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Biomedical subjects

P Ackrill

Publications and source records attributed to P Ackrill.

At least 19 recordsLinked to original sources
PubMed1999

Long-hours home haemodialysis--the best renal replacement therapy method?

Two hundred and eighty-six patients (190 males and 96 females) with end-stage renal failure (ESRD) started haemodialysis (HD) at Withington Hospital between 1 January 1968 and 31 December 1986. Of these, 152 (53.1%) were successfully transplanted, while 134 had only HD or one transplant lasting < 3 months (i.e. total HD interruption < 3 months). For the whole group, the probabilities of being alive on long-hours home HD at 10 and 20 years were 58.7% and 33.2%, respectively. Mean gross mortality 1968-1986 was 6.5 +/- 3.2% per year. The main causes of death were cardiovascular (36.6%), infection-related (19.2%) and malignancy (9.6%). Males and younger cohorts had a significantly (p < 0.05) higher probability of being alive on long-hours home HD than did females and older cohorts. Eighty-two patients (29% of the total group) survived more than 10 years, of whom 54 were still alive at 1 January 1996: 44 continuing on HD while the other ten had been successfully transplanted. In these 54 patients, mean 24-h ambulatory blood pressure recorded at the date of the study was 117.6/68.9 mmHg; mean BP for the last 5 years on HD was 136.4/81.2 mmHg. Only four (7.4%) were regularly taking antihypertensive medication. Left ventricular hypertrophy (LVH) (by ECG) was present in 64.8% of the 54 patients; its prevalence by echocardiography (LVM index > 130 g/m2 for men and > 110 g/m2 for women) was 77.5%. Only 10 (18.5%) had symptoms or clinical signs of ischaemic heart disease and/or peripheral vascular disease. None had cardiac failure symptoms NYHA class 3-4. Our data show a low incidence of all-cause and cardiovascular mortality, confirming those from the Tassin unit in France, and make a medical case for extended haemodialysis treatment hours.

Adolescent↗
PubMed1998

Kinetics of uptake and elimination of silicic acid by a human subject: a novel application of 32Si and accelerator mass spectrometry.

Silicon is possibly important in human physiology in protecting against the toxic effects of aluminium, but the kinetics of uptake and excretion of silicic acid, the bioavailable form, are not well characterised. We have used 32Si as a tracer in a human uptake experiment to determine a gastrointestinal uptake factor for silicic acid, and to elucidate the kinetics of renal elimination. Urine collections were made for extending intervals from 2 to 12 h over 2 days following ingestion by a single human subject of a neutral silicic acid solution containing tracer levels of 32Si (t1/2 approximately 150 y). Silicon was isolated as SiO2 and the 32Si content determined by accelerator mass spectrometry (AMS), using a gas-filled magnet technique to eliminate a prolific isobaric interference from 32S. Silicon uptake appears to have been essentially complete within 2 h of ingestion. Elimination occurred by two simultaneous first-order processes with half-lives of 2.7 and 11.3 h, representing around 90% and 10%, respectively, of the total output. The rapidly eliminated 32Si was probably retained in the extracellular fluid volume, whilst the slower component may represent intracellular uptake and release. Elimination of absorbed 32Si was essentially complete after 48 h and was equivalent to 36% of the ingested dose. This establishes only a lower limit for gastrointestinal absorption as, although there was no evidence for longer term retention of additional 32Si, the possibility could not be excluded by these results.

Administration, Oral↗
PubMed1998

Result of angioplasty of brescia-cimino haemodialysis fistulae: medium-term follow-up.

AIM: To determine the results of transluminal angioplasty in patients with Brescia-Cimino arteriovenous fistulae. PATIENTS AND METHODS: Thirty-one patients underwent transluminal angioplasty of 36 stenotic lesions related to Brescia-Cimino arteriovenous fistulae over a 5-year period. The lesions treated were characterized by review of pre-angioplasty fistulograms. Medical and radiological records were reviewed to assess medium-term patency of each patient's fistula. RESULTS: Angioplasty was performed successfully in 28 out of 31 patients initially (90% technical success rate). Duration of follow-up for the 31 patients ranged from 4 to 65 months (median = 34 months). At 6 months, seven patients required further surgical or endovascular intervention (18 patients remained event-free) and at 1 year, 10 patients required further endovascular or surgical intervention (14 patients remained event-free). Life-table analysis revealed primary patency rates of 77%, 64% and 39% at 6 months, 1 year and 2 years, respectively. At 6 months and 1 year, four and five patients, respectively, required surgical revision or closure of fistula. Secondary patency rates were 85%, 81% and 65% at 6 months, 1 year and 2 years, respectively. All patients with a primary patency at 2 years remained event-free during the follow-up period. CONCLUSIONS: Transluminal angioplasty is an effective treatment for stenoses developed in relation to Brescia-Cimino haemodialysis fistulae. Further endovascular procedures may be required, especially in the first 24 months, to preserve patency. These techniques extend the lifetime of fistulae, thereby preserving proximal venous access sites for future use. Our result is in broad agreement with results from other series.

Angioplasty, Balloon↗
PubMed1998

The treatment of nephrotic syndrome caused by primary (light chain) amyloid with vincristine, doxorubicin and dexamethasone.

Three out of four patients with primary (light chain) amyloid nephrotic syndrome treated with vincristine, doxorubicin and dexamethasone (VAD) induction obtained a partial response and are alive in continuing remission at 4.1, 6.5 and 9.3 years. These preliminary results are of considerable interest and suggest that prospective evaluation of this regimen is warranted in patients with this condition.

Aged↗
PubMed1998

Urea kinetic modelling--are any of the 'bedside' Kt/V formulae reliable enough?

BACKGROUND: Longevity on dialysis is determined by many factors. One of these has increasingly been seen to be 'dialysis dose'. There are several methods for calculating dialysis dose. We wanted prospectively to test 'gold-standard' UKM-Kt/V with various shortcut bedside formulae, to see whether reliance on the latter approach was likely to lead to errors in over- or underprescribing dialysis regimens. METHODS: Ten bedside formulae for the calculation of Kt/V (urea) were compared with UKM Kt/V values, in a month-long study involving 507 dialysis sessions in 50 patients in a single-centre in-patient haemodialysis unit. RESULTS: For patients with UKM Kt/V<0.8 (median 0.69, n=140), simplified formulae had a difference (delta) of 0.094-0.396 from the calculated UKM resulting in an inter-method variability ranging from 13 to 57%. The least difference was seen with the Calzavara formula (P=NS), maximum difference with the Barth formulae (P<0.05). No statistically significant differences were seen when comparing Daugirdas 1 and 2 and Keshaviah formulae with UKM, for patients with UKM Kt/V<0.8. For patients with UKM Kt/V in the range 0.8-1.4 (median 1.06, n=285) the extreme recorded values from simplified formulae were 0.012 (least different) and 0.245 (most different) from the UKM mean, with an inter-method variability ranging between 1.1% (Basile method) to 23.1% (Calzavara). No statistically significant difference were seen when comparing Daugirdas 1 and 2, Keshaviah, and Lowrie formulae with UKM, for patients with UKM Kt/V 0.8-1.4. For patients with the highest UKM Kt/V values (>1.4; median 1.58, n=72), all simplified formulae gave Kt/V values lower than UKM Kt/V: the minimum difference was 0.070 using Jindal (P=NS, intermethod variability of 4.4%), while the maximum was seen when using Calzavara (P<0.05; difference = 0.69; intermethod variability of 43.7%). There was also no statistically significant difference for Basile and Kerr methods. For the group as a whole the biggest difference from UKM mean values was obtained using Barth's and Calzavara's formulae (delta of 0.171 and 0.140 respectively (P<0.05)). CONCLUSIONS: The best correlations were seen with the Daugirdas 2 formula (r2=0.953). Also, comparing grouped formulae containing ln(Co/Ct) terms with those incorporating the (Co-Ct)/Co ratio (i.e. the urea reduction) there was a better correlation for all formulae employing the logarithmic transformation (r2=0.951-0.953 cf. r2=0.939-0.940). Nevertheless no bedside formula had the accuracy of UKM-Kt/V.

Adult↗
PubMed1997

Ambulatory blood pressure monitoring in renal dialysis and transplant patients.

Blood pressure (BP) elevation and left ventricular hypertrophy are important factors in the high cardiovascular mortality rate in patients on the renal replacement program. Ambulatory BP monitoring is widely regarded as superior to random BP monitoring in predicting end-organ damage from elevated BP. One hundred seventeen patients (60 on hemodialysis [35 with long sessions and 25 with short sessions], 29 on continuous ambulatory peritoneal dialysis, and 28 transplant recipients) underwent ambulatory BP monitoring, with target organ assessment by electrocardiography. Mean 24-hour BP for the patients with the long hemodialysis sessions (LHD) was 115.5/66.6 mm Hg, without the regular use of antihypertensive drugs. The parathormone (PTH) level was the major determinant of BP on ambulatory BP monitoring analysis, with interdialytic weight gain and age each having weaker associations. The BPs of the other three patient cohorts were much higher (short hemodialysis session [SHD], 143.2/82.1 mm Hg; continuous ambulatory peritoneal dialysis, 137.1/76.8 mm Hg; transplant recipients, 135.9/79.2 mm Hg). Overall, two thirds of the patients had reduced diurnal BP variability. Electrocardiogram voltage criteria for left ventricular hypertrophy were exceeded in approximately one third to one half of the patients. Our findings show that good control of BP is possible without recourse to antihypertensive drugs in the context of dialysis with slow ultrafiltration.

Blood Pressure↗
PubMed1997

Vascular calcification in long-term haemodialysis patients in a single unit: a retrospective analysis.

Vascular calcification (VC), which is described in the elderly and in diabetics, is frequently seen in uraemia. It is usually regarded as having little significance. We studied the roentgenological appearance of VC in a homogeneous group of 38 long-hours haemodialysis patients whose longevity on dialysis allowed sustained (10-25 years) follow-up, including annual skeletal surveys and thrice-yearly clinical examinations and biochemical profiles. We compiled a dossier of clinical and laboratory parameters from the start of dialysis to the present day. We were able to analyze the natural history of VC and to determine which clinical parameters were linked with progression. We found that VC became steadily more prevalent-at dialysis onset present in 39% of the patients, but in 92% after an average dialysis duration of 16 years, with a mean onset 9.7 years after starting dialysis. As well as becoming more prevalent, the calcification became progressively more severe in most patients. There were two patterns of VC: axial (aorta and iliac and femoral arteries), seen alone in 32% of the patients, and peripheral (digital arteries), seen alone in 3% of patients. Most patients (65%) had evidence of both types. Calcification was scored for site and severity. Patient age (r = 0.57, p < 0.001), systolic blood pressure (r = 0.54, p < 0.001), hyperparathyroidism (reduced progression after parathyroidectomy), plasma phosphate (r = 0.34, p = 0.042), and vitamin D concentrations (r = 0.53, p < 0.001) were the principal determinants of severity and rate of progression of VC in this population. There was a weak negative association between progression and serum ferritin (r = -0.33, p = 0.046). The reduced vessel compliance that results from VC is likely to be cardiovascularly deleterious. In severe cases, tissue perfusion or vascular access for haemodialysis can be compromised. VC and accelerated cardiovascular mortality are common to uraemia, diabetes, and systolic hypertension in the elderly. Better understanding of these pathological processes may permit intervention and possibly lead to a reduction in cardiovascular mortality.

Calcinosis↗
PubMed1996

Prevention and treatment of aluminum toxicity including chelation therapy: status and research needs.

The prevention and treatment of aluminum (Al) accumulation and toxicity are reviewed. Recommendations to further our understanding of desferrioxamine (deferoxamine, DFO) treatment and to develop more effective chelation approaches are provided. Reduction of Al accumulation and toxicity may benefit end-stage renal disease (ESRD) patients and perhaps those suffering from specific neurodegenerative disorders as well as workers with Al-induced neurocognitive disorders. The clearance of Al may be increased by extracorporeal chelation, renal transplantation, perhaps complexation with simple ligands such as silicon (Si), and systemic chelation therapy. The abilities of extracorporeal chelation and Si to reduce Al accumulation require further evaluation. Although it may not be possible to design Al-specific chelators, chelators with greater Al selectivity are desired. Aluminum-selective chelation might be achieved by targeted chelator distribution or by the use of adjuvants with the chelator. The ability of carboxylic acids to facilitate Al elimination, under specific conditions, warrants further study. Desferrioxamine does not produce significant biliary Al excretion. A chelator with this property may be useful in ESRD patients. The necessity for an Al chelator to distribute extravascularly to be effective is unknown and should be determined to guide the selection of alternatives to DFO. The lack of oral efficacy and occasional side effects of DFO encourage identification of orally effective, safer Al chelators. The bidentate 3-hydroxypyridin-4-ones are currently the most encouraging alternatives to DFO. They have been shown to increase urinary Al excretion in rats and rabbits, but to have toxicity comparable to, or greater than, DFO. Their toxicity may relate to incomplete metal complexation. The ability of orally effective chelators to increase absorption of chelated metal from the gastrointestinal (Gl) tract needs to be evaluated. Orally effective, safe Al chelators would be of benefit to peritoneal dialysis patients and those with neurodegenerative disorders, if Al chelation therapy is indicated. The reduction of Alzheimer's disease (AD) progression and the reversal of Al-induced behavioral deficits and neurofibrillary tangles by DFO encourage further study of Al chelation therapy for selected neurodegenerative disorders.

Aluminum↗
PubMed1996

Cyclosporin A and multiple fibroadenomas of the breast.

Multiple bilateral fibroadenomas are uncommon. This finding in four women who had received renal transplants prompted further inquiry. A prospective study was performed on 39 women under the age of 55 years who had received a renal transplant at least 1 year earlier. Clinical examination and breast ultrasonography were performed. Factors considered included immunosuppressive therapy, concurrent medication and renal function. Blood was taken for estimation of oestradiol, prolactin, follicle-stimulating hormone (FSH) and sex hormone binding globulin levels. Fibroadenomas were found in 13 of 29 women who had received cyclosporin A: multiple in ten and bilateral in five. No abnormal breast findings were seen in 10 patients immunosuppressed with steroids and azathioprine alone (chi 2 = 7.30, 1 d.f., P < 0.01). Serum oestradiol concentration was raised in women with fibroadenomas compared with that in those with normal breasts (P < 0.05) and the level of FSH was lower (P < 0.01). Cyclosporin A may act on breast fibroblasts by humoral mechanisms and direct action.

Adult↗
PubMed1996

Blood pressure reduction after parathyroidectomy for secondary hyperparathyroidism: further evidence implicating calcium homeostasis in blood pressure regulation.

A link between plasma calcium, dietary cations, and blood pressure has been suspected for some time, with human, experimental animal, and epidemiological data adduced to support this hypothesis. We identified 21 patients receiving regular maintenance hemodialysis, but not receiving any regular antihypertensive treatment, who had undergone 22 surgical removals of the parathyroid glands in the period 1978 to 1992. These patients' records were then scrutinized. The group preparathyroidectomy mean systolic blood pressure (BP) was 142.6 +/- 19.4 mm Hg. After the operation, the mean systolic BP was 133.6 +/- 21.9 mm Hg (P = 0.004). Plasma calcium decreased from 2.72 +/- 0.18 mmol/L to 2.52 +/- 0.19 mmol/L (P < 0.001). There was a correlation between the decreases in systolic blood pressure (SBP) (9.4%) and plasma calcium (7.3%); r = 0.60, P = 0.012. The decrease in SBP was not immediate, but delayed some months and complete by approximately 9 months after the operation. Furthermore, using ambulatory BP monitoring in a group of long-term hemodialysis patients, we found that parathyroidectomized patients had lower BP and pulse rates than those with intact parathyroid glands (SBP, 122.9 +/- 16.3 mm Hg v 102.9 +/- 9.9 mm Hg; pulse rates, 87.5 +/- 12.7 v 72.0 +/- 7.5 beats/min, P < .001, nonparathyroidectomy v postparathyroidectomy, both comparisons). These data support a link between plasma calcium and BP in patients receiving maintenance hemodialysis.

Adult↗
PubMed1996

Treating paracetamol overdose by charcoal haemoperfusion and long-hours high-flux dialysis.

After serious paracetamol overdose, charcoal haemoperfusion was used to remove paracetamol from the circulation, aiming to reduce the severity of subsequent hepatic damage. Daily long-hours high-flux dialysis was given to patients with grade III-IV hepatic encephalopathy, and also to those at risk of developing encephalopathy. We reviewed patients treated in this manner who had not received N-acetylcysteine within the first 15 h after overdose. From January 1983 to January 1993, 73 patients with serious paracetamol overdose were seen, of whom 51 received charcoal haemoperfusion and/or high-flux dialysis. Patients who were admitted within the first 42 h after overdose and who received haemoperfusion and/or dialysis had significantly lower peak levels of prothrombin time, bilirubin and creatinine than those who were admitted after 42 h. Mortality was also lower amongst patients admitted before 42 h, at 2/18 (11%) vs. 15/33 (45%), p < 0.05.

Acetaminophen↗
PubMed1996

Vasculitis and rapidly progressive glomerulonephritis in the elderly.

The proportion of patients with vasculitis and rapidly progressive nephritis aged 70 years or over has risen from about 10% in the 1980s to over 30% in series reported in the 1990s. This study was undertaken to examine the presentation and outcome of such older patients. Seventeen of 56 patients (30%) who presented at two renal units were aged 70 years or over. Mean creatinine level at presentation was 530 mumol/l, and five patients received dialysis at presentation. Outcome was dependent on three factors, namely comorbid pathology, response to immunosuppressive therapy, and the occurrence in three cases of temporary spontaneous partial remission. Overall patient survival at one and two years was 62.5% and 50%, respectively, and 90% and 100% of surviving patients were independent of dialysis at one and two years, respectively. Response to chemotherapy was excellent, with full rehabilitation in many cases and no deaths directly attributable to adverse effects of immunosuppressive therapy. We conclude that diagnosis of vasculitis and rapidly progressive glomerulonephritis by renal biopsy and the subsequent administration of chemotherapy (including cyclophosphamide in many cases) resulted in a worthwhile benefit in these elderly patients.

Aged↗
PubMed1996

Echocardiographic findings in long-term, long-hour hemodialysis patients.

This article describes the echocardiographic structural and functional findings in a cohort of 30 patients on ten or more years of uninterrupted long-hour (24 hours per week dialysis schedule) hemodialysis (mean duration 187.7 months, range 120 to 299 months). Cardiac structural analysis was remarkable for the prevalence of LVH (76%), very rarely asymmetric (3%). Hemoglobin and (log) plasma renin activity were determinants of the LV wall thickness ratio (r = -0.57 and 0.54, p = 0.003 and 0.044 respectively). Markers of systolic contractile function were frequently normal (100% MVCFS; 85% FSI). Diastolic ventricular compliance was abnormal in 59% of patients. Blood pressure history appeared important in determining LVH, but office/ABPM measures of BP were not. Patients after parathyroidectomy (PTx) had a smaller LVPWTN (8.68 mm/m2 without PTx cf 7.01 mm/m2 after PTx, p = 0.036). Left ventricular cavity size was rarely enlarged (10%), with hemoglobin (r = -0.47, p = 0.012) and PTH (r = -0.65, p < 0.001) the major determinants of EDDN. Left atrial diameter was increased in 77% of patients. Cardiac valvular calcification was seen in 50% of patients. Our findings show that despite good BP control without recourse to antihypertensive drugs, LVH with good LV systolic function is very common in these long-survivors.

Aortic Valve↗
PubMed1995

Severe theophylline poisoning: charcoal haemoperfusion or haemodialysis?

Theophylline poisoning with a blood level of 183 mg/l in a 38-year-old man was treated with activated charcoal by mouth, but despite this the blood level of theophylline rose and there was circulatory collapse with rhabdomyolysis, acute renal failure and hyperthermia. Treatment with charcoal haemoperfusion and simultaneous haemodialysis was given, followed by continuous arteriovenous haemodialysis (CAVHD). Mean extraction rates of theophylline were 26% during CAVHD, and 86% during combined dialysis and charcoal haemoperfusion. During combined treatment, the mean extraction rate of haemodialysis was 62%, compared with 48% for charcoal haemoperfusion. In summary, activated charcoal given by mouth may be unable to prevent a rise in blood levels and the development of complications after substantial theophylline overdose. If theophylline is to be removed from the blood, a combination of charcoal haemoperfusion and haemodialysis will give the best clearance, but haemodialysis alone may be effective.

Adult↗