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Biomedical subjects

G R Giles

Publications and source records attributed to G R Giles.

At least 19 recordsLinked to original sources

Ureteric complications of renal transplantation.

Of 507 consecutive recipients of renal allografts, 45 developed a urological complication. In 39 patients (7.7%) ureteric problems were implicated and these comprised 30 cases of obstruction and 9 cases of ureteric necrosis presenting as urinary leakage. In 7 patients ureteric obstruction resolved following a period of nephrostomy decompression; 10 patients were reconstructed surgically and this was successful in 8, with 2 patients requiring further surgical procedures. Ten patients were successfully treated by percutaneous stenting after dilatation of the stricture. Stenting failed in 4 patients and in 1 patient caused rupture of a calix. All 10 stents have now been removed and there is no recurrence of stricture (follow-up 32.0 +/- 8.6 months). Of the remaining 3 grafts, 2 were removed and the other graft had percutaneous removal of a ureteric calculus. The 1-year survival rate of allografts in the ureteric complication group was 84.6%; in the recipients without a urological complication it was 81%. It was concluded that an active approach to ureteric problems following renal transplantation results in the rescue of the majority of allografts.

Adolescent

Early computed colour echo Doppler imaging following renal transplantation.

Thirty patients with renal allografts were monitored for 15 postoperative days by colour-coded Doppler imaging and categorized as stable, rejection, acute tubular necrosis and cyclosporine toxicity. All forms of graft dysfunction showed significantly raised resistance (P less than 0.01) and pulsatility (P less than 0.01) indices (RI and PI, respectively). It was not possible to use Doppler imaging to differentiate the cause of graft dysfunction, but stable grafts in patients with high cyclosporin levels had significantly higher RI (P less than 0.04) and PI (P less than 0.04) than similar grafts in patients with cyclosporine levels in the therapeutic range.

Adolescent

Ultrasonography of renal allografts: collecting system dilatation and its clinical significance.

Reports and ultrasound scans (658 studies) of 135 renal allografts, transplanted in the years 1987 and 1988, have been reviewed. Records of the recipients were also studied in order to determine the clinical status of the kidney at the time of each ultrasound examination and to obtain long-term follow-up of allograft function. Seventy-seven allografts (57%) never showed pelvicalyceal dilatation on 342 serial examinations. Forty-two kidneys (31%) had mild dilatation reported on at least one scan, which did not progress. However, 11 mildly dilated allografts developed moderate to severe dilatation on later examinations and these, together with 5 allografts reported as exhibiting moderate to severe hydronephrosis on their first dilated scan, were classed as moderate to severe (n = 16 = 12%). Thirty-eight patients (90%) with mild dilatation of the collecting system had no evidence of obstruction. However, in allografts with moderate to severe dilatation and poor or deteriorating function, ten patients (70%) were found to have ureteric obstruction. There was no significant difference in 1-year graft survival (87% versus 81.8%) and the median serum creatinine at 3 and 12 months after transplantation between non obstructed 'dilated' and non-dilated allografts (149 mumol/l versus 153.7 mumol/l; 139 mumol/l versus 147.3 mumol/l). All 14 obstructed allografts were salvaged with a graft survival of 85.7% at 1 year. Median serum creatine in these patients was significantly elevated at 200 mumol/l and 189 mumol/l at 3 and 12 months; P = 0.05 and 0.01 compared to dilated non-obstructed allografts. Our results indicate that grafts with moderate to severe dilatation should be urgently investigated to minimise further allograft damage.

Adult

Improved porcine renal preservation with a simple extracellular solution--PBS140.

In this prospective randomized trial a porcine model of renal autotransplantation was used to compare quality of preservation, as reflected by detailed analysis of posttransplant renal function, following 24-hr cold storage in phosphate-buffered sucrose (PBS140), hyperosmolar citrate (HOC), and University of Wisconsin (UW) preservation solutions. There were 6 deaths with primary nonfunction: 3 of 5 HOC, 2 of 5 UW, but only 1 of 5 PBS140. Analysis of the whole group and separate analysis of the survivors demonstrated significantly better renal function following preservation with PBS140 when compared with both HOC and UW, with a lower peak serum creatinine (P = 0.02) and improved loop of Henle function (P = 0.02). The animals in the PBS140 group also demonstrated a more rapid return to normal creatinine, higher GFR, improved tubular function, and higher effective renal plasma flow, with figures approaching statistical significance (P = 0.06-0.07). The proposal of UW as a universal storage medium prompted this study, and its results suggest the need for a clinical comparison of renal preservation using UW and PBS140 in a prospective randomized trial.

Adenosine

Interaction of intravenous methylprednisolone with oral cyclosporin.

The plasma cyclosporin values during 17 consecutive rejection episodes in 13 renal allograft recipients have been monitored by high-performance liquid chromatography and radioimmunoassay. In response to anti-rejection therapy with intravenous methylprednisolone, there was a significant increase of greater than 100 ng/ml on only three occasions. We suggest that elevated cyclosporin values during rejection episodes should not be dismissed as the result of steroid therapy and that the original diagnosis must be reviewed.

Administration, Oral

Ranolazine--a new drug with beneficial effects on renal preservation.

Ranolazine is a new drug with a novel mode of action as a metabolic modulator and membrane stabilizer. In this prospective randomized double-blind trial, a porcine model of renal autotransplantation was used to assess the effects of this drug during preservation and reperfusion of kidneys cold-stored for 24 hr in phosphate-buffered sucrose (PBS140). Three groups of 10 animals were compared: a Placebo group (placebo given intravenously to the animal before nephrectomy, added to the preservation solution, and given again to the animal during reperfusion); a Storage group (Ranolazine before and during storage, placebo during reperfusion); and a Reperfusion group (placebo before and during storage, Ranolazine during reperfusion). Detailed analysis of posttransplant renal function was carried out over a 14-day follow-up period. There were 7 deaths with primary nonfunction: 2 Placebo, 1 Storage, 4 Reperfusion. Analysis of the whole group and separate analysis of the survivors demonstrated significantly improved glomerular (P less than 0.05), tubular (P less than 0.05), and loop of Henle (P less than 0.05) function in the Storage group. The results of this study clearly demonstrate the beneficial effects of Ranolazine during the storage phase of porcine renal preservation, and further investigation of this drug is warranted.

Acetanilides

Does the Warren shunt correct hypersplenism?

It has been suggested that patients with bleeding varices and hypersplenism will show significant improvements in leucocyte and platelet counts following distal splenorenal (Warren) shunt surgery. Whilst this may be true in the short term, this report shows that in the long term hypersplenism is not relieved, whereas the lienorenal shunt is associated with a return of normal haematological values.

Esophageal and Gastric Varices

Urinary aluminium excretion following renal transplantation and the effect of pulse steroid therapy.

Urinary aluminium was measured in 48 patients with primary graft function for 14 days following renal transplantation. The plasma aluminium prior to transplantation was greater in those prescribed aluminium-containing phosphate binders (1.7 +/- 0.2 vs 0.6 +/- 0.2 mumol/L, P less than 0.05) and correlated with the duration of dialysis therapy (r = 0.42, P less than 0.008). After an initial reduction the plasma aluminium returned to pre-transplant values by the fifth day. The 24 h urinary aluminium excretion, aluminium clearance and fractional aluminium excretion all increased during the first week to a maximum around the sixth postoperative day, thereafter returning to values obtained during the first postoperative days, suggesting an early 'wash-out' of a readily accessible aluminium pool followed by a lower steady state determined by the rate of release of aluminium from tissue stores. For the whole group, aluminium excretion, at this steady state, was five times that of urinary aluminium excretion in normal subjects. Acute allograft rejection was diagnosed in 25 patients, who were treated with pulsed methyl prednisolone. Apart from improving graft function, no additional effect was observed on aluminium excretion, suggesting that the readily accessible aluminium pool does not come from lysosomal release, but probably from aluminium bound to small molecular weight protein.

Adolescent

Improved 72-hour renal preservation with phosphate-buffered sucrose.

The result of this study shows that a simple phosphate buffered sucrose solution (PBS) is better than hyperosmolar citrate (HOC) solution in the flush perfusion and hypothermic storage of canine kidneys for 72 hr prior to autotransplantation with immediate contralateral nephrectomy. The peroperative measurement of postreperfusion renal blood flow revealed a significant reduction after 60 min in kidneys preserved with HOC solution. All grafts and animals in the PBS group (5/5) survived with primary renal function compared with one in the HOC group (1/5), which functioned after a period of oliguria. The early serum creatinine and urea levels were significantly lower in the PBS group, with a return to normal range within two weeks. This is reflected in higher inulin clearances and a more rapid recovery of proximal tubular function in the PBS animals, which also demonstrated a more rapid return of loop function and the ability to concentrate urine.

Animals

Inappropriate use of metronidazole in gastrointestinal surgery.

Pharmacokinetic data suggest that current treatment regimens of metronidazole in abdominal surgery are not always appropriate. We have examined antibiotic concentrations during emergency and elective surgery using a specific and sensitive high pressure liquid chromatography assay. Serum and tissue concentrations were measured after intravenous infusion during intra-abdominal surgery and after suppositories given before appendicectomy. After intravenous dosage, bactericidal concentrations were reached in serum (13.6 +/- 7.8 micrograms/ml), bowel (9.0 +/- 6.6 micrograms/g), tumour (9.9 +/- 7.1 micrograms/g) and subcutaneous fat (4.9 +/- 3.2 micrograms/g). After suppositories the concentrations were: serum 4.6 +/- 2.7 micrograms/ml, appendix 1.1 +/- 0.6 micrograms/g, fat 1.5 +/- 0.9 micrograms/g and peritoneal fluid 4.7 +/- 4.3 micrograms/g. These values were obtained at a mean interval of 86.9 +/- 27.5 min following administration of the drug. Serum concentrations were measured during post-surgical infusion of 500 mg i.v. 8 or 12 hourly. Mean concentrations after 8 hourly doses were 16.3 +/- 4.85 micrograms/ml pre-dose and 28.7 +/- 6.76 micrograms/ml post-dose, with evidence of drug accumulation by detection of metabolites. Twelve hourly infusions gave pre-dose levels of 7.4 +/- 3.86 micrograms/ml and post-dose levels of 17.1 +/- 3.69 micrograms/ml. Metronidazole (500 mg) intravenously at induction of anaesthetic gives effective prophylactic concentrations in all tissues including tumour, but a metronidazole 1 g suppository before appendicectomy does not provide reliable tissue concentrations. Metronidazole (500 mg) i.v. 12 hourly gives effective bactericidal concentrations of the drug and is more economical.

Aged

Recurrent pyogenic cholangiohepatitis.

Three cases of complicated oriental cholangiohepatitis are described in patients of Asian origin. The development of high biliary strictures in two patients required liver resection; in the third patient the process was complicated by a presumed bile duct malignancy. Oriental cholangiohepatitis may be expected in UK surgical practice given the increased frequency of migration from Asia.

Adult

Distal splenorenal versus lienorenal shunt for acute variceal haemorrhage: is the selective shunt an advance?

Retrospective analysis of 81 patients (average age 48 years) undergoing lienorenal shunt (28) or distal splenorenal (Warren) shunt (53) surgery over a 15-year period (1971-1986) revealed important predictive factors for survival, but showed no significant differences between the two shunt groups in terms of accepted follow-up data over a period of up to 15 years. In 52 patients (64%) active haemorrhage was occurring at the time of operation, or was temporarily controlled by tamponade, and 17 of the 18 deaths (22% operative mortality) occurred in this group. Patients in whom prolonged conservative resuscitation had been attempted fared worse (64% survival), as did patients with poor hepatic reserve (Pugh grade C: 32% survival). Twenty-two patients (27%) rebled within 30 days, 18 following urgent shunts, and 12 died. Seven (11%) of the long-term survivors have suffered recurrent variceal haemorrhage with a clear relationship to shunt or portal system thrombosis. Portasystemic encephalopathy occurred in 13 survivors (20%) with six requiring hospital treatment.

Acute Disease