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Biomedical subjects

J S Cameron

Publications and source records attributed to J S Cameron.

At least 163 records · Page 9Linked to original sources

Treatment of proteinuric idiopathic glomerulonephritides in adults: a retrospective survey.

PURPOSE: A review of the worldwide medical literature was undertaken to determine whether treatment with currently available drugs has been beneficial in patients with glomerulonephritides. MATERIALS AND METHODS: Thirty-five articles, involving 1,653 adult patients with chronic primary glomerulonephritis with proteinuria and/or nephrotic syndrome, were analyzed. The criteria for inclusion of data were strict, and only complete and well-studied cases were included in the analysis. The papers were grouped into prospective controlled trials, retrospective comparisons of treated and untreated patients, and retrospective studies without an untreated group. RESULTS AND CONCLUSIONS: Analysis of the data shows that patients with minimal change disease clearly benefited from the administration of corticosteroids and/or cytotoxic drugs, since 89 percent and 79 percent of patients had a complete remission in controlled trials and in retrospective studies, respectively. A low incidence of complete and partial remissions was found in the group of patients with focal segmental glomerulosclerosis, proteinuria disappeared in 19 percent, and only 36 percent of these patients had stable renal function after a mean follow-up period of 6.3 years. The incidence of uremia and the number of patients requiring dialysis were very high. In patients with membraneous glomerulonephritis, conflicting results were obtained in controlled trials, retrospective comparisons, and retrospective studies, since a high percentage of complete and partial remissions was present in treated patients from both controlled and retrospective comparisons, whereas the percentage of complete and partial remission in untreated patients increased as the length of the follow-up period increased. Long-term studies carried out on untreated patients confirmed the high percentage of remissions. These data suggest that it is necessary to await future long-term results from controlled trials in order to determine whether or not corticosteroids alone or associated with cytotoxic drugs have a beneficial effect. Finally, the data from patients with mesangiocapillary glomerulonephritis show that therapy appears to have no beneficial effect on renal function. Nephrologists need new drugs that interfere more decisively with the immune process in the pathogenesis of primary glomerulonephritis.

Azathioprine↗

Severe Guillain-Barré syndrome: an association with IgA anti-cardiolipin antibody in a series of 92 patients.

To determine whether anti-cardiolipin antibodies (ACA) are associated with acute Guillain-Barré syndrome (GBS), we studied sera from 92 patients with GBS, 82 age- and sex-matched hospital controls and 24 patients with uncomplicated cytomegalovirus or Campylobacter jejuni infection, using an isotype-specific ACA enzyme-linked immunosorbent assay (ELISA). IgA ACA titres (but not IgG ACA or IgM ACA) were significantly elevated (P = 0.002) in GBS patients compared to controls, and associated with peak disease severity (P = 0.01), but not initial or residual disability, nor duration of neuropathy. Abnormal IgG ACA may cause or result from myelin damage in GBS.

Acute Disease↗

Prevention of hypertension is associated with reduced susceptibility to histamine-induced arrhythmias in SHR.

Two groups of spontaneously hypertensive rats (SHR) were treated with alpha-methyldopa (2.5 g/L in drinking water) for 12-17 weeks. One group was treated during the normal time course for development of hypertension and myocardial hypertrophy (beginning at age 4 weeks), while the other was treated after stabilization of hypertension/hypertrophy (21 weeks). Appropriate age-matched controls (WKY strain) also were treated. Intracellular microelectrodes were used to monitor action potential configuration, automaticity, and the incidence of arrhythmias (including delayed afterdepolarizations and repetitive tachyarrhythmias) in isolated left ventricles from each group. The younger rats did not develop hypertension of left ventricular hypertrophy; susceptibility of isolated left ventricles to histamine-induced (10(-5) M) arrhythmogenesis was significantly reduced. The older rats showed decreased blood pressure, although not to normal levels; further left ventricular hypertrophy was prevented, though the existing enlargement did not regress. These hearts were as susceptible to the development of histamine-induced arrhythmias as were hearts of untreated SHR. Enhanced susceptibility to arrhythmias in hypertrophied hearts reflects a preventable alteration of the myocardial cell membrane that occurs during the course of blood pressure elevation. This change may be associated with defective sarcolemmal calcium transport in hypertrophied myocardium.

Animals↗

Improved prognosis of renal microscopic polyarteritis in recent years.

To determine if the short- and long-term prognosis of renal micropolyarteritis (including Wegener's granulomatosis) had improved in our Unit in the last 5 years compared to our previous series from 1965 to 1980, we examined data from 26 recent patients, 1981-1986. Twenty were admitted during acute phase and six after a mean of 7.1 months of disease. The acute phase showed mild to severe impairment of renal function, and renal biopsies showed necrotising glomerulitis in all acute patients with extensive crescents in 67%. Acute patients (20) were treated with 'aggressive' immunosuppression including i.v. methylprednisolone (15), plasmapheresis (seven) and cyclophosphamide (ten). Chronic immunosuppressive treatment was continued in most patients. In the 20 acute-onset patients, life survival at 2 and 5 years was 77%; four of five deaths occurred during the acute phase in aged patients with severe renal failure. The notable improvement in life and kidney survival (only one patient underwent chronic dialysis) probably resulted from greater awareness of vasculitis in general practice with early referral of patients to specialised units, and to more aggressive treatment.

Acute Disease↗

ATP-sensitive K+ channels are altered in hypertrophied ventricular myocytes.

Unitary K+ currents in single cells isolated from normal and hypertrophied feline left ventricles were studied with regard to ATP sensitivity using patch-clamp single-channel recording. Data were obtained from excised inside-out membrane patches with symmetrical transmembrane K+ concentration [K+] (140 mM) at 22 +/- 1 degree C and in the absence of divalent cations. In the absence of ATP at the intracellular membrane surface, K+ channel activity was observed during depolarizing and hyperpolarizing pulses ranging from 10 to 120 mV from the K+ equilibrium potential. The current voltage (I-V) curve displayed some inward rectification, with slope conductances becoming nonlinear at strong depolarizations. Rectification was particularly pronounced in cells from hypertrophied left ventricles relative to normal. Single-channel conductance determined from the linear portion of the I-V curve was 77 pS in both groups. The channels were blocked by intracellular Ca2+ (1 mM), extracellular tetraethylammonium (TEA; less than or equal to 2 mM) or 4-aminopyridine (0.5 mM); 2 mM ATP produced a total but reversible inhibition. The effect of ATP was to reduce channel openings; conductance was unaffected. The ATP concentration [( ATP]) that induced half-maximal inhibition of channel activity was 75 microM in normal myocytes but was 250 microM in cells from hypertrophied hearts. Rapid channel activation at diminished [ATP] may provide a protective function by maintaining resting potential or promoting vasodilation in hypertrophied myocardium.

4-Aminopyridine↗

Cellular electrophysiological changes during ischemia in isolated, coronary-perfused cat ventricle with healed myocardial infarction.

Cellular electrophysiological consequences of acute ischemia superimposed on healed myocardial infarction were studied in isolated, coronary-perfused cat left ventricles 2-4 months after ligation of multiple distal tributaries of the left anterior descending and circumflex coronary arteries. Oxygenated Tyrode's solution was perfused through the left anterior descending and circumflex coronary arteries, and the preparations were superfused with Tyrode's solution gassed with 95% N2-5% CO2. Transmembrane action potentials were recorded from the endocardial cells in normal and infarcted zones. There were no significant differences in measured action potential variables and refractory periods between cells in the normal and infarcted zones before acute ischemia. When coronary perfusion was discontinued ("ischemia"), resting potential, action potential amplitude, and action potential duration were reduced, and the refractory period was shortened progressively in cells of the normal zone. However, the action potential changes were less prominent, and the refractory period was unchanged in cells in the infarcted zone. As a result, there were significant differences in resting membrane potential, action potential amplitude, action potential duration, and refractory period between cells in the normal and infarcted zones at 10 minutes of ischemia. These differences became larger as the ischemic period was prolonged. Spontaneous rapid ventricular activity was observed during the last 20-30 minutes of ischemia in four of eight preparations with healed myocardial infarction, whereas no spontaneous rapid ventricular activity was recorded in any of six normal heart preparations. Our data suggest that superimposition of acute ischemia on healed myocardial infarction produces electrophysiological inhomogeneities that may enhance arrhythmogenesis.

Action Potentials↗

Acute renal disease in vasculitis.

Vasculitis is commoner than supposed, since its manifestations are Protean. A simple classification of vasculitis is outlined and an approach to renal vasculitis described. Recent papers on the subject are summarized, and recent advances in understanding of the role of cell-mediated immunity in the pathogenesis of vasculitis outlined. The treatment of renal vasculitis accompanied by renal insufficiency is summarized, with a note on Henoch-Schönlein purpura. The prognosis for patients with severe renal vasculitis, whether Wegener's granuloma or microscopic polyarteritis, has improved considerably over the past three decades, using immunosuppression with corticosteroids, orally or intravenously, cytotoxic agents, and plasma exchange backed up by dialysis as necessary. The principal problems now relate to the management of immunosuppression in the long term survivors.

Actuarial Analysis↗

Cellular electrophysiology of coronary artery ligation in chronic pressure overload.

We evaluated ischemia-induced cellular electrophysiologic abnormalities in chronic pressure overload ventricular myocardium in vitro. Left ventricular systolic hypertension was induced in cats via partial supracoronary aortic constriction (overload); at 1 1/2-3 months, resulting pressure overload was accompanied by ventricular hypertrophy (25-35% by weight) and patchy endocardial fibrosis. Two hours of subsequent acute myocardial ischemia (ischemia) was imposed on overload (ischemia/overload) via total occlusion of distal branches of the left coronary artery system. Spontaneous premature depolarizations in vitro were increased in ischemia/overload compared to control, ischemia or overload alone; bursts of spontaneous, repetitive depolarizations were also unique to these preparations. Multiple site recordings of endocardial transmembrane action potentials overlying the borders (interface) of fibrotic areas in ischemia/overload demonstrated numerous electrophysiologic abnormalities, including several not observed in control, ischemia or overload. Unique to the border areas of ischemia/overload preparations was the presence of maintained but depressed resting potential without action potentials; also, the incidence of depolarizations at the onset of the plateau phase was highest in these preparations. In non-fibrotic areas, electrophysiologic properties including resting potential and action potential amplitude and rate of rise were diminished in ischemia/overload compared to ischemia or overload preparations. These data demonstrate that acute myocardial ischemia in the setting of chronic pressure overload leads to additional cellular electrophysiologic abnormalities compared to ischemia or overload alone.

Action Potentials↗

Vasoactive intracavernous pharmacotherapy for the treatment of erectile impotence in men with spinal cord injury.

A total of 66 spinal cord injury patients with erectile dysfunction entered a protocol of penile intracavernous pharmacotherapy with papaverine hydrochloride (30 mg. per ml.) or a combination of papaverine (25 mg. per ml.) and phentolamine mesylate (0.83 mg. per ml.) in an attempt to restore erectile function. Of the patients 52 completed the protocol and all achieved transient functional penile erections after administration of the drug. Of the 52 responders 71 per cent currently practice self-injection as a method to restore erectile function. Sustained erections that required irrigation of the cavernous bodies with alpha-adrenergic agents developed in 4 patients and 1 suffered localized intracorporeal induration. If the long-term followup shows that complications remain relatively minor, undoubtedly vasoactive intracavernous pharmacotherapy will have a major role in the restoration of erectile function in the motivated man with spinal cord injury. However, in view of the unknown long-term effects and potential dangers of this approach it is important that patients adhere to a strict drug injection protocol under the supervision of qualified urologists who are familiar with the potential risks and complications.

Adult↗

The nephrotic syndrome and its complications.

Modern views of the pathogenesis and natural history of nephrotic syndrome have changed substantially since the early studies by Cotugno and Bright. Contrary to beliefs held 20 years ago, we do not possess a unique satisfying explanation for the induction, maintenance, and resolution of nephrotic edema, and many concepts firmly established as "classic" are now being revised or reconsidered. These include the relationship between urinary protein losses and hypoalbuminemia, which is complicated by several factors such as daily protein intake, albumin catabolism, and the possible role of albumin loss at extrarenal sites. The influence of lowered plasma albumin on the decrease in plasma volume is also quite complex, due to technical difficulties in measuring plasma volume and turnover of radio-labeled albumin. The most contentious areas are how sodium and water retention are initiated and maintained and the relationship between hypoalbuminemia, plasma oncotic pressure, and edema. While aldosterone excretion and plasma concentrations are elevated in nephrotic patients, data on the renin-angiotensin system are controversial and the renal handling of sodium is related to a host of factors including glomerular filtration rate, altered proximal tubular reabsorption, and the role of vasodilators or vasoconstrictors. The complications of nephrotic syndrome are protean and relatively common. Among those are acute renal failure, thrombosis, infections, and hyperlipidemia. Since the introduction of percutaneous biopsy, the spectrum of lesions underlying nephrotic syndrome has widened considerably, the most common being minimal change, especially in children. There are very few prognostic indicators by which response to treatment may be predicted and these include persistent microscopic hematuria.

Acute Kidney Injury↗