Nodular lymphocyte-predominant Hodgkin’s lymphoma

Lymphocyte-predominant Hodgkin’s lymphoma (LPHL) differs in histologic and clinical presentation from classical Hodgkin’s lymphoma (cHL). Treatment of LPHL patients using standard Hodgkin’s lymphoma protocols leads to complete remission in more than 95% of patients. Survival and freedom from treatment failure are substantially worse in advanced-stage patients than for early-stage patients. Thus, patients in advanced stages and those in early stages with unfavorable risk factors should be treated similar to those with cHL. In contrast, patients with early-stage LPHL without risk factors might be sufficiently treated with reduced-intensity programs having less severe adverse effects. As a result, treatment of early LPHL is rather heterogeneous, including radiotherapy using extended-fleld technique, involved-fleld radiotherapy (IF-RT), combined-modality treatment, and, more recently, monoclonal antibodies. Watch-and-wait strategy plays an important role in pediatric oncology, to avoid adverse effects associated with therapy. IF-RT seems to be emerging as a treatment of choice for patients with stage IA LPHL; most larger study groups, such as the German Hodgkin Study Group and the European Organisation for Research and Treatment of Cancer, have adopted IF-RT as the treatment of choice for these patients.     

Intimal hyperplasia and coronary flow reserve after heart transplantation: association with big endothelin-1

BACKGROUND: Endothelin, a peptide with strong vasoconstrictive and mitogenic properties, has been found to increase after cardiac transplantation. We therefore assessed the association between its precursor peptide, big endothelin-1, and intimal hyperplasia and coronary flow reserve after heart transplantation. METHODS: Thirty-five patients without hemodynamically significant coronary artery disease after heart transplantation were investigated: Average peak flow velocity in the left anterior descending artery (LAD) was assessed by intracoronary Doppler at baseline as well as after injection of adenosine; coronary flow reserve was calculated as a ratio of both and was corrected for patient age and baseline average peak flow velocity. Lumen, intima + media and total vessel area were measured by intracoronary ultrasound. The plasma concentration of big endothelin-1 in venous blood was determined by radioimmunoassay. RESULTS: Patients with elevated big endothelin-1 levels (>2 fmol/ml) tended to have a decreased corrected coronary flow reserve (2.60 +/- 0.9 vs 3.21 +/- 1.0, p = 0.078). They also had a significantly larger intima + media area (5.82 +/- 2.9 vs 2.37 +/- 2.9 mm(2), p = 0.004) and total vessel area (18.36 +/- 5.8 vs 12.81 +/- 4.8 mm(2), p = 0.012) than those with normal plasma concentrations. CONCLUSIONS: Our study suggests an association between elevated big endothelin-1 plasma levels and the development of intimal hyperplasia and reduction of coronary flow reserve after cardiac transplantation.     

Immunoglobulin Gene Rearrangement in Plasma Cell Dyscrasias: Detection of Small Clonal Cell Populations in Peripheral Blood and Bone Marrow

The bone marrow (BM) and peripheral blood (PB) samples of 71 patients with plasma cell dyscrasias were analysed by the Southern blot technique for the presence of clonal immunoglobulin (Ig) gene rearrangements. 53% of BM samples examined were archival material such as air dried BM slides or frozen trephine biopsies. The results were related to bone marrow plasmacytosis as determined by cytology and flow cytometry, and other clinical parameters. Clonal Ig gene rearrangements were found in BM samples of 45 (83%) of 54 MM patients and in 3 of 6 patients with monoclonal gammopathy of unknown significance (MGUS). Clonal cell populations in the PB were detected in 11 (30%) of 37 examined MM patients, but in none of the patients with MGUS or solitary plasmacytoma of bone. PB involvement was associated with progressive disease. Circulating monoclonal cells were significantly associated with higher M-protein levels (p 0.05). Thus, circulating clonal precursor cells are encountered more frequently in active MM.     

Mapping scores onto stages: mini-mental state examination and clinical dementia rating.

OBJECTIVE: Although the clinical course of Alzheimer disease (AD) is gradual, it is useful for a number of reasons to distinguish between different levels of severity. The Clinical Dementia Rating (CDR) has demonstrated high validity and reliability for this purpose, but it requires a considerable amount of data to be collected both from the patient and from an informant. In the present study, the authors mapped Mini-Mental State Examination (MMSE) scores onto CDR categories to determine how well the MMSE performs as a surrogate of the CDR as a timesaving method of staging dementia. METHOD: Eight hundred sixty-three probands, including 524 patients with probable AD, 92 patients with questionable dementia, and 247 with memory complaints but no objective cognitive impairment, were included. Cutoff scores were identified on one-half of the sample using a receiver operating characteristic analysis. The cutoff values were then applied to the other half of the sample, and the agreement between MMSE score ranges and CDR stages was determined by calculating Cohen's kappa. RESULTS: The MMSE discriminated well between CDR stages 0.5, 1, 2, and 3 but performed poorly in the separation between CDR stages zero and 0.5. The MMSE ranges were 30 for no, 26-29 for questionable, 21-25 for mild, 11-20 for moderate, and 0-10 for severe dementia. Substantial agreement between the two instruments was obtained for the categories mild (kappa=0.62, p<0.001, N=115), moderate (kappa=0.69, p<0.001, N=114), and severe dementia (kappa=0.76, p<0.001, N=39), whereas the agreement was moderate for no (kappa=0.44, p<0.001, N=120) and only fair for questionable dementia (kappa=0.28, p<0.001, N=42). CONCLUSION: The MMSE can be used as a surrogate measure for the CDR for the staging of dementia in AD.     

Analysis of epidermal growth factor receptor and activated epidermal growth factor receptor expression in pituitary adenomas and carcinomas.

Epidermal growth factor receptor plays an important role in the pathogenesis of many malignancies. Various growth factors, including epidermal growth factor receptor, have been shown to influence pituitary tumor growth and differentiation. To analyze the role of epidermal growth factor receptor in pituitary tumor development, we examined normal pituitaries (n=8), pituitary adenomas (n=158), and pituitary carcinomas (n=7) for expression of epidermal growth factor receptor protein and messenger RNA using tissue microarrays and RT-PCR. We also examined (a) the expression of phospho-epidermal growth factor receptor, the activated form of epidermal growth factor receptor, in pituitary tumors and normal pituitaries by immunohistochemistry and (b) the effects on epidermal growth factor receptor expression of treating pituitary cells (HP75 cell line) with epidermal growth factor. Epidermal growth factor receptor and the phosphorylated variant expression were present in normal pituitary cells. Epidermal growth factor receptor messenger RNA was also detected in normal pituitaries, pituitary adenomas, and carcinomas by in situ hybridization and RT-PCR. Most pituitary adenomas showed expression of epidermal growth factor receptor and the phosphorylated variant. Nonfunctional adenomas showed higher levels of expression of epidermal growth factor receptor (76 vs 34%) and of phospho-epidermal growth factor receptor (26 vs 8%) as compared to functional adenomas. Five of seven pituitary carcinomas showed strong expression of both epidermal growth factor receptor and phospho-epidermal growth factor receptor. When a human pituitary cell line (HP75) was cultured in the presence of epidermal growth factor receptor, there was an increase in the levels of both epidermal growth factor receptor and phospho-epidermal growth factor receptor after 5 h of treatment, thus confirming that epidermal growth factor receptor signaling was active in pituitary tumors. These results indicate that activated epidermal growth factor receptor is expressed in pituitary adenomas and carcinomas. Higher levels in pituitary carcinomas suggest a role in pituitary tumor progression.     

Leukopenia, neutropenia, and reduced hemoglobin levels in healthy American blacks

Hematologic profiles of 462 persons, mostly active-duty service members, were studied to determine whether hematologic differences between blacks and whites exist in a healthy population. Whites had significantly greater mean concentrations of leukocytes (6.73 vs 5.95 x 10(9)/L), neutrophils (3.96 vs 3.16 x 10(9)/L), and hemoglobin (153 vs 135 g/L for men, 147 vs 125 g/L for women). The mean differences were largely due to relatively symmetric shifts in the frequency distributions for these cell concentrations. No significant correlation was found between neutrophil count and morbidity from infection as measured by a standardized questionnaire. The use of separate hematologic reference values for blacks and whites should be considered.