Identification of risk groups for development of central nervous system leukemia in adults with acute lymphocytic leukemia

The risk of development of CNS leukemia was investigated in 153 adults with acute lymphocytic leukemia (ALL) who received systemic combination chemotherapy without CNS prophylaxis. Overall, 31 patients (20%) developed CNS leukemia after a median of 6 months of therapy; the estimated 1-year incidence of CNS leukemia was 21% (SE, 3.9%). Characteristics significantly associated with CNS involvement included the presence of elevated hemoglobin creatinine, alkaline phosphatase, fibrinogen, and lactic dehydrogenase levels; B-cell leukemia; and high leukemic cell proliferative activity. Multivariate analysis identified lactic dehydrogenase levels of greater than or equal to 600 U/L and greater than or equal to 14% of cells in the S + G2M compartment to have independent additive poor prognostic significance. Patients were categorized into different risk groups for CNS leukemia with 1-year incidences ranging from 4% to 55%. While related to a high occurrence of CNS leukemia at diagnosis (33%) and subsequently (100%), the low incidence of B-cell disease excluded it from the multivariate analysis. The use of systemic chemotherapy containing multiple agents with good CNS penetration and in high doses (VAD regimen) in 90 patients was associated with a trend for lower CNS leukemia at 1 year (15% v 31%), especially in the low-risk category. We propose to develop future therapies for adults with ALL that include risk-oriented CNS prophylactic approaches.     

Heparin-Coated Coronary Stents

The development of the heparin-coated (HC)-stent should be viewed against the backdrop of the early unfavorable results with noncoated stents in the pre-intravascular ultrasound and pre-ticlopidine era. Notwithstanding, results of pilot and randomized trials show a surprisingly low incidence of (sub)acute stent thrombosis under challenging circumstances, such as acute coronary syndromes. Considering the quite low incidence of early complications with noncoated second-generation stents, it may require large trials to prove the clinical efficacy of the heparin- coating against noncoated devices. However, even if the "added value" of the heparin-coating will never be clinically proven, it has helped to enhance the penetration of stent therapy in interventional cardiology. Unlike the situation in 1992, very few cardiologists will now disagree with the statement that stents contribute to the state-of-the-art treatment of patients with angina pectoris or acute myocardial infarction. A preliminary comparison of available trials also suggests that the heparin-coated Palmaz-Schatz stent (Cordis Corp., Waterloo, Belgium) is as effective as the noncoated stent plus abciximab treatment.     

Microbiologic contamination of peripheral blood progenitor cells collected for hematopoietic cell transplantation

BACKGROUND: Peripheral blood progenitor cells (PBPCs) rather than bone marrow are used increasingly to provide hematologic reconstitution when transfused after marrow-ablative chemotherapy. PBPCs often are collected via central venous catheters that have remained in place for long periods of time and that may become infected. STUDY DESIGN AND METHODS: The investigators reviewed their 5-year experience in collecting PBPCs for the prevalence of bacterial contamination. Except for cotrimoxazole therapy given to prevent Pneumocystis cariini pneumonia, patients were not given antibiotic prophylaxis. RESULTS: Each patient underwent a median of 7 (range, 2–21) PBPC collections; 0.2 percent (3/1040 collections) were culture positive for bacteria (two collections contained coagulase-negative staphylococci and one contained Serratia marcescens). All culture-positive collections were discarded; no PBPCs were culture positive at the time of thawing and transfusion. CONCLUSION: This contamination rate is below that previously reported for bone marrow harvests and platelet concentrate collections. Obtaining PBPCs through large-bore central venous catheters has not added to the risk of infection in transplant patients. A program of screening in vitro cultures and strict adherence to sterility techniques can result in very low microbiologic contamination and thus obviates the need for prophylactic antimicrobials in the PBPCs and in the patient.     

CLIMACTERIC SYMPTOMS IN HEALTHY MIDDLE-AGED WOMEN

SUMMARY The incidence of climacteric symptoms was determined in 247 healthy premenopausal women in a community setting. These volunteers had been recruited to a longitudinal study of bone density. Of these subjects, 46 ceased to menstruate during the study, and in this subgroup symptoms were compared before and after cessation of menstruation. Only hot flushes increased after cessation of menstruation in the longitudinal study and showed age correlation in the cross-sectional study. Hot flushes thus emerged as a true menopausal symptom. Although evidence for this is weaker, cold sweats and suffocation seem likely to be genuinely menopausal. Breast discomfort and the four mood symptoms of irritability, excitability, depression and poor concentration improved after cessation of menstruation, and this study gives no support for their being part of the menopausal syndrome; it suggests that these symptoms are more likely to be related to menstruation than to the menopause.     

The Feasibility of Longitudinal Patient Contacts in a Large Medical School

Problem: Longitudinal patient contacts are being implemented worldwide as a way to enhance a patient-centered orientation among medical students. In large medical schools, longitudinal integrated clerkships may not be feasible, so other ways must be sought to expose students to prolonged contact with patients. Intervention: Medical students were attached to a family practice and assigned a panel of 4 patients to follow over the 3 years of their clinical training. Their role was that of companion on the patient’s medical journey. The program consisted of several encounters, joining the patient in the medical setting for significant events, and written assignments. This intervention was piloted with 35 students. We describe our experiences from the 1st pilot year of this program. Context: The intervention was performed with 3rd-year students—of a 6-year curriculum—at a large medical school in the Netherlands. Outcome: Finding enough patients per practice was feasible. On the whole, students fulfilled the program’s expectations regarding frequency of patient encounters and assignments. The most frequent problems encountered by the students were uncertainty about their role and setting boundaries in their contact with the patients. They needed more preceptor supervision and coaching than they received. Lessons Learned: For junior students, close and structured supervision led by the faculty is necessary to help them navigate and learn from a panel of patients. Students need guidance about what role they should take on and on how to manage both their own and their patient’s expectations. Guided reflection is necessary to help students give meaning to their experiences with patients.     

Oxidised- and total non-protein bound glutathione and related thiols in gallbladder bile of patients with various gastrointestinal disorders

Background  

Glutathione is a tripeptide composed of glutamate, cysteine and glycine, accomplishing a broad range of vital functions. Synthesis of glutathione and cysteine is performed mainly in the liver, whereas most other tissues are supplied with these thiols via sinusoidal efflux into the blood. Since canalicular efflux also occurs, thiols may be present in human bile. However, thiol composition of human gallbladder bile is largely unknown, which makes it difficult to speculate on the exact function of thiols in bile. In this study we report on the levels of non-protein bound thiols in gallbladder bile of patients with various gastrointestinal disorders.     

Interleukin-3, GM-CSF, and G-CSF receptor expression on cell lines and primary leukemia cells: receptor heterogeneity and relationship to growth factor responsiveness

Recombinant human granulocyte-macrophage (GM) colony-stimulating factor (GM-CSF), G-CSF, and interleukin-3 (IL-3) labeled with 125I were used to study the characteristics and distribution of receptors for these factors on in vitro cell lines and on cells from patients with acute nonlymphocytic leukemia (ANL) and acute lymphocytic leukemia (ALL). Receptors for GM-CSF and G-CSF were restricted to a subset of myelomonocytic cell lines whereas IL-3 receptors were also found on pre- B- or early B-cell lines. Receptors for all three CSFs were broadly distributed on ANL cells, with considerable variability in levels of expression. Measurement of the colony-forming ability of ANL cells in response to the CSFs showed that there was no direct correlation between the ability of the cells to respond to a growth factor and the absolute number of receptors expressed for that growth factor. Binding of radiolabeled IL-3 and GM-CSF to ANL cells produced complex biphasic curves. Further analysis showed that both IL-3 and GM-CSF were able to partially compete for specific binding of the heterologous radiolabeled ligand to cells from several ANL patients, suggesting that heterogeneity may exist in human CSF receptors. These results provide new insights into the complex role that CSFs may play in ANL.     

Peripheral blood harvest of unaffected CD34+ CD38- hematopoietic precursors in paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) arises from somatic mutation of a bone marrow progenitor that disrupts glycosylinositol phospholipid (GPI) anchoring of cell surface proteins. We recently characterized the expression of GPI-anchored decay acclerating factor (DAF) and CD59 during hematopoietic development in PNH marrow. We found that, although a subset of early hematopoietic precursors identified by the CD34+CD38- phenotype exhibits normal DAF and CD59 expression, DAF and CD59 are absent on the majority of CD34+CD38- cells. Pluripotent CD34+CD38- hematopoietic stem cells normally circulate in the peripheral blood and can be collected by apheresis, cryopreserved, and later used for reconstitution of hematopoiesis. In this study, we examined the phenotypes of CD34+ cells that are released into the blood of PNH patients. Analyses of apheresis samples from three affected individuals showed discrete populations of circulating DAF+CD59+CD34+ and DAF-CD59- CD34+ cells. Variable proportions of CD34+CD38- cells were present within the peripheral blood CD34+ cells of each patient, but in all three cases the DAF+CD59+CD34+CD38- cell subset subset. Because CD34+ cells lacking CD38 antigen are highly enriched for self-renewing hematopoietic stem cells, these findings indicate that apheresis samples can serve as a source of unaffected stem cells for autologous marrow transplantation of PNH patients.     

Cyclooxygenase-2 polymorphisms and the risk of esophageal adeno- or squamous cell carcinoma

AIM： TO determine whether -1195 A→G and/or -765 G→C polymorphisms in Cyclooxygenase-2 CCOX-2） may have a risk modifying effect on the development of esophageal carcinoma in a Dutch Caucasian population. METHODS： Two study groups were recruited, 252 patients with esophageal carcinoma and 240 healthy controls, matched for race, age, gender and recruiting area. DNA was isolated from whole blood and used for genotyping. PCR products were digested with restriction enzymes and products were analyzed by agarose gel electrophoresis. Odds ratios （OR） and 95% confidence intervals （CI） were estimated. RESULTS： The distribution of the -1195A→G polymorphism was significantly different in esophageal cancer patients compared to controls. The -1195 GG genotype resulted in a higher risk of developing esophageal adenocarcinoma （OR = 3.85, 95% CI： 1.45-10.3） compared with the -1195AA genotype as a reference. The -765 G→C genotype distribution was not different between the two groups. The GG/ GG haplotype was present more often in esophageal adenocarcinoma patients than in controls （OR = 3.45, 95% CI： 1.24-9.58; with AG/AG as a reference）. The same trends were observed in patients with squamous cell carcinomas, however, the results did not reach statistical significance. CONCLUSION： Presence of the COX-2 -1195 GG genotype and of the GG/GG haplotype may result in a higher risk of developing esophageal carcinoma.