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Biomedical subjects

A G MacDonald

Publications and source records attributed to A G MacDonald.

18 recordsLinked to original sources

Effect of pregnancy on bone mineral density and biochemical markers of bone turnover in a patient with juvenile idiopathic osteoporosis.

Juvenile idiopathic osteoporosis (JIO) is rare, presenting with vertebral fractures in the immediate prepubertal years; however, recovery is normally observed. We report the case of a 19-year-old pregnant woman previously diagnosed with JIO. She experienced three vertebral fractures in the third trimester of pregnancy. She delivered by caesarean section at 38 weeks gestation. Spinal bone mineral density decreased by 25%, hip bone mineral density by 10%, and forearm bone mineral density by 3% during pregnancy. Bone resorption markers, free pyridinoline and deoxypyridinoline (fPYD and fDPD), were elevated at baseline and markedly increased during pregnancy (fPYD/fDPD at 0, 10, 15, 20, and 28 weeks and immediately postpartum: 36.2/11.5, 52.9/15.8, 54.3/13.3, 51.1/13.3, 90/21.8, and 95.6/22.7 nmol/mmol creatinine, respectively) The bone formation marker, bone-specific alkaline phosphatase (BSAP), was within the reference range at baseline and increased in the third trimester. (BSAP at 0, 10, 15, 20, and 28 weeks and immediately postpartum: 20.5, 18.3, 17.7, 19.8, 26.9, and 30.0 U/liter, respectively). Parathyroid hormone (PTH) was measured by two methods to assess the possible effect of PTH fragments. PTH(1-84) (Roche) showed little change during the pregnancy, whereas the Nichols assay [(1-84) and(7-84) PTH fragment], revealed increases paralleling the changes in bone resorption. This young woman's bone turnover showed an exaggerated response to pregnancy, with bone resorption predominating over formation. PTH fragments may have partially mediated this effect.

Adult↗

A method of patch clamp recording in hyperbaric oxygen.

A method of patch clamp recording in hyperbaric oxygen is described which is derived from a method for patch clamping at high hydrostatic pressure. Excised patches equilibrate with hyperbaric oxygen within 10 minutes. Experiments with BK channels expressed in HEK 293 cells showed that 1 MPa O2 caused an increase in the ionic permeability of the patch, an effect accelerated in the presence of ferrous ions. Seal resistance was unaffected. Small negative currents, (VH - 40 to - 65 mV, symmetrical KCl solutions), apparent in skewed all-points amplitude histograms, reduced the signal to noise ratio. In some patches the BK channel activity was inhibited and in others it persisted with the currents becoming irresolvable in the increased noise.

Cell Line↗

Biochemical markers of bone turnover in seronegative spondylarthropathy: relationship to disease activity.

To investigate bone turnover in patients with seronegative spondylarthropathy, a bone formation marker, type 1 procollagen carboxy-terminal propeptide (P1CP), and resorption markers, the pyridinium cross-links of collagen [urinary free (f) PYR and DPYR], were measured. The median f-PYR, f-DPYR and P1CP (+/-interquartile range) were 15.8 (6.00) nmol/mmol creatinine, 3.8 (2.2) nmol/mmol creatinine and 101.5 (38) micrograms/1, respectively. There was a positive correlation between resorption markers and acute-phase reactants such as C-reactive protein (r = 0.42 for PYR, r = 0.42 for DPYR, P < 0.05), and a negative correlation observed between P1CP and the erythrocyte sedimentation rate (r = -0.64, P < 0.05). In the subgroup of patients with an elevated CRP concentration, the concentration of PYR and DPYR was significantly increased (f-PYR 25.7 vs 15.8 and f-DPYR 6.6 vs 3.8, P < 0.01 for f-PYR, P < 0.05 for f-DPYR). This study suggests than an elevation in acute-phase response in patients with seronegative spondylarthropathy is associated with increased concentration of bone resorption markers with a tendency for reduction in bone formation markers. This may represent uncoupling of bone formation and resorption, leading to bone loss in such patients.

Acute-Phase Reaction↗

Microwave thermography as a noninvasive assessment of disease activity in inflammatory arthritis.

Microwave thermography is the technique of measuring natural thermal radiation from body tissues of clinical interest. It is safe, requires no control of environmental conditions and exposes the patient to no ionising radiation. In this study, we found that microwave thermography of the knee joints showed weak correlation with some global parameters of disease activity. Bed rest alone for three days had no significant effect on microwave thermographic index (MTI). Intra-articular steroid injection, however, was associated with a marked fall in MTI both in the injected knee and the contra-lateral knee. We conclude that microwave thermography can measure inflammatory activity in the knee joints of patients with inflammatory arthritis and can respond to clinical change brought about by major treatment intervention.

Adrenal Cortex Hormones↗

A short history of fires and explosions caused by anaesthetic agents.

The first recorded fire resulting from the use of an anaesthetic agent occurred in 1850, when ether caught fire during a facial operation. Many subsequent fires and explosions have been reported, caused by ether, acetylene, ethylene and cyclopropane, and there has been one reported explosion involving halothane. Although some of the earlier incidents caused more consternation than injury, many of the later ones caused much death and destruction, particularly after the practice of administering oxygen, instead of air, became established. Many incidents have never been reported and many of those which have reached publication do not record essential details. The use of flammable agents has decreased significantly in recent years and although fires and explosions from nonanaesthetic causes, for example gastrointestinal gases, skin sterilizing agents and laser surgery, may continue to occur, those from gaseous and volatile anaesthetic agents may now be of historical interest only. This article reviews some of the more relevant and enlightening reports of the past 150 yr.

Acetylene↗

Relationship of urinary pyridinium crosslinks to disease extent and activity in osteoarthritis.

Urinary crosslinks, pyridinoline and deoxypyridinoline, have been shown to be elevated in RA and OA. This study confirmed this elevation, with levels in patients with predominantly knee OA higher than those with nodal OA and hip OA. Intra-articular corticosteroid injection was followed by a significant fall in urinary crosslinks, which was associated with a corresponding improvement in articular index and pain score, although there was no overall correlation between crosslink levels and the clinical indices studied. Collagen crosslinks may be of value as markers of disease activity in OA.

Adrenal Cortex Hormones↗

Useful investigations in a refractory case of 'myositis'.

The diagnosis of polymyositis is made on the basis of clinical features, muscle enzymes, EMG studies and muscle biopsy. Treatment requires corticosteroids often in combination with immunosuppressive agents, and relapse in spite of treatment may render management difficult. The case described below appeared to demonstrate features from which the diagnosis could be made, but in which the almost complete resistance to conventional therapy led to a correct reappraisal of the diagnosis. This illustrates an unusual cause for diagnostic confusion and the value of diagnosis reassessment under such circumstances.

Adult↗

Effects of hormone replacement therapy in rheumatoid arthritis: a double blind placebo-controlled study.

AIMS: To study the effects of ovarian hormone replacement therapy (HRT) on bone mineral density and disease activity in postmenopausal women with rheumatoid arthritis (RA). METHOD: A placebo controlled double-blind study was carried out on 62 patients with RA, 22 on placebo and 40 on HRT (transdermal oestradiol patches twice weekly for 48 weeks plus norithisterone tablets when clinically indicated). Bone mineral density of spine, hip and wrist was measured at 0 and 48 weeks and clinical and laboratory measures of general well-being and disease activity at 0, 12, 24 and 48 weeks. RESULTS: Thirteen of 22 (59%) of placebo and 31 of 40 (78%) of the HRT group completed 48 weeks in the study. At entry, bone mineral density (BMD) values in the lumbar spine and femoral neck were similar to those in age and sex matched controls in both treatment groups, whereas at the distal radius, BMD was significantly reduced to approximately 50% of control values (both p < 0.001 from controls). In the HRT group, spine BMD increased significantly by a median of +0.94% at 48 weeks (p = 0.024), but did not change significantly in the placebo group. BMD at the femoral neck and distal radius did not change in either group. In the HRT group, there was significant improvement in well being as assessed by the Nottingham Health Care Profile (p < 0.01) and in the articular index (p < 0.05). There were no significant changes in ESR or CRP in either group. CONCLUSION: Transdermal HRT was well tolerated, increased well being, reduced articular index and increased lumbar spine bone density over a one year period in postmenopausal women with RA. Although no laboratory evidence was found of a disease modifying effect, the symptomatic benefits and improvements in bone density indicate that HRT may be a valuable adjunct to conventional antirheumatic therapy in RA.

Activities of Daily Living↗

Effects of gas bubbling and other forms of convection on platelets in vitro.

Citrated platelet-rich human plasma was subjected to one of three experimental treatments at 37 degrees C for 15 min: stirring, bubbling (with stirring), and gentle agitation achieved by a rocking motion. The last two were "equiconvective" as judged by equilibration rates with CO2 and O2 but presumably differed in the shear stress they imposed on the cells. Stirring platelets in normal air or 5% CO2-air caused no significant aggregation. Bubbling air through platelet-rich plasma increased its pH and marked aggregation occurred. Bubbling CO2-air caused the platelet-rich plasma pH to attain its physiological level of 7.4 with less aggregation. In both cases, subsequent ADP-induced aggregation was diminished. Rocking (without stirring) in the presence of CO2-air caused negligible aggregation in platelets and an enhanced response to ADP. Because of the marked difference between the two equiconvective treatments, bubbling and rocking, the main factor in activating the human platelets is suggested to be shear stress (potentiated by high pH), with perhaps a lesser contribution from the air-plasma interface.

Adenosine Diphosphate↗

Effect of high hydrostatic pressure on 86Rb+ influx in the erythrocyte of the plaice (Pleuronectes platessa).

1. 86Rb+ influx in the erythrocyte of the plaice (Pleuronectes platessa) has been measured at hydrostatic pressures between 1 and 600 atm at 10 degrees C. 2. The measurements were performed with an experimental medium containing 1% (w/v) bovine serum albumin. In this medium the cells achieved a steady state level of ionic regulation. 3. At normal atmospheric pressure 46% of the 86Rb+ influx was inhibited by furosemide while 42% was inhibited by ouabain, the remainder being inhibited by neither drug. 4. It was found that all three fluxes defined by these drugs were sensitive to pressure. 5. The ouabain sensitive influx was progressively inhibited by increasing pressure, the inhibition at 600 atm being 30%. 6. The furosemide sensitive influx was inhibited by 35% between 100 and 600 atm. 7. In contrast the ouabain + furosemide insensitive influx was doubled by 400 atm. 8. This pattern of pressure inhibition and stimulation resembles that seen in comparable studies in human erythrocytes.

Animals↗

The effects of hydrostatic pressure on the spontaneous release of transmitter at the frog neuromuscular junction.

1. The effects of hydrostatic pressure (0.1-15.55 MPa) on the spontaneous release of transmitter at the frog neuromuscular junction were investigated. 2. The major effect of high pressure is on the release mechanism, pressure (0.1-10.40 MPa) producing an exponential decrease in frequency of the miniature end-plate currents in normal Ringer solution. The frequency decreases to 0.52 and 0.24 of the control value at 5.25 and 10.40 MPa respectively. This effect is reversible on decompression. 3. The sensitivity of the release process to high pressure is unaltered in 10 mM-K+, 6 mM- and 10 mM-Ca2+ and hypertonic (165 mM-NaCl) Ringer solution, although the high Ca2+ media shift the threshold for the pressure effect to higher pressures. 4. Higher pressure (10.40-15.55 MPa) produces a small increase in the time constant of decay (tau D) of m.e.p.c.s with no effect on the growth phase. A pressure of 15.55 MPa increases tau D to 1.35 of the control value. 5. The possible actions of high pressure on both the pre- and post-synaptic processes are briefly discussed.

Animals↗

Effects of gaseous anaesthetics and inert gases on the phase transition in smectic mesophases of dipalmitoyl phosphatidylcholine.

The phase transition in smectic mesophase of dipalmitoyl phosphatidyl-choline was studied under high pressures of helium (340 atm), nitrogen (340 atm), nitrous oxide (43 atm), cyclopropane (4.4 atm) and n-propane (8.2 atm), using a turbidimetric technique. Helium and nitrogen increased the transition temperature by 0.021 and 0.006 degree C/atm, respectively, compared with 0.024 degrees C/atm for hydrostatic pressure. Nitrous oxide reduced the transition by 0.58 degree C/atm. The hydrocarbon gases spread the transition width and lowered the transition temperature with increasing effect at higher doses. Comparisons with other membrane probes are made and the concentration of gases in the bilayer which lower the transition temperature by 1 degree C are estimated, in mol%: He, 10.2; N2, 13.2: N2O, 9.04; n-C3H8, 6.3 and cyclopropane, 12.8.

Anesthetics↗

The effect of helium and of hydrogen at high pressure on the cell division of Tetrahymena pyriformis W.

The rate of cell division of Tetrahymena growing in an observational high pressure vessel was measured at selected pressures of helium, hydrogen and at high hydrostatic pressure. Pressures greater than 100 atm reduced the rate of division, but the gases inhibited division to a lesser degree than pure hydrostatic pressure. Hydrogen's effect was distinguishable from that of hydrostatic pressure at 130 atm or more, while helium's effect appeared at 175 atm. These inert gases probably counteract the action of pressure by stabilising apolar pressure-labile targets.

Animals↗