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Biomedical subjects

J Allen

Publications and source records attributed to J Allen.

At least 127 records · Page 7Linked to original sources
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↗
PubMed1998

On memories of childhood abuse: a phenomenological study.

OBJECTIVE: To explore the phenomenon of memories and reported recovered memories of childhood abuse, and to examine ways in which clients and therapists assess the veridicality of such memories. METHOD: Qualitative methodology utilizing phenomenological inquiry. Within the context of a wider study exploring perceptions of helpful and unhelpful factors in the therapeutic process, a sub-sample of 36 in-depth interviews with clients, therapists, and therapists who considered themselves to have been abused as children included a focus on abuse-memory experiences. Data were analyzed according to Grounded Theory principles. RESULTS: Participants described six types of abuse-memory experiences. The most frequently reported type was where abuse was known about but kept "out of mind." The six types can be collapsed into three main categories: (1) continual knowledge of abuse (69.5%); (2) unexpected abuse-memories recovered from a prior state of partial knowledge of abuse (16.5%); and (3) abuse-memories recovered from a prior state of no knowledge of abuse (30%). Independent corroboration of recovered memories was rare; and criteria which were reportedly used to assess the veridicality of such memories were problematic when viewed in the light of cognitive psychology research on memory processes. CONCLUSION: It seems that most people who were abused as children have always had continual knowledge of this, although it is often only much later than many connect problems in adult life with the consequences of such abuse. People also experience the recovery of memories of abuse about which they were previously unaware. There is a danger that the specific controversy surrounding "false memories" may become over-generalized contributing to increased public scepticism about the prevalence and negative impact of child abuse, and the potential effectiveness of appropriate therapeutic services.

Adult↗
PubMed1998

Use of the esophageal detector device in a newborn-piglet model.

STUDY OBJECTIVE: To determine the accuracy of the esophageal detector device (EDD) in predicting correct endotracheal tube (ETT) placement in a newborn-piglet model. METHODS: We used an EDD, comprising a 5-, 10- or 20-mL syringe attached to 4-mm tubing fitted to a 15-mm ETT adapter, to aspirate gas from cuffed or uncuffed ETTs placed in the trachea or esophagus of each newborn piglet. During aspiration, we noted any resistance encountered while pulling back the plunger of the syringe and recorded the total volume of gas aspirated into the syringe. A positive test, signifying tracheal ETT placement, was defined as the ability to freely aspirate gas without resistance and the aspiration of enough gas to fill the entire volume of the syringe. A negative test, signifying esophageal ETT placement, was defined as resistance encountered during the aspiration of gas into the syringe and rebound of the syringe plunger, leading to aspiration of a volume of gas less than the total volume of the syringe. RESULTS: We conducted 444 trials (222 for uncuffed ETTs, 222 for cuffed ETTs). ETT size ranged from 3.0 to 4.5 mm. For cuffed ETTs, the 5-mL syringe had a sensitivity of 100% and a specificity of 5%, the 10-mL syringe had a sensitivity of 95% and a specificity of 16%, and the 20-mL syringe had a sensitivity of 86% and a specificity of 97%. For uncuffed ETTs, the 5-mL syringe had a sensitivity of 100% and a specificity of 5%, the 10-mL syringe had a sensitivity of 97% and a specificity of 24%, and the 20-mL syringe had a sensitivity of 81% and a specificity of 100%. CONCLUSION: No syringe had 100% sensitivity and specificity in correctly predicting ETT placement. The 20-mL syringe had the highest combination of sensitivity and specificity. Further studies are warranted to determine whether the EDD using a 20-mL syringe would aid in the prediction of correct ETT placement in the pediatric population.

Animals↗
PubMed1998

Drug-induced linear IgA disease with antibodies to collagen VII.

Linear IgA disease (LAD) is characterized by circulating and tissue-bound IgA antibodies against heterogeneous antigens in the cutaneous basement membrane zone. In most cases the cause is unknown, but a minority of cases has been drug induced. We report a 76-year-old man who developed an acute blistering eruption following high-dose penicillin treatment for pneumococcal septicaemia. Indirect immunofluorescence demonstrated dermal binding IgA antibodies, and Western blotting of serum showed reactivity with a 250 kDa dermal antigen corresponding to collagen VII of anchoring fibrils. Indirect immunoelectron microscopy showed antibody labelling in the lamina densa and sublamina densa zone. This is one of the few cases of drug-induced LAD in which the target antigen profile has been characterized, and the first in which the antigen has been shown to correspond to collagen VII.

Aged↗
PubMed1998

Blister fluid for the diagnosis of subepidermal immunobullous diseases: a comparative study of basement membrane zone autoantibodies detected in blister fluid and serum.

The subepidermal immunobullous diseases bullous pemphigoid (BP), cicatricial pemphigoid (CP), pemphigoid gestationis (PG) and linear IgA disease (LAD) are characterized by circulating and in vivo deposition of antibodies to antigens in the cutaneous basement membrane zone (BMZ). Indirect immunofluorescence (IMF) of serum is a routine diagnostic test to detect circulating BMZ antibodies in these diseases. We have compared the titres of IgG and IgA and their subclasses, also of IgM and IgE BMZ antibodies in serum and aspirated blister fluid in 35 adult patients with subepidermal immunobullous diseases: BP (n = 30), PG (n = 2), CP (n = 1), and LAD (n = 2), by indirect IMF on intact and salt-split skin. The antibody titre in blister fluid was the same or one dilution less than serum in most cases and there was no significant difference between these results (P > 0.05). IgG1 and IgG4 were the predominant subclasses in both blister fluid and serum in BP. Indirect IMF of serum and blister fluid was also carried out on trypsinized epidermal cells in a subgroup of patients with BP (n = 19). Typical polar fluorescence was obtained in all 14 cases which had positive indirect IMF on intact and split skin. Our findings demonstrate that blister fluid can be used as an alternative to serum for indirect IMF in subepidermal immunobullous diseases. This avoids the need for venesection and has a practical application in children and those with poor venous access.

Adult↗