PubMed Health⌕ Search

Biomedical subjects

J Allen

Publications and source records attributed to J Allen.

At least 127 records · Page 7Linked to original sources
PubMed1999

Childhood vulval pemphigoid: a clinical and immunopathological study of five patients.

We describe five girls with vulval pemphigoid: two had bullous pemphigoid confined to the vulva and three had cicatricial pemphigoid. They demonstrate a spectrum of severity from localized disease to extensive vulval scarring necessitating long-term immunosuppressive therapy and surgical correction. The age at onset of their disease ranged between 6 and 13 years. All presented with vulval discomfort and erosions. Three had oral lesions, two perianal and one eye and cutaneous involvement. Two girls with only vulval lesions and one with vulval and oral lesions responded well to topical steroids. In two, systemic treatment with prednisolone and dapsone or azathioprine was required. The diagnosis was made on the basis of histology and immunofluorescence (IF). All had positive direct IF with IgG and C3. Indirect IF demonstrated circulating IgG binding to the basement membrane zone in four, with dermal or epidermal binding on salt-split skin substrate. Immunoblotting revealed antibodies to the BP230 and BP180 antigens. Immunoelectron microscopy in the child with dermal binding IgG and BP180 and BP230 on immunoblotting showed labelling at the lamina densa-lamina lucida interface adjacent to hemidesmosomes.

Adolescent↗
PubMed1999

A comparison of the expression of known basement membrane components with the linear IgA disease antigens using the novel substrate cylindroma.

Linear IgA disease (LAD) is characterized by IgA basement membrane zone autoantibodies. Immunofluorescence, immunoblotting and immunoelectron microscopy studies have established the complexity and heterogeneity of the target antigens. We have studied the expression of the LAD antigens by cylindroma, a benign epithelial tumour that secretes abundant basement membrane, using 57 LAD sera categorized by indirect immunofluorescence on intact and salt-split skin. The expression of known components of hemidesmosomes, the anchoring filaments, extracellular matrix and the anchoring fibrils could be differentiated and were compared with the expression of the LAD antigens. The results showed that the LAD sera bound to the cylindroma tumour in two distinctive patterns. Thirty-three sera were positive on cylindroma. Twenty-seven sera bound to the basement membrane around the tumour clusters and the islets within the clusters in a thin linear band that was occasionally discontinuous. This was similar to the pattern observed with antibodies to the hemidesmosome components, the alpha6beta4 integrin and the bullous pemphigoid antigens BP230 and BP180. This pattern was observed with sera that bound to the epidermal (11) and the dermal (3) aspects of split skin or were negative (11), and with one serum which bound only to intact skin. Seven sera, all binding to the dermal aspect of split skin, bound the tumour cluster basement membrane in a thick band that was identical in appearance to that seen with antibodies to collagen VII; however, binding to the islets was either identical to collagen VII or similar but differentiated with double staining. Some sera were negative on cylindroma. Using fluorescence overlay antigen mapping we demonstrated colocalization of some epidermal-associated LAD target antigens with known hemidesmosome proteins, and colocalization of some dermal-associated LAD target antigens with anchoring fibril components. The results using cylindroma as substrate suggest that LAD autoantibodies may react with three or more target antigens. We propose from the results of this study that the autoantibodies in LAD target multiple antigens associated with hemidesmosomes and anchoring fibrils.

Adult↗
PubMed1999

Serum soluble transferrin receptor and the prediction of marrow aspirate iron results in a heterogeneous group of patients.

Serum soluble transferrin receptor (sTfR) concentration has been evaluated in the diagnosis of iron deficiency in otherwise healthy individuals and in patients with rheumatoid arthritis, but has not been studied in a general population of patients with complicated clinical presentations. In this study, 145 anaemic patients with a variety of medical conditions undergoing diagnostic bone marrow aspiration for any reason were tested by a complete blood count, a panel of biochemical tests to evaluate iron status, bone-marrow aspirate iron stain, and serum sTfR concentration. Sixteen per cent lacked stainable iron in the marrow aspirate. All biochemical parameters differed significantly between patients with or without stainable marrow iron. The sTfR assay was significantly more sensitive but less specific than other iron status assays in identifying the absence of stainable iron. Logistic regression analysis demonstrated that only sTfR and ferritin contributed independently to the prediction of marrow iron status. Serum ferritin alone was highly specific but insensitive. A decision algorithm combining serum ferritin and sTfR was as sensitive as TfR and as specific as serum ferritin. The measurement of serum sTfR, especially in conjunction with serum ferritin, is a valuable addition to the existing methods for predicting the results of marrow aspirate iron stains.

Adolescent↗
PubMed1999

Does class switching contribute to remission in bullous pemphigoid?

A correlation between the titre of circulating IgG autoantibodies and disease activity has been difficult to demonstrate in bullous pemphigoid. We postulate that isotype switching from "inflammatory" IgG1 to "blocking" IgG4 subclass antibodies might contribute to disease remission. We studied 16 patients with bullous pemphigoid, 3 patients with cicatricial pemphigoid and 2 patients with epidermolysis bullosa acquisita at different stages of the disease. The titres of IgG subclass and total IgG basement membrane zone autoantibodies were correlated with clinical activity. Ten of the 16 bullous pemphigoid patients went into remission. The total IgG autoantibody levels showed variable changes. IgG1 autoantibody decreased in 7 patients (3 were unchanged) and IgG4 autoantibody increased in 9 patients. The 6 patients with clinical activity did not show such changes in IgG1 and IgG4 autoantibodies. Similar results were observed with the other bullous diseases. Our data suggest that isotype switching from "inflammatory" IgG1 to "blocking" IgG4 antibody correlates with improvement in bullous pemphigoid.

Aged↗
PubMed1999

Modelling the relationship between peripheral blood pressure and blood volume pulses using linear and neural network system identification techniques.

The relationships between peripheral blood pressure and blood volume pulse waveforms can provide valuable physiological data about the peripheral vascular system, and are the subject of this study. Blood pressure and volume pulse waveforms were collected from 12 normal male subjects using non-invasive optical techniques, finger arterial blood pressure (BP, Finapres: Datex-Ohmeda) and photoelectric plethysmography (PPG) respectively, and captured to computer for three equal (1 min) measurement phases: baseline, hand raising and hand elevated. This simple physiological challenge was designed to induce a significant drop in peripheral blood pressure. A simple first order lag transfer function was chosen to study the relationship between blood pressure (system input) and blood volume pulse waveforms (system output), with parameters describing the dynamics (time constant, tau) and input-output gain (K). Tau and K were estimated for each subject using two different system identification techniques: a recursive parameter estimation algorithm which calculated tau and K from a linear auto-regressive with exogenous variable (ARX) model, and an artificial neural network which was trained to learn the non-linear process input-output relationships and then derive a linearized ARX model of the system. The identification techniques allowed the relationship between the blood pressure and blood volume pulses to be described simply, with the neural network technique providing a better model fit overall (p < 0.05, Wilcoxon). The median falls in tau following the hand raise challenge were 26% and 31% for the linear and neural network based techniques respectively (both p < 0.05, Wilcoxon). This preliminary study has shown that the time constant and gain parameters obtained using these techniques can provide physiological data for the clinical assessment of the peripheral circulation.

Adult↗
PubMed1999

Effects of epinephrine and amrinone on contractility and cyclic adenosine monophosphate generation of tumor necrosis factor alpha-exposed cardiac myocytes.

OBJECTIVE: This study utilized an in vitro neonatal rat cardiac myocyte assay to evaluate potential differences in the response of TNF-alpha-exposed myocytes to stimulation with the adrenergic agent, epinephrine, and the phosphodiesterase III inhibitor, amrinone. DESIGN: Contractility was assessed by measuring the maximum extent of the contraction of electrically paced neonatal rat cardiac myocytes in tissue culture using a closed-loop video tracking system. Myocytes were incubated in control or media containing TNF-alpha (50 ng/mL) for 20 mins and were then stimulated with increasing concentrations of either epinephrine (0.1 to 100 ng/mL) for 15 mins or amrinone lactate (0.25 to 10 microg/mL) for 20 mins. MEASUREMENTS AND MAIN RESULTS: Compared with control myocytes, TNF-alpha-exposed myocytes stimulated with increasing concentrations of epinephrine demonstrated a decreased peak augmentation of contractility (p<.0001 analysis of variance). This decrease was paralleled by a decrease in epinephrine-stimulated generation of cyclic AMP, as measured by enzyme-linked immunoassay (p = .05 polynomial regression). In contrast, increasing concentrations of amrinone produced increased peak augmentation of contractility (p = .003 analysis of variance) in TNF-alpha-exposed cardiac myocytes (relative to controls). However, this increase was not reflected by increased amrinone-stimulated generation of cyclic AMP relative to control myocytes not exposed to TNF-alpha (p = NS polynomial regression). CONCLUSIONS: Our data suggest that TNF-alpha induces a defect in beta-adrenergic signal transduction and catecholamine-stimulated contractility in neonatal rat cardiac myocytes. In addition, TNF-alpha augments the inotropic response of myocardial tissue to phosphodiesterase inhibitors through a mechanism independent of cyclic AMP generation. Phosphodiesterase inhibitors such as amrinone may be found to exert significant inotropic effects in catecholamine-refractory septic shock with myocardial depression and other conditions of inflammatory myocardial dysfunction.

Amrinone↗
PubMed1999

Effects of familial pain models on daily pain indices and performance during the cold pressor task.

To understand better the role of pain history in current response to pain episodes, this research examined pain-related indices from the patient's family of origin and their relationships to the patient's coping with acute pain. Participants were 42 healthy men and women who provided information about their own and their family's pain history and then were administered a cold pressor task. High frequency of family pain modeling was associated with higher frequency of current pain episodes, more types of pain, greater intensity, and also lower physiological arousal and subjective pain ratings during the cold pressor. The findings underscore the relationships between familial pain modeling and current pain-related functioning.

Acute Disease↗
PubMed1999

Pediatric brain tumors.

The first section of this article focuses on epidemiology, cause, diagnosis, and treatment of brain tumors in children and adolescents. The second section addresses the long-term consequences of tumors and their treatment, and a special emphasis is paid to cognitive and psychological outcomes.

Adolescent↗
PubMed1998

Seroepidemiology of rinderpest in bovids in Sri Lanka using the enzyme linked immunosorbent assay (ELISA) technique.

Approximately 0.2% (n = 4397) of the bovids (cattle and buffalo) in Sri Lanka were sampled, from June 1992 using a multi-stage sampling procedure. Serum antibodies for the rinderpest virus were detected using the competitive enzyme-linked immunosorbent assay. The age, the agroclimatic zone, the management system practiced in the farms, and the vaccination history of the sampled bovids were studied as potential risk factors for being seropositive. The prevalence of rinderpest antibodies in non-vaccinated bovids was 3.5% (n = 4101). The prevalence was higher in the dry zone (9%; where the outbreak emerged in 1987), compared to bovids in the other zones (1%). Seropositive bovids over three years of age were approximately at fourfold higher chances of being seropositive compared to those that were < or = 3 years old. The higher prevalence in older animals is probably due to exposure to the virus during the 1987 epidemic. Bovids from the dry zone (annual rainfall 20 to 35 inches) were at higher odds of being seropositive even after controlling for the possible effects of age, agroclimatic zone, management system and vaccination. The fact that 62% of bovids from the dry zone in this study were reared under extensive management system (free grazing) which allow unrestricted contact between animals, may be the reason for the above finding. A relatively poor response to vaccination observed in vaccinated bovids (seroprevalence = 12%; n = 296) could be attributed to difficulties in maintaining the vaccine at recommended temperatures in the field. This is the first island-wide study on seroprevalence of rinderpest in Sri Lanka.

Animals↗
PubMed1998

Low dihydrotestosterone and weight loss in the AIDS wasting syndrome.

24 consecutive AIDS patients with wasting, and who had never received anabolic therapies, were evaluated to determine their profile of sex hormones and whether transformation of testosterone (T) to the nuclear androgen, dihydrotestosterone (DHT), was impaired. Eleven (46%) patients had normal testosterone and DHT (group I), 10 (42%) had normal testosterone but low DHT (group II), and 3 (12%) had low testosterone and low DHT (group III). Age, prior opportunistic complications, symptoms, serum albumin, hemoglobin levels, and CD4 lymphocyte counts were similar in the groups. DHT was significantly lower (22.2 +/- 6.8 microg/dl) in group II compared with group I (50.8 +/- 15.3 microg/dl). The ratio of T/DHT, a measure of the conversion of testosterone to DHT, in group I was 15.1 +/- 3.5, which was within the range for eugonadal young men. In group II, the ratio was 22.3 +/- 1.5, indicating a defect in generation of DHT. Patients in group II had lost 9.2 +/- 3.5 kg compared with 5.6 +/- 2.6 kg in group I (p = .015). Thus, a syndrome of low DHT with normal testosterone was associated with significantly greater weight loss than in patients with normal testosterone and DHT. Further studies are needed to clarify whether low DHT is a result of AIDS wasting or is causally related to weight loss and whether androgen therapy in the form of DHT could reverse some of the metabolic changes associated with AIDS wasting.

Adult↗
PubMed1998

Patterns of recurrence in brain stem gliomas: evidence for craniospinal dissemination.

PURPOSE: The 3-year survival rate of pediatric patients with infiltrating brain stem gliomas (BSG) is < 10%. Treatment involves local field radiation, and local failure has been the hallmark of recurrence. With therapeutic advances and improved radiographic monitoring, perceived and actual patterns of failure may change. We report patterns of recurrence in a group of patients with close follow-up, treated on an institutional protocol incorporating hyperfractionated involved-field radiation therapy and concomitant carboplatin, who have been uniformly staged and treated and have undergone MRI surveillance. METHODS AND MATERIALS: From 1990-1995, 18 pediatric patients with BSG were treated on a Phase I-II trial of concurrent carboplatin and hyperfractionated radiotherapy. Eight had surgical procedures to document histology. Nine had hydrocephalus prior to death. All had pretreatment brain and spine MRIs, with and without gadolinium, that showed no other evidence of disease. Treatment consisted of 72.00 Gy involved-field hyperfractionated radiation therapy and dose-escalating concomitant carboplatin. RESULTS: Fifteen children have had progression of disease (median PFS = 9 months); and 13 have died (median OS = 14 months). Fourteen of the 15 children with progression had local failures, 8 of whom had evidence of noncontiguous spinal (4) or intracranial (7) disease documented by MRI or autopsy. One child with local control developed an intracranial metastasis. None had clinical manifestations of leptomeningeal disease. CONCLUSION: Leptomeningeal dissemination occurred within 1 month of local progression in nearly 30% of our patients and, overall, occurred in 50% prior to death. This high incidence may reflect close MRI surveillance or a changing pattern of recurrence. Because the majority of leptomeningeal disease occurs in the setting of local progression, treatment efforts must be directed primarily toward local control. However, management of leptomeningeal dissemination at recurrence is of increasing concern.

Antineoplastic Agents↗
PubMed1998

Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men.

BACKGROUND: The intercellular adhesion molecule ICAM-1 mediates adhesion and transmigration of leucocytes to the vascular endothelial wall, a step proposed to be critical in the initiation and progression of atherosclerosis. Whether concentrations of soluble ICAM-1 (sICAM-1) are raised in apparently healthy individuals who later suffer acute myocardial infarction is unknown. METHODS: We obtained baseline plasma samples from a prospective cohort of 14,916 healthy men enrolled in the Physicians' Health Study. With a nested case-control design, we measured sICAM-1 concentrations for 474 participants who developed a first myocardial infarction, and 474 controls (participants who remained healthy throughout the 9-year follow-up). Cases were matched to controls according to age and smoking status at the time of myocardial infarction. FINDINGS: We found a significant association between increasing concentration of sICAM-1 and risk of future myocardial infarction (p = 0.003), especially among participants with baseline sICAM-1 concentrations in the highest quartile (> 260 ng/mL; relative risk 1.6 [95% Cl 1.1-2.4], p = 0.02). This association was present overall as well as among non-smokers, and persisted after control for lipid and non-lipid risk factors. In multivariate analyses, the risk of future myocardial infarction was 80% higher for participants with baseline sICAM-1 concentrations in the highest quartile (relative risk 1.8 [1.1-2.8], p = 0.02). Similar risk estimates were seen among non-smokers. We found slight but significant correlations between sICAM-1 and fibrinogen, high-density-lipoprotein cholesterol, homocysteine, triglycerides, tissue-type plasminogen-activator antigen, and C-relative protein, but adjustment for these altered the risk little. The risk of myocardial infarction associated with raised concentrations of sICAM-1 seemed to increase with length of follow-up. INTERPRETATION: Our data support the hypothesis that cellular mediators of inflammation have a role in atherogenesis and provide a clinical basis to consider antiadhesion therapies as a novel means of cardiovascular disease prevention.

Antioxidants↗
PubMed1998

Conduction aphasia in a 3-year-old with a left posterior cortical/subcortical abscess.

A 3-year-old, right-handed girl developed a conduction-type aphasia following a second generalized seizure in the setting of a developing abscess involving left subcortical and cortical angular gyrus and arcuate fasciculus, and the posterior corpus callosum. The language disorder was fluent, characterized by age appropriate mean length of utterance and syntax, but with markedly reduced spontaneity of output, rapid rate of speech and mild dysarthria. Comprehension was relatively, but not completely spared. Naming, repetition, and reading (letters) were initially markedly impaired. Improvements in naming and repetition were associated with both literal and semantic paraphasias. Writing skills in the form of drawing were spared, but a mild apraxia to verbal command and imitation was initially present. Despite her young age, this child's fluent conduction aphasia and lesion localization were adult-like. Multimodal memory difficulties appeared to underlie what is best described as conduction aphasia.

Abscess↗
PubMed1998

Benign methylmalonic acidemia in a sibship with distal renal tubular acidosis.

Two male infants born to consanguineous parents were investigated for feeding difficulties in the 1st month of life. Both were found to have distal renal tubular acidosis (dRTA) with hypercalciuria. Nephrocalcinosis was present in the first child but not in the second. Urinary organic acid profile demonstrated an excess of methylmalonic acid (MMA) in both children in the absence of any other organic acid. MMA mutase activity and propionate incorporation were normal. There have been no neurological symptoms in either child. The first child has normal growth and psychomotor development at 4 years. His brother, who also has significant gastrooesophageal reflux, has failed to thrive and currently requires nasogastric feeding and caloric supplements to maintain weight along the 3rd percentile. Urinary and plasma MMA continue to be raised in both cases. The association of increased urinary and plasma MMA and dRTA presenting in the 1st month of life has not previously been reported and may represent a new syndrome of autosomal recessive inheritance.

Acidosis, Renal Tubular↗