate and aortic pressure, while there was an associated small reduction in dP/dt, used as a measure for changes in contractility. In vitro studies using the isolated, paced papillary muscle from cat, guinea-pig and rat, and spontaneously beating right atria from the guinea-pig, demonstrated no effect of NPY on active tension or beating frequency. The results indicate that NPY has vasoconstrictor properties, but under the test circumstances to lack both positive and negative inotropic and chronotropic effects.     

Tailoring Antireflux Surgery: A Randomized Clinical Trial

A hypothesis has been formulated that mandates the adjustment of antireflux surgery to either a total or a partial wrap depending on the motor function of the esophagus to avoid dysphagia and other obstructive complaints. This hypothesis has been tested in a randomized, clinical trial where 106 chronic gastroesophageal reflux patients were allocated to either a total Nissen-Rossetti (n= 53) or a Toupet partial posterior (n= 53) fundoplication, irrespective of their preoperative esophageal motor function. All patients were followed at least 3 years, during which time none had a relapse of moderate to severe reflux symptoms. Motor dysfunctions defined as peristaltic amplitude ≤ 30 mmHg in the distal third and failed primary peristalsis with or without > 20% simultaneous contractions were noted in 67 patients preoperatively, but these patients did not have a specific symptom profile (e.g., dominated by obstructive symptoms) nor did seven patients with “aperistaltic esophagus.” The incidence of dysphagia decreased from 20% preoperatively to 8% (mild) at 3 years after the operation with no difference between the surgical procedures. We were unable to demonstrate a relation between preoperative manometric findings and postoperative symptoms when assessed in the total group or when subdivided by the type of fundoplication (r < 0.3). Flatulence occurred more frequently among those with a total fundic wrap (p < 0.01). When patients representing motor dysfunction (see above) were specifically analyzed, we again observed no difference in outcome between those having a total or a partial fundic wrap. In conclusion, the concept of tailoring antireflux surgery based on the preoperative motor function of the esophagus in patients with chronic gastroesophageal reflux disease was not supported by the results of this clinical trial.     

Accommodative facility training with a long term follow up in a sample of school aged children showing accommodative dysfunction

The primary aim of this project was to study the effect of flip lens-training on the accommodative function in a group of children with accommodative dysfunction and subjective symptoms such as asthenopia, headache, blurred vision, and avoidance of near activity. We also wanted to measure the accommodative facility among the children in comparison with a control group. Another aim of the study was whether flip lens-training increased accommodative facility, and to find out if it also had a positive effect on their asthenopia and related problems also in long term. Following the training period the accommodative facility and accommodative function significantly increased and two years after finishing the training period no child had regained any subjective symptoms and the objective findings were almost the same as at the end of facility training period. These results suggest that accommodative facility training is an efficient method built on loss of symptoms among children with accommodative infacility. This revised version was published online in July 2006 with corrections to the Cover Date.     

A new method for quantification of image distortion due to pile-up in scintillation cameras

Characterization of the count-rate performance of scintillation cameras should include not only the specification of count losses. At high count rates, there is also an image distortion due to the mispositioning of pile-up events. In this paper a simple and clinically relevant procedure to quantify this distortion is presented. The images of a square uniform technetium-99m phantom at high and low count rates are used. The fraction of the total counts being correctly positioned is determined as the peripheral count density divided by the total average count density. This ratio, corrected for the camera non-uniformity at low count rates, is called the positioning ability. According to the National Electrical Manufacturers' Association (NEMA), the system count rate performance with scatter should be reported as the measured count rate giving 20% count losses. In this paper it is suggested that this measure be complemented by a measure of the fraction correct positioned events at this count rate. This fraction, the high count rate positioning ability', can be easily and accurately measured using our method. The method has been tested on two different scintillation cameras. For one of them the high count rate positioning ability was determined as 91% at a measured count rate of 30000 s^–1 with 20% count losses. For the other camera, the corresponding figures were 88% at 59000 s^–1 and close to 100% at 38000 s^–1, before and after the installation of a new pile-up rejection circuit, respectively. Offprint requests to: C. Ceberg     

Loss of heterozygosity of 3p markers in neuroblastoma tumours implicate a tumour-suppressor locus distal to the FHIT gene.

Neuroblastoma is a heterogeneous childhood tumour of the sympathetic nervous system, in which deletions of chromosomal region 1p and amplification of the MYCN oncogene correlate with aggressive tumour behaviour. However, the majority of neuroblastoma tumours show neither of these aberrations, indicating that other chromosomal regions may be involved in tumorigenesis. Here, we report findings of loss of heterozygosity (LOH) on chromosome 3. In our neuroblastoma material, nine of 59 (15.3%) tested tumours showed allelic loss of chromosome 3p markers. We found significant clinical and biological differences between tumours with the loss of one entire chromosome 3 vs tumours with partial loss in chromosome region 3p. All children with tumours with whole chromosome 3 loss are long-term survivors, whereas all children with tumours showing partial 3p LOH have died from tumour progression. A consensus region found to be deleted in all the tumours with 3p deletions was defined by markers D3S1286 and D3S1295, i.e. 3p25.3-p14.3, distal to the FHIT gene.     

Leptin and asthma in overweight children at 12 years of age

Obesity is suggested as a risk factor for asthma, but the mechanisms are unclear. The relationship between obesity and asthma has not been considered in children born with very low-birth weight (VLBW). We hypothesized that overweight was a contributing factor for asthma in VLBW children, and that leptin and leptin-associated cytokines might play roles in overweight-related asthma. Seventy-four VLBW and 64 normal birth weight (NBW) children participated in a 12-yr follow up study assessing asthma and allergy. Twenty-seven (12 VLBW) of the 138 children were overweight according to the proposed international definition. The diagnosis of current asthma was made by a pediatrician. Serum levels of leptin and interferon (IFN)-gamma were analyzed by enzyme-linked immunosorbent assay (ELISA). Leptin levels were considerably higher in the overweight than in the non-overweight children (median value: 18.1 vs. 2.8 ng/ml, p < 0.001). In the overweight children, current asthmatics had twice as high levels of leptin as children without current asthma (median value: 30.8 vs. 14.3 ng/ml, p = 0.14), but this was not the case in the non-overweight children. IFN-gamma was more often detected in the overweight than in the non-overweight children (61% vs. 12%, p < 0.001), and there was a positive correlation between the levels of leptin and the levels of IFN-gamma (Rho = 0.40, p < 0.001). In the VLBW group, the overweight children had a significantly increased risk for current asthma compared with the non-overweight children after adjustment for the neonatal risk factors [adjusted odds ratio (OR) 5.8, 95% confidence interval (CI): 1.2-27]. Thus, overweight was associated with asthma in the VLBW children. Our hypothesis remained that leptin might be involved in the pathogenesis of asthma in the overweight children, and IFN-gamma might be a pathway in the process of leptin-induced inflammation.     

Long-term results in children with AML: NOPHO-AML Study Group--report of three consecutive trials.

In all, 447 children with acute myeloid leukaemia (AML) have been treated on three consecutive NOPHO studies from July 1984 to December 2001. NOPHO-AML 84 was of moderate intensity with an induction of three courses of cytarabine, 6-thioguanine and doxorubicin followed by four consolidation courses with high-dose cytarabine. The 5-year event-free survival (EFS), disease free survival (DFS) and overall survival (OS) were 29, 37 and 38%. NOPHO-AML 88 was of high intensity with the addition of etoposide and mitoxantrone in selected courses during induction and consolidation. The interval between the induction courses should be as short as possible, that is, time intensity was introduced. The 5-year EFS, DFS and OS were 41, 48 and 46%. In NOPHO-AML 93, the treatment was stratified according to response to first induction course. The protocol utilised the same induction blocks as NOPHO-AML 88, but after the first block, children with a hypoplastic, nonleukaemic bone marrow were allowed to recover before the second block. Consolidation was identical with NOPHO-AML 88. The 5-year EFS, DFS and OS in NOPHO-AML 93 were 48, 52 and 65%. The new NOPHO-AML protocol has been based on experiences from previous protocols with stratification of patients with regard to in vivo response and specific cytogenetic aberrations.     

Food effects on tablet disintegration.

The aims of the present study was to investigate if food components, as represented by a multi-component nutritional drink for tube feeding, could affect tablet disintegration of standard tablets in vitro as well as in vivo and propose a mechanism for potential food effects on tablet disintegration. The tablet disintegration was delayed between 5 min and more than 1h in the simulated gastric fed medium compared to a simple buffer. This effect was dependent on the tablet composition. A similar delay in tablet disintegration was also found in vivo after administration of the nutritional drink to three Labradors as observed by removing the tablet from the stomach at different times through a gastric fistula. The delay in tablet disintegration appeared to be caused by precipitation of a film, mainly consisting of protein, on the tablet surface as indicated by disintegration studies with pure nutrients, identification by IR spectroscopy of contents of precipitates obtained in a model study were the nutrients were incubated with different tablet excipients and visual observations of tablets exposed to the simulated fed medium. The drug dissolution of a soluble compound, metoprolol tartrate, from a standard tablet was also strongly delayed in the simulated fed medium. In conclusion, food, could significantly delay tablet disintegration and drug dissolution in the stomach by formation of a film around the tablets. This effect could be monitored by a simple in vitro disintegration test using a test medium based on a nutritional drink. More studies are needed to investigate the significance of the slow tablet disintegrations on bioavailability and for which types of food the present effect occurs.