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Biomedical subjects

J J Brown

Publications and source records attributed to J J Brown.

At least 19 recordsLinked to original sources
PubMed2006

Plant polyphenols and multidrug resistance: effects of dietary flavonoids on drug transporters in Caco-2 and MDCKII-MDR1 cell transport models.

The hypothesis tested was that specific flavonoids such as epicatechin gallate, epigallocatechin gallate, genistein, genistin, naringenin, naringin, quercetin and xanthohumol will modulate cellular uptake and permeability (P(e)) of multidrug-resistant substrates, cyclosporin A (CSA) and digoxin, across Caco-2 and MDCKII-MDR1 cell transport models. (3)H-CSA/(3)H-digoxin transport and uptake experiments were performed with and without co-exposure of the flavonoids. Aglycone flavonoids reduced the P(e) of CSA to a greater extent than glycosylated flavonoids with 30 microM xanthohumol producing the greatest effect (7.2 x 10(-6) to 6.6 x 10(-7) and 17.9 x 10(-6) to 4.02 x 10(-6) cm s(-1) in Caco-2 and MDCKII-MDR1 cells, respectively); while no measurable effects were seen with digoxin. Xanthohumol significantly demonstrated (1) saturable efflux, (2) increased uptake of (3)H-digoxin and (3) decreased uptake of (3)H-CSA in the Caco-2 cells. The transport data suggests that xanthohumol effects transport of CSA in a manner that is distinct from the digoxin efflux pathway and suggests that intestinal transport of these MDR1 substrates is more complex than previously reported.

Animals↗
PubMed2006

TNF-alpha SNP haplotype frequencies in equidae.

Tumour necrosis factor alpha (TNF-alpha) is a pro-inflammatory cytokine that plays a crucial role in the regulation of inflammatory and immune responses. In all vertebrate species the genes encoding TNF-alpha are located within the major histocompatability complex. In the horse TNF-alpha has been ascribed a role in a variety of important disease processes. Previously two single nucleotide polymorphisms (SNPs) have been reported within the 5' un-translated region of the equine TNF-alpha gene. We have examined the equine TNF-alpha promoter region further for additional SNPs by analysing DNA from 131 horses (Equus caballus), 19 donkeys (E. asinus), 2 Grant's zebras (E. burchellii boehmi) and one onager (E. hemionus). Two further SNPs were identified at nucleotide positions 24 (T/G) and 452 (T/C) relative to the first nucleotide of the 522 bp polymerase chain reaction product. A sequence variant at position 51 was observed between equidae. SNaPSHOT genotyping assays for these and the two previously reported SNPs were performed on 457 horses comprising seven different breeds and 23 donkeys to determine the gene frequencies. SNP frequencies varied considerably between different horse breeds and also between the equine species. In total, nine different TNF-alpha promoter SNP haplotypes and their frequencies were established amongst the various equidae examined, with some haplotypes being found only in horses and others only in donkeys or zebras. The haplotype frequencies observed varied greatly between different horse breeds. Such haplotypes may relate to levels of TNF-alpha production and disease susceptibility and further investigation is required to identify associations between particular haplotypes and altered risk of disease.

Animals↗
PubMed2005

Proposals for prevention and management of steroid-induced osteoporosis in children and adolescents.

The adverse effects of glucocorticoids on bone health are well recognized. In adults, evidence-based guidelines exist to base management of patients with glucocorticoid-induced osteoporosis. Osteoporosis is also recognized in children and adolescents with chronic disease requiring steroid treatment. Additional complexities in the assessment and management of growing children mean that evidence-based guidelines for this complex patient group have not been produced. Factors, which need to be taken into account, include defining osteoporosis in childhood and addressing the effects of chronic disease and glucocorticoid treatment on a number of parameters including the skeleton, growth, puberty, nutrition and vitamin D status. In the absence of randomized controlled trials to guide clinical practice, we provide proposals for the prevention and management of steroid-induced osteoporosis, drawing on the available evidence and our clinical experience of managing children and adolescents with steroid-induced osteoporosis.

Adolescent↗
PubMed2005

Attempted randomized controlled trial of pamidronate versus calcium and calcitriol supplements for management of steroid-induced osteoporosis in children and adolescents.

OBJECTIVES: To describe an attempted interventional trial for glucocorticoid-induced osteoporosis in children and adolescents and to discuss the reasons for trial failure to inform future interventional studies in this important group of patients. METHODS: Prospective randomized controlled trial comparing the effect of bisphosphonate therapy with calcium and vitamin D supplementation on bone mineral accrual is described. For non-trial patients, retrospective analysis of the effect of calcium and vitamin D supplementation combined with bisphosphonate treatment on bone mineral accrual. RESULTS: Only 12 patients were enrolled in the trial over 4 years. Bisphosphonate recipients (n = 5) had a mean annual percentage increase in lumbar spine bone mineral density of 8.76 +/- 5.2% compared to 6.6 +/- 4.0% in the calcium/vitamin-treated group (difference not significant). Mean annual change in lumbar spine areal bone mineral density in non-trial patients (n = 11) was 3.72 +/- 2.5%. CONCLUSION: Conducting a randomized controlled trial in this group of corticosteroid users is difficult, given the unpredictable nature of the underlying disease and intermittent need for steroid treatment. The trial failed through inadequate recruitment combined with discontinued interventions.

Adolescent↗
PubMed2004

Achieving early surgery for undescended testes: quality improvement through a multifaceted approach to guideline implementation.

BACKGROUND: Surgery for undescended testes is recommended before the age of 2 years. However, boys are still undergoing surgery for undescended testes at a much later age than recommended. METHODS: An initial audit reviewed all orchidopexies performed at Northampton General Hospital between 1992 and 1994. This demonstrated that only 19% of boys had surgery by the age of 2 years, and the key reason for late surgery was late referral. Guidelines for referral of undescended testes were established in which referral to a surgeon was advised following the 8-month child health surveillance check if undescended testis was suspected. This would enable surgery before the age of 2 years. Audit results were disseminated and we implemented a package of measures based on evidence based change management techniques. These included written advice to general practitioners (GPs), a parent information leaflet and an amended personal child health record advising timing of referral. A reminder to the GP to refer following the 8-month check was generated using computer recall from the Child Health System records. Guideline implementation was monitored by annual audit and feedback. RESULTS: The baseline audit for the years 1992-94 found a median age at surgery of 4 years. Implementation of the new policies in 1998 resulted in a reduction in median age at surgery to 2.0 years in the 12 months ending September 2001. CONCLUSIONS: While concern about the age at orchidopexy has been highlighted in many previous studies, this is the first to show that improvement in the age at orchidopexy can be achieved. Implementing locally agreed guidelines with written information to GPs and parents combined with computerized recall from Child Health System records achieved the target within 3 years. Similar systems could be implemented nationally at minimal cost.

Age Factors↗
PubMed2004

Polymorphisms of the equine major histocompatibility complex class II DRA locus.

The full extent of the polymorphism of ELA-DRA in Equidae is not yet known. Given the apparent differences in DRA polymorphisms between Equidae and other species, the aims of this study were to more fully characterize ELA-DRA, determine the extent of gene polymorphism and establish the allele-frequency distribution. An allele reference panel for the second exon of ELA-DRA was established by sequence-based typing of 69 equine DNA samples consisting of various breeds of domestic horse (Equus caballus), together with donkeys (Equus asinus), Grant's zebras (Equus boehmi) and one onager (Equus hemionus). Five of the six previously reported alleles detected using single-strand conformation polymorphism were found: ELA-DRA*0101, ELA-DRA*0201, ELA-DRA*0301, ELA-DRA*0501 (Albright-Fraser DG et al. Polymorphism of DRA among equids. Immunogenetics 1996: 43: 315-7) and ELA-DRA*0601 (GenBank accession number AF5419361). In addition to the previously reported alleles, five novel ELA-DRA alleles were detected within the ELA-DRA allele reference panel. One of these was identified in E. caballus (ELA-DRA*JBH11), one in E. boehmi and E. hemionus (ELA-DRA*JBZ185) and three in E. asinus (ELA-DRA*JBD3, ELA-DRA*JBD17 and ELA-DRA*JBH45). A total of 565 equine DNA samples were screened using reference-strand-mediated conformation analysis, a double-stranded conformation-based mutation detection system that can be used to type existing ELA-DRA alleles and identify new variants. Based on our findings, at least 11 ELA-DRA alleles are now known to exist, and this level of polymorphism at the DRA locus appears to be unique to the genus Equus. Both the previously reported alleles and the new alleles displayed a species-specific distribution.

Amino Acid Sequence↗
PubMed2004

Graves' disease in DiGeorge syndrome: patient report with a review of endocrine autoimmunity associated with 22q11.2 deletion.

DiGeorge syndrome, which falls within a wider phenotypic spectrum associated with deletions of 22q11.2, is associated with a number of endocrine disorders. These include hypoparathyroidism, hypothyroidism and growth hormone deficiency. We report an unusual case of autoimmune hyperthyroidism (Graves' disease) presenting in a 3 year-old male with DiGeorge syndrome. The development of endocrine specific autoimmune disease in a syndrome associated with immune deficiency and the spectrum of endocrine autoimmunity associated with deletions of 22q11.2 are described. Paediatricians and patients with 22q11.2 deletions should be particularly aware of the risks of developing disorders of thyroid function.

Antithyroid Agents↗
PubMed2004

24-hour ambulatory blood pressure profile in patients with congenital adrenal hyperplasia--a preliminary report.

BACKGROUND: Blood pressure (BP) is maintained within normal limits by the interplay of various mechanisms including the action of cortisol and aldosterone. However, these hormones when exogenously administered are not under the regulatory feedback mechanisms that maintain BP homeostasis. Treatment of congenital adrenal hyperplasia (CAH) requires glucocorticoid replacement (with or without additional mineralocorticoid) at supra-physiological doses to normalize the pituitary adrenocortical axis. HYPOTHESIS: Long-term use of glucocorticoids at supra-physiological doses may result in high BP. OBJECTIVE: To document any changes in BP in patients with CAH following long-term conventional glucocorticoid replacement therapy. PATIENTS AND METHODS: 24-hour ambulatory BP (AmBP) monitoring was performed in 11 patients with CAH, all of whom were on glucocorticoid replacement at supra-physiological doses. In addition, a single random BP measurement was taken in each patient at enrolment. Mean systolic and diastolic pressure during awake and sleep periods, systolic and diastolic BP loads, and systolic and diastolic BP dips were calculated from the 24-hour AmBP profile of each patient, which was correlated with demographic and treatment details. AmBP readings were compared to Task Force references for casual BP and also to recently available AmBP specific reference values. RESULTS: None of the patients had significant BP loads at the 95th percentile (hypertensive BP range) using references for casual BP readings. However, in the subgroup of patients who had significant BP load at the 90' percentile (high normal BP range), higher mean systolic and diastolic pressures were noticed during the awake period. Seven patients did not have a systolic dip with or without a diastolic dip. There was no significant correlation between various BP parameters and demographic or treatment details in our sample. However, one patient had daytime systolic hypertension and six had nocturnal hypertension using AmBP specific reference values. CONCLUSIONS: In this preliminary study, longterm glucocorticoid replacement therapy at supra-physiological doses does not seem to be associated with hypertension in young people with CAH when using casual BP references. However, higher mean BP was noticed in the subgroup of patients with significant systolic or diastolic BP load at high normal BP range, and evidence of daytime and nocturnal hypertension was uncovered using AmBP specific reference values. Further large trials using appropriate BP references are necessary to clarify the significance of these findings.

Adolescent↗
PubMed2004

Chloride/phosphate ratio in primary hyperparathyroidism.

The chloride/phosphate (Cl:PO4) ratio is known to help distinguish between the hypercalcemia of primary hyperparathyroidism (HPT) and hypercalcemia from other causes. The Cl:PO4 ratio of 106 patients with surgically proven primary HPT was compared with that of 126 normocalcemic healthy outpatients to examine its usefulness as a confirmatory test for primary HPT. The Cl:PO4 ratio was significantly higher in patients with HPT (42.5 +/- 7.0) compared with healthy controls (28.7 +/- 4.6). Patients with HPT and mild renal insufficiency (serum creatinine, 1.5-2.4 mg/dL) also showed a significant increase in the Cl:PO4 ratio (37.3 +/- 6.6) as did those with HPT with borderline elevations in serum calcium (calcium < 11; Cl:PO4, 40.3 +/- 5.6). A Cl:PO4 ratio > or = 33 is a reliable diagnostic test for primary HPT when compared with a normal population. The Cl:PO4 ratio is also of value in the evaluation of the patient with suspected HPT and borderline calcium elevation and those with mild renal impairment. These data suggest that an inexpensive Cl:PO4 ratio might replace serum parathormone assay as a confirmatory test in the evaluation of suspected primary HPT, especially for those patients in whom a localizing study (sestamibi scan) is obtained before neck exploration.

Chlorides↗
PubMed2003

Chilling affects allatal cell proliferation via antennae and protocerebral neurons in the cockroach Diploptera punctata.

The corpora allata (CA) cells in a mated female of the cockroach Diploptera punctata undergo numerous mitotic divisions before an increase in juvenile hormone synthesis. A previous study demonstrated that this mitotic wave could be suppressed by exposure of the mated female to melting ice. Herein, we report that chilling suppresses CA mitosis via antennal perception. Cell proliferation-suppressing stimuli from chilling were acquired in proportion to the length of time of exposure to the low temperature and the physical length of the antennae exposed to chilling. Sixty basal antennal annuli should remain exposed to chilling for at least 1.5 h in order to suppress mitotic divisions in CA. Mitotic divisions in corpus allatum are suppressed by stimuli from contralateral antenna, predominantly via pars intercerebralis neurons. Selective disconnection of pars intercerebralis neurons from CA, prior to chilling, restored the mitotic wave in CA. Cellular divisions did not occur in CA of chilled females if either pars lateralis neurons were severed or left intact.

Animals↗
PubMed2003

Resolution of complex feline leukocyte antigen DRB loci by reference strand-mediated conformational analysis (RSCA).

The DRB genes of the domestic cat are highly polymorphic. Studies based on clonal sequence analysis have suggested the existence of two distinct loci within individual animals and good evidence for 24 distinct FLA-DRB alleles. This variability, the complexity of clonal sequence analysis and its susceptibility to PCR-induced artefacts has represented a bottleneck to further progress. In this study we have applied reference strand-mediated conformational analysis (RSCA) to FLA-DRB. This protocol has been shown to be highly reproducible. Using five reference strands including two derived from non-domestic felines, we could distinguish 23 FLA-DRB alleles. We used RSCA to explore genetic polymorphism of FLA-DRB in 71 cats including 31 for which clonal sequence analysis was also available. On average, RSCA identified 0.9 more alleles within cats than clonal sequence analysis. Reference strand-mediated conformational analysis was also able to identify animals containing new alleles that could be targeted for sequence analysis. Analysis of allele patterns showed clear evidence for different allele distributions between breeds of cats, and suggested the Burmese breed may have highly restricted FLA-DRB polymorphism. Results from two families provided clear evidence for variation in the number of DRB genes on different haplotypes, with some haplotypes carrying two genes and some containing three. This study highlights the utility of RSCA for the resolution of complex amplicons containing up to six distinct alleles. A simple, rapid method for characterizing FLA-DRB makes possible studies on vaccine response and susceptibility/resistance to viral infections, which are a significant clinical problem in cats.

Alleles↗
PubMed2003

Suppression of TSH in congenital hypothyroidism is significantly related to serum levels and dosage of thyroxine.

AIM: To assess thyrotropin (thyroid-stimulating hormone; TSH) suppression and serum thyroxine (T(4)) concentrations in infants with congenital hypothyroidism in relation to T(4) dose and pretreatment parameters. METHOD: A retrospective study of all cases treated in a single centre since neonatal screening began was performed. RESULTS: In 54 infants treated with a mean daily T(4) dose of 9.8 microg/kg, the TSH concentration was suppressed (<6 mU/l) in 65% of the cases by 6 months with the serum T(4) level at the upper end of the infant reference range. Infants who suppressed their TSH later did not differ in pretreatment serum TSH or T(4) concentration. T(4) dose and serum T(4) level were lower in infants whose TSH was not suppressed. CONCLUSIONS: TSH suppression in congenital hypothyroidism is significantly related to serum levels and dosage of T(4). We suggest that a delay in TSH suppression is mainly due to undertreatment.

Aging↗
PubMed2003

Evaluation of metallothionein and p53 expression as potential prognostic markers for laryngeal squamous cell carcinoma.

The aim of the study was to determine the contribution of metallothionein (MT) and p53 expression in predicting laryngeal squamous cell carcinoma (SCC) recurrence. This was a retrospective study in which MT and p53 immunopositive staining in 32 laryngeal SCC paraffin-embedded sections, were correlated with clinical recurrence. Recurrence was observed in 8 cases with MT expression (42.1%) and 1 case with no expression (7.7%). Moderate and strong MT expression was associated with 14.3% and 58.3% recurrence, respectively. Recurrence was similar for both p53-negative (21.1%) and p53-positive (27.3%) groups. One third of the patients expressing both p53 and MT simultaneously had recurrence. Thus, the combined expression of p53 and MT did not improve the predictive value for recurrence compared to MT alone. MT over-expression may be an independent risk factor for laryngeal SCC recurrence.

Biomarkers, Tumor↗
PubMed2001

Identification of differentially expressed genes in human papillomavirus type-16 infected oral cancer cells.

OBJECTIVE: The goal of this study was to determine the genes required for head and neck cancer development. STUDY DESIGN AND SETTING: Differential mRNA display analysis was performed using human papillomavirus Type-16 infected immortalized human oral keratinocytes (HOK-16B) and its benzo(a)pyrene-exposed tumorigenic derivative (HOK-16B-BaP-T). RESULTS: Twenty-one differentially expressed cDNA clones were identified between the 2 cell lines. Clone 4 with no known homology showed lower expression in tumorigenic cells compared with either normal or immortalized oral keratinocytes. Clone 6 expression was elevated in several head and neck cancer cells, in addition to Burkitt's lymphoma Raji harboring latent Epstein-Barr virus. CONCLUSION: These findings suggested that clone 6 may be involved in the oncogenic transformation whereas clone 4 may potentially function as a tumor suppressor gene. SIGNIFICANCE: Differential mRNA analysis using the in vitro oral carcinogenesis model may help to identify important genetic markers for the early detection and progression of head and neck cancer.

Blotting, Northern↗
PubMed2001

Surgery and religiosity.

Variances in religious practices and beliefs require health care providers to find alternative ways of meeting medical standards of care in cases where religious beliefs preclude the use of blood transfusions or blood products. We report a case of head and neck tumor with low hemoglobin in which we utilized temporary arterial ligation to aid in minimal blood loss.

Adult↗
PubMed2000

Safety and efficacy of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the U.S. multicenter phase III clinical trials (safety).

The short-term safety of mangafodipir trisodium (MnDPDP) injection was studied in 546 adults with known or suspected focal liver lesions. An initial contrast-enhanced computed tomography examination was followed by unenhanced magnetic resonance imaging (MRI), injection of MnDPDP (5 micromol/kg), and enhanced MRI. Adverse events were reported for 23% of the patients; most were mild to moderate in intensity, did not require treatment, and were not drug related. The most commonly reported adverse events were nausea (7%) and headache (4%). The incidence of serious adverse events was low (nine events in six patients) and not drug related. Injection-associated discomfort was reported for 69% of the patients, and the most commonly reported discomforts included heat (49%) and flushing (33%). Changes in laboratory values and vital signs were generally transient, were not clinically significant, and did not require treatment. There were no clinically significant short-term risks from exposure to MnDPDP.

Abdominal Pain↗
PubMed2000

Artery and vein separation using susceptibility-dependent phase in contrast-enhanced MRA.

In magnetic resonance angiography, contrast agents are frequently used to help highlight arteries over background tissue. Unfortunately, enhancing veins hamper the visualization of arteries when data are collected over a long period of time after the arterial phase of the contrast agent. To overcome this problem, we have developed a novel imaging and postprocessing method that is capable of eliminating veins by utilizing the susceptibility difference between veins and surrounding tissue. This method was applied in the peripheral vasculature where the vessels are predominantly parallel to the main field and where the blood oxygen level-dependent effect is most pronounced. Results are presented for both long (15.8 msec) and short echo times (7.8 msec) and for sequential and centrally reordered acquisition schemes. The short echo scan approach appears to be the most promising, making it possible to obtain good suppression of the venous signal even when the timing is not perfect or when repeat scans are necessary.

Arteries↗