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Biomedical subjects

D Alderson

Publications and source records attributed to D Alderson.

At least 19 recordsLinked to original sources
PubMed1992

Ambulatory measurement of oesophageal function: clinical use of a new pH and motility recording system.

Conventional oesophageal manometric studies are open to criticism in that they take place on fasted immobile subjects in the artificial setting of a motility laboratory. A new 24-h pH and motility recording system combined with computerized data analysis was used to study patients with gastro-oesophageal reflux disease and oesophageal motor abnormalities under ambulant conditions. Acid reflux episodes were found to be precipitated by a variety of events with recognizable pressure patterns. Acid clearance abnormalities were demonstrated in patients with erosive oesophagitis but were confined to those with abnormal oesophageal motor function. Improved diagnostic accuracy was demonstrated in the recognition of oesophageal motor disorders.

Circadian Rhythm↗
PubMed1991

The sphinctometer: a new device for measurement of lower oesophageal sphincter function.

Current evidence suggests that lower oesophageal sphincter (LOS) competence depends upon both pressure and length. Existing devices can measure length and pressure, but not simultaneously. This methodological problem is a fundamental drawback to understanding LOS function and its role in oesophageal disease. A 'sphinctometer' has been developed, consisting of an oil-filled 3-mm diameter Silastic chamber, 6 cm in length, incorporating a pressure microtransducer designed to provide an integrated pressure reading as a function of length. Its performance has been tested in vitro using human cadaver oesophagus in a specially constructed chamber in which sphincter length and pressure can be varied independently. Comparisons were made with a conventional pull-through technique. Sphinctometer response was linear throughout the LOS pressure range of 0 to 50 mmHg at a fixed LOS length (RS = 0.99; P less than 0.001). Sphinctometer response was also linear at fixed LOS pressure for sphincter lengths from 1 to 6 cm (RS = 0.99; P less than 0.001). This device thus appeared suitable for monitoring function of the human LOS, and has subsequently been successfully incorporated into an ambulatory system for patient use.

Biometry↗
PubMed1990

Laser recanalization versus endoscopic intubation in the palliation of malignant dysphagia.

Forty patients with widely disseminated or locally advanced malignant obstruction of the middle or lower third of the oesophagus underwent endoscopic treatment by either NdYAG laser recanalization or intubation. Groups were matched on the basis of tumour location and swallowing was graded clinically before and after treatment. Technical success was achieved in 17 of 20 laser treated and 18 of 20 intubated patients. Pretreatment swallowing ability, histology, tumour location and overall length were unrelated to functional outcome in both groups. However, circumferential tumour length identified endoscopically strongly influenced the quality of swallowing after laser recanalization. Patients with excellent swallowing quality (n = 7) had significantly shorter circumferential tumour lengths, 3.1(1.0) cm, than those with poorer quality swallowing (n = 10), 6.3(1.6)cm, (P less than 0.001). Both methods of treatment had low complication rates and there was one death in the series in the laser-treated group. Laser recanalization provides a better functional result than intubation for short (less than 4 cm) circumferential tumour. Intubation at a single session seems more appropriate than repeated laser therapy when tumour length exceeds 4 cm.

Aged↗
PubMed1989

Prior renal transplantation does not facilitate subsequent canine islet allograft survival.

Successful islet allografts can be established in rats bearing long surviving renal allografts, without additional immunosuppression, when kidney and islet donor animals are of the same strain. The applicability of such a scheme to clinical practice has been investigated in a large animal model of diabetes: the pancreatectomized dog. Eight dogs with previously established renal allografts and immunosuppressed with cyclosporin A received islet allografts from their respective original kidney donors. The median islet graft functional survival was only 10.5 days, significantly less than for six similarly immunosuppressed dogs receiving islet allografts alone (48.5 days, P less than 0.05). Three of the sequentially transplanted dogs had had no renal graft rejection episodes before islet transplantation, yet their islet grafts were all rejected within 19 days. In the pancreatectomized dog, prior donor specific renal transplantation has an adverse effect upon subsequent islet graft survival.

Animals↗
PubMed1989

Diurnal insulin and glucose profiles following transplantation of fresh and cryopreserved canine pancreatic islets.

Dispersed islet autotransplants (fresh and cryopreserved) can produce normal fasting insulin and glucose concentrations. Following an intravenous glucose challenge, however, the insulin response is impaired and glucose clearance delayed. This study examines the diurnal insulin and glucose response to feeding in recipients of fresh islet autografts (n = 6), recipients of cryopreserved islet autografts (n = 3), normal unoperated controls (n = 10) and insulin treated pancreatectomized diabetic dogs (n = 7). Mean fasting insulin and glucose levels were similar in all groups. After feeding, insulin profiles in both transplant groups were near normal while significant hyperinsulinaemia occurred in insulin treated diabetic dogs. Mild postprandial carbohydrate intolerance was observed in transplant recipients but glycosylated haemoglobin levels were similar (mean(s.d.] to normals (6.88(0.86) per cent, 6.86(0.5) per cent respectively). Dispersed islet autotransplantation with portal insulin delivery produces near normal insulin and glucose profiles suggesting that this may represent a suitable treatment for insulin dependent diabetes.

Animals↗
PubMed1989

Acid resistant lipase as replacement therapy in chronic pancreatic exocrine insufficiency: a study in dogs.

Conventional treatment of pancreatic steatorrhoea in man has been unsatisfactory because 90% of the lipase content of therapy is inactivated by acid in the stomach and large doses of replacement treatment are needed to provide adequate supplementation. An acid stable agent (fungal lipase) was investigated in the treatment of pancreatic deficiency steatorrhoea in 11 pancreatectomised dogs maintained on a fixed dietary intake of fat and treated with pancreatin or fungal lipase. Ten grams (60,000 U lipase) of pancreatin was compared with 400mg (4800 U lipase) of fungal lipase administered with each meal against a no treatment group. There was no significant difference in stool bulk and faecal fat excretion between pancreatin and lipase treated animals. Both groups showed a significant reduction in stool bulk and fat excretion when compared with the no treatment group (p less than 0.01). A markedly diminished treatment volume, in the form of fungal lipase, is as effective in controlling steatorrhoea as pancreatin and may prove to be a potentially valuable therapy for patients with pancreatic insufficiency.

Animals↗
PubMed1989

Prolonged cryopreservation of purified human pancreatic islets.

Long-term islet storage would facilitate many aspects of islet research and clinical islet transplantation. Collagenase-isolated, Ficoll-purified islets from eight cadaveric pancreases were stored in liquid nitrogen for 44 +/- 9 days after dimethyl sulfoxide equilibration and slow cooling. Rapid rewarming and 48 h of culture preceded repeat evaluation of recovery by islet counts, insulin extraction, and glucose-stimulated perifusion. Islet recovery was 94 +/- 4% by count and 90 +/- 22% by insulin extraction immediately after thawing. After an additional 48 h in culture, recovery was 74 +/- 12% by insulin extraction and 79% by quantitative perifusion culture. Perifusion demonstrated normal baseline and first-phase insulin secretion with decreased second-phase insulin secretion after cryopreservation. Insulin-stained sections and electron microscopy revealed preserved islet morphology and ultrastructure. Granulated islets with preserved morphology were recovered 14 days after renal subcapsular xenografting into nude mice. This study demonstrates high recovery and good functional activity of human islets after prolonged cryopreservation.

Freezing↗
PubMed1989

Failure of canine islet allotransplantation after kidney transplantation.

Eight dogs with previously established kidney allografts, immunosuppressed with cyclosporin A, received islet allografts from their respective original kidney donors. The median islet-graft functional survival was only 10.5 days, significantly less than for six similarly immunosuppressed dogs receiving only islet allografts (48.5 days, P less than .05). Three of the eight dogs that received sequential kidney and islet allografts had experienced no kidney-graft rejection episodes before islet transplantation, but their islet grafts were all rejected within 19 days. In the pancreatectomized dog, prior donor-specific kidney transplantation has an adverse effect on subsequent islet-graft survival.

Animals↗
PubMed1989

Long-term cryogenic storage of purified adult human islets of Langerhans.

Reliable high-recovery human islet storage would facilitate tissue matching, organ sharing, and immune manipulation of donor islets and prospective diabetic recipients. Collagenase-isolated, Ficoll-purified pancreatic islets (median 21,000, 15% of total islet yield) from eight cadaver pancreases were cultured in vitro for 24 h, equilibrated in three steps with dimethyl sulfoxide (DMSO) to a 2-M concentration, supercooled, nucleated, and cooled at 0.25 degree C/min to -40 degrees C before storage at -196 degrees C for 44.25 +/- 8.75 days. Rewarming at 200 degrees C/min and removal of DMSO with 0.75 M sucrose preceded 48 h of culture and retesting. Recovery postthaw by microscope count on duplicate aliquots was 94.2 +/- 3.5% of prefreeze counts and by triplicate assay of extractable insulin was 90.0 +/- 22.3% on day 0 and 74.1 +/- 12.6% after a 48-h culture. Nonfrozen islets increased basal insulin secretion 7.7 +/- 2.8 times after stimulation with 300 mg/dl glucose in perifusion, whereas islets frozen-thawed and cultured 48 h increased 6.2 +/- 0.8 times (NS). Peak stimulated insulin release was 0.92 +/- 0.14 microU.islet-1.min-1 before storage and 0.73 +/- 0.14 microU.islet-1.min-1 (79% of control, NS) after freeze-thaw and a 48-h culture. Total insulin secretion (area under curve) was 66% of prefreeze values at 48 h. Immunocytochemical stains revealed preservation of islet morphology postthaw. Electron microscopy showed intact cellular and nuclear membranes and intracellular organelles. Frozen-thawed islets harvested 14 days after renal subcapsular xenografting in nude mice were revascularized and well granulated. Cryopreservation can achieve prolonged storage of large numbers of human islets with high recovery numerically and functionally, making this a feasible approach for future trials of human islet transplantation.

Culture Techniques↗
PubMed1987

Dispersed pancreatic graft cryopreservation in the dog: in vivo assessment of preservation protocols.

Dispersed canine pancreatic grafts were cryopreserved and the in vivo function was studied following intrasplenic autotransplantation. Four protocols were employed, examining the effects of cooling and thawing rates and cryoprotectant (dimethylsulfoxide) concentration on graft survival. The degree of graft injury by each protocol was assessed by examining the requirement for exogenous insulin following transplantation. Cooling at 5 degrees C/min and thawing at 80 degrees C/min allowed three successful grafts from seven when thawed at 80 degrees C/min using 1.4 or 2 M Me2SO but only one success from eight when thawed at 8 degrees C/min. Of the seven experiments where successful preservation was achieved graft injury was estimated as less than 50% in four but for three it was probably greater than 50%. Each protocol exhibited considerable variability of islet survival. When sufficient islet mass was transplanted to restore fasting euglycaemia, graft function, as assessed by glucose-stimulated insulin release and intravenous glucose disposal, was identical to fresh grafts. Successful graft implantation, however, does not guarantee indefinite survival as six of seven grafts in this study became exhausted within 13 months of implantation.

Animals↗
PubMed1987

Long-term normoglycemia in pancreatectomized dogs following pancreatic islet allotransplantation and cyclosporine immunosuppression.

Pancreatectomized dogs received intrasplenic autotransplants or allotransplants of unpurified islets prepared from the pancreata of unrelated outbred dogs, by a standard collagenase ductal perfusion method. Allograft immunosuppression consisted of tapering azathioprine-prednisone (AP), low level cyclosporine (CsA, through whole blood high-pressure liquid chromatography (HPLC) level 300-600 micrograms/L), or high CsA (600-1000 micrograms/L). While AP and low CsA failed to delay rejection, high CsA achieved prolonged (greater than 100 days) graft function in 5 of 12 dogs, with a median duration of 85.5 days. (P less than .01 vs. AP and low CsA). While no interference with islet engraftment was seen in CsA-treated dogs, late graft failure (greater than 30 days) was seen in 3 of 6 CsA autografts and 5 of 12 high CsA allografts. CsA at whole-blood HPLC levels of 600-1000 micrograms/L can achieve prolonged normoglycemia in pancreatectomized canine recipients of islet allografts. The effects of such doses of CsA on islet function may be substantial.

Animals↗