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The objectives of this study were to establish reference values and define the determinants of left atrial appendage (LAA) flow velocities in the general population. LAA flow velocities (contraction and filling velocities) were assessed by transesophageal echocardiography in 310 subjects aged > or = 45 years, sampled from the population-based Stroke Prevention: Assessment of Risk in a Community study. All subjects were in sinus rhythm, with preserved left ventricular systolic function (ejection fraction > or = 50%), and without valvular disease. Values of LAA contraction and filling velocities were established for various age groups in the population. Age was negatively associated with LAA contraction and filling velocities, which decreased by 4.1 cm/s (p < 0.001) and 2.0 cm/s (p < 0.01) for every 10 years of age, respectively. Contraction velocities were 5 cm/s higher in men than in women (p < 0.05). After adjusting for age and sex, heart rate was independently associated with LAA contraction velocities (p < 0.001; nonlinear association). Body surface area, left atrial size, left ventricular mass index, and a history of previous cardiac disease or hypertension showed no significant association with LAA flow velocities (p > 0.05). Furthermore, detailed analysis of 24-hour ambulatory blood pressure data (available in 253 subjects) showed no association between various blood pressure parameters (systolic and diastolic blood pressure, out-of-bed and in-bed measurements) and LAA flow velocities (all p > 0.05). In summary, the present study establishes the reference values for LAA flow velocities in a large sample of the general population. LAA flow velocities progressively decline with age in subjects with preserved left ventricular systolic function. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim was to evaluate the well-being of professional pilots using a survey that included the World Health Organization (WHO)-5 Well-Being Index. METHODS: An electronic survey was sent to pilots between June 17-August 2, 2021. Pilots self-categorized as: airline transport pilot (ATP), commercial pilot, or both. Chi-squared and Fisher's exact tests were used to evaluate differences between variables. Logistic regression was used to estimate the odds of impaired well-being. RESULTS: A total of 639 individuals returned the survey. The majority of respondents were ATPs and a majority identified as male. The average well-being score was 68.0 out of 100 possible, with 22% of respondents meeting the threshold definition of impaired well-being. The odds of having impaired well-being were not dependent on gender. In unadjusted analysis, the odds of impaired well-being were higher for those flying as commercial pilots as compared to airline transport pilots/both. Age was also strongly associated with impaired well-being, with younger pilots having greater odds of impaired well-being as compared to older pilots. Only a little over half of the surveyed pilots agreed or strongly agreed that pilot risk of occupational exposure to COVID-19 was appropriately controlled. CONCLUSION: This survey suggests an important connection between pilot age and impaired well-being scores during the COVID-19 pandemic. Future studies targeting the well-being of younger pilots will be of interest. Additionally, measures to reduce occupational risk of COVID-19 exposure may be helpful in view of the substantial fraction of pilots expressing concern regarding that risk. Stratton E, Haddon R, Murad MH, Petterson T, Nelson M, Cowl CT. COVID-19 pandemic effects on the well-being of professional pilots . Aerosp Med Hum Perform. 2022; 93(10):734-738.

Background: Fibromyalgia (FM) is a contested, chronic widespread pain syndrome on which recommended therapies have short-lasting, moderate effects. Nevertheless, some patients become symptom-free, and their recovery experiences inspired us to develop a patient-centred recovery-oriented programme (PROP) delivered in a group format. Presently, we describe the theoretical rationale, purpose and content of the PROP, and its meanings for clinicians and patients., Methods: A multidisciplinary clinical team, a leader of a rehabilitation unit, and two researchers coproduced the PROP. Five full-day seminars were arranged to bridge research and clinical experiences. Qualitative studies about patients' illness and recovery experiences and questions by researchers facilitated reflections on clinical experiences. The meaning of the PROP was examined using focus group and individual interviews with patients and clinicians immediately after completing the course and after 1-1.5 years., Results: The biopsychosocial model displays the research evidence across biological, mental and social impacts of FM, justifying that life stress can be an illness-maintaining factor in FM. The content addresses enabling patients to heal their own life and self by modifying life stress. Patients engage in making sense of the relationship between FM, themselves, and life through exploring, discovering and creating appropriate solutions for their daily social life. The PROP reduced uncertainties and brought a positive attitude and hope to the groups. After 1 year, patients are still engaged in recovery work, experience more good days, and maintain hope for further recovery. By sharing and reflecting on clinical experiences, a unified clinical team was established that continues to develop their competency., Conclusion: To our knowledge, the PROP is the first programme for patients with FM that results from a process of coproducing knowledge, is based on explicit theoretical rationale, and facilitates a personal experiential recovery process. PROP is found to be meaningful and to work by patients and clinicians.

Background: Hepatic sinusoidal obstruction syndrome (SOS) is a serious complication of autologous stem cell transplant (ASCT) in children with historically high mortality rates. Defibrotide has shown proven benefit in its treatment and may have a modest role in prevention. We report our experience with SOS in children undergoing autologous transplant., Methods: Case records of 82 consecutive patients undergoing ASCT following high-dose chemotherapy between 2010 and 2017 were reviewed. Defibrotide was used for treatment of all with SOS and prophylactically in patients receiving busulfan-based conditioning until 2014., Results: Fourteen of the 82 children (17%) were diagnosed with SOS. The incidence was higher in those receiving busulfan-based conditioning (13/42 vs 1/40, P = 0.008). Mean (±SD) time to diagnosis of SOS was 19 (±5.6) days following stem cell rescue. Bilirubin levels and ultrasound were normal in 7/14 and 3/14 patients. Coagulopathy was noted in 10/14; one child developed multiorgan involvement. Nine children had mild SOS, whereas two and three had moderate and severe SOS, respectively. Intensive care was required for four of five non-mild cases. Patients with SOS had significantly delayed platelet recovery, higher transfusion requirement, and longer hospital stay. Unavailability of defibrotide prophylaxis for 17/42 receiving busulfan did not change the incidence of SOS (7/25 with defibrotide vs 6 /17 without defibrotide, P = 0.74). There was no significant difference in the severity of SOS between these groups., Conclusion: Hepatic SOS was more commonly seen in children receiving busulfan-based conditioning. Stopping the use of prophylactic defibrotide did not increase incidence or severity of SOS. Overall outcome was excellent with supportive care and timely treatment with defibrotide., (© 2020 Wiley Periodicals LLC.)

Background: Parenthood during medical training is common and impacts trainee well-being. However, current graduate medical education parental health policies are often limited in scope. We explored current fellowship trainees' knowledge of/satisfaction with current policies as well as interest in potential changes/additions to existing policies., Methods: Fellowship program directors/coordinators at a three-site academic institution were surveyed and information was collected from 2015 to 2019 regarding fellow demographics and parental health policies. We distributed an electronic survey to fellows containing Likert-type-scale questions rating knowledge/level of satisfaction with current parental health policies and interest in potential additions/modifications to current policies., Results: Thirty-five of 47 (74%) fellowship programs responded. An average of 11% of female fellows and 15% of male fellows took parental leave during the study period. Three (9%) of the programs had at least one additional parental health policy beyond institutional graduate medical education policies. In the fellow survey, 175 of 609 fellows responded (28.7%), of which 84 (48.6%) were female. Although 89.1% agreed/strongly agreed that parental health is an important part of health and well-being for fellows, only 32% were satisfied/very satisfied with current policies (no significant sex-related differences). Fellows reported the following potential interventions as important/very important: 79.2% increased (paid) maternity leave (72.7% male, 86.7% female, p  = 0.02), 78% increased (paid) paternity leave (76.4% male, 81.9% female, p  = 0.37), 72.3% part-time return to work (60.2% male, 84.3% female, p  = 0.0005), 63% coverage for workup/management of infertility (52.3% male, 74.7% female, p  = 0.002), and 79.9% on-site day care (70.7% male, 89.2% female, p  = 0.003)., Conclusions: Parental health includes multiple domains, not all of which are covered by current policies. Fellows feel that parental health is an important part of overall health and well-being, but most are not satisfied with current policies. Expanded access to parental leave and new policies (part-time return to work, infertility management, and on-site day care) are opportunities for innovation.

Introduction: For patients with primary refractory and relapsed acute leukaemias allogeneic stem cell transplantation is the only hope for cure, but morphological remission is not always achieved after standard salvage regimens. Here we review the experience with high-dose etoposide and cyclophosphamide (HD-Et/Cy) in relapsed/refractory acute leukaemias at the Royal Marsden Hospital., Patients and Methods: Twenty-three patients (15 adults, 8 children) with refractory/relapsed acute myeloblastic (n = 18; 78%), lymphoblastic (n = 4; 17%) or biphenotypic (n = 1; 4%) leukaemia who had failed to respond to at least one previous line of chemotherapy received HD-Et/Cy at our institution between 2006 and 2015., Results: Overall response rate was 21.7% (95%CI 4.0-40.0). Median overall survival was 14.8 months (95%CI 9.1-49.1). Eight (35%) patients (7 AML, 1 biphenotypic leukaemia) proceeded to allogeneic transplant after one cycle of HD-Et/Cy: four of them (50%; 3 adults, 1 child) in complete remission and another four children (50%) with aplastic bone marrow with scattered blasts. Among the transplant recipients, three with AML (38%), ie. one adult (responder) and two children with aplastic bone marrow with scattered blasts, became long-term survivors 9.8, 4.4 and 2.5 years post-HD-Et/Cy, respectively. Toxicity profile was comparable to similar regimens with no treatment-related deaths. The most common grade 3-4 toxicity was febrile neutropenia (96%)., Conclusions: HD-Et/Cy can salvage patients with refractory/relapsed AML who remain candidates for allogeneic stem cell transplantation after failure of standard salvage regimens and do not have access to clinical trials., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A contact-active antibacterial approach based on the physical adsorption of a cationic polyelectrolyte onto the surface of a cellulose material is today regarded as an environment-friendly way of creating antibacterial surfaces and materials. In this approach, the electrostatic charge of the treated surfaces is considered to be an important factor for the level of bacteria adsorption and deactivation/killing of the bacteria. In order to clarify the influence of surface charge density of the cellulose on bacteria adsorption as well as on their viability, bacteria were adsorbed onto cellulose model surfaces, which were modified by physically adsorbed cationic polyelectrolytes to create surfaces with different positive charge densities. The surface charge was altered by the layer-by-layer (LbL) assembly of cationic polyvinylamine (PVAm)/anionic cellulose nanofibril/PVAm onto the initially differently charged cellulose model surfaces. After exposing the LbL-treated surfaces to Escherichia coli in aqueous media, a positive correlation was found between the adsorption of bacteria as well as the ratio of nonviable/viable bacteria and the surface charge of the LbL-modified cellulose. By careful colloidal probe atomic force microscopy measurements, it was estimated, due to the difference in surface charges, that interaction forces at least 50 nN between the treated surfaces and a bacterium could be achieved for the surfaces with the highest surface charge, and it is suggested that these considerable interaction forces are sufficient to disrupt the bacterial cell wall and hence kill the bacteria.

Adenovirus (AdV) is an increasingly recognized threat to recipients of allogeneic hematopoietic stem cell transplantation (allo-HCT), particularly when infection is prolonged and unresolved. AdVance is the first multinational, multicenter study to evaluate the incidence of AdV infection in both pediatric and adult allo-HCT recipients across European transplantation centers. Medical records for patients undergoing first allo-HCT between January 2013 and September 2015 at 50 participating centers were reviewed. The cumulative incidence of AdV infection (in any sample using any assay) during the 6 months after allo-HCT was 32% (95% confidence interval [CI], 30.9% to 33.4%) among pediatric allo-HCT recipients (n = 1736) and 6% (95% CI, 4.7% to 6.4%) among adult allo-HCT recipients (n = 2540). The incidence of AdV viremia ≥1000copies/mL (a common threshold for initiation of preemptive treatment) was 14% (95% CI, 13.0% to 14.8%) in pediatric recipients and 1.5% (95% CI, 1.1% to 2.0%) in adult recipients. Baseline risk factors for developing AdV viremia ≥1000copies/mL included younger age, use of T cell depletion, and donor type other than matched related. Baseline demographic factors were broadly comparable across patients of all ages and identified by multivariate analyses. Notably, the incidence of AdV infection decreased stepwise with increasing age; younger adults (age 18 to 34 years) had a similar incidence as older pediatric patients (<18 years). This study provides a contemporary multicenter understanding of the incidence and risk factors for AdV infection following allo-HCT. Our findings may help optimize infection screening and intervention criteria, particularly for younger at-risk adults., (Copyright © 2018 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Paediatric therapy-related acute myeloid leukaemia (t-AML) is rare and the outcome is poor. While allogeneic haematopoietic stem cell transplantation (HSCT) is generally the accepted modality of treatment, data regarding salvage chemotherapy, remission induction, conditioning regimens, transplant-related mortality and outcome is scarce. Between 2000 and2016, 36 children with t-AML were treated in seven UK paediatric HSCT centres. The most common salvage protocol for remission induction was FLAG with or without idarubicin and 28 patients were in complete morphological remission prior to BMT. Only 12 patients survived (33%). Transplant-related mortality (TRM) was the leading cause of death.

Cidofovir is preemptively used for controlling adenoviremia and preventing disseminated viral disease in hematopoietic cell transplant (HCT) recipients but does not lead to resolution of viremia without T-cell immune-reconstitution. The lipid-conjugated prodrug of cidofovir, brincidofovir, has improved oral bioavailability and achieves higher intracellular concentrations of active drug. We present retrospective multicenter data comparing the kinetics of viremia and toxicities following preemptive treatment with and brincidofovir in children and adolescents diagnosed with HCT-related adenoviremia. Forty-one episodes (18 = brincidofovir; 23 = cidofovir) of antiviral therapy were observed in 27 patients. The 2 groups had comparable immune-reconstitution and viral burden. Major (≥2 log-reduction in 2 weeks; n = 13) and minor (≥1 to ≤2 log-reduction in 2 weeks; n = 2) virological responses were observed in 15 (83%) brincidofovir episodes compared to only 2 (9%) major virological responses with cidofovir ( P < .0001). Brincidofovir mediated major responses in 9 of 11 cidofovir-unresponsive patients and resulted in complete responses (CR) despite significant lymphopenia (Brincidofovir vs cidofovir; CR = 13 (80%) vs 8 (35%); median lymphocyte count = 320/μl vs 910/μl; P < .05). One patient experienced abdominal cramps and diarrhea necessitating interruption of brincidofovir and none developed nephrotoxicity with brincidofovir. Thus, brincidofovir is well-tolerated and highly efficacious in controlling adenoviremia during the lymphopenic phase of HCT., (© 2017 by The American Society of Hematology.)

Biologic TNF alpha blocker medication was started for a patient having active rheumatoid arthritis, because the disease was unresponsive to conventional drugs and the patient also 'had reactive amyloidosis. Due to weakening efficiency and simultaneously occurring gout the medication was replaced by an IL-1 receptor blocker, which in addition to controlling rheumatoid arthritis also acts by suppressing gouty attacks. Finding an optimized drug combination for rheumatoid patients will become easier with the increasing number of biologic drugs functioning through different mechanisms of action.

Aim: The aims of this study were to determine the incidence and types of haemoglobinopathies in Australian children and their distribution among ethnic groups, and to collect information on timing of diagnosis of haemoglobinopathies in Australia., Methods: Between January 2004 and March 2006, the Australian Paediatric Surveillance Unit asked paediatricians to report all children under 15 years of age with a newly diagnosed haemoglobinopathy. A questionnaire requesting further information was forwarded to those clinicians. Carrier states such as thalassaemia minor were excluded., Results: Eighty-four notifications of haemoglobinopathy were received by the Australian Paediatric Surveillance Unit, with 59 confirmed cases giving a national incidence of 0.74 per 100,000 children < 15 years of age per annum. Of 59 cases, 42 (71%) were Australian born. Twenty-nine (35.6%) children had sickle cell disease, 17 (28.8%) had Hb H disease, six (10.2%) had beta-thalassaemia major and 15 (25.4%) had compound heterozygous conditions. One child died from sickle cell disease. Of Australian born children, at least 10 mothers (23.8%) and 11 fathers (26.2%) were unaware of their carrier status pre-partum (information unavailable for 13 mothers and 17 fathers). Only 11 parents (18.6%) had risks of haemoglobinopathy discussed with them antenatally and only three cases (5.1%) were diagnosed antenatally., Conclusions: We found that a small but significant number of children with haemoglobinopathies are being born in Australia despite existing programmes of testing at-risk groups and neonatal screening. Haemoglobinopathies were also diagnosed in recent immigrants. Greater awareness of these conditions and enhancements of screening and detection programmes may be needed as the genetic diversity of the Australian population continues to develop., (© 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

Background: Retinoic acid-inducible gene 1-like receptors (RLRs) are a novel family of pattern recognition receptors that include retinoic acid-inducible gene 1 (RIG-1), melanoma differentiation-associated gene 5 (MDA-5), and laboratory of genomics and physiology 2 (LGP-2). The knowledge of RLRs and their function in the human airway is limited. This study explores the role of RLRs in the upper respiratory tract., Methods: Tonsils, adenoids, nasal polyps, and biopsy specimens from the nasal mucosa were examined for the occurrence of the RIG-1, MDA-5, and LGP-2 using real-time reverse-transcription polymerase chain reaction and immunohistochemistry. The nasopharyngeal epithelial cell line FaDu was cultured with the RIG-1/MDA-5 ligand poly(I:C)/LyoVec (Invivogen, San Diego, CA) and analyzed for cytokine release using ELISA., Results: RIG-1, MDA-5, and LGP-2 mRNA were found in all tissues tested. The airway epithelium appeared to be their most prominent location. The RIG-1 and MDA-5 mRNA levels were higher in nasal polyps than in normal nasal mucosa, a state that seemed to be reversed by local steroid treatment. Culture of FaDu with poly(I:C)/LyoVec resulted in IL-6 and IL-8 release. No alteration in RLR expression in tonsils was seen on infection., Conclusion: This study shows the presence and functional activity of RLRs in the human upper airways. It also suggests a role for RLRs in nasal polyposis.

NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs) are newly discovered pattern-recognition receptors. They detect substructures of bacterial peptidoglycan and viral RNA, respectively, thereby initiating an immune response. However, their role in eosinophil activation remains to be explored. The aim of this study was to characterize the expression of a range of NLRs and RLRs in purified human eosinophils and assess their functional importance. Expression of NOD1, NOD2, NLRP3, RIG-I and MDA-5 was investigated using real-time reverse transcription PCR, flow cytometry and immunohistochemistry. The effects of the corresponding agonists iE-DAP (NOD1), MDP (NOD2), alum (NLRP3) and poly(I:C)/LyoVec (RIG-I/MDA-5) were studied in terms of cytokine secretion, degranulation, survival, expression of adhesion molecules and activation markers, and chemotactic migration. Eosinophils expressed NOD1 and NOD2 mRNA and protein. Low levels of RIG-I and MDA-5 were found, whereas expression of NLRP3 was completely absent. In accordance, stimulation with iE-DAP and MDP was found to induce secretion of interleukin-8, up-regulate expression of CD11b, conversely down-regulate CD62 ligand, increase expression of CD69 and induce migration. The MDP also promoted release of eosinophil-derived neurotoxin, whereas iE-DAP failed to do so. No effects were seen upon stimulation with alum or poly(I:C)/LyoVec. Moreover, the NOD1-induced and NOD2-induced activation was mediated via the nuclear factor-κB signalling pathway and augmented by interleukin-5 and granulocyte-macrophage colony-stimulating factor, but not interferon-γ. Taken together, the NLR system represents a novel pathway for eosinophil activation. The responses are enhanced in the presence of cytokines that regulate T helper type 2 immunity, suggesting that the NLRs constitute a link between respiratory infections and exacerbations of allergic disease., (© 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd.)

Nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) and retinoic acid-inducible gene (RIG)-like receptors (RLRs) are recently discovered cytosolic pattern-recognition receptors sensing mainly bacterial components and viral RNA, respectively. Their importance in various cells and disorders is becoming better understood, but their role in human tonsil-derived T lymphocytes remains to be elucidated. In this study, we evaluated expression and functional relevance of NLRs and RLRs in human tonsillar CD3(+) T lymphocytes. Immunohistochemistry, real-time RT-PCR and flow cytometry revealed expression of NOD1, NOD2, NALP1, NALP3, NAIP, IPAF, RIG-1, MDA-5 and LGP-2 at mRNA and protein levels. Because of the limited number of ligands (iE-DAP, MDP, Alum, Poly(I:C)/LyoVec), functional evaluation was restricted to NOD1, NOD2, NALP3 and RIG-1/MDA-5, respectively. Stimulation with the agonists alone was not enough to induce activation but upon triggering via CD3 and CD28, a profound induction of proliferation was seen in purified CD3(+) T cells. However, the proliferative response was not further enhanced by the cognate ligands. Nonetheless, in tonsillar mononuclear cells iE-DAP, MDP and Poly(I:C)/LyoVec were found to augment the CD3/CD28-induced proliferation of tonsillar mononuclear cells. Also, iE-DAP and MDP were found to promote secretion of interleukins 2 and 10 as well as to up-regulate CD69. This study demonstrates for the first time a broad range of NLRs and RLRs in human tonsillar T cells and that NOD1, NOD2 and RIG-1/MDA-5 act synergistically with αCD3 and αCD28 to induce proliferation of human T cells. Hence, these results suggest that these receptors have a role in T-cell activation., (© 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd.)

NLRs are recently discovered PRRs detecting substructures of peptidoglycans and triggering innate immunity. NLRs are expressed in several cell types, but the presence in human B lymphocytes is still unknown. This study aimed to investigate expression and function of NLRs in human B lymphocytes. B cells were isolated and analyzed for mRNA and protein expression. The functional responsiveness of NOD1 and NOD2 was investigated upon stimulation with the cognate ligands, with or without stimulation via IgM/IgD/CD40 and/or selected TLR agonists. A differential expression of NLRs was demonstrated in blood-derived and tonsillar B cells, whereas no variations were found among naive, germinal center, or memory B cells. Stimulation with the ligands alone did not induce B cell activation. However, upon concomitant BCR triggering, an increase in proliferation was seen, together with an induction of cell surface markers (CD27, CD69, CD71, CD80, CD86, and CD95) and prolonged survival. Peripheral B cells were activated by NOD1 and NOD2 ligands, whereas tonsil-derived B cells responded solely to NOD1. In contrast, costimulation with CD40L failed to induce activation. Additionally, it was found that NLR ligands could enhance TLR-induced proliferation of B cells. The present study demonstrates expression of functional NLRs in human B cells. We show that NOD1 and NOD2 have the ability to augment the BCR-induced activation independently of physical T cell help. Hence, NLRs represent a new pathway for B cell activation and a potentially important host defense system against bacterial infections.

The Stevens-Johnson syndrome (SJS) classically involves a rash, conjunctivitis and mucositis. We describe the case of a young adult male with isolated mucositis and conjunctivitis . Previous rare reports of severe SJS like syndromes without a rash are confined to children, usually with mycoplasma pnemoniae infection.(1) Terminology for this syndrome includes - "Stevens-Johnson Syndrome without skin lesions", or "Atypical Stevens - Johnson Syndrome".(2) This case highlights the importance of maintaining an open mind when a "full house" of clinical features is absent. It also illustrates the use of a rapid electronic literature review as a clinical tool. The importance of updating records when a drug has been cleared of causing harm is highlighted.

Patients presenting to the "front door" with acute neuromuscular symptoms are challenging. Toxins need consideration as possible causative agents if there is the possibility of relevant exposure. This requires a thorough history1 and an awareness of local ethnic, social and industrial cultures within the practice locality. We describe a case of lead poisoning in a 35 year old man who presented with severe, progressive, myalgia. We consider that basic errors in clinical processing delayed a potentially difficult and serious diagnosis and these are discussed. The importance of maintaining a thorough initial clerking process within the Acute Medical Unit is highlighted. This should include a comprehensive occupational history. Acute physicians should familiarize themselves with local industry and the toxic syndromes they can produce.

Context: The definitive diagnosis of Cushing's syndrome (CS) in the setting of mild disease, as well as exclusion of CS in the setting of conditions that might mimic this clinical entity (pseudo-Cushing's syndrome), continues to present a significant challenge to the clinician., Objective: The aim of the study was to review characteristics of the combined dexamethasone-suppressed CRH stimulation test in patients evaluated at an academic center for the possibility of mild CS., Design, Patients, and Methods: We conducted a retrospective review of 66 patients. A total of 51 patients underwent final statistical analysis: 21 (41%) had Cushing's disease, and 30 were considered to have pseudo-CS based on the clinical scenario, comorbidities, and follow-up. Sensitivity, specificity, and diagnostic accuracy of cortisol and ACTH levels for the diagnosis of Cushing's disease were calculated at 1 min before, and 15, 30, 45, and 60 min after CRH administration. Diagnostic cutoffs for each parameter were determined by minimizing the absolute difference between sensitivity and specificity. Diagnostic accuracy was characterized by the area under the receiver operating characteristic curve, determined using the trapezoid rule., Results: The highest diagnostic accuracy was provided by the serum ACTH level at 15 min post-CRH, in which the area under the receiver operating characteristic curve was 99.7%, and a cutoff of more than 27 pg/ml (>5.9 pmol/liter) provided a sensitivity of 95% and specificity of 97% for the diagnosis of CS. A 15-min post-CRH cortisol greater than 2.5 mug/dl (70 nmol/liter) provided a sensitivity and specificity of 90 and 90%, respectively., Conclusions: Our results differ from previous studies because our data suggest that when using the combined dexamethasone-suppressed CRH stimulation test, a 15-min post-CRH ACTH value greater than 27 pg/ml (5.9 pmol/liter) had the highest diagnostic accuracy for the detection of CS. However, the sensitivity and specificity for this test were not statistically different from the sensitivity and specificity of other tests, such as those measuring post-CRH stimulated ACTH levels or post-CRH cortisol levels at other time points. Therefore, clinicians should be cautious about interpretation of suppression and stimulation tests in the diverse population of patients with hypercortisolism.

Objective: To estimate the incidence rates of deep venous thrombosis (DVT) and pulmonary embolism (PE) in hospitalized patients and to compare these with incidence rates in community residents., Patients and Methods: We performed a retrospective review of the complete medical records from a population-based inception cohort of patients who resided in Olmsted County, Minnesota, and had an incident DVT or PE from 1980 through 1990., Results: From 1980 through 1990, 911 Olmsted County residents experienced their first lifetime event of definite, probable, or possible venous thromboembolism. Of these residents, 253 had been hospitalized for some reason other than a diagnosis of DVT or PE (in-hospital cases), and 658 were not hospitalized at onset of venous thromboembolism (community residents). The average annual age- and sex-adjusted incidence of in-hospital venous thromboembolism was 960.5 (95% confidence interval, 795.1-1125.9) per 10,000 person-years and was more than 100 times greater than the incidence among community residents at 7.1 (95% confidence interval, 6.5-7.6) per 10,000 person-years. The incidence of venous thromboembolism rose markedly with increasing age for both groups, with PE accounting for most of the age-related increase among in-hospital cases. Incidence rates in the 2 groups changed little over time despite a reduction in the average length of hospital stay between 1980 and 1990., Conclusions: Venous thromboembolism is a major national health problem, especially among elderly hospitalized patients. This finding emphasizes the need for accurate identification of hospitalized patients at risk for venous thromboembolism and a better understanding of the mechanisms involved so that safe and effective prophylaxis can be implemented.

Objective: To determine the occurrence of fat-soluble vitamin deficiencies and to identify clinical factors that may predict vitamin deficiency in patients with primary biliary cirrhosis (PBC)., Methods: Review of our data from a randomized, placebo-controlled trial that evaluated the efficacy of UDCA in 180 patients with PBC. We use the first available measurements of vitamin levels in each study participant. Vitamin levels for A, D, and E were measured in serum. The prothrombin time (PT) was used as a surrogate marker for vitamin K., Results: The proportion of patients with fat-soluble vitamin deficiencies in the treatment and placebo groups was similar and the data sets were combined. The proportion with vitamin A, D, E or K deficiency was 33.5%, 13.2%, 1.9%, and 7.8%, respectively. In multivariate analysis, the Mayo risk score, advanced histological stage, and total cholesterol were independently associated with vitamin A deficiency whereas serum albumin levels was independently associated with vitamin D deficiency. No factors were associated with vitamin E or K deficiency in multivariate analysis owing to the few vitamin E and K deficient patients. Factors predictive of vitamin K deficiency by univariate analysis included Mayo risk score, advanced histological stage, HDL, total bilirubin, AST, and albumin. The cut-off value of the Mayo risk score with the highest sensitivity and specificity for vitamin A deficiency was 5.0., Conclusion: Other than deficiency of vitamin A, deficiency of fat-soluble vitamins occurs uncommonly in patients with PBC. A Mayo risk score > or = 5 helps in selecting patients with PBC for surveillance for vitamin A deficiency.

Objectives: Practice guidelines should improve care, but they are not routinely followed, in part because of lack of proven benefit. We evaluated the effect of introducing guidelines for inflammatory bowel disease (IBD) on practice variation and the IBD Quality of Life (IBDQ) score., Methods: This was a prospective, controlled, cohort study. A total of 65 patients were matched according to month of visit, diagnosis, and disease activity with control subjects seen 1 yr earlier. Physicians were educated throughout the study regarding the guidelines. Variation was measured by the Mayo Practice Guideline Score (MPGS), a 15-point assessment of documentation of diagnosis, nutrition, social support, education, functional status, and treatment. The IBDQ was measured at baseline and at 1 yr in the intervention group and after 1 yr in the control group., Results: The MPGS was significantly higher in the intervention group compared to the controls (p = 0.002), with median values of 12 versus 11. The IBDQ median score increased significantly in the intervention group (p < 0.001), baseline median of 133 versus 15-month median of 184. However, the final IBDQ was not significantly higher in the intervention group than in the controls (p = 0.33)., Conclusions: Practice guidelines for IBD reduce practice variation. The quality of life improved significantly compared to baseline with practice guidelines, but not compared to controls, perhaps because of the small sample size and homogenous practice setting. The MPGS is a tool that can be used in day-to-day management of IBD patients.

The incidence of venous thromboembolism exceeds 1 per 1000; over 200,000 new cases occur in the United States annually. Of these, 30% die within 30 days; one-fifth suffer sudden death due to pulmonary embolism. Despite improved prophylaxis, the incidence of venous thromboembolism has been constant since 1980. Independent risk factors for venous thromboembolism include increasing age, male gender, surgery, trauma, hospital or nursing home confinement, malignancy, neurologic disease with extremity paresis, central venous catheter/transvenous pacemaker, prior superficial vein thrombosis, and varicose veins; among women, risk factors include pregnancy, oral contraceptives, and hormone replacement therapy. About 30% of surviving cases develop recurrent venous thromboembolism within ten years. Independent predictors for recurrence include increasing age, obesity, malignant neoplasm, and extremity paresis. About 28% of cases develop venous stasis syndrome within 20 years. To reduce venous thromboembolism incidence, improve survival, and prevent recurrence and complications, patients with these characteristics should receive appropriate prophylaxis.

Background & Aims: The identification of any high-grade dysplasia (HGD) in Barrett's esophagus has been considered to be an indication for esophagectomy because of the increased risk of cancer. The aim of this study was to determine if a limited extent of HGD has the same potential for cancer as diffuse HGD., Methods: A retrospective cohort study was performed to assess the risk of developing adenocarcinoma in relationship to the extent of HGD found on endoscopic surveillance. The extent of HGD was defined as focal if cytologic and/or architectural changes of HGD were limited to a single focus of 5 or fewer crypts and diffuse if more than 5 crypts were involved in a single biopsy specimen or if HGD involved more than one biopsy fragment. The relative risk of cancer was assessed using a Cox proportional hazard model, and cancer-free survival was determined using survival curves., Results: Sixty-seven patients with diffuse HGD and 33 with focal HGD satisfied selection criteria. Cancer-free survival rates at 1 and 3 years were 93% and 86% for focal HGD compared with 62% and 44% for diffuse HGD (P < 0.001). On univariate analysis, extent of HGD (relative risk, 5.36; 95% confidence interval, 1.84-15.56), nodularity on endoscopy (relative risk, 3.98; 95% confidence interval, 1.97-8.04), and lack of acid suppression (relative risk, 2.48; 95% confidence interval, 1.16-5.28) were associated with an increased risk of esophageal adenocarcinoma. Diffuse HGD had a 3.7-fold increase in the risk of esophageal cancer compared with focal HGD (P = 0.02) on multivariate analysis., Conclusions: Patients with focal HGD are less likely to have cancer during the first year after diagnosis or on subsequent follow-up compared with diffuse HGD.

Background: The incidence rates of venous stasis syndrome and venous ulcer are uncertain, and trends in incidence are unknown., Methods: We performed a retrospective review of the complete (inpatient and outpatient) medical records of a community population (Olmsted County, Minnesota) to estimate the incidence of venous stasis syndrome and venous ulcer during the 25-year period, 1966 to 1990, and to describe trends in incidence., Results: A total of 1131 patients received a first lifetime diagnosis of venous stasis syndrome. A total of 263 patients received a first lifetime diagnosis of venous ulcer. The overall incidence of venous stasis syndrome and venous ulcer were 76.1 and 18.0 per 100,000 person-years, respectively. The incidence of both was higher in women than in men (83.7 vs 67.4 per 100,000 person-years for venous stasis syndrome; 20.4 vs 14.6 per 100,000 for venous ulcer) and increased with age for both sexes. There was no clear trend in the incidence of venous stasis syndrome over the 25-year period. Compared with 1966 to 1970, the incidence of venous ulcer decreased in 1971 to 1980, but was unchanged after 1981. Among 945 patients with venous stasis only, 60 subsequently had a venous ulcer. The average (+/- SD) time from venous stasis diagnosis to development of a venous ulcer was 5.0 (+/- 5.0) years., Conclusion: Venous stasis syndrome and venous ulcer are common, especially in the elderly population. The incidence of venous stasis syndrome has not changed since 1966, and venous ulcer incidence is unchanged since 1981. More accurate identification of patients at risk for venous stasis syndrome and venous ulcer and more effective prevention are needed.

Objective: To examine the association between atrial fibrillation (AF) and aortic atherosclerosis in the general population., Subjects and Methods: Transesophageal echocardiography was performed in 581 subjects, a random sample of the adult Olmsted County, Minnesota, population (45 years of age or older) participating in the Stroke Prevention: Assessment of Risk in a Community (SPARC) study. The frequency of aortic atherosclerosis was determined in 42 subjects with AF and compared with that in 539 subjects without AF (non-AF group)., Results: Subjects with AF were significantly older than non-AF subjects (mean +/- SD age, 82+/-10 vs 66+/-13 years, respectively; P<.001) and more commonly had hypertension (28 [66.7%] vs 288 [53.4%], respectively; P=.10). The 2 groups were similar in sex and frequency of diabetes mellitus, hyperlipidemia, or smoking history (P>.10). The odds of aortic atherosclerosis (of any degree) were 2.87 times greater (95% confidence interval [CI], 1.41-5.83; P=.004) and the odds of complex atherosclerosis (protruding atheroma >4 mm thick, mobile debris, or plaque ulceration) were 2.71 times greater (CI, 1.13-6.53; P=.03) in the AF group than in the non-AF group. Age was a significant predictor of aortic atherosclerosis (P<.001). After adjusting for age, the odds of atherosclerosis and complex atherosclerosis were not significantly different between the 2 groups (P=.13 and P=.75, respectively)., Conclusions: In the general population, AF is associated with aortic atherosclerosis, including complex atherosclerosis. This association is related to age since both AF and aortic atherosclerosis are more frequent in the elderly population.

Objective: We sought to determine risk factors for deep vein thrombosis and pulmonary embolism during pregnancy or post partum., Study Design: We performed a population-based case-control study. All Olmsted County, Minnesota, residents with a first lifetime deep vein thrombosis or pulmonary embolism during pregnancy or post partum from 1966 to 1990 were identified (N = 90). Where possible, a resident without deep vein thrombosis or pulmonary embolism was matched to each patient by date of the first live birth after the patient's child. The medical records of all remaining patients and all control subjects were reviewed for >25 baseline characteristics, which were tested as risk factors for deep vein thrombosis or pulmonary embolism., Results: In multivariate analysis smoking (odds ratio, 2.4) and prior superficial vein thrombosis (odds ratio, 9.4) were independent risk factors for deep vein thrombosis or pulmonary thrombosis during pregnancy or post partum., Conclusion: Venous thromboembolism prophylaxis may be warranted for pregnant women with prior superficial vein thrombosis. Smoking cessation should be recommended, especially during pregnancy and the postpartum period.

Objectives: To estimate the incidence and determine predictors of venous stasis syndrome and venous ulcers after deep venous thrombosis and pulmonary embolism., Patients and Methods: This population-based retrospective cohort study reviewed medical records of 1527 patients with incident deep venous thrombosis or pulmonary embolism between 1966 and 1990. We recorded baseline characteristics, event type (deep venous thrombosis with or without pulmonary embolism or pulmonary embolism alone), leg side and site of deep venous thrombosis (proximal with or without distal deep venous thrombosis vs distal deep venous thrombosis alone), and venous stasis syndrome and venous ulcer., Results: Two hundred forty-five patients developed venous stasis syndrome. One-year, 5-year, 10-year, and 20-year cumulative incidence rates were 7.3%, 14.3%, 19.7%, and 26.8%, respectively. By 20 years the cumulative incidence of venous ulcers was 3.7%. Patients with deep venous thrombosis with or without pulmonary embolism were 2.4-fold (95% confidence interval, 1.7-fold-3.2-fold) more likely to develop venous stasis syndrome than patients with pulmonary embolism and no diagnosed deep venous thrombosis. In patients aged 40 years or younger with proximal compared with distal-only deep venous thrombosis, venous stasis syndrome was 3.0-fold more likely (95% confidence interval, 1.6-fold-4.7-fold). In patients with unilateral leg deep venous thrombosis, venous stasis syndrome usually developed in the concordant leg (P < .001). There was a 30% (95% confidence interval, 2%-62%) increased risk for venous ulcer per decade of age at the incident venous thromboembolism., Conclusions: The cumulative incidence of venous stasis syndrome continues to increase for 20 years after venous thromboembolism. Pulmonary embolism alone is less likely to cause venous stasis syndrome.

Background: The appropriate duration of oral anticoagulation after a first episode of venous thromboembolism (VTE) is uncertain and depends upon VTE recurrence rates., Objective: To estimate VTE recurrence rates and determine predictors of recurrence., Methods: Patients in Olmsted County, Minnesota, with a first lifetime deep vein thrombosis or pulmonary embolism diagnosed during the 25-year period from 1966 through 1990 (N = 1,719) were followed forward in time through their complete medical records in the community for first VTE recurrence., Results: Four hundred four patients developed recurrent VTE during 10,198 person-years of follow-up. The overall (probable/definite) cumulative percentages of VTE recurrence at 7, 30, and 180 days and 1 and 10 years were 1.6% (0.2%), 5.2% (1.4%), 10.1% (4.1%), 12.9% (5.6%), and 30.4% (17.6%), respectively. The risk of recurrence was greatest in the first 6 to 12 months after the initial event but never fell to zero. Independent predictors of first overall VTE recurrence included increasing age and body mass index, neurologic disease with paresis, malignant neoplasm, and neurosurgery during the period from 1966 through 1980. Independent predictors of first probable/definite recurrence included diagnostic certainty of the incident event and neurologic disease in patients with hospital-acquired VTE. Recurrence risk was increased by malignant neoplasm but varied with concomitant chemotherapy, patient age and sex, and study year., Conclusions: Venous thromboembolism recurs frequently, especially within the first 6 to 12 months, and continues to recur for at least 10 years after the initial VTE. Patients with VTE with neurologic disease and paresis or with malignant neoplasm are at increased risk for recurrence, while VTE patients with transient or reversible risk factors are at less risk.

Background: Reported risk factors for venous thromboembolism (VTE) vary widely, and the magnitude and independence of each are uncertain., Objectives: To identify independent risk factors for deep vein thrombosis and pulmonary embolism and to estimate the magnitude of risk for each., Patients and Methods: We performed a population-based, nested, case-control study of 625 Olmsted County, Minnesota, patients with a first lifetime VTE diagnosed during the 15-year period from January 1, 1976, through December 31, 1990, and 625 Olmsted County patients without VTE. The 2 groups were matched on age, sex, calendar year, and medical record number., Results: Independent risk factors for VTE included surgery (odds ratio [OR], 21.7; 95% confidence interval [CI], 9.4-49.9), trauma (OR, 12.7; 95% CI, 4.1-39.7), hospital or nursing home confinement (OR, 8.0; 95% CI, 4.5-14.2), malignant neoplasm with (OR, 6.5; 95% CI, 2.1-20.2) or without (OR, 4.1; 95% CI, 1.9-8.5) chemotherapy, central venous catheter or pacemaker (OR, 5.6; 95% CI, 1.6-19.6), superficial vein thrombosis (OR, 4.3; 95% CI, 1.8-10.6), and neurological disease with extremity paresis (OR, 3.0; 95% CI, 1.3-7.4). The risk associated with varicose veins diminished with age (for age 45 years: OR, 4.2; 95% CI, 1.6-11.3; for age 60 years: OR, 1.9; 95% CI, 1.0-3.6; for age 75 years: OR, 0.9; 95% CI, 0.6-1.4), while patients with liver disease had a reduced risk (OR, 0.1; 95% CI, 0.0-0.7)., Conclusion: Hospital or nursing home confinement, surgery, trauma, malignant neoplasm, chemotherapy, neurologic disease with paresis, central venous catheter or pacemaker, varicose veins, and superficial vein thrombosis are independent and important risk factors for VTE.

Background: Because reported survival after venous thromboembolism (VTE) varies widely, we performed a population-based retrospective cohort study to estimate survival, compare observed with expected survival, and determine predictors of short-term (< or =7 days) and long-term survival (>7 days) after VTE., Methods: We followed the 25-year (1966-1990) inception cohort (n = 2218) of Olmsted County, Minnesota, patients with deep vein thrombosis alone (DVT) or pulmonary embolism with or without deep vein thrombosis (PE+/-DVT) forward in time until death or the last clinical contact., Results: During 14 629 person-years of follow-up, 1333 patients died. Seven-day, 30-day, and 1-year VTE survival rates were 74.8% (DVT, 96.2%; PE+/-DVT, 59.1%), 72.0% (DVT, 94.5%; PE+/-DVT, 55.6%), and 63.6% (DVT, 85.4%; PE+/-DVT, 47.7%), respectively. Observed survival after DVT, PE+/-DVT, and overall was significantly worse than expected for Minnesota whites of similar age and sex (P<.001). More than one third of deaths occurred on the date of onset or after VTE that was unrecognized during life. Short-term survival improved during the 25-year study period, while long-term survival was unchanged. After adjusting for comorbid conditions, PE+/-DVT was an independent predictor of reduced survival for up to 3 months after onset compared with DVT alone. Other independent predictors of both short- and long-term survival included age, body mass index, patient location at onset, malignancy, congestive heart failure, neurologic disease, chronic lung disease, recent surgery, and hormone therapy. Additional independent predictors of long-term survival included tobacco smoking, other cardiac disease, and chronic renal disease., Conclusions: Survival after VTE, and especially after PE+/-DVT, is much worse than reported, and significantly less than expected survival. Compared with DVT alone, symptomatic PE+/-DVT is an independent predictor of reduced survival for up to 3 months after onset, implying that treatment for the 2 disorders should be different.

Background: The incidence of venous thromboembolism has not been well described, and there are no studies of long-term trends in the incidence of venous thromboembolism., Objectives: To estimate the incidence of deep vein thrombosis and pulmonary embolism and to describe trends in incidence., Methods: We performed a retrospective review of the complete medical records from a population-based inception cohort of 2218 patients who resided within Olmsted County, Minnesota, and had an incident deep vein thrombosis or pulmonary embolism during the 25-year period from 1966 through 1990., Results: The overall average age- and sex-adjusted annual incidence of venous thromboembolism was 117 per 100000 (deep vein thrombosis, 48 per 100000; pulmonary embolism, 69 per 100000), with higher age-adjusted rates among males than females (130 vs 110 per 100000, respectively). The incidence of venous thromboembolism rose markedly with increasing age for both sexes, with pulmonary embolism accounting for most of the increase. The incidence of pulmonary embolism was approximately 45% lower during the last 15 years of the study for both sexes and all age strata, while the incidence of deep vein thrombosis remained constant for males across all age strata, decreased for females younger than 55 years, and increased for women older than 60 years., Conclusions: Venous thromboembolism is a major national health problem, especially among the elderly. While the incidence of pulmonary embolism has decreased over time, the incidence of deep vein thrombosis remains unchanged for men and is increasing for older women. These findings emphasize the need for more accurate identification of patients at risk for venous thromboembolism, as well as a safe and effective prophylaxis.

Purpose: Graft-related complications must be factored into the long-term morbidity and mortality rates of abdominal aortic aneurysm (AAA) repair. However, the true incidence may be underestimated because some patients do not return to the original surgical center when a problem arises., Methods: To minimize referral bias and loss to follow-up, we studied all patients who underwent AAA repair between 1957 and 1990 in a geographically defined community where all AAA operations were performed and followed by a single surgical practice. All patients who remained alive were asked to have their aortic grafts imaged., Results: Among 307 patients who underwent AAA repair, 29 patients (9.4%) had a graft-related complication. At a mean follow-up of 5.8 years (range, < 30 days to 36 years), the most common complication was anastomotic pseudoaneurysm (3.0%), followed by graft thrombosis (2.0%), graft-enteric erosion/fistula (1.6%), graft infection (1.3%), anastomotic hemorrhage (1.3%), colon ischemia (0.7%), and atheroembolism (0.3%). Complications were recognized within 30 days after surgery in eight patients (2.6%) and at late follow-up in 21 patients (6.8%). These complications were observed at a median follow-up of 6.1 years for anastomotic pseudoaneurysm, 4.3 years for graft-enteric erosion, and 0.15 years for graft infection. Kaplan-Meier 5- and 10-year survival free estimates were 98% and 96% for anastomotic pseudoaneurysm, 98% and 95% for combined graft-enteric erosion/infection, and 98% and 97% for graft thrombosis., Conclusions: This 36-year population-based study confirms that the vast majority of patients who undergo standard surgical repair of an abdominal aortic aneurysm remain free of any significant graft-related complication during their remaining lifetime.

Objective: To estimate the incidence of and identify risk factors for hemorrhage and thromboembolism during long-term anticoagulant therapy., Design: We conducted a population-based retrospective cohort study of all residents of Rochester, Minnesota, in whom a course of warfarin therapy intended to last for more than 4 weeks was initiated between Sept. 1, 1987, and Dec. 31, 1989., Methods: Medical records were reviewed, and pertinent data were compiled. All bleeding complications were classified as minor or major on the basis of the bleeding severity index, and thromboembolic events were classified as major if they were fatal or life-threatening. Cumulative incidences of adverse events were analyzed statistically., Results: During the study period, 261 patients had incident courses of anticoagulation (52% were male, 61% were 65 years of age or older, and 31% were 75 years of age or older), with 221 patient-years of warfarin exposure. The primary indications for anticoagulation were venous thromboembolism (39%); stroke or transient ischemic attack (21%); atrial fibrillation (11%); and coronary artery disease, procedures for coronary artery disease, or cardiomyopathy (7%). The cumulative incidence of major hemorrhage at 1, 3, 12, and 24 months was 1.6%, 3.3%, 5.3%, and 10.6%, respectively, and of major or minor thromboembolic events was 2.3%, 5.0%, 7.4%, and 13.1%, respectively. In multivariate analysis, (1) a malignant condition was significantly associated with major hemorrhage; (2) malignant disease and history of peptic ulcer were significantly associated with the combined outcome of major or minor hemorrhage; and (3) malignant disease was significantly associated with any thromboembolism. Age, sex, atrial fibrillation, history of gastrointestinal hemorrhage, history of peptic ulcer, alcohol abuse, hypertension, stroke, and the Charlson comorbidity index were not significantly associated with major hemorrhage., Conclusion: In this population-based study, including a high proportion of elderly patients, malignant disease at initiation of warfarin anticoagulation was significantly associated with both major hemorrhage and any thromboembolism. Advanced age is not a contraindication to anticoagulant therapy.

Purpose: This study was designed to evaluate progress in diagnosis, management, and clinical outcome of mesenteric venous thrombosis (MVT)., Methods: We retrospectively reviewed the clinical course of 72 patients treated for mesenteric venous thrombosis between 1972 and 1993., Results: Fifty-three patients had acute and 19 had chronic mesenteric venous thrombosis. Fifty-seven patients had secondary mesenteric venous thrombosis; previous abdominal surgical procedure and hypercoagulable states were the most prevalent associated conditions. Computed tomography was abnormal in all patients who underwent this test for acute mesenteric venous thrombosis and in 93% of those who had chronic disease. Angiography diagnosed acute mesenteric venous thrombosis in five (72%) of seven patients. Acute mesenteric venous thrombosis presented most frequently as abdominal pain (83%), anorexia (53%), and diarrhea (43%). Thirty-three (75%) had symptoms longer than 48 hours. Thirty-four (64%) patients with acute mesenteric venous thrombosis underwent a surgical procedure. Bowel resection was necessary in 31 patients. One patient had unsuccessful mesenteric venous thrombectomy. Seven patients with acute mesenteric venous thrombosis underwent anticoagulation without a surgical procedure, and 12 were observed. All patients with chronic mesenteric venous thrombosis were observed; nine of the 19 underwent anticoagulation. The median delay in diagnosis for patients with acute mesenteric venous thrombosis was 48 hours and did not decrease during the last decade. Mesenteric venous thrombosis recurred in 19 (36%) patients. The 30-day mortality was 27%. Long-term survival of patients with acute mesenteric venous thrombosis was significantly worse than that of those with chronic disease (36% vs 83% survival at 3 years). The patients with acute mesenteric venous thrombosis who underwent anticoagulation with and without surgical procedure had improved survival when compared with the observed group., Conclusion: Acute mesenteric venous thrombosis remains a lethal disease. Mortality has not improved in the last 22 years. Computed tomography is the most sensitive diagnostic test. Anticoagulation and surgical procedure enhanced survival in the acute subgroup. The underlying disease determined survival in chronic disease.

Objective: To address the frequency and outcome of celiac disease in a United States community., Methods: We identified all Olmsted County, Minnesota, residents diagnosed with this condition during the period, 1960 through 1990, using the resources of the Rochester Epidemiology Project. Twenty-eight incident cases (19 women, nine men) were identified., Results: The overall age- and gender-adjusted incidence of celiac disease in the community was 1.2 per 100,000 person-yr (95% CI 0.7, 1.6). There were no significant changes in incidence over time, although rates did increase; the incidence was similar in men and women and rose with age in both genders (p < 0.05). Survival in this inception cohort was 100% at 6 months and 96% at 5 yr, which was not significantly different from expected. The estimated prevalence on January 1, 1991, was 21.8 per 100,000., Conclusion: This study provides the first epidemiologic data on celiac disease in the United States.

The readability of 70 hospital information leaflets was compared with that of outside publications. Clarify of language was assessed by calculation of a 'reading score' for each document using the Gunning FOG test. Layout was assessed in terms of typeface, style of print and use of illustrations. Reading scores were generally satisfactory and illustrations were used effectively in most cases. However, seven (10%) of the leaflets had scores of 14 and above (equivalent to the British Medical Journal). Only 12 (17%) of the leaflets met the recommendations of the Royal National Institute for the Blind for size of typeface. The Gunning FOG test provides a reasonable assessment of readability. Documents scoring 12 and over may be incomprehensible, particularly to elderly patients.

Two young women developed oligomenorrhoea and galactorrhoea 4 and 7 years after whole brain irradiation for brain tumours. Both had mild hyperprolactinaemia due to irradiation-induced hypothalamic damage. In both patients, oral bromocriptine normalized prolactin levels and menstruation resumed. One patient then had a successful pregnancy.

This article describes the utilisation of a physiologically based research technique developed to facilitate the nursing care of patients with skeletal muscle wasting. The technique, which involved electrotherapeutic stimulation to the first dorsal interosseous muscle of a group of arthritic patients, demonstrates that patterned neuromuscular stimulation of skeletal muscle can have enormously beneficial effects in preserving and regenerating skeletal muscle. The reasons for the muscle wasting, and the subsequent vicious spiral of immobility, were reviewed in Part 1 (1), and both articles build on the concepts described in a previous paper published in Nursing Standard (2).

This article, which develops the concepts introduced in the authors' paper in last week's edition (1), is the first of two which review and summarise recent studies describing techniques to test the hypothesis that uniform frequency stimulation of skeletal muscle deprives the muscle of the type of signals that are necessary for rapid, appropriate and effective adaptation. Next week, clinical trials which have tested this hypothesis will be described, and the implications of the results for nurses involved in rehabilitation work discussed; Part 1 sets out the methodology of extracting the firing patterns of single motor units from a fatiguing muscle.

The lack of an appropriate and objective measuring scale or tool has ensured that rehabilitation nurses' assessments of patients' muscle function have tended to be subjective and, arguably, inconsistent. Such inexact methods are no longer acceptable to the increasingly audit-conscious health service and research-oriented nursing profession. The authors introduce a means of completing an objective assessment of patients' muscle function which, they claim, will enable nurses to evaluate the efficacy of current and potential treatment options. In follow-up articles appearing in the next two editions of Nursing Standard, they discuss electrotherapeutic rehabilitation of skeletal muscle function.