Busulfan-based regimens and allogeneic bone marrow transplantation in patients with myelodysplastic syndromes

Preparative regimens containing busulfan (BU) followed by allogeneic bone marrow transplantation (BMT) were used in 27 consecutive patients with myelodysplastic syndromes (MDS). The median age was 33 years (range, 4 to 54). Ten were female and 17 male. Sixteen patients had primary MDS, 11 other patients had antecedent hematologic diseases or developed MDS after cytotoxic and/or radiation therapy. Six patients had leukemic transformation and received antileukemic therapy before BMT. Pre-BMT cytogenetic studies showed complex chromosomal abnormalities in 13 patients, a simple abnormality in 5 patients, and normal chromosome in 8 patients. Three BU-based preparative regimens were used: 1 patient received BU 4 mg/kg orally (PO) daily for 4 days and cyclophosphamide (CY) 50 mg/kg intravenously (IV) daily for 4 days (BUCY-4); 24 patients received BU 4 mg/kg PO daily for 4 days, cytosine arabinoside (ara-C) 2 g/m2 IV every 12 hours for 4 doses, and CY 60 mg/kg IV daily for 2 days (BAC); and 2 patients with preceding Fanconi anemia received BU 2 mg/kg PO daily for 4 days followed by total lymphoid irradiation of 5 Gy. Seventeen of 27 patients are alive with no evidence of disease. Ten patients have died: 2 from hepatic veno-occlusive disease, 3 from sepsis, 1 from a cerebral bleed, 1 from a massive gastrointestinal (GI) bleed associated with acute graft-versus-host disease, 1 from hemolytic uremic syndrome with adult respiratory distress syndrome, 1 from bronchiolitis obliterans, and the only patient who did not engraft died from acute myeloid leukemia. Regimen-related toxicities (RRT) include GI tract (diarrhea, 14; stomatitis, 11), liver (9), cardiac (1), and skin (5). Patients who received a genotypically matched marrow graft had a significantly better disease-free survival (DFS) than patients who received a nongenotypic marrow graft (P = .02). The Kaplan-Meier analysis projects an overall DFS of 56% +/- 13% and 78% +/- 10% for patients who received a genotypically matched marrow graft. With the exception of a child who did not engraft, there was no relapse of MDS or leukemia. Excellent DFS, acceptable RRT, and the ease of administration are advantages of this regimen.     

Sustained activity in the medial wall during working memory delays

We have taken advantage of the temporal resolution afforded by functional magnetic resonance imaging (fMRI) to investigate the role played by medial wall areas in humans during working memory tasks. We demarcated the medial motor areas activated during simple manual movement, namely the supplementary motor area (SMA) and the cingulate motor area (CMA), and those activated during visually guided saccadic eye movements, namely the supplementary eye field (SEF). We determined the location of sustained activity over working memory delays in the medial wall in relation to these functional landmarks during both spatial and face working memory tasks. We identified two distinct areas, namely the pre-SMA and the caudal part of the anterior cingulate cortex (caudal-AC), that showed similar sustained activity during both spatial and face working memory delays. These areas were distinct from and anterior to the SMA, CMA, and SEF. Both the pre-SMA and caudal-AC activation were identified by a contrast between sustained activity during working memory delays as compared with sustained activity during control delays in which subjects were waiting for a cue to make a simple manual motor response. Thus, the present findings suggest that sustained activity during working memory delays in both the pre-SMA and caudal-AC does not reflect simple motor preparation but rather a state of preparedness for selecting a motor response based on the information held on-line.     

Epinephrine in digital blocks: revisited

STATEMENT OF PROBLEM: Implant treatment in the United Kingdom has been provided mainly in specialist, regional dental hospitals. However, increasingly, general dentists are providing implant-supported prostheses in a private office setting. PURPOSE: This study investigated the nature, timing, and frequency of complications associated with single tooth implant therapy in a dental hospital and two dental offices. METHODS: The dental records of 58 patients provided with 76 implants during the period of 1989-95 were reviewed retrospectively. Fifty-three single tooth crowns on implants were placed by general dentists and 23 by specialists in the dental hospital. RESULTS: Implant survival rate was 96%. Twenty-eight guided bone regeneration procedures were required, including 13 unplanned ones. Prosthodontic complications included the need for recontouring of three crowns and the recementation of three crowns. Only two abutment screws required retightening. Peri-implant soft tissue inflammation occurred around six crowns and recession around two. CONCLUSION: The single tooth implant-supported crown appears to be an effective and durable restorative treatment with a relatively low prevalence of postoperative complications.     

Center-specific graft and patient survival rates: 1997 United Network for Organ Sharing (UNOS) report

CONTEXT: Multiple comprehensive, risk-adjusted studies evaluating short-term surgical mortality have been reported previously. This report analyzes short-term and long-term outcomes, both nationally and at each individual transplant program, for all solid organ transplantations performed in the United States. OBJECTIVES: To report graft and patient survival rates for all solid organ transplantations, both nationally and at each specific transplant program in the United States, and to compare the expected survival rate with the actual survival rate of each individual program. DESIGN AND SETTING: Multivariate regression analysis of donor and recipient factors affecting graft and patient survival of all kidney, liver, pancreas, heart, lung, and heart-lung transplants reported to the United Network for Organ Sharing from 742 separate transplant programs. PATIENTS: A cohort of 97587 solid organ transplantations performed on 92966 recipients in the United States from January 1988 through April 1994. MAIN OUTCOME MEASURES: Short-term and conditional 3-year national and individual transplant program graft and patient survival rates overall and from 2 separate eras (era 1, January 1988-April 1992; era 2, May 1992-April 1994); comparison of actual center-specific performance with risk-adjusted expected performance and identification of centers with better-than-expected or worse-than-expected survival rates. RESULTS: One-year graft follow-up exceeded 98% and conditional 3-year follow-up exceeded 91% for all organs. Graft and patient survival improved significantly in era 2 compared with era 1 for all cadaver organs except heart, which remained the same. One-year cadaveric graft survival ranged from 81.5% for heart to 61.9% for heart-lung and 3-year conditional graft survival ranged from 91.3% for pancreas to 74.7% for lung. The percentage of programs whose actual 1-year graft survival was not different from or was better than their risk-adjusted expected survival ranged from 98.3% for heart-lung to 75.7% for liver. Most kidney, liver, and heart programs whose actual survival was significantly less than expected performed small numbers (less than the national average) of transplantations per year. CONCLUSIONS: Graft and patient survival for solid organ transplantations showed improvement over time. Conditional 3-year graft and patient survival rates were approximately 90% for all organs except for lung and heart-lung. The conditional 3-year survival rates were better than 1-year survival rates, indicating the major risk after transplantation occurs in the first year. The majority of transplant programs achieved actual survival rates not significantly different from their expected survival rates. Center effects were most significant within the first year after transplantation and had much less influence on long-term survival outcomes.     

Catecholamine response during 12 days of high-altitude exposure (4, 300 m) in women

Atrial natriuretic peptide (ANP) has been considered a potential candidate participating in the inhibitory control of pituitary-adrenal secretory activity. Here, we investigated the influence of ANP, infused at two different doses and over infusion intervals of two different durations, on the release of ACTH and cortisol after stimulation with CRH and with combined administration of CRH and vasopressin (VP). In young healthy men, three experiments were conducted. In Exp I, ACTH/cortisol secretory responses to CRH (50 microg) were examined during and after a 45-min period of ANP infusion at a rate of 4.4 microg/min (starting 15 min before CRH injection). In Exp II, ACTH/cortisol secretory responses to CRH (50 microg) were examined during and after a 90-min infusion period of ANP administered at rates of 4.4 and 8.8 microg/min. In Exp III, ANP was infused at a rate of 4.4 microg/min over 90 min, but instead of CRH, a combined administration of CRH (50 microg) and VP (0.5 IU infused within 5 min) was employed to stimulate ACTH/cortisol release. ANP diminished pituitary-adrenal secretory responses within the first hour after stimulation with exogenous secretagogues. Thereafter, the effect of ANP turned in the opposite direction, with distinctly enhanced concentrations of ACTH and cortisol during the third hour after stimulation. The inhibitory effect of ANP during the first hour of the pituitary-adrenal response was more pronounced on concentrations of cortisol than ACTH and was also more pronounced after combined administration of CRH/VP than after stimulation with CRH alone. Increasing the dose of ANP enhanced the late stimulatory effect on ACTH/cortisol release, thereby terminating the early period of inhibited ACTH/cortisol release more abruptly. The late stimulatory effect was enhanced with prolonged infusion of ANP. In addition, it was associated with reduced hematocrit, increased urine volumes collected, increased heart rate, and enhanced plasma VP concentrations. Together, these changes suggest that the late stimulatory effect of ANP on ACTH/cortisol release reflects an effect secondary to its hypovolemic actions. This stimulatory effect originating from peripheral systemic actions of ANP after exogenous administration appears to override a more direct inhibitory action of the peptide on pituitary-adrenal secretory activity. Therefore, we would expect that with localized release into portal hypophyseal blood the inhibitory component of the action of ANP on pituitary-adrenal secretory activity prevails.     

Anticipatory dementia: a link between memory appraisals and concerns about developing Alzheimer's disease

This exploratory study examines the link between memory appraisals and personal concerns about developing Alzheimer's disease. The sample of persons ages 40-60 includes adult children with a living parent who has Alzheimer's disease (N = 25) and a matched group with no family history of dementia (N = 25). Using two composite measures of memory appraisals, the results show significant bivariate and multivariate relationships between self-assessments of memory functioning and concerns about developing the disease. The findings also suggest that negative memory appraisals evoke concerns about developing Alzheimer's disease within both of the subsamples.     

Denervation of pigment cells lead to a receptor that is ultrasensitive to melatonin and noradrenaline

Pigment granule aggregation and dispersal can be studied in the melanophores of isolated scales from the cuckoo wrasse (Labrus ossifagus L.). Stimulation of a melanophore alpha2-adrenoceptor or the sympathetic nerve innervating the cell causes pigment aggregation. When the stimulation ceases, the pigment granules disperse throughout the cell. Studying this migration has been a useful tool in pharmacological research, particularly in investigations of the alpha2-adrenoceptor. Denervation of melanophores creates a receptor that is ultrasensitive to noradrenaline and melatonin. After three to four weeks of isolation, the denervated melanophores exhibit a 10(9)-fold increase in sensitivity. The efficacy of melatonin is increased from a negligible pigment-aggregation ability to the level of a full agonist. The melatonin-induced aggregation can, however, be counteracted by the alpha2-adrenoceptor antagonist yohimbine, but not by alpha1-adrenoceptor antagonist prazosin, indicating that the ultrasensitive receptor possesses alpha2-adrenoceptor features. Consequently, we conclude that the ultrasensitive receptor may represent an alpha2-adrenoceptor that has, due to denervation of the melanophore, become sensitive to melatonin.     

Animal models of respiratory syncytial virus infection

Over the past two decades, animal models of respiratory syncytial virus (RSV) infection have been developed using primates, cotton rats, mice, calves, guinea pigs, ferrets, and hamsters. Use of these models has shed light on the mechanisms of vaccine-enhanced disease seen in clinical trials of a formalin-inactivated RSV vaccine and has provided a means for testing efficacy and safety of candidate prophylactic and therapeutic strategies. The development of multiple animal models has coincided with the realization that RSV disease in humans is a multifaceted disease whose clinical manifestations and sequelae depend upon age, genetic makeup, immunologic status, and concurrent disease within subpopulations. There is no single human subpopulation in whom all forms of RSV disease manifest, nor is there a single animal model that duplicates all forms of RSV disease. The choice of an experimental model will be governed by the specific manifestation of disease to be studied.