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D Mullins

Publications and source records attributed to D Mullins.

At least 19 recordsLinked to original sources
PubMed2001

Identification of potent and selective neuropeptide Y Y(1) receptor agonists with orexigenic activity in vivo.

Neuropeptide Y (NPY) binds to a family of G-protein coupled receptors termed Y(1), Y(2), Y(3), Y(4), Y(5), and y(6). The use of various receptor subtype-selective agonists and antagonists has facilitated identification of the receptor subtypes responsible for mediating many of the biological effects of NPY. For example, the potent orexigenic activity of NPY is believed to be mediated by both the Y(1) and Y(5) receptor subtypes. Several selective Y(5) receptor agonists that stimulate food intake in rodents are available, but no selective Y(1) receptor agonist has been reported. We have identified several NPY analogs that bind the NPY Y(1) receptor with high affinity and exhibit full agonist activity, measured as inhibition of forskolin-stimulated cAMP production in cells expressing the cloned NPY Y(1) receptor. [D-Arg(25)]-NPY, [D-His(26)]-NPY, Des-AA(10--17)[Cys(7,21),Pro(34)]-NPY, Des-AA(11--18)[Cys(7,21),D-Lys(9)(Ac)]-NPY, Des-AA(11--18)[Cys(7,21),D-Lys(9)(Ac),Pro(34)]-NPY, Des-AA(11--18)[Cys(7,21),D-Lys(9)(Ac),D-His(26)]-NPY and Des-AA(11--18)[Cys(7,21),D-Lys(9)(Ac),D-His(26), Pro(34)]-NPY bind the NPY Y(1) receptor with K(i) values of 0.9 +/- 0.2, 2.0 +/- 0.3, 0.2 +/- 0.05, 0.7 +/- 0.1, 0.2 +/- 0.01, 2.2 +/- 0.3, and 1.2 +/- 0.3 nM, respectively, and inhibit forskolin-stimulated cAMP production with EC(50) values of 0.2 +/- 0.02, 0.5 +/- 0.04, 0.3 +/- 0.03, 0.5 +/- 0.05, 0.4 +/- 0.16, 5.3 +/- 0.32, and 5.1 +/- 0.97 nM, respectively. These peptides are highly selective for the NPY Y(1) receptor relative to the NPY Y(2), Y(4), and Y(5) receptors. [D-Arg(25)]-NPY, [D-His(26)]-NPY and Des-AA(11--18)[Cys(7,21), D-Lys(9)(Ac),D-His(26),Pro(34)]-NPY stimulate food intake dose-responsively in Long-Evans rats for at least 4 h after intracerebroventricular administration. Although the involvement of Y(1) receptors in several physiological activities, such as vasoconstriction and anxiolysis, remains to be investigated, adequate tools are now available.

Animals↗
PubMed1999

Activation of the NPY Y5 receptor regulates both feeding and energy expenditure.

Intracerebroventricular (ICV) administration of neuropeptide Y (NPY) has been shown to decrease energy expenditure, induce hypothermia, and stimulate food intake. Recent evidence has suggested that the Y5 receptor may be a significant mediator of NPY-stimulated feeding. The present study attempts to further characterize the role of NPY Y5-receptor subtypes in feeding and energy expenditure regulation. Satiated Long-Evans rats with temperature transponders implanted in the interscapular brown adipose tissue (BAT) displayed a dose-dependent decrease in BAT temperature and an increase in food intake after ICV infusion of NPY. Similar effects were induced by ICV administration of peptide analogs of NPY that activate the Y5 receptor, but not by analogs that activate Y1, Y2, or Y4 receptors. Furthermore, ICV infusion of the Y5 selective agonist D-[Trp(32)]-NPY significantly reduced oxygen consumption and energy expenditure of rats as measured by indirect calorimetry. These data suggest that the NPY Y5-receptor subtype not only mediates the feeding response of NPY but also contributes to brown fat temperature and energy expenditure regulation.

Adipose Tissue, Brown↗
PubMed1999

Tretinoin-induced sticky skin: a case report and review of the literature.

Sticky skin has been reported relatively infrequently in the literature in association with etretinate and doxorubicin/ketoconazole administration. It has a poorly understood pathogenesis, and the associated histologic changes have not been described. We report a case of a patient who experienced sticky skin in areas treated with tretinoin. These reverted to normal after cessation of treatment. In comparison to a biopsy taken while the skin was not sticky, the histologic findings included a thickened, compact stratum corneum and granulosum. The basal epithelial cells showed proliferation with slight crowding and a tall, columnar shape. To our knowledge, this is the first report of sticky skin occurring in response to topical retinoid application. We suggest that the histologic changes observed could represent a modified keratin maturation profile.

Administration, Cutaneous↗
PubMed1998

Can we improve the uptake of gastroscopy in the population at risk for gastric cancer? The effect of home letter information.

The poor outlook for gastric cancer in Britain is largely due to late diagnosis. Earlier diagnosis will require both easy access to endoscopy and increased public awareness of dyspeptic symptoms. We used information by personal letter to encourage reporting of potentially significant symptoms in patients over 40 years of age. The aim of this study was to measure the acceptability and effect on gastroscopy rates of home letter information. Patients over 40 registered with 12 general practices were used in the study (practice population 80,000). Patients over 40 from another nine practices (practice population 46,500) acted as controls. A letter encouraging consultation for new dyspeptic symptoms was sent to all study subjects. Gastroscopy rates were compared in both study and control populations. Questionnaires on symptoms were sent to 500 study subjects. The principal outcome measure was the gastroscopy rate in people over 40 in both populations, before and during the intervention. The gastroscopy rate was 23% higher in the study than in the control population during the study (3.32 vs. 2.7%, P = 0.00016, chi 2 = 14.25). Gastroscopy uptake increased by 85% from 1991/2 to 1993/4 in the study group and by 34% in the control group (chi 2 = 14.02, P = 0.00018). Thirty-one per cent of questionnaire respondents had dyspeptic symptoms; only 3% had 'significant' symptoms of between 2 and 52 weeks duration. Home letters are an acceptable and efficient method of increasing gastroscopy uptake in dyspeptic patients over 40.

Adult↗
PubMed1997

The reliability of color duplex ultrasound in diagnosing total carotid artery occlusion.

BACKGROUND AND PURPOSE: Color duplex ultrasound has been advocated as an alternative to arteriography before carotid endarterectomy. However, one limitation of color duplex ultrasound is that it sometimes fails to differentiate high-grade stenosis from total carotid occlusion. This study was done to determine (1) the accuracy of carotid duplex ultrasound in diagnosing total carotid occlusion, and (2) when angiography is necessary. PATIENT POPULATION AND METHODS: Carotid duplex ultrasound and angiography results were compared for 520 carotid arteries, and 103 of these had a duplex diagnosis of total carotid occlusion or suspected almost total-to-total occlusion. The diagnosis of total carotid occlusion was primarily based on the absence of flow in the internal carotid artery as visualized on B-mode imaging for at least 1 inch beyond the bifurcation (optimal study). If the internal carotid artery was not optimally seen beyond the bifurcation, but secondary criteria were present, such as dampening of the common carotid signal and internalization of the external carotid artery, a diagnosis of suspected subtotal to total occlusion was made (limited study). RESULTS: In the optimal studies, 91 arteries had total carotid occlusions and of these, 87 were confirmed by angiography. The accuracy of carotid duplex ultrasound in diagnosing total carotid occlusion was 97% with a positive predictive value of 96%, negative predictive value of 98%, sensitivity of 91%, and specificity of 99%. Twelve arteries were diagnosed as suspected subtotal to total occlusion (limited studies), and of these, three were occluded on angiography, eight had stenoses ranging from 90% to 99%, and one had 80% stenosis. CONCLUSIONS: A carotid duplex ultrasound study is an acceptable method for predicting total carotid occlusion when the study is optimal, and angiography is unnecessary in asymptomatic patients. Angiography is recommended for patients who are surgical candidates with a limited duplex study.

Adult↗
PubMed1997

Congenital cutaneous candidiasis associated with respiratory distress and elevation of liver function tests: a case report and review of the literature.

We describe congenital cutaneous candidiasis (CCC) in a term newborn. The mother had candidal vaginitis 1 week before delivery. At birth, the infant had a generalized, intensely erythematous, papulovesicular eruption, respiratory distress and elevation of liver function tests. The child responded well to intravenous amphotericin B plus topical and oral nystatin. There have been 13 previously reported cases of CCC in infants weighing more than 1500 gm who had evidence of systemic infection. Two deaths were attributed to candidal pneumonia and sepsis. The majority of infants with CCC have infection localized to the skin, but if there is any evidence of respiratory distress or signs of sepsis the possibility of systemic candidiasis and the need for parenteral antifungal therapy must be considered.

Amphotericin B↗
PubMed1996

Fibro-osseous pseudotumor of the digit: a comparison to myositis ossificans by light microscopy and immunohistochemical methods.

Fibro-osseous pseudotumor of the digit is an unusual cutaneous process characterized histologically by a fibroblastic proliferation admixed with reactive/metaplastic osteoid formation. The osteoid formation can be florid and immature, mimicking the appearance of malignant osteoid-forming neoplasms. Fibro-osseous pseudotumor of the digit has histologic and clinical features in common with myositis ossificans. This has led many to consider the two to be synonymous. We studied three cases of fibro-osseous pseudotumor, compared to five cases of myositis ossificans, using routine light microscopy and a battery of immunohistochemical stains. Both entities displayed a "zoning" pattern of immature spindled areas admixed with more mature areas having osteoid metaplasia. This was more pronounced in myositis ossificans. In each lesion, the spindle cells stained positively for vimentin and actin. CD34 and Factor VIII highlighted the vasculature. No stromal staining for MAK-6 (cytokeratin) or S-100 was identified. Ki-67, a proliferation marker, showed positive staining of the stromal cells in both lesions, which was strongest in the immature spindled areas. The immunohistochemical and histologic similarities of the lesions support fibro-osseous pseudotumor of the digit being a cutaneous variant of myositis ossificans.

Adolescent↗
PubMed1995

A new technique for transbronchial biopsy in infants and small children.

We describe a technique of transbronchial biopsy (TBB) in small children, using a plastic suction catheter as the working channel through which biopsy forceps are introduced. An ultrathin (2.2 mm) flexible fiberoptic bronchoscope (FFB) was used to direct the catheter visually into the desired lung segment and to biopsy selectively. This technique was used nine times to obtain biopsy specimens in six different patients, ranging in age from 3 months to 3 and 4/12 years (mean, 19.2 months). Adequate specimens were obtained in eight of nine procedures (89%). Complications included one pneumothorax that did not require evacuation and one episode of sedation-induced hypoventilation that required brief bag-mask ventilation. No significant bleeding occurred. This technique enabled us to obtain lung tissue in infants and small children without resorting to general anesthesia and rigid bronchoscopy.

Biopsy, Needle↗
PubMed1995

Prenatal diagnosis of fetal disseminated intravascular coagulation associated with umbilical cord arteriovenous malformation.

BACKGROUND: Congenital disseminated intravascular coagulation (DIC) has been reported in a variety of clinical settings, but to our knowledge, it has never been documented before birth. We describe prenatal identification of an umbilical cord vascular tumor and echogenic foci in the fetal liver leading to the diagnosis of fetal DIC by funipuncture. CASE: A large vascular tumor of the umbilical cord was identified using prenatal sonography. At 31 weeks' gestation, echogenic areas, which were thought to represent infarcts or thrombi, were seen in the liver. When funipuncture revealed florid fetal DIC, delivery was accomplished by cesarean to prevent intracranial bleeding. Pathologic examination of the umbilical cord tumor showed it to be a large arteriovenous malformation. CONCLUSION: Arteriovenous malformations may cause fetal coagulopathy. This case illustrates that funipuncture may be used to diagnose this condition and that timely cesarean delivery may contribute to a favorable outcome.

Adult↗