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Biomedical subjects

J S Cameron

Publications and source records attributed to J S Cameron.

At least 235 records · Page 13Linked to original sources
PubMed1984

Delayed afterdepolarizations and triggered activity induced in feline Purkinje fibers by alpha-adrenergic stimulation in the presence of elevated calcium levels.

We studied the ability of alpha-adrenergic stimulation to induce delayed afterdepolarizations and triggered activity in Purkinje fibers from cat hearts in the presence of an elevated Ca++ concentration. Delayed afterdepolarizations could not be induced at drive cycle lengths of 200 to 500 msec in the presence of extracellular Ca++ concentrations of 2.7 to 8.1 mM. However, the addition of 10(-5)M phenylephrine in the presence of 5 X 10(-7)M propranolol elicited delayed afterdepolarizations in eight of 10 preparations at a Ca++ concentration of 8.1 mM; nondrive-triggered action potentials were recorded from three of the preparations. These afterpotentials were completely suppressed by 5 X 10(-7)M prazosin or 10(-6)M phentolamine. In the presence of 5 X 10(-7)M propranolol, 10(-5)M phenylephrine prolonged action potential duration and this effect was suppressed by 5 X 10(-7)M prazosin. Methoxamine, at a concentration of 5 X 10(-6)M, was also observed to potentiate delayed afterdepolarizations in all of three preparations studied. These results demonstrate that alpha-adrenergic stimulation can induce afterpotentials in the presence of elevated Ca++ levels in cat hearts. Stimulation of alpha-adrenoceptors may be responsible for arrhythmias under Ca++-loaded conditions such as ischemia and coronary reperfusion.

Action Potentials↗
PubMed1984

End-stage renal failure in systemic lupus erythematosus with nephritis.

The survival of patients in end-stage renal failure from lupus nephritis offered renal substitution therapy has been the subject of conflicting reports. Trying to clarify the reasons for this discrepancy, we analysed our experience with dialysis and transplantation in systemic lupus erythematosus (SLE). Of our 138 patients with lupus nephritis, 26 reached end-stage renal failure, of whom 24 received replacement therapy. Fourteen patients had a marked acute deterioration in renal function immediately before reaching terminal uremia, associated with active SLE in 12 and acute tubular necrosis after hypotension in one. Nine patients in this group died, 8 within 1 month of beginning dialysis. Nine patients progressed slowly to endstage renal failure over 2 to 7 years, without evidence of active SLE: only 1 required aggressive treatment and only 3 patients died, 1 five years after transplantation. Eight patients received altogether 10 allografted kidneys; 4 still functioning 10-24 months later; 2 patients are back on dialysis and 2 died, 1 of a myocardial infarct. There was no evidence of active SLE after transplantation. Ten patients were dialysed for more than 3 months; most were maintained on prednisolone and azathioprine whilst on dialysis and lupus activity tended to abate. The exclusion of the group of patients with rapid pre-terminal decrease in renal function from some series may explain some of the differences in reported survival. Stable patients with SLE present few problems in end-stage renal failure or after transplantation.

Adult↗
PubMed1984

Impaired vessel wall response to venous occlusion in patients with chronic renal failure on maintenance hemodialysis.

We have studied vessel wall function in two groups of patients with chronic renal failure - 1) conservative treatment only and 2) maintenance hemodialysis. Three proteins synthesized by vascular endothelium-plasminogen activator (PA), factor VIII related antigen (VIII:RAg) and antithrombin III (ATIII) - were assayed before and after a fifteen minute period of venous occlusion. The release of PA was significantly reduced in patients on maintenance hemodialysis as compared to both undialyzed uremics and controls. Lesser amounts of VIII:RAg were also released by hemodialysis patients than by undialyzed uremics. These defects, which are suggestive of vessel wall dysfunction on maintenance hemodialysis, may contribute to the high incidence of arteriopathy and thrombotic disease observed in this group of patients.

Adult↗
PubMed1984

Vasculitis affecting the kidney: presentation, histopathology and long-term outcome.

Fifty-three patients who by clinical and/or histological criteria were judged to have vasculitis affecting the kidney were reviewed. Patients with systemic lupus or Schönlein-Henoch purpura were excluded. Segmental necrotising glomerulitis was taken as a manifestation of vasculitis ('microscopic polyarteritis'). Those patients in whom vasculitis was confined to glomerular capillaries were compared with those who in addition had vascular lesions outside the glomeruli. The two groups were found to have identical clinical features. Clinical presentation was predominantly extrarenal, and exclusively renal in only two. Three patients were classified histologically as Wegener's granulomatosis, four had malignant tumours and two relapsing polychondritis. Hepatitis B surface antigen was absent in all of 37 patients tested. Renal disease presented with microscopic haematuria and minor proteinuria in the majority (32) but 16 patients presented with rapid deterioration of renal function, including seven with anuria. Histologically 42 patients showed segmental necrotising glomerulitis ('microscopic polyarteritis'), six diffuse proliferative glomerulonephritis,and in five only minor or ischaemic glomerular changes were present. Crescents were found in 41/42 of those with segmental necrotising glomerulitis, nd involved more than 50 per cent of glomeruli in 15 patients. Immunohistochemical studies were generally negative except the fibrin. Electron microscopy showed no evidence of immune deposits in necrotising glomerulitis, but these were present in 2/6 patients with diffuse proliferative glomerulonephritis. Overall prognosis was poor, 35 patients having died, 20 early in the course of the disease and 15 later. Oligoanuria and extensive crescent formation were adverse signs. Survivals were 54, 38 and 34 per cent at one, five and 10 years respectively. Of those who survived the initial illness, 12 were stable with apparently inactive disease, whilst 16 continued to show clinical signs of activity and required treatment. A variety of treatments was employed including oral and intravenous corticosteroids, immunosuppressive agents, anticoagulants; only one patient was treated by plasmapheresis. It is difficult to draw any firm conclusions as to the efficacy of treatment and survival rates remain unsatisfactory.

Acute Disease↗
PubMed1984

The natural history of renal function in untreated idiopathic membranous glomerulonephritis in adults.

Sixty-four patients (47 male, 17 females) aged between 20 and 70 years with idiopathic membranous glomerulonephritis, never having received steroid or immunosuppressive drugs prior to and subsequent to biopsy, have been followed to terminal renal failure or for a minimum of two up to fifteen years. Presentation was with asymptomatic proteinuria in 12 and nephrotic syndrome in 52. The serum creatinine at time of biopsy was less than or equal to 99 mumoles/l in 25, 100-119 mumoles/l in 18 and greater than or equal to 120 mumoles/l in 21. During the follow up there was no deterioration in renal function in 30 patients (48%). In 27 patients (43.5%) there was a steady deterioration in renal function, on the average 30 months (range 5-60) for the serum creatinine to double and 32 months (range 5-49) for the serum creatinine to reach 400 mumoles/l. In five patients there was a slow deterioration. A plot of the reciprocal of the sequential serum creatinine values with time indicates that the rate of deterioration is essentially constant in any patient but that there is a wide variation between patients. The reciprocal of the serum creatinine is a useful means of following the evolution of the disease. In two patients there was a change in the rate of deterioration and a cause could be identified (one with renal vein thrombosis, one with interstitial nephritis). Poor prognostic indicators were: nephrotic syndrome at presentation, impaired function at time of diagnosis, male patients and older age.

Adult↗
PubMed1983

Complement activation during cardiopulmonary bypass: quantitative study of effects of methylprednisolone and pulsatile flow.

Forty four patients undergoing open heart surgery were divided into three groups. Group 1 (17 patients) underwent routine anaesthesia and surgery; group 2 (17 patients) received two doses of methylprednisolone (30 mg/kg), one during induction of anaesthesia and the other immediately before induction of cardiopulmonary bypass; and group 3 (10 patients) received pulsatile flow while undergoing pulsatile perfusion by the heart-lung machine. A modification of the previously described technique was used to detect and measure complement activation in plasma before and during the bypass period using crossed immunoelectrophoresis. About 45% of all patients showed measurable complement activation (greater than 4.5%) during cardiopulmonary bypass and the mean activation in this group was 6.4%. There was no significant difference between the three groups in complement activation. In group 2, however, women showed significantly more complement activation than men (p less than 0.05). It is suggested that neither corticosteroids nor pulsatile flow affect complement activation, but caution should be exercised in women receiving methylprednisolone.

Animals↗
PubMed1983

Successful treatment of middle aged and elderly patients with end stage renal disease.

Many patients over the age of 55 with end stage renal disease in the United Kingdom are denied dialysis or transplantation. Although the reasons are complex, anticipation of a poor prognosis for these patients might explain why most British renal units impose an arbitrary age limit on the acceptance of patients for treatment. A study was therefore conducted to examine the prognosis and quality of life of 84 patients (mean age 59.6 years, range 55-72) accepted into our renal replacement programme from the beginning of 1975. The five year survival of the patients was 62.0% with 78.1% of the survivors either having successful transplants or caring for themselves using home haemodialysis or continuous ambulatory peritoneal dialysis. The results show that in terms of survival, economics, and rehabilitation it is both feasible and reasonable to treat middle aged and elderly patients with end stage renal disease. These patients should therefore not be denied dialysis or transplantation on the basis of age alone, and the lack of resources and other factors that allow this state to persist in Britain should be rapidly redressed.

Age Factors↗
PubMed1983

Regional sensitivity to verapamil in ventricular myocardium.

The effects of verapamil (0.1-4.0 micrograms/ml) on transmembrane action potential configuration was examined in various regions of the normal cat left ventricular endocardium. Surface electrograms showed that the sequence of activation of anterior papillary muscle fibers was from the base of the muscle to its apex, while overlying Purkinje fibers were activated in the opposite direction. Action potential duration in basal muscle fibers was relatively unaffected by verapamil, while cells at the tip of the papillary muscle showed increased slope in phase 2 and a more rapid rate of early repolarization. Regional sensitivity to verapamil may reflect disparate patterns of endocardial activation, and could influence the effectiveness of the drug against ventricular arrhythmias.

Action Potentials↗
PubMed1983

Synthesis of thromboxane B2 in uraemia and the effects of dialysis.

The generation of thromboxane B2 (TxB2) from its natural precursor, arachidonic acid, was studied in vitro in order to assess further the prostaglandin pathway in the platelets of patients with chronic renal failure. Some, but not all patients with conservatively treated uraemia synthesised significantly less TxB2 then controls and the same patients were also hypo-aggregable to arachidonic acid. The synthesis of TxB2 appeared normal in a group of patients on chronic ambulatory peritoneal dialysis (CAPD). In contrast, a group of patients on long-term maintenance haemodialysis produced significantly greater amounts of TxB2 and were hyper-aggregable to arachidonic acid, a finding which may be relevant to the high incidence of atherosclerosis and vascular disease in these patients.

Adult↗
PubMed1983

High versus "low" dose corticosteroids in recipients of cadaveric kidneys: prospective controlled trial.

Corticosteroids have the major role in the immunosuppressive treatment of patients who have received renal transplants. Despite their extensive use there is still debate about the appropriate dose that will prevent rejection of the renal allograft with the least morbidity. From March 1979 to November 1981 a randomised controlled trial of high (33 patients) v low oral dose (34 patients) of prednisolone along with azathioprine was conducted in recipients of first cadaveric transplants who had received a blood transfusion within six months of transplantation. The main difference in outcome between the two groups was a high incidence of some infections in the high dose group. Patient mortality, graft survival, transplant function, and number of rejection episodes were indistinguishable in the two groups, but rejection episodes tended to occur later in the high dose group. These findings suggest that the use of lower doses of corticosteroids soon after cadaveric renal transplantation does not jeopardise graft survival and results in lower patient morbidity.

Adolescent↗
PubMed1983

Idiopathic mesangiocapillary glomerulonephritis. Comparison of types I and II in children and adults and long-term prognosis.

Of 104 patients with idiopathic mesangiocapillary glomerulonephritis studied for at least two years, 69 patients had type I disease and 35 had type II. Forty-five patients were children, and 59 were adults. Type II mesangiocapillary glomerulonephritis was more common in children than in adults, but no other clinical feature distinguished the two types at onset. Complement studies revealed that patients with type II had lower serum C3 concentrations and more frequently showed C3-splitting activity (C3 nephritic factor) in the serum. Children had hypertension or a lowered glomerular filtration rate less frequently at onset than did adults, but children had a higher incidence of a hematuric onset; C3 nephritic factor was also more frequent in the children. During a follow-up period of two to 21 years (mean eight years), only seven patients (five with type I and two with type II) showed clinical remission, whereas 38 percent of patients with type I and 49 percent of patients with type II died or required dialysis; a further 23 percent of patients with type I and 16 percent of patients with type II had continuing disease and reduced glomerular filtration rate. Only the presence and persistence of a nephrotic syndrome in type I predicted renal failure. In both types, the presence of sclerosis or crescents in the initial renal biopsy specimen was associated with a poorer prognosis, but no other feature was of major prognostic value.

Adolescent↗
PubMed1983

Electrophysiologic consequences of chronic experimentally induced left ventricular pressure overload.

Cardiac electrophysiologic alterations were evaluated 1 to 8 months after partial supracoronary aortic constriction in cats. This procedure induced left ventricular systolic hypertension and hypertrophy with marked connective tissue infiltration. In situ, premature ventricular complexes were observed during or after vagal slowing of sinus rate in 8 (26%) of the 31 experimental animals, while an additional 3 of the 31 developed ventricular fibrillation. No arrhythmias were recorded in 31 normal or 7 sham-operated cats. In vitro, 29% of the left ventricular preparations from cats with pressure overload and 5% from control cats showed spontaneous ectopic activity. During stimulation at cycle lengths of 800 to 1,000 ms, multiple site impalements of subendocardial muscle cells within fibrotic regions revealed heterogeneous electrical abnormalities. These included short action potential duration, low amplitude action potentials generated from low resting potentials, split upstrokes and electrically silent areas. Impalements in nonfibrotic areas of the left ventricle showed prolongation of muscle action potential duration. Long-term disturbances in cellular electrophysiologic properties may favor the development of arrhythmias and thereby contribute to sudden cardiac death in left ventricular hypertension and hypertrophy.

Animals↗
PubMed1983

In vivo platelet activation with in vitro hyperaggregability to arachidonic acid in renal allograft recipients.

Renal allograft recipients were investigated to determine the extent and possible nature of in vivo platelet activation. In 92 allografted patients stable for more than 4 months' duration, intraplatelet serotonin in circulating platelets was depleted significantly. In a further 16 patients studied serially for 12 to 16 weeks following transplantation, intraplatelet serotonin fell abruptly within 4 days from transplantation to very low levels, and remained thus for 10 weeks, rising toward normal at about 12 weeks. Although some patients showed abrupt falls in intraplatelet serotonin coincident with acute rejection episodes, there was no difference in intraplatelet serotonin in seven patients whose grafts functioned well immediately and remained stable, and seven in whom repeated rejection led to graft loss within 3 months. Thus, these tests of platelet function do not permit diagnosis of rejection or prediction of graft outcome. Plasma platelet factor 4 (PF4) concentrations, in contrast, were normal in most patients during the first 6 weeks after grafting, then rose and remained abnormal up to 13 years following the allograft in the long-term stable graft recipients. This discrepancy suggests a different mode of platelet activation in the first few weeks after grafting from subsequent months. Despite universal depletion of intraplatelet amines and alpha-granule contents only four out of 14 early allograft recipients had an abnormal bleeding time, and platelet aggregation thresholds with adenosine-5'-diphosphate and collagen were not different from controls. However, thresholds for platelet aggregation with arachidonic acid were reduced significantly (P less than 0.01) and thromboxane B2 generation was increased in vitro. There was no correlation between depletion of intraplatelet serotonin and circulating platelet-agglutinating material, but nine of 17 biopsy specimens from rejecting allografts taken during the first 3 months showed extensive glomerular localization of platelet membrane antigens and PF4.

Adenosine Diphosphate↗