Showing papers by "Leicester General Hospital published in 1984"

Pharmacokinetics of single-dose i.v.morphine in normal volunteers and patients with end-stage renal failure

Abstract: Morphine 0.125 mg kg-1 was administered i.v. to 11 normal subjects and nine patients with chronic renal failure requiring regular haemodialysis. Plasma morphine concentrations were measured using high pressure liquid chromatography (HPLC). Although there was considerable individual variation in both groups, mean plasma concentrations of morphine were significantly higher in the patients with renal failure for 15 min after administration. The decay of plasma concentration fitted a three-compartment mamillary pharmacokinetic model in all subjects. Derived values (mean +/- SEM) of T 1/2 alpha, volume of distribution of the second compartment (V2), total volume of distribution at steady state (Vss) and transfer rate constant from the first to the second compartment (k12), were significantly different between groups. Mean values of terminal elimination half-life (T 1/2 gamma) and total body clearance were similar in the two groups. It was concluded that elimination of unchanged morphine is not impaired significantly in patients with chronic renal failure, although accumulation of morphine-3-glucuronide probably occurs. Although the pharmacological effect of morphine is not related temporally to plasma morphine concentrations, the higher values in patients with renal failure may be implicated in their increased sensitivity to the drug.

Pseudo-lymphoma associated with carbamazepine.

Abstract: An unusually severe adverse reaction to carbamazepine is described, in which the patient developed features suggestive of a lymphoma. A pseudo-lymphoma syndrome has been well documented with phenytoin (Saltzstein & Ackerman, 1959). However, to date there has only been one report of this complication with carbamazepine (Taylor, Smith & Hern, 1981), although this drug has been in wide clinical use for many years. We are therefore reporting a patient who developed an illness with features suggestive of a lymphoma whilst taking carbamazepine.

The effect of ageing on the response to frusemide in normal subjects

Abstract: The effect of IV frusemide was studied in six healthy young (mean age 26.5 years, range 21–33) and six healthy old (mean age 72.8 years, range 66–80) volunteers. A 24-h urine collection before frusemide showed no difference in volume and sodium excretion, although the old excreted less potassium. Creatinine clearance was significantly reduced in the older subjects. After frusemide, 20 mg IV, the pattern of sodium and water excretion over a 5-h period was different in the two groups. The peak effect was greater in the young and occurred within the first 30 min, but was delayed to between 30 and 60 min in the old. Thus in the young the time for 50% of the total sodium and water to be excreted was half that in the old. This delay in sodium and water excretion was related to baseline creatinine clearance. However, the total water, sodium and potassium excreted in the 5 h after frusemide did not differ in the two groups. These results suggest that the renal effects of frusemide are different in healthy elderly subjects as compared to the young. The delayed and reduced peak response is consistent with fewer nephrons in the elderly kidney.

Haemodynamics of the adjunctive arteriovenous fistula in femorodistal bypass grafting: an experimental study

Abstract: The results of femorotibial bypass for limb salvage vary a great deal. One of the reasons for this might be the discrepancy between potential inflow and run-off into the foot. An arteriovenous fistula at the distal graft anastomosis may improve results but the best anatomical arrangement for the fistula is unknown. Ileofemoral grafts were performed in dogs after the hind limb was rendered ischaemic. The distal end of the graft was anastomosed proximal to, superimposed upon, or distal to an arteriovenous fistula between the femoral artery and its accompanying femoral vein. The effect of the fistula on graft/run-off haemodynamics was then measured. The adjunctive arteriovenous fistula increased inflow by a mean of 900 per cent and reduced systemic pressure by 10 per cent. Peripheral resistance was reduced by 85 per cent. Distal arterial run-off was maximized with respect to total graft flow when the graft was placed distal to the fistula (P less than 0.05). The venous steal of flow and perfusion pressure produced by the fistula was minimized with the same configuration compared to the two other arrangements (P less than 0.01 and P less than 0.05). Placement of the graft distal to the adjunctive arteriovenous fistula maximized distal arterial flow and pressure, and significantly increased graft flow.

Protein Losses in Con Tinuous Ambulatory and Continuous Cyclic Peritoneal Dialysis (CAPD and CCPD)

Abstract: Initially, daily protein losses in patients on acute or chronic intermittent peritoneal dialysis has varied from 25 to more than 200 9 per dialysis ( 1-3). In 1978 Popovich et al reported daily losses of bet ween 12 and 18.9 9 (4) and other authors found regular losses of approximately 10 9 per day (5, 6). In 1981 in two surveys Blumenkrantz (7,8) described daily losses of 8.8 and 9.4 9 respectively. In contrast Katirtzoglou et al (9) calculated that the daily loss on four exchanges per day was 5.69 g in patients who had never had peritonitis, and 9.7 g per day in those who had at least one episode of peritonitis within the previous three months. They found no significant difference with the various dialysate dextrose concentrations but significant differences with variations in duration of dwell period. This letter reports results of a metabolic study in which we compared CAPD and CCPD patients in several aspects. The daily protein losses in the CAPD group (10 patients: three with peritonitis, four exchanges; 1.36% (3 x 2L Dextrose), 3.86% (1 x 2L Dextrose) were 5.92 ± 0.71 g (SEM), (range: 3.27 10.69 g). When the values were calculated with reference to dwell time and glucose concentration, the figures were similar (5.49 ± 0.44 g/day). We excluded from the study patients who had had an episode of peritonitis in the previous month. Proteins, when analyzed by two different chemical methods -semi-automatic colorimetric method (10), and by standard Biuret method, gave results, which were not statistically different (5.52 ± 0.46 vs. 5.92 ± 0.71 g/day). We found no correlation between previous epiodes of peritonitis and daily protein losses (r = 0.194). In patients on CCPD, daily protein losses amounted to 6.11 ± 1.13 g/daycalculated mean values derived from the patient's routine pattern of dialysis, usually six nights out of seven. As previous investigators have reported (9) we found no correlation between glucose concentration in dialysis fluid and protein losses, but found that protein losses depended on dwell time. This could be demonstrated best in CCPD patients, where dwell times varied from 2 hrs to 40 hrs. 2 hr 0.57 ± 0.10 g/1 16 hr 1.58 ± 0.33 g/1 (r = 0.8825) 40hr 8.40±1.30g/1 Reports with decreasing protein losses in the last 20 years are explained only partly by the reduction of the daily volumes of dialysis fluid: especially when one considers that, during the last six years, when dialysis methods have not changed fundamentally, the reported losses are decreasing. Differences in techniques of protein measurement may in some way account for these discrepancies. We found no dependence between glucose concentrations and protein losses and thus have confirmed the results of earlier investigators.

Insulin injection technique and diabetic control

Abstract: A major cause of unreliable and variable insulin absorption may be ‘scar’ formation at the site of repeated injection, revealed as lipohypertrophy. 60 patients with poor diabetic control (HbA1, ⪖11%), increased insulin requirements (⪖1u/kg/24 hrs) and poor injection sites were initially studied. Intensive reeducation improved 34 patients within 2 months; 26 patients continued to be poorly controlled. These patients were further studied following re-instruction in injection technique and prescription of ‘disposable’ injection equipment. Analysis of BM 20–800 readings, HbA1, and insulin dosage was performed at change-over, 2 months, 6 months and 12 months. Mean daily dosage fell from 83u/24 hrs initially to 51u at 2 months, 53u at 6 months and 47u at 12 months. At the same time intervals, mean HbA1 was 12.0%, 10.4%, 10.7%, 10.1% (P<0.05), frequency of symptomatic hypoglycemia per week was 2.0, 0.5, 0.4, 0.6 (P<0.01) and BM 20-800 stick readings ⪖22 mmol/l were 5.0, 1.0, 0.0, 0.5 (P< 0.01). Specific instruction on injection technique with disposable equipment produced improved control with less frequent hypoglycemic episodes and reduced insulin requirements. Strict attention to injection sites improved diabetic control.

Fatal Self-poisoning with Benoxaprofen

Abstract: 1 A report of the first fatal self-poisoning due to primary toxicity of benoxaprofen.2 Benoxaprofen is toxic in acute overdosage to the central nervous system, myocardium and kidneys, but appears to spare the liver.

Pre‐operative bowel preparation with oral mannitol

Abstract: immune reaction or an anaphylactoid response. given the most immunologically safe anaesthetic agents However, might I raise the possibility that patients on long-term histamine-H, receptor antagonists might Department of Anaesthetics, S. BARRETT display an undue sensitivity to histamine release or might develop an increased capacity for histamine release. May I advise that patients in this category be available.

Painful symptoms due to a spinal tumour in a man with insulin‐dependent diabetes mellitus and spinal muscular ‐atrophy

Abstract: Pain is a well recognised feature of diabetic neuropathy (Ref1). However, not all neuropathic or radiculopathic pains in the diabetic subject occur invariably as a consequence of diabetes and it is important that other correctable causes be ruled out. Our recent experience in this respect leads us to report the following case.