Biomedical subjects

J Falconer

Publications and source records attributed to J Falconer.

At least 19 recordsLinked to original sources

PubMed2006

Ovine placental eluate immunoglobulins recognise isologous and third party acid-treated trophoblast microvesicle antigens in vitro.

Placental microvesicles were prepared from ovine placentae and immunoglobulins eluted with 0.5 M glycine buffer pH 2.5. The ability of eluate immunoglobulins to re-associate with isologous (self) and third party acidified microvesicles was tested by ELISA. Ovine placental immunoglobulins re-associated with isologous and third party acidified microvesicles suggesting that at least 2 types of antigenic epitopes I and II maybe expressed on the ovine placentae. Type I antigens may be present on placentae of all ovines while type II epitopes may be paternally derived, hence unique to each pregnancy. Analysis by SDS PAGE revealed the heavy and light chains of IgG at 57 and 27 kDa, respectively, together giving a relative molecular weight of 158 kDa. Results suggest that immunoglobulins produced to placental microvesicle antigens may be directed to some but not all antigenic epitopes expressed on the trophoblast, possibly defining a mechanism by which the foetus evades maternal immunological rejection.

Acids↗

PubMed2005

Human placental immunoglobulins show unique re-association patterns with isologous and third party acid treated trophoblast microvesicles in vitro.

OBJECTIVE: To study re-association pattern of human placental eluate immunoglobulins with acid treated isologous and third party trophoblast derived placental microvesicles. DESIGN: Laboratory based experimentation. SETTING: Biological Sciences Department and Discipline for Reproductive Medicine University of Newcastle, Australia and the Department of Biochemistry, University of Nairobi, Kenya. RESULTS: Placental eluate immunoglobulins re-associated with isologous and third party acidified microvesicles in three distinct patterns. I: eluate immunoglobulins re-associated more strongly with isologous and third party acid treated placental microvesicles, II: eluate immunoglobulins re-associated strongly with isologous but weakly with third party acid treated placental microvesicles, III: eluate immunoglobulins did not show preferential re-association with isologous and third party acid treated placental microvesicles. CONCLUSION: Two types of antigenic epitopes I and II may be expressed on the human placentae. Type I antigens may be present on all human placentae while type II epitopes may be paternally derived hence unique to each pregnancy. Also, immunoglobulins produced to placental microvesicle antigens may be directed to some but not all antigenic epitopes expressed on the human placental trophoblast.

Acids↗

PubMed2005

Immunoglobulin G bound to ovine placenta is eluted by surgical cannulation and acid perfusion in situ.

OBJECTIVE: To elute placental bound immunoglobulin G (IgG) in situ. DESIGN: Laboratory based experimentation. SETTING: Biological Sciences Department, The University of Newcastle Australia and the Department of Biochemistry, University of Nairobi, Kenya. SUBJECTS: Twelve pregnant ewes 10 to 15 days before the onset of natural parturition. RESULTS: Placental eluates were rich in IgG, and IgG2. The relative molecular weight of placental IgG was estimated at 158kDa by gel filtration chromatography. Analysis of eluate by SDS PAGE revealed the heavy and light chains of IgG at 57 and 27kDa respectively together giving a relative molecular weight of 168kDa. CONCLUSION: Placental bound IgG may be crucial in immunology of pregnancy and together with the cognate antigen thereof may be useful as models for the study of maternal-fetal interaction in human pregnancy and in the development of experimental immunotherapy to immunologically compromised pregnancies in humans and livestock.

Acids↗

PubMed2001

Dietary n-3 fatty acids alter the contractile response to thromboxane A(2) agonists of porcine coronary arteries.

Dietary supplementation with marine fish oils rich in n-3 fatty acids reduces circulating thromboxane A(2) (TxA(2)). However, the effects on thomboxane A(2) receptor mediated vascular reactivity are uncertain. The aim of this study was to test the hypothesis that dietary modification of TxA(2) levels alters vascular responsiveness to TxA(2) analogues. Juvenile female white pigs were fed a diet enriched in either 5% (w/w) fish oil or beef tallow for 6 weeks. Serum and myocardial tissue levels of eicosapentaenoic and docosahexaenoic acid reached a plateau during this period. Vascular responses were measured in isolated coronary arterial rings with intact endothelium by isometric tension measurement. Arteries from pigs fed fish oil produced a greater maximum vasoconstrictor tension to the TxA(2) analogue U46619 than did rings from pigs fed beef tallow (120 +/- 6% compared to 92 +/- 8%, values represented as a percentage relative to the maximum vasoconstrictor effect obtained to KCl, regression analysis, analysis of variance, P </= 0.05). The vasoconstrictor potency of U46619 was similar in both treatment groups. The vasoconstrictor EC(50) was 10.3 (6.8-15.7) nmol/L (mean, 95% confidence interval) for fish oil and 9.5 (5.7-15.8) nmol/L for beef tallow treated animals. Changes in vascular responses to U46619 were associated with a fourfold difference in plasma thromboxane B(2) levels between treatment groups (12.1 +/- 2.6 pg/mL fish oil, 48.3 +/- 3.1 pg/mL beef tallow, Students' unpaired t-test P </= 0.05). Vasoconstrictor responses obtained to endothelin-1, KCl and 5-hydroxtryptamine and the vasodilator response to sodium nitroprusside were not different between treatment groups. Dietary manipulation of thromboxane A(2) levels by n-3 fatty acids alters vascular reactivity to U46619, possibly as a result of agonist-induced desensitization of thromboxane A(2) receptors.

Journal Article↗

PubMed2000

Recurrent pregnancy losses and the role of immunotherapy.

Post implantation pregnancy losses are psychologically and economically stressful to the childbearing population. The etiology in the vast majority of cases is unknown but is partly thought to result from a break-down of the maternal tolerance to the fetoplacental unit. Immunologically based therapy remains controversial but no alternative therapy is available at the moment. This article reviews the conceived immunological basis of recurrent pregnancy losses, discussing the controversies arising, and recommending the use of intravenous immunoglobulin, IVIg, in well controlled experiments for further clinical trials.

Abortion, Habitual↗

PubMed1999

Cardiac (n-3) non-esterified fatty acids are selectively increased in fish oil-fed pigs following myocardial ischemia.

The effect of fish oil supplementation on the nonesterified fatty acid (NEFA) concentration and composition in the normoxic and hypoxic myocardium of pigs was examined. Two groups of female pigs (n = 7) were fed a diet supplemented with either 5 g beef tallow/kg (as control) or 5 g fish oil/kg (MaxEPA) rich in (n-3) fatty acids. After 6 wk of supplementation, the pigs were anesthetized, hearts exposed by thoracotomy followed by occlusion of the left anterior descending artery. Normoxic and hypoxic regions of the heart were examined for NEFA concentration and composition by using a combination of thin layer and gas chromatography. Nonesterified (n-6) and (n-3) fatty acid concentration and composition differed significantly between the two groups in both the normoxic and hypoxic areas of the heart. Eicosapentaenoic and docosahexaenoic acid concentration in the NEFA fraction of the normoxic myocardium were higher in the fish oil group than in the beef tallow group (P < 0.001). In the fish oil-fed pigs, the (n-3) NEFA concentration was significantly higher in the hypoxic compared to the normoxic region of the heart. The fish oil-fed group had lower levels of arachidonic acid in the NEFA fraction compared to the beef tallow-fed group, whereas the hypoxic myocardium had higher levels of arachidonic acid, regardless of the dietary fat supplementation. Despite large differences in the proportions of saturated fatty acids in the experimental diets, there was little or no difference in the saturated fatty acid content of cardiac phospholipid and NEFA fractions. Following myocardial ischemia, (n-3) fatty acids in the NEFA fractions were selectively increased in the fish oil-fed pigs, implicating the possible role of nonesterified (n-3) polyunsaturated fatty acids in the prevention of arrhythmias.

Animals↗

PubMed1998

A corticotropin-releasing hormone type I receptor antagonist delays parturition in sheep.

In sheep, corticotropin-releasing hormone (CRH) can stimulate the fetal release of ACTH to produce a cortisol surge which leads to the onset of parturition. We tested the hypothesis that fetal CRH is a primary factor in the onset of parturition in sheep by using a Type I CRH receptor antagonist, antalarmin, to block the endogenous action of CRH. Pregnant ewes were cannulated at 130-135 days of gestation. Five catheters were placed into the amniotic sac, fetal femoral artery, fetal tarsal vein, maternal jugular vein and carotid artery. After 5 days' recovery, blood samples from maternal and fetal vessels were collected at the following times: a day before the start of infusion, at [-1, 0, 1, 2, 4, 8 and 24]h, on the first day of infusion, and thereafter daily throughout a 10-day infusion. Animals (n=6 per group) received infusions into a fetal vein of either a vehicle comprising 1:1 mixture of ethanol and polyethoxylated castor oil (Cremophor EL) or antalarmin (50 g/L) in the vehicle at a rate of 0.3 mL/h. The plasma samples were assayed for ACTH and cortisol using commercial RIA kits. Fetuses infused with vehicle delivered at a mean gestational age of 141.8 +/- 0.9 days compared with antalarmin-infused sheep at 148.8 +/- 1.6 days (P = 0.0036, unpaired Student's t-test). Fetal ACTH and cortisol did not change in the antalarmin-infused sheep after 3 days' infusion compared to significant increases in vehicle-infused sheep (P=0.004 and P = 0.016 respectively, ANOVA). These data show that CRH receptor antagonism in the fetus can delay the onset of parturition. It supports the hypothesis that hypothalamic CRH drives fetal production of ACTH and is essential for the onset of parturition triggered by a surge in fetal cortisol.

Adrenocorticotropic Hormone↗

PubMed1997

Ovine fetal umbilical artery Doppler systolic diastolic ratios and nitric oxide synthase.

OBJECTIVE: To evaluate the effect of nitric oxide synthase activity inhibition on the fetal lamb umbilical artery flow velocity waveform. METHODS: Five pregnant Corriedale cross ewes were operated on at 125-130 days' gestation. Fetal and maternal vascular catheters were inserted along with a Doppler flow meter cuff on the fetal common umbilical artery. Each fetus received a 40-minute intravenous (i.v.) infusion of N omega-nitro-D-arginine as a control, and then after a recovery period of 1 hour, a 40-minute i.v. infusion of N omega-nitro-L-arginine, an inhibitor of nitric oxide synthase activity. Maternal and fetal heart rate, blood pressure, blood gases, and fetal umbilical artery flow velocity waveforms were recorded at basal time and after the 40-minute i.v. infusions. RESULTS: There were no differences in fetal or maternal heart rate, blood pressure, or blood gases with the infusion of the nitric oxide synthase inhibitor N omega-nitro-L-arginine. However, N omega-nitro-L-arginine caused a significant increase (41%) in the fetal umbilical artery flow velocity waveform systolic to diastolic ratio (S/D) above the baseline levels. CONCLUSIONS: Inhibition of nitric oxide synthase activity in the lamb fetoplacental circulation with N omega-nitro-L-arginine is associated with an increase in the umbilical artery S/D.

Animals↗

PubMed1997

Elution and partial characterization of immunoglobulins bound to ovine placenta.

Immunoglobulins were eluted from ovine placentae and characterized by immunoprecipitation, electrophoresis, western blotting and ELISA. IgG was shown to comprise the bulk of placental-bound immunoglobulins while smaller amounts of IgM and only trace amounts of IgA were demonstrated. Results suggest that ovine placental IgG eluted by surgical cannulation of the uterine blood vessels in situ is similar to that eluted from postpartum placentae in vitro, implying that there may be some transfer of antibodies across the maternal side of the placental barrier to the trophoblast. These antibodies are rich in IgG1 and IgG2, have a relative molecular weight of 158 kDa, and bind to an 80 kDa peptide prepared from pre-acidified ovine placental cotyledons. We propose that the binding of placental IgG to the 80 kDa antigen may prevent immunological rejection of the foetus by competitively excluding cytotoxic cells of maternal origin such as NK cells. Also, given that a similar antigen (80 kDa) has been reported in humans and equines, and shown to be saturated with IgG in term placentae, we propose that this antigen may be conserved in several mammalian species for reproductive purpose. Consequently, we suggest that the ovine placental IgG and the 80 kDa antigen may be suitable as models for the study of maternal-foetal interactions in mammalian pregnancies.

Animals↗

PubMed1997

Prevention of cardiac arrhythmia by dietary (n-3) polyunsaturated fatty acids and their mechanism of action.

The role of marine fish oil (n-3) polyunsaturated fatty acids in the prevention of fatal ventricular arrhythmia has been established in experimental animals. Prevention of arrhythmias arising at the onset of ischemia and reperfusion is important because if untreated, they result in sudden cardiac death. Animals supplemented with fish oils in their diet developed little or no ventricular fibrillation after ischemia was induced. Similar effects have also been observed in cultured neonatal cardiomyocytes. Several mechanisms have been proposed and studied to explain the antiarrhythmic effects of fish oil polyunsaturated fatty acids, but to date, no definite mechanism has been validated. The sequence of action of these mechanisms and whether more than one mechanism is involved is also not clear. Some of the mechanisms suggested to explain the antiarrhythmic action of fish oils include the incorporation and modification of cell membrane structure by (n-3) polyunsaturated fatty acids, their direct effect on calcium channels and cardiomyocytes and their role in eicosanoid metabolism. Other mechanisms that are currently being investigated include the role of (n-3) polyunsaturated fatty acids in cell signalling mediated through phosphoinositides and their effect on various enzymes and receptors. This article reviews these mechanisms and the antiarrhythmic studies using (n-3) polyunsaturated fatty acids.

Animals↗

PubMed1997

Realtime ultrasound diagnosis over a wide-area network (WAN) using off-the-shelf components.

A trial system was developed for relaying realtime ultrasound images from an obstetric referral centre, the Maitland Hospital, to a tertiary-care centre, the John Hunter Hospital in Newcastle. The sites were approximately 30 km apart and connected by a microwave link at 2 Mbit/s. The pilot study demonstrated the feasibility of realtime ultrasound transmission using commonly available components.

Female↗

PubMed1994

An examination of Cyriax's passive motion tests with patients having osteoarthritis of the knee.

BACKGROUND AND PURPOSE: We explored the construct validity and test-retest reliability of the passive motion component of the Cyriax soft tissue diagnosis system. We compared the hypothesized and actual patterns of restriction, end-feel, and pain/resistance sequence (P/RS) of 79 subjects with osteoarthritis (OA) of the knee and examined associations among these indicators of dysfunction and related constructs of joint motion, pain intensity, and chronicity. SUBJECTS: Subjects had a mean age of 68.5 years (SD = 13.3, range = 28-95), knee stiffness for an average of 83.6 months (SD = 122.4, range = 1-612), knee pain averaging 5.6 cm (SD = 3.1, range = 0-10) on a 10-cm visual analogue scale, and at least a 10-degree limitation in passive range of motion (ROM) of the knee. METHODS: Passive ROM (goniometry, n = 79), end-feel (n = 79), and P/RS during end-feel testing (n = 62) were assessed for extension and flexion on three occasions by one of four experienced physical therapists. Test-retest reliability was estimated for the 2-month period between the last two occasions. RESULTS: Consistent with hypotheses based on Cyriax's assertions about patients with OA, most subjects had capsular end-feels for extension; subjects with tissue approximation end-feels for flexion had more flexion ROM than did subjects with capsular end-feels, and the P/RS was significantly correlated with pain intensity (rho = .35, extension; rho = .30, flexion). Contrary to hypotheses based on Cyriax's assertions, most subjects had noncapsular patterns, tissue approximation end-feels for flexion, and what Cyriax called pain synchronous with resistance for both motions. Pain intensity did not differ depending on end-feel. The P/RS was not correlated with chronicity (rho = .03, extension; rho = .01, flexion). Reliability, as analyzed by intraclass correlation coefficients (ICC[3,1]) and Cohen's kappa coefficients, was acceptable (> or = .80) or nearly acceptable for ROM (ICC = .71-.86, extension; ICC = .95-.99, flexion) but not for end-feel (kappa = .17, extension; kappa = .48, flexion) and P/RS (kappa = .36, extension; kappa = .34, flexion). CONCLUSION AND DISCUSSION: The use of a quantitative definition of the capsular pattern, end-feels, and P/RS as indicators of knee OA should be reexamined. The validity of the P/RS as representing chronicity and the reliability of end-feel and the P/RS are questionable. More study of the soft tissue diagnosis system is indicated.

Adult↗

PubMed1994

Reducing hospital costs for the geriatric patient admitted from the emergency department: a randomized trial.

OBJECTIVE: To test the impact of a geriatric evaluation and management model on the costs of acute hospital management of emergently admitted older adults. DESIGN: Randomized controlled trial. Patients were followed in the acute hospital from admission through discharge. Results based on both univariate and multiple regression analyses. SETTING: Private, nonprofit, academic medical center in a densely populated urban area. PATIENTS: Adults 70 years of age and older admitted from the Emergency Department to the medicine service (non-ICU admission) who did not have an internist on staff at the admitting hospital. Of 141 randomized patients, 111 (78.7%) met eligibility criteria. INTERVENTION: Assignment of a geriatrician and a social worker as the primary managing team during the hospital stay. MAIN OUTCOME MEASURES: Length of stay, total cost of acute hospital care, cost of laboratory, pharmacy, and rehabilitation services. RESULTS: Patients in the intervention group had 2.1 fewer days of hospitalization, but this shorter length of stay was not statistically significant (P = 0.108). There were no differences in mortality or discharge disposition. In risk-adjusted, multiple regression analysis the intervention group had a statistically significant lower predicted total cost per patient than the usual care group (-$2,544, P = 0.029); assignment to the intervention group was associated with a lower predicted cost per patient for laboratory (including cardiology graphics) services (P = 0.007) and pharmacy costs (P = 0.047). CONCLUSIONS: When controlled for important predictors of expected resource use, care provided by a geriatric management team resulted in a significant reduction in the cost of hospitalization. A reduction in the cost of laboratory, cardiographic, and pharmacy services is consistent with the team's philosophy of defining the services needed based on goals related to functional outcomes.

Academic Medical Centers↗

PubMed1993

A randomized, controlled trial of arthroscopic surgery versus closed-needle joint lavage for patients with osteoarthritis of the knee.

OBJECTIVE: To compare arthroscopic surgery and closed-needle joint lavage for patients with non-end-stage osteoarthritis (OA) of the knee under controlled, experimental conditions. METHODS: Thirty-two subjects who met specific clinical, radiologic, medical, and rehabilitation criteria were randomized to receive arthroscopic surgery (n = 18) or joint lavage (n = 14). Outcome measures evaluated at baseline and at 3 and 12 months of followup included 3 standard clinical parameters, self-reported pain and functional status (by the Arthritis Impact Measurement Scales), 50-foot walk time, 2 global scales, and direct and indirect medical costs. RESULTS: At 3 months of followup, there were no significant between-group differences in pain, self-reported and observed functional status, and patient and "blinded" physician global assessments. The arthroscopic procedure cost $3,840 more than did closed-needle joint lavage. After 1 year, there were no between-group differences in medication costs, utilization of medical services, or indirect costs related to employment or use of household help. After 1 year, 44% of subjects who underwent arthroscopy reported improvement and 58% of subjects who underwent joint lavage improved. Patients with tears of the anterior two-thirds of the medial meniscus or any lateral meniscus tear had a higher probability of improvement (by "blinded" physician assessment) after arthroscopic surgery (0.63) than did patients with other intraarticular pathology (0.20). CONCLUSION: The search for and removal of soft tissue abnormalities via arthroscopic surgery does not appear justified for all patients with non-end-stage OA of the knee who fail to respond to conservative therapy, but it may be beneficial for certain subgroups.

Aged↗

PubMed1993

Differential strength decline in patients with osteoarthritis of the knee: revision of a hypothesis.

A quadriceps-to-hamstring isometric peak torque ratio (Q/H ratio) of approximately 2.0 is considered necessary for appropriate knee biomechanics. Lower ratios may affect the function of persons with osteoarthritis (OA) and the progression of the disease. This study examined the isometric Q/H ratio in subjects with and without OA of the knee and explored the effect of age, pain, and joint enlargement on the ratio. Twenty-one pairs of subjects (OA, control) were matched on age (mean = 62.6 years; SD = 13.9), gender (F = 17, M = 4), and leg dominance (Dominant = 10, Nondominant = 11). Isometric quadriceps and hamstring peak torque, knee pain, and joint enlargement were measured. Paired t-tests demonstrated that the OA group had significantly lower quadriceps peak torque than the control group but did not have significantly lower hamstring peak torque or gravity-corrected isometric Q/H ratio. Age correlated with the ratio in subjects without OA (rho = -0.46; P = 0.03) but not in subjects with OA. Pain was not significantly correlated with the ratio in either group. Joint enlargement correlated with the ratio in the OA group (rho = -0.45; P = 0.03). The gravity-corrected isometric Q/H ratio appears to decrease with age in subjects without OA. In subjects with OA, the Q/H ratio appears not to change with disease, pain, or age. Joint enlargement may decrease the ratio and merits further study.

Age Factors↗

PubMed1992

Differential muscle strength decline in osteoarthritis of the knee. A developing hypothesis.

The ratio of quadriceps to hamstrings muscle strength (Q/H ratio) is important for the stability of the knee and for protection from excessive stress. The purpose of this study was to explore whether the Q/H ratio is altered in patients with osteoarthritis (OA). Subjects were 43 patients with physician-diagnosed OA of the knee (mean age, 65.61 years; SD, 12.74). Isometric knee flexor and extensor strength was measured with a hand-held dynamometer. Both muscle groups were weak, with relatively greater weakness in the quadriceps muscles. The mean Q/H ratio of 1.43 (SD, 0.39) was below ratios reported for young healthy adults (2.0). The low Q/H ratio might be caused by the inability to correct the measurement for gravity, but a liberal estimate of gravity correction raised the ratio only to 1.71 (SD, 0.47). The low Q/H ratio was probably not caused by physiologic changes due to aging, because the correlation between the ratio and age was low (-0.04). Since the correlation of the Q/H ratio with the usual level of pain (measured by a visual analogue scale) was negative (-0.26), the low ratio might be explained by reflex inhibition due to pain associated with disease.

Adult↗

PubMed1992

Effect of ultrasound on mobility in osteoarthritis of the knee. A randomized clinical trial.

Ultrasound increases soft tissue extensibility and may be an effective adjunct in the treatment of knee contractures secondary to connective tissue shortening. A randomized clinical trial was conducted to determine the effectiveness of ultrasound in relieving stiffness and pain in patients (age mean = 67.5 years, SD = 13.0) who had osteoarthritis (OA) and a chronic knee contracture. Subjects received 12 treatments of exercise preceded by either ultrasound (n = 34) or sham ultrasound (n = 35) and a blinded evaluation at baseline, after treatment, and 2 months after treatment. MANCOVA controlling for baseline scores showed that there were no significant differences in knee active range of motion (ROM) (goniometry) or pain (visual analogue scale) between experimental and control groups. Possible explanations for the no difference finding involve dosage issues, muscle shortening, transiency of effects, and the effects of exercise. Paired t-tests revealed that both groups significantly improved (p less than 0.05) in active ROM, pain, and gait velocity, and maintained improvement for at least 2 months. Although ultrasound may not contribute to the management of patients with chronic knee stiffness and OA, benefits of the exercise program and increased activity secondary to program participation probably influenced the overall improvement.

Aged↗

PubMed1992

Self-reported functional status predicts change in level of care in independent living residents of a continuing care retirement community.

OBJECTIVE: To test the hypothesis that self-reported functional status predicts change in level of care from independent to dependent in residents of a continuing care retirement community (CCRC). DESIGN: Two-year longitudinal descriptive study of change in level of care and survival. SUBJECTS: One hundred fifty-two residents in the independent-living unit of a non-profit CCRC. Mean age at initial evaluation was 82.3 years, SD 6.2. MEASUREMENT: Predictor variables assessed at baseline were age, sex, physician estimate of functionally significant disease, self-reported functional status, and performance-based hand function. Criterion variables collected at 2-year follow-up were level of care (independent/dependent) and survival (alive/dead). MAIN RESULTS: Self-reported functional status (P less than 0.01) and age (P less than 0.05) were significant predictors of change in level of care in a logistic regression analysis containing all predictor variables. No variable predicted survival. CONCLUSIONS: Self-reported functional status may help to predict dependency in older adults in good health who have few markers of dependency risk.

Activities of Daily Living↗