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Biomedical subjects

L W Fleming

Publications and source records attributed to L W Fleming.

At least 19 recordsLinked to original sources

Limb amputation on renal replacement therapy.

Ten (10) diabetic and 7 non-diabetic patients on renal replacement therapy have undergone limb amputation in the authors' unit in the 1988 to 1996 period. The article examines the course of illness and survival patterns in this distinct and increasing sub-set in the amputee population. Rehabilitation and survival were significantly better in the diabetic group and it is recommended that it would be helpful for both prognosis and analysis if the sub-set of amputees on treatment for chronic renal failure is further divided into diabetic and non-diabetic sub-sets.

Aged↗

A medical bouquet. Poppies, cinchona and willow.

The poppy, the cinchona tree and the willow tree have all provided medicines of undoubted value during past millennium and form a "medical bouquet" worthy of consideration as this century ends. The use of these plants by ancient peoples has gradually evolved into a more informed understanding and application of the compounds initially isolated and purified from their extracts. There has been a Scottish contribution to the medical history of all three plants.

Benzyl Alcohols↗

Survival on renal replacement therapy in Europe: is there a 'centre effect'?

OBJECTIVE: Survival is the ultimate outcome measure in renal replacement therapy (RRT) and may be used to compare performance among centres. Such comparison, however, is meaningless if the influences of comorbidity, age and early deaths are not considered. We therefore studied survival rates on RRT in seven centres in Europe after taking into account the influence of age, early deaths, primary renal diagnoses, and comorbidity. DESIGN: A retrospective survival analysis was carried out on 1407 patients who commenced RRT in seven centres across five European countries during a 7-year period. Patients were stratified into low-, medium- and high-risk groups based mainly on comorbidity and to a lesser extent on age at commencement of RRT. Kaplan-Meier survival and Cox's proportional hazards model were used to compare survival. RESULTS: Before risk stratification overall 2-year survival across the seven centres ranged from 60.2 to 85.3% (69.3-89.9%) after excluding early deaths) masking a range of survivals of 27.4% for the high-risk group with the worst survival to 100% in the low-risk group with the best survival. After excluding early deaths 2-year survival in the low risk groups (n=622) was greater than 90% in all centres. Multivariate analysis showed that the mortality risk increased four fold from low- to medium- and a further 1.6-fold from medium- to high-risk group. However, despite this adjustment for comorbidity and age there still remained a significant difference in survival among some centres, i.e. a 'centre effect' which ranked the centres. CONCLUSION: Risk stratification diminishes the variance in survival between centres but a centre effect remains despite adjusting for age and comorbidity. Multicentre prospective studies are urgently required to identify the reasons for this apparent centre effect.

Adult↗

The Röntgen centenary.

One hundred years ago in November 1895, when Wilhelm Conrad Rontgen discovered X-rays, a new scientific age began which has dominated our own century. Rontgen himself was one of the late 19th century physicists involved in the exciting investigations opening up at that time into the possibilities which electrical applications were creating. To understand the significance of Rontgen's discovery, it is helpful to look at the years preceding his discovery and the context within which his work took place.

Germany↗

Erythropoietin response and route of administration.

The effect of route of erythropoietin (EPO) administration was assessed in sixteen hemodialysis patients who completed a randomised crossover study of thrice weekly subcutaneous (SC) and intravenous (IV) erythropoietin with an EPO-free washout period separating the two phases of treatment. Route of EPO administration had no significant effect on absolute reticulocyte counts, and change in hemoglobin (Hb) during the first six weeks of therapy, at a constant EPO dose (120 iu/kg/week). Similarly, there was no significant difference in EPO dose requirement between the two routes, both during and after correction of anemia, and after maintenance of target Hb (10-12 g/dl) for an eight-week period (end of maintenance period dose; median [range]; SC EPO: 120 [30-367] iu/kg/week, IV EPO: 124.5 [37-377] iu/kg/week). Following EPO withdrawal, Hb fell at a rate of 0.38 (0.14-0.69) g/dl/week. Route of EPO administration did not influence the incidence of thrombotic and hypertensive side effects, or increases in dialysis heparin requirement and albumin, and decreases in ferritin, alpha-1-antitrypsin and ceruloplasmin during the study period. In conclusion, thrice weekly SC and IV EPO are comparable in terms of efficacy and safety.

Adult↗

Influence of coexisting disease on survival on renal-replacement therapy.

Survival of patients on renal-replacement therapy (RRT) is no longer improving. Increasingly, such patients are older and have co-morbid conditions affecting organs other than the kidney. In a retrospective study, we calculated actuarial survival of 375 patients starting RRT during a 6 1/2 year period at renal units in Aberdeen and Dundee, UK, after stratification of patients into three risk groups (low, medium, and high) based predominantly on co-morbidity and to a lesser extent on age. 2-year survival differed significantly between low, medium, and high risk groups both before (86%, 60%, and 35%, respectively; p < 0.002 for all comparisons) and after (90%, 70%, 46%; p < 0.004 for all comparisons) excluding early deaths (within 90 days of starting RRT). Overall survival was 61% in Aberdeen and 68% in Dundee (p = 0.04), but 73% and 74%, respectively, when deaths in the first 90 days were excluded (p = 0.73). We conclude that RRT is a highly successful treatment (86% 2-year survival) for patients aged under 70 with no co-morbid conditions (low-risk group); that coexisting non-renal disease has an important influence on survival of patients on RRT; and that risk stratification and analysis of data including and excluding early deaths should allow more valid comparison of data from different centres.

Adolescent↗

Urine transparency as an index of absence of infection.

A visual assessment of the clarity of urine was used as an exclusion test to indicate the absence of infection; verified by dipslide culture, it was applied to 363 urine samples collected from patients attending 2 adult nephrology clinics over a period of 6 months. The crimped aluminium bowl used for collection of samples assisted the assessment of clarity. The sensitivity of the method compared with dipslide culture was 73%, with specificity and efficiecy both 58%. The predictive value of a negative test (clarity) was 97% with a false negative rate of 3%, enabling this simple examination to be used as an exclusion test for further testing. In simple terms, a clear urine is unlikely to be infected. It is also an advantage to have an immediate indicator of the absence of infection available at the clinic. Analysis of only those urines assessed as cloudy could result in financial savings and, from the clinics, a 56% reduction in workload.

Adolescent↗

Dextran antibodies, complement conversion and circulating immune complexes after intravenous iron dextran therapy in dialysed patients.

Serum immune complexes, plasma dextran antibodies and percentage conversion of complement have been measured in 20 dialysed patients before and after an intravenous infusion of iron dextran providing 600 mg elemental iron. Complement conversion was unmeasurable and there were no changes in circulating immune complexes. The presence of dextran antibodies in nine patients before the infusion was not related to prior exposure to iron dextran. They became undetectable in these patients within hours after the infusion, reappearing 1 month later in three. Two of three patients reporting mild aches and shivers on the day following the infusion had no detectable dextran antibodies. An adverse reaction involving inflamed joints occurred 1-2 days after a second infusion given to one of the patients studied above. The parameters under study were again measured and did not appear to relate to the reaction. The presence of dextran antibodies does not preclude the giving of iron dextran to patients on dialysis, and the immune complex and complement systems remain undisturbed by iron dextran infusions.

Adolescent↗

Aluminium content of water for injection used with recombinant human erythropoietin.

Human recombinant erythropoietin is of proven value in the treatment of the anaemia of renal failure. The aluminium content of 36 ampoules of water for injection supplied for use with recombinant erythropoietin has been measured and ranged from 24 to 450 micrograms/l, with a median of 251 micrograms/l. In three samples, which may have been contaminated on opening, the range was from 1770 to 6160 micrograms/l. In Water for Injection BP, values ranged from 66 to 140 micrograms/l with a median of 99 micrograms/l. Reconstituted erythropoietin did not contain any more aluminium than could be accounted for by the water. Ampoules of a second brand of erythropoietin, supplied already in solution, contained from 506 to 837 micrograms/l aluminium (median 682 micrograms/l). In view of the lifelong duration of erythropoietin therapy clinicians and pharmaceutical companies should be aware of this potential problem. Although the amount of aluminium delivered with each injection is usually less than 4 micrograms, it is suggested that active steps are taken to establish a British Pharmacopoeia limit on the aluminium content of injections.

Aluminum↗

Oral ciprofloxacin in the treatment of peritonitis in patients on continuous ambulatory peritoneal dialysis.

Oral ciprofloxacin in doses of 0.75 to 2 g daily for 8-16 (median 10) days was given as first-line treatment of 33 unselected episodes of CAPD-associated peritonitis in 20 patients. Treatment was well tolerated and effective, curing 25 episodes. Treatment was withdrawn in five episodes, four because of resistant organisms and in the other because of vomiting. Infection relapsed twice in one patient during follow-up and one patient had persistence of the infecting organism (Pseudomonas aeruginosa) despite clinical improvement. Plasma and dialysate ciprofloxacin levels ranged from 1 to 8 mg/l. Assay between days 2 and 4 of treatment indicated the ciprofloxacin steady state concentration. If this proves to be greater than 7 mg/l the dose may be reduced and if less than 2 mg/l the dose should be increased. Overall a single course of oral ciprofloxacin was 76% successful as a first-line treatment for CAPD-associated peritonitis, caused by a wide range of organisms.

Administration, Oral↗

Hepatic iron in dialysed patients given intravenous iron dextran.

Five percutaneous biopsy and 17 necropsy liver specimens were analysed histologically and chemically for iron content in 22 patients receiving dialysis for chronic renal failure, 13 of whom were given intravenous iron-dextran. Brissot scores for assessing histological hepatic iron deposition and chemically measured liver iron concentrations correlated closely. Both variables depended on total cumulative dose of iron, and to a lesser extent, on time since the last dose. Fibrosis (seen in five patients) was minimal and non-specific. Electron microscopic examination showed that there was no generalised damage and confirmed the presence of iron in the hepatocytes in the form of ferritin. High liver iron concentrations, in excess of 1000 micrograms/100 mg dry weight, were seen in two patients. Four others given comparable cumulated amounts (18-23 g iron) did not have such high concentrations. Plasma ferritin concentrations were high in eight patients, some with and some without fibrosis. The risk of temporarily high iron deposition in the liver causing damage seemed to be minimal when weighed against the benefit of increased haemoglobin in most of the patients. Intravenous iron treatment merits further evaluation, particularly with the advent of erythropoietin treatment, which requires continuously available iron.

Adult↗

Chemical reactivity of aluminium-based pharmaceutical compounds used as phosphate-binders.

Several aluminium-containing substances, including antacids used as phosphate-binders in treating renal failure, have been analysed in-vitro under different pH conditions for the release of Al3+ ions and for binding of phosphate. Control experiments on different forms of pure aluminium hydroxide validated the methods. At pH 2 it was the most amorphous forms which released Al3+ most rapidly. These aluminium ions, available for absorption by the patient, were released from all antacids tested, but no firm phosphate-binding was detected while the pH remained at 2. Phosphate was bound at pH 8, by adsorption onto the surface of aluminium hydroxide. No significant amounts of free Al3+ exist in solution at pH 8, since at that pH aluminium hydroxide is precipitated. The most amorphous forms of this solid were the most efficient phosphate-binders. Alumino-silicate salts require prior exposure to acid to produce free Al3+ before they can act as phosphate-binders, whereas amorphous aluminium hydroxide acts as an efficient phosphate-binder without prior exposure to acid. Chemical principles are employed to show why aluminium release and phosphate-binding are separate and independent processes. Methods are proposed for maximizing the activity of phosphate- binders in-vivo, while minimising aluminium release.

Aluminum↗