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Biomedical subjects

D Gale

Publications and source records attributed to D Gale.

At least 19 recordsLinked to original sources
PubMed2006

Urinary pentosidine does not predict cartilage loss among subjects with symptomatic knee OA: the BOKS Study.

OBJECTIVE: Age-related changes in articular cartilage are likely to play a role in the etiology of osteoarthritis (OA). One of the major changes in the extracellular matrix of cartilage is the age-related accumulation of advanced glycation end products (AGEs). Pentosidine, an AGE crosslink, is one of the few characterized AGEs and is considered an adequate marker for the many AGEs that are formed in vivo. We used data from a longitudinal observation study to determine if urinary pentosidine could serve as a marker to predict cartilage loss. METHODS: We conducted a prospective analysis of data from the Boston Osteoarthritis of the Knee Study (BOKS); a completed natural history study of knee OA. All subjects in the study met American College of Rheumatology (ACR) criteria for knee OA. Knee magnetic resonance (MR) images were scored for cartilage in 14 plates of the knee using the Whole Organ Magnetic Resonance Imaging Score (WORMS) semiquantitative grading scheme. Within the BOKS population, a nested sample of 127 subjects (39% of the whole sample) who had both baseline pentosidine and longitudinal magnetic resonance imaging (MRI) measurements (MRIs performed at baseline and 30 months later) was assessed. Urinary pentosidine was assayed and normalized to creatinine to account for differences in urine concentrations. We analyzed the data using three different methods to assess if baseline measures of pentosidine predicted subsequent cartilage loss on MRI. These were (1) analysis 1: logistic regression with the outcome cartilage loss in any plate; (2) analysis 2: proportional odds model where the outcome was defined as 0=no cartilage loss, 1=cartilage loss in one plate, 2=cartilage loss in two plates, and 3=cartilage loss in at least three plates; and (3) analysis 3: Poisson regression with the outcome the number of plates with cartilage loss. All analyses were adjusted for age, sex and Body Mass Index (BMI). RESULTS: At baseline the mean (standard deviation) age was 67 (9) years and 54% were male. The results for the three analytic steps are as follows: Analysis 1: the odds ratio for cartilage loss is 1.01 (95% confidence interval (CI) 0.93-1.09) with 1 unit increase in pentosidine. Analysis 2: the odds ratio for more cartilage loss is 0.99 (95% CI 0.92-1.06) with 1 unit increase in pentosidine. Analysis 3: the relative number of plates with cartilage loss decreased was 1.00 (95% CI 0.95-1.03) with a 1 unit increase in pentosidine. CONCLUSION: Urinary pentosidine does not predict knee cartilage loss. Previous studies have suggested that local content within cartilage of AGEs is elevated in persons at high risk for progression. Our data suggest that these changes are not measurable systemically. Alternatively, urinary pentosidine levels reflect cartilage degradation in all joints (thus whole body cartilage breakdown) and may therefore not relate to OA severity in a single knee joint.

Aged↗
PubMed2006

High signal in knee osteophytes is not associated with knee pain.

OBJECTIVE: Our understanding of the local source of pain in osteoarthritis (OA) remains unclear. We undertook this study to determine if the presence of high-signal osteophytes on magnetic resonance imaging (MRI) was associated with pain presence, location or severity. METHODS: Subjects were chosen from the Boston Osteoarthritis of the Knee Study, a natural history study of symptomatic knee OA. Assessments included knee MRI, pain assessments and information on weight and height. Osteophyte signal was defined as areas of increased signal intensity in the osteophyte on fat-suppressed T2 weighted images, and graded in the joint margins where osteophyte size is graded. All patients were evaluated with the frequent knee symptoms question for pain presence, the Western Ontario McMasters Osteoarthritis Index (WOMAC) for pain severity, and location of self-reported pain was recorded as present or absent based on locations identified on a standardized diagram. The osteophyte signal measures anywhere within one given knee were summed, creating an osteophyte signal aggregate. Logistic regression was conducted with quartile of osteophyte signal aggregate as the independent predictor and frequent knee symptom question as the dependent outcome. Association between quartile of osteophyte signal aggregate and pain severity on WOMAC was assessed using a linear regression. Logistic regression was used to evaluate the association between compartment-specific high-signal osteophytes aggregates (independent variable) and compartment-specific knee pain (dependent variable). Analyses were adjusted for gender, body mass index (BMI), and age. RESULTS: Two hundred and seventeen subjects were included in this analysis. They were predominantly male and 75% of subjects had radiographic tibio-femoral (TF) OA, and the remainder had patello-femoral (PF) radiographic OA. We did not find any association of high-signal osteophytes with presence of pain, pain severity or self-reported pain location. CONCLUSION: High-signal osteophytes detected on MRI are not associated with the presence of pain, pain severity or the self-reported location of pain.

Aged↗
PubMed2006

The association of meniscal pathologic changes with cartilage loss in symptomatic knee osteoarthritis.

OBJECTIVE: To explore the role of meniscal tears and meniscal malposition as risk factors for subsequent cartilage loss in subjects with symptomatic osteoarthritis (OA). METHODS: Study subjects were patients with symptomatic knee OA from the Boston Osteoarthritis of the Knee Study. Baseline assessments included knee magnetic resonance imaging (MRI) with followup MRI at 15 and 30 months. Cartilage and meniscal damage were scored on MRI in the medial and lateral tibiofemoral joints using the semiquantitative whole-organ magnetic resonance imaging score. Tibiofemoral cartilage was scored on MR images of all 5 plates of each tibiofemoral joint, and the meniscal position was measured using eFilm Workstation software. A proportional odds logistic regression model with generalized estimating equations was used to assess the effect of each predictor (meniscal position factor and meniscal damage as dichotomous predictors in each model) on cartilage loss in each of the 5 plates within a compartment. Models were adjusted for age, body mass index (BMI), tibial width, and sex. RESULTS: We assessed 257 subjects whose mean +/- SD age was 66.6 +/- 9.2 years and BMI was 31.5 +/- 5.7 kg/m2; 42% of subjects were female, and 77% of knees had a Kellgren/Lawrence radiographic severity grade > or = 2. In the medial tibiofemoral joint, each measure of meniscal malposition was associated with an increased risk of cartilage loss. There was also a strong association between meniscal damage and cartilage loss. Since meniscal coverage and meniscal height diminished with subluxation, less coverage and reduced height also increased the risk of cartilage loss. CONCLUSION: This study highlights the importance of an intact and functioning meniscus in patients with symptomatic knee OA, since the findings demonstrate that loss of this function has important consequences for cartilage loss.

Aged↗
PubMed2006

Change in joint space width: hyaline articular cartilage loss or alteration in meniscus?

OBJECTIVE: To explore the relative contribution of hyaline cartilage morphologic features and the meniscus to the radiographic joint space. METHODS: The Boston Osteoarthritis of the Knee Study is a natural history study of symptomatic knee osteoarthritis (OA). Baseline and 30-month followup assessments included knee magnetic resonance imaging (MRI) and fluoroscopically positioned weight-bearing knee radiographs. Cartilage and meniscal degeneration were scored on MRI in the medial and lateral tibiofemoral joints using a semiquantitative grading system. Meniscal position was measured to the nearest millimeter. The dependent variable was joint space narrowing (JSN) on the plain radiograph (possible range 0-3). The predictor variables were MRI cartilage score, meniscal degeneration, and meniscal position measures. We first conducted a cross-sectional analysis using multivariate regression to determine the relative contribution of meniscal factors and cartilage morphologic features to JSN, adjusting for body mass index (BMI), age, and sex. The same approach was used for change in JSN and change in predictor variables. RESULTS: We evaluated 264 study participants with knee OA (mean age 66.7 years, 59% men, mean BMI 31.4 kg/m(2)). The results from the models demonstrated that meniscal position and meniscal degeneration each contributed to prediction of JSN, in addition to the contribution by cartilage morphologic features. For change in medial joint space, both change in meniscal position and change in articular cartilage score contributed substantially to narrowing of the joint space. CONCLUSION: The meniscus (both its position and degeneration) accounts for a substantial proportion of the variance explained in JSN, and the change in meniscal position accounts for a substantial proportion of change in JSN.

Aged↗
PubMed2004

The measurement and lateral comparison of the peak torque caused by the fast abduction exercise of stretched upper extremities in normal and trained adults.

The maximal torque effect of the middle portion of action of the deltoid muscle while raising an out-stretched upper limb was measured from left and right sides of normal untrained young adults and of the same age elite athletes. Seventeen strongly right-handed untrained males and females and 10 elite tennis players were tested. All participants were required to raise (abduct) one arm (right and then left, or vice versa) as fast as possible with maximal amplitude while standing on an electronic platform scale which measured to 0.001 kg. An assumed force at the centre of mass of the entire upper limb was considered. The force consisted of two components, namely static weight force of the upper limb and a dynamic force component created by upward acceleration of the limb. Using regression equations and scaling methods the static weight of the upper limb was derived and combined with the dynamic component to produce the total force, applied to the centre of mass of the limb. The total force multiplied by the distance from the centre of mass to point of rotation of the limb equated to the torque produced by deltoid muscle. Using video system analyses the angle of abduction was measured for each individual exercise. The additional anthropometrical tests identified proportionality and body mass indices for each participant. There was no significant difference in dynamic force and torque between left and right limb from the three groups. Sportsmen demonstrated greater lateral abduction when performing the exercise from the dominant side of the body. Sportsmen also demonstrated greater range of abduction, bigger dynamic force and torque on both sides in comparison to untrained adults. Remarkably, the absolute and relative length of arms of athletes were shorter in comparison to untrained males, but the radius of gyration from the stretched upper limb (from its centre of gravity to the shoulder joint) were greater. This phenomenon may be due to distal shifting of the gravity center of the entire upper limb in elite athletes, perhaps, because greater investment of the distal portion of the limb with skeletal muscle tissue.

Adult↗
PubMed2003

Are temporal characteristics of fast repetitive oscillating movement invariant?

Validation of the proportional duration model was attempted using very fast single-joint repetitive horizontal abductive-adductive movements of the stretched upper extremity with minimal cognitive input. Participants drew oscillating horizontal lines during 20 sec. over relatively short distances as quickly as possible without visual feedback. Spatial, temporal, and kinetic parameters were analysed. The amplitude and the time spent accelerating, decelerating, and reversing in both directions of each experimental line were recorded and related to the centre of gravity of the upper extremity. The accelerations of the centre of mass of the upper extremity were calculated and used to calculate the forces involved. The ratios of durations were compared and intercorrelated for the two fastest, two average, and two slowest cycles from each participant. Results exhibited significant standard deviations and variability of temporal and kinetic parameters within individual trials. The number of significant coefficients of correlation within individual trials was small despite the controlling influence of the same generalised motor program. The proportional duration model did not hold for our data. Peripheral factors (probably the length-tension relationship rule for skeletal muscles and viscosity of muscle) may be important in this type of action.

Biomechanical Phenomena↗
PubMed2001

Characterisation of gene expression changes following permanent MCAO in the rat using subtractive hybridisation.

Failure of several putative neuroprotectants in large multicentred clinical trials has re-focussed attention on the predictability of pre-clinical animal models of stroke. Model characterisation and relationship to heterogeneous patient sub-groups remains of paramount importance. Information gained from magnetic resonance imaging (MRI) signatures indicates that the Zea Longa model of rat middle cerebral artery occlusion may be more representative of slowly evolving infarcts. Understanding the molecular changes over several hours following cerebral ischaemia will allow detailed characterisation of the adaptive response to brain injury. Using a fully characterised model of Zea Longa middle cerebral artery occlusion we have used the representational difference analysis (RDA) subtractive hybridisation method to identify transcripts that accumulate in the ischaemic cortex. Along with a number of established ischaemia-induced gene products (including MCP-1, TIMP-1, hsp 70) we were also able to identify nine genes which have not previously been shown to accumulate following focal ischaemia (including SOCS-3, GADD45gamma, Xin).

Animals↗
PubMed2000

The effects of torque control spurs in twin-block appliances.

The study compared the effects of torque control spurs on upper incisor retroclination and extrusion with two designs of a twin-block functional appliance in Class II/1 cases. The two designs were also compared with respect to anchorage loss in the lower arch and for patient compliance rates. Consecutively started cases were chosen - 90 patients with a design incorporating a labial bow (CTB group) and 110 with upper incisor 'torquing' spurs (STB group) and used to calculate failure rates. Thirty consecutive patients with satisfactory records from each group were analysed cephalometrically. The STB group experienced substantially less upper incisor retroclination, reduced upper incisor extrusion and slightly more favourable mandibular growth. The labial movement of lower incisors and the patient compliance were not significantly different in the two groups. Overall, 82.5% of patients fully reduced their overjet with 9% failing to reduce the overjet below 6 mm.Fig. 1f

Journal Article↗
PubMed1999

Phase I evaluation of humanized OKT3: toxicity and immunomodulatory effects of hOKT3gamma4.

Murine anti-CD3 (OKT3, Muromonab-CD3) is a potent human T-lymphocyte mitogen. A previous clinical Phase I trial examined OKT3 as an immunomodulator for the treatment of cancer. However, the murine monoclonal antibody triggered a potent humoral response that neutralized the antibody activity during subsequent administration. Thus, a "humanized" form of OKT3 (hOKT3gamma4) was developed to minimize immunogenicity. The genetically engineered human anti-CD3 retained its binding activity and effectively activated T cells in vitro. Therefore, we evaluated the safety and activity of hOKT3gamma4 in a Phase I clinical trial. hOKT3gamma4 was administered as a 10-min i.v. infusion every 2 weeks for three injections (one course of therapy). Six dose levels ranging from 50 to 1600 microg/injection were evaluated. Headache and fever were common, transient toxicities but were not dose limiting. The dose-limiting toxicities were rigors and dyspnea at the 1600-microg dose level, which defined 800 microg as the maximally tolerated dose in this trial. A dose-dependent in vivo T-lymphocyte activation was produced by this treatment, and the most significant T-lymphocyte activation occurred in patients treated at the two highest dose levels (800 and 1600 microg). Persistent CD3 modulation occurred after administration of 1600 microg of hOKT3gamma4. Anti-idiotypic antibodies were detected in only 6 of 24 patients after multiple injections and were not associated with attenuation of T-lymphocyte activation. Malignant ascites resolved in three patients, one each with peritoneal mesothelioma, pancreatic adenocarcinoma, and ovarian adenocarcinoma. hOKT3gamma4 can induce T-lymphocyte activation in patients with cancer, and the immunogenicity of the "humanized" antibody is sufficiently reduced relative to its murine "parent" to permit immunostimulation by repetitive i.v. administration. The therapeutic potential of biweekly i.v. hOKT3gamma4 at a dose of 800 microg should be further evaluated.

Adjuvants, Immunologic↗
PubMed1999

Combination of chemotherapy with interleukin-2 and interferon alfa for the treatment of metastatic melanoma.

PURPOSE: The primary objective of this clinical study was to assess the feasibility of administering recombinant interleukin-2 and recombinant interferon alfa-2a before and after combination cytotoxic chemotherapy. After encouraging initial responses, the study was expanded to further evaluate the therapeutic potential, clarify the toxicities of this regimen, and explore any associated immunologic changes. PATIENTS AND METHODS: Eighty-four patients with metastatic melanoma, including patients with brain metastases, were treated on this 6-week protocol. Patients received combination cisplatin (25 mg/m2/d) and dacarbazine (220 mg/m2/d) on days 1 through 3 and 22 through 24 plus carmustine (150 mg/m2) on day 1. Interleukin 2 (13.5 million IU/m2/d) and interferon alfa (6 MU/m2/d) were administered on days 4 through 8 and 17 through 21. RESULTS: Among 83 patients assessable for response, 12 complete and 34 partial responses were documented (55% response rate). The median time to disease progression was 7 months, the median survival from study entry was 12.2 months, and the median survival from diagnosis of metastatic disease was 15.5 months. Although patients were hospitalized to receive treatment, intensive care unit support generally was not needed. Dose-limiting toxicities were related to elevations in serum bilirubin and serum creatinine levels. No patient developed a grade 4 clinical toxicity. Treatment produced a skin depigmentation, which was associated with prolonged survival. CONCLUSION: A plateau in both the survival and time to progression curves beyond 2 years (15% of the patients) and a greater than 10% disease-free survival beyond 4 years indicate that there may be a long-term benefit for some patients. The limited toxicity of this regimen should permit its use in most oncology settings. A randomized trial of chemoimmunotherapy versus chemotherapy should be performed to establish the value of chemoimmunotherapy for melanoma.

Adult↗
PubMed1999

Adenosquamous carcinoma of the mouth: a rare variant of squamous cell carcinoma.

Adenosquamous carcinoma is a rare tumour in the oral cavity and is characterised histologically by carcinomatous change in surface epithelium, in association with adenocarcinoma affecting the ducts of minor salivary glands. Only a dozen cases have previously been reported in the oral cavity, but all have shown an aggressive course with 60% of patients dying of disease. We report three further cases and review the literature, which suggests that this lesion should be regarded as a high-grade variant of squamous cell carcinoma.

Aged↗
PubMed1997

[Left-handedness in dental undergraduates and orthodontic specialists].

A questionnaire was devised involving a group of dental students (n = 70) and a group comprising all consultant orthodontists in the UK (n = 170) to investigate the prevalence and the role of handedness in dental specialisation. Subjects were classified as being pure left-, mixed- or pure right-handed according to responses to a hand preference questionnaire and the results were compared with a very similar previous study of the general population. The prevalence of sinistrality (classified by writing) was recorded as 8.6% among dental students and 17.2% among orthodontists; this compares with 7.4% among the general population. More mixed-handers presented in both the dental groups compared to the general population. This agreed with the right shift theory of laterality. No significant correlation was noted between handedness and any other variable between the two dental groups.

Female↗
PubMed1996

Left-handedness in dental undergraduates and orthodontic specialists.

A questionnaire was devised involving a group of dental students (n = 70) and a group comprising all consultant orthodontists in the UK (n = 170) to investigate the prevalence and role of handedness in dental specialisation. Subjects were classified as being pure left-, mixed- or pure right-handed according to responses to a hand preference questionnaire and the results were compared with a very similar previous study of the general population. The prevalence of sinistrality (self-classified by writing) was recorded as 8.6% among dental students and 17.2% amongst orthodontists; this compares with 7.4% among the general population. More mixed-handers presented in both the dental groups compared to the general population. This agreed with the right shift theory of laterality. No significant correlation was noted between handedness and any other variable between the two dental groups.

Dentists↗
PubMed1995

Trigeminal neuralgia and multiple sclerosis. A complex diagnosis.

Trigeminal neuralgia is a well-recognized complication in patients with multiple sclerosis. A case report is presented that describes multiple sclerosis in a middle-aged man with otherwise classical unilateral trigeminal neuralgia who demonstrated a variable response to pharmacologic and surgical intervention. The case highlights the difficulties of diagnosis when trigeminal neuralgia occurs concurrently with multiple sclerosis.

Adult↗
PubMed1992

Exacerbation of experimental colitis by nonsteroidal anti-inflammatory drugs is not related to elevated leukotriene B4 synthesis.

The ability of nonsteroidal anti-inflammatory drugs to exacerbate experimental colitis, and the possible contributions of the "shunting" of arachidonate via the 5-lipoxygenase pathway, were investigated using a rat model in which colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid in a vehicle of 50% ethanol. Twice daily treatment with indomethacin (0.1-1 mg/kg SC) during the first week after trinitrobenzene sulfonic acid/ethanol administration resulted in dose-dependent increases in the severity of colitis and in the incidence of mortality. Mortality was not observed in vehicle-treated colitic rats or in normal rats treated with indomethacin. Similar exacerbation of colitis was observed in rats treated with naproxen (5 mg/kg). Whereas treatment with a 5-lipoxygenase inhibitor, PF-5901 (100 mg/kg PO), resulted in a significant reduction of the severity of colitis, concomitant administration of PF-5901 and indomethacin (0.5 mg/kg SC) did not inhibit the exacerbative effects of the indomethacin in this model. In separate studies, administration of indomethacin was found to significantly increase colonic myeloperoxidase activity (a measure of tissue granulocyte numbers) and suppress colonic prostaglandin E2 synthesis, while not significantly affecting colonic leukotriene B4 synthesis. The effect on myeloperoxidase activity was seen during the period 21-24 hours after trinitrobenzene sulfonic acid ethanol administration, but not during the period 45-48 hours after induction of colitis. In in vitro studies using samples of inflamed colon and in vivo studies in which colonic eicosanoid production was measured by colonic dialysis, inhibition of prostaglandin E2 synthesis was not accompanied by significant changes in leukotriene B4 synthesis. These results suggest that inhibitors of colonic prostaglandin synthesis can markedly exacerbate colitis, and that this effect is unrelated to alterations in colonic leukotriene B4 synthesis. Endogenous prostaglandins may exert anti-inflammatory effects during the acute stages of colitis.

Animals↗