The molecular pathology of urological malignancies

BACKGROUND: Effective esophageal peristalsis is a major determinant of esophageal clearance function. The relation of esophageal body function with a mechanically defective lower esophageal sphincter and the development of esophageal mucosal injury in patients with gastroesophageal reflux disease is unclear. STUDY DESIGN: We analyzed the relations among the manometrically determined esophageal clearance function, lower esophageal sphincter dysfunction, esophageal acid exposure, and the presence and severity of esophageal mucosal injury in patients with gastroesophageal reflux disease. Normal values for the manometric assessment of esophageal clearance function were established in 50 normal volunteers and subsequently applied to 160 symptomatic patients with increased esophageal exposure to gastric juice and various grades of esophageal mucosal injury (no minimal surgery, esophagitis, stricture, and Barrett's esophagus). RESULTS: Defective clearance function was present in 47.5% of the patients; a defective lower esophageal sphincter was documented in 63.1%. Compromised esophageal clearance function was significantly more common in patients with a defective lower esophageal sphincter than in those with normal sphincter function (55% versus 33.8%). Esophageal acid exposure time and the prevalence and severity of esophageal mucosal injury were highest in patients with a defective sphincter and compromised clearance function. CONCLUSIONS: These data show that esophageal motor function deteriorates with increasing severity of mucosal injury. This appears to be due to persistent reflux of gastric juice across a mechanically defective lower esophageal sphincter. This may influence the choice and outcome of antireflux surgery. Surgical correction of a mechanically defective sphincter before the loss of esophageal body function is advocated.     

Intestinal lipid absorption in the nephrotic rat

Phage display technology represents a powerful tool for the identification of peptides reacting with disease-related antibodies present in human sera. The application of this technology to type 1 diabetes could provide a set of novel reagents for diabetes prediction and could also lead to the identification of novel autoantigens or even of environmental factors possibly causing the disease. In the present study, sera of prediabetic and high risk individuals were used to select candidate peptides from phage-displayed random peptide libraries. Diabetes specific phage clones were then identified from these through screening and counter screening, using sera from diabetic and non-diabetic individuals. The results presented in this paper demonstrate the feasibility of this methodology to identify peptides reacting preferentially with antibodies present in the serum of diabetic patients.     

Oral calcium phosphate: a new therapy for Crigler-Najjar disease?

BACKGROUND & AIMS: Calcium phosphate binds unconjugated bilirubin in vitro, and dietary calcium phosphate supplementation reduces the serum bilirubin level in rats with hereditary unconjugated hyperbilirubinemia (Gunn rats). The aim of this study was to evaluate the effect of oral calcium phosphate supplementation on plasma bilirubin levels in patients with Crigler-Najjar disease. METHODS: A placebo-controlled, double-blind, crossover design was used. Eleven patients, 2-42 years of age, participated. The group included 5 patients with type I disease who were all treated with phototherapy and 6 patients with type II disease who were primarily treated with phenobarbital. In addition to plasma bilirubin levels, dietary intake and urinary and fecal excretion of calcium and phosphate were evaluated. RESULTS: A modest but significant decrease in serum bilirubin was observed in patients with type I disease (18% +/- 6%, P = 0.03) but not in patients with type II disease during treatment with calcium phosphate. Urinary output of calcium and phosphate did not change during the treatment period. CONCLUSIONS: Oral calcium phosphate may be a useful adjuvant to photo-therapy in Crigler-Najjar type I disease.     

Denaturant m values and heat capacity changes: relation to changes in accessible surface areas of protein unfolding

Denaturant m values, the dependence of the free energy of unfolding on denaturant concentration, have been collected for a large set of proteins. The m value correlates very strongly with the amount of protein surface exposed to solvent upon unfolding, with linear correlation coefficients of R = 0.84 for urea and R = 0.87 for guanidine hydrochloride. These correlations improve to R = 0.90 when the effect of disulfide bonds on the accessible area of the unfolded protein is included. A similar dependence on accessible surface area has been found previously for the heat capacity change (delta Cp), which is confirmed here for our set of proteins. Denaturant m values and heat capacity changes also correlate well with each other. For proteins that undergo a simple two-state unfolding mechanism, the amount of surface exposed to solvent upon unfolding is a main structural determinant for both m values and delta Cp.     

Vascular patterns of gestational trophoblastic tumors by color Doppler ultrasound

BACKGROUND: Destruction of uterine vasculature is a common phenomenon in gestational trophoblastic tumors. The authors categorized such uterine vasculature by color Doppler ultrasound and studied its clinical significance. METHODS: Color Doppler ultrasound was performed in 28 patients with gestational trophoblastic tumors. The vascular morphologic manifestations were recorded, and the peak systolic velocity and resistance index of uterine artery were calculated. Serum beta-human chorionic gonadotropin (hCG) levels were measured periodically to monitor chemotherapy response. Seventeen uneventful postmole uteri were used as controls. Two-tailed Student's t-test and Fisher's exact test were used for statistical analysis. RESULTS: The gestational trophoblastic tumors were categorized as diffuse type (N = 7), lacunar type (N = 16), and compact type (n = 5) according to their vascular patterns. The mean serum beta-hCG level at diagnosis in diffuse type lesions (6608 +/- 6320 mIU/mL) was significantly lower than in the lacunar type (40462 +/- 39735 mIU/mL; P = 0.04) and compact type (212114 +/- 205126 mIU/mL; P = 0.02), whereas the level in compact type lesions was significantly higher than in the lacunar type (P = 0.003). Lacunar type lesions exhibited a significantly lower uterine artery resistance index (0.51 +/- 0.13) than diffuse type (0.66 +/- 0.10; P = 0.03) or compact type lesions (0.70 +/- 0.06; P = 0.02). All lesions exhibited significantly higher peak systolic velocity than control subjects (P < 0.001); however, no significant difference was observed among them. Brief courses (< 5 cycles) of chemotherapy cured more diffuse type (6 of 7) than lacunar type (3 of 15, P = 0.006) or compact type lesions (0 of 5, P = 0.008). Histopathologic diagnosis was available for 11 lesions. They were invasive mole in seven lacunar type lesions and choriocarcinoma in four compact type lesions. CONCLUSION: Vascular morphologic patterns of gestational trophoblastic tumors by color Doppler ultrasound correlated well with beta-hCG levels, uterine hemodynamics, chemotherapy response, and possibly the histopathologic diagnosis.     

Urolithiasis related to laxative abuse

Urinary calcareous disease related to laxative abuse is rare. The gastrointestinal loss of fluid and electrolytes leads to chronic depletion of the urinary volume, relative supersaturation and many other pathophysiologic derangements. These calculi are generally radiolucent with uric acid and ammonium acid urate as major components. We report on a female patient with frequent, repetitive formation of urinary calculi and rapid double J stent encrustation, which were related to the chronic abuse of bisacodyl. Although these stones can be fragmented successfully by extracorporeal shockwave lithotripsy, it seems that the better treatment for this type of stone formation is to avoid the abuse of laxatives.