Increase in allergy following donor lymphocyte infusions.
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Adult↗
Biomedical subjects
J Maher
Publications and source records attributed to J Maher.
The development of an EORTC quality of life questionnaire to assess chemotherapy-induced peripheral neuropathy: the QLQ-CIPN20.
Chemotherapy-induced peripheral neuropathy (CIPN) is a common phenomenon, often resulting in serious limitations in daily functioning and compromised quality of life. Currently available toxicity grading systems typically use a combination of clinical and paraclinical parameters and relies on the judgment of clinicians and/or nurses. However, because many of the symptoms of CIPN are subjective in nature, it is only logical that an assessment of CIPN be based, at least in part, on patient self-report data. We report on the development of a patient self-report questionnaire, the CIPN20, intended to supplement the core quality of life questionnaire of the European Organization for Research and Treatment of Cancer (EORTC). Following EORTC guidelines, relevant CIPN-related issues were identified from a literature survey and interviews with health professionals (n=15) and patients (n=112). The resulting 20-item questionnaire was pre-tested in three languages and four countries and is currently being examined in a large, international clinical trial. The EORTC CIPN20 should provide valuable information on CIPN-related symptoms and functional limitations of patients exposed to potentially neurotoxic chemotherapeutic and/or neuroprotective agents.
Adult↗
Targeting cytotoxic T lymphocytes for cancer immunotherapy.
In light of their preeminent role in cellular immunity, there is considerable interest in targeting of cytotoxic T-lymphocytes to cancer. This review summarises the active and passive immunotherapeutic approaches under development to achieve this goal, emphasising how recent advances in tumour immunology and gene transfer have impacted upon this field.
Gene Transfer Techniques↗
Quality assessments of HMO diagnosis databases used to monitor childhood vaccine safety.
OBJECTIVE: To assess the quality of automated diagnoses extracted from medical care databases by the Vaccine Safety Datalink (VSD) study. METHODS: Two methods are used to assess quality of VSD diagnosis data. The first method compares common automated and abstracted diagnostic categories ("outcomes") in 1-2% simple random samples of study populations. The second method estimates positive predictive values of automated diagnosis codes used to identify potential cases of rare conditions (e.g., acute ataxia) for inclusion in nested case-control medical record abstraction studies. RESULTS: There was good agreement (64-68%) between automated and abstracted outcomes in the 1-2% simple random samples at 3 of the 4 VSD sites and poor agreement (44%) at 1 site. Overall at 3 sites, 56% of children with automated cerebella ataxia codes (ICD-9 = 334) and 22% with "lack of coordination" codes (ICD-9 = 781.3) met objective clinical criteria for acute ataxia. CONCLUSIONS: The misclassification error rates for automated screening outcomes substantially reduce the power of screening analyses and limit usefulness of screening analyses to moderate to strong vaccine-outcome associations. Medical record verification of outcomes is needed for definitive assessments.
Child, Preschool↗
Molecular and functional characterization of genes encoding horse MHC class I antigens.
Sequence and functional analyses were undertaken on two cDNAs and a genomic clone encoding horse major histocompatibility complex (MHC) class I molecules. All of the clones were isolated from a single horse that is homozygous for all known horse MHC class I and class II antigens. The two cDNAs (clones 8-9 and 1-29) were isolated from a lymphocyte library and encode polymorphic MHC antigens from two loci. The genomic cosmid clone, isolated from a sperm library, contains the 8-9 gene. All three genes were expressed in mouse L-cells and were recognized by alloantisera and, for the cDNAs, by alloreactive cytotoxic T lymphocytes. A total of 3815 bp of the genomic clone were sequenced, extending from 429 bp upstream (5') of the leader peptide through the 3' untranslated region. Promoter region motifs and an intron-exon structure characteristic of MHC class I genes of other species were found. A subclone containing 407 bp of the promoter region was inserted into a chloramphenicol acetyl transferase reporter plasmid, tested in transient transfection assays, and found to have promoter activity in heterologous cells. This genomic clone will enable detailed studies of MHC class I gene regulation in horse trophoblasts, and in horse retroviral infections.
Amino Acid Sequence↗
Double-blind randomized phase II study of hyperbaric oxygen in patients with radiation-induced brachial plexopathy.
BACKGROUND: Radiation-induced brachial plexopathy (RIBP) is an untreatable complication of curative radiotherapy for early breast cancer, characterized by chronic neuropathic pain and limb paralysis. Hyperbaric oxygen (HBO2) therapy is known to promote healing of tissue rendered ischaemic by radiotherapy, but is untested in RIBP. METHODS: Thirty four eligible research volunteers suffering from RIBP were randomized to HBO2 or control group. The HBO2 group breathed 100% oxygen for 100 min in a multiplace hyperbaric chamber on 30 occasions over a period of 6 weeks. The control group accompanied the HBO2 group and breathed a gas mixture equivalent to breathing 100% oxygen at surface pressure. All volunteers and investigators, except the operators of the hyperbaric chamber and the trial statistician, were blind to treatment assignments. The warm sensory threshold, which measures the function of small sensory fibres, was selected as the primary endpoint. FINDINGS: Pre-treatment neurophysiological tests were grossly abnormal in the affected hand compared to the unaffected hand in both HBO2 and control groups, as expected, but no statistically significant differences were noted in either group at any time up to 12 months post-treatment. However, normalization of the warm sensory threshold in two of the HBO2 group was reliably recorded. Two cases with marked chronic arm lymphoedema reported major and persistent improvements in arm volume for at least 12 months after treatment with HBO2. IINTERPRETATION: There is no reliable evidence to support the hypothesis that HBO2 therapy slows or reverses RIBP in a substantial proportion of affected individuals, although improvements in warm sensory threshold offer some suggestion of therapeutic effect. Improvement in long-standing arm lymphoedema was not anticipated, and justifies further investigation.
Action Potentials↗
The CYP2E1 knockout delivers another punch: first ASH, now NASH. Alcoholic steatohepatitis. Nonalcoholic steatohepatitis.
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Animals↗
Antidiabetic treatment for NASH?
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Animals↗
Family functioning in subjects with pseudoseizures and epilepsy.
The purpose of this study was to identify differences in family functioning between subjects with pseudoseizures and their families, and control subjects with epilepsy. Thirty-one adult subjects with pseudoseizures and 31 controls with intractable epilepsy, whose diagnoses were confirmed using video-EEG, were recruited from the epilepsy unit of a tertiary care hospital over a 4-year period. Each study participant and their first-degree adult family members completed two standardized questionnaires designed to measure family functioning: the McMaster Family Assessment Device (FAD) and the Beavers Self-Report Family Inventory (SFI). Individuals with pseudoseizures, when compared with epileptic subjects, exhibited significantly elevated scores in three scales of the FAD and in one scale of the SFI, indicating greater psychopathology within the family, as perceived by the individual. Statistically significant differences with the FAD were on measures of affective involvement (p = .044), communication (p = .004), and general functioning (p = .013). The SFI revealed significantly greater difficulty with conflict (p = .050). No differences were noted between subjects with both pseudoseizures and epilepsy and subjects with pseudoseizures alone. In comparison with the families of the epileptic group, the families of subjects with pseudoseizures displayed statistically significant elevations in their responses on the roles scale (p = .003) of the FAD. The responses of the family members did not differ in regard to the role they assumed within the family unit (i.e., spouse, parent). In summary, individuals with pseudoseizures view their families as being more dysfunctional, particularly in the area of communication, whereas their family members perceived difficulties in defining roles. This suggests that family education and interventions focusing on these areas, may be an important aspect of the treatment of patients with pseudoseizures.
Adult↗
Report investigating the importance of head restraint positioning in reducing neck injury in rear impact.
Neck injury resulting from rear impact (often known as whiplash) is a serious cause of road trauma. It is often underestimated or overlooked because such injuries are minor on traditional injury scales but can result in long term pain and disability. The paper begins with a brief review of research into head restraints and whiplash done so far. A review of international head restraint regulations revealed the absence of any horizontal offset requirements. A review of seat strength requirements and testing procedures showed that a regulation that required a collapsible seat would involve significant compliance testing. This paper concludes a preliminary project conducted by the Federal Office of Road Safety (FORS) where the head restraints for twenty Australian market vehicles were assessed using known performance criteria. A key finding of the report was that most of the vehicles allowed for vertical adjustment of the head restraint. Also important was that none of the vehicles measured allowed horizontal adjustment and on some of the head restraints the horizontal displacement increased as the vertical height increased. As the understanding of neck injury mechanisms in rear impact develops, there may be some scope for FORS to facilitate the improvement of these standards. Further research into neck injury mechanisms may reveal yielding seat backs or new 'active' head restraint technology as a more effective countermeasure. In the meantime, educating occupants to correctly adjust their head restraints seems to be an effective way to reduce injuries in existing vehicles.
Accidents, Traffic↗
Quality of life evaluation in oncological clinical trials - the EORTC model. The EORTC Quality of Life Study Group.
The European Organization for Research and Treatment of Cancer (EORTC) has taken a leading role in the development of the methodology of quality of life (QL) measurement. In the EORTC Quality of Life Study Group (QLSG) valid instruments to assess QL in a general manner and disease-specific modules have been developed to be used in oncological clinical trials. Statistical and methodological aspects of QL research are discussed. The application of QL assessments in clinical trials represents a subsequent challenge. To improve the practice of QL assessment in clinical trials an 'EORTC model' has been developed. This model requires the collaboration of liaison persons, the EORTC Cooperative Tumour Groups and the EORTC Data Centre Quality of Life Unit (QL Unit). Cooperation between these parties, protocol development and advantages and concerns of the model are mentioned in this paper. Finally, suggestions for improvement are proposed.
Clinical Protocols↗
Management of antiepileptic drugs following epilepsy surgery: a review.
The favourable impact of surgery for intractable epilepsy on seizures is well documented. However, few studies have determined what changes in antiepileptic drug (AED) therapy occur following surgery. Alterations in AED blood levels in the immediate postoperative period can result in breakthrough seizures. In long term follow-up, one-third to one-half of seizure-free patients after temporal lobectomy, the most common type of epilepsy surgery, still require AED treatment which usually has been reduced from polytherapy to monotherapy. In our study of 93 patients followed two years after temporal lobectomy, polytherapy decreased from 78% before surgery to 14% postoperatively, while medication was discontinued in 44%. Early reduction from polytherapy to monotherapy can often be carried out in the immediate postoperative period but the most appropriate timing of cessation of AED treatment has yet to be determined. Patients undergoing extratemporal resections and other forms of epilepsy surgery associated with less favourable postoperative seizure control may achieve comparatively less reduction in antiepileptic medication. We generally do not recommend stopping AEDs prior to one year after surgery.
Anticonvulsants↗
Timing of antenatal corticosteroids and neonatal pulmonary mechanics.
OBJECTIVE: We sought to compare lung mechanics in infants treated with multiple courses of antenatal corticosteroids with those in matched control infants delivered >7 days from dosing and those of matched untreated infants. STUDY DESIGN: Eighteen infants who received multiple courses of corticosteroids and were delivered within 7 days of dosing were matched with 18 infants who received 1 course of corticosteroids >7 days before delivery (remote) and 18 untreated infants. Respiratory compliance and functional residual capacity were measured within 36 hours. Differences were compared by analysis of variance. RESULTS: Infant demographics were similar. Respiratory compliance was higher in the multiple-course group than in the remote or untreated group (P <.02). Functional residual capacity was higher in the multiple-course group than in the untreated group (P <.05) but similar to that found in the remote group. CONCLUSION: Babies delivered after multiple courses of corticosteroids and within 7 days of dosing demonstrated improved respiratory compliance compared with untreated and remotely treated infants. This suggests that the enzyme system responsible for surfactant production can be repetitively induced despite prior treatment with corticosteroids. The increased functional residual capacity in remotely treated infants may reflect a maturation of lung architecture independent of surfactant production.
Betamethasone↗
Evidence favoring genetic heterogeneity for febrile convulsions.
PURPOSE: Two large Canadian kindreds appearing to segregate febrile convulsions as an autosomal dominant trait were evaluated for linkage to three known FC loci, as well as other epilepsy loci. METHODS: Members of the two families were genotyped with microsatellite markers linked to the previously identified febrile convulsion loci, FEB1, FEB2, and GEFS+, and we performed two-point linkage analyses by assuming an autosomal dominant mode of inheritance. RESULTS: We report the exclusion of the FC trait in our families to FEB1 on 8q13-21 and to a second febrile convulsion locus on 19p13. Furthermore, we also excluded the GEFS+ locus on 19q13.1 as the cause of febrile convulsions in both kindreds. Microsatellite markers linked to juvenile myoclonic epilepsy (EJM1), benign neonatal familial convulsions EBN1 and EBN2, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), idiopathic generalized epilepsy (EGI), progressive myoclonic epilepsy of Unverricht-Lundborg (EPM1), and partial epilepsy with auditory features (EPT), were also excluded as potential loci linked to the FC trait in our families. CONCLUSIONS: These findings favor considerable genetic heterogeneity for febrile convulsions.
Age of Onset↗
Central nervous system effects of H1-receptor antagonists in the elderly.
BACKGROUND: The potential adverse central nervous system effects of H1-receptor antagonists have not been optimally studied in the elderly. OBJECTIVE: We hypothesized that newer H1-receptor antagonists such as cetirizine and loratadine would cause less central nervous system dysfunction than the older H1-receptor antagonists diphenhydramine and chlorpheniramine in this population, as they do in younger subjects. METHODS: We performed a randomized, double-blind, single-dose, placebo-controlled, 5-way crossover study in 15 healthy elderly subjects (mean age 71 +/- SD 5 years). On study days at least 1 week apart, they received cetirizine 10 mg, loratadine 10 mg, diphenhydramine 50 mg, chlorpheniramine 8 mg, or placebo. Outcome measures, recorded before and 2 to 2.5 hours after dosing were latency of the P300 event-related potential in which increased latency reflects a decreased rate of cognitive processing, visual analogue scale for subjective somnolence, and histamine skin tests for measurement of peripheral H1-blockade. RESULTS: The changes in P300 following each treatment yielded variances that were not equal (P > .05), precluding usual statistical analysis of the means. These variances were ranked: chlorpheniramine > diphenhydramine > loratadine > placebo > cetirizine. The rank of mean differences in the visual analogue scale increase from pre-dose baseline was: diphenhydramine > chlorpheniramine > cetirizine > loratadine > placebo. All H1-receptor antagonists suppressed the histamine-induced wheal and flare significantly compared to baseline. CONCLUSION: In the elderly, the new H1-receptor antagonists cetirizine and loratadine are less likely to cause adverse central nervous system effects than the old H1-antagonists chlorpheniramine or diphenhydramine, but this requires confirmation using additional objective tests of central nervous system function.
Aged↗
Diagnostic difficulties in myasthenia gravis.
Four patients with myasthenia gravis presented with severe, largely isolated, bulbar and respiratory muscles weakness. Tensilon tests were positive and antiacetylcholine receptor (anti-AChR) antibody titers were negative in all patients. Only 1 patient had a greater than 10% decremental response during the period of respiratory failure. Although routine nerve conduction studies were normal, all had very low-amplitude diaphragmatic compound muscle action potentials. Three patients had abundant fibrillation potentials and positive sharp waves largely restricted to respiratory muscles. Clinical and electrophysiological findings improved with corticosteroids, and surprisingly, decremental responses became positive in all patients. The assessment of patients with largely isolated bulbar and respiratory muscle weakness due to myasthenia gravis may be difficult and misleading, as anti-AChR antibody titers may be negative, decremental responses may be absent, and electrophysiological assessment atypical. Due consideration of clinical symptomatology, a Tensilon test, and a trial of immunosuppression may be necessary to establish the diagnosis.
Adult↗
Cytokine overproduction in healthy first degree relatives of patients with IDDM.
Healthy family members of patients with insulin-dependent diabetes mellitus (IDDM) are known to share a number of immunological abnormalities with their affected relatives. Since monocyte and type 1 T-cell-derived cytokines contribute to the pathogenesis of IDDM, we studied the production of these cytokines in the healthy first degree relatives of 29 children with IDDM. We report that circulating tumour necrosis factor-alpha (TNF-alpha) and soluble interleukin-2 (sIL-2) receptor were present in increased amounts in non-diabetic family members at levels similar to those found in the diabetic children (duration of disease 3 months-5 years). Furthermore, marked hypersecretion of IL-1alpha and TNF-alpha by mitogen-stimulated peripheral blood mononuclear cells was found in both diabetic and healthy family members. Abnormalities of cytokine production in healthy relatives did not correlate with the presence of islet cell antibodies or with HLA DR type. These data indicate that healthy family members of patients with IDDM exhibit overproduction of a number of cytokines that have been implicated in diabetogenesis.
Adolescent↗
Molecular interaction of CD1b with lipoglycan antigens.
The ability of human CD1b molecules to present nonpeptide antigens is suggested by the T cell recognition of microbial lipids and lipoglycans in the presence of CD1b-expressing antigen-presenting cells. We demonstrate the high-affinity interaction of CD1b molecules with the acyl side chains of known T cell antigens, lipoarabinomannan, phosphatidylinositol mannoside, and glucose monomycolate. Furthermore, CD1b-antigen binding was optimal at acidic pH, consistent with the known requirement for endosomal acidification in CD1b-restricted antigen presentation. The mechanism for CD1b-ligand interaction involves the partial unfolding of the alpha helices of CD1b at acidic pH, revealing a hydrophobic binding site that could accommodate lipid. These data provide direct evidence that the CD1b molecule has evolved unique biochemical properties that enable the binding of lipid-containing antigens from intracellular pathogens.
Anilino Naphthalenesulfonates↗