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Biomedical subjects

J S Cameron

Publications and source records attributed to J S Cameron.

At least 19 recordsLinked to original sources
PubMed2002

Characteristics and outcome of membranous nephropathy in older patients.

Many patients with idiopathic membranous nephropathy are elderly, but little is known about the natural or treated history of these patients. We have studied a cohort of 155 patients with membranous nephropathy who were recruited and followed-up over a 20 year period. We have compared the clinical features and outcome of the older (>60 years) and younger age groups. There was a higher incidence of an identifiable cause for the nephropathy in older patients. At presentation with idiopathic disease, older patients were more often hypertensive and had worse renal impairment than the younger cohort, but had a similar levels of proteinuria, hypoalbuminemia and hematuria. Thrombotic complications and minor rheumatological complaints were more common in the older patients. Prognosis for life and renal survival was worse in the older onset patients. Treatment was well tolerated in selected older patients and was associated with a better outcome in those selected for treatment.

Adrenal Cortex Hormones↗
PubMed2002

Early treatment with allopurinol in familial juvenile hyerpuricaemic nephropathy (FJHN) ameliorates the long-term progression of renal disease.

BACKGROUND: The efficacy of allopurinol in autosomal dominant familial juvenile hyperuricaemic nephropathy (FJHN) has been disputed. AIM: To address this question, in the absence of controlled trials. DESIGN: Retrospective long-term follow-up study. METHODS: All kindreds were biochemically screened. Measurements included uric acid clearance, creatinine clearance, serum creatinine, and glomerular filtration rate (GFR). We used five siblings who had died or progressed to transplantation, ten other deceased relatives, and two index cases (one untreated, one non-compliant) as controls to assess the effects of allopurinol. RESULTS: Of eight families with FJHN, six had a strong history of renal disease and early parental death (mean age 41 years, n=10). Of 27 patients started immediately on allopurinol and treated uninterruptedly, 21 responded well, including three children born subsequently. Eight siblings (mean age 19 years) with a normal plasma creatinine at start (<120 micromol/l, mean GFR 80 ml/min/1.73 m(2)) retained stable renal function (mean 14.5 years, mean age 34 years, GFR 85 ml/min/1.73 m(2)). Of the 13 other responders, treated for up to 34 years, 10 with a creatinine <200 micromol/l at diagnosis (mean age 28 years, mean creatinine 137 micromol/l at start) now have a mean creatinine of 210 micromol/l. In contrast, five patients (mean age 26 years) with a creatinine >200 micromol/l (GFR <35 ml/min/1.73 m(2)) when allopurinol commenced, plus one untreated index case, all progressed rapidly (mean 6 years) to end-stage renal failure. In two others (one non-compliant, one initially untreated), GFR fell by >50% in 7 years. Introduction of allopurinol in the latter has stabilized GFR. DISCUSSION: Allopurinol reduced the morbidity and mortality from renal failure seen in untreated siblings and previous generations of these families. Early diagnosis of FJHN is important, so that treatment can begin before irreversible renal damage has developed.

Adolescent↗
PubMed2001

beta -Neuregulin-1 is required for the in vivo development of functional Ca2+-activated K+ channels in parasympathetic neurons.

The development of functional Ca(2+)-activated K(+) channels (K(Ca)) in chick ciliary ganglion (CG) neurons requires interactions with afferent preganglionic nerve terminals. Here we show that the essential preganglionic differentiation factor is an isoform of beta-neuregulin-1. beta-Neuregulin-1 transcripts are expressed in the midbrain preganglionic Edinger-Westphal nucleus at developmental stages that coincide with or precede the normal onset of macroscopic K(Ca) in CG neurons. Injection of beta-neuregulin-1 peptide into the brains of developing embryos evoked a robust stimulation of functional K(Ca) channels at stages before the normal appearance of these channels in CG neurons developing in vivo. Conversely, injection of a neutralizing antiserum specific for beta-neuregulin-1 inhibited the development of K(Ca) channels in CG neurons. Low concentrations of beta-neuregulin-1 evoked a robust increase in whole-cell K(Ca) in CG neurons cocultured with iris target tissues. By contrast, culturing CG neurons with iris cells or low concentrations of beta-neuregulin-1 by themselves was insufficient to stimulate K(Ca). These data suggest that the preganglionic factor required for the development of K(Ca) in ciliary ganglion neurons is an isoform of beta-neuregulin-1, and that this factor acts in concert with target-derived trophic molecules to regulate the differentiation of excitability.

Animals↗
PubMed2001

The continued care of children with renal disease into adult life.

Today in developed countries the majority of paediatric patients in hospital units suffer from conditions which will continue into adult life, and paediatric nephrology is no exception to this. Despite its obvious importance, the problem of the transition of these children with continuing renal diseases from paediatric to adult clinics is little discussed and often timed and managed badly, with failures on the part of both paediatricians and internists. However, a number of simple principles and actions can help to make the transition more successful and avoid medical and psychological harm. Nephrology can learn from the similar experience in other areas of paediatrics and medicine, such as diabetes, congenital heart disease and cystic fibrosis. Access to facilities for adolescent medicine remains limited and needs to be expanded. Whilst the management of those clearly needing continued care remains paramount, in addition guidelines for the follow-up management of apparently well young adults following attacks of conditions such as Henoch-Schonlein purpura, the haemolyticuraemic syndrome and acute renal failure are needed.

Aging↗
PubMed2000

Renal transplantation in the elderly.

Recent data show that, despite a long period during which few elderly patients in end-stage renal failure received grafts, there are neither medical nor ethical grounds for avoiding kidney transplantation, at least in those aged under 70 or even 75 years of age. Units in which transplantation in older recipients is routine show a good survival of recipients, and comparable survival of grafts to those placed in younger recipients. This equality of graft survival with age arises because, although death with a functioning graft is more common in the elderly (principally from cardiovascular disease and infections, with malignant diseases becoming more important with time), graft losses from rejection are lower, and so overall outcomes are similar. Long-term patient survival is better, quality of life is improved and treatment is cheaper than in comparable elderly patients maintained on hemodialysis or chronic ambulatory peritoneal dialysis. In terms of allocation to older recipients, this success presents major practical and ethical difficulties given the shortage of cadaver organs. Data do not support the idea of 'age-matching' older or marginal kidneys to older recipients: like their younger counterparts, older recipients do better with organs from younger donors. Living donors can be used successfully even in those over 70, and elderly living donors have a place in the treatment of the elderly. The optimum immunosuppressive regimes for elderly recipients have not been determined, given their poorer immune responsiveness and lower rejection rates compared with younger individuals.

Adolescent↗
PubMed2000

High blood pressure and the kidney: the forgotten contribution of William Senhouse Kirkes.

The realization of the key role for raised intra-arterial pressure as a pathogenetic agent in hypertension is usually credited to Ludwig Traube, but Traube in his writings gives credit for the idea to a little-known English doctor, William Senhouse Kirkes (1822-1864). Kirkes' main interest was in cardiology and vascular disease, and he gave the first account of embolism from vegetations in infective endocarditis in 1852. Three years later, he published a study of apoplexy in Bright's disease, in which he pointed clearly to the role of raised intra-arterial tension in the causation of arterial disease, a point that had eluded Bright, Johnson, and other contemporaries. Kirkes died at the age of only 42 while working on a book summarizing his work on cardiology and renal disease, and the neglect of his contribution probably resulted from his early death. We have traced his life history from the few available records; as a boy, Kirkes was apprenticed to become a surgeon and only later trained as a physician. We place his contributions within the setting of the development during the 19th century of understanding of the relationship between the kidney, vascular disease, and high blood pressure.

Cardiomegaly↗
PubMed2000

Causes of end-stage renal failure in black patients starting renal replacement therapy.

In the United States, blacks are more frequently diagnosed than whites with end-stage renal failure (ESRF) from primary hypertension or diabetic nephropathy. We performed a validation retrospective case-note study of all blacks with ESRF who started renal replacement therapy (RRT) at three teaching hospitals in London, England, during 1991 to 1995 to investigate and validate the causes of primary renal disease using standard criteria. We identified 144 black patients with a mean age of 52.0 +/- 16.0 (SD) years; 59% were men and 32% had renal histological data. One hundred forty-four whites who were matched for age, sex, and onset of RRT (42% with renal histological data) underwent a similar validation exercise. Before the validation, the principal working diagnosis in the black patients had been diabetic nephropathy in 35% (89%, type 2; 11%, type 1); primary hypertension, 19%; glomerulonephritis (GN), 18%; and uncertain cause, 15%. After validation analysis, this changed to diabetes, 38% (16% biopsy proven); uncertain, 24%; GN, 20%; and primary hypertension, only 10% (28% biopsy proven). Among the uncertain cases (n = 34), 19 patients had hypertension, but this could not be established as the primary disease; 94% of all blacks had hypertension, accelerated in 21%. Among whites, only 3.5% had primary hypertension, and this proportion was not changed by the validation study. Type 2 diabetes is the most common single cause of ESRF in black patients in London, and although hypertension is more common and more severe in blacks, the proportion of renal failure attributed to primary hypertension is overestimated, and the diagnosis is often made using inadequate criteria.

Black or African American↗
PubMed2000

Effects of temperature and calcium availability on ventricular myocardium from rainbow trout.

We studied the mechanical and electrophysiological properties of ventricular myocardium from rainbow trout (Oncorhynchus mykiss) in vitro at 4, 10, and 18 degrees C from fish acclimated at 10 degrees C. Temperature alone did not significantly alter the contractile force of the myocardium, but the time to peak tension and time to 80% relaxation were prolonged at 4 degrees C and shortened at 18 degrees C. The duration of the action potential was also prolonged at 4 degrees C and progressively shortened at higher temperatures. An alteration of the stimulation frequency did not affect contraction amplitude at any temperature. Calcium influx via L-type calcium channels was increased by raising extracellular calcium concentration (¿Ca(2+)(o)) or including Bay K 8644 (Bay K) and isoproterenol in the bathing medium. These treatments significantly enhanced the contractile force at all temperatures. Calcium channel blockers had a reverse-negative inotropic effect. Unexpectedly, the duration of the action potential at 10 degrees C was shortened as ¿Ca(2+)(o) increased. However, Bay K prolonged the plateau phase at 4 degrees C. Caffeine, which promotes the release of sarcoplasmic reticulum (SR) calcium, increased contractile force eightfold at all three temperatures, but the SR blocker ryanodine was only inhibitory at 4 degrees C. Our results suggest that contractile force in ventricular myocardium from Oncorhynchus mykiss is primarily regulated by sarcolemmal calcium influx and that ventricular contractility is maintained during exposure to a wide range of temperatures.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2000

BK-Type K(Ca) channels in two parasympathetic cell types: differences in kinetic properties and developmental expression.

The intrinsic electrical properties of identified choroid and ciliary neurons of the chick ciliary ganglion were examined by patch-clamp recording methods. These neurons are derived from a common pool of mesencephalic neural crest precursor cells but innervate different target tissues and have markedly different action potential waveforms and intrinsic patterns of repetitive spike discharge. Therefore it is important to determine whether these cell types express different types of plasma membrane ionic channels, and to ascertain the developmental stages at which these cell types begin to diverge. This study has focused on large-conductance Ca(2+)-activated K(+) channels (K(Ca)), which are known to regulate spike waveform and repetitive firing in many cell types. Both ciliary ganglion cell types, identified on the basis of size and somatostatin immunoreactivity, express a robust macroscopic K(Ca) carried by a kinetically homogeneous population of large-conductance (BK-type) K(Ca) channels. However, the kinetic properties of these channels are different in the two cell types. Steady-state fluctuation analyses of macroscopic K(Ca) produced power spectra that could be fitted with a single Lorentzian curve in both cell types. However, the resulting corner frequency was significantly lower in choroid neurons than in ciliary neurons, suggesting that the underlying K(Ca) channels have a longer mean open-time in choroid neurons. Consistent with fluctuation analyses, significantly slower gating of K(Ca) channels in choroid neurons was also observed during macroscopic activation and deactivation at membrane potentials positive to -30 mV. Differences in the kinetic properties of K(Ca) channels could also be observed directly in single-channel recordings from identified embryonic day 13 choroid and ciliary neurons. The mean open-time of large-conductance K(Ca) channels was significantly greater in choroid neurons than in ciliary neurons in excised inside-out patches. The developmental expression of functional K(Ca) channels appears to be regulated differently in the two cell types. Although both cell types acquire functional K(Ca) at the same developmental stages (embryonic days 9-13), functional expression of these channels in ciliary neurons requires target-derived trophic factors. In contrast, expression of functional K(Ca) channels proceeds normally in choroid neurons developing in vitro in the absence of target-derived trophic factors. Consistent with this, extracts of ciliary neuron target tissues (striated muscle of the iris/ciliary body) contain K(Ca) stimulatory activity. However, K(Ca) stimulatory activity cannot be detected in extracts of the smooth muscle targets of choroid neurons.

Animals↗
PubMed1999

The ethics of organ transplantation reconsidered: paid organ donation and the use of executed prisoners as donors.

We examine the arguments for and against the practice of paid organ donation and the use of judicially executed prisoners as seen in a world context. Although Western opinion is almost universally against both practices, we seek to establish that this has arisen largely from justification of an initial revulsion against both and not from reasoned ethical debate. In examining the most commonly cited arguments against these practices, we demonstrate that this revulsion arises mainly from the abuses to which both processes have been subjected, rather than the acts themselves, together with opposition to a death penalty. At the moment and for some future time, in the absence or shortage of dialysis in large parts of the developing world, transplanted organs represent the only means of treating end-stage renal failure. Thus, a clear ethical conflict arises as to whether greater harm or good is done by allowing individuals to die or adopting strategies for obtaining organs that raise ethical problems. We call for continued reasoned ethical debate on both issues, rather than accepting that the argument is already over.

Cadaver↗
PubMed1999

The early introduction of percutaneous renal biopsy in Italy.

BACKGROUND: Percutaneous renal biopsy, based on the use of an aspiration needle and the patient in the sitting position, was first described by Iversen and Brun in 1951. In 1954, Kark and Muehrcke described the use of the cutting Vim-Silverman needle on patients in the prone position, with a substantial improvement in the rate of success. The 1961 CIBA Foundation Symposium on renal biopsy marked the coming of age of this technique. During the 1950s in Italy, several individuals played a part in promoting and developing percutaneous renal biopsy. Because this pioneer work has received insufficient attention, we describe the contributions of Italians to the early introduction of this technique. METHODS: The Italian and international literature about percutaneous renal biopsy of the period 1951 through 1965 was reviewed. In addition, structured interviews with surviving members of the Italian researchers who first used renal biopsy were conducted. RESULTS: The first renal biopsies in Italy were performed in 1951 in Pisa by the group of Ernico Fiaschi (1913-1989). In their hands, renal biopsy became a tool to investigate the pathogenesis of renal diseases in particular, while simultaneously using the early application of immunofluorescence and electron microscopy. In 1954, Pietro Leonardi (1914-1991) and Arturo Ruol (born 1924) introduced renal biopsy in Padova; they used this technique extensively and published one of the first monographs on the subject. In 1957, Vittorio Bonomini (born 1928) introduced renal biopsy in Bologna, and in subsequent years used this technique to focus on the study of pyelonephritis. CONCLUSIONS: Our historical research shows that Italian groups were among the first to use and develop percutaneous renal biopsy both as a clinical tool and an investigative tool. This article gives international credit to their work.

Biopsy, Needle↗
PubMed1999

European best practice guidelines for the management of anaemia in patients with chronic renal failure.

Best practice guidelines recommend management strategies and attempt to set standards for optimal patient care. The momentum towards formulating guidelines comes not only from health care professionals, but also from health care management organizations, who need some way of measuring the quality of the services they purchase. The European Best Practice Guidelines for the Management of Anaemia in Patients with Chronic Renal Failure have been drawn up by a Working Party including representatives of the European Renal Association/European Dialysis and Transplantation Association (ERA-EDTA) and the national nephrology societies of a cross-section of European countries. The guidelines draw on the National Kidney Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI) Clinical Best Practice Guidelines for the Treatment of Anemia in Chronic Renal Failure, but reflect European clinical practice and experience. They include additional publications, and new analysis and interpretation of the evidence base. Topics covered in the European guidelines include diagnosis of the anaemia of chronic renal failure, indications for starting treatment with epoetin, recommended minimum target haemoglobin concentrations, epoetin dosage and route of administration, assessing and optimizing iron stores, causes and management of epoetin resistance, and possible adverse effects of epoetin treatment. The guidelines are not intended to be prescriptive but rather to provide clinical guidance based on the best available evidence. The evidence supporting each guideline is graded, so that physicians may judge its reliability.

Anemia↗
PubMed1999

The very long-term prognosis and complications of lupus nephritis and its treatment.

Although the short- and medium-term (5-10 years) outcome of patients with lupus nephritis has been studied extensively, there are very few data on the second and subsequent decades. We studied outcome in 110 local patients investigated at a single centre before 1986, who all had potential follow-up of more than 10 years (actual 2-31 years, median 15.5 years). At last follow-up, 40 patients were dead and 70 alive, nine of whom were on maintenance dialysis or transplanted, actuarial survivals being 84%, 72%, 62%, 61% and 54% at 5, 10, 15, 20 and 25 years for the group as a whole. Survival was better in the cohort 1976-86 (n = 60) than in that from 1963-75 (n = 50) (90, 81 and 76% vs. 78, 56 and 43% at 5, 10 and 15 years, p < 0.001). Sepsis (12) and myocardial infarction (8) were the principal causes of death. Of living patients with renal function, 38% had normal urine and renal function, 11 were off all treatment (19%), 62% had persistent proteinuria and 18% had reduced but generally stable renal function. Renal failure, in those patients who developed it, occurred during the first decade and none of 67 patients actually followed more than 10 years subsequently went into renal failure. Induction treatment was with prednisolone, combined with azathioprine in more severe forms of nephritis, and from the middle 1970s to 1986, 30 with methylprednisolone and in 12 cases plasma exchange. Seventeen other patients were treated using oral cyclophosphamide during the 1960s. No patient received i.v. cyclophosphamide as induction therapy, although nine patients had this form of treatment later, largely because of non-compliance. Serious complications of lupus and/or its treatment occurred in 49%: sepsis in 32, ischaemic heart disease in 20, thrombosis in one and avascular necrosis of bone in eight. In contrast, fracturing osteoporosis occurred in only three, and cataracts requiring surgery and diabetes mellitus in none. The very long-term outlook of lupus nephritis, especially its more severe forms, has improved, but that with current management strategies only a minority of patients are able to stop treatment altogether, and the incidence of serious complications is high.

Adolescent↗