Biomedical subjects

M Malone

Publications and source records attributed to M Malone.

At least 37 records · Page 2Linked to original sources

PubMed2003

Isolated EBV lymphoproliferative disease in a child with Wiskott-Aldrich syndrome manifesting as cutaneous lymphomatoid granulomatosis and responsive to anti-CD20 immunotherapy.

Patients with primary immunodeficiencies such as the Wiskott-Aldrich syndrome (WAS) are prone to develop Epstein-Barr virus (EBV) related lymphoproliferative disorders (LPDs). EBV LPD is most frequently seen in patients receiving immunosuppressive treatment after organ transplantation (post-transplant lymphoproliferative disorder), but can also arise in the primary immunodeficiencies. Typically, EBV LPD presents as a diffuse systemic disease with lymphadenopathy and organ involvement. A rare angiocentric and angiodestructive form of EBV associated B cell LPD, lymphomatoid granulomatosis (LyG), has also been reported in association with WAS. LyG most commonly involves the lung, but can also be seen in brain, kidney, liver, and skin. This report describes the case of a 16 year old boy with WAS who presented with an isolated non-healing ulcerating skin lesion. Biopsy revealed an EBV related LPD with the histological features of LyG. This cutaneous lesion responded dramatically to treatment with specific anti-CD20 immunotherapy and the patient remains clinically free of LPD at 18 months.

Adolescent↗

PubMed2003

Health visiting at the crossroads: which way to the 21st century?

This article presents a response from a group of lecturers at Florence Nightingale School of Nursing and Midwifery, King's College London and one service user to the perception of a crisis of confidence within health visiting. Changes in registration procedures and shifts in policy have led health visiting to question its place within primary care and the model of preparation for health visiting practice. The group argues that this debate is based on a misunderstanding of the changing health care environment and that health visiting can find a place within the primary care team. Key to this is the continued adherence to a basic nursing training. The authors suggest an incremental model of health visitor training to provide the fullest scope to implement the new health agenda.

Attitude of Health Personnel↗

PubMed2002

Functioning adrenocortical neoplasms in children.

OBJECTIVE: To describe the clinical features, treatment and outcome of functioning adrenocortical tumours in children, and to assess the value of tumour size as a marker for malignant potential. PATIENTS AND METHODS: Twenty-one children (mean age at presentation 4.9 years, range 0.6-11; 12 girls and nine boys) who presented with a functioning adrenal mass over a 29-year period (1972-2000) were assessed. Clinicopathological features and outcome information were obtained from a structured review of the case-notes. Before 1980 the diagnosis and staging was mainly obtained by intravenous pyelography and plain X-ray. Since 1980, ultrasonography, computed tomography and more recently magnetic resonance imaging were the methods of choice. RESULTS: The mean (range) duration of symptoms before diagnosis was 31 (2-108) months. The symptoms and signs at presentation comprised virilization (18 children), Cushingoid features (three), precocious puberty (three) and hypertension (four). Three children had malignant neoplasms, one presented with metastasis and of the other two, one died from the disease within 6 months, despite adjuvant chemotherapy and radiotherapy. The third girl is disease-free 11 years after complete excision of the neoplasm. Eighteen children had a benign neoplasm and all are alive and free of recurrence. In most of the children surgical extirpation was relatively simple, blood loss minimal, recovery uneventful and the hospital stay short (mean 5 days). The virilizing effects of all the neoplasms gradually resolved after surgery within a median (range) of 27 (6-108) months. CONCLUSIONS: Functioning adrenocortical neoplasms in children are rare, with a peak incidence in the first decade, are predominantly unilateral and more common in girls. Most are benign, but both benign and malignant lesions can present with virilizing and Cushingoid features. The malignant neoplasms have an extremely poor prognosis, especially if excision is incomplete, despite adjuvant chemotherapy and radiotherapy. Although there is an association between tumour size and malignancy, this cannot be used as a reliable individual discriminator.

Adrenal Cortex Neoplasms↗

PubMed2002

Mobilization of calcium in glasshouse tomato plants by localized scorching.

It is postulated here that significant amounts of calcium will be mobilized into the plant by the scorching of one old leaf. This postulate was tested using large (6 m) tomato plants in the glasshouse. Brief scorching with a blowlamp was shown to release some 35% of the leaf's water into the plant. A range of measurements was used to estimate the kinetics and magnitude of this flow. The flow was found to carry a pulse of up to 50% of the leaf's total calcium into the plant, probably via the xylem, and was estimated to increase xylem calcium levels transiently by a factor of about 80. The potential value of scorching treatments in combating calcium-deficiency disorders is discussed.

Adaptation, Physiological↗

PubMed2001

Linkage study of polymorphisms in the gene for myelin oligodendrocyte glycoprotein located on chromosome 6p and attention deficit hyperactivity disorder.

Family and twin studies have shown that there is a substantial genetic contribution to both reading disabilities (RD) and attention deficit hyperactivity disorder (ADHD), and recent twin studies have suggested that the overlap between these phenotypes is largely due to common genetic influences. Studies using a linkage approach to search for genes for susceptibility to RD and ADHD have identified regions linked to each of these phenotypes separately, with recent studies suggesting that some chromosomal regions may contribute to both. Linkage to the human leukocyte antigen (HLA) region has been targeted in particular for RD and ADHD, as both of these disorders have been suggested to be autoimmune. Linkage to the HLA region of 6p for RD has now been reported by several groups. Alleles at two genes in the HLA (C4B and DRB1) have also been reported to be associated with ADHD, prompting one investigator to suggest a possible connection between the linkage of RD and ADHD to this region. The location of the gene for myelin oligodendrocyte glycoprotein (MOG), in the region of 6p with the strongest evidence for linkage to RD, and its proposed role as a minor component of myelin in the central nervous system suggest that it may be a factor in neuronal functioning and therefore a candidate for RD and ADHD. In this study, we tested the gene for linkage to ADHD by genotyping two polymorphisms in the MOG gene-a dinucleotide repeat located upstream from the MOG transcription start site and a Val145Ile substitution in exon 3-in a sample of 104 nuclear families identified through a proband with ADHD. We examined the transmission of the alleles of the Val145Ile and the dinucleotide repeat polymorphisms using the transmission disequilibrium test. We did not observe biased transmission of the alleles at either polymorphism to ADHD probands or siblings. Our findings using this sample do not support the role of the MOG gene in ADHD.

Amino Acid Substitution↗

PubMed2001

Linkage study of the alpha2A adrenergic receptor in attention-deficit hyperactivity disorder families.

Attention-deficit hyperactivity disorder (ADHD) is a common childhood psychiatric disorder, characterized by marked and pervasive inattention, hyperactivity, and impulsiveness. An alteration in the expression or function of the adrenergic system has been suggested to be involved in ADHD based on animal models, pharmacological interventions, and the neural circuitry of attentional processes. The efficacy of clonidine in reducing disruptive behaviors in some children with ADHD argues for a causal role of the adrenergic system and more specifically for the alpha2A receptors as clonidine is an alpha2A agonist that inhibits release of noradrenaline into the synapse. In animal studies, alpha2A receptor agonists have also been shown to improve performance on working memory tasks under distracting conditions, indicating that these receptors function in the regulation of attention. We examined the possibility that the gene for the alpha2A adrenergic receptor (ADRA2A) is linked to ADHD by testing a polymorphism located in the promoter region of the ADRA2A gene in a sample of 94 nuclear families with an ADHD proband. We found no evidence for linkage of the ADRA2A gene with ADHD, using the transmission disequilibrium test in this set of families.

Adolescent↗

PubMed2001

Haplotype study of three polymorphisms at the dopamine transporter locus confirm linkage to attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is often treated using methylphenidate, a psychostimulant that inhibits the dopamine transporter. This led E.H. Cook and colleagues to consider the dopamine transporter locus (DAT1) as a primary candidate gene for ADHD. That group reported a significant association between ADHD and the 480-base pair (bp) allele of the variable number of tandem repeats (VNTR) polymorphism located in the 3' untranslated region of the DAT1 gene. This association was later replicated in additional studies. METHODS: The DAT1 gene has additional common polymorphisms in intron 9 and exon 9. We investigated the possibility of linkage of DAT1 and ADHD using the VNTR polymorphism and two additional common polymorphisms in 102 nuclear families with an ADHD proband. Using the transmission disequilibrium test, we examined the transmission of the alleles of each of these polymorphisms, as well as the haplotypes of the polymorphisms. RESULTS: We did not observe significant evidence for the biased transmission of the alleles of either the VNTR or the additional two polymorphisms when examined individually, although there was a trend for the biased transmission of the 480-bp allele of the VNTR. When we examined the haplotypes of the three polymorphisms we found significant evidence for biased transmission of one of the haplotypes containing the 480-bp VNTR allele. We also genotyped six additional DNA sequence variants of the DAT1 gene. However, these variants were not sufficiently polymorphic in our sample to be informative. Two of the DNA variants that result in an amino acid change, Ala559Val and Glu602Gly, were not observed in our sample. CONCLUSIONS: Our results support previous findings of an association between the DAT1 gene and ADHD.

Alleles↗

PubMed2001

Congenital alveolar rhabdomyosarcoma: clinical and molecular distinction from alveolar rhabdomyosarcoma in older children.

BACKGROUND: Congenital alveolar rhabdomyosarcoma (RMS) is extremely rare and invariably fatal with current therapy. Its clinical presentation is unusual and is distinct from RMS in older children, with > 50% of patients presenting with multiple cutaneous metastases. To the authors' knowledge, the biology of this condition has not been studied to date. METHODS: The clinical and pathologic findings of four cases of congenital RMS are presented along with those of other cases found in the literature. Molecular analysis was undertaken to detect the characteristic chromosomal translocations of alveolar RMS in three cases with suitable material. RESULTS: To the authors' knowledge, there are no recorded survivors of congenital alveolar RMS. Clinical and histopathologic findings in four patients with congenital alveolar RMS are detailed along with treatment responses. It now is recognized that tumor specific translocations can be detected in the majority of cases of alveolar RMS using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. However, detailed molecular analysis using RT-PCR was unable to detect the presence of either the classic t(2;13) or variant t(1;13) translocation in three cases analyzed at the molecular level. CONCLUSIONS: To the authors' knowledge the optimal treatment for this rare tumor is not known. The longest survivor in the current series underwent myeloablative therapy with peripheral stem cell support, suggesting that more intensive treatment may be of value in this rare condition. None of the three tumors analyzed by RT-PCR harbored characteristic RMS translocations. The molecular biology of this highly malignant and aggressive congenital tumor appears to be different from alveolar RMS in older children and warrants further investigation.

Female↗

PubMed2001

5'-untranslated region of the dopamine D4 receptor gene and attention-deficit hyperactivity disorder.

Recently the molecular genetic basis of attention-deficit hyperactivity disorder (ADHD) has been the focus of a number of studies with the majority of these investigating the role of dopamine system genes. A great deal of attention has been focused on the possible involvement of the dopamine D4 receptor gene (DRD4) following a report of an association of ADHD with the allele containing seven copies of the 48-bp repeat in the third exon. In this paper we extended the search for the molecular explanation for the observed association by testing three polymorphisms in the region 5' to the dopamine receptor D4 gene transcription start site for linkage to ADHD. We specifically targeted polymorphisms in the region 5' to the start site of transcription as DNA variants in this region could alter the transcription level of the gene and hence the phenotype. We did not observe significant evidence for biased transmission of any of the alleles at these three polymorphisms to ADHD probands using the transmission disequilibrium test. We conclude that these three polymorphisms are not related to the ADHD phenotype.

5' Untranslated Regions↗

PubMed2001

Crystal structure of the human prion protein reveals a mechanism for oligomerization.

The pathogenesis of transmissible encephalopathies is associated with the conversion of the cellular prion protein, PrP(C), into a conformationally altered oligomeric form, PrP(Sc). Here we report the crystal structure of the human prion protein in dimer form at 2 A resolution. The dimer results from the three-dimensional swapping of the C-terminal helix 3 and rearrangement of the disulfide bond. An interchain two-stranded antiparallel beta-sheet is formed at the dimer interface by residues that are located in helix 2 in the monomeric NMR structures. Familial prion disease mutations map to the regions directly involved in helix swapping. This crystal structure suggests that oligomerization through 3D domain-swapping may constitute an important step on the pathway of the PrP(C) --> PrP(Sc) conversion.

Crystallography, X-Ray↗

PubMed2001

Attention-deficit hyperactivity disorder and the adrenergic receptors alpha 1C and alpha 2C.

The adrenergic system has been hypothesized to be involved in the etiology of attention-deficit hyperactivity disorder (ADHD) based on pharmacological interventions and animal models. Noradrenergic neurons are implicated in the modulation of vigilance, improvement of visual attention, initiation of adaptive response, learning and memory. In this study we tested the genes for two adrenergic receptors, alpha 1C (ADRA1C) located on chromosome 8p11.2, and alpha 2C (ADRA2C) located on chromosome 4p16, as genetic susceptibility factors in ADHD. For the adrenergic receptor alpha 1C we used a C to T polymorphism that results in a change of Cys to Arg at codon 492 for the linkage study. For the adrenergic receptor alpha 2C gene we examined a dinucleotide repeat polymorphism located approximately 6 kb from the gene. We examined these polymorphisms in a sample of 103 families ascertained through an ADHD proband. Using the transmission disequilibrium test, we did not observe biased transmission of any of the alleles of these polymorphisms. We conclude that the alleles at the polymorphisms tested in these two genes are not linked to the ADHD phenotype in this sample of families.

Attention Deficit Disorder with Hyperactivity↗

PubMed2001

Juvenile xanthogranuloma as a sequel to Langerhans cell histiocytosis: a report of three cases.

We report three children who had multisystem Langerhans cell histiocytosis (LCH) with cutaneous involvement and subsequently developed juvenile xanthogranuloma (JXG). JXG appeared 3--6 years after the initial manifestation of LCH. JXG lesions, which presented as yellowish papules, revealed typical Touton giant cells and were factor XIIIa positive but S100 and CD1a negative. Non-LCH histiocyte disorders, such as JXG, are known to occur as a reaction to a variety of external stimuli such as infection and trauma. It is therefore conceivable that the inflammatory reaction associated with LCH may have precipitated the development of JXG in our patients. Alternatively, one could speculate that this association might be due to a common histogenetic precursor of the cell types involved.

Child↗

PubMed2001

Facial features of widespread neuroblastoma: a case report.

A case report of stage IV neuroblastoma which presented with periorbital swelling and ecchymosis originally misdiagnosed as facial trauma. The child soon developed a sinister pancytopenia, which following extensive investigations was revealed to be due to an underlying neuroblastoma. Periorbital ecchymosis associated with neuroblastoma is termed 'raccoon eyes' and is a diagnostic trap for the unwary.

Aortic Diseases↗

PubMed2001

Diversion procto-colitis: response to treatment with short-chain fatty acids.

BACKGROUND/PURPOSE: Diversion procto-colitis (DPC) results from a deficiency of luminal short-chain fatty acids (SCFAs). Endoscopic and histopathologic features of the disorder are almost universally present in defunctioned bowel, but symptomatic DPC is less common. METHODS: Five children with symptomatic DPC underwent endoscopy and rectosigmoid biopsies. An endoscopic index (EI) was used to quantify disease severity. An SCFA mixture was administered into the defunctioned bowel. RESULTS: A good clinical response and improvement in the endoscopic index occurred in all children. Undiversion or rectal excision was carried out in 4 and was curative in each case. One child is awaiting a redo pull through. CONCLUSIONS: DPC should be considered in children with a defunctioned colon presenting with evidence of colitis. Histopathology provides supportive evidence and SCFAs may provide effective relief of symptoms. Stoma reversal or rectal excision is curative.

Child↗

PubMed2001

Direct measurement of sodium and potassium in the transpiration stream of salt-excluding and non-excluding varieties of wheat.

The xylem-feeding insect Philaenus spumarius was used to analyse sodium and potassium fluxes in the xylem of intact, transpiring wheat plants. Two cultivars were compared: the salt-excluding (Chinese Spring) and the non-excluding (Langdon). Chinese Spring accumulated much less sodium in its leaves than the salt-sensitive Langdon. After 7 d in 150 mol m(-3) NaCl, the sodium concentration in the leaf sap of Langdon reached over 600 mol m(-3). This was some three-fold greater than that in Chinese Spring. Similar findings have previously been reported from these cultivars. The reduced ion accumulation was specific to sodium; accumulation of K(+) was unaffected by NaCl in Chinese Spring, such that it developed a much lower leaf Na(+)/K(+) ratio than Langdon. The spittlebug, P. spumarius was used to sample xylem sap from both cultivars. This approach showed that the leaf xylem sap of Chinese Spring had much lower levels of sodium than that of Langdon. In the 150 mol m(-3) NaCl treatment, sodium levels in the leaf xylem reached only 2-3 mol m(-3) in Chinese Spring, compared with 8-10 mol m(-3) in Langdon. Transpiration rates were found to be similar in the two varieties. The lower leaf xylem content alone was thus sufficient to account for the reduced accumulation of sodium in leaves of Chinese Spring. The mechanisms by which xylem sodium might be lowered are discussed and it is concluded that sodium is probably excluded from the xylem in the root of Chinese Spring.

Animals↗

PubMed2001

Serotonin syndrome induced by fluvoxamine and mirtazapine.

OBJECTIVE: To document a case of serotonin syndrome associated with the combined use of fluvoxamine and mirtazapine, and to discuss the pharmacodynamic and pharmacokinetic interactions that were the likely causes of this potentially serious adverse drug reaction (ADR). CASE SUMMARY: A 26-year-old white woman with a 12-year history of anorexia nervosa was being treated with fluvoxamine. After mirtazapine was added to her therapy, she developed tremors,restlessness, twitching, flushing, diaphoresis, and nausea,symptoms that are consistent with serotonin syndrome. DISCUSSION: The possible causes of this ADR are discussed, including the effects of fluvoxamine and mirtazapine alone, the possible pharmacodynamic and pharmacokinetic interactions of these two drugs, and the patients underlying anorexia nervosa. CONCLUSIONS: An increasing number of drugs that affect serotonin are available and are indicated for various disorders. Since there is a significant likelihood of these agents being prescribed concomitantly, clinicians must be aware of possible interactions that could lead to serotonin syndrome.

Adrenergic alpha-Antagonists↗

PubMed2000

Maxillary myxoma: a rare midfacial mass in a child.

The case of a maxillary myxoma in a 13-month-old child is presented. This case highlights the difficulties associated with managing such cases. The tumour was found at operation to be unencapsulated and infiltrative. This was contrary to the preoperative CT scan findings and necessitated a change from a sublabial to a lateral rhinotomy approach. This case illustrates a potential pitfall of CT scanning in such cases: it is likely that a MRI scan would have demonstrated the invasive nature of this tumour. To the authors' knowledge this is the second youngest reported case of maxillary myxoma in the literature.

Humans↗

PubMed2000

Further evidence from haplotype analysis for linkage of the dopamine D4 receptor gene and attention-deficit hyperactivity disorder.

Several studies have suggested a possible association of a polymorphism at the dopamine D4 receptor gene and attention-deficit hyperactivity disorder [LaHoste et al., 1996; Rowe et al., 1998; Smalley et al., 1998; Sunohara et al., submitted; Swanson et al., 1998]. The allele reported to be associated with attention-deficit hyperactivity disorder (ADHD) is the allele with seven copies of the 48 bp repeat in the third exon. We extend our study of the dopamine D4 gene and ADHD by testing for linkage using two additional polymorphisms in the dopamine D4 receptor gene and a polymorphism in the closely linked gene, tyrosine hydroxylase. We also searched for two previously reported deletions, a 13 bp and a 21 bp deletion in the first exon. We examined the haplotypes of three polymorphisms of the D4 receptor gene and observed biased transmission of two of these haplotypes. Our findings further support the role of the dopamine D4 gene in ADHD.

Adolescent↗