Differential expression of BCL-6, CD138/syndecan-1, and Epstein-Barr virus-encoded latent membrane protein-1 identifies distinct histogenetic subsets of acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas

This study was aimed at defining the histogenesis of the pathologic spectrum of acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas (AIDS-NHL), including AIDS-related small noncleaved cell lymphoma (AIDS-SNCCL), AIDS-related large noncleaved cell lymphoma (AIDS-LNCCL), AIDS-related large cell immunoblastic lymphoma plasmacytoid (AIDS-IBLP), and AIDS-related primary effusion lymphoma (AIDS-PEL). Forty-six cases of AIDS-NHL were investigated for the expression pattern of BCL-6, a protein specifically expressed by germinal center (GC) B-cells, and CD138/syndecan-1 (syn-1), a marker of post-GC B-cell differentiation. Expression of BCL-6 and syn-1 segregated two major phenotypic patterns among AIDS-NHL: (1) the BCL-6+/syn-1- pattern associated with AIDS-SNCCL and AIDS-LNCCL; (2) the BCL-6-/syn-1+ pattern associated with AIDS-IBLP and AIDS-PEL. Among systemic AIDS-NHL infected by Epstein-Barr virus (EBV), expression of the EBV-encoded latent membrane protein-1 (LMP-1) preferentially associated with the BCL-6-/syn-1+ profile. Analysis of nonneoplastic lymph nodes showed that the two phenotypic patterns detected in AIDS-NHL correspond to physiologic stages of B-cell development, i.e., GC B-cells (BCL-6+/syn-1-) and preterminally differentiated post-GC B-cells (BCL-6-/syn-1+). Thus, BCL-6+/syn-1- AIDS-NHL reflects a GC stage of differentiation, whereas AIDS-NHL which are BCL-6-/syn-1+, and LMP-1+ when infected by EBV, derive from B cells that have entered post-GC plasmacell differentiation. These findings are relevant for the pathogenesis and differential diagnosis of AIDS-NHL.     

Fetal and maternal contributions to risk of pre-eclampsia: population based study

OBJECTIVE: To use familial patterns of recurrence of pre-eclampsia to investigate whether paternal genes expressed in the fetus contribute to the mother's risk of pre-eclampsia and whether mother's susceptibility to pre-eclampsia is related to maternal inheritance by mitochondrial DNA. DESIGN: Linked data on pregnancies of different women who had children with the same father, and subsequently linked data on pregnancies of half sisters who either had same mother and different fathers or had same father and different mothers. SETTING: Population based data from the Medical Birth Registry of Norway covering all births since 1967 (about 1.7 million) and the Norwegian Central Population Register. MAIN OUTCOME MEASURES: Relative risk of pre-eclampsia after a previous pre-eclamptic pregnancy in the family. Relative risks approximated by odds ratios. RESULTS: If a woman becomes pregnant by a man who has already fathered a pre-eclamptic pregnancy in a different woman her risk of developing pre-eclampsia is 1.8 (95% confidence interval 1.2 to 2.6). If the woman has a half sister who had pre-eclampsia and with whom she shares the same mother but different fathers the risk of pre-eclampsia is 1.6 (0.9 to 2.6). If the two sisters have the same father but different mothers the risk is 1.8 (1.01 to 2.9). CONCLUSIONS: Both the mother and the fetus contribute to the risk of pre-eclampsia, the contribution of the fetus being affected by paternal genes. Mitochondrial genes, which are transmitted by mothers, do not seem to contribute to the risk.     

Maternal viral genotypic zidovudine resistance and infrequent failure of zidovudine therapy to prevent perinatal transmission of human immunodeficiency virus type 1 in pediatric AIDS Clinical Trials Group Protocol 076

Maternal samples were assessed from 96 women enrolled in Pediatric AIDS Clinical Trials Group protocol 076 to determine the prevalence of human immunodeficiency virus type 1 (HIV-1) genotypic zidovudine resistance at entry, if zidovudine resistance developed on study, and the role of zidovudine resistance in vertical transmission of HIV-1 despite zidovudine therapy. Low and high levels of genotypic resistance were assessed by differential hybridization, oligoligation, or direct sequencing of plasma HIV-1 RNA for codons K70R and T215Y/F. None of the women had high-level genotypic resistance to zidovudine at study entry or delivery. For low-level zidovudine resistance, the 95% confidence intervals were 0.3%-6.8% for baseline prevalence and 0.3%-14% for delivery incidence. Low-level zidovudine resistance, adjusted for plasma viral RNA level at delivery, was not strongly associated with an increase in vertical transmission risk (odds ratio, 4.8; 95% confidence interval, 0.2-131; P = .35).     

Ovarian metastases from cervical carcinomas other than pure adenocarcinomas. A report of 12 cases

Twelve cases of ovarian metastases from cervical carcinomas, most with clinical manifestations of ovarian involvement, are reported. The patients were 23-73 years of age (average, 43 years). The ovarian and cervical tumors were synchronous in eight patients; in three, ovarian tumors were discovered 10 months, 2.5, and 3 years after the detection of a cervical neoplasm. In one patient, the cervical tumor was not discovered until autopsy 7 months after presentation. Four patients had abdominal swelling or distention, three had vaginal bleeding, three had an abnormal Papanicolaou smear, and two had masses discovered during pelvic examination. The ovarian tumors, six of which were bilateral, ranged from 5-17 cm (average, 9.5 cm) in maximal dimension in 11 patients; in the 12th patient, the involved ovary was not enlarged. The cervical tumors were grossly evident in 10 patients. They were usually deeply invasive, often with extracervical extension. Four were squamous cell carcinomas; two, small cell carcinomas; one, a mixed small cell carcinoma and adenocarcinoma; one, a mixed poorly differentiated carcinoid and adenocarcinoma; two, adenosquamous carcinomas; one, a transitional cell carcinoma; and one, an undifferentiated carcinoma. Various features, including bilaterality of the ovarian tumors, the finding that the histologic features of the ovarian tumors typically were unusual for a primary ovarian neoplasm, and the presence of extensive extracervical disease, led to the conclusion that the ovarian tumors were metastatic from the cervix. Although ovarian metastases of cervical carcinoma are uncommon, this series illustrates that, occasionally striking examples with clinical manifestations of ovarian involvement occur.     

Iatrogenic diaphragmatic hernia following abdominal esophagogastrofundoplication: report of a case

The authors describe diagnosis and surgical treatment of a patient with iatrogenic diaphragmatic hernia following esophagogastrofundoduplication by Nissen's operation. The patient had presented a hiatal hernia with esophagitis chronic regurgitation and was submitted to esophagogastrofundoduplication. On the third postoperative day, the patient showed signs of dysphagia and intense dyspnea. The computerized tomography showed the presence of the gastric fundus and it's contents inside the leftpleural cavity. The patient was submitted to a left posterolateral thoractomy and an ischemic peptic ulcer in the gastric fundus, blocked by lung parenchyma was sutured. Then, the stomach was reduced into the abdominal cavity with diaphragmatic suture associated with esophageal and gastric fundus fixation to the right diaphragmatic pilar. The patient presented satisfactory immediate and late postoperative follow-up (1 year). The authors discuss and document aspects of diagnosis as well as surgical indication.     

Pegaspargase: an alternative?

OBJECTIVE: To review the chemistry, pharmacology, pharmacokinetics, clinical activity, adverse effects, dosage, and administration guidelines for pegaspargase. DATA SOURCES: A MEDLINE search (1980-1996), a CANCERLIT search (1983-1996), and a CURRENT CONTENTS search (1980-1996) using the terms pegaspargase, PEG-asparaginase, PEG-L-asparaginase, polyethylene glycol L-asparaginase, polyethylene glycol conjugated L-asparaginase, and Oncaspar were conducted. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in this review. Abstracts were included only when they were judged to add critical information not otherwise available in the medical literature. DATA SYNTHESIS: L-Asparaginase has been a main component of treatment regimens for acute lymphocytic leukemia. A key limiting factor of L-asparaginase use has been the development of hypersensitivity to the drug. Recently, a polyethylene glycol (PEG) conjugated form of L-asparaginase, pegaspargase, has been made available. PEG modification of L-asparaginase has been shown to alter the tendency of the enzyme to induce an immune response and to extend the half-life of the drug. The majority of patients with hypersensitivity to the native enzyme preparations tolerate pegaspargase without further clinical hypersensitivity. The adverse effect profile of pegaspargase is similar to that of the native forms of L-asparaginase. The recommended dosage of pegaspargase is 2500 IU/m2 administered by intramuscular or intravenous injection every 2 weeks in combination with other chemotherapeutic agents. CONCLUSIONS: Pegaspargase is a safe, effective alternative to L-asparaginase in patients who have had clinical hypersensitivity reactions to both Escherichia coli- and Erwinia carotovora-derived L-asparaginase. However, pegaspargase should not be routinely substituted for L-asparaginase.     

Caregivers and HIV infection. Services and issues

Because of the complexity of their illness, patients infected with HIV may require many services to facilitate the management of the disease. The primary care provider must understand and facilitate the services that are needed and needs to be familiar with the individuals responsible for the care of each patient. There are many stresses that have been identified in HIV caregiving, for informal caregivers and health care workers. These stresses are described, and suggestions for appropriate interventions are outlined.     

The effects of sleep loss on task performance and the electroencephalogram in young and elderly subjects

The effects of 28-h sleep loss on performance, reaction time (RT) distribution functions, and spectral composition of the EEG were evaluated in three choice-RT tasks for young (N = 12, aged 18-24 years) and old (N = 12, aged 62-73 years) subjects. Manipulations of stimulus degradation, stimulus-response compatibility, and interstimulus interval variability were to affect encoding, response selection, and motor adjustment stages, respectively. In order to discriminate between independent variables that were presumed to be computational or energetical in nature, effects on EEG spectra and RT-distributions were studied. Spectra of the EEG indicated higher cortical arousal levels for the elderly than for the young. The most dramatic effect of sleep loss on performance was a marked increase in the number of omitted responses. This effect was smaller for the elderly than for the young. The results suggest that the detrimental effects of sleep loss are smaller in the elderly, which is consistent with an inverted-U relationship between arousal and performance. The age effects on the processing stages were mainly limited to response selection.