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Purpose: Patients with malignancy sometimes develop painful mucositis and require patient-controlled analgesia (PCA) to treat their pain. Pain disrupts sleep and there is some evidence that analgesic medications also disrupt sleep. This study examined whether treatment with the sedative hypnotic eszopiclone could improve self-reports of sleep, fatigue, and pain as well as decrease opioid self-administered via PCA.Methods: Inpatients who developed mucositis severe enough to require PCA treatment were randomized double-blind to a 2-day trial on eszopiclone or placebo-administered at bedtime. Patients completed questionnaires which assessed sleep, pain, and fatigue. PCA medication was calculated in terms of morphine equivalents. Data were analyzed with unpaired t tests and repeated measures analysis of variance.Results: Twenty-two patients were randomized to placebo and 23 to eszopiclone. Groups were comparable in age and treatment characteristics. Mean pain scores were lower in the eszopiclone group at all time points (morning p = 0.01, afternoon p = 0.04, evening p = 0.04). The eszopiclone group reported increased sleep time (p < 0.05), fewer nighttime awakenings (p < 0.001), better self-reported sleep quality (p = 0.01), and depth (p = 0.04). There were no significant differences between eszopiclone and placebo in terms of self-reports of fatigue or opioid usage.Conclusion: Sedative hypnotic agents improve sleep and analgesia even in the setting of considerable pain and discomfort. [ABSTRACT FROM AUTHOR]

Background. Patients with anorexia nervosa (AN) overestimate their size despite being severely underweight. Whether this misperception echoes an underlying emotional disturbance or also reflects a genuine body-representation deficit is debatable. Current measures inquire directly about subjective perception of body image, thus distinguishing poorly between top-down effects of emotions/attitudes towards the body and disturbances due to proprioceptive disorders/distorted body schema. Disorders of body representation also emerge following damage to the right parietal lobe. The possibility that parietal dysfunction might contribute to AN is suspected, based on the demonstrated association of spatial impairments, comparable to those found after parietal lesion, with this syndrome. Method. We used a behavioral task to compare body knowledge in severe anorexics (n=8), healthy volunteers (n=11) and stroke patients with focal damage to the left/right parietal lobe (n=4). We applied a psychophysical procedure based on the perception, in the dark, of an approaching visual stimulus that was turned off before reaching the observer. Participants had to predict whether the stimulus would have hit/missed their body, had it continued its linear motion. Results. Healthy volunteers and left parietal patients estimated body boundaries very close to the real ones. Conversely, anorexics and right parietal patients underestimated eccentricity of their left body boundary. Conclusions. These findings are in line with the role the parietal cortex plays in developing and maintaining body representation, and support the possibility for a neuropsychological component in the pathogenesis of anorexia, offering alternative approaches to treatment of the disorder. [ABSTRACT FROM AUTHOR]

Autologous or allogeneic SCT with conventional conditioning (chemotherapy with or without irradiation) has emerged as an effective and potentially curative therapy in patients with hematologic malignancies and in other selected solid tumors; however, several patients experience significant early and delayed side effects, including long-term endocrine imbalance and infertility. In spite of several reproductive recovery and pregnancy reports published in the oncology literature, review of medical literature reveals a paucity of comparable information in the SCT field. We report here four cases of ovarian recovery in patients who received hormonal replacement therapy after diagnosis of primary ovarian failure due to high-dose chemotherapy and SCT.Bone Marrow Transplantation (2008) 41, 275–278; doi:10.1038/sj.bmt.1705893; published online 22 October 2007 [ABSTRACT FROM AUTHOR]

Background and purpose:Calcitonin gene-related peptide (CGRP), a capsaicin-sensitive neuromodulator of splanchnic vascular tone in several animal species, remains poorly investigated in mouse models. We therefore assessed whether endogenous CGRP is a non-adrenergic/non-cholinergic (NANC) neuromodulator in the mesenteric vascular bed of the mouse.Experimental approach:Arterial and venous changes in perfusion pressure in response to perivascular nerve stimulation (PNS) were monitored in the mouse mesenteric bed under basal conditions or precontracted with KCl (artery) or U46619 (vein) in circuits pretreated with guanethidine, atropine, indomethacin and prazosin. Arterial responses to NANC were also characterized with a CGRP1 antagonist, hαCGRP8−37. Finally, the PNS-induced release of arterial CGRP was measured by enzyme immunoassay.Key results:HαCGRP8−37 enhanced PNS-induced arterial increases in perfusion pressure under basal tone. PNS-induced stimulation of NANC triggered an hαCGRP8−37 or capsaicin- sensitive reduction in perfusion pressure of the pre-contracted arterial bed only. Chemical removal of the endothelium inhibited PNS- and hαCGRP- induced reduction in perfusion pressure in the arterial mesenteric bed. Responses to NANC nerves were reduced by guanylate and adenylate cyclase inhibitors (1H-[1,2,4]oxadiazole[4,3-a] quinoxalin-1-one (ODQ)) and [9-(tetrahydro-2-furanyl)-9H-purin-6-amine] (SQ 22 536), respectively. A neuronal NOS inhibitor (7-nitroindazole; 7-NI) also enhanced the response to NANC in vessels from wild-type, eNOS KO but not iNOS KO mice. Finally, PNS enhanced the release of immunoreactive CGRP from the perfused arterial mesenteric bed.Conclusions and implications:Our study demonstrates a role for CGRP in the NANC-dependent reduction in perfusion pressure of the arterial but not venous mesenteric bed of the mouse.British Journal of Pharmacology (2007) 152, 1049–1059; doi:10.1038/sj.bjp.0707475; published online 1 October 2007 [ABSTRACT FROM AUTHOR]

BACKGROUND: Interpatient variability in the kinetics of peripheral blood progenitor cell (PBPC) mobilization is commonly seen with conventional chemotherapy-based mobilization regimens. This necessitates the availability of leukapheresis (LP) facilities 7 days a week. STUDY DESIGN AND METHODS: The efficacy of an approach where LP was invariably commenced on Day 11 after intermediate-dose cyclophosphamide followed by sequential administration of granulocyte-macrophage-colony-stimulating factor (CSF) and granulocyte-CSF (Cy/GM/G) was retrospectively analyzed in 225 consecutive, unselected patients undergoing autologous hematopoietic stem cell transplantation for all diagnoses other than acute leukemia at our center. Cy/GM/G was scheduled to avoid weekend LP. RESULTS: After Cy/GM/G, a CD34+ cell yield of at least 2.0x10(6) per kg was achieved in 90.7 percent of patients. Optimal yield (OY; >or=5x10(6) or 10x10(6) CD34+ cells/kg depending on diagnosis) was achieved in 67.6 percent of patients. Only three patients (1.3%) required LP on Saturday or Sunday. Febrile neutropenia (FN) was encountered in 5.3 percent. PBPC yield was highest on Day 1 of LP (p<0.001). In multivariate analyses, platelet (PLT) count on Day 1 of LP (PLT-D1LP) was positively associated with achievement of OY (p<0.001). PLT-D1LP and diagnosis of myeloma were associated with a shorter time to achieve a CD34+ cell yield of at least 5x10(6) per kg (p<0.001 and p=0.002, respectively). CONCLUSION: Cy/GM/G with scheduled LP commencement on Day 11 enables optimal CD34+ cell yields in most patients undergoing autologous transplantation, despite a low risk of FN and avoidance of weekend LP. [ABSTRACT FROM AUTHOR]

Summary:Between January 1996 and July 2002, 72 patients with non-Hodgkin's lymphoma or Hodgkin's disease underwent high-dose chemotherapy with autologous stem cell transplant conditioned with either cyclophosphamide, etoposide, carmustine (CEB) or carmustine, etoposide, cytarabine, melphalan (BEAM) at a single institution. In all, 52 patients received CEB and 20 patients received the BEAM regimen. Patient characteristics that were significantly different between the two groups are tumor grade and extranodal involvement (P=0.0196, 0.0341, respectively). Regimen-related toxicities examined yielded only diarrhea occurring at a higher rate in the BEAM group (81 vs 51%, P=0.0026), although cases were milder (92 vs 57%). Patients treated with CEB developed mucositis at a slightly higher rate (79%) than patients treated with BEAM (75%), but this difference did not reach statistical significance. However, the mucositis that occurred within the BEAM group was predominately mild (67%) in contrast to the predominance of moderate to severe cases in the CEB group (74%). In addition, patients treated with CEB required growth factor support for a longer time than patients treated with BEAM (P=0.0399). Response rates were high in both groups, with trends favoring the BEAM group. Overall survival was higher after treatment with BEAM than with CEB (84 vs 60%).Bone Marrow Transplantation (2004) 34, 581-587. doi:10.1038/sj.bmt.1704637 Published online 26 July 2004 [ABSTRACT FROM AUTHOR]

Background The adequacy of HPC collection for BMT is typically assessed by the number of CD34 + cells. However, during a series of leukapheresis procedures (LP) the CD34 value on the final HPC product may not be available for testing until late evening, sometimes resulting in additional, retrospectively unnecessary, LP in order to ensure an adequate HPC collection (>5×10 6 CD34/kg). We hypothesized that an estimate of the CD34 content of HPC products prior to 16:00 h on the day of LP would permit improved HPC collection planning. We therefore assessed the effectiveness of predicting the total amount of CD34 cells that would be collected in a given LP by either (a) the concentration of CD34 cells/μL in peripheral blood prior to LP (pre-CD34) or (b) the predicted total amount of CD34 cells to be collected based on sampling the LP product at the mid-point of each LP. We also compared the number of LP per patient and total HPC collected for the study group with data from the previous calendar year. Methods Allogeneic and autologous BMT donors who completed a 20-L HPC collection between September 2002 and February 2003 were eligible. CD34 cells were measured on blood drawn prior to LP and from the HPC product at the mid-point (10 L) of LP. The CD34 content of the final LP was predicted by doubling the value of total CD34 cells at the mid-run (MRp-CD34). The MRp-CD34/kg and the cumulative CD34/kg collected were made available before 16:00 h and used to determine the need for additional LP. The true CD34 content of each HPC collection was also measured from the final product the next day (CD34-FP). Results A 20-L LP was completed and data were available from 31 patients and nine allogeneic donors who underwent a total of 85 LP for diagnoses, including 11 myeloma, 10 lymphoma, seven HD, three acute leukemia and five others. The mean (range) and correlation ( R 2 ) vs. the CD34-FP were, for pre-CD34, 54 CD34/μL (0.3-232), R 2 =0.66 ( P <0.01), and for MRp-CD34, 3.2 × 10 6 CD34/kg (0.04-22.48), R 2 =0.90 ( P <0.01). The mean number of CD34/kg collected per LP in the patients/donors was 3.4 × 10 6 CD34/kg (0.05-18.94). The median number of CD34 cells employed for transplant in the study group vs. controls (5.7 vs. 5.6 × 10 6 /kg) and the time to engraftment of neutrophils (12 vs. 11 days) and platelets (12 vs. 12 days) was similar to historical controls. However, the study group had a significantly lower median number of LP (three vs. two; P <0.02) to obtain the required collection of 5 × 10 6 CD34 cells/kg. Discussion Both the pre-CD34 and the MRp-CD34 were significantly correlated with CD34-FP. However, the CD34-FP was more reliably predicted by MRp-CD34. Early availability of mid-run CD34 values was associated with a significant reduction in the number of LP required to collect 5 × 10 6 CD34 cells/kg, without reduction in the number of CD34 cells for transplant or prolongation of days to neutrophil or platelet engraftment. [ABSTRACT FROM AUTHOR]

Summary:A 38-year-old woman with agnogenic myeloid metaplasia complicated by the poor prognostic factors of severe osteosclerosis, prominent hepatosplenomegaly, and profound anemia was treated with FLAG chemotherapy to decrease her organomegaly before undergoing a nonmyeloablative allogeneic stem cell transplant from a matched-sibling donor. The patient's pre- and post transplant course were complicated by an autoimmune disorder and her post transplant course was complicated by severe hepatic and gastrointestinal GVHD. A technetium-99m sulfur colloid scan 4 months post transplant and bone marrow studies 8 months post transplant demonstrated intramedullary hematopoiesis, complete resolution of marrow fibrosis, and partial resolution of osteosclerosis.Bone Marrow Transplantation (2003) 32, 581-585. doi:10.1038/sj.bmt.1704172 [ABSTRACT FROM AUTHOR]

The endothelin-converting enzyme (ECE) is the main enzyme responsible for the genesis of the potent pressor peptide endothelin-1 (ET-1). It is suggested that the ECE is pivotal in the genesis of ET-1, considering that the knockout o1 both genes generates the same lethal developments during the embryonic stage. Several isoforms of the ECE have been disclosed, namely ECE-1, ECE-2, and ECE-3. Within each of the first two groups, several sub-isoforms derived through splicing of single genes have also been identified. In this review, the characteristics of each subisoform fur ECE-1 and 2 will be discussed. It is important to mention that the ECE is, however, not the sole enzyme involved in the genesis of endothelins. Indeed, other moieties, such as chymase and matrix metalloproteinase II, have been suggested to be involved in the production of ET intermediates, such as ET-1 (1-31) and ET-1 (1-32), respectively. Other enzymes, such as the neutral endopeptidase 24-II, is curiously not only involved in the degradation and inactivation of ET-1, but is also responsible for the final production of the peptide via the hydrolysis of ET-1 (1-31). In this review, we will attempt to summarize, through the above-mentioned characteristics, the current wisdom on the role of these different enzymes in the genesis and termination of effect of the most potent pressor pcptide reported to date. [ABSTRACT FROM AUTHOR]

Background A proportion of candidates for high-dose chemotherapy with autologous PBPC support (HDC-PBPCS) will not provide an adequate PBPC yield from their first mobilization. The value of re-mobilization and the best regimen for re-mobilization in these patients is unclear. Methods: In 23 patients who failed to provide ≥ 3 × 10[sup 6] CD34[sup +] cells/kg after their first mobilization, PBPC were re-mobilized using a regimen of simultaneous administration of G-CSF and GM-CSF (10 μg/kg/day each) with leukaphereses (LP) starting Day 4 or 5 of CSF administration. Yields of WBC/kg, MNC/kg and CD34[sup +] cells/kg/L of processed blood total CD34[sup +] were compared between the first and second mobilization in each patient. The ability of the combined yield from the two mobilizations to achieve the desired threshold PBPC yield and the tolerability of the re-mobilization were determined. Results: The re-mobilization regimen was well-tolerated and no patient discontinued the regimen because of toxicity. Median collected WBC/kg/L (1.37 × 10[sup 7] versus 2.62 × 10[sup 7], p = 0.0065), MNC/kg/L (0.77 × 10[sup 7] versus 1.97 × 10[sup 7], p = 0.0003), CD34[sup +]cells/kg/L (1.64 × 10[sup 7] versus 4.18 × 10[sup 7], p = 0.001) were significantly higher after the second mobilization (G-CSF/GM-CSF combination). Percentage of CD34[sup +] cells in the leukapheresis was also significantly higher after the second mobilization (median 0.104% versus 0.195%, p = 0.036). Twelve of 22 patients achieved the target PBPC dose (> 3 × 10[sup 6]/CD34[sup +] cells/kg) after two mobilizations (six patients achieved the target from the second mobilization alone). A further eight underwent HDC-PBPCS without achieving the target PBPC dose. These patients experienced a significant delay in neutrophil and platelet engraftment when compared with those patients achieving the target dose. Discussion: This study demonstrates that the combination of G-CSF and GM-CSF is an effective and tolerable method for re-mobilization of PBPC in patients who fail to provide an adequate yield from their first mobilization. [ABSTRACT FROM AUTHOR]

We report two cases of refractory chronic graft-versus-host disease after donor lymphocyte infusions in which the skin lesions improved dramatically with the use of intravenous pulses of lidocaine. This form of therapy has been used successfully for the cutaneous involvement of scleroderma and may have vasodilator and anti-inflammatory effects. Bone Marrow Transplantation (2001) 28, 97–99. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor related to T-cell depletion.

The medical use of low level laser (LLL) irradiation has been occurring for decades, primarily in the area of tissue healing and inflammatory conditions. Despite little mechanistic knowledge, the concept of a non-invasive, non-thermal intervention that has the potential to modulate regenerative processes is worthy of attention when searching for novel methods of augmenting stem cell-based therapies. Here we discuss the use of LLL irradiation as a "photoceutical" for enhancing production of stem cell growth/chemoattractant factors, stimulation of angiogenesis, and directly augmenting proliferation of stem cells. The combination of LLL together with allogeneic and autologous stem cells, as well as post-mobilization directing of stem cells will be discussed. [ABSTRACT FROM AUTHOR]

Critical limb ischemia (CLI) is an advanced form of peripheral artery disease which is responsible for approximately 100,000 amputations per year in the US. Trials to date have reported clinical improvement and reduced need for amputation in CLI patients receiving autologous bone marrow or mobilized peripheral blood stem cells for stimulation of angiogenesis. While such treatments are currently entering Phase III trials, practical and scientific pitfalls will limit widespread implementation if efficacy is proven. Hurdles to be overcome include: a) reduced angiogenic potential of autologous cells in aged patients with cardiovascular risk factors; b) invasiveness/adverse effects of bone marrow extraction and G-CSF mobilization, respectively; and c) need for on-site cellular manipulation. The Endometrial Regenerative Cell (ERC) is a mesenchymal-like stem cell derived from the menstrual blood that is believed to be associated with endometrial angiogenesis. We discuss the possibility of using allogeneic ERCs as an "off the shelf" treatment for CLI based on the following properties: a) High levels of growth factors and matrix metalloprotease production; b) Ability to inhibits inflammatory responses and lack of immunogenicity; and c) Expandability to great quantities without loss of differentiation ability or karyotypic abnormalities. [ABSTRACT FROM AUTHOR]

Presents a correction to the article "T-Cell Depletion Improves Outcome After Autologous Stem Cell Transplant in Patients With Systemic Lupus Erythematosus," previously published in the journal "Bone Marrow Transplantation."

Summary:At Northwestern University, a phase I/II trial of hematopoietic stem cell transplant (HSCT) for systemic lupus erythematosus (SLE) has shown promising results. A phase III HSCT trial is being developed to confirm efficacy of HSCT vs continuing the currently accepted standard of care, intravenous pulse cyclophosphamide.Bone Marrow Transplantation (2003) 32, S49-S51. doi:10.1038/sj.bmt.1703943 [ABSTRACT FROM AUTHOR]