Life events occurring in families of children with recurrent abdominal pain

Thirty children with recurrent abdominal pain (RAP) were compared to 67 behaviorally disordered (BD) children and 42 healthy children on number of life events experienced within the last 12 months and on amount of readjustment necessitated by these life events. The parents of these children were also compared on these variables as well as on a subjective rating of stress which they assigned to the life events. The results revealed that the children in the RAP and BD groups had significantly more life events and more stress associated with them than did the healthy children. However, the children in the RAP and BD groups differed in type of life events, with the RAP group more likely to have experienced life events related to illness, hospitalization, and death. There were no significant differences between the parents in the RAP group and the parents of the two comparisons groups. Due to methodological limitations of the study, caution should be exercised in drawing conclusions from these findings until such time that future research provides confirmatory data.     

Treatment with rosiglitazone reduces hyperinsulinemia and improves arterial elasticity in patients with type 2 diabetes mellitus

OBJECTIVE: The aim of this study was to determine whether reduction of hyperinsulinemia with rosiglitazone will improve vascular elasticity in patients with non-insulin dependent diabetes mellitus. METHODS: In an open label study 52 patients with non-insulin dependent diabetes mellitus and at least one additional cardiovascular risk factor, were treated for 6 months with 4 mg of rosiglitazone, and uptitrated to 8 mg after 3 months of treatment, if needed. At the beginning of the study and at its end, blood was drawn for insulin, C- peptide, and 24-h urine collected for microalbuminuria/proteinuria. Glucose, chemistry, lipid profile, and hemoglobin A1C were determined at 0, 3, and 6 months. Vascular compliance was measured in monthly intervals. RESULTS: Treatment increased significantly small artery elasticity from 1.45 to 2.43 mL/mm Hg x 100. Large artery elasticity tended to increase toward the end of the study (P = not significant). Systolic blood pressure (BP)decreased from 144 to 124 mm Hg and diastolic BP decreased from 80 to 62.5 mm Hg, despite mild weight gain [corrected]. Heart rate tended to decrease from 76.3 to 74.7 beats/min (P = not significant). Systemic vascular resistance decreased from 1789.8 to 1329.4 dyne sec/cm(5). Plasma insulin, in patients not treated with insulin, decreased from 42.45 +/- 24.90 to 27.86 +/- 14.86 IU/mL (P =.0001). CONCLUSIONS: Treatment with rosiglitazone reduced hyperinsulinemia and improved small artery elasticity with a tendency to improve large artery elasticity, in hypertensive and in normotensive patients. Because rosiglitazone improves insulin receptor sensitivity (IRS), it is logical to assume that the reduction in hyperinsulinemia reflects improvement in IRS. Our data support the hypothesis that hyperinsulinemia and IRS participate in the mechanisms of tissue injury and their improvement induces improvement in arterial elasticity.     

Functional outcome of transplanted knee joints in dogs

Total knee joint transplantation has been performed in animal models and humans. This study investigates the impact of this operation on knee joint function in a dog model. Therefore, replantation was compared to transplantation during a 6-month follow-up period in four dogs in each group. The peak vertical ground reaction force normalized in all legs undergoing replantation and in two of four after transplantation. A third transplant recipient reduced loading from the 4th month due to a local complication, and the fourth succumbed to sepsis 3 months postoperatively. A weight-bearing index (WBI), defined as loading of the grafted divided by loading of both hindlimbs decreased from 0.48 ± 0.08 preoperatively to 0.13 ± 0.10 by 1 month after replantation and from 0.53 ± 0.07 to 0 after transplantation. After 6 months, weight-bearing of all replant recipients was restored, but reduced in two transplant recipients with graft function. Full recovery after replantation, but impaired function after transplantation, was also reflected in the histological results: normal histological pictures of blood vessels, cartilage, bone and soft tissues were found in all replant recipients, but infiltrative vasculopathy indicating chronic rejection was found in the transplanted joints. The results of this animal study confirm that the procedure can lead to satisfactory functional results but also emphasize the need for perfect control of immunosuppression. Received: 30 September 1999     

Investigative pathology: leading the post-genomic revolution

The completion of the Human Genome Project and the development of genome-based technologies over the past decade have set the stage for a new era of personalized medicine. By all rights, molecularly trained investigative pathologists should be leading this revolution. Singularly well suited for this work, molecular pathologists have the rare ability to wed genomic tools with unique diagnostic skills and tissue-based pathology techniques for integrated diagnosis of human disease. However, the number of pathologists with expertise in genome-based research has remained relatively low due to outdated training methods and a reluctance among some traditional pathologists to embrace new technologies. Moreover, because budding pathologists may not appreciate the vast selection of jobs available to them, they often end up choosing jobs that focus almost entirely on routine diagnosis rather than new frontiers in molecular pathology. This review calls for changes aimed at rectifying these troubling trends to ensure that pathology continues to guide patient care in a post-genomic era.     

Fibrosis in genotype 3 chronic hepatitis C and nonalcoholic fatty liver disease: Role of insulin resistance and hepatic steatosis

Hepatic steatosis has been associated with fibrosis, but it is unknown whether the latter is independent of the etiology of fat infiltration. We analyzed the relationship between clinical characteristics, insulin resistance (HOMA-R) and histological parameters in 132 patients with "viral" steatosis caused by genotype 3 chronic hepatitis C (CHC-3) and 132 patients with "metabolic" steatosis caused by nonalcoholic fatty liver disease (NAFLD), matched by age, BMI, and degree of liver fat accumulation. Tests of liver function were comparable in the two study populations. The prevalence of features of insulin resistance was higher in NAFLD, as was HOMA-R (P = .008). Logistic regression analysis confirmed that steatosis was associated with a high viral load and low serum cholesterol in CHC-3, and with high aminotransferase, glucose, ferritin and hypertriglyceridemia in NAFLD. At univariate analysis, advanced fibrosis was associated with steatosis in NAFLD, but not in CHC-3. Other parameters related to fibrosis severity were HOMA-R and a low platelet count in CHC-3, and high aminotransferases, HOMA-R, ferritin and low HDL-cholesterol in NAFLD. On multivariate analysis, only low platelet count (OR = 0.78; 95% CI, 0.67-0.92) and HOMA-R (OR = 2.98; 1.13-7.89) were independent predictors of advanced fibrosis in CHC-3. In NAFLD, severe fibrosis was predicted by fat grading (OR = 3.03; 1.41-6.53), ferritin (OR = 1.13; 1.03-1.25) and HOMA-R (OR = 1.16; 1.02-1.31). In conclusion, insulin resistance is an independent predictor of advanced fibrosis in both NAFLD and CHC-3, but the extent of steatosis contributes to advanced disease only in NAFLD. Virus-induced hepatic steatosis as seen in CHC-3 does not contribute significantly to liver fibrosis.