Changing clinical features of coeliac disease

The classical clinical picture of coeliac disease includes prolonged diarrhoea with failure to thrive. During the past two decades this type of active presentation of coeliac disease has decreased in many European countries, giving the impression that coeliac disease is a disappearing disease. However, this is not true. The disease can be found in older children with a more or less silent presentation. Silent coeliac disease can be detected by active screening with serological tests. Coeliac disease can be suspected in children suffering from mild gastrointestinal symptoms, such as abdominal pain, and in those with signs of nutritional deficiencies, as well as in children of first-degree relatives of already diagnosed coeliacs, patients with IgA-deficiency, patients suffering from dental enamel hypoplasia or dermatitis herpetiformis, and patients with some other disease known to be associated with coeliac disease, such as diabetes mellitus. According to the fundamental criteria of coeliac disease, the intestinal mucosa is flat when the individual is eating gluten-containing foods. However, this is not strictly true. Intolerance to gluten is obviously variable and the intestinal mucosa may be normal. This type of latent coeliac disease can be detected by analysing genetic markers, measuring antibodies in intestinal fluid or counting the density of intra-epithelial gamma/delta T cells which are increased greatly even in the latent phase of coeliac disease. Thus the general concept of the natural history of coeliac disease is changing.     

Celiac disease: helping families adapt

Lifelong dietary compliance prevents the long-term effects associated with celiac disease. However, this simple solution, diet, has many long-reaching effects on the children affected with celiac disease and their families. Assisting families in coping with this chronic illness is necessary for children and families to develop a sense of control. An overview of celiac disease is presented through the use of a case study. Guidelines are given to enable the healthcare provider to understand and help families through the process of adapting to a child with a chronic illness. Recommendations for nutritional management with helpful suggestions related to making celiac disease an everyday part of family life are discussed.     

Clinical criteria for the use of a decision-making framework for the medically compromised patient: hypertension and diabetes mellitus

In this article, clinical criteria for the staging of disease severity in patients with hypertension and diabetes mellitus are presented. This paper is intended to supplement a previous article by the authors on the use of clinical criteria for the classification of patients with ischemic heart disease and chronic obstructive pulmonary disease and the use of a decision-making framework for the medically compromised patient. Hypertension and diabetes mellitus are discussed in terms of pathophysiology, risk factors, clinical manifestations of disease and disease progression. The article will allow practitioners to stage patients with hypertension and diabetes mellitus and to apply this staging to the previously established clinical decision-making framework for medically compromised patients.     

Severe colitis in mucoviscidosis

We report the association of severe indeterminate colitis with cystic fibrosis in a 21 year old woman, with mild pulmonary involvement, and without digestive or pancreatic symptoms or pancreatic enzyme preparation. Ten cases of inflammatory bowel disease associated with a cystic fibrosis have been reported. Most fit with the diagnostic criteria of Crohn's disease. Although this case was compatible with this diagnosis, we have retained the diagnosis of "severe indeterminate colitis" because of the lack of specific histological features of Crohn's disease. The association between inflammatory bowel disease and cystic fibrosis is probably not fortuitous, although the pathophysiological link between the two diseases is unknown.     

The clinical outcome in pregnancies of grand grand multiparous women

Recent public health concern about the Jacob-Creutzfeld disease related to administration of growth hormone in children or the "mad cow" disease in cattle fed contaminated products requires a review of the association between Jacob-Creutzfeldt disease and pregnancy. Four cases of this transmissible spongiform encephalopathy have been described in pregnant women and none of the offspring, currently 22, 10, 7 and 3 years of age, have developed the disease. Vertical transmission of Jacob-Creutzfeldt disease cannot however be excluded as it occurs in animals and since injections of cord blood and placenta extracts of women with this disease into mice brains has proven the presence of the infectious agent. The rarity of Jacob-Creutzfeldt disease in women of reproductive age and the particularly long incubation period of this type of encephalopathy would incite prudence and long-term follow-up to determine outcome in children born from disease women or who developed signs of the disease during the years following delivery.     

Identification of WASP mutations, mutation hotspots and genotype-phenotype disparities in 24 patients with the Wiskott-Aldrich syndrome

The Wiskott-Aldrich syndrome (WAS), an X-linked immunodeficiency disease caused by mutation in the recently isolated gene encoding WAS protein (WASP), is known to be associated with extensive clinical heterogeneity. Cumulative mutation data have revealed that WASP genotypes are also highly variable among WAS patients, but the relationship of phenotype with genotype in this disease remains unclear. To address this issue we characterized WASP mutations in 24 unrelated WAS patients, including 18 boys with severe classical WAS and 6 boys expressing mild forms of the disease, and then examined the degree of correlation of these as well as all previously published WASP mutations with disease severity. By analysis of these compiled mutation data, we demonstrated clustering of WASP mutations within the four most N-terminal exons of the gene and also identified several sites within this region as hotspots for WASP mutation. These characteristics were observed, however, in both severe and mild cases of the disease. Similarly, while the cumulative data revealed a predominance of missense mutations among the WASP gene lesions observed in boys with isolated thrombocytopenia, missense mutations were not exclusively associated with milder WAS phenotypes, but also comprised a substantial portion (38%) of the WASP gene defects found in patients with severe disease. These findings, as well as the detection of identical WASP mutations in patients with disparate phenotypes, reveal a lack of phenotype concordance with genotype in WAS and thus imply that phenotypic outcome in this disease cannot be reliably predicted solely on the basis of WASP genotypes.     

Pieces of a puzzle: Toward a better understanding of intraocular inflammation associated with human immunodeficiency virus disease

Periductal mastitis (mammary duct ectasia) is a little appreciated, often unrecognized entity that may present to the dermatologist. We present our experience with this disease and hope to familiarize the reader with a condition not well known to most dermatologists. Periductal mastitis is a benign mammary duct disease that begins with periductal inflammation and progresses to ductal dilatation with minimal inflammation (ductal ectasia). The clinical and radiographic appearance of this disease can be indistinguishable from carcinoma of the breast.     

Coronary revascularization and abdominal aortic aneurysm repair in a patient with Beh?et's diseases

Beh?et's disease is a systemic disease characterized by oral aphta, genital ulcer, and ocular lesion. Arterial involvement is an uncommon complication of Beh?et's disease, and it most frequently affects the abdominal aorta followed by the femoral artery and the pulmonary artery. Coronary lesions in Beh?et's disease have been little reported in the literature. In this communication, we present a case with coronary artery stenosis and with subsequently developed supra-renal abdominal aortic aneurysm. The coronary lesions were revasculized with gastroepiploic artery, right internal mammary artery, and saphenous vein graft. Abdominal aortic repair was performed with partial cardiopulmonary stand by, because of the risk of coronary ischemia during the cross clamp including the celiac artery. To our knowledge, this is the first report of successful repair of combined lesions of the coronary and the abdominal aorta in a patient with Beh?et's disease.     

Advances in the management of Crohn's disease: economic and clinical potential of infliximab

New therapies for Crohn's disease are being developed based on improvements in our understanding of the disease's immune and inflammatory properties. One of these new therapies is infliximab, a monoclonal antibody directed against the proinflammatory cytokine tumor necrosis factor-alpha. Recent studies indicate that treatment of moderately to severely ill Crohn's disease patients with infliximab produces a rapid and profound reduction in the signs, symptoms, and severity of this disease. Beyond its clinical impact, Crohn's disease also carries significant economic consequences. Earlier reports on the costs of managing this disease estimated the average annual medical costs per patient at $9197, with the total annual cost of illness estimated to exceed $1.7 billion. Hospitalizations and surgeries represented 80% of these costs. Additional analyses have been conducted for this review to reflect more current treatment patterns. Assuming that proven increases in response and remission rates lead to diminished disease severity, infliximab can be expected to reduce the number of hospitalizations and surgeries in moderately to severely ill patients, with substantial cost savings. Moreover, improvement in disease status and quality of life may allow Crohn's disease patients to lead more productive lives.     

Effects of immobilization and subsequent low- and high-intensity exercise on morphology of rat calf muscles

The patient presented is a 58-year-old man with newly diagnosed prostate cancer who likely has at least a 10- to 15-year life expectancy. In staging this man's extent of disease, several preoperative clinical variables are provided to assess whether the patient has local disease before offering definitive surgical therapy. It has been demonstrated that the combination of several of these variables in a multivariate analysis has greater predictive power than any of these variables do alone. Multivariate analysis using clinical stage, prostate-specific antigen (PSA), and Gleason score will provide both the physician and patient with 95% confidence intervals for determining the probability of having organ-confined disease, extracapsular penetration, seminal vesicle involvement, and lymphatic metastases. Several of the clinical variables given indicate that this patient has advanced disease, such as a PSA of 12 ng/mL, a stage T2b lesion, Gleason sum 7 disease in 2 of 3 cores from the right side associated with perineural invasion, and an additional Gleason sum 7 biopsy from the contralateral apex. For a man with these preoperative variables, there is a 13% chance of organ-confined disease, an 18% probability of seminal vesicle invasion, and a 17% chance of positive pelvic lymph nodes based on a nomogram constructed from multivariate analysis. Using this information, this man should be counseled that he has a high probability (87%) of extracapsular disease and a significant risk (15% to 20%) of having either seminal vesicle or lymph node involvement. Recognizing the risks and benefits of various forms of definitive therapy for prostate cancer, the patient has additional information to make an informed decision.     

Calbistrins, novel antifungal agents produced by Penicillium restrictum. I. Production, taxonomy of the producing organism and biological activity

Over a 14-year period, from 1971 to 1985, there were 15 patients referred to the Princess Margaret Hospital in Toronto for postoperative radiotherapy to the cervical lymph nodes following radical neck surgery for metastatic cancer. An intensive investigation failed to yield a primary site in any patient. All of the patients had extensive neck disease with significant indications for postoperative radiotherapy (massive neck nodes, invasion of extra nodal structures or fixation to unresectable adjacent structures). Of this highly selected group of patients with advanced neck disease: 4/15 (27%) died within one year of uncontrolled local disease, a further 2/15 (13%) died within four years of metastatic/recurrent disease, 6/15 (33%) died of intercurrent disease and 3/15 (20%) were alive with at least four years follow-up. Although all patients presented with advanced disease, survival and significant palliation was possible in this select group of patients.     

Inheritance of susceptibility to experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis is a disease of the central nervous system that can be readily induced in a variety of species by immunization with myelin proteins. It is one of the most commonly studied models of cell-mediated autoimmune disease and consequently has been important in the elucidation of many immunological functions in vivo. Nevertheless, very little is understood about the genetic and environmental factors that control the disease. Several groups have begun undertaking systematic genetic analyses in mice to identify loci that associate with increased susceptibility to disease. In this review, we will summarize the work that has been done to understand the genetic predisposition that makes certain inbred animals susceptible to disease and others resistant, and we will discuss some of the difficulties in the genetic analysis that have arisen due to the complexities of this disease model.     

Coronary artery revascularization in an adult with coronary aneurysms probably secondary to childhood Kawasaki disease

Kawasaki disease is an acute febrile illness affecting mainly infants and children. The fatal complication of Kawasaki disease is coronary involvement pertaining to coronary artery aneurysms. Surgical experience of adults that had childhood Kawasaki disease with coronary lesion has been rarely reported. We experienced coronary artery bypass grafting in a 44 year old man with no risk factors for atherosclerosis but with coronary lesions possibly secondary to Kawasaki disease. Coronary artery sequelae of Kawasaki disease may become part of a cause of coronary disease in young adults and we should recognize this condition in such patients with coronary disease but no coronary risk factors.     

Effect of thrombolytic therapy on platelet expression and plasma concentration of PECAM-1 (CD31) in patients with acute myocardial infarction

OBJECTIVE: Cholelithiasis is a common problem in hospitals of the Peruvian Andes; however, its prevalence in Andean communities is unknown. To estimate the prevalence of gallstone disease in this locale, we conducted a cross-sectional community study in three high-altitude Peruvian rural villages (i.e., > 3000 m above sea level). METHODS: We examined 911 volunteers > 15 yr of age from three villages for gallstone disease by history and ultrasonography. Risk factors for gallstone disease were examined in 382 volunteers from one village. RESULTS: The age-adjusted prevalence of gallstone disease ranged from 4-10% in men and from 18-20% in women. Women had significantly higher age-adjusted prevalence rates than did men. The prevalence of gallstone disease increased significantly with age and decreased significantly with alcohol consumption. Although not statistically significant, we found a positive association between gallstone disease and body mass index. CONCLUSION: The results of this study indicate that gallstone disease, commonly perceived as a disease of the developed world, is also a common problem in high-altitude Peruvian communities.     

Copper disposition of the fetus and placenta in a patient with untreated Wilson's disease

A patient with untreated Wilson's disease showed the possibility of fetal liver damage and copper accumulation in the placenta by this disease. This is the first report of copper disposition on the fetus and placenta in a patient with untreated Wilson's disease.     

Predisposing factors for individuals' Lyme disease prevention practices: Connecticut, Maine, and Montana

OBJECTIVES: This study examined factors that predispose individuals to protect against Lyme disease. METHODS: Knowledge, attitude, and practice questions concerning Lyme disease prevention were included in the Behavioral Risk Factor Surveillance surveys in Connecticut, Maine, and Montana. A total of 4246 persons were interviewed. RESULTS: Perceived risk of acquiring Lyme disease, knowing anyone with Lyme disease, knowledge about Lyme disease, and believing Lyme disease to be a common problem were significantly associated with prevention practices. CONCLUSIONS: Predisposing factors differ substantially between states and appear related to disease incidence. Personal risk, knowing someone with Lyme disease, and cognizance about Lyme disease and acting on this information are consistent with social learning theories.     

Production of endothelin-1 by cultured human synoviocytes

Langerhans-cell histiocytosis (LCH) is a rare condition with a wide clinical spectrum and variable prognosis. Patients with multisystem LCH have been treated with a variety of agents but may develop resistant and progressive disease. Based on a preliminary encouraging report on the activity of 2 chlorodoxyadenosine in this disease, we administered this agent to a patient with LCH which was resistant to corticosteroids and etoposide. After 4 courses of treatment the patient achieved a complete remission which is currently ongoing for 12 months. 2 CdA appears to be effective in patients with resistant LCH and warrants investigation in previously untreated patients with poor risk disease.     

Treatment of spondylolysis with external electrical stimulation and bracing in adolescent athletes: a report of two cases

BACKGROUND: An epidemic of bilateral optic neuropathy is affecting large numbers of people aged between 10 and 40 in Dar es Salaam, the capital city of Tanzania. The disease is characterised by acute onset of bilateral visual impairment, bilateral impairment of colour vision, and a characteristic temporal pallor of the optic discs. The disease often occurs in association with peripheral neuropathy and sensorineural hearing loss. This report presents the first data on disease prevalence in adolescents, based on a rapid assessment of schoolchildren. METHODS: Three schools in Dar es Salaam were visited and all children aged between 10 and 16 were screened for the disease. RESULTS: The prevalence of bilateral optic neuropathy among the schoolchildren is estimated to be 1.0% (95% CI 0.5-1.4%). This suggests that 5000 children (95% CI 2600-7300) aged 10-16 in Dar es Salaam may have the disease. CONCLUSION: The results of this rapid assessment indicate this epidemic is a major public health problem. The prevalence of the disease in the community is likely to be far higher than found in this survey because children with the disease may have withdrawn from school. As the disease predominantly affects young adults, resulting in impaired vision and hearing, the economic and social consequences are enormous.