Inherited prothrombotic defects in Budd-Chiari syndrome and portal vein thrombosis: a study from North India

We studied 57 patients with Budd-Chiari syndrome (BCS) and 48 with portal vein thrombosis (PVT) for underlying inherited prothrombotic defects such as protein C, protein S, and antithrombin III deficiencies. Genetic mutations for factor V Leiden, prothrombin gene 20210A, and methyltetrahydrofolate reductase (MTHFR) C677T were studied in 29 patients in each group. Inherited prothrombotic defects were detected in 16 (28%) of 57 patients with BCS and 7 (15%) of 48 patients with PVT. Factor V Leiden mutation was the most common prothrombotic defect in BCS (5/29 [17%]) followed by protein C deficiency (7/57 [12%]) and protein S deficiency (4/57 [7%]), whereas in PVT, protein C deficiency was the most common inherited prothrombotic defect (4/48 [8%]) followed by protein S deficiency (2/48 [4%]). The factor V Leiden mutation was detected in only 1 (3%) of 29 cases of PVT. The heterozygous MTHFR C677T mutation was detected in 7 (24%) of 29 patients with BCS and 6 (21%) of 29 patients with PVT. Antithrombin III deficiency, homozygous MTHFR C677T mutation, and prothrombin G20210A mutation were not detected in any patients.     

Germinal center and activated b-cell profiles separate Burkitt lymphoma and diffuse large B-cell lymphoma in AIDS and non-AIDS cases

Morphologic features of Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) overlap. No single phenotypic marker or molecular abnormality is pathognomonic. We tested a panel of 8 germinal center (GC) and activated B-cell (ABC) markers for their ability to separate BL and DLBCL. We diagnosed 16 BL and 39 DLBCL cases from 21 patients with AIDS and 34 without AIDS based on traditional morphologic criteria, Ki-67 proliferative index, and c-myc rearrangement (fluorescence in situ hybridization). After immunohistochemically staining tissue microarrays of BL and DLBCL for markers of GC (bcl-6, CD10, cyclin H) and ABC (MUM1, CD138, PAK1, CD44, bcl-2), we scored each case for the percentage of positive cells. Hierarchical clustering yielded 2 major clusters significantly associated with morphologic diagnosis (P < .001). For comparison, we plotted the sum of the GC scores and ABC scores for each case as x and y data points. This revealed a high-GC/low-ABC group and a low-GC/high-ABC group that were associated significantly with morphologic diagnosis (P < .001). Protein expression of multiple GC and ABC markers can separate BL and DLBCL.     

Benign lesions mimicking malignant tumors of the esophagus

Three cases of benign lesions which mimicked malignant tumors of the esophagus are described. In all three cases, two inflammatory pseudotumors and one case of diffuse leiomyomatosis, the clinical presentations, radiologic features, and gross pathologic findings led to the mistaken diagnosis of carcinoma at thoracotomy. The benign nature of the processes was recognizable only on microscopic examination. Although most benign tumors of the esophagus are localized solitary lesions that are easily distinguished from carcinoma, occasionally benign conditions may present as infiltrative, ulcerated mass lesions. Inflammatory pseudotumor and diffuse leiomyomatosis should be included in the differential diagnosis of esophageal malignancies.     

Clonal chromosome abnormalities in human breast carcinomas I. Twenty-eight cases with primary disease

Cytogenetic analysis was performed on a selected series of short-term cultures of primary breast carcinomas from 28 patients. All patients had histopathologically confirmed malignancies, with the majority (25/28 cases) demonstrating infiltrating ductal carcinoma. All 28 cases evidenced clonal chromosome abnormalities, with 10/28 displaying only numeric aberrations, whereas 18/28 displayed clonal structural alterations. In near-diploid tumors the most common numeric changes were — 17 and — 19. However, trisomy 7 was the only numeric change in two near-diploid tumors. Structural chromosome alterations were primarily isochromosomes, apparent terminal deletions, and unbalanced non-reciprocal translocations. Chromosomes 1 (10/18–56%) and 6 (8/18–44%) were most frequently altered in this series. Breakpoints of clonal structural abnormalities were shown to cluster to several chromosome segments, including 1p22-q11, 3p11, 6p11–13, 7p11-q11, 8p11-q11, and 19q13. Analysis of the gain or loss of specific chromosome segments revealed that the most consistent tendency was over-representation of 1q, 3q, and 6p. © 1993 Wiley-Liss, Inc.     

Development and Application of a Serum C-Telopeptide and Osteocalcin Assay to Measure Bone Turnover in an Ovariectomized Rat Model

Biochemical markers applicable to the ovariectomized rat model can provide important tools for studying the bone remodeling process in this animal model of postmenopausal osteoporosis. We describe the development and application of two biochemical markers, a C-telopeptide (of type-I collagen) enzyme-linked immunosorbent assay (ELISA) for measuring bone resorption and an osteocalcin radioimmunoassay (RIA) for measuring bone formation in rat serum. The C-telopeptide ELISA is based on an affinity purified polyclonal antibody generated against human sequence DFSFLPQPPQEKAHDGGR. The antibody epitope involves amino acid sequence, which is similar in rat and human carboxyl terminal peptide of type-I (alpha 1) collagen. Sensitivity of the ELISA was 0.3 ng/ml. The averaged intra- and interassay variation was CV <7%. Averaged dilution and spiked recoveries were 91% and 105%, respectively. The second marker developed is a synthetic peptide-based osteocalcin RIA, which does not require isolation and purification of intact osteocalcin from rat bone. Osteocalcin antiserum used in the RIA was generated in rabbits against a synthetic peptide comprising amino acids 33–49 of the rat osteocalcin sequence. The sensitivity of the RIA was 0.15 ng/ml of peptide. The averaged intra (n = 10) and interassay variations for two controls were CV <9% and 12%, respectively. The averaged dilution and spiked recoveries were 99.6%. In vivo validation of the C-telopeptide ELISA and osteocalcin RIA was performed in an ovariectomized (OVX) rat model. In 12-week-old OVX Sprague Dawley rats, the C-telopeptide and osteocalcin concentrations were approximately 65% and 40%, respectively, higher than the sham group. Estradiol repletion significantly lowered the C-telopeptide and osteocalcin concentration to the levels of the sham group. In addition, changes in serum C-telopeptide concentration correlated negatively with trabecular BMD measured by pQCT (r =−0.51, P < 0.001). In conclusion, the C-telopeptide ELISA and osteocalcin RIA exhibited required sensitivity, accuracy, and adequate discriminatory power to be used for measuring bone resorption and bone formation in the ovariectomized rat model. Received: 20 August 1999 / Accepted: 5 January 2000     

Glutamatergic dysfunction in OCD.

The role of glutamatergic dysfunction in the pathophysiology of OCD has hardly been explored despite recent reports implicating glutamatergic dysfunction in OCD. We decided to investigate CSF glutamate levels in adult OCD probands compared to psychiatrically normal controls. In total, 21 consenting psychotropic drug-na?ve adult OCD patients, diagnosed using SCID-IV-CV, and 18 consenting psychiatrically normal controls with age within 10 years of age of the patients, who did not have any history of head injury or neurological illness, were included into the study. Aseptically collected and stored CSF samples obtained from the patients and control subjects were used for glutamate estimation, which was carried out by a modification of the procedure described by Lund (1986). CSF glutamate (micromol/l) level was found to be significantly higher [F(1,31)=6.846, p=0.014] in OCD patients (47.12+/-4.25) compared to control subjects (41.36+/-3.63) on analysis of covariance. There was no effect of gender, age, duration of illness, Y-BOCS score, or CGI-S score on CSF glutamate levels. Our study provides preliminary evidence implicating glutamatergic excess in the pathophysiology of OCD, which needs to be further explored by studies from other centers involving larger sample sets from different age groups.     

A systematic review of the role of proton pump inhibitors for symptoms of laryngopharyngeal reflux

? Proton pump inhibitors are currently used widely for the treatment of laryngopharyngeal reflux. ? This systematic review assessed the efficacy of proton pump inhibitors in the treatment of symptoms of laryngopharyngeal reflux. ? Outcome measures used to assess efficacy of proton pump inhibitors included endoscopic laryngeal signs and pH recordings. ? Only two small randomized‐controlled trials included patients with objective evidence of reflux in the 24‐h ambulatory oesophageal pH monitoring. ? Pooled analysis of these two randomized‐controlled trials failed to show any effect in favour of treatment with proton pump inhibitors. ? Further randomized‐controlled trials are required to ascertain the role of proton pump inhibitors in the treatment of laryngopharyngeal reflux.