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Biomedical subjects

D R Fletcher

Publications and source records attributed to D R Fletcher.

At least 19 recordsLinked to original sources

Flexible sigmoidoscopy screening for colorectal cancer in average-risk subjects: a community-based pilot project.

OBJECTIVE: To test a pilot screening program for colorectal cancer. DESIGN: Subjects, chosen at random and recruited by mail, were examined by flexible sigmoidoscopy. PARTICIPANTS AND SETTING: Normal-risk, asymptomatic men and women aged 55-59 years recruited from the community, July to December, 1995. MAIN OUTCOME MEASURES: Number of polyps detected and cancers diagnosed, and compliance with screening. RESULTS: Letters of invitation were sent to 3500 subjects; of these, 2881 were eligible for inclusion in the study and 342 (12%) consented to participate. A further 3.5% of non-compliant subjects attended the screening program after a telephone survey assessing reasons for non-attendance. Common reasons for non-attendance were a lack of interest (30%) or a lack of time, mainly due to work commitments (28%). A third of subjects had polyps and 46% of these were adenomas. Three subjects were found to have adenocarcinoma: in two the cancer was confined to a polyp and treated with polypectomy, and one subject underwent anterior resection (overall prevalence of cancer, 0.9%). The median depth of insertion achieved with flexible sigmoidoscopy was 55 cm (range, 25-100 cm). Median pain level (on a scale of 0 = no pain to 10 = worst pain imaginable) was 2 (range, 0-8.5), and 99% of the subjects would have the test again if required. CONCLUSIONS: Flexible sigmoidoscopy was well tolerated and had an acceptable detection rate of adenomatous polyps and early cancer. Subject compliance emerged as a major issue which requires further evaluation to maximise participation in future programs.

Adenocarcinoma

Hepatic pathology resulting from mouse hepatitis virus S infection in severe combined immunodeficiency mice.

Mouse hepatitis virus (MHV) is a pervasive pathogen that causes morbidity and mortality in mouse colonies worldwide. Although it is not a major cause of mortality in immunocompetent mice, infections from MHV strains of lower virulence can be fatal to athymic nude mice. The histopathologic features and alterations of serum biochemical parameters resulting from infection with a low-virulence MHV strain in severe combined immunodeficiency (scid) mice has not been well described. Thus we recently studied the disease caused by MHV-S in scid mice after intranasal inoculation. Mouse hepatitis virus infection in scid mice, which have severe defects of B and T cells, may be highly lethal, resulting in immediate mortality. However, our results indicate that scid mice survived for an average of 12 to 14 days after infection with doses of MHV up to 10(7) PFU/mouse. The virus caused a significant increase in serum enzyme activities and bilirubin concentration associated with histologically demonstrable hepatocellular injury at postinoculation days 3, 4, and 8. Furthermore, virus was detected in mouse liver homogenates and nasal and bronchial lavage specimens. These results provide valuable information regarding the histopathologic and biochemical consequences of MHV-S infection in scid mice.

Alanine Transaminase

Laparoscopic cholecystectomy: what national benefits have been achieved and at what cost?

Changes in the practice of surgery following the introduction of laparoscopic cholecystectomy (removing asymptomatic gallstones, duplicating procedures for diagnosing and managing common bile duct stones, and deferring laparoscopic management of complicated gallstones) as well as the increased rate of complications (particularly duct injury), have eroded the economic benefits to health care funders of shorter hospital stays. However, these benefits may be achieved if laparoscopic procedures are performed only by experienced surgeons and if the procedure is offered to all patients with gallstones, including complicated cases. Benefits to the community remain in terms of productivity savings as a result of an earlier return to work for patients.

Australia

Biliary tract complications of laparoscopic cholecystectomy are detected more frequently with routine intraoperative cholangiography.

Controversy over whether intraoperative cholangiography (IOC) should be done routinely has intensified since the advent of laparoscopic cholecystectomy (LC). As yet, no study has demonstrated a clear benefit to its use, although their have been suggestions in the literature that routine use may confer an advantage to detection of injuries. One-hundred seventy-seven biliary tract complications occurring secondary to LC were identified from the combined data of seven institutions. The goal of this retrospective study was to examine the impact of IOC on the occurrence, recognition, and correction of such complications. The complications identified include 39 cystic duct leaks, 69 major ductal leaks or strictures, and 69 major ductal transection or excision injuries. Whether IOC was performed was known in 157 (88%) patients with 53 patients definitely having and 104 not having an IOC. Data concerning IOC were unavailable in 20 cases. More injuries were detected intraoperatively in the group having IOC (P < 0.001). Conversion of the LC to a laparotomy, often for repair of the injury, occurred more commonly in the group having a correctly interpreted IOC (P < 0.001). Conversion resulted in detection of injuries sooner, resulting in fewer operative procedures to correct the injury (P < 0.001). A transecting injury was prevented in at least seven patients when no visualization of the proximal biliary tree was documented by IOC. These partial ductal incisions were treated by t-tube placement. Incorrect interpretation of the IOC occurred in at least eight patients, with no identification of the proximal biliary tree in six.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile Ducts

The carcinogenic risks of alcoholic beverages: implications for cancer education.

The proper analysis of the data generated by studies of carcinogenic risks of drinking alcoholic beverages would be the application of models from the relatively new approach of meta-analysis. In this study, 441 articles were generated by a 1992 MEDLINE search of the key words "alcohol drinking" and "cancer." Of these, only 29 met the criteria for a formal meta-analysis. For these 29 research reports, the 95% confidence limits for the odds ratio were 1.28 and 1.15, suggesting a weak association between drinking and cancer. This conclusion was rendered even less decisive by the following problems in the studies analyzed: 1) absence of comparable measures of either dosages or drinking patterns; 2) absence of comparable methods of data analysis; 3) absence of comparable measures of other population characteristics; and 4) widely varying results from study to study. For example, the 95% confidence limits for the odds radio of the 16 European studies were 1.14 and 0.98, indicating not even a reliable directional difference between drinking and nondrinking populations. Although the World Health Organization International Agency for Research on Cancer concluded in 1987 that alcoholic beverages are carcinogenic, the scientific literature extant in 1992 provides only very weak support for that finding. There is a need for multiple nonexperimental investigations using methods that will produce results sufficiently comparable to justify the application of the statistical models being generated for the meta-analysis of important questions not subject to direct experimentation.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking

Intracellular neutralization of influenza virus by immunoglobulin A anti-hemagglutinin monoclonal antibodies.

Traditionally, immunoglobulin A (IgA) was thought to neutralize virus by forming complexes with viral attachment proteins, blocking attachment of virions to host epithelial cells. Recently we have proposed an intracellular action for dimeric IgA, which is actively transported through epithelial cells by the polymeric immunoglobulin receptor (pIgR), in that it may be able to bind to newly synthesized viral proteins within the cell, preventing viral assembly. To this effect, we have previously demonstrated that IgA monoclonal antibodies against Sendai virus, a parainfluenza virus, colocalize with the viral hemagglutinin-neuraminidase protein within infected epithelial cells and reduce intracellular viral titers. Here we determine whether IgA can interact with influenza virus hemagglutinin (HA) protein within epithelial cells. Polarized monolayers of Madin-Darby canine kidney epithelial cells expressing the pIgR were infected on their apical surfaces with influenza virus A/Puerto Rico/8-Mount Sinai. Polymeric IgA anti-HA, but not IgG anti-HA, delivered to the basolateral surface colocalized with HA protein within the cell by immunofluorescence. Compared with those of controls, viral titers were reduced in the supernatants and cell lysates from monolayers treated with anti-HA IgA but not with anti-HA IgG. Furthermore, the addition of anti-IgA antibodies to supernatants did not interfere with the neutralizing activity of IgA placed in the basal chamber, indicating that IgA was acting within the cell and not in the extracellular medium to interrupt viral replication. Thus, these studies provide additional support for the concept that IgA can inhibit replication of microbial pathogens intracellularly.

Animals

An evaluation of laparoscopic versus open cholecystectomy.

OBJECTIVE: To compare open cholecystectomy (OC) with laparoscopic cholecystectomy (LC) in terms of clinical aspects and a limited review of costs. SETTING: The Austin Hospital, Melbourne, a university teaching hospital. DESIGN: Prospective LC patients were compared with a retrospective group of OC patients whose surgery had been performed by the same surgeons. METHODS: Consecutive patients undergoing LC were interviewed, their medical records were analysed and the cost of their hospitalisation was assessed. Similar data, collected previously from patients undergoing OC, were used for comparison. RESULTS: There were 108 patients in each group, 93.5% treated electively. All had gallstones. No deaths or common bile duct injury occurred. The mean operating room time was 131 +/- 3.7 minutes for OC and 164 +/- 4.7 minutes for LC. Operative cholangiography was attempted in 80% in each group, being successful when attempted in all OCs and in 95% of LCs. The conversion rate of LCs to OCs was 4.5%. Minor complications were more frequent with OCs. The mean duration of hospital stay was 6.5 +/- 0.3 days for OCs and 2.0 +/- 0.2 days for LCs. The amount and period of analgesia were significantly less in the LC group. Patients recovered significantly faster after LC (P < 0.01) during the first eight weeks after surgery. There was no difference by 12 weeks. The overall cost for each LC was $838 less than OC for the entire hospital stay. CONCLUSION: These results support the view that LC is a safe and justified replacement for OC in the elective situation, with benefits to the patient, hospital and general community. The hospital cost for LC was less than for OC.

Adolescent

Changes in the practice of biliary surgery and ERCP during the introduction of laparoscopic cholecystectomy to Australia: their possible significance.

Two and a half years after the introduction of laparoscopic cholecystectomy to Australia in February 1990, estimates from Medicare statistics suggest that by July 1992, 69% of cholecystectomies were being performed laparoscopically. There was a smaller decline in the numbers of open cholecystectomies performed, suggesting a 28% rise in the rate of cholecystectomy. This has been associated with a 66% decline in the use of intra-operative cholangiography. Whereas 87% of cholecystectomies had an operative cholangiogram performed, now only 23% of all cholecystectomies do. It is suggested that in approximately half the patients, no attempt is made to exclude common duct stones. With those patients in whom an attempt is made, most surgeons rely on endoscopic retrograde cholangiopancreatography, as evidenced by a 43% increase in its use, or, more recently, a small proportion of surgeons have been using intravenous cholangiography, as evidenced by a 26% increase in its use. Once diagnosed, these stones are no longer being treated by open exploration of the bile duct, indicated by a 46% decrease in this procedure, but are being treated by endoscopic sphincterotomy, which has shown a 242% increase in its use. From the published results of the outcome of these treatments, the added risk, nationally, of these additional procedures in managing uncomplicated bile duct stones is predicted to increase mortality 1-3-fold and morbidity 10-15-fold. This risk can be reduced by the use of laparoscopic bile duct exploration. These techniques are already well established and can be learnt quickly if practice is achieved by performing routine intra-operative cholangiography.(ABSTRACT TRUNCATED AT 250 WORDS)

Australia

The role of the kidney in the clearance of calcitonin gene related peptide (CGRP).

Calcitonin gene-related peptide (CGRP) is a 37 amino-acid peptide, undetectable in the plasma in health but elevated in certain disease states such as medullary thyroid cancer, and potentially causes symptoms. The kidney is a major site of and influence on the clearance of exogenously infused CGRP. As CGRP might cause symptoms in renal dysfunction, this study was performed to determine the clearance of CGRP in humans and animals with altered renal function. In chronic renal failure patients, CGRP was not detected in plasma either before or after haemodialysis. In sheep, before and after bilateral nephrectomy, there was an approximate halving of plasma clearance and doubling of the circulating half-life of infused CGRP. This reduction in clearance was greater than that which could be accounted for by the reduction in degradation by renal substance alone. This renal influence on extra-renal CGRP metabolism was not due to the renal production of a circulating peptidase as evidenced by the absence of such peptidase in the plasma of normal and anephric sheep. Further, severity of uraemia had no influence on the extra-renal metabolism. The mechanism by which the kidney influences the extra-renal metabolism of CGRP remains obscure.

Animals

Laparoscopic adrenalectomy.

Minimal access surgery continues to expand its applications now including laparoscopic adrenalectomy. Two differing intraperitoneal techniques are described in six patients, three with Conn's Syndrome, one with a Cushing's tumour, one with a phaeochromocytoma and one with a large non-functioning cortical adenoma. This initial Australasian experience with the procedure followed careful preparation in the cadaver and pig.

Adrenal Gland Diseases

The effect of incisional infiltration of bupivacaine upon pain and respiratory function following open cholecystectomy.

A controlled, prospective, double-blind trial of wound infiltration with bupivacaine in elective open cholecystectomy was performed to determine if this was an effective method of pain relief and reduced respiratory complications. Additionally, dextran was added to the bupivacaine in an attempt to prolong the effect. The solutions used were, bupivacaine alone 0.25% (n = 14), bupivacaine 0.25% with dextran 70 (n = 16) and saline (n = 16) as a control. To determine the effect of each solution, the subjects were assessed for pain perception and respiratory function before and after surgery. Pain was assessed using a visual analogue scale and narcotic usage, and respiratory function was assessed by spirometry, chest X-rays and arterial blood gases. The study did not demonstrate any objective improvement in either pain relief or respiratory function. This may reflect inadequate infiltration by the surgeons in the study or that infiltration should have been performed prior to incision.

Adult

Attitudes towards liver transplantation in Victoria, Australia.

Liver transplantation commenced on a regular basis in Australia in 1985. This followed the first successful orthotopic transplant in Brisbane in 1985 and the setting up of a National Centre for Liver Transplantation in Sydney in 1985 with clinical transplantation beginning there in 1986. A centre was subsequently developed in Melbourne in 1988. As this procedure was perceived to be expensive, and because of discussion on rationing of medical services, the authors were prompted to test the Victorian community awareness and attitude to government funding of transplantation. One year after the establishment of the Victorian Liver Transplantation Programme, a random survey of the Victorian population and of general practitioners in Melbourne was conducted with the assistance of a professional polling company. Sixty-five per cent of the Victorian population knew liver transplantation was available in Victoria, 12% said it was not available and 23% did not know. Among general practitioners, 79% knew liver transplantation was available 14% said it was not available and 7% did not know. Eighty-eight per cent of Victorians and a similar proportion of general practitioners said the State Government should provide funding. Forty-seven per cent of the Victorian population said government should provide total funding and a further 39% funding of more than 50%. Among general practitioners, 33% said total funding should be provided and a further 46% thought that more than 50% of funding should be provided. This survey has revealed convincingly that Victorians have decided that their health care should include the expense of liver transplantation paid for by government. Awareness of the availability of the operation of liver transplantation is developing rapidly.

Attitude to Health

Common bile duct calculi at laparoscopic cholecystectomy: a technique for management.

Laparoscopic cholecystectomy was attempted in 150 unselected patients. The use of routine intraoperative cholangiography prevented serious bile duct injury in one patient. It also showed 75% of patients suspected pre-operatively of having common duct stones, had passed them by the time of cholecystectomy. Eight of 12 diagnosed duct stones (5 suspected, 7 unsuspected) were removed laparoscopically. A technique is described using inexpensive and readily available equipment that allows the transcystic duct treatment of the majority of common duct stones. The development and use of such techniques to laparoscopically treat duct stones will once more allow surgeons to treat all biliary calculi at the one procedure and reduce unnecessary dependence on endoscopic retrograde cholangiopancreatography/sphincterotomy.

Cholangiography

The morbidity of surgical access: a study of open versus laparoscopic cholecystectomy.

A prospective non-randomized study of 37 adult patients undergoing open cholecystectomy and 40 patients undergoing laparoscopic cholecystectomy was undertaken to test the hypothesis that surgical access alone has a significant impact on postoperative morbidity. Specifically the study examined the deterioration of pulmonary function, development of pulmonary complications, postoperative narcotic requirement and total bed stay as markers of postoperative morbidity. The results showed that significantly less deterioration of pulmonary function occurred in patients treated using the laparoscopic approach. In this group there was also significantly less requirement for postoperative narcotics, less consequent development of pulmonary complications and a shorter bed stay in hospital. The study documents the substantial impact of surgical access on postoperative morbidity and highlights the benefits of the laparoscopic 'minimal access' approach.

Adult