Recombinant human interleukin-11 stimulates multilineage hematopoietic recovery in mice after a myelosuppressive regimen of sublethal irradiation and carboplatin

Interleukin-11 (IL-11) is a novel multifunctional hematopoietic cytokine capable of stimulating cells of the myeloid, lymphoid, erythroid, and megakaryocytic lineages in vitro. We have tested the pleiotropic properties of this cytokine on the hematopoietic recovery of mice after a combined regimen of sublethal irradiation and carboplatin administration. This regimen results in severe myelosuppression, characterized by a prolonged period of thrombocytopenia and severe anemia. Administration of recombinant human IL-11 (rhIL-11; 250 micrograms/kg/d) had multilineage effects on bone marrow and spleen hematopoietic activity, increasing the number of megakaryocyte, erythroid, granulocyte, and macrophage progenitors compared with the vehicle-treated controls. This was reflected in the peripheral circulation by a reduction of both the platelet and hematocrit nadirs and a significantly reduced period of thrombocytopenia and anemia in the rhIL-11-treated mice. The results from this study support the broad spectrum of biologic activities that have been attributed to rhIL-11 in vitro and suggest that this cytokine may be an effective agent in the treatment of myelosuppression associated with cancer chemotherapy and bone marrow transplantation.     

Indeterminate biliary strictures: a simplified approach

Introduction: Pre-operative evaluation of biliary strictures remains challenging. The dilemma that exists is how to balance the risk of failing to detect malignancy and the potential morbidity caused by unnecessary surgery in patients with benign etiologies. With emerging novel diagnostic modalities, this study aims to assess the efficacy of diagnostic techniques and facilitate a clinical approach to indeterminate biliary strictures.

Areas covered: Conventional imaging modalities are crucial in identifying the location of a stricture and are helpful for choosing further diagnostic modalities. Utilization of endoscopic techniques, including endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS), is key in establishing a diagnosis. The emergence of novel diagnostic modalities, such as fluorescence in-situ hybridization (FISH), peroral cholangioscopy (POC), intraductal endoscopic ultrasound (IDUS) and confocal laser endomicroscopy (CLE), enhance the diagnostic yield in the evaluation of indeterminate biliary strictures.

Expert commentary: More reliable and validated visual criteria for differentiating malignancy from benign biliary conditions, utilizing advanced imaging modalities such as POC and CLE, need to be established. It is of significance to further evaluate these novel diagnostic modalities through ongoing trials and to develop a diagnostic algorithm that reconciles cost-effectiveness with diagnostic accuracy.     

High-dose chemoradiotherapy and autologous blood stem cell transplantation in multiple myeloma: results of a phase II trial involving 63 patients

Sixty-three patients with high tumor mass multiple myeloma were treated with high-dose chemotherapy and total body irradiation supported by autologous blood stem cell transplantation. After high-dose therapy, they were monitored for a median of 44 months. Seven patients died early from toxicity. All the other patients, including those whose disease was resistant to previous therapies, showed a tumor mass reduction. At 6 months postengraftment, 40 (71%) of the surviving patients had minimal residual disease and 11 (20%) were in apparent complete remission. During follow-up, 25 out of the 63 (39%) patients relapsed and 16 of these died; 31 (49%) had a sustained remission. The median overall and event-free survival times after transplantation were 59 and 43 months, respectively. The initial serum beta 2-microglobulin value (> or < 2.8 mg/L) and length of previous therapy (> or < 6 courses of chemotherapy) were the only significant prognostic factors. In all surviving patients, blood stem cell autograft provided satisfactory and sustained haematopoietic reconstitution most often within 15 days. High dose chemoradiotherapy followed by autologous blood stem cell transplantation is thus an important therapeutic option for young patients with aggressive multiple myeloma.     

Serial changes in the T1 magnetic relaxation parameter after myocardial infarction in man

A low field resistive nuclear magnetic resonance imaging system (0.08 Tesla) was used to study the in vivo changes in the relaxation parameter T1 of the left ventricular myocardium from the first day to six months after acute myocardial infarction in 41 consecutive patients admitted to a coronary care unit. T1 maps were constructed from transverse and coronal images at various times after infarction. Thrombolytic treatment had been successful in 28 patients. Thirty three of the 34 patients studied within two weeks of infarction had a significantly increased T1 value but this developed only after the third day in four. At day 1-3 the mean (1 SD) maximum T1 was 413 (29) ms (n = 23) compared with 430 (41) ms (n = 22) at day 4-7, 433 (35) ms (n = 24) at day 8-14, 420 (34) at one month (n = 22), 388 (39) (n = 20) at three months, and 361 (24) (n = 14) at six months. The number of regions of interest with an increased T1 followed a similar time course. Although the increase in T1 measured at three months correlated with the initial maximum creatine kinase and with the left ventricular ejection fraction measured at one month, the number of regions with abnormal T1 from day 4 through to one month correlated best with left ventricular ejection fraction. There was no significant difference in T1 between patients with or without reperfusion. The rise in T1 over the first few days together with the prolonged time course of T1 increase suggests that the increase in T1 may reflect cellular infiltration as much or more than tissue oedema.     

How useful are high vaginal swabs in general practice? Results of a multicentre study

Vulvovaginal symptoms are a common reason for consultation with a general practitioner (GP). High vaginal swabs (HVS) are used to investigate symptoms, but their usefulness is poorly evaluated and microbiological tests performed vary between laboratories. In this multicentre study of 797 women with genital symptoms attending GPs, diagnostic yield of HVS was poor except for Candida spp. (22%). There is an urgent need to establish the most cost-effective approach for the management of these women.     

Fetal liver cells produce both fetal and adult erythrocytes in semiallogeneic radiation chimeras: possible influence of adult environment

Two kinds of erythrocytes are released in the blood of irradiated adult hybrid mice grafted with parental fetal liver cells: fetal antigen- bearing erythrocytes (Ft+ cells) and adult-type Ft- erythrocytes. Both are of parental origin, as determined by immune lysis using histocompatibility alloantigens. The latter cells make up all the recipient's red blood cells 2 mo after receipt of the graft, Ft+ cells then being no longer detected. The transient duality of erythropoiesis in irradiated adults grafted with fetal liver cells has been confirmed by studying the kinetics of CFU-E populations, as characterized by their ability to give rise to Ft+ or Ft- erythrocytes. The results are discussed in terms of environmental factors that influenc erythroid differentiation.     

Assessment of aldehyde dehydrogenase in viable cells

Cytosolic aldehyde dehydrogenase (ALDH), an enzyme responsible for oxidizing intracellular aldehydes, has an important role in ethanol, vitamin A, and cyclophosphamide metabolism. High expression of this enzyme in primitive stem cells from multiple tissues, including bone marrow and intestine, appears to be an important mechanism by which these cells are resistant to cyclophosphamide. However, although hematopoietic stem cells (HSC) express high levels of cytosolic ALDH, isolating viable HSC by their ALDH expression has not been possible because ALDH is an intracellular protein. We found that a fluorescent aldehyde, dansyl aminoacetaldehyde (DAAA), could be used in flow cytometry experiments to isolate viable mouse and human cells based on their ALDH content. The level of dansyl fluorescence exhibited by cells after incubation with DAAA paralleled cytosolic ALDH levels determined by Western blotting and the sensitivity of the cells to cyclophosphamide. Moreover, DAAA appeared to be a more sensitive means of assessing cytosolic ALDH levels than Western blotting. Bone marrow progenitors treated with DAAA proliferated normally. Furthermore, marrow cells expressing high levels of dansyl fluorescence after incubation with DAAA were enriched for hematopoietic progenitors. The ability to isolate viable cells that express high levels of cytosolic ALDH could be an important component of methodology for identifying and purifying HSC and for studying cyclophosphamide-resistant tumor cell populations.     

Comparing human and mouse salivary glands: A practice guide for salivary researchers

Mice are a widely utilized in vivo model for translational salivary gland research but must be used with caution. Specifically, mouse salivary glands are similar in many ways to human salivary glands (i.e., in terms of their anatomy, histology, and physiology) and are both readily available and relatively easy and affordable to maintain. However, there are some significant differences between the two organisms, and by extension, the salivary glands derived from them must be taken into account for translational studies. The current review details pertinent similarities and differences between human and mouse salivary glands and offers practical guidelines for using both for research purposes.