Recovery of reproductive function in rats treated with the aromatase inhibitor fadrozole

We report three cases of L-2-hydroxyglutaric acidemia and three cases of Canavan disease. The L-2-hydroxyglutaric acidemia cases are the first biochemically proven Turkish cases. Magnetic resonance imaging findings in the cases and similarities between the two diseases are emphasized. Both diseases are characterized by predominant subcortical white-matter involvement and dentate nuclei lesions with variable basal ganglia involvement. Canavan disease differs from L-2-hydroxyglutaric acidemia by the presence of typical brainstem involvement.     

Identification of the second cluster of ligand-binding repeats in megalin as a site for receptor-ligand interactions

Megalin is a large cell surface receptor that mediates the binding and internalization of a number of structurally and functionally distinct ligands from the lipoprotein and protease:protease inhibitor families. To begin to address how megalin is able to bind ligands with unique structurally properties, we have mapped a binding site for apolipoprotein E (apoE)-beta very low density lipoprotein (beta VLDL), lipoprotein lipase, aprotinin, lactoferrin, and the receptor-associated protein (RAP) within the primary sequence of the receptor. RAP is known to inhibit the binding of all ligands to megalin. We identified a ligand-binding site on megalin by raising mAb against purified megalin, selected for a mAb whose binding to megalin is inhibited by RAP, and mapped the epitope for this mAb. mAb AC10 inhibited the binding of apoE-beta VLDL, lipoprotein lipase, aprotinin, and lactoferrin to megalin in a concentration-dependent manner. When cDNA fragments encoding the four cysteine-rich ligand-binding repeats in megalin were expressed in a baculovirus system and immunoblotted with AC10, it recognized only the second cluster of ligand-binding repeats. The location of the epitope recognized by mAb AC10 within this domain was pinpointed to amino acids 1111-1210. From these studies we conclude that the binding of apoE-beta VLDL, lactoferrin, aprotinin, lipoprotein lipase, and RAP to megalin is either competitively or sterically inhibited by mAb AC10 suggesting that these ligands bind to the same or closely overlapping sites within the second cluster of ligand-binding repeats.     

Ultrasound guided percutaneous fine needle aspiration cytology of pancreas: a review of 61 cases

The study includes 61 cases which were subjected to ultrasound (US) guided fine needle aspiration cytology (FNAC) to find out the utility of this technique in the diagnosis of pancreatic lesions. Age of the patients ranged from 23 to 85 years with a median of 50 years. Male to female ratio was 36:25. One or more clinical diagnoses were offered in 16 and in 9 of these, the disease was related to pancreas. Subsequent to US, the lesions were localized to pancreas in 57 and the nature of pathology in the pancreatic lesion could be diagnosed in 31. By FNAC, 31 cases (50.8%) were diagnosed to have pancreatic malignancy which included adenocarcinoma (23 cases), papillary cystic tumour (1), muco-epidermoid carcinoma (1), acinic cell carcinoma (1), islet cell tumor (1), and non Hodgkin lymphoma (4). FNAC of liver in 2 cases and retroperitoneal lymph node in a case of pancreatic adenocarcinoma revealed metastasis. During follow up, 1 case of non Hodgkin's lymphoma showed CSF involvement. Three cases (4.9%) were suspected to have epithelial malignancy of which one was confirmed as an adenocarcinoma following surgery and histology. Four (6.6%) were benign lesions which included nonspecific inflammation (2 cases), tuberculous pancreatitis (1) and pseudopancreatic cyst (1). The remaining 23 cases (37.7%) had normal or inadequate cytology. Of these, FNAC of liver showed metastasis in 2 cases and one case each were diagnosed as adenocarcinoma and pseudopancreatic cyst respectively following surgery. None of the patients had any complication following FNAC. We recommend US guided FNAC to be routinely used for diagnosis of pancreatic lesion.     

Discovering asymptomatic biochemical abnormalities on a Baltimore internal medicine service

To assess the frequency of abnormalities that could be discovered through biochemical profile screening on patients admitted to a city hospital internal medicine ward service, we conducted a prospective cross-sectional chart and laboratory review. All unassigned patients admitted to the general medicine service during 1- to 2-month period in late 1993 and the spring of 1994 were eligible. The main outcome measures were frequency of abnormal test results and identification of significance. Admitted patients (N = 222) were evaluated with a 24-panel biochemical profile. Of 5,328 tests, 29% were outside the standard reference range. Of 3,851 tests classified as screening, 1,049 (27%) were outside the reference range. Of overall screening tests, 741 (19%) were judged potentially important by the predetermined criteria. The prevalence did not differ significantly when analyzed by age, race, gender, or history of substance abuse. Our experience indicates that asymptomatic biochemical abnormalities are common in patients admitted to a city hospital medical service and that admission biochemical screening is an effective method of identifying potential comorbidity. Further studies are needed to assess the impact of this approach.