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Biomedical subjects

M Gardiner

Publications and source records attributed to M Gardiner.

At least 19 recordsLinked to original sources
PubMed2004

Comparative effects of desloratadine, fexofenadine, and levocetirizine on nasal adenosine monophosphate challenge in patients with perennial allergic rhinitis.

Summary Background There are no data directly comparing the relative efficacy of modern H(1)-antihistamines in allergic rhinitis using nasal provocation challenge. Objective We elected to study the comparative effectiveness of usual clinically recommended doses of desloratadine (DES), fexofenadine (FEX), and levocetirizine (LEV), on nasal adenosine monophosphate (AMP) challenge in patients with perennial allergic rhinitis (PAR). Methods 16 patients with PAR were randomized in double-blind cross-over fashion to receive single doses of DES 5 mg, FEX 180 mg, LEV 5 mg, or placebo (PL), with nasal AMP challenge performed 12 h after dosing. Measurements of peak nasal inspiratory flow (PNIF) were made over 60 min after nasal AMP challenge. Results Pre-challenge values (mean+/-SEM) for PNIF (L/min) were not significantly different comparing all groups; DES (129+/-9), FEX (128+/-11), LEV (128+/-13), and PL (128+/-12). The maximum % PNIF fall from baseline over 60 min after nasal AMP challenge was significantly attenuated (P<0.05) compared to PL (50+/-4), with DES (32+/-5), FEX (36+/-4), and LEV (36+/-4). The area under the 60-min time-response curve (%.min) was also significantly attenuated (P<0.05) compared to PL (2110+/-268), with DES (1126+/-285), FEX (1225+/-255), and LEV (1261+/-194). There were no significant differences between the three H(1)-antihistamines for any outcomes. Conclusion DES, FEX, and LEV were equally effective in attenuating the response to nasal AMP challenge. However, further long-term studies will be required to study their comparative effects on nasal symptoms, quality of life, as well as on nasal inflammatory cells.

Adenosine Monophosphate↗
PubMed2001

Incorporating language phenotypes strengthens evidence of linkage to autism.

We investigated the effect of incorporating information about proband and parental structural language phenotypes into linkage analyses in the two regions for which we found the highest signals in our first-stage affected sibling pair genome screen: chromosomes 13q and 7q. We were particularly interested in following up on our chromosome 7q finding in light of two prior reports of linkage of this region to developmental language disorder, since one of the diagnostic criteria for autism is absent or abnormal language development. We hypothesized that if the language phenotype were genetically relevant to linkage at the chromosome 7q locus, then incorporating parents phenotypes would increase the signal at that locus, and most of the signal would originate from the subset of families in which both probands had severe language delay. The results support these hypotheses. The linkage signals we obtained on chromosome 7q as well as at least one signal on chromosome 13q are mainly attributable to the subgroup of families in which both probands had language delay. This became apparent only when the parents' history of language-related difficulties was also incorporated into the analyses. Although based on our data, we were not able to distinguish between epistasis or heterogeneity models, we tentatively concluded that there may be more than one autism susceptibility locus related to language development.

Autistic Disorder↗
PubMed2000

"I would rather be size 10 than have straight A's": a focus group study of adolescent girls' wish to be thinner.

The study aimed to investigate the body concerns of adolescent girls, together with the underlying motivations for the wish to be thinner. Focus group methodology was employed in order to access participants' experience in their own language. Altogether 67 girls of Year 11 (aged approximately 16 years) took part in five groups. Audiotaped and transcribed discussions were systematically coded for themes and rated on frequency, extensiveness, intensity, specificity and level of agreement. As expected, sociocultural influences, in particular the media, were reported as exerting the strongest pressures to be thin. More importantly, however, the girls displayed an unexpected sophistication in their conceptualization of the role of both media effects and body image in the construction of their self-image. Contrary to assumptions made in quantitative research, despite clearly articulating a desire to be thinner, the girls also described how this did not necessarily mean they were dissatisfied with their bodies. The findings suggest that the girls' meta-awareness and sophisticated understanding of the media and other pressures, may serve to moderate against these forces which would otherwise seem overwhelming.

Achievement↗
PubMed2000

Genetics of the epilepsies.

Molecular genetic analysis of mendelian epilepsies in humans and mice has revealed a diversity of underlying genes in symptomatic epilepsies associated with disordered brain development and neuronal survival. In contrast, the idiopathic mendelian epilepsies have emerged as a new category of channelopathies. New epilepsy loci have been mapped and one new epilepsy gene isolated. Functional analysis of epilepsy genes is providing new insights into the pathways that lead from mutant gene to hyperexcitable neurones. The major challenge for the future is the analysis of genetic epilepsies with complex inheritance.

Animals↗
PubMed1999

Molecular genetics of human epilepsies.

The term epilepsy encompasses a heterogeneous group of disorders, with a lifetime cumulative incidence of 3%. Genetic factors are thought to contribute to the aetiology in up to 60% of cases. Various molecular and cellular mechanisms give rise to epilepsy, and epilepsy genes fall into several distinct categories. They include genes in which mutations cause abnormal ion-channel function, disordered brain development, progressive neurodegeneration and disturbances of cerebral energy metabolism. In this review, we have focused on current understanding of the molecular genetic bases of human inherited epilepsies. Particular reference has been given to specific idiopathic epilepsies, neuronal migration disorders (cortical dysgeneses) and the progressive myoclonic epilepsies, and how information about this group of disorders might be used to develop new treatment strategies.

Journal Article↗
PubMed1999

Molecular genetics of the neuronal ceroid lipofuscinoses.

The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders characterised by the accumulation of autofluorescent storage material in neurons and other cell types. The clinical features include visual impairment, progressive myoclonic epilepsy, and cognitive decline reflecting progressive neurodegeneration. The NCLs are subdivided into several subtypes according to age of onset, clinical course, and ultrastructure of the storage material. The molecular genetic basis of this group of disorders has recently been clarified. Mutations in the gene encoding a lysosomal enzyme, palmitoyl protein thioesterase (PPT), cause infantile NCL (locus CLN1 on chromosome 1p32) or Haltia-Santavuori disease. This Finnish disease is characterised ultrastructurally by granular osmiophilic deposits (GRODs). Juvenile-onset NCL with GRODs also is caused by mutations in PPT. Classic late-infantile NCL (Jansky-Bielschowsky disease) is caused by mutations in a gene encoding a pepstatin-insensitive lysosomal peptidase (CLN2 on chromosome 11p15), and juvenile-onset NCL (Batten disease) is caused by mutations in a gene encoding a 438-amino-acid membrane protein (CLN3 on chromosome 16p12) of unknown function. A locus for Finnish variant late-infantile NCL, CLN5, has been mapped to chromosome 13q22 and a locus for variant late-infantile NCL, CLN6, to chromosome 15q21-23. These and further advances will allow the molecular basis of the NCLs to be elucidated and may lead to new strategies for diagnosis and treatment.

Adolescent↗
PubMed1996

Clinical assessment of the 1987 American College of Rheumatology criteria for rheumatoid arthritis.

The 1987 American College of Rheumatology (ACR) criteria for the classification of rheumatoid arthritis (RA) were clinically assessed. These criteria do not include findings of synovial fluid (SF) analysis and require no exclusion criteria. We have studied sequential patients with arthritis seen in four rheumatology centers in the Philadelphia area. Classifications by the ACR criteria were compared with our clinical diagnoses. Two hundred ninety eight patients were evaluated, 113 with RA and 185 with other diagnoses. Classifications as RA by the ACR criteria corresponded to our clinical diagnosis in 95% of the cases, corroborating the high sensitivity previously reported. However, we found a lower specificity (73%) than that reported (89%). False positive classifications as RA were found in 71% of patients with psoriatic arthritis, 48% of patients with SLE, and 31% of patients with gout. The specificity could be improved to 89% by excluding disorders with obvious distinguishing extraarticular features such as psoriasis or by SF findings of monosodium urate crystals. Awareness of these possible sources of confusion will further increase the teaching and epidemiologic value of these useful simplified criteria.

Adult↗
PubMed1996

Genetic evidence for the neuronal nitric oxide synthase gene (NOS1) as a susceptibility locus for infantile pyloric stenosis.

The etiological role of the gene for neuronal nitric oxide synthase (NOS1) in infantile pyloric stenosis (PS) was investigated by analysis of two intragenic polymorphisms (NOS1a and NOS1b) in 27 families. There was significant overall transmission disequilibrium between PS and NOS1a (P = .006). Consideration of each allele independently revealed a highly significant tendency for allele 7 (210 bp) to be preferentially transmitted to the affected offspring (P = .0006). These observations suggest that NOS1 is a susceptibility locus for PS.

Alleles↗
PubMed1995

Linkage analysis of late-infantile neuronal ceroid-lipofuscinosis.

The neuronal ceroid-lipofuscinoses (NCL) are a group of neurodegenerative disorders with an autosomal-recessive pattern of inheritance. There are 3 main categories of childhood NCL, namely, infantile, late-infantile, and juvenile NCL. These can be distinguished on the basis of age of onset, clinical course, and histopathology. A number of variant forms of NCL have also been described, and these show symptoms intermediary between the main classical forms. The genes for both the infantile and juvenile forms of NCL have previously been mapped to chromosome areas 1p32 and 16p12, respectively. The gene for late-infantile NCL (LINCL), CLN2, has been excluded from both these loci, but its location is as yet unknown. Recently, CLN5, the gene for the Finnish variant form of LINCL, was mapped to 13q21.1-32. Using the 3 microsatellite markers which were most tightly linked to CLN5, we have excluded CLN2 from this region using a subset of 17 families. Thus, CLN2 represents a fourth distinct genetic locus involved in the pathogenesis of NCL.

Age of Onset↗
PubMed1995

Genetics of the epilepsies.

The epilepsy gene map has been refined and extended with new information concerning benign familial neonatal convulsions, benign familial infantile convulsions, Unverricht-Lundborg disease, epilepsy with progressive mental retardation and juvenile myoclonic epilepsy. Understanding of the molecular basis of paroxysmal disorders affecting the central nervous system has been revolutionalized with the identification of mutations in genes for the neurotransmitter receptors, GLRA1 and CHRNA4, and a voltage-gated potassium channel, KCNA1, as causes of inherited neurological disease.

Adolescent↗