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Anxiety is common in those with medical conditions and has significant impacts on mental well‐being as well as physical health outcomes. While several systematic reviews have examined the prevalence of anxiety in specific dermatological conditions, no reviews have examined the prevalence across the entire dermatology outpatient setting. This systematic review aims to provide an overview to dermatologists of the prevalence of, and trends in, anxiety in their outpatient clinics. As such, prevalence of anxiety in dermatology outpatient clinics was examined, and variations across type of anxiety and dermatological conditions were assessed. A search of PubMed, Embase, Cochrane and PsycINFO was conducted for studies that assessed anxiety prevalence in dermatology outpatients, with the last search conducted on 7 September 2022. Results underwent title/abstract and full‐text screening, followed by data extraction. Studies of patients 16 years and older and representative of dermatology clinics were included. Risk of bias was assessed using Joanna Briggs Institute Critical Appraisal Checklist. Meta‐analysis was conducted using CMA software, and subgroup analysis was conducted on relevant variables. 5423 studies were identified, and 32 included, with a total n = 12,812 participants. Under the random effects model, prevalence was estimated at 26.7% (95%CI 22.4–31.4; 95%PI 9.7–55.4). Subgroup analysis revealed a higher prevalence among studies of psoriasis patients than general dermatology studies. Estimates of prevalence were higher when assessed via self‐report screening than diagnostic interview. Anxiety occurred frequently among dermatology outpatients, especially psoriasis outpatients, at a higher rate than common estimates of prevalence in the general population. Given the effect of anxiety on patient outcomes and well‐being, dermatologists are encouraged to consider how anxiety may impact patients in their clinic, and how they can best identify patients with anxiety and subsequently support them. [ABSTRACT FROM AUTHOR]

We expand on a recent determination of the first global energy spectrum of the ocean's surface geostrophic circulation (Storer et al., 2022, https://doi.org/10.1038/s41467-022-33031-3) using a coarse‐graining (CG) method. We compare spectra from CG to those from spherical harmonics by treating land in a manner consistent with the boundary conditions. While the two methods yield qualitatively consistent domain‐averaged results, spherical harmonics spectra are too noisy at gyre‐scales (>1,000 km). More importantly, spherical harmonics are inherently global and cannot provide local information connecting scales with currents geographically. CG shows that the extra‐tropics mesoscales (100–500 km) have a root‐mean‐square (rms) velocity of ∼15 cm/s, which increases to ∼30–40 cm/s locally in the Gulf Stream and Kuroshio and to ∼16–28 cm/s in the ACC. There is notable hemispheric asymmetry in mesoscale energy‐per‐area, which is higher in the north due to continental boundaries. We estimate that ≈25%–50% of total geostrophic energy is at scales smaller than 100 km, and is un(der)‐resolved by pre‐SWOT satellite products. Spectra of the time‐mean circulation show that most of its energy (up to 70%) resides in stationary eddies with characteristic scales smaller than (<500 km). This highlights the preponderance of "standing" small‐scale structures in the global ocean due to the temporally coherent forcing by boundaries. By coarse‐graining in space and time, we compute the first spatio‐temporal global spectrum of geostrophic circulation from AVISO and NEMO. These spectra show that every length‐scale evolves over a wide range of time‐scales with a consistent peak at ≈200 km and ≈2–3 weeks. Plain Language Summary: Traditionally, "eddies" are identified as time‐varying features relative to a background time‐mean flow. As such, "mean" does not imply large length‐scale. Standing eddies or meanders due to topography have little time‐variation, but can have significant energy at small length‐scales that are unresolved and need to be parameterized in coarse climate simulations. Similarly, "eddy" or "time‐varying" do not imply small length‐scale, such as large‐scale motions from Rossby waves or fluctuations of the Kuroshio. Another common method is Fourier analysis in "representative" ocean boxes that cannot capture the circulation's planetary scales. We overcome these limitations thanks to recent advances: (a) a method for calculating spectra by coarse‐graining, (b) properly defining convolutions on the sphere, which "blur" oceanic flow in a way that preserves its underlying symmetries, opening the door for global "wavelet" analysis and, more generally, spatial coarse‐graining, and (c) FlowSieve: an efficient parallel code. We employ coarse‐graining in space‐time to gain new insights into the global oceanic circulation, including how much energy resides in its different spatial structures and how they vary in time. Key Points: Coarse‐graining, which disentangles flow concurrently in scale and space, reveals hemispheric asymmetry in mesoscale energy‐per‐area due to boundariesCoarse‐graining spectra of the time‐mean velocity show that most (up to 70%) of its energy resides in "standing" small‐scale eddies <500 kmWe estimate that ≈25%–50% of total geostrophic energy is at scales smaller than 100 km, and is un(der)‐resolved by pre‐SWOT satellite products [ABSTRACT FROM AUTHOR]

Recent studies have reported that statin use may be associated with improved outcomes in patients with sepsis or respiratory viral infections. In the setting of allogeneic hematopoietic cell transplantation (HCT), it has been shown that donor and recipient statin use is associated with reduced risks of GVHD. We assessed in retrospective analysis whether donor or recipient statin use impacts infection risk after allogeneic HCT (n=1191). Although recipient statin use was associated with the increased incidence of Gram-negative bacteremia (adjusted hazard ratio (aHR) 2.22, (95% confidence interval (CI) 1.2-4.2), P=0.01) without affecting mortality, donor statin use was associated with an increased incidence of respiratory viral infections in recipients (aHR 2.84 (95% CI 1.3-6.0), P=0.007). The overall incidence of invasive fungal infections and CMV reactivation and CMV disease were not impacted by recipient or donor statin use. In conclusion, this study suggests that recipient or donor statin use may be associated with an increased incidence of some infections without adversely affecting mortality. [ABSTRACT FROM AUTHOR]

Minimal residual disease (MRD) is associated with adverse outcome in acute myeloid leukemia (AML) after myeloablative (MA) hematopoietic cell transplantation (HCT). We compared this association with that seen after nonmyeloablative (NMA) conditioning in 241 adults receiving NMA (n=86) or MA (n=155) HCT for AML in first remission with pre-HCT bone marrow aspirates assessed by flow cytometry. NMA patients were older and had more comorbidities and secondary leukemias. Three-year relapse estimates were 28% and 57% for MRDneg and MRDpos NMA patients, and 22% and 63% for MA patients. Three-year overall survival (OS) estimates were 48% and 41% for MRDneg and MRDpos NMA patients and 76% and 25% for MA patients. This similar OS after NMA conditioning was largely accounted for by higher non-relapse mortality (NRM) in MRDneg (30%) compared with MRDpos (10%) patients, whereas the reverse was found for MRDneg (7%) and MRDpos (23%) MA patients. A statistically significant difference between MA and NMA patients in the association of MRD with OS (P<0.001) and NRM (P=0.002) but not relapse (P=0.17) was confirmed. After adjustment, the risk of relapse was 4.51 times (P<0.001) higher for MRDpos patients. These data indicate that the negative impact of MRD on relapse risk is similar after NMA and MA conditioning. [ABSTRACT FROM AUTHOR]

We hypothesized that clinical risk factors could be identified within 2 weeks of onset of severe (stage 3 or 4) acute gut GVHD for identifying a patient population with a very poor outcome. Among 1462 patients who had allogeneic hematopoietic cell transplantation (HCT) between January 2000 and December 2005, 116 (7.9%) developed stage 3-4 gut GVHD. The median time for onset of stage 3-4 gut GVHD was 35 (4-135) days after allogeneic HCT. Eighty-five of the 116 patients (73%) had corticosteroid resistance before or within 2 weeks after the onset of stage 3-4 gut GVHD. Significant risk factors for mortality included corticosteroid resistance (hazards ratio (HR)=2.93; P=0.0005), age >18 years (HR=4.95; P=0.0004), increased serum bilirubin (HR 2.53; P=0.0001) and overt gastrointestinal bleeding (HR 2.88; P=0.0004). Among patients with stage 3-4 gut GVHD, the subgroup with 0, 1 or 2 risk factors had a favorable prognosis, whereas the subgroup with 3 or 4 risk factors had a dismal prognosis. This information should be considered in designing future studies of severe gut GVHD and in counseling patients about prognosis. [ABSTRACT FROM AUTHOR]

Chronic GVHD (cGVHD) is associated with mortality, disability and impaired quality of life. Understanding the role of comorbidity in patients with cGVHD is important both for prognostication and potentially for tailoring treatments based on mortality risks. In a prospective cohort study of patients with cGVHD (n=239), we examined the performance of two comorbidity scales, the Functional Comorbidity Index (FCI) and the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI). Both scales detected a higher number of comorbidities at cGVHD cohort enrollment than pre-hematopoietic cell transplant (HCT) (P<0.001). Higher HCT-CI scores at the time of cGVHD cohort enrollment were associated with higher non-relapse mortality (HR: 1.21:1.04-1.42, P=0.01). For overall mortality, we detected an interaction with platelet count. Higher HCT-CI scores at enrollment were associated with an increased risk of overall mortality when the platelet count was 100 000/μL (HR: 2.01:1.20-3.35, P=0.01), but not when it was >100 000/μL (HR: 1.05:0.90-1.22, P=0.53). Comorbidity scoring may help better to predict survival outcomes in patients with cGVHD. Further studies to understand vulnerability unrelated to cGVHD activity in this patient population are needed. [ABSTRACT FROM AUTHOR]

Developing a preclinical canine model that predicts outcomes for hematopoietic cell transplantation in humans requires a model that mimics the degree of matching between human donor and recipient major histocompatibility complex ( MHC) genes. The polymorphic class I and class II genes in mammals are typically located in a single chromosome as part of the MHC complex. However, a divergent class I gene in dogs, designated dog leukocyte antigen-79 ( DLA-79), is located on chromosome 18 while other MHC genes are on chromosome 12. This gene is not taken into account while DLA matching for transplantation. Though divergent, this gene shares significant similarity in sequence and exon-intron architecture with other class I genes, and is transcribed. Little is known about the polymorphisms of DLA-79 and their potential role in transplantation. This study was aimed at exploring the reason for high rate of rejection seen in DLA-matched dogs given reduced intensity conditioning, in particular, the possibility that DLA-79 allele mismatches may be the cause. We found that about 82% of 407 dogs typed were homozygous for a single, reference allele. Owing to the high prevalence of a single allele, 87 of the 108 dogs (∼80%) transplanted were matched for DLA-79 with their donor. In conclusion, we have developed an efficient method to type alleles of a divergent MHC gene in dogs and identified two new alleles. We did not find any statistical correlation between DLA-79 allele disparity and graft rejection or graft-versus-host disease, among our transplant dogs. [ABSTRACT FROM AUTHOR]

Allogeneic stem cell transplant for multiple myeloma (MM) is one treatment associated with long-term disease-free survival. The high incidence of treatment-related mortality and relapses, however, are important reasons for controversy about the role of allografting in the management of MM. We reviewed our results of allografting for MM spanning a period of 34 years in order to better define long-term outcomes and identify areas of progress as well as areas requiring improvement. A total of 278 patients received allogeneic marrow or PBSCs after high-dose myeloablative (N=144) or reduced intensity, non-myeloablative (N=134) regimens. In multivariable analysis, adjusting for differences in patient groups, reduced intensity/non-myeloablative transplants were associated with significantly less acute GVHD, lower transplant mortality, better PFS and overall survival. There were no significant differences in relapse, progression or chronic GVHD, when adjusted. In multivariable analysis of patients receiving only non-myeloablative transplants, decreased overall survival and PFS were associated with relapse after a prior autograft and a β2 microglobulin >4.0. Transplant mortality was reduced and only influenced by a prior tandem autograft. [ABSTRACT FROM AUTHOR]

Survival rates after myeloablative hematopoietic cell transplantation (HCT) in childhood have improved. We conducted a cross-sectional study evaluating the quality of life (QOL) of 214 adult survivors of a childhood HCT compared with controls using standardized self-report measures with strong psychometric properties to evaluate physical function, psychological function and cognitive symptoms. From these results we conducted a multivariate analysis of risk factors. This analysis for physical functioning showed poorer function among myeloid disease survivors compared with patients with all other diagnoses (P=0.02), men functioned better than women (P=0.05) and those >18 years after transplant functioned more poorly than those <18 years after transplant (P=0.05). Psychological functioning showed that those who received more therapy and females were more likely to be depressed (P=0.03) and (P=0.005). Perceived cognitive symptoms showed that female survivors had more symptoms than male survivors (P=0.01), and those receiving more preceding therapy compared with those with less preceding therapy (P=0.001) or cranial irradiation compared with those without cranial irradiation (P=0.002) had more perceived cognitive symptoms. Overall, these data indicate that the majority of adult survivors of a childhood transplant are functioning well, but some have problems that need to be addressed. [ABSTRACT FROM AUTHOR]

We evaluated the pharmacokinetics and efficacy of oral mycophenolate mofetil (MMF) for treatment of refractory GVHD. In a prospective study of acute GVHD, 9 of 19 patients (47%) had a response and 10 (53%) had no improvement. Survival at 6 and 12 months after the start of MMF was 37 and 16%, respectively. In a retrospective study of acute GVHD, 14 of 29 patients (48%) had a response and 15 (52%) had no improvement. Survival at 6 and 12 months was 55 and 52%, respectively. In a prospective study of chronic GVHD, the cumulative incidence of disease resolution and withdrawal of all systemic immunosuppressive treatment was 9, 17 and 26% at 12, 24 and 36 months, respectively, after starting MMF. Thirteen patients (59%) required additional systemic immunosuppressive treatment for chronic GVHD. Nine of the 42 patients (21%) in the prospective studies discontinued MMF treatment because of toxicity. The area under the curve plasma concentrations of mycophenolic acid seemed to be suboptimal among patients with acute GVHD but not among those with chronic GVHD. MMF can be used effectively for treatment of GVHD. [ABSTRACT FROM AUTHOR]

We previously reported a 25% incidence of serious graft-versus-host disease (GVHD) (that is, acute or chronic GVHD that caused death, lengthy hospitalization or disability, or resulted in recurrent major infections) among 171 hematopoietic cell transplantation (HCT) recipients after nonmyeloablative (NMA) regimen. Here we present a retrospective study applying the same criteria to 264 recipients of peripheral blood HCT after myeloablative (MA) regimen, and compare the results with the previous study after additional follow-up. The MA group was younger and had lower comorbidity scores at HCT than those in the NMA group. The overall incidence of serious GVHD was 17% (44/264) in the MA group versus 28% (48/171) in the NMA group. The adjusted hazard ratio (HR) of serious GVHD in the MA group compared to the NMA group was 0.65 (95% CI, 0.4–1.1); P=0.13, and if follow-up was censored at the onset of recurrent or progressive malignancy, HR was 0.67 (95% CI, 0.4–1.3), P=0.22. We conclude that the choice between MA and NMA regimens does not greatly affect the risk of serious GVHD as an overall indicator of outcomes related to either acute or chronic GVHD. Serious GVHD may be considered as an endpoint in clinical trials with GVHD-related outcomes.Bone Marrow Transplantation (2008) 41, 887–893; doi:10.1038/sj.bmt.1705987; published online 21 January 2008 [ABSTRACT FROM AUTHOR]

Myeloablative conditioning regimens commonly lead to prolonged anorexia and poor oral intake. In a prospective study of 147 patients receiving CY, total body irradiation and allogeneic hematopoietic cells, we determined the extent of decline in oral intake and assessed plasma cytokine levels and development of acute GVHD as explanations for protracted anorexia. For each patient, daily oral caloric intake was expressed as a percent of estimated basal requirements, calculated as basal energy expenditure, through day 20. Oral caloric intake was significantly reduced in 92% of patients and remained low. The nadir in oral intake occurred at days 10–12, when median oral caloric intake was 3% of basal energy requirements. Plasma cytokines known to affect appetite (IL2, IL6, tumor necrosis factor-alpha) were significantly elevated above normal following conditioning therapy (P<0.001 for each cytokine). Acute GVHD did not appear to affect oral intake to transplant day 20 in this cohort of patients; however, plasma levels of IL6 rose steeply before the clinical onset of GVHD. Persistent fever occurred with the greatest frequency in patients with most profound reduction in oral intake. We conclude that prolonged alterations in oral intake following this myeloablative regimen may be related to circulating cytokines known to alter eating behavior.Bone Marrow Transplantation (2007) 40, 765–772; doi:10.1038/sj.bmt.1705816; published online 13 August 2007 [ABSTRACT FROM AUTHOR]

Transplant outcome was analyzed in 150 patients with myelodysplastic syndrome (MDS) or acute myelogenous leukemia transformed from MDS (tAML) conditioned with nonmyeloablative or myeloablative regimens. A total of 38 patients received nonmyeloablative regimens of 2 Gy total body irradiation alone (n=2) or with fludarabine (n=36), 90mg/m2. A total of 112 patients received a myeloablative regimen of busulfan, 16mg/ kg (targeted to 800-900 ng/ml), and cyclophosphamide 120 mg/ kg. Nonmyeloablative patients were older (median age 62 vs 52 years, P<0.001), more frequently had progressed to tAML (53 vs 31%, P=0.06), had higher risk disease by the International Prognostic Scoring System (53 vs 30%, P=0.004), had higher transplant specific comorbidity indices (68 vs 42%, P=0.01) and more frequently had durable complete responses to induction chemotherapy (58 vs 14%). Three-year overall survival (27%/48% (P=0.56)), progression-free survival (28%/4 44%, (P=0.60)), and nonrelapse mortality (41%/34%, (P=0.94)) did not differ significantly between nonmyeloblative/myeloablative conditioning. Overall (HR=0.9, P=0.84) and progression-free survivals (HR=1, P=0.93) were similar for patients with chemotherapy-induced remissions irrespective of conditioning intensity. Graft vs leukemia effects may be more important than conditioning intensity in preventing progression in patients in chemotherapy-induced remissions at the time of transplantation. Randomized prospective studies are needed to further address the optimal choice of transplant conditioning intensity in myeloid neoplasms. [ABSTRACT FROM AUTHOR]

This report examines the impact of graft composition on outcomes in 130 patients with hematological malignancies given unrelated donor granulocyte-colony-stimulating-factor-mobilized peripheral blood mononuclear cells (G-PBMC) (n = 116) or marrow (n = 14) transplantation after nonmyeloablative conditioning with 90 mg/m(2) fludarabine and 2 Gy TBI. The median number of CD34(+) cells transplanted was 6.5 x 10(6)/kg. Higher numbers of grafted CD14(+) (P = 0.0008), CD3(+) (P = 0.0007), CD4(+) (P = 0.001), CD8(+) (P = 0.004), CD3(-)CD56(+) (P = 0.003), and CD34(+) (P = 0.0001) cells were associated with higher levels of day 28 donor T-cell chimerism. Higher numbers of CD14(+) (P = 0.01) and CD34(+) (P = 0.0003) cells were associated with rapid achievement of complete donor T-cell chimerism, while high numbers of CD8(+) (P = 0.005) and CD34(+) (P = 0.01) cells were associated with low probabilities of graft rejection. When analyses were restricted to G-PBMC recipients, higher numbers of grafted CD34(+) cells were associated with higher levels of day 28 donor T-cell chimerism (P = 0.01), rapid achievement of complete donor T-cell chimerism (P = 0.02), and a trend for lower risk for graft rejection (P = 0.14). There were no associations between any cell subsets and acute or chronic GVHD nor relapse/progression. These data suggest more rapid engraftment of donor T cells and reduced rejection rates could be achieved by increasing the doses of CD34(+) cells in unrelated grafts administered after nonmyeloablative conditioning. [ABSTRACT FROM AUTHOR]

We have studied the influence of cell subsets [CD34, CD3, CD4, CD8, CD14, CD20, natural killer (NK; CD3−/CD56+), NKT (CD3+/CD56+), DC1, and DC2 cells] of granulocyte colony-stimulating factor mobilized peripheral blood stem cells (PBSC) on early T-cell chimaerism and later clinical outcomes in 125 patients with haematological malignancies who received human leucocyte antigen (HLA)-matched related grafts after non-myeloablative conditioning. Conditioning consisted of 2 Gy total body irradiation (TBI) alone (n = 28), or 2 Gy TBI preceded by either 90 mg/m2 fludarabine (n = 62) or planned autologous haematopoietic cell transplantation (HCT) (n = 35). Post-transplant immunosuppression included mycophenolate mofetil and ciclosporin. Multivariate analysis showed that higher numbers of grafted NK cells predicted higher early T-cell chimaerism (P = 0·03), while higher numbers of B cells were associated with better clinical outcomes and a higher risk for chronic graft-versus-host disease (P = 0·05). Higher numbers of CD14+ cells were associated with worse overall survival (P = 0·03), while higher numbers of CD34+ cells showed better survival (P = 0·03). The addition of fludarabine or autologous HCT predicted higher early T-cell chimaerism (P = 0·001), while advanced donor age predicted lower chimaerism (P ≤ 0·02). Patients with aggressive diseases were at higher risk for relapse/disease progression, and shorter progression-free and overall survival (P < 0·01). These results suggest that the dosing of certain cellular subsets of PBSC products can influence important outcomes post-HCT after non-myeloablative conditioning. [ABSTRACT FROM AUTHOR]

Summary:The efficacy of allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning depends on the balance between the desirable antineoplastic effects of donor cells weighed against the undesirable morbidity of graft-versus-host disease (GVHD). Development of serious acute or chronic GVHD was analyzed retrospectively in 171 consecutive patients, who had related or unrelated nonmyeloablative HCT for hematologic malignancies. GVHD was defined as serious when it resulted in (1) death, (2) disability, (3) three or more major infections in 1 year, (4) prolonged hospitalization or (5) suicide or hospitalization for suicidal ideation. According to this definition, 43 of 171 (25%) patients developed serious GVHD with a median follow-up of 30 (range, 12-65) months. The incidence of serious GVHD was similar after related and unrelated HCT. Among the 43 patients with serious GVHD, 20 had grade III-IV acute GVHD, and 30 had extensive chronic GVHD. Among the 171 patients, seven had grade III acute GVHD and 84 had extensive chronic GVHD that did not meet criteria for serious GVHD. Assessment of serious GVHD provides additional useful information to acute GVHD grades and classification of limited and extensive chronic GVHD in describing the overall risk and impact complications caused by donor cells.Bone Marrow Transplantation (2005) 35, 277-282. doi:10.1038/sj.bmt.1704767 Published online 22 November 2004 [ABSTRACT FROM AUTHOR]

Features a study which tested the efficacy of polyclonal rabbit antiserum specific for human T cells before T cell-replete unrelated donor marrow transplantation. Serological matching of bone marrow donors; Administration of prophylaxis treatment to patients; Characteristics of cohorts.

Objectives: To evaluate whether smoking modifies the risk of endometrial cancer associated with body mass index (BMI), postmenopausal hormone use, and other hormonal factors.Methods: Using multivariate adjusted models we examined interview data from a population-based case-control study of Wisconsin women (n = 740 cases, n = 2,372 controls).Results: The relative risk for endometrial cancer associated with current smoking was 0.8 (95% CI: 0.6-1.0) compared to never smokers. No clear dose-response relationship was evident for pack-years smoked. When examined according to smoking status the risk associated with the highest quartile of BMI seemed to be greater among non-smokers (OR = 3.6, 95% CI: 2.4-5.3) than among current smokers (OR = 2.8, 95% CI: 1.4-5.6). Among postmenopausal women the risk associated with current use of postmenopausal hormones appeared to be greater among non-smokers (OR = 3.3, 95% CI: 2.3-4.9) than among current smokers (OR = 2.7. 95% CI: 1.3-5.5). Risk for long-term use (10 or more years) compared with never users was 8.3 (95% CI: 4.6-15.1) among never smokers and 2.5 (95% CI: 0.8-7.9) among current smokers. The risk associated with non-insulin-dependent diabetes was greater among non-smokers (OR = 2.5, 95% CI: 1.7-3.6) than current smokers (OR = 1.1, 95% CI: 0.4-3.1). There was no modifying effect of smoking on the risk associated with parity.Conclusion: These results suggest that smoking moderates the risk associated with endometrial cancer among women at greatest risk, specifically women who are obese or who use postmenopausal hormones. [ABSTRACT FROM AUTHOR]

Human narcolepsy is a neurological disorder known to be tightly associated with HLA-DQB1*0602. A clinically similar disorder has been described in various dog breeds. The canine form of the disease is inherited as an autosomal recessive disorder in Labrador retrievers and Doberman pinschers (canarc-1) but occurs sporadically in other breeds, most typically dachshunds and poodles. In this study, we have examined if there is a relationship between the development of narcolepsy and specific dog leukocyte antigen (DLA)-DQB1 alleles. Ninety-nine dogs were typed for DLA-DQB1-- 31 with narcolepsy and 68 control animals. Recent studies have linked the development of autosomal recessive canine narcolepsy to a disruption of the hypocretin receptor 2 (Hcrtr2) gene on the same chromosome as the canine MHC region (CFA12), but not close to the DLA. Four Hcrtr2-positive families (two Doberman pinscher families, one Labrador retriever family, one dachshund family) were analyzed at the DLA-DQ level. No relationship was found between narcolepsy and DLA in Hcrtr2-mediated narcolepsy but loose genetic linkage was observed (Zmax52.3 at q525%, m5 40). Bone marrow transplantation between two DLA identical affected (Hcrtr2 .../...) and unaffected (Hcrtr2 ¹/...) siblings was also performed and found not to be successful neither in transmitting narcolepsy nor in relieving the symptoms in Doberman pinschers. DLA-DQB1 was next studied in 11 dogs with sporadic (non-familial) narcolepsy and in unrelated control animals of the same and different breeds. The allelic and carrier frequencies of various DLA-DQB1 alleles were analyzed. There was no strong positive or negative correlation between the development of narcolepsy and specific DLA-DQB1 alleles. These results do not support the involvement of DLA-DQ in canine narcolepsy, whether of sporadic or familial origin. [ABSTRACT FROM AUTHOR]

Between 1985 and 1998, 161 patients with primary acute myeloid leukemia (AML) received T-replete bone marrow transplantation (BMT) from unrelated donors in Seattle. Median age was 30 (range 1–55) years. Conditioning for BMT consisted of cyclophosphamide and total body irradiation in 154 (96%) cases and graft-versus-host disease prophylaxis was the standard methotrexate and cyclosporine combination in 134 (83%) cases. Median post-transplant follow-up was 2.9 years. Leukemia-free survival (LFS) at 5 years was 50 ± 12% for transplants during first complete remission (n = 16), 28 ± 8% during second CR (n = 40), 27 ± 17% during subsequent CR (n = 8), 7 ± 3% during relapse (n = 81) and 19 ± 10% during primary induction failure (n = 16). The cumulative incidences of relapse were 19%, 23%, 25%, 44% and 63%, for the five groups, respectively. Transplantation during remission, a marrow cell dose above 3.5 × 108/kg, and cytomegalovirus seronegative status before BMT in both patient and donor were favorable prognostic factors. Adults in any CR who received a marrow cell dose above 3.5 × 108/mg had a LFS of 54 ± 9% at 5 years. These data extend our previous findings on the association between a high marrow cell dose and improved survival and support the use of unrelated donor BMT for treatment of patients with high risk AML when a family match is not available. Bone Marrow Transplantation (2000) 26, 397–404. [ABSTRACT FROM AUTHOR]

Objective: Although many studies have shown that higher weight increases the risk of postmenopausal breast cancer, some aspects of this association are unclear. In order to examine the risk associated with different patterns of weight change, we analyzed data from a large case-control study of postmenopausal breast cancer.Methods: Participants included women aged 50 79 years (n = 5031) who are newly diagnosed with invasive breast cancer in Massachusetts, New Hampshire, and Wisconsin. Similarly-aged population controls (n = 5255) were selected at random from driver's license files and Medicare beneficiary lists. Height, weight, and information on other breast cancer risk factors were ascertained by structured telephone interviews from 1992 to 1995, and logistic regression was used to estimate multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI).Results: Women in the top quintile groups for height at age 20, recent weight, and recent body mass index had significantly increased risks of breast cancer. Among women who reached their highest adult weight at younger ages (<45 years), increasing weight loss since that age was associated with a reduced risk of postmenopausal breast cancer (OR 0.90, CI 0.84 0.98, per 5 kg). However, weight loss among women whose highest weight occurred after age 45 was not associated with risk (OR 1.00, CI 0.95 1.05, per 5 kg). Weight gain since the lowest adult weight increased risk by 8% for each 5 kg of gain (OR 1.08, CI 1.06-1. 11). Temporary weight cycling (weight loss followed by weight gain) was not associated with increased risk.Conclusions: Weight gain clearly increased risk of postmenopausal breast cancer. These data lend further support to efforts aimed at helping women avoid weight gain as they age. [ABSTRACT FROM AUTHOR]

Background: The increased risk for esophageal adenocarcinoma associated with long-segment (> or =3 cm) Barrett esophagus is well recognized. Recent studies suggest that short-segment (<3 cm) Barrett esophagus is substantially more common; however, the risk for neoplastic progression in patients with this disorder is largely unknown.Objective: To examine the relation between segment length and risk for aneuploidy and esophageal adenocarcinoma in patients with Barrett esophagus.Design: Prospective cohort study.Setting: University medical center in Seattle, Washington.Patients: 309 patients with Barrett esophagus.Measurements: Patients were monitored for progression to aneuploidy and adenocarcinoma by repeated endoscopy with biopsy for an average of 3.8 years. Cox proportional hazards analysis was used to calculate adjusted relative risks and 95% Cls.Results: After adjustment for histologic diagnosis at study entry, segment length was not related to risk for cancer in the full cohort (P > 0.2 for trend). When patients with high-grade dysplasia at baseline were excluded, however, a nonsignificant trend was observed; based on a linear model, a 5-cm difference in segment length was associated with a 1.7-fold (95% CI, 0.8-fold to 3.8-fold) increase in cancer risk. Among all eligible patients, a 5-cm difference in segment length was associated with a small increase in the risk for aneuploidy (relative risk, 1.4 [CI, 1.0 to 2.1]; P = 0.06 for trend). A similar trend was observed among patients without high-grade dysplasia at baseline.Conclusions: The risk for esophageal adenocarcinoma in patients with short-segment Barrett esophagus was not substantially lower than that in patients with longer segments. Although our results suggest a small increase in risk for neoplastic progression with increasing segment length, additional follow-up is needed to determine whether the patterns of risk occurred by chance or represent true differences. Until more data are available, the frequency of endoscopic surveillance should be selected without regard to segment length. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses a case-control study on macrophage infiltration following acute graft-versus-host disease (GvHD).

Lee J A H [School of Public Health and Community Medicine, Department of Epidemiology SC 36, University of Washington, Seattle, USA] and Storer B E. Further Studies on skin melanomas apparently dependent on female sex hormones. International Journal of Epidemiology 1982, 11: 127–131. In the British Isles the incidence and mortality rates from melanoma of the skin have been shown to be higher in females than in males in the later years of reproductive life. In populations with higher rates for malignant melanoma of skin (Scandinavia, australasla etc), and also in Japan, where the rates are low, the of female to male deaths is lower than in the British Istes. However, a similar pattern of-agespecific sex ratios (risks for femals compared with males peaking at some age in the latter half of repoductive life, and relatively low in middle age) is found in these populations. This ‘gynaecologic’ factor is not an artifaft of interactions between age and yaer of birth effects, and apperears to act multiplicatively with other astiologic features. These findings have implications for studies of the aetiology and pathogenesis of malignant malanoma, as well as for the descriptive mathematical modelling of the rates for purposes of environemntal legislation. [ABSTRACT FROM PUBLISHER]

In vitro culture of human peripheral blood lymphocytes (PBL) with Daudi (Burkitt lymphoma) cells results in selective proliferation of Vγ9/Vλ52 T cells with high cytotoxicity against Daudi cells. After adoptive transfer into severe combined immunodeficient (SCID) mice, these cells exert specific anti-tumour activity against Daudi lymphoma. To test whether cytotoxic Vγ9/Vλ2 T cells are induced in SCID mice, human PBL injected intraperitoneally were stimulated with irradiated Daudi cells (PBL/ Daudi-SCID). After 7-14 days, PBL/Daudi-SCID had a significantly higher percentage of human γλ T cells in their peritoneal cavity, lymph nodes and blood than controls (PBL-SCID). DNA content analysis of T cell subsets from PBL/Daudi-SCID showed a significantly higher percentage of cells in S+G&sub2;+M phases of the cell cycle in the TCR-γλ-1+ than in CD3+ cell population. Human cells recovered from PBL/Daudi-SCID showed specific cytotoxicity against Daudi cells. PBL/Daudi- SCID inoculated with a lethal dose of Daudi lymphoma survived significantly longer than controls. This protection was specific for Daudi cells and was not mediated by murine natural killer (NK) cells. Thus human peripheral blood T cells grafted in SCID mice proliferate in response to antigen and confer specific immunity. [ABSTRACT FROM AUTHOR]

Purpose: The activity of 5-fluorouracil (5-FU) against colon cancer is enhanced by leucovorin and the combination of 5-FU and levamisole has activity in the adjuvant treatment of colonic malignancies. The combination of 5-FU with both leucovorin and levamisole may provide additional benefit in the treatment of colon cancer.Methods: A phase I study to assess qualitative and quantitative toxicities of this three-drug combination and to determine a dose for further phase II testing was undertaken. The role of levamisole as an immunomodulator was also assessed.Results: A group of 38 patients with incurable metastatic malignancies received 119 cycles of treatment at eight dose levels. 5-FU (375 mg/m2 per day) and leucovorin (200 mg/m2 per day) were administered intravenously (days 1-5). Levamisole was administered orally (days 1-3 and 15-17) at doses from 30 to 470 mg/m2 per day. Patients received both 5FU/leucovorin and 5-FU/leucovorin/levamisole in random order for their initial two cycles. All subsequent treatments were with the three-drug combination. Toxicities included nausea, vomiting, stomatitis, thrombocytopenia and granulocytopenia. Diarrhea was the dose-limiting toxicity at 470 mg/m2 per day levamisole. The addition of levamisole resulted in more toxicity than 5-FU and leucovorin alone. No clinical responses were seen with this regimen. The addition of levamisole resulted in more immunomodulation than 5-FU and leucovorin alone as evidenced by release of neopterin from monocytes.Conclusion: With this schedule and dose of 5-FU and leucovorin, the maximum tolerated dose of levamisole was 354 mg/m2. However, given the lack of response and the absence of dose-dependent immunomodulation, this may not be the appropriate dose for further phase 11 studies. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses hematopoietic cell transplantation comorbidity index (HCT-CI).

Presents a correction to the article "Serious Graft-Versus-Host Disease After Hematopoietic Cell Transplantation Following Nonmyeloablative Conditioning," in a previous issue of the periodical "Bone Marrow Transplantation."