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.     

Therapy of hepatocellular carcinoma

The therapeutic modalities in patients with hepatocellular carcinoma (HCC) depend on the number, size and location of the lesions as well as the stage of the underlying liver disease and the physical condition of the patient. In patients with small and solitary lesions, resection, liver transplantation and in some cases percutaneous ethanol injection (PEI) can be curative. In more advanced stages of the disease with larger or multiple lesions, PEI and/or transarterial chemotherapy with or without embolization (TACE or TAC) can slow the progression of the disease. In disseminated disease, a radiotherapeutic approach can be taken in selected cases. The therapeutic strategy in patients with HCCs should be individualized, frequently involving a combination of therapeutic modalities. In contrast to the earlier dismal prognosis, for most HCC patients there is today a therapeutic strategy that results in prolongation of life and in some cases even cure.     

Fat-soluble vitamin therapy in senile dementia and Parkinson's disease

In the pathogenesis of Parkinson's disease and senile dementia of the Alzheimer type, free radicals might play a role. Fat-soluble vitamins are a kind of anti-oxidative substance. Therefore, fat-soluble vitamins, such as vitamin E, may be useful in treatment of Parkinson's disease and senile dementia of the Alzheimer type. However, it is still unclear whether the concentration of vitamin E in the blood or in the brain tissue, in patients with Parkinson's disease or with of the senile dementia Alzheimer type, is higher than or the same as that in normal subjects. Furthermore, although the effectiveness of vitamin E in the treatment of Parkinson's disease has been reported, the usefulness of vitamin E is still obscure. Further study will be necessary, in order to clarify the role of fat-soluble vitamins in the treatment of Parkinson's disease and senile dementia of the Alzheimer type.     

Non-isotopic in situ hybridization to detect chick Sox gene mRNA in plastic-embedded tissue

OBJECTIVES: Evaluate the ability of two bone alkaline phosphatase (ALPB) immunoassays (Ostase, Hybritech Inc and Alkphase-B, Metra Biosystems) to clinically differentiate between osseous and non-osseous ALP sources. DESIGN AND METHODS: Specimens from patients with either liver or bone disease (Paget's disease or metastatic cancer) were analyzed by both methods. RESULTS: There was a good correlation between these two assays. Values for ALPB, whether determined as a concentration by the Ostase assay or as an activity by the Alkphase-B assay, were similar for subjects with liver disease or bone disease. However, total ALP (ALPT) activity was higher in liver disease compared to bone. When ALPB was expressed in relation to ALPT, ratios were significantly greater in subjects with bone disease than in those with liver disease. ALPB/ALPT ratios improved the specificity of the Ostase assay from 52% to 86% and the Alkphase-B assay from 58% to 74%. CONCLUSIONS: These two ALPB assays have good analytical performance and their clinical utility can be enhanced by expressing ALPB values in relation to ALPT activity.     

Refractory IBD: medical management

Refractory inflammatory bowel disease (IBD) can be defined as persistent acute symptomatic disease despite anti-inflammatory therapy or as chronically active disease requiring continuous treatment for relief of symptoms. Treatment options include azathioprine (AZA), 6-mercaptopurine (6-MP), methotrexate (MTX), cyclosporine (CYA), and experimental therapies that are cytokines or cytokine antagonists. AZA and 6-MP have identical actions in IBD. 6-MP is effective in about 75% of patients with inflammatory Crohn's disease. The mean time until the onset of action is 3.1 months. AZA is effective in ulcerative colitis as a steroid-sparing agent. Side-effects occur in 10-15% of patients on AZA or 6-MP for IBD. MTX induces symptomatic remission in about 40% of patients with Crohn's disease. The potential for hepatic fibrosis from MTX is a concern. CYA appears effective in the acute management of severe ulcerative colitis. CYA has not proven useful in the long-term management of Crohn's disease. Potentially serious side-effects include hypertension and renal insufficiency. The cytokine antagonist, anti-tumor-necrosis-factor-alpha antibody, and the anti-inflammatory cytokine, interleukin 10, appear promising for the treatment of Crohn's disease.     

Autoantibodies in central nervous system lupus

Central nervous system (CNS) involvement in patients with lupus remains both a diagnostic and a therapeutic challenge. The role of autoantibodies in the pathogenesis of CNS lupus and/or as markers for disease activity is reviewed. Doubt is cast on the value of measuring anti-neuronal antibodies. Those antibodies binding ribosomal-P protein antigens or certain phospholipids appear to have greater utility, although even in these cases there is no uniform agreement as to their precise role in CNS disease induction, or how well antibody levels reflect disease activity.     

Coronary calcification by electron beam computed tomography and obstructive coronary artery disease: a model for costs and effectiveness of diagnosis as compared with conventional cardiac testing methods

OBJECTIVES: The purpose of this study was to determine if electron beam computed tomography (EBCT) has potential as a cost-effective approach to diagnosis of obstructive coronary disease. BACKGROUND: Coronary calcification quantified by EBCT is closely related to the extent of atherosclerosis. METHODS: A model based upon published sensitivities (Se)/specificities (Sp) for diagnosis in an ambulatory patient of obstructive coronary disease (> or =50% stenosis) and population prevalence was tested for angiography alone, or treadmill exercise, stress echocardiography, stress thallium or predetermined EBCT calcium score outpoints, followed by angiography if indicated. RESULTS: Total direct testing costs increased in proportion to disease prevalence whereas cost-effectiveness, direct costs/patient diagnosed correctly with disease, decreased as a function of prevalence. Using an EBCT calcium score of 168 (Se/Sp = 71%/90%) provided for the least costly and most cost-effective noninvasive pathway. Calcium scores of 80 (Se/Sp = 84%/84%) and 37 (Se/Sp = 90%/77%) were also cost-effective when prevalence of disease was < or =70%; but results for a >0 calcium score (Se/Sp = 95%/46%) cutpoint were not superior to conventional methods. Calcium score cutpoints of 37, 80 or 168 provided similar or superior overall negative and positive predictive values to conventional noninvasive testing pathways across all prevalence subgroups. CONCLUSIONS: In ambulatory patients evaluated for obstructive coronary disease, a testing pathway utilizing quantification of coronary calcium by EBCT as an initial noninvasive testing approach minimized direct costs, and maximized cost-effectiveness in population groups with low/ moderate disease prevalence (< or =70%); as expected, direct angiography as the first and only test proved most cost-effective in patients with a high prevalence (>70%) of disease.     

Pericarditis in chronic inflammatory bowel disease: underlying disease or side effects of therapy? Clinical problem solving

Pericarditis and myocarditis are rare extraintestinal manifestations of chronic inflammatory bowel disease (ulcerative colitis and Crohn's disease). Pericarditis as a side effect induced by sulfasalazine or 5-aminosalicylic acid, drugs used in the therapy of these diseases, was first described only 7 years ago. In older case reports the relationship between the use of these drugs and pericarditis is unclear. We analyze the reported cases of 68 patients (38 men, 24 women) with ulcerative colitis (n = 45) or Crohn's disease (n = 15) who had one or more episodes of pericarditis or myopericarditis. Pericarditis was not associated with high activity of bowel disease in all cases. In most cases therapy with corticosteroids led to uneventful recovery. In drug induced pericarditis omission of the 5-ASA therapy was sufficient in a few cases. There was one fatal case (with myocarditis). The decision whether pericarditis is a symptom of the underlying disease or a side effect of the drug used for the treatment of the disease is not always easy. We present an analysis (clinical problem solving) of a pertinent observation in a patient with Crohn's disease and pericarditis, showing the dilemma of pericarditis in chronic inflammatory bowel disease and its therapy.     

A transitional variant of Castleman's disease presenting as a chylous pleural effusion

Castleman's disease is an uncommon clinicopathologic entity that results in unregulated growth of lymphoid tissue. It may present as benign involvement of one lymph node group or as multicentric disease with serious systemic symptoms. Pleural effusions are an uncommon manifestation of Castleman's disease. We present a patient with Castleman's disease who initially presented with a chylous pleural effusion.     

Comparison of long-term efficacy of medical treatment versus coronary artery bypass grafting (CABG) in multivessel coronary artery disease

The long-term results of medical therapy and coronary artery bypass grafting (CABG) were compared in patients with multivessel disease. All patients were confirmed to have > or = 75% luminal narrowing of major coronary arteries by coronary arteriogram. When multivessel disease was stratified into double- and triple- vessel disease, the outcomes varied. In triple-vessel disease, the outcome with CABG was good, but the outcome was unfavorable in those employing medical therapy, particularly in patients with decreased left ventricular (LV) function. In patients with double-vessel disease with good LV function, the long-term results with medical therapy were just as favorable as those with CABG. However, double-vessel disease complicated by reduced LV function (ejection faction < or = 40%) had a clearly less favorable outcome when treated with medical therapy than with CABG. Thus, it is important for patients with multivessel disease to undergo revascularization if indicated, to improve their prognosis. On the other hand, the incidence of cardiac events arising from vein graft occlusions tended to increase in CABG patients after 5 years or more following surgery.     

The delivery of preventive services in primary care practices according to chronic disease status

OBJECTIVES: The current study examined the relationship between chronic disease status and the receipt of cancer preventive services over a 3-year period. METHODS: Adults (n = 4320) cared for by 167 nonacademic physicians in 42 primary care group practices were studied. Medical records were audited for each patient, as were patient responses to two questionnaires assessing health and sociodemographic characteristics. RESULTS: While the odds of having received counseling to obtain regular checkups were increased for men (1.56) and women (1.46) with hypertension, the odds were reduced (range = 0.32 to 0.81) for having received a sigmoidoscopy (women with diabetes or hypertension, men with hypertension or heart disease), fecal occult blood test (men with diabetes or heart disease, women with heart disease), mammogram or counseling about smoking (women with diabetes), clinical breast exam (women with heart disease), and Pap test (women with diabetes or heart disease). CONCLUSIONS: The presence of common chronic health problems in older adults is associated with lower levels of cancer screening services.     

Valvular heart disease in pregnancy. A contemporary perspective

Valvular heart disease may have a significant impact on the course and outcome of pregnancy with implications for fetal as well as maternal health. Optimally, serious symptomatic valvular heart disease should be detected and treated before pregnancy. Whether a pregnant woman is known to have valvular heart disease or is diagnosed during pregnancy, it is imperative that she is managed by an experienced multidisciplinary team. Although medical therapy may alleviate symptoms of heart failure in some patients, definitive intervention either with percutaneous balloon valvuloplasty or with surgical valve replacement may be necessary.     

Pathophysiology of the respiratory system related to anesthesia

The pathophysiology of the respiratory system can be viewed by simply evaluating the status of a functional residual capacity (FRC). More specifically, patients with airways that are characterized as extremely compliant or "floppy" will have an increased FRC, which is the hallmark of chronic obstructive pulmonary disease. Patients with noncompliant, "stiff" lungs suffer from a form of restrictive disease with a resultant reduction in the FRC. Hence, the implications for anesthesia care focus on the FRC; that is, raising the FRC in the restrictive disease patient and normalizing or preventing further increase in the FRC in the patient with chronic obstructive pulmonary disease.     

Oncological implications of RET gene mutations in Hirschsprung's disease

BACKGROUND: Germline mutations of the RET proto-oncogene identical to those found in the tumour predisposition syndrome multiple endocrine neoplasia type 2A (MEN2A), were detected in 2.5-5% of sporadic and familial cases of Hirschsprung's disease. Some patients with Hirschsprung's disease may therefore be exposed to a highly increased risk of tumours. AIMS: To define clinical use of RET gene testing in Hirschsprung's disease and related patient management from an oncological point of view. METHODS: Sixty patients with Hirschsprung's disease were screened for RET mutations. In three, MEN2A type RET mutations were detected. Case reports for these three patients are presented. RESULTS AND CONCLUSIONS: Only 22 families or sporadic patients with Hirschsprung's disease and MEN2A type RET mutations have been reported. Therefore, it is difficult to predict tumour risk for patients with familial or sporadic Hirschsprung's disease, and their relatives, who carry these mutations. For these mutation carriers, periodic screening for tumours as in MEN2A is advised, but prophylactic thyroidectomy is offered hesitantly. RET gene testing in familial or sporadic Hirschsprung's disease is not recommended at present outside a complete clinical research setting. In combined MEN2A/Hirschsprung's disease families RET gene testing, tumour screening, and prophylactic thyroidectomy are indicated as in MEN2A.     

Anal lesions complicating Crohn disease

Of 503 patients with Crohn disease seen at the New York Hospital-Cornell Medical Center, 138 (28%) developed an anorectal abscess, anal fissure, or anal fistula during the course of their disease. In 9.3% of patients the anal lesion preceded the onset of intestinal symptoms by two weeks to 12 years. Patients in our series with large bowel disease were twice as likely to develop an anal lesion as were patients with small bowel disease. Likewise, patients with large bowel disease were twice as likely to have had an anal lesion as a presenting symptom. A patient with an anal lesion, however, was more apt to develop small bowel disease simply because the small bowel was a far commoner site of Crohn disease in this series. The cause of the anal lesions is still not clear. Specific evidence of Crohn disease was not found in histological examination of material from any of the patients.     

Familial Hodgkin's disease and associated cancer. A clinical-pathologic study

The etiology of Hodgkin's disease is complex, as is evident in studies suggesting the importance of horizontal transmission, occupational factors, racial and ethnic background, and familial, genetic factors, or both, including HL-A associations. The present study is of a remarkable kindred in which Hodgkin's disease was histologically verified in two sibships involving second-cousins related through maternal great-grandparents. Cancer of the lung, breast, endometrium, ovary, pancreas, and brain, as well as leukemia and Wilms' tumor, occurred in first and second-degree relatives of the Hodgkin's patients. HL-A haplotypes in patients with Hodgkin's disease in this family showed HL-AB5 or HL-ABW35, an association confirmed in other reports. The findings of associated malignant neoplasms in familial Hodgkin's disease, here and elsewhere in the literature, suggest that in the quest for etiology of Hodgkin's disease one must view the disorder eclectically, with a painstaking search for multiple etiologies, genetic and environmental.     

Reproductive performance of two generations of female semidomesticated mink fed diets containing organic mercury contaminated freshwater fish

OBJECT: This study was conducted to determine the prevalence of cerebrovascular disease and its risk factors among patients with normal-pressure hydrocephalus (NPH) and to assess the influence of these factors on the outcome of shunt placement. METHODS: A cohort of 101 patients with NPH underwent shunt placement and was followed for 1 year. Gait disturbance and dementia were quantified using an NPH scale and handicap was determined using a modified Rankin scale (mRS). Primary outcome measures consisted of the differences between preoperative and last NPH scale and mRS scores. The presence of risk factors such as hypertension, diabetes mellitus, cardiac disease, peripheral vascular disease, male gender, and advancing age was recorded. Cerebrovascular disease was defined as a history of stroke or a computerized tomography (CT) scan revealing infarcts or moderate-to-severe white matter hypodense lesions. The prevalence of risk factors for cerebrovascular disease was higher in the 45 patients with cerebrovascular disease than the 56 without it. Risk factors did not influence outcome after shunt placement. Intent-to-treat analysis revealed that the mean improvement in the various scales was significantly less for patients with a history of stroke (14 patients), CT scans revealing infarctions (13), or white matter hypodense lesions (32 patients) than for those without cerebrovascular disease. The proportion of patients who responded to shunt placement was also significantly lower among patients with than those without cerebrovascular disease (p=0.02). CONCLUSIONS: The authors identified a subgroup of patients with NPH and cerebrovascular disease who showed disappointing results after shunt placement. Cerebrovascular disease was an important predictor of poor outcome.     

Variable memory profiles in Parkinson's disease

Thirty-nine patients with Parkinson's disease (PD) were categorized into one of three subgroups using discriminant function analysis and three key indices from the California Verbal Learning Test (CVLT). Patients were classified as having one of three memory profiles: (a) a normal memory profile; (b) a memory profile often observed in patients with Huntington's disease (HD); or (c) a memory profile often observed in patients with Alzheimer's disease (AD). Twenty of the patients with PD were classified as having a normal profile, 10 as having an HD profile, and 9 as having an AD profile. The three subgroups did not differ on measures of global cognitive functioning, letter fluency, confrontation naming, or visuo-construction, suggesting that the patients with PD with an AD memory profile were not experiencing AD, per se. These results demonstrate that the memory deficits associated with PD can be similar to those found in patients with either HD or AD, and argues against the notion that the behavioral manifestations of PD are homogeneous.