We previously established pluripotent transformed rat islet cell lines, MSL-cells, of which certain clones have been used to study processes of islet beta-cell maturation, including the ...transcriptional activation of the insulin gene induced by in vivo passage. Thus, successive sc transplantation in NEDH rats resulted in stable hypoglycemic insulinoma tumor lines, such as MSL-G2-IN. Occasionally, hypoglycemia as well as severe weight loss were observed in the early tumor passages of MSL-G and the subclone, NHI-5B, which carry the transfected neomycin and human insulin genes as unique clonal markers. By selective transplantation, it was possible to segregate stable anorectic normoglycemic tumor lines, MSL-G-AN and NHI-5B-AN, from both clones. These tumors cause an abrupt onset of anorexia when they reach a size of 400-500 mg (< 0.3% of total body weight), and the observed weight loss parallels that of starved rats until death results from cachexia. After tumor resection, animals immediately resume normal feeding behavior. Comparative studies of hormone release and mRNA content in anorectic lines, MSL-G-AN and NHI-5B-AN, vs. those in the insulinoma line, MSL-G2-IN, revealed selective glucagon gene expression in both of the anorectic tumors, whereas insulin and islet amyloid polypeptide gene expression were confined to the insulinoma. Both tumor phenotypes produced cholecystokinin and gastrin in variable small amounts, making it unlikely that these hormones contribute to the anorectic phenotype. Tumor necrosis factor (cachectin) was not produced by any of the tumors. Proglucagon was processed as in the fetal islet to products representative of both pancreatic alpha-cell and intestinal L-cell phenotypes, with glucagon and Glp-1 (7-36)amide as the major extractable products. In contrast to the administration of cholecystokinin, neither glucagon, Glp-1 (7-36)amide, nor their combination, affected feeding behavior in fasted mice, suggesting the presence of a hitherto unidentified anorectic substance released from the glucagonoma. We conclude 1) that glucagonomas and insulinomas can be derived from a common clonal origin of pluripotent MSL cells, thus supporting the existence of a cell lineage relationship between islet alpha- and beta-cell during ontogeny; and 2) that our glucagonomas release an anorexigenic substance(s) of unknown nature that causes a severe weight loss comparable to that reported in animals carrying tumor necrosis factor-producing experimental tumors.
A patient, 50 years of age, underwent cholecystectomy for gallstones. 62 hours later the first symptoms of a clostridial infection of the abdominal wall could be observed. 8 hours later the ...re-operation was carried out. Three quarters of the muscles of the abdominal wall had to be removed, the peritoneum could be preserved. The patient recovered. One and a half year later pressure readings of the abdomen were taken.
Release of calprotectin and interleukin-8 (IL-8), changes in leukocyte counts and subsets and influence of extracorporeal ultrafiltration were evaluated during and after cardiopulmonary bypass (CPB) ...in 18 children undergoing open-heart surgery for congenital heart anomalies. Ultrafiltration was used in nine cases and nine were controls. Calprotectin concentration rose after start of CPB, peaking 48 hours postoperatively, with no significant intergroup difference. Positive correlation was found between duration of CPB and calprotectin (peak level and accumulated total). Circulating IL-8 was detected in all patients perioperatively, peaking at wound closure in the ultrafiltration group and at termination of bypass in the controls. CPB duration correlated significantly to peak level and accumulated total of IL-8. Seven of nine ultrafiltrate samples contained IL-8 at levels similar to the plasma concentration. Changes in white cell counts were mainly attributable to neutrophils. The two subgroups did not differ significantly in neutrophil counts. Neutropenia found after 10 minutes of CPB was replaced by neutrophilia, with maximal values postoperatively. Calprotectin and IL-8 thus were released into the circulation during CPB in children. Ultrafiltration did not affect the plasma concentrations of these substances, and only IL-8 was detected in the ultrafiltrate.
The results of new methods for catheter treatment of congenital heart defects are presented. Between 1989 and 1996 closure of a patent ductus arteriosus was performed in 66 instances on 63 patients, ...eight of which were with coils. Three patients were treated twice, one with an additional umbrella, two with coils. The overall complete closure rate for umbrellas was 75%, after two ducts, which were initially totally occluded, recanalized. In six more patients the procedure was either aborted or indication was not present. All six ducts treated with coils as the first procedure were completely closed. One of two patients who had residual leak after previous umbrella treatment achieved complete closure after subsequent coil implantation. Closure of atrial septal defects in the oval fossa was performed using the Amplatzer septal occluder in seven children. Complete closure was achieved in all of them. There have been no complications, in particular there have been no cases of embolization in any of the groups. The results seem to indicate that coil occlusion of a persistently patent duct may be at least as good as the umbrella in terms of complete closure. So far both methods have been safe, but experience with coils is limited. The closure of atrial septal defects shows encouraging results. We will continue to offer this treatment as an alternative to open heart surgery in carefully selected patients.
The diagnostic validity of ECG criteria for left ventricular hypertrophy (LVH) was assessed in 100 men aged 22-64 (mean 47) years with moderate hypertension (Group 1) and 95 age-matched normotensive ...men (Group 2) using echocardiographic recordings of LV mass index (MI) as reference. A diagnosis of LVH was made in subjects with LVMI greater than or equal to 125 g/m2. Mean LVMI was 126 +/- 34 g/m2 in Group 1 vs. 100 +/- g/m2 in Group 2 (P less than 0.001), and the prevalence of LVH was 48% and 11% respectively (P less than 0.001). The mean ECG voltage according to Sokolow-Lyon (S-L) was 28 +/- 8 mm in Group 1 and 27 +/- 7 mm in Group 2 (NS); with 19% having LVH in Group 1 and 14% in Group 2 (NS). Using the Cornell criterion Group 1 had on average 15 +/- 6 mm vs. 12 +/- 5 mm in Group 2 (P less than 0.001), but only two Group 1 patients had LVH. In Group 2 a significant negative correlation between age and S-L voltage was found (r = 0.33, P less than 0.001). LVMI was not correlated with any of the two voltage criteria using linear regression analysis whereas multiple regression analysis revealed a weak, but significant correlation between LVMI and S-L voltage in Group 1 (t = 2.06, P = 0.04). No subject had LV strain pattern or LVH according to the Romhilt Estes point score system. In the assessment of possible LVH in normal or moderately hypertensive men less than 65-70 years of age, ECG has limited value.
We examined 87 men with moderate hypertension (diastolic blood pressure, DPB, greater than or equal to 95 and less than 110 mmHg) (mean age 45, range 22-64, years) with echocardiography and maximal ...ergometer bicycle test. Left ventricular mass index (LVMI) was calculated according to the Penn convention. Mean LVMI was 126 (60-210) g/m2. The maximal systolic blood pressure (SBP) during exercise was on average 217 (155-260) mmHg. Linear regression analysis revealed a significant correlation between LVMI and SBP at rest (r = 0.48, P less than 0.001) and during exercise (r = 0.39, P less than 0.001). Multiple regression analysis correcting for differences in age, cumulative work and cholesterol level revealed a significant correlation between LVMI and SBP at rest (t = 4.07, P less than 0.0001) and during exercise (t = 3.25, P = 0.002). Thus in patients with established, moderate hypertension exercise SBP is not more predictable for LVMI than is SBP at rest.
