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Biomedical subjects

R Fraser

Publications and source records attributed to R Fraser.

At least 181 records · Page 10Linked to original sources

Renal, cardiovascular and hormonal characteristics of young adults with autosomal dominant polycystic kidney disease.

We studied young adults with autosomal dominant polycystic kidney disease (ADPKD) to determine the characteristics that precede renal impairment. Nineteen affected (A) and 20 unaffected (U) offspring from families with ADPKD showed no significant differences in basal glomerular filtration rate (A: mean 97, SD 19; U: 100, SD 23 ml/min/1.73 m2) or renal functional reserve, but effective renal plasma flow was significantly lower in affected offspring (A: 532, SD 86; U: 605, SD 118 ml/min/1.73 m2, P less than 0.01). Plasma renin activity [A: median 26 (95% CI: 15 to 37); U: 14 (11 to 27) microU/ml, P less than 0.05, one-tailed test] and aldosterone [A: 2.5 (2.0 to 3.0), U: 1.0 (1.5 to 2.0) micrograms/100 ml, P less than 0.04, one-tailed test] were increased in affected offspring despite the higher systolic blood pressure (A: mean 123, SD 5; U: 115, SD 3 mm Hg, P less than 0.02) and significant expansion of total exchangeable sodium (A: 40.8, SD 2.3; U: 38.0, SD 3.5 mmol/kg, P less than 0.01). The ouabain-sensitive component of red cell sodium efflux was less in affected offspring (A: 0.258; SD 0.040; U: 0.288, SD 0.042 hr-1, P less than 0.04) and in both groups was correlated inversely with total exchangeable sodium. Echocardiography revealed no difference in left ventricular mass index nor prevalence of mitral valve prolapse. Potential cyst growth factors such as the glucocorticoids and somatomedin C were similar in both affected and unaffected groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effect of insulin-induced hypoglycaemia on antral, pyloric and duodenal motility in fasting subjects.

1. Hyperglycaemia alters gastric motility and delays gastric emptying. By contrast, there is little information regarding the effect of sub-normal blood glucose concentrations on gastric and, in particular, pyloric motility, although limited data suggest that hypoglycaemia is associated with accelerated gastric emptying despite an apparently increased basal pyloric pressure. 2. To determine the effects of hypoglycaemia on pyloric motility, we compared the effects of an intravenous injection of insulin (0.15 units/kg) with those of a placebo injection of saline in eight healthy human volunteers during phase I of the interdigestive migrating motor complex. 3. All subjects developed profound hypoglycaemia (mean blood glucose concentration 1.6 mmol/l compared with 4.0 mmol/l in the control group). 4. There was no significant difference in the number of antral (9 versus 7, P = 0.34), pyloric (3 versus 0, P = 0.31) or duodenal (21 versus 13, P = 0.42) pressure waves or in the basal pyloric pressure (0.3 mmHg versus 0.1 mmHg, P = 0.37) in the 45 min after insulin injection (hypoglycaemia) when compared with the 45 min after saline injection (euglycaemia). In both the euglycaemic and hypoglycaemic studies there was a time-dependent increase in the numbers of antral and duodenal waves consistent with the expected changes in the interdigestive migrating motor complex. 5. These results indicate that insulin-induced hypoglycaemia has no significant effect on pyloric motility during phase I of the interdigestive migrating motor complex.

Adolescent↗

The role of potassium and other ions in the control of aldosterone synthesis.

Fast and slow K+ efflux components, independently regulated by angiotensin II (AII), have been identified in bovine adrenocortical cells. We have further investigated the role of potassium in the control of aldosterone synthesis in two ways. Firstly, isotopic tracers, in conjunction with channel modulators, have been used to study the interrelationship of K+ and Ca2+ in the control of AII-stimulated aldosterone synthesis. Secondly, electron probe X-ray microanalysis (EPXMA) was used to quantify potassium, sodium, chlorine and phosphorous in control and AII-stimulated cells. The effects of verapamil on 43K efflux were measured at two stages during AII stimulation. During the first ten minutes of treatment, when efflux via the fast component predominates, AII and verapamil both slowed efflux and their effects were additive. If verapamil was added later, at the time when efflux by the fast component appeared exhausted and the stimulatory effect of AII on the slow efflux component was apparent, it again slowed efflux. These data suggest that verapamil prevents calcium-gated K+ channels from opening by blocking Ca2+ channels. However, verapamil had no effect on AII-stimulated calcium efflux. In addition to blocking Ca2+ channels, verapamil may directly inhibit potassium efflux. EPXMA showed a bimodal distribution of potassium concentrations in control cells. However, in cells stimulated with AII for five minutes, the mean potassium content was less than in controls and was not bimodally distributed. Sodium content was increased by AII-treatment, chlorine was lowered and phosphorus remained unchanged. The data confirm previous observations that AII inhibits Na+/K+ ATPase activity.

Adrenal Glands↗

Axial rotation of the lumbar spine and the effect of flexion. An in vitro and in vivo biomechanical study.

A series of experiments were performed on eight whole, cadaveric lumbar spines and on eight male volunteers to determine whether axial rotation changed with subjects bending forward compared with being in a neutral posture and whether rotation was affected by articular tropism. Kirschner wires were inserted into the spinous processes of the eight cadaveric lumbar spines, and the axial rotation of the wires was measured while the spine was rotated in a torsion apparatus. Similarly, Steinmann pins were inserted into the spinous processes of L3, L4, and L5 of the eight volunteers, and the axial rotation of the pins was measured while the subjects rotated in a torsion apparatus. Axial rotation was found to be less when combined with forward flexion, and articular tropism did not influence the amplitude of rotation.

Adult↗

Evidence for a contribution of the motor cortex to the long-latency stretch reflex of the human thumb.

1. In normal subjects, transcranial magnetic stimulation of the hand region of the motor cortex evokes motor responses only in contralateral hand muscles at a latency of about 19-24 ms. In contrast, stimulation of the motor cortex of three mirror movement subjects evoked, nearly simultaneously, motor responses in hand muscles on both sides of the body at latencies similar to those of normal subjects. In these subjects no other neuroanatomical pathways appear to be abnormally directed across the mid-line. Thus, their mirror movements are probably due to a projection of the corticospinal tract to homologous motoneurone pools on each side of the body. 2. We reasoned that if the motor cortex contributes to the generation of long-latency stretch reflex responses then in these mirror movement subjects stretching a muscle on one side of the body should produce long-latency reflex responses in the ipsilateral and the homologous contralateral muscle. 3. To test this idea experiments were done on normal human subjects and on the subjects with mirror movements. The electromyographic (EMG) activity of the flexor pollicis longus muscle (FPL) on each side of the body was recorded. Stretch of the distal phalanx of the thumb of one hand produced a series of distinct reflex EMG responses in the ipsilateral FPL. The earliest response, when present, began at 25 ms (S.D. = 3.5 ms) and was followed by responses at 40 (S.D. = 3.9 ms) and 56 ms (S.D. = 4.3 ms). There was no difference, either in timing or intensity, between the ipsilateral FPL EMG responses of normal subjects and those of the mirror movement subjects. 4. No response of any kind was observed in the contralateral (unstretched) FPL of normal subjects. In contrast, we observed in all three mirror movement subjects EMG responses in the contralateral (unstretched) FPL beginning at 45-50 ms. The latency of this response is considerably shorter than the fastest voluntary kinaesthetic reaction time, which was on average 130 ms (S.D. = 11 ms). The contralateral long-latency EMG response observed in the mirror movement subjects was on average 30% (range 5-60%) of that on the ipsilateral side. No short-latency response (25 ms) was ever observed in the contralateral FPL of these subjects. 5. These observations are quite consistent with the idea that the long-latency stretch reflex responses of hand and finger muscles are produced, at least in part, by the motor cortex.

Electromyography↗

Hyperglycaemia stimulates pyloric motility in normal subjects.

The motor correlates of the delay in gastric emptying produced by hyperglycaemia were investigated in 11 healthy volunteers. Fasting gastroduodenal motility was measured during euglycaemia (blood glucose concentration 3-5 mmol/l) and during hyperglycaemia induced by intravenous dextrose (blood glucose concentration 12-16 mmol/l). Antral, pyloric, and proximal duodenal pressures were recorded by a sleeve/sidehole manometric assembly positioned across the pylorus, with the aid of measurements of transmucosal potential difference. During hyperglycaemia there was stimulation of isolated pyloric pressure waves when compared with the euglycaemia period (p less than 0.05). This was associated with inhibition of antral pressure waves (p less than 0.05). In nine of the 11 subjects an episode of duodenal 'phase III like' activity occurred within 15 minutes of the onset of hyperglycaemia. It is proposed that the stimulation of localised pyloric contractions and inhibition of antral contractions contribute to the delayed gastric emptying induced by hyperglycaemia. Abnormal gastric motility in patients with diabetes mellitus may be the result of hyperglycaemia itself, rather than irreversible autonomic neuropathy.

Adolescent↗

Influence of colour Doppler echocardiography on the ultrasonic assessment of congenital heart disease: a prospective study.

OBJECTIVE: To evaluate the additional information provided by colour Doppler in the ultrasonic assessment of congenital heart disease. PATIENTS AND METHODS: A prospective study of 215 children (age range 1 day-16 years) presenting with clinical signs of congenital heart disease. RESULTS: Colour Doppler was essential for the diagnosis of an anomalous left coronary artery and altered the management of a patient initially diagnosed as having cardiomyopathy. Colour Doppler provided extra information, but without major impact on management, in the following: the diagnosis of ventricular septal defects associated with other defects, of multiple ventricular septal defects, of anomalous pulmonary venous drainage, and of mild mitral regurgitation; the demonstration of site of coarctation, of stenotic or hypoplastic pulmonary artery branches, of unobstructed flow through a right atrial membrane, and of left ventricle to right atrium regurgitation; the assessment of the width of the duct and of flow through the patent foramen ovale in transposition and tricuspid atresia; the differentiation of pulmonary atresia from critical pulmonary stenosis and the measurement of maximum velocity of tricuspid regurgitation. CONCLUSIONS: Ideally all patients should undergo colour Doppler studies before cardiac surgery to ensure a more accurate diagnosis. However, since the additional information provided does not affect the management in most patients, machines without colour Doppler can provide a satisfactory service in paediatric cardiology centres in countries where resources are limited.

Abnormalities, Multiple↗

Successful treatment of steroid-resistant double-lung allograft rejection with Orthoclone OKT3.

An 18-yr-old woman with cystic fibrosis who received a double-lung transplant developed a severe episode of acute lung rejection. Bronchoalveolar lavage and transbronchial biopsy were used to establish the diagnosis. The rejection was refractory to administration of high-dose pulse steroids. OKT3 therapy was successfully used to reverse this episode. This is the first case report of a steroid-resistant double-lung allograft rejection successfully treated with OKT3.

Adolescent↗

Efflux of potassium ions in angiotensin II-stimulated bovine adrenocortical cells.

Angiotensin II (AII) stimulation of steroidogenesis is known to be associated with depolarization of the adrenocortical cell membrane. In these cells, membrane permeability to potassium ions governs electrical potential. The effects of AII on the rate of efflux of K+ in relation to the control of aldosterone synthesis has been investigated in bovine adrenocortical cells preloaded with 43K. In static incubations, the pattern of 43K efflux fitted a model with two exponential components with t1/2 values of 47.7 +/- 1.7 and 14.2 +/- 0.6 (S.E.M.) min. AII increased the efflux rate of the slow-exchange component (t1/2 37.1 +/- 0.6 min) and retarded efflux from the fast-exchange component. With ouabain present to prevent reuptake of the isotope, the rate of efflux for both components was increased in unstimulated cells (t1/2 28.4 +/- 1.1 and 12.0 +/- 0.7 min). AII again increased the rate of efflux from the slow component (t1/2 = 24.2 +/- 1.7 min, P less than 0.01) and retarded efflux from the fast component. These biphasic effects were apparent in cells treated with a range of AII concentrations (0.1 nmol/l-1 mumol/l) but the point in time at which increased efflux from the slower component predominated over retardation of the slow component was earlier for cells treated with 1 mumol AII/l than for cells treated with lower concentrations. We suggest that decreases and increases in K+ efflux caused by AII are associated with depolarization and repolarization respectively. Changes in intracellular concentrations of Ca2+ may link these events.

Adrenal Cortex↗

Small cell lung cancer presenting as a solitary pulmonary nodule.

Small cell lung cancer (SCLC) rarely presents radiographically as a solitary pulmonary nodule (SPN). Twenty-five patients with this feature were identified among 408 individuals with SCLC at McGill University (Montreal, Quebec) from 1979 through 1984. Of these, 15 (60%) were confirmed on pathologic review as SCLC (ten intermediate cell, four oat cell, one indeterminate). Pathologic review of a control group comprising 24 other limited-disease patients who were long-term survivors (greater than 20 months) confirmed 20 (84%) as SCLC (eight intermediate cell, 12 oat cell). Ten of the 15 patients with SPN were resected whereas five had chemotherapy and/or radiotherapy as primary treatment. Postoperative chemotherapy was administered to most of the resected patients. The median survival of the 15 patients with SPN was 24 months, a significantly longer survival than the other patients with SCLC. This improved prognosis in patients with SPN may be due to smaller initial tumor burden or to a fundamental biologic difference between SPN and other forms of SCLC.

Actuarial Analysis↗

Intractable neck pain.

A retrospective survey of 1,661 patients seen over a 10-year period at a pain clinic yielded 55 patients with intractable neck pain as the presenting complaint. In 89% there was an industrial or motor vehicle accident as the precipitating event, 78% were involved in legal proceedings relating to the accident, and in 87% the pain radiated to neighboring structures. Diagnostically, 36% had no physical signs, and cervical radiographs were normal for 46%. There was a high incidence of previous psychiatric treatment (53%) and major intrafamily problems (60%). Treatment mainly by psychotherapy or tricyclic antidepressants resulted in some benefit for 56% of patients. Legal compensation and change in occupation were not major factors influencing the outcome of treatment.

Accidents, Occupational↗

Increased sensitivity to noradrenaline in glucocorticoid-treated rats: the effects of indomethacin and desipramine.

Vascular responsiveness was evaluated in perfused mesenteric arteries from rats infused with dexamethasone (2 micrograms/day). Full dose-response curves to noradrenaline, vasopressin and potassium chloride were established. In order to investigate whether prostaglandins or noradrenaline uptake were involved in dexamethasone-induced pressor changes, vascular responses were compared before and during treatment with either indomethacin (a cyclo-oxygenase inhibitor) or desipramine (an inhibitor of neuronal catecholamine uptake). Dexamethasone-treated tissues showed an increased vascular sensitivity to noradrenaline compared with controls; the maximal response was greater and the concentrations of agonist required for a 50% response (EC50) was less in dexamethasone-treated tissues. The responses to vasopressin and potassium chloride were not affected. Systolic blood pressure in dexamethasone-treated rats was not significantly different from that in controls. Indomethacin infusion decreased the vascular responsiveness to noradrenaline in control and dexamethasone-treated rats to a similar degree. Noradrenaline responses after indomethacin treatment were not significantly different in control and dexamethasone-treated tissues. 6-Keto-prostaglandin-F1 alpha output during stimulation with noradrenaline was not affected by dexamethasone. Desipramine lowered pressor responses to noradrenaline at all concentrations and decreased the maximal response in tissues from dexamethasone-treated but not control rats. However, during infusion with desipramine, the EC50 for noradrenaline after dexamethasone was still less than in controls. Dexamethasone at low doses appears to selectively increase vascular sensitivity to noradrenaline in rats at a prehypertensive stage by changing prostaglandin synthesis and, possibly, neuronal uptake of noradrenaline.

Animals↗

Effects of dexamethasone on body fluid and electrolyte composition of rats.

Low-dose infusions of dexamethasone (2 micrograms/day for 2 and 4 weeks) increased systolic blood pressure and decreased body weight gain in male rats. Total body sodium, calcium and magnesium were increased by dexamethasone treatment; potassium was unaffected. These changes have been evaluated bearing in mind that glucocorticoids have profound catabolic effects. Relative to pretreatment values, dexamethasone decreased exchangeable body sodium for the first two weeks of treatment although values were not significantly different from vehicle-treated controls. Hematocrit, plasma cholesterol and transaminase activities were increased by dexamethasone; white cell numbers and plasma volumes were decreased; plasma Na+, K+ and Ca2+, red cell numbers, extracellular fluid volume, and glomerular filtration rate were not significantly affected. It is concluded that glucocorticoids cause plasma volume to contract, possibly as a result of glucocorticoid-induced natriuresis. Any effects of dexamethasone on whole-body ionic composition are obscured by simultaneous changes of intermediary metabolism.

Animals↗