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Biomedical subjects

A Groll

Publications and source records attributed to A Groll.

At least 19 recordsLinked to original sources

Infections due to emerging and uncommon medically important fungal pathogens.

The emergence of less common but medically important fungal pathogens contributes to the rate of morbidity and mortality, especially in the increasingly expanding population of immunocompromised patients. These pathogens include septate filamentous fungi (e.g., Fusarium spp., Scedosporium spp., Trichoderma spp.), nonseptate Zygomycetes, the endemic dimorphic pathogen Penicillium marneffei, and non-Cryptococcus, non-Candida pathogenic yeast (e.g., Trichosporon spp.). The medical community is thus called upon to acquire an understanding of the microbiology, epidemiology and pathogenesis of these previously uncommon pathogens in order to become familiar with the options for prevention and treatment.

Humans↗

A case of chronic pancreatic insufficiency due to valproic acid in a child.

A 14-year-old child treated with valproic acid over several years for a seizure disorder developed abdominal pain with radiological evidence of acute pancreatitis. The association with valproic acid was not recognized, and the child continued to take the drug. The patient eventually developed steatorrhea and weight loss that improved with pancreatic enzyme replacement. Radiological evaluation showed an atrophic pancreas. Without evidence of other etiological factors, valproic acid by itself appeared to be the cause of chronic pancreatitis with exocrine pancreatic insufficiency in this patient.

Adolescent↗

Concepts in design of comparative clinical trials of antifungal therapy in neutropenic patients.

Fundamental to the successful implementation of antifungal compounds in neutropenic patients is the appropriate design of comparative clinical trials investigating their safety and efficacy. The key elements of comparative clinical trial design include issues of enrollment, stratification, randomization, blinding, administration of study drugs, monitoring of drug toxicity, definitions, and key statistical elements of end points, sample size, and tools for data analysis. The initial selection of compounds and the timing of initiation of antifungal therapy in comparative clinical trials are predicated to a large degree on the in vitro and in vivo activities, plasma pharmacokinetics, profiles of safety and toxicity of the study drugs. Phase I and II studies have a critical role in designing comparative clinical trials of antifungal therapy by providing data on safety, tolerance, and plasma pharmacokinetics of the investigational agent. As new antifungal agents are developed in response to the challenge of invasive fungal infections in immunocompromised patients with cancer, thoughtfully designed and carefully implemented clinical trials will be essential in determining the future utility of these promising compounds.

Antifungal Agents↗

The Pediatric Bowel Management Clinic: initial results of a multidisciplinary approach to functional constipation in children.

The multifactorial nature of functional constipation in children suggests that a multidisciplinary management approach may be effective. The authors tested this hypothesis in a newly created pediatric Bowel Management Clinic (BMC). Detailed data were collected prospectively on all patients seen in the clinic over the first 16 months. Both quantitative and qualitative analyses were performed to describe the index population and to demonstrate the impact of the intervention. Satisfaction with care in the clinic was measured using the Measure of Processes of Care tool, then compared with a normative sample. One hundred fourteen patients, all previously treated unsuccessfully for constipation, were referred to a team comprised of a physician, nurse practitioner, nurse educator, dietitian, and psychosocial nurse specialist. The mean age was 5.4 years with equal gender distribution. Between the first and last visits recorded, several variables including stool consistency and frequency, soiling frequency, abdominal pain, rectal pain, and rectal bleeding all showed statistically significant (P < .05) improvement. Qualitative data analysis showed the significant psychosocial impact of constipation on patients and their families. In the Measures of Processes of Care questionnaire, scores for the BMC were higher than normal on all scales except in provision of information. A multidisciplinary approach to functional constipation leads to both patient and parent satisfaction and significant short-term improvement. Further studies will examine the long-term impact of the clinic.

Adolescent↗

Activation of the CD95 system increases with disease progression in human immunodeficiency virus type 1-infected children and adolescents.

BACKGROUND: Increased apoptosis in infected as well as noninfected cells has been invoked in CD4+ T helper cell depletion during HIV-1 infection. A strong increase in the expression of CD95 (APO-1/Fas) and CD95 ligand, key regulators of apoptosis in normal T cells, has previously been described in freshly isolated T cells from HIV-1-positive children when compared with healthy age-matched controls. We also found an increase in spontaneous as well as specific CD95-mediated apoptosis in CD4+ and CD8+ T cells from these patients. However, the relationship of these findings to disease progression in children with HIV infection is not known. MEASUREMENTS AND SUBJECTS: We studied expression of CD95 and CD95 ligand as well as sensitivity towards spontaneous and anti-CD95-triggered apoptosis of T cells in 33 HIV-1-positive children and adolescents in different disease stages. RESULTS: Loss of CD4+ T cells in vivo was paralleled by an increase in the percentage of CD95 high T cells and an increase in anti-CD95-induced apoptosis of CD4+ T cells. CD95L mRNA was constantly up-regulated in T cells from patients in intermediate disease stages whereas patients with normal CD4 counts and patients with advanced T cell loss showed CD95 ligand-mRNA levels in or slightly above the range of normal controls. CONCLUSIONS: Disturbed regulation of the CD95 system may play an important role in the development of immunodeficiency during the course of HIV infection in children.

Acquired Immunodeficiency Syndrome↗

The pathogenic role of Staphylococcus epidermidis capsular polysaccharide/adhesin in a low-inoculum rabbit model of prosthetic valve endocarditis.

BACKGROUND: The capsular polysaccharide/adhesin (PS/A) antigen of Staphylococcus epidermidis was required to produce endocarditis in a rabbit model in which infection resulted from hematogenous spread of bacteria from a contaminated catheter in the jugular vein. However, many prosthetic valve endocarditis (PVE) infections probably result from direct contamination of the valve with small numbers of bacteria during surgery. The role of PS/A in this situation was evaluated by modifying a rabbit model of endocarditis to partially mimic PVE. METHODS AND RESULTS: A Teflon catheter was contaminated with graded inocula of either PS/A-positive S epidermidis strain M187sp11 or the PS/A-negative, isogenic strain M187sn3 and inserted into the left ventricle through the aortic valve. The PS/A-positive strain had a 50% infectious dose of 1.1 x 10(2) cfu (95% CI, 3.3 to 3.7 x 10(3)) compared with 8.5 x 10(4) cfu of the PS/A-negative strain (95% CI, 8.6 x 10(3) to 8.5 x 10(5)). The odds for developing endocarditis were estimated to be 42 times higher for any given inoculum level of the PS/A-positive strain (P = .1). When the PS/A-positive strain was adherent to a catheter surface it survived in rabbit blood, whereas under the same conditions the PS/A-negative strain was killed approximately 90% in 1 hour. CONCLUSIONS: Direct contamination of an intraventricular foreign body by low levels of PS/A-positive S epidermidis results in endocarditis in rabbits, but at suitably high doses PS/A-negative strains have sufficient virulence to infect cardiac vegetations. PS/A enhances but is not absolutely required for bacterial virulence in a rabbit model of PVE.

Animals↗

Low-dose cyclosporine for the treatment of Crohn's disease. The Canadian Crohn's Relapse Prevention Trial Investigators.

BACKGROUND: Long-term corticosteroid therapy for Crohn's disease is associated with important types of morbidity, such as osteoporosis. Safe and effective alternative treatments are required. Although a short-term benefit of cyclosporine in active Crohn's disease has been suggested, the long-term safety and efficacy of this treatment have not been established. METHODS: We conducted a randomized, double-blind, placebo-controlled evaluation of the effect of 18 months of low-dose cyclosporine treatment on the course of Crohn's disease. Adult patients whose disease had been active within the previous two years were randomly assigned to receive cyclosporine (151 patients) or placebo (154 patients) in addition to their usual therapy. Randomization was stratified according to center and score on the Crohn's Disease Activity Index (193 patients had scores of 150 or less, and 112 had scores greater than 150). The primary outcome measure was clinically important worsening of Crohn's disease, defined as a 100-point increase in the Crohn's Disease Activity Index from the patient's base-line value. Secondary outcomes were the use of prednisone and 5-amino-salicylates, mean score on the Crohn's Disease Activity Index and mean quality-of-life score, and the need for surgery. RESULTS: The condition of more patients worsened with cyclosporine than with placebo (91 of 151, or 60.3 percent, vs. 80 of 154, or 51.9 percent; P = 0.10). The median time to worsening of disease in patients receiving cyclosporine was 338 days, as compared with 492 days in patients receiving placebo (P = 0.25; relative risk, 1.22; 95 percent confidence interval, 0.86 to 1.72). Analyses of the mean Crohn's Disease Activity Index and quality-of-life scores and of the use of prednisone and 5-aminosalicylates also failed to demonstrate benefit. CONCLUSIONS: In our patient population, the addition of low-dose cyclosporine to conventional treatment for Crohn's disease did not improve symptoms or reduce requirements for other forms of therapy.

Adult↗

Quality of life: a valid and reliable measure of therapeutic efficacy in the treatment of inflammatory bowel disease. Canadian Crohn's Relapse Prevention Trial Study Group.

BACKGROUND/AIMS: Quality of life (QOL), a subjective index of health perception and function, embraces physical, social, and emotional performance but has not had a prominent role in clinical trials of inflammatory bowel disease (IBD). To test the robustness of the Inflammatory Bowel Disease Questionnaire (IBDQ), a disease-specific QOL index, this study assessed its validity, reliability, and responsiveness during a multicenter trial. METHODS: Three hundred five patients with stable Crohn's disease received cyclosporin or placebo for 18 months. IBDQ and dimensional scores (bowel, social, systemic, and emotional) were correlated with disease activity (Crohn's disease activity index [CDAI] and Harvey-Bradshaw index). Concordance of IBDQ scores was tested in 280 stable subjects. Linear regression evaluated change in IBDQ scores over time. RESULTS: IBDQ scores correlated highly with CDAI (r = -0.67; P < 0.0001). The reliability coefficient for IBDQ score was 0.70 vs. 0.66 for CDAI and 0.55 for Harvey-Bradshaw index. Regression line slopes of IBDQ scores were significantly different in patients who deteriorated from those who remained stable ([b] < 0.15; P < 0.0001). QOL scores were lower in patients who required surgery. CONCLUSIONS: The IBDQ is a valid reliable assessment tool that reflects important changes in the health status of patients with IBD. The IBDQ is a robust measure of therapeutic efficacy and should be used in future clinical trials in IBD.

Adult↗

[Infectious endocarditis from the morphologic viewpoint: on the pathology and clinical aspects of 97 autopsy cases].

In continuous autopsy material between 1978 and 1987 an infectious endocarditis was present in 97 cases of 8745 postmortem examinations. Hospital acquired or iatrogenic infections were at the top of the list with 60% contribution and intravasal devices, cardiovascular or abdominal surgery acting as predominant entrance spots of the infection. In community acquired disease the portal of entry could not be ascertained in most of the cases. The spectrum of causative organisms showed staphylococcus aureus in first position (37%), followed by enterococci (20%), candida (12%) and gram-negative rods (10%). Streptococcus viridans could be isolated in only one case. The majority of patients already had cardiac valve lesions before the onset of infection (48%), immune-defence tangent illnesses (47%) and/or were treated immunosuppressively (14%). In many of the patients, however, no predisposing factors could be established. Factors determining the clinical outcome were - independent of the localization - the local destruction (47%), purulent and non-purulent myocarditis (58%), fresh myocardial infarction (17%) and embolization to various organs (76%), whereby the central nervous system was affected to a high degree (43%). Only 39% of the analyzed cases were discovered at lifetime; especially mural (n = 10) and tricuspidal (n = 9) infections were overlooked. In spite of highly suspicious infection parameters, blood-cultures were drawn from only 59% of the patients; however, an antibiotic therapy had been given to 85%. Only through an early diagnosis before serious complications set in, the poor prognosis of infectious endocarditis can be improved by specific chemotherapy and well-timed surgical measures.

Adolescent↗

[The morphology and clinical significance of pathologic changes of the adrenals and hypophysis in AIDS].

A semiquantitative morphometric technique (point counting) was applied to the pituitary and adrenals taken at necropsy from 130 AIDS patients (4 women, 126 men, mean age 39 [22-71] years) to ascertain the nature, extent and location of the pathological lesions. Abnormalities were found in 32% of the pituitaries and 76% of the adrenals. Only 17 patients had normal findings in both organs. The predominant lesions were due to opportunistic infections or infiltration by Kaposi's sarcoma or non-Hodgkin lymphoma. The commonest finding was necrotizing cytomegalovirus adrenalitis (n = 68); in one third of the cases this had caused severe destructive lesions involving over 50% of the parenchyma. The almost total destruction of the adrenals noted in some cases suggests that cytomegalovirus adrenalitis may run a progressive course; its clinical significance has hitherto been underestimated.

Acquired Immunodeficiency Syndrome↗

[Teichoic acid antibody assay in infections of the bones and joints caused by Staphylococcus aureus].

For detecting antibodies against the teichoic acids of Staphylococcus aureus (SA), a commercially available Ouchterlony double-diffusion procedure kit was chosen. Thirteen of 26 patients with chronic SA osteomyelitis, 2 of 2 with SA spondylitis and 5 of 6 with arthritis had a positive assay (58%) in contrast to 8 of 24 patients of the control groups (33%). High titers correlated well with the extent and duration of antigen presentation in the bloodstream for cells of representing the specific immunity. Localized infections with minor antigenemia elicited a detectable but weak antibody response.

Antibodies, Bacterial↗

Bile duct carcinoma and biliary tract dysplasia in chronic ulcerative colitis.

A case of chronic ulcerative colitis with a moderately differentiated adenocarcinoma of the common hepatic duct is described. Throughout the entire biliary tree, there was extensive epithelial dysplasia associated with changes of primary sclerosing cholangitis. The development of primary sclerosing cholangitis in the biliary tract of patients with ulcerative colitis appears to precede dysplasia and may be a marker of patients at risk for developing biliary tract carcinomas.

Adenocarcinoma↗

Response to steroids in Budd-Chiari syndrome caused by idiopathic granulomatous venulitis.

A 31-yr-old man presented with the Budd-Chiari syndrome. A liver biopsy specimen demonstrated noncaseating centrilobular granulomas and an idiopathic necrotizing granulomatous venulitis involving hepatic vein radicles with superimposed thrombotic occlusion. High-dose prednisone therapy produced dramatic clinical improvement with resolution of the hepatomegaly, ascites, and portal hypertension and normalization of the hepatic venous angiogram. A repeat liver biopsy specimen showed resolution of the venulitis and disappearance of the hepatic vein thrombosis. Idiopathic granulomatous venulitis that is reversible with prednisone therapy should be considered in the differential diagnosis of the Budd-Chiari syndrome.

Adult↗

Indium-111-labeled autologous leukocyte imaging and fecal excretion. Comparison with conventional methods of assessment of inflammatory bowel disease.

This study was designed to evaluate the role of 111In-labeled leukocyte imaging and fecal excretion in the assessment of inflammatory bowel disease. We compared these tests to various indices of disease activity in Crohn's disease, to Truelove's grading in ulcerative colitis, and to endoscopy, x-ray, and pathology in both diseases. Eleven controls, 16 patients with Crohn's disease, 13 with ulcerative colitis, and 3 with other types of acute bowel inflammation were studied (positive controls). Indium scanning was performed at 1, 4, and 24 hr. Fourteen of 16 patients with active Crohn's disease had positive scans but in only five was localization accurate. One patient had inactive ulcerative colitis, and the scan was negative. Of 12 patients with active ulcerative colitis, 10 had positive scans but disease localization was accurate in only four. Disease extent was correctly defined in 1 of the 3 Positive Controls. There was no significant difference in the accuracy of scanning at 1, 4, or 24 hr. 111In fecal excretion was significantly higher in patients with inflammatory bowel disease than in controls, and there was correlation between 111In fecal excretion and most of the indices of disease activity in Crohn's disease. In ulcerative colitis, 111In fecal excretion did not correlate with Truelove's grading but reflected colonoscopic assessment of severity. In conclusion, 111In-labeled leukocyte scanning lacks sensitivity with respect to disease extent, but fecal excretion of 111In correlates well with disease severity as determined by other methods.

Colectomy↗

Cimetidine prophylaxis for gastrointestinal bleeding in an intensive care unit.

The efficacy of cimetidine in the prevention of gastrointestinal haemorrhage in a general intensive care unit was evaluated in 221 patients by a placebo controlled double blind randomised study. Criteria for bleeding were (i) haematemesis or gastric aspirate greater than 50 ml fresh blood, (ii) melaena or fresh blood per rectum with an upper source verified by endoscopy if the gastric aspirate was clear, (iii) a fall in haemoglobin level greater than 2 g/dl in a 24 hour period associated with either 4+ occult blood in stools, or coffee ground gastric drainage of at least 100 ml. The drug and placebo groups were similar for age, sex, duration of study and risk factors. One hundred and fourteen received cimetidine and 107 placebo. Only 8% of the patients bled with no significant difference between the two groups (6/114 cimetidine, 11/107 placebo; p = 0.16). There was no correlation between the frequency of bleeding and either the number of risk factors per patient or the duration of intensive care unit stay. Thirteen patients died in each study group, resulting in overall mortality of 12%. The low incidence of haemorrhage, the lack of statistical benefit from cimetidine and the similar mortality all argue against the routine use of this drug in intensive care unit patients.

Adolescent↗

Short stature as the primary manifestation of coeliac disease.

Thirty-four patients with short stature of undetermined cause and no gastrointestinal symptoms underwent jejunal biopsy for exclusion of coeliac disease. Eight had subtotal or severe partial villous atrophy and seven showed a significant acceleration in height and weight velocity after the introduction of a gluten-free diet. Short stature by itself, in the complete absence of gastrointestinal symptoms, is an indication for jejunal biopsy, particularly if bone age is delayed by more than 4 years and/or there are associated haematological abnormalities.

Adolescent↗