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Biomedical subjects

M Malone

Publications and source records attributed to M Malone.

At least 55 records · Page 3Linked to original sources
PubMed2000

Linkage study of two polymorphisms at the dopamine D3 receptor gene and attention-deficit hyperactivity disorder.

Data from animal studies suggest that the dopamine D3 receptor gene may have a role in locomotion and behavioral regulation. Therefore, this gene has been suggested as a candidate for attention-deficit hyperactivity disorder (ADHD). The dopamine D3 receptor gene (DRD3) has two common polymorphisms, one in exon I that changes a Serine to Glycine (Ser9Gly) and alters the recognition site for the restriction enzyme MscI [Lannfelt et al., 1992]. The other common polymorphism is located in intron 5 and results in the change of a restriction site for MspI [Griffon et al., 1996]. We investigated the possibility of linkage of the dopamine D3 receptor gene in 100 small, nuclear families consisting of a proband with ADHD, their parents, and affected siblings. We examined the transmission of the alleles of each of these polymorphisms and the haplotypes of both polymorphisms using the transmission disequilibrium test [Spielman et al., 1993]. We did not observe biased transmission of the alleles at either polymorphism or any haplotype. Our findings using this particular sample do not support the role of the dopamine D3 gene in ADHD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:114-117, 2000.

Attention Deficit Disorder with Hyperactivity↗
PubMed2000

Identification of DNA variants in the SNAP-25 gene and linkage study of these polymorphisms and attention-deficit hyperactivity disorder.

The gene for the synaptic vesicle docking fusion protein, synaptosomal-associated protein of 25 kDa (SNAP-25), has been implicated in the etiology of attention-deficit hyperactivity disorder (ADHD) based on the mouse mutant strain coloboma. This neutron-irradiation induced mouse strain is hemizygous for the deletion of the SNAP-25 gene and displays spontaneous hyperactivity that is responsive to dextroamphetamine. Because of these characteristics, this strain has been suggested to be a mouse model for ADHD. We identified using single stranded conformational polymorphism analysis (SSCP) four DNA sequence variants in the 3' untranslated region of the human SNAP-25 gene. We searched for polymorphisms in the 3' untranslated region because the intron/exon structure of this gene has not yet been determined. We tested for linkage of this gene and ADHD using two of the identified polymorphisms that change a restriction enzyme recognition site. We examined the transmission of the alleles of each of these polymorphisms and the haplotypes of both polymorphisms using the transmission disequilibrium test in a sample of 97 small nuclear families consisting of a proband with ADHD, their parents, and affected siblings. We observed biased transmission of the haplotypes of the alleles of these two polymorphisms. Our findings are suggestive of a role of this gene in ADHD.

Adolescent↗
PubMed2000

Attention-deficit hyperactivity disorder and the gene for the dopamine D5 receptor.

A recent study has suggested a possible association of a polymorphism near the dopamine D5 receptor gene (DRD5) and attention-deficit hyperactivity disorder. The polymorphism studied was a (CA)n repeat located in the cosmid containing the D5 receptor gene2 and the allele that was reported to be associated with attention-deficit hyperactivity disorder (ADHD) was the 148-bp allele. In this study we sought to replicate this finding by testing for biased transmission of the alleles at this same polymorphism in a sample of 92 families with an ADHD proband. We did not observe significant evidence for biased transmission of the 148-bp allele, however we did observe biased transmission of two other alleles, the 136-bp allele and the 146-bp allele. For these two alleles the bias was for these two alleles not to be transmitted to the ADHD children. The number of informative transmissions for these two alleles was small, therefore it would be premature to make any conclusions from our study concerning the role of DRD5 in ADHD.

Adolescent↗
PubMed2000

Evidence for the serotonin HTR2A receptor gene as a susceptibility factor in attention deficit hyperactivity disorder (ADHD).

A recent study demonstrated that treatment of hyperactive mice with psychostimulants and serotonergic agents produced a calming effect that was dependent on serotonergic neurotransmission and was not associated with any changes in extracellular dopamine levels. The complex interaction between the serotonergic and dopaminergic neurotransmitter systems suggests that a balance between the two systems may be necessary for mediating hyperactive behaviour. Defects in serotonin system genes, therefore, may disrupt normal brain serotonin function causing an imbalance between these neurotransmitter systems leading to the development of attention deficit hyperactivity disorder (ADHD). Using the transmission disequilibrium test (TDT), the current study assesses for linkage disequilibrium between polymorphisms in the serotonin HTR2A receptor gene and ADHD. One hundred and fifteen families with a total of 143 children diagnosed with ADHD (DSM-IV) were genotyped for the His452 Tyr and the T102C polymorphisms in the serotonin HTR2A receptor gene. TDT analysis revealed a preferential transmission of the 452Tyr allele to the affected offspring (P = 0.03), suggesting linkage disequilibrium of this polymorphism with ADHD. This may open a new door in ADHD molecular genetics research, expanding the existing view of a catecholaminergic hypothesis to include a serotonergic hypothesis and should help elucidate the complex interplay among the neurotransmitter systems in the etiology of ADHD.

Adolescent↗
PubMed2000

Lipoatrophic panniculitis and chromosome 10 abnormality.

We report a 3-year-old girl with a 12-month history of an acquired lipoatrophy that was rapidly progressive. Her karyotype revealed additional material on chromosome 10 at the 10q26 location. The human pancreatic lipase gene maps to chromosome 10q24-26, and we postulate an association. Lipoatrophic panniculitis describes the panniculitides in which atrophy is a feature. The classification of these diseases is confusing in the literature and the precise diagnosis still relies on a combination of clinical and laboratory assessment. Our finding of a chromosomal abnormality on chromosome 10q26 has not been described previously.

Child, Preschool↗
PubMed2000

Linkage of the dopamine D4 receptor gene and attention-deficit/hyperactivity disorder.

OBJECTIVE: There is considerable evidence supporting a genetic component in the etiology of attention-deficit/hyperactivity disorder (ADHD). Because stimulant medications act primarily on the dopaminergic system, dopamine system genes are prime candidates for genetic susceptibility factors for ADHD. Previous studies by several groups have observed a significant association of ADHD and an allele with 7 copies of the 48 base pair repeat in the third exon of the dopamine D4 receptor. METHOD: The authors sought to replicate these previous findings by collecting an independent sample of families from Toronto, Ontario, Canada, and confirming this finding in an expanded sample of ADHD families collected from Irvine, California. Using the transmission disequilibrium test (TDT), the authors tested for biased transmission of the 7-repeat allele at the exon III polymorphism of the dopamine D4 receptor locus in these samples of ADHD subjects. RESULTS: Biased transmission of the 7-repeat allele from parents to ADHD probands and their affected siblings was observed in the 2 new samples of families collected in Toronto and Irvine (TDT chi2 = 2.711, 1 df, one-sided p value = .050) and for these samples combined with the 52 families previously reported from Irvine (TDT chi2 = 6.426, 1 df, one-sided p value = .006). CONCLUSIONS: The results of this study further support the possibility of a role of the dopamine D4 receptor locus in ADHD.

Adolescent↗
PubMed2000

A history of health visiting and parenting in the last 50 years.

Although the nineteenth century origins of health visiting have been well documented, rather less attention had been paid to the development of this profession in the last 50 years. Similarly, although 'parenting' is of concern and interest to contemporary society less is known about its development during the past half-century. This paper draws upon two, hitherto much underused data sources - the 'Jameson Report (1956) and the work of John and Elizabeth Newson (1963 and 1968) to explore the history of health visiting and 'parenting'. The sources suggest that health visiting and parenting are intertwined with health visiting supporting of parenting in two main ways - one focusing on interventions with individual families and the other addressing the social context in which 'parenting' has taken place. Four phases of health visiting practice are identified and analyzed according to the nature of parenting support offered therein.

Community Health Nursing↗
PubMed1999

Linkage study of catechol-O-methyltransferase and attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder is the most common child psychiatric disorder with a prevalence rate in an Ontario study of 9% in boys and 3% in girls [Szatmari et al., 1989]. This disorder is characterized by problems in the areas of attention, overactivity, impulse control, and distractibility. Strong evidence for a genetic component has been provided from twin, family, and adoption studies [for review see Levy et al., 1998] and molecular genetic studies are in progress by several groups worldwide. The Catechol-O-Methyltransferase (COMT) gene is an interesting candidate for ADHD as it is involved in the breakdown of dopamine and norepinephrine, neurotransmitters strongly implicated in the etiology of ADHD. In addition, children with velo-cardio-facial syndrome, a deletion syndrome of the chromosomal region 22q11 where the COMT gene has been localized, often have symptoms of ADHD suggesting this gene may have an etiological role in ADHD. In this study, we have tested for linkage in ADHD families using the functional polymorphism at codon 158 that determines COMT activity [Lachman et al., 1996] and analyzed the data with the transmission disequilibrium test (TDT). A total of 77 nuclear families collected from Toronto were genotyped. We find no evidence for linkage of this polymorphism and ADHD in our sample. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:710-713, 1999.

Adolescent↗
PubMed1999

Beneficial effects of pharmacotherapy on weight loss, depressive symptoms, and eating patterns in obese binge eaters and non-binge eaters.

OBJECTIVE: The purpose of this study was to compare the impact of drug therapy on weight loss, Beck Depression Inventory (BDI) scores, and binge eating patterns (BES) between obese binge eaters and non-binge eaters. RESEARCH METHODS AND PROCEDURES: 22 severe binge eaters, 17 moderate binge eaters, and 16 non-binge eaters received phentermine resin 15mg/day and dl-fenfluramine 20mg three times daily over a 6 month period for weight loss. All data are reported as mean+/-S. RESULTS: The percent weight loss compared to baseline within the 3 groups ranged from 8.9% to 11.3% at 3 months and 10.6% to 14.9% at 6 months. After 6 months, 73% of the severe binge eaters, 59% of moderate binge eaters and 69% of non-binge eaters had experienced more than 10% weight loss. BDI scores were significantly higher in the severe group at baseline when compared to non-binge eaters (p<0.006). After 3 and 6 months BDI scores improved in all groups but remained significantly different between the severe and non-binge eaters until the 6-month assessment. BES scores declined in all groups over the 6-month period. Echocardiograms were performed in 35 of 55 subjects following reports of a possible association between fenfluramine and valvular changes. Fifteen (43%) of subjects had no abnormal findings and 20 (57%) had evidence of valvular insufficiency occurring in one or more valves. Seven patients (20%) had significant valve damage according to the DHHS and FDA criteria. CONCLUSION: After 24 weeks of treatment severe binge eaters improved their eating pattern, depression scores, and achieved weight loss similar to non-binge eaters. These data suggest that pharmacologic intervention for weight loss and subsequent weight maintenance can be as successful in binge eaters as non-binge eaters. A relationship was seen between duration of drug treatment and valvular insufficiency in subjects treated for an average of 52 weeks. These findings validate the FDA requirement for studies of at least 1 year duration to evaluate both the safety and efficacy of pharmacologic treatment for obesity.

Adult↗
PubMed1999

Colon involvement in Langerhans' cell histiocytosis.

BACKGROUND: Langerhans' cell histiocytosis (LCH), a granulomatous disorder of unknown cause, most often affects the bony skeleton and skin. Obvious gut involvement is uncommon, and colon involvement has been cited in only a small number of case reports, probably because most patients who have LCH with diarrhoea and/or failure to thrive are not investigated by colonoscopy and biopsy. The current study was conducted to determine the incidence of symptomatic colon involvement among patients with multisystem LCH treated at a single institution. METHOD: A retrospective review of cases in hospital records and the literature. RESULTS: Of the 275 children with LCH in the database, 5 were identified as having biopsy-confirmed colonic involvement. Another 14 cases were identified by a literature review. CONCLUSION: Colonic involvement in patients with multisystem LCH is probably more common than currently recognised. In addition to the other investigations recommended by the Writing Group of the Histiocyte Society, it is recommended that patients with any symptoms suggestive of gut involvement undergo colonoscopy and biopsy of the colonic mucosa.

Colonic Diseases↗
PubMed1999

Aspirin administration for cardiac-related acute chest pain/angina: increased use in Medicare patients.

BACKGROUND: Coronary heart disease (CHD), the leading cause of death in the United States, accounted for approximately 490,000 deaths in 1993. Angina pectoris, a manifestation of CHD, accounted for 13,586 Medicare discharges in 1993 in Texas. A pilot project showed aspirin prophylaxis that reduces cardiovascular morbidity and mortality in individuals with acute angina is underused. Texas Medical Foundation collaborated with 10 acute-care facilities to improve aspirin prophylaxis. METHODS: Collaborators assessed processes of care and implemented clinical pathways to improve aspirin administration. Data were abstracted from medical records before and after pathway implementation to evaluate impact. RESULTS: Aspirin administration during hospital stay increased 10.8%, aspirin administration on discharge increased 11.7%, and average time from arrival to aspirin administration decreased 2.9 hours. CONCLUSIONS: Results suggest collaborator-implemented clinical pathways significantly improved care received by Medicare patients admitted for cardiac-related acute chest pain/angina. Data suggest room for further improvement.

Acute Disease↗
PubMed1998

Ingested interferon alpha suppresses type I diabetes in non-obese diabetic mice.

Type I diabetes mellitus is a chronic disorder that results from autoimmune destruction of the insulin-producing pancreatic beta cell. The non-obese diabetic mouse is a model of the human autoimmune disease Type I diabetes [1-3]. We have previously shown that ingested type 1 interferon inhibits chronic relapsing experimental autoimmune encephalomyelitis and the adoptive transfer of experimental autoimmune encephalomyelites by T cells, and decreases both antigen-specific and mitogen-induced pro-inflammatory cytokine secretion in this disorder. We therefore tried to determine whether ingested murine interferon alpha inhibits insulinitis and suppresses Type I diabetes mellitus in non-obese diabetic mice. Murine interferon alpha, given daily, decreased islet inflammation and suppressed diabetes. It increased the concanavalin A and ionomycin plus myristic acid palmitic ester-induced production of interleukin 4 and 10 and interferon gamma-secretion in spleen cells from treated mice. Adoptive transfer of unstimulated splenocytes secreting interleukin 4 and interleukin 10 from fed interferon alpha donors suppressed spontaneous diabetes mellitus in recipients. The protective effect of adoptively transferred unstimulated splenocytes shows the presence of ingested interferon alpha-activated regulatory splenic cell populations that may work via increased interleukin 4 or interleukin 10 production. Ingested interferon alpha administered during vulnerable periods in at-risk populations may potentially provide a continuous, convenient, non-toxic and effective treatment for Type I diabetes.

Adoptive Transfer↗
PubMed1998

Liver failure associated with mitochondrial DNA depletion.

BACKGROUND/AIMS: Liver failure in infancy can result from several disorders of the mitochondrial respiratory chain. In some patients, levels of mitochondrial DNA are markedly reduced, a phenomenon referred to as mitochondrial DNA depletion. To facilitate diagnosis of this condition, we have reviewed the clinical and pathological features in five patients with mitochondrial DNA depletion. METHODS: Cases were identified by preparing Southern blots of DNA from muscle and liver, hybridising with appropriate probes and quantifying mitochondrial DNA relative to nuclear DNA. RESULTS: All our patients with mitochondrial DNA depletion died of liver failure. Other problems included hypotonia, hypoglycaemia, neurological abnormalities (including Leigh syndrome) and cataracts. Liver histology showed geographic areas of fatty change, bile duct proliferation, collapse of liver architecture and fibrosis; some cells showed decreased cytochrome oxidase activity. Muscle from three patients showed mitochondrial proliferation, with loss of cytochrome oxidase activity in some fibres but not in others; in these cases, muscle mitochondrial DNA levels were less than 5% of the median control value. The remaining two patients (from a single pedigree) had normal muscle histology and histochemistry associated with less severe depletion of mitochondrial DNA in muscle. CONCLUSIONS: Liver failure is common in patients with mitochondrial DNA depletion. Associated clinical features often include neuromuscular disease. Liver and muscle histology can be helpful in making the diagnosis. Mitochondrial DNA levels should be measured whenever liver failure is thought to have resulted from respiratory chain disease.

DNA, Mitochondrial↗
PubMed1998

Familial persistent pulmonary hypertension of the newborn resulting from misalignment of the pulmonary vessels (congenital alveolar capillary dysplasia).

Misalignment of the pulmonary veins with congenital alveolar capillary dysplasia, although rare, has been reported as a cause of persistent pulmonary hypertension of the newborn. Reported cases have been mainly sporadic. Familial occurrence has been reported in only three instances. We present affected sibs with this condition. In addition to pulmonary abnormalities, urogenital abnormalities, including ureteric and urethral obstruction, seem to be common. Autosomal recessive inheritance is suggested.

Arteriovenous Malformations↗
PubMed1998

Update on the pharmacotherapy of obesity.

OBJECTIVE: To review recent developments in the pharmacotherapy of obesity, including the agents currently approved for use in the management of obesity and those under development. DATA SOURCES: A MEDLINE search from January 1990 to July 1997 was conducted to identify English literature available on the pharmacotherapy of obesity. The search was supplemented by a review of the bibliographies of identified literature. STUDY SELECTION: All controlled and uncontrolled trials were reviewed. When available, double-blind, placebo-controlled trials were used preferentially. DATA EXTRACTION: Agents were reviewed with regard to mechanism of action, clinical trial data regarding efficacy, adverse effects, pharmacokinetics, drug interactions, and contraindications where information was available. Study design, selected population, results, and adverse effect information were included. DATA SYNTHESIS: The anorexiants currently available or under development for the management of obesity regulate food intake and satiety via the adrenergic and/or serotonergic pathways. Clinical trials have shown a 10-15% weight loss can typically be anticipated; however, little long-term safety and efficacy data are available. Adverse events tend to be mild and self-limiting, but serious adverse events can occur. Treatment options under development include thermogenic agents, digestive inhibitors, and analogs and antagonists of hormones that regulate food intake and satiety. CONCLUSIONS: Several mechanisms to control weight are currently under investigation for the management of obesity. Since obesity is a chronic condition, further studies should be conducted to evaluate the long-term safety and efficacy of these agents and the role of combination therapy using different modalities.

Adrenergic Agents↗