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G L Warnock

Publications and source records attributed to G L Warnock.

At least 37 records · Page 2Linked to original sources
PubMed1997

A brief history of endoscopy, laparoscopy, and laparoscopic surgery.

The ideas that form the framework for laparoscopic surgery were initially reported over a century ago. However, the introduction of the technique into the field of general surgery has been a relatively recent development. Laparoscopic surgery owes much of its history to the development of endoscopic technique. Early physicians such as the Arabian, Albukasim (936-1013 A.D.), and later in 1805, the Frankfurt-born physician, Phillip Bozzini, were among the first to develop methods to examine body orifices. Throughout the mid 1800's, several scientists attempted to construct endoscope-like instruments. The first effective open-tube endoscope was developed in 1853 by Desormeaux. This instrument was used to examine the urethra and the bladder. In the late 1800's, other physicians including Kussmaul and Nitze refined the original endoscopic models and began utilizing their new tools in their medical practice. Laparoscopy or endoscopically examining the peritoneal cavity was first attempted in 1901 by George Kelling who called this examining procedure "Celioscopy". In the early 1930's, the first reports of laparoscopic interventions for nondiagnostic purposes were published. Initial procedures included lysis of abdominal adhesions and diagnostic biopsies of abdominal organs under direct visualization. Throughout the 1960's and 1970's, laparoscopy became a vital part of gynecological practice. Despite these technological advances, it was not until after 1986, following the development of a video computer chip that allowed the magnification and projection of images onto television screens, that the techniques of laparoscopic surgery truly became integrated into the discipline of general surgery. The first laparoscopic cholecystectomy performed on a human patient was done in 1987 by the French physician Mouret. The rapid acceptance of the technique of laparoscopic surgery by the general population is unparalleled in surgical history. It has changed the field of general surgery more drastically and more rapidly than any other surgical milestone. This paper examines the history behind this exciting surgical technique.

Endoscopy↗
PubMed1997

Characterization and transplantation of agarose microencapsulated canine islets of Langerhans.

The bioartificial pancreas was designed to incorporate islet tissues and a selectively permiable membrane that isolates islets from the immune system of the recipient. The efficacy of agarose, a nontoxic polysaccharide, has been evaluated as a material of microcapsules to prevent allo- and xenograft rejection in rodents. The aim of this study is to demonstrate the possibility of the agarose microcapsule containing allo-islets as a bioartificial pancreas in canine model. In vitro viability of islets was determined by glucose challenge during perifusion experiments (n = 4). Insulin secretion from both encapsulated (enc.) and non-encapsulated (non-enc.) canine islets rose from initial basal levels of 0.09 (encap.), 0.07 (non-encap.) to the peak of 0.2 (encap.), 0.1 (non-encap.) in microU/islet/min after 5 minutes, then decreased to the basal level when the glucose challenge was discontinued. Auto-transplantation was performed in two dogs to evaluated in vivo viability and biocompatibility of encapsulated islets implanted into the splenic sinus by venouse reflux. Two weeks after auto-transplantation, the plasma insulin levels in the splenic vein and artery of two dogs were assayed. In the first dog, serum insulin level was 1 microU/ml both in the vein and the artery and increased, after glucagon (1.0 mg) injection, to levels of 9 microU/ml in the vein, but still kept 1 microU/ml in artery, as well as in the second one. Histological and electron-microscopical examination of the spleen revealed that encapsulated islets remained morphologically intact and the surface of agarose capsules showed no significant adherence of fibroblasts and inflammatory cells. Functional efficacy of the microencapsulated islets was determined using five totally-pancreatectomized diabetic dogs as recipients without immunosuppression. Defined quantity of microencapsulated islets from outbred mongrel donors were grafted through the catheter into omental tissue of the pancreatectomized recipients. All dogs had various degrees of reduced insulin requirements. In three of five recipients, the average fasting glucose values were controlled under 120 mg/dl for 28, 42, 49 days without exogenous insulin, which received totally 4.3 x 10(3), 7.3 x 10(3) and 1.0 x 10(4) (IE/kg) of microencapsulated islets, respectively. In conclusion, the present study indicates that the agarose-based microencapsulated islets can function in large diabetic animals, resulting in the independence of exogenous insulin therapy for prolonged periods without the need for immunosuppression.

Animals↗
PubMed1996

Successful biolistic transformation of mouse pancreatic islets while preserving cellular function.

To utilize gene therapy, we required an efficient method to transfect intact islets before their use in transplantation. The biolistic method transforms cells by bombarding them with microprojectiles coated with DNA. Once internalized, the DNA is solubilized and expressed. We used the firefly luciferase gene driven by the human cytomegalovirus immediate early promoter as a reporter construct in freshly isolated BALB/c mouse islets to compare the transfection efficiency using either the biolistic method, lipofection, or recombinant adenoviral infection (n=4 in each case). The biolistic method achieved, on average, a 35-fold higher level of luciferase activity than the lipofection method (mean +/- SEM: 42.6 +/- 14.2 vs. 1.1 +/- 0.2 relative light units (RLU)/islet). Adenoviral infection achieved, on average, a further 25-fold higher level of luciferase activity than the biolistic method (1136.0 +/- 542.0 RLU/islet). The average proportion of islets recovered 48 hr after the biolistic blast was 53% (n=20). The average number of dissociated cells found to express the foreign gene product using beta-galactosidase as a reporter construct was 3% (n=6). Furthermore, nontransformed and biolistically transformed islets responded similarly to an in vitro glucose challenge (stimulation index of insulin release at 20.0 mM glucose/insulin release at 2.8 mM glucose = 2.8 and 3.0, respectively, P=0.9). Syngeneic, biolistically transfected islets functioned to reverse the diabetic state when transplanted (500 islets) beneath the renal capsule of alloxan-induced diabetic BALB/c recipients (n=7). This methodology can achieve efficient transfection of pancreatic islets while preserving their function and thus holds promise for ex vivo gene therapy of isolated islets prior to transplantation.

Animals↗
PubMed1996

Large scale isolation, growth, and function of porcine neonatal islet cells.

Based upon existing methods of isolating fetal porcine islet tissue, a simple, reliable procedure was developed for the preparation of porcine neonatal islet cell aggregates with a reproducible and defined cellular composition. After 9 d of in vitro culture, tissue from one neonatal pig pancreas yielded approximately 50,000 islet cell aggregates, consisting of primarily epithelial cells (57%) and pancreatic endocrine cells (35%). During the culture period, the total beta cell mass decreased initially, but subsequently increased 1.5-fold between days 3 and 9. Transplantation of grafts consisting of 3 x 10(5) beta cells (1,000 aggregated) under the kidney capsule of alloxan-diabetic nude mice corrected hyperglycemia in 75% (10/13) of the animals, whereas, 100% (20/20) of recipients implanted with 6 x 10(5) beta cells (2,000 aggregates) achieved euglycemia within 8 wk posttransplantation. Nephrectomy of the graft bearing kidney at 14 wk posttransplantation resulted in hyperglycemia in all recipients, and examination of the grafts revealed the presence of numerous well-granulated insulin- and glucagon-containing cells. The cellular insulin content of these grafts was 20 to 30-fold higher than at the time of transplantation. These results indicate that the neonatal porcine pancrease can be used as a source of large numbers of viable islet cells, which have the potential for growth both in vitro and in vivo, and exhibit the metabolic capacity to correct diabetes in nude mice.

Animals↗
PubMed1996

Variables in organ donors that affect the recovery of human islets of Langerhans.

In an attempt to reduce the variability in the yields of human islets isolations and to identify donor factors that were potentially deleterious, we retrospectively reviewed 153 human islets isolations in our center over a 3-year period. Isolations were performed using controlled collagenase perfusion via the duct, automated dissociation, and Ficoll purification. Factors leading to successful isolations (recovery of >100,000 islet equivalents at a purity >50%) were analyzed retrospectively using univariate and multivariate analysis. Critical factors in the multiorgan cadaveric donors that were identified using univariate analysis included donor age (P<0.01), body mass index (BMI)(P<0.01), cause of death (P<0.01), and prolonged hypotensive episodes (systolic blood pressure <90 mmHg or mean arterial pressure <60 mmHg for > 15 min) requiring high vasopressors (>15 microgram/kg/min dopamine or >5 microgram/kg/min Levophed) (P>0.01). Independent analysis of 19 donor variables using multivariate logistic stepwise regression showed six factors were statistically significant. Odds ratio (OR) showed that donor age (OR 1.1, P<0.01), local procurement team (OR 10.9, P<0.01), and high BMI (OR 1.4, P<0.01) had a positive correlation with islet recovery. In contrast, hyperglycemia (all blood glucose >10 mmol/L) (OR 0.63, P<0.01), frequency and duration of cardiac arrest (OR 0.7, P<0.01), and increased duration of cold storage before islet isolation (OR 0.83, P<0.01) had negative correlation. Using these combinations of factors, the prediction of success was 85% accurate. By donor age, success was 13% for 2.5- to 18-year-old donors (n=23), 37% for 19- to 28-year-old donors (n=30), 65% for 29- to 50-year-old donors (n=70), and 83% for 51- to 65-year-old (n=29) donors. However, when vitro function was assessed by perifusion, the insulin secretory capabilities of islets isolated from the >50-year-old donor group was significantly reduced as compared with the 2.5- to 18-year-old group (P<0.02). Multiple regression analysis using postdigestion and postpurification islet recovery as outcome variables identified BMI, procurement team, pancreas weight, and collagenase digestion time factors tht can affect the recovery of human islets. Locally procured pancreases and donors with elevated minimum blood glucose levels were identified as factors that affect the insulin secretory capabilities of the isolated islets. This review of parameters suggests an improved approach to the prediction of successful islet isolation from human pancreases. Selection of suitable pancreases for processing may improve consistency in human islet isolation and thereby decrease costs.

Adult↗
PubMed1996

Intrathymic transplantation of fresh and cryopreserved islets for the induction of a state of unresponsiveness in rats.

The aim of this study was to assess the survival and function of cryopreserved islets in the thymus and to determine whether small numbers of allogeneic islets could induce a state of unresponsiveness to subsequent allogeneic islet grafts. Isografts of 1500 freshly isolated (n = 8) or 2500 frozen-thawed (n = 6) Wistar-Furth (RT1u/u) islets induced long-term normoglycemia after intrathymic transplantation (median survival time [MST] > 100 days in both groups), whereas isografts of 1500 frozen-thawed islets (n = 5) were inconsistent in restoring long-term normoglycemia. Transplantation of 1500 fresh (n = 6) or 2500 frozen-thawed (n = 6) Lewis (RT1l/l) islets induced long-term normoglycemia (MST > 100 days in both groups) when islets were transplanted in conjunction with a single injection of antilymphocyte serum. Intrathymic transplants of 500 freshly isolated Lewis islets induced a state of unresponsiveness to a second extrathymic allotransplant (MST > 100 days, n = 7). However, transplantation of 500 (n = 10) or 800 (n = 5) cryopreserved Lewis islets intrathymically did not prolong survival of a second extrathymic transplant (MST 19 and 21 days, P < 0.05 vs. fresh group, Mann-Whitney U test). These results demonstrate that cryopreserved intrathymic islets can normalize and maintain euglycemia providing the islet mass is augmented. Prolonged survival of cryopreserved islets in the thymus was observed; however, small numbers of allogeneic cryopreserved islets were unable to induced a state of unresponsiveness to a subsequent extrathymic islet graft.

Animals↗
PubMed1996

Does volume of clinical experience affect performance of clinical clerks on surgery exit examinations?

BACKGROUND: Controversy persists over the educational value of student clerkship clinical activities. METHODS: Students (109) from the class of 1995 recorded their clinical experiences in a logbook during their surgical clerkship at one of four affiliated teaching hospitals. The influence of clinical experience on examination scores and on correlations between prerotation and postrotation examination performance was determined. RESULTS: Between sites, marked variation in clinical experience was observed but postrotation scores were similar. High-volume experience in emergency admissions and feedback was associated with better objective structured clinical examination (OSCE) performance, but high-volume outpatient clinic experience was associated with less satisfactory OSCE performance. Correlations between prerotation examination performance and the OSCE was increased by feedback on emergency and elective admissions, in a positive and negative direction, respectively. CONCLUSIONS: These data show that surgical clerks' clinical skills were enhanced by an increased volume of some but not all clinical experiences and that feedback does not necessarily enhance performance. These data suggest that both the volume of clinical experience and the quality of feedback should be carefully monitored by surgical clerkship directors.

Alberta↗
PubMed1995

Human pancreas preservation prior to islet isolation. Cold ischemic tolerance.

We have retrospectively evaluated islet isolation records collected from 230 consecutive adult pancreases with 146 pancreases fulfilling all criteria for our evaluation. Fifty-six pancreases procured by our local organ procurement team (33 before in situ vascular flush and 23 after in situ vascular flush with University of Wisconsin [UW] solution) were compared with 90 pancreases received from distant centers that were shipped in UW solution after in situ vascular flushing. Cold storage of 3-26 hr preceded islet isolation using collagenase digestion and Ficoll purification. Recoveries of islets were assessed by duplicate counts of dithizone-stained aliquots before and after purification. Isolations were considered successful if > 100,000 viable islets (islet equivalents to 150 microns) were recovered after purification. Islet function was assessed by in vitro glucose-stimulated perifusion and islets were considered viable if the stimulation index (glucose stimulated over basal insulin secretion) was > 2. Eighty-three percent of the isolations from locally procured, UW-flushed pancreases were successful, as compared with 86% for pancreases that were stored for 3 to 8 hr, 73% for 8 to 16 hr of storage, and 38% for isolations following > 16 hr of cold storage. Increasing the duration of cold storage prior to islet isolation was associated with an increased proportion of failed isolations and decreased measures of islet viability. The actual numbers of islets per gram of pancreas before and after purification were significantly reduced if the hypothermic cold storage was > 16 hr. In vitro viability of isolated islets during glucose-stimulated perifusion showed a higher percentage of viable islets from pancreases with shorter durations of cold storage. For pancreases with > 16 hr of cold storage prior to islet isolation, islet viability was significantly reduced. We conclude that, with the current methods available to recover and store cadaver donor pancreases and the methods currently used to isolate human islets, yields of purified islets decline significantly from human pancreases that have been subjected to cold storage of > 16-18 hr.

Adenosine↗
PubMed1995

Microbial surveillance of human islet isolation, in vitro culture, and cryopreservation.

The aim of these studies was to investigate microbiological contamination during the isolation and preservation of islets of Langerhans in a low-temperature tissue bank. Islets were isolated from the pancreases of 117 organ donors, then cryopreserved. In the initial 47, microbial culture was completed only after thawing: Enterobacter cloacae (n = 4) and gram-negative bacilli (n = 9) were isolated for a positive culture rate of 27.6%. It was not possible to ascertain the source of the contaminants, since cultures were taken only at the conclusion. A total of 70 consecutive pancreases were then subjected to islet isolation and cryopreservation while prospectively culturing at these steps: step 1, from the pancreas transport media; step 2, after intraductal perfusion of collagenase; step 3, after dissociation; step 4, after purification; step 5, following a 6-48-h in vitro culture; step 6, post-thaw; step 7, after dilution of the cryoprotective agent; and step 8, after final 48-h in vitro culture. The transport fluid was infected with aerobic gram-negative (n = 6), gram-positive (n = 5), and yeast microorganisms (n = 2) for an overall step 1 contamination rate of 19%. These contaminants were found in 9% of our local program vs. 26% from distantly procured pancreases. Contaminants at subsequent steps were 10% (step 2), 9% (step 3), so that only 3% were infected at the conclusion of isolation (step 4), and 0% after initial culture (step 5). Amongst pancreases that were initially sterile, new contaminants could be identified in 12% at step 2 and 8% at step 3; however, these also became undetectable.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteria↗
PubMed1995

Problem-based learning: its role in undergraduate surgical education.

OBJECTIVE: To familiarize the surgeon with problem-based learning (PBL) and to discuss the current and future role of PBL in undergraduate surgical education. DATA SOURCES: Two meta-analyses comparing the outcome of a PBL curriculum with a traditional curriculum and other studies in the English-language literature. STUDY SELECTION: Data on the effectiveness of PBL can best be assessed by a meta-analysis in which the conclusions of many studies are reviewed and combined to provide a more comprehensive picture. The studies chosen represent those from the only two recent meta-analyses of the problem that have appeared in reputable journals. DATA EXTRACTION: Results reported are those obtained using appropriate techniques and published in reputable journals. Information relevant to the major issues in undergraduate surgical training was selected for inclusion. DATA SYNTHESIS: PBL depends on self-directed learning, triggered by a clinical problem. The students meet in small groups led by a facilitator and discuss carefully designed clinical cases. At the conclusion, the students will have encountered all the information necessary to solve the case and, in so doing, will have gained knowledge that in a conventional curriculum would usually have been disseminated by lecture. There were only small differences between graduates from the two types of curricula. Those from a PBL curriculum had comparable examination results to those from a traditional curriculum on both basic science and clinically based examinations but were happier with their educational experiences. CONCLUSIONS: Centres that have adopted a PBL approach have found improved student motivation and enjoyment, but there has been no convincing evidence of improved learning. An intelligent combination of both traditional and PBL approaches will likely provide the most effective training for undergraduate surgical clerks.

Canada↗