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Biomedical subjects

K Gaffney

Publications and source records attributed to K Gaffney.

36 records · Page 2Linked to original sources

Detection and investigation of the molecular nature of low-molecular-mass copper ions in isolated rheumatoid knee-joint synovial fluid.

Low-molecular-mass copper(II) species have been detected and quantified in ultrafiltrates (n = 7) of rheumatoid synovial fluid (SF) by a highly-sensitive HPLC-based assay system with the ability to determine Cu(II) concentrations of < 10(-7) mol.dm-3. High field 1H NMR spectroscopy demonstrated that addition of Cu(II)(aq.) to isolated samples of RA SF ultrafiltrates resulted in complexation by histidine > alanine > formate > threonine > lactate > tyrosine > phenylalanine, their effectiveness in this context being in the given order. CD spectra of Cu(II)-treated samples of intact SF exhibited absorption bands typical of copper(II)-albumin complexes, in addition to a band attributable to a low-molecular-mass histidinate complex (lambda min 610 nm). Since both albumin and histidine are potent radical scavengers, these results indicate that any .OH radical generated from bound copper ions will be 'site-specifically' scavenged. Hence, low-molecular-mass copper complexes with the ability to promote the generation of .OH radical which can then escape from the metal ion co-ordination sphere (and in turn, cause damage to critical biomolecules) appear to be absent from inflammatory SF.

Adult↗

Quantification of rheumatoid synovitis by magnetic resonance imaging.

OBJECTIVE: To develop a method for quantifying acute synovial inflammation in rheumatoid arthritis (RA), utilizing magnetic resonance imaging (MRI). METHODS: Gadolinium-diethylenetriamine pentaacetic acid-enhanced MRI was performed in 21 patients with knee synovitis. Changes in synovial membrane signal intensity were identified and quantified by line profile analysis. Multiple synovial biopsies were obtained by a blind biopsy technique, and standard clinical and laboratory measurements of disease activity were recorded. RESULTS: The rate of synovial membrane enhancement correlated with histologic features of acute inflammation (r = 0.63, P < 0.01), but not with clinical or laboratory assessments. CONCLUSION: Dynamic MRI is a valuable technique for assessing acute synovial inflammation in RA.

Adult↗

Mucocutaneous criteria for the diagnosis of Behçet's disease: an analysis of clinicopathologic data from multiple international centers.

BACKGROUND: Although four of five of the new international criteria for the diagnosis of Behçet's disease relate to mucocutaneous lesions, disagreement exists as to the exact nature of cutaneous lesions (e.g., vessel-based vs follicular). OBJECTIVE: Our purpose was to review clinical data, clinical photographs, and skin biopsy specimens from multiple medical centers throughout the world to monitor current practice in the implementation of mucocutaneous diagnostic criteria for Behçet's disease. METHODS: Ten medical centers responded to a request to collaborate by sending clinical data, photographs of cutaneous lesions, and biopsy specimens from 22 patients. RESULTS: Of specimens from 22 patients, 14 revealed a histopathologic pattern of neutrophils containing perivascular and interstitial inflammation, whereas specimens from three patients revealed only mononuclear cells in a vessel-based pattern. Biopsy specimens from three patients revealed primarily folliculocentric inflammation and an additional two specimens were from erythema nodosum-like lesions. CONCLUSION: Perivascular inflammation was the predominant histopathologic finding in specimens of cutaneous lesions in this clinical series. Folliculocentric lesions could not be predicted on the basis of review of clinical photographs. Histopathologic assessment of cutaneous lesions is crucial if the proposal is accepted that exclusion of folliculocentric lesions is important to ensure accurate implementation of diagnostic criteria in patients with suspected Behçet's disease.

Adult↗

Intra-articular triamcinolone hexacetonide in knee osteoarthritis: factors influencing the clinical response.

OBJECTIVE: To assess the efficacy of a single intra-articular injection of triamcinolone hexacetonide (THA) in knee osteoarthritis (OA) and examine factors which may relate to treatment efficacy. METHODS: Eighty four patients with clinical and radiographic evidence of knee OA were recruited and randomly allocated to receive either THA (20 mg in 1 ml) or placebo (0.9% normal saline, 1 ml). Follow up assessments evaluated the following outcome variables: patient opinion of overall change in the treated knee, visual analogue pain score (VAS), distance walked in one minute (WD), and Health Assessment Questionnaire modified for lower limb function (HAQ). RESULTS: Seventy eight percent of THA and 49% of placebo treated patients reported overall improvement at week 1 (p < 0.05). At week 6, improvement was reported in 57% and 55% of patient groups, respectively. VAS improved in both groups at week 1 (THA, p < 0.001; placebo, p < 0.05) and week 6 (both p < 0.01). Improvement in VAS was significantly greater among THA treated patients at week 1 only (p < 0.01). Subgroup analysis of THA treated patients revealed greater improvement in VAS among patients with clinical evidence of an effusion (p < 0.05), and those who had synovial fluid successfully aspirated at the time of injection (p < 0.01). WD improved in THA treated patients at week 1 (p < 0.001), and in both groups at week 6 (THA, p < 0.001; placebo, p < 0.01). Improvements in HAQ were seen in THA patients only at weeks 1 and 6 (p < 0.05). Regression analysis did not identify any additional clinical, radiographic, or synovial fluid characteristics which influenced the response. CONCLUSIONS: THA provided short term pain relief in knee OA. Increased benefit was associated with both clinical evidence of joint effusion and successful aspiration of synovial fluid at the time of injection.

Administration, Topical↗

Intra-articular pressure changes in rheumatoid and normal peripheral joints.

OBJECTIVE: To investigate the intraarticular pressure (IAP) dynamics of a spectrum of joints in rheumatoid and normal subjects in order to determine whether a reperfusion event is likely to occur at these sites. METHODS: IAP was measured in the metacarpophalangeal (MCP) (n = 8), wrist (n = 8), ankle (n = 4), and elbow joints (n = 4) of rheumatoid subjects, in addition to the MCP (n = 8), wrist (n = 6), and ankle joints (n = 1) of normal healthy controls, using the hand held portable 295-1 Intra-Compartmental Pressure Monitor System (Stryker, UK). RESULTS: Resting IAP was positive in all rheumatoid joints, and subatmospheric or weakly atmospheric in normal subjects (p < 0.01). Exercise produced an increase in IAP in rheumatoid subjects only (p < 0.01). The addition of saline to normal joints mimicked the IAP changes seen in the rheumatoid group. CONCLUSION: These observations suggest that increased resting IAP is a marker for chronic joint inflammation. The IAP increase seen in the rheumatoid group during exercise supports the concept of hypoxic reperfusion mediated joint injury.

Adult↗

Message of nexin 1, a serine protease inhibitor, is accumulated in the follicular papilla during anagen of the hair cycle.

A group of specialized mesenchymal cells located at the root of the mammalian hair follicle, known as the follicular or dermal papillary cells, are involved in regulating the hair cycle, during which keratinocytes of the lower follicle undergo proliferation, degeneration and regrowth. Using the arbitrarily primed-PCR approach, we have identified a 1.3 kb messenger RNA that is present in large quantities in cultured rat follicular papillary cells, but not in skin fibroblasts. This mRNA encodes nexin 1, a potent protease inhibitor that can inactivate several growth-modulating serine proteases including thrombin, urokinase and tissue plasminogen activator. In situ hybridization showed that nexin 1 message is accumulated in the follicular papilla cells of anagen follicles, but is undetectable in keratinocytes or other skin mesenchymal cells. In addition, nexin 1 message level varies widely among several immortalized rat vibrissa papillary cell lines, and these levels correlate well with the reported abilities of these cell lines to support in vivo follicular reconstitution. These results suggest a possible role of nexin 1 in regulating hair follicular growth.

Amyloid beta-Protein Precursor↗

Neutrophil collagenase in sputum from patients with cystic fibrosis.

The potential role of neutrophil elastase in causing lung damage and exacerbating the inflammatory response in cystic fibrosis (CF) has received considerable attention. Although another potent neutrophil-derived enzyme, collagenase, is implicated in tissue destruction in several interstitial lung disorders, there has been no reference to this enzyme in CF. The objective of this study was to determine whether neutrophil collagenase is present in active form in CF sputum and, if so, whether it is related to disease severity. High levels of active collagenase were detected in sputum from patients with CF, and the majority of the enzyme present was of neutrophil origin. In a group of 16 patients with CF, negative relations between sputum collagenase activity and Shwachman score (r = -0.55, p < 0.05) and FEV1 (r = -0.59, p < 0.02) were noted, indicating an association between high collagenase activity and severity of disease. A positive correlation was observed between sputum collagenase and elastase activity (r = 0.62, p < 0.05). These results suggest that both neutrophil elastase and collagenase may play a significant role in lung destruction in CF.

Adolescent↗

Eosinophilic fasciitis: a good response with conservative treatment.

A 52 year old man developed progressive painful swelling of both calves and difficulty walking. Physical examination showed asymmetrical localised swelling with induration and tenderness on palpation. Peripheral blood eosinophilia was noted. Biopsy of deep fascia and muscle showed typical features of eosinophilic fasciitis. He was treated with non-steroidal anti-inflammatory drugs and intensive physiotherapy. The clinical features had completely resolved six months later.

Anti-Inflammatory Agents, Non-Steroidal↗

Amyloidosis complicating cystic fibrosis.

Two patients with cystic fibrosis developed acute onset nephrotic syndrome and died within three months of presentation. Examination of renal biopsy specimens indicated amyloid. The onset of proteinuria or a fall in baseline renal function should alert the physician to this rare complication.

Adolescent↗

alpha 1-Proteinase inhibitor, elastase activity, and lung disease severity in cystic fibrosis.

The potential role of neutrophil elastase in exacerbating pulmonary infection and tissue damage in cystic fibrosis (CF) has led to proposals for treatment of lung disease in CF with the elastase inhibitor, alpha 1-proteinase inhibitor (alpha 1PI). Reports that alpha 1PI is inactivated in the CF lung suggest that the effectiveness of alpha 1PI therapy depends on the quantity of elastase present and the extent of alpha 1PI inactivation, both of which are expected to vary with disease severity. In this study we assessed the elastase-alpha 1PI profile in sputum and plasma from CF patients with various degrees of pulmonary involvement. Levels of active elastase in sputum samples increased with severity of pulmonary disease (F ratio = 5.63, p < 0.01), as did sputum levels of alpha 1PI (F ratio = 4.88, p < 0.01). A positive correlation was observed between sputum levels of active elastase and alpha 1PI (r = 0.68, p < 0.005). Plasma alpha 1PI levels were also elevated in CF patients compared with control subjects (p < 0.005), indicating a compensatory increase in plasma and sputum levels of alpha 1PI in response to increased elastase load. Molar levels of total immunogenic neutrophil elastase were, on average, 12 times higher than alpha 1PI in CF sputum. These results suggest that the major contributor to the elevated levels of active elastase observed in the CF lung is an increase in elastase release rather than inactivation of alpha 1PI.

Adolescent↗

Characteristics of colon cancer at time of presentation.

OBJECTIVE: To evaluate the relationships between demographic and clinical characteristics and the stage and site of colon cancer at the time of presentation. METHODS: New cases of colon cancer identified through a tumor registry at a teaching hospital during 1989 were reviewed retrospectively. Of the 110 cases, 53% of the subjects were female, 95% were white, and 63% were more than 70 years of age. RESULTS: Early stages of colon cancer (Dukes A [11%] or B [41%]) occurred in 52%, and late stages (Dukes C [26%] or D [22%]) in 48%. Most patients (88%) presented with symptoms; 12% of the cases were detected in asymptomatic patients. Of the 13 asymptomatic patients, 7 were identified by positive occult blood in the stool, 5 by colonoscopy, and 1 during a hysterectomy. The stage of colon cancer was more likely to be early in asymptomatic patients (85% Dukes A or B) compared to those with symptoms (47% Dukes A or B) (p < 0.02). Sixty-two percent (62%) of the cecum/ascending colon cancer were early compared to 46% of the cancers in other locations (p = 0.11). Seventy-seven percent (77%) of the asymptomatic cancers were located in the cecum/ascending colon compared to 33% of the symptomatic patients (p < 0.02). Age and gender were not associated with site or stage of colon cancer. CONCLUSION: The majority of patients with colon cancer are diagnosed when symptomatic. When colon cancer is diagnosed while still asymptomatic, it is more likely to be at an early stage. The most common screening procedure leading to diagnosis in asymptomatic patients is the identification of fecal occult blood. Colon cancer is more likely to be located in the cecum/ascending colon when diagnosed at an asymptomatic stage.

Aged↗

Phlebotomy practices/needles stick injuries/hepatitis B status/among interns in a Dublin hospital.

Needlestick injury is the most important risk event for human immunodeficiency virus (HIV) and hepatitis B Virus (HBV) transmission to health-care workers. We examined phlebotomy practices, the frequency of needle stick injuries, the reporting of such injuries and hepatitis B status among interns in St James's Hospital during a six month period. This study took the form of a questionnaire. The response rate was 100%. 72% had at least one needlestick injury during this time period, 23% had injuries from known HIV sero-positive or hepatitis B surface antigen positive patients, less than 5% of all injuries were reported and only 41% of interns were definitely hepatitis B immune. The majority (77%) resheated needles by hand.

Accidents, Occupational↗

The impact of HIV disease on an Irish prison population.

Between January 1987 and January 1991, 168 known HIV-infected prisoners have been incarcerated in Dublin's Mountjoy prison. This figure constitutes 16.6% of the total HIV-infected population in the Republic of Ireland over the same period. One hundred and forty-one (84%) of these prisoners have attended the Department of Genitourinary Medicine, St James's Hospital, Dublin. This group displayed considerable morbidity from HIV-related disease. Respiratory tract infection was the most frequent complication seen. Much additional morbidity was directly attributable to intravenous drug use. A survey of a representative group of inmates revealed that 64.7% were diagnosed HIV-positive in prison. The mean length of time spent incarcerated since the diagnosis of HIV infection was 38.9 months. Twenty-nine of 34 individuals who answered a questionnaire were imprisoned for drug-related crimes and 32 of 34 prisoners admitted to parenteral drug use within the prison. As the HIV epidemic unfolds in Dublin, increasing numbers of prisoners with symptomatic HIV disease will spend time incarcerated in Mountjoy prison. This will pose a considerable burden on prison and hospital medical services alike.

Acquired Immunodeficiency Syndrome↗