Aluminium accumulation and immunosuppression.
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Aluminum↗
Biomedical subjects
G R Giles
Publications and source records attributed to G R Giles.
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↗
Subcutaneous heparin therapy for cyclosporine-immunosuppressed renal allograft recipients.
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Adult↗
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↗
Clinical evaluation of PBS140 solution for cadaveric renal preservation.
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Cadaver↗
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↗
Augmentation of lymphokine-activated killer cell activity in patients with gastrointestinal cancer.
Adoptive cellular immunotherapy with lymphokine-(interleukin 2) activated killer (LAK) cells is not as successful in patients with gastrointestinal cancer as with other tumour types. This may be because the cytotoxic capacity of LAK cells from such patients is suboptimal. In this study we have sought to augment this activity by stimulating the lymphocytes with recombinant human interferon-gamma (r-HuIFN-gamma) in addition to interleukin 2 or by depleting the lymphocytes of adherent suppressive mononuclear cells. Both procedures augment LAK activity in gastrointestinal cancer patients but adherent cell depletion results in fewer cells being available for adoptive cellular immunotherapy. No further augmentation of LAK activity of adherent cell depleted cells could be accomplished by addition of r-HuIFN-gamma. Co-stimulation of unfractionated peripheral lymphocytes with r-HuIFN-gamma is the preferable procedure for the generation of LAK cells for adoptive cellular immunotherapy in patients suffering from gastrointestinal cancer.
Cell Separation↗
Effects of low dose perioperative interferon on the surgically induced suppression of antitumour immune responses.
General surgical procedures are followed by a period of generalized immunosuppression that may favour the deposition of metastases seeded at operation in patients with malignant disease. In an attempt to prevent the suppression of host-antitumour immune mechanisms following surgery we have studied the immunological effects of low-dose perioperative interferon-alpha (r-HuIFN alpha). Patients were randomly allocated pre-operatively to the control (n = 15) or treatment group (n = 15). Patients in the treatment arm received a 1-week course of subcutaneous recombinant human interferon-alpha 2a (Roferon-A) at a dose of 2 megaunits daily starting on the evening before surgery. Natural killer cell, lymphokine activated killer cell cytotoxicities and endogenous interleukin 2 production were measured 1 day before surgery and on the first, third, fifth and tenth postoperative days. Treatment with r-HuIFN alpha did not prevent the postoperative impairment of interleukin 2 production or lymphokine activated killer cell cytotoxicity. However it prevented the fall in natural killer cell activity normally observed following surgery. This may have important consequences in controlling metastatic dissemination of tumour in this vulnerable period.
Antibody Formation↗
Fine-needle aspiration cytology monitoring of elective conversion from cyclosporin to azathioprine and prednisolone.
The elective conversion of renal allograft recipients from cyclosporin (CsA) to azathioprine and prednisolone has the advantage that the long-term risk of CsA nephrotoxicity is reduced, but it may precipitate a rejection episode. We have monitored this period by fine-needle aspiration cytology (FNAC) in 24 patients undergoing conversion of immunosuppression 6 months after transplantation. As expected the serum creatinine and alkaline phosphatase were significantly reduced and the mean creatinine clearance was significantly increased after conversion. FNAC exhibited increased mononuclear cellular infiltration in 13 of the 24 patients. In nine patients there was a transient infiltration of lymphocytes and monocytes without changes in the normal parameters of renal function. In four others 'blast' cell infiltration was evident in association with rejection episodes. All four responded to pulsed doses of methylprednisolone. However, two other patients had late rejection episodes (2 and 6 months after conversion) which were steroid resistant and required reintroduction of CsA. No grafts were lost (median follow-up 9 months). This study has shown that although overt rejection occurred in only 16.6% of patients, cellular infiltration was present in over 50% during conversion of immunosuppression. FNAC failed to identify clearly the patients at risk of rejection during conversion of therapy.
Adolescent↗
Budd-Chiari syndrome treated by Senning operation.
Budd-Chiari syndrome was diagnosed in a 13 year old boy who presented with ascites. Angiographic studies showed occlusion at the ostia of the hepatic veins. This was treated surgically by the Senning operation of transcaval dorsocranial resection of the liver and hepatocaval anastomosis. The patient's ascites cleared and he remains well 10 months after surgery.
Adolescent↗
Retrospective comparative study on the influence of preservation solutions on human renal allograft function and survival.
This retrospective study has revealed that human cadaveric renal grafts preserved with hypertonic citrate solution have a significantly higher proportion with primary graft function compared with EuroCollins preserved grafts. Furthermore, Hypertonic citrate-preserved grafts have better early renal function. Those grafts with primary function show an improved graft survival at 12 months when compared with those grafts which had delayed function. There was no difference in renal graft function at 6 months following transplantation between the hypertonic citrate and EuroCollins-preserved grafts nor in the graft losses from rejection. Although the overall graft failure rate in the hypertonic citrate group is higher, this is due to patient mortality and not to rejection.
Adult↗
Is there a therapeutic range for monitoring plasma cyclosporin in renal allograft recipients?
Sixty-two consecutive adult cadaveric renal allograft recipients have been monitored by high-performance liquid chromatography estimations of trough plasma cyclosporin (CsA) concentrations within 30 days of transplantation. The CsA estimations during graft rejection (mean + 1 SD 218.6 + 126.4 ng/ml) were not significantly different from those obtained during stable renal function (232.3 + 172.8 ng/ml), whereas the estimations during episodes of nephrotoxicity (476.0 + 267.3 ng/ml) were significantly greater (P less than 0.001). During stable renal function 73.7% of estimations were within the therapeutic range of 100-350 ng/ml. However, 37.9% of estimations during nephrotoxicity and 76.7% of estimations during rejection episodes were also within this range. The therapeutic window for trough plasma CsA estimations is not clearly defined. It seems that rejection episodes may occur at apparently adequate CsA concentrations, and although most nephrotoxic episodes are associated with elevated concentrations, acute nephrotoxicity may occur at apparently therapeutic values. However, in this study, some patients at risk of nephrotoxicity within 30 days of transplantation were identified as early as 7 days post-transplantation by the simple determination of the mean trough CsA concentration for days 1-7.
Acute Kidney Injury↗
Combination fine-needle aspiration cytology and intrarenal manometry at the onset of renal dysfunction.
Twenty-three consecutive cadaveric renal allograft recipients immunosuppressed with cyclosporin have been monitored three times a week by fine-needle aspiration cytology and intrarenal manometry until discharge from hospital or until 30 days post-transplant. Standard criteria were used to determine the cause of allograft dysfunction. The onset of allograft rejection was marked by an elevation of the total corrected increment score by fine-needle aspiration cytology in 80 per cent of rejection episodes whereas intrarenal pressure was raised in only 46.6 per cent. However, intrarenal pressure was greater than 40 mmHg on a single occasion in 16 measurements performed on allografts showing evidence of cyclosporin nephrotoxicity. By combining fine-needle aspiration cytology and intrarenal manometry the sensitivity of these tests for allograft rejection was increased to 93.3 per cent at the onset of renal dysfunction. Our results demonstrate that fine-needle aspiration cytology is more sensitive than intrarenal manometry as a single investigation. However, the combined test may have an important role in the differentiation of allograft rejection and cyclosporin nephrotoxicity in the early management of renal allograft recipients.
Biopsy, Needle↗
Hepatic perfusion index and the evolution of liver metastases.
A total of 150 patients with primary carcinoma of the gastrointestinal tract had first-pass technetium colloid scintigraphy to estimate the hepatic perfusion index (HPI). Postoperative follow-up over 2-4 years shows that the HPI remains a sensitive method of detecting hepatic metastases, even in patients whose liver appeared normal at laparotomy. HPI was elevated in 94% of patients with liver metastases found at laparotomy; 87% of patients with occult metastases which became overt within 3 years of surgery had elevated HPI; and 91% of all patients who have to date developed hepatic metastases had elevated HPI at presentation. Of all patients with elevated HPI, 82% had metastases which were either apparent at surgery or became detectable by other means within 3 years.
Gastrointestinal Neoplasms↗
Initial clinical experience with degradable starch microspheres.
Four patients with advanced hepatic malignancy have been investigated with a view to intra-arterial treatment with degradable starch microspheres (DSM) and mitomycin-C (MMC). Computer-assisted interpretation of data gathered during the administration of technetium-labelled albumin allows the degree of arteriovenous shunting within the liver to be measured. In a similar way, the effectiveness of DSM in blocking hepatic arterial flow is determined. Two patients showed unacceptably high levels of shunting (75% and 100%) and were excluded from further study. One patient with hepatocellular carcinoma shunted only 24% of the macroaggregated albumin, and flow through the liver was reduced to 48% by DSM therapy. This patient has undergone four courses of MMC without significant toxic complications. The last patient had 25% shunting. The DSM titration and the first MMC administration had to be abandoned because of severe abdominal pain and nausea related to a fracture of the intra-arterial catheter. Complications directly associated with the procedures have been acceptable. The relationship between flow reduction and the amount of DSM administered is non-linear, and the appropriate dose of DSM for each treatment must be titrated against both the patient's symptoms and the computer-generated flow indices.
Adult↗
Lectin and mucin histochemistry as an aid to cancer surveillance in ulcerative colitis.
In a preliminary study, we assessed 10 lectins for the identification of dysplasia in colectomy specimens from patients with ulcerative colitis. Peanut agglutinin (PNA) binding was found in all cases of dysplasia. In the main study the relationship between PNA staining, high iron-diamine/alcian blue (HID-AB) histochemistry, and dysplasia was investigated in 115 pre-operative colonoscopic biopsies and the subsequent resection specimens from patients with ulcerative colitis complicated by carcinoma (n = 6) and patients undergoing proctocolectomy for failure of medical management (n = 8). Peanut lectin was of no value in the assessment of pre-malignant changes or cancer risk. However, the HID-AB stain appears to clarify the interpretation of less severe pre-malignant changes and may be usefully applied to the interpretation of colonoscopic biopsies for cancer surveillance in ulcerative colitis.
Alcian Blue↗
Lymphokine activated killer (LAK) cells in patients with gastrointestinal cancer.
Lymphokine activated killer (LAK) cells are a recently described cellular immune phenomenon with exciting potential for the treatment of tumours arising from solid organs. A comparison of some aspects of LAK cell precursors and LAK cell function was undertaken in 44 control subjects and 44 preoperative patients suffering from gastrointestinal cancer (20 localised and 24 advanced). Lymphokine activated killer cell precursor (natural killer (NK) cell) activity was significantly diminished in patients with advanced tumours (p less than 0.02) as was fully mature LAK cell activity against an NK resistant target cell (p less than 0.012). T-lymphocyte responses were not significantly different between the three groups. The reduced LAK cell generation was associated with a significantly diminished proliferative response of LAK precursors to stimulation with high dose IL-2 in vitro (p less than 0.012). Impaired LAK cell generation may explain the failure of adoptive cellular immunotherapy with LAK cells in some patients with advanced gastrointestinal cancer and prompts the search for means of augmenting this activity in such patients.
Aged↗