Search PubMed⌕ Search

Biomedical subjects

M Duncan

Publications and source records attributed to M Duncan.

At least 19 recordsLinked to original sources
PubMed2006

Oral EBV and KSHV infection in HIV.

The gamma herpesviruses, Kaposi's-sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), are tightly associated with the development of AIDS-associated oral disease and malignancy during immune suppression. The objective of this investigation was to characterize oral infection and pathogenesis in healthy and immune-suppressed individuals. To characterize oral EBV and KSHV infection, we examined throat washings and oral epithelial cells from HIV-positive and HIV-negative individuals. Quantitative/real-time polymerase-chain-reaction (PCR) assays, transmission electronmicroscopy, immunostaining, and sequence analysis were used to identify viral infection. Virus was isolated from throat-wash samples and was used to infect epithelial and lymphoid cell lines. We detected EBV and KSHV in the oral cavity in healthy and immune-suppressed individuals. Viral strain analysis of KSHV K1 in multiple clones from the oral cavities of healthy persons and immunosuppressed patients detected several strains previously detected in KS lesions, with minor strain variation within individuals. Immunoelectron microscopy for multiple viral antigens detected consistent expression of viral proteins and oral epithelial specimens. In oral epithelial cells infected with wild-type KSHV in vitro, the K8.1 glycoprotein associated with lytic KSHV infection was detected in both primary and telomerase immortalized oral epithelial cultures by 24 hours post-infection. Virions were detected, subsequent to infection, by scanning electron microscopy. Oral epithelial cells were also infected in vitro with wild-type EBV originating from throat washes. Analysis of these data suggests that, like EBV, KSHV infection is present in the oropharynx of healthy individuals, is transmissible in vitro, and may be transmitted by saliva.

AIDS-Related Opportunistic Infections↗
PubMed2006

Prevalence of vitamin D inadequacy in Belfast following fragility fracture.

BACKGROUND: It is well established that vitamin D levels are sub-optimal in older people and that adults with fragility fracture have low levels of serum vitamin D. OBJECTIVES: To investigate the prevalence of vitamin D inadequacy in an elderly population with fragility fractures and to compare data with previously published work from Glasgow. RESEARCH DESIGN AND METHODS: Two retrospective patient audits were carried out using records from the out-patient Osteoporosis Clinic at Musgrave Park Hospital and from in-patient hip fracture admissions at the Royal Victoria Hospital. RESULTS: There were data for 86 patients with fragility fracture from the Osteoporosis Clinic, 40.7% patients had vertebral fractures and 10.5% multiple fractures. Patients with hip fracture were excluded from the analysis. 69.8% of the patients were women. The mean age at the time of fracture was 65.3 years and 70.9% of patients were aged 60 years or over and 32.6% were aged 75 years or over. At the time of out-patient attendance, 73.3% were receiving supplementation with calcium and vitamin D. The mean vitamin D level was 52.3 nmol/L (21.0 ng/mL), SD = 23.4 (9.4). There were 83.7% of patients who had a vitamin D level < 80 nmol/L, 73.3% < 70 nmol/L and 55.8% < 50 nmol/L. There were no significant differences by patient age or sex. Data were also analysed according to supplementation status, in patients not taking supplements (n = 23) mean vitamin D level was 48.1 nmol/L (19.3 ng/mL), SD = 27.4 (11.0) compared with 53.8 nmol/L (21.6 ng/mL), SD = 21.8 (8.7) in the 63 patients taking supplements. Prevalence of inadequacy was higher in the patients not taking supplements 82.6% versus 67.1% at the 70 nmol/L threshold. There were data for 43 hip fracture patients, 95.3% of the patients were women. The mean age at the time of fracture was 78.3 years, 95.3% of patients were aged 60 years or over and 69.8% were aged 75 years or over. Data were not available on whether these patients were receiving supplementation. The mean vitamin D level was 36.1 nmol/L (14.5 ng/mL), SD = 24.8 (9.9). 90.7% of patients had a vitamin D level < 80 nmol/L, 88.4% < 70 nmol/L ( approximately 28 ng/mL) and 88.4% < 50 nmol/L ( approximately 20 ng/mL). CONCLUSIONS: The levels of vitamin D inadequacy revealed in this audit were similar to those in an earlier audit carried out in Glasgow. Thus studies at two locations in the UK confirm the high prevalence of vitamin D inadequacy, furthermore, the prevalence of inadequacy appears to be higher in those patients with a hip fracture.

Adult↗
PubMed2005

Review article: endocannabinoids and their receptors in the enteric nervous system.

The therapeutic actions of cannabinoids have been known for centuries. In the last 25 years this area of research has grown exponentially with the discovery of specific cannabinoid receptors and endogenous ligands. In the enteric nervous system of gastrointestinal tract, cannabinoid receptors are located on enteric nerve terminals where they exert inhibitory actions on neurotransmission to reduce motility and secretion. Endogenous cannabinoids are present in the enteric nervous system, as are the degradative enzymes necessary to inhibit their action. The cellular mechanism of action of endocannabinoids has not been established in the enteric nervous system. Endocannabinoids not only act at cannabinoid receptors, but potentially also at vanilloid and 5-HT3 receptors, both of which are expressed in the gastrointestinal tract. The interactions between endocannabinoids and these other important receptor systems have not been extensively investigated. A greater understanding of the endocannabinoid system in the enteric nervous system could lead to advances with important therapeutic potential in the treatment of gastrointestinal disorders such as irritable bowel syndrome, inflammatory bowel disease, secretory diarrhoea and gastro-oesophageal reflux disease.

Animals↗
PubMed2004

Chronic eosinophilic dermatitis associated with persistent feline herpes virus infection in cheetahs (Acinonyx jubatus).

A chronic ulcerative and eosinophilic dermatitis occurred in 20 captive cheetahs (Acinonyx jubatus) with persistent feline herpes virus 1 (FHV1) infection. Affected animals had erythematous, ulcerated plaques primarily on the face and forelegs in sites of contact with lachrymal and salivary secretions. The dermatitis was characterized by dense infiltrates of eosinophils and plasma cells and pseudoepitheliomatous hyperplasia. Rare keratinocytes within the lesions had nuclei with marginated chromatin and small eosinophilic inclusions composed of herpes virus nucleocapsids. Virus isolated from lesions was confirmed to be FHV1. Lesions persisted and progressed unless removed by cryoexcision. The occurrence of this unusual reaction to FHV1 in approximately 5% of captive North American cheetahs suggests a species propensity for a Th2-dominant response to herpes virus infection. This atypical immune reaction may indicate a heritable trait or modulation of the immune response by other factors such as chronic stress.

Acinonyx↗
PubMed2003

Oral and intestinal mucositis - causes and possible treatments.

Chemotherapy and radiotherapy, whilst highly effective in the treatment of neoplasia, can also cause damage to healthy tissue. In particular, the alimentary tract may be badly affected. Severe inflammation, lesioning and ulceration can occur. Patients may experience intense pain, nausea and gastro-enteritis. They are also highly susceptible to infection. The disorder (mucositis) is a dose-limiting toxicity of therapy and affects around 500 000 patients world-wide annually. Oral and intestinal mucositis is multi-factorial in nature. The disruption or loss of rapidly dividing epithelial progenitor cells is a trigger for the onset of the disorder. However, the actual dysfunction that manifests and its severity and duration are greatly influenced by changes in other cell populations, immune responses and the effects of oral/gut flora. This complexity has hampered the development of effective palliative or preventative measures. Recent studies have concentrated on the use of bioactive/growth factors, hormones or interleukins to modify epithelial metabolism and reduce the susceptibility of the tract to mucositis. Some of these treatments appear to have considerable potential and are at present under clinical evaluation. This overview deals with the cellular changes and host responses that may lead to the development of mucositis of the oral cavity and gastrointestinal tract, and the potential of existing and novel palliative measures to limit or prevent the disorder. Presently available treatments do not prevent mucositis, but can limit its severity if used in combination. Poor oral health and existing epithelial damage predispose patients to mucositis. The elimination of dental problems or the minimization of existing damage to the alimentary tract, prior to the commencement of therapy, lowers their susceptibility. Measures that reduce the flora of the tract, before therapy, can also be helpful. Increased production of free radicals and the induction of inflammation are early events in the onset of mucositis. Prophylactic administration of scavengers or anti-inflammatories can partially counteract or limit some of these therapy-mediated effects, as can the use of cryotherapy. The regular use of mouthwashes, mouth coatings, antibiotics and analgesics is essential, prior to and during loss and ablation of the epithelial layer. Granulocyte-macrophage colony-stimulating factor/granulocyte colony-stimulating factor or the use of laser light therapy may aid restitution and repair. Glutamine supplements may be beneficial in the repair/recovery phase.

Age Factors↗
PubMed2002

Interdigitating dendritic cell sarcoma: a rare malignancy responsive to ABVD chemotherapy.

Interdigitating dendritic cell sarcoma (IDCS) is an aggressive neoplasm of which fewer than 25 cases have been reported in the world literature. This malignancy is difficult to diagnose because of its rarity, and because of the subtle histopathologic features that distinguish IDCS from similar tumors arising from reticular cells. To date, there exists no consensus on a standard chemotherapeutic regimen for IDCS. Patients with this malignancy have been treated with chemotherapy regimens used against non-Hodgkin's lymphomas. Responses to these regimens have been variable, but mostly unsuccessful. In this article we describe a case of IDCS occurring in a 44 year old female who presented with abdominal pain and inguinal adenopathy. Staging of the tumor with CT scan, PET scan, and bone marrow biopsy demonstrated inguinal and abdominal lymphadenopathies, a large mass encasing the small bowel, and extensive liver infiltration. Morphologic and cytochemical analysis of biopsies from the abdominal mass and inguinal node were consistent with a diagnosis of IDCS, and immunohistochemical stains of the lymph node were positive for CLA, Kp-1, S-100, while negative for CD1a, CD3, CD20, CKER, and HMB45. Treatment of this patient with ABVD chemotherapy resulted in rapid clinical improvement with a marked decrease in tumor burden after two cycles of ABVD, and a complete response after six cycles of therapy.

Adult↗
PubMed2001

A profile of neurology practice based on Medicare services: an AAN Medical Economics and Management Committee report. American Academy of Neurology.

OBJECTIVE: This report uses Medicare data to provide insight into the patient care services most often provided by neurologists. METHODS: The 1998 Medicare data set for physician services was obtained from the Health Care Financing Administration. Neurologists' services were tabulated and compared to the 1998 American Academy of Neurology Member Demographic and Practice Characteristics Report. A profile was derived of neurologists' typical services. RESULTS: Patient visits represent 70% of neurologists' services when evaluated by income. Office was the site of service for 62% of patient visit income. Established patients were 29% of patient visit income. Neurologists frequently code patient visits at levels of service higher than used by other physicians. EMG and nerve conduction velocity together represent 55% of neurodiagnostic services when evaluated by income. CONCLUSIONS: Patient care continues to be the main service of neurologists, with office care more than hospital care. Established patient care is an important part of patient services, confirming the role of the neurologist in principal care. Neurologists' patient care levels of service are higher than for other physicians.

Medicare↗
PubMed2001

Genotypic diversity of mutans streptococci in Brazilian nursery children suggests horizontal transmission.

Streptococcus mutans strains were isolated from cohorts of Brazilian nursery school children and genotyped by arbitrarily primed PCR and restriction fragment length polymorphism analysis. Of 24 children with two to five S. mutans isolates, 29% carried two or more genotypes. The presence of matching genotypes of S. mutans among children attending one nursery suggests horizontal transmission.

Brazil↗
PubMed1999

Surgical intervention and understanding of diseases of the stomach and duodenum.

The stomach and duodenum are organs of complex physiology and cell biology. Neoplastic disease of these organs represents a difficult surgical challenge, and gastric and duodenal cancer mortality rates remain high despite advances in surgical technique, perioperative care, and adjuvant therapy. True "cures" elude the surgeon all too often. Fortunately, our understanding of the genetics and molecular biology of upper gastrointestinal neoplasms is increasing and is now significantly affecting the clinical management of these tumors as surgical therapies continue to improve. The care of benign disease of the stomach and duodenum is also evolving as medical therapy and surgical technology improve to lessen the morbidity associated with peptic ulcer disease and other benign conditions. The event that may have the greatest effect on surgical intervention in peptic ulcer disease is the Centers for Disease Control and Prevention launching of an educational campaign to promote treatment of Helicobacter pylori. This article reviews the most significant advances published in the past year on surgical intervention of the stomach and duodenum.

Journal Article↗
PubMed1998

Comparative analysis of Haemophilus influenzae hifA (pilin) genes.

Adherence of Haemophilus influenzae to epithelial cells plays a central role in colonization and is the first step in infection with this organism. Pili, which are large polymorphic surface proteins, have been shown to mediate the binding of H. influenzae to cells of the human respiratory tract. Earlier experiments have demonstrated that the major epitopes of H. influenzae pili are highly conformational and immunologically heterogenous; their subunit pilins are, however, immunologically homogenous. To define the extent of structural variation in pilins, which polymerize to form pili, the pilin genes (hifA) of 26 type a to f and 16 nontypeable strains of H. influenzae were amplified by PCR and subjected to restriction fragment length polymorphism (RFLP) analysis with AluI and RsaI. Six different RFLP patterns were identified. Four further RFLP patterns were identified from published hifA sequences from five nontypeable H. influenzae strains. Two patterns contained only nontypeable isolates; one of these contained H. influenzae biotype aegyptius strains F3031 and F3037. Another pattern contained predominantly H. influenzae type f strains. All other patterns were displayed by a variety of capsular and noncapsular types. Sequence analysis of selected hifA genes confirmed the 10 RFLP patterns and showed strong identity among representatives displaying the same RFLP patterns. In addition, the immunologic reactivity of pili with antipilus antisera correlated with the groupings of strains based on hifA RFLP patterns. Those strains that show greater reactivity with antiserum directed against H. influenzae type b strain M43 pili tend to fall into one RFLP pattern (pattern 3); while those strains that show equal or greater reactivity with antiserum directed against H. influenzae type b strain Eagan pili tend to fall in a different RFLP pattern (pattern 1). Sequence analysis of representative HifA pilins from typeable and nontypeable H. influenzae identified several highly conserved regions that play a role in bacterial pilus assembly and other regions with considerable amino acid heterogeneity. These regions of HifA amino acid sequence heterogeneity may explain the immunologic diversity seen in intact pili.

Amino Acid Sequence↗
PubMed1998

Role of Arg-gingipain A in virulence of Porphyromonas gingivalis.

In order to access the role of the Porphyromonas gingivalis Arg-gingipain proteases in the virulence of this organism, a mutant defective in the rgpA gene was constructed in strain 381. This mutant, MT10, displayed only 40% of the Arg-specific cysteine protease activity of the wild-type strain. In addition, MT10, as well as the recently characterized protease mutant G-102, which is defective in the rgpB gene, displayed reduced self-aggregation, hemagglutination, and the ability to bind to immobilized type I collagen compared to levels of the wild-type parent. However, unlike mutant G-102, the rgpA mutant displayed increased binding to epithelial cells relative to that of the parental organism. Mutant MT10 also did not express detectable levels of the FimA protein as assessed by both Western and Northern blotting or fimbriae visible by electron microscopy of the cells. Furthermore, the ability of MT10 to degrade rat tail collagen fibers when it was cultured at 37 degrees C was markedly attenuated compared to that of strain 381. These results suggest that Arg-gingipain A may play a significant role in the pathogenicity of P. gingivalis by altering the colonization and toxic properties of the organism.

Adhesins, Bacterial↗
PubMed1998

How is whole body protein turnover perturbed in growth hormone-deficient adults?

Adult patients with GH deficiency have reduced lean body mass (LBM), muscle mass, and muscle strength, suggesting an underlying abnormality of protein metabolism. As acute GH administration has previously been reported to decrease protein oxidation and increase protein synthesis in GH-deficient (GHD) adults, we investigated whether the converse might occur in untreated GH deficiency by undertaking studies of whole body protein turnover in 10 GHD and 13 normal subjects using a 3-h primed constant infusion of 1-[13C]leucine. Dual energy x-ray absorptiometry was used to quantify LBM and fat mass (FM). In normal subjects, LBM was the major, independent determinant of leucine appearance (Ra; r=0.80; P=0.0009), leucine oxidation (r=0.81; P=0.0008), and leucine incorporation into protein (r=0.75; P= 0.003). However, in an analysis of covariance, FM was also a significant independent determinant of leucine Ra (P=0.002) and leucine incorporation into protein (P=0.003). After correcting for LBM and FM, GHD patients had significantly reduced rates of leucine Ra (109.9+/-4.4 vs. 125.5+/-3.7 micromol/min, respectively; P=0.02) and leucine incorporation into protein (87.0+/-3.9 vs. 100.3+/-3.3 mmol/ min; P=0.02) compared to normal subjects. There was no significant difference in the corrected rates of leucine oxidation between the two groups (22.9+/-1.3 vs. 25.2+/-1.0, GHD vs. normal; P=0.20). In summary, GHD adults have reduced rates of protein synthesis and protein breakdown, but normal rates of irreversible oxidative loss; these findings are discordant with what was predicted from the acute changes in protein metabolism observed with GH administration. We conclude that normalization of protein oxidation may be a homeostatic mechanism that operates to constrain protein loss in GHD adults.

Adipose Tissue↗