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Biomedical subjects

G Keogh

Publications and source records attributed to G Keogh.

13 recordsLinked to original sources

Desmoplastic reaction in pancreatic cancer: role of pancreatic stellate cells.

OBJECTIVES: Pancreatic cancer has a very poor prognosis, largely due to its propensity for early local and distant spread. Histopathologically, most pancreatic cancers are characterized by a prominent stromal/fibrous reaction in and around tumor tissue. The aims of this study were to determine whether (1) the cells responsible for the formation of the stromal reaction in human pancreatic cancers are activated pancreatic stellate cells (PSCs) and (2) an interaction exists between pancreatic cancer cells and PSCs that may facilitate local and distant invasion of tumor. METHODS: Serial sections of human pancreatic cancer tissue were stained for desmin and glial fibrillary acidic protein (stellate cell selective markers) and alpha-smooth muscle actin (alphaSMA), a marker of activated PSC activation, by immunohistochemistry, and for collagen using Sirius Red. Correlation between the extent of positive staining for collagen and alphaSMA was assessed by morphometry. The cellular source of collagen in stromal areas was identified using dual staining methodology, ie, immunostaining for alphaSMA and in situ hybridization for procollagen alpha1I mRNA. The possible interaction between pancreatic cancer cells and PSCs was assessed in vitro by exposing cultured rat PSCs to control medium or conditioned medium from 2 pancreatic cancer cell lines (PANC-1 and MiaPaCa-2) for 24 hours. PSC activation was assessed by cell proliferation and alphaSMA expression. RESULTS: Stromal areas of human pancreatic cancer stained strongly positive for the stellate cell selective markers desmin and GFAP (indicating the presence of PSCs), for alphaSMA (suggesting that the PSCs were in their activated state) and for collagen. Morphometric analysis demonstrated a close correlation (r = 0.77; P < 0.04; 8 paired sections) between the extent of PSC activation and collagen deposition. Procollagen mRNA expression was localized to alphaSMA-positive cells in stromal areas indicating that activated PSCs were the predominant source of collagen in stromal areas. Exposure of PSCs to pancreatic cancer cell secretions in vitro resulted in PSC activation as indicated by significantly increased cell proliferation and alphaSMA expression. CONCLUSIONS: Activated PSCs are present in the stromal reaction in pancreatic cancers and are responsible for the production of stromal collagen. PSC function is influenced by pancreatic cancer cells. Interactions between tumor cells and stromal cells (PSCs) may play an important role in the pathobiology of pancreatic cancer.

Actins↗

Modern management of pancreatic carcinoma.

Pancreatic cancer remains a fearsome disease. New insights into the molecular pathogenesis may influence choice of treatment modalities and provide avenues for novel therapeutic strategies for testing in the clinic. The survival rate of patients with all stages of disease is poor and clinical trials are appropriate alternatives for treatment and should be considered. Surgical resection, when possible, remains the primary treatment modality and can result in long-term cure. Less invasive techniques such as laparoscopy may reduce the rate of unnecessary laparotomies. The role of adjuvant therapy is re-emerging. Patients with unresectable and metastatic disease are incurable and optimal palliation is the goal. These patients may benefit from palliative bypass of biliary or duodenal obstruction if symptomatic. Pain associated with local tumour infiltration may be palliated with radiation, with or without chemotherapy, or with coeliac nerve blocks or local neurosurgical procedures. Chemotherapy with gemcitabine has modest objective response rates but has been shown to improve symptoms.

Antineoplastic Agents↗

Error reduction: academic detailing as a method to reduce incorrect prescriptions.

OBJECTIVES: Clinical decision making can be influenced by academic detailing, and it was hypothesised that this technique may be used to reduce simple errors when prescribing drugs of addiction. These prescriptions require specific details to be included, otherwise the prescription has to be returned to the prescriber and re-written, wasting the time of the dispenser and prescriber alike. METHODS: The legal requirements for the prescription of addictive drugs were used to define prescription errors. Prescription error rates at six hospitals were assessed, including a control and an intervention hospital where academic detailing was carried out. Prescription error rates were documented before and after an academic detailing visit to junior doctors, including the provision of a bookmark containing the requirements for these drugs. These errors were expressed as a percentage of the total written for a 4-week period. RESULTS: At the intervention hospital, there was a significant decrease in error rate (from 41% to 24%, P<0.0001) with an improvement in all the requirements stated on the bookmark. At this hospital, the confidence of the junior doctors on a self-rating 5-point scale in writing prescriptions for these drugs increased from a mean of 3.25 (95% CI 2.92-3.58) to 4.14 (95%CI 3.90-4.38) after the intervention (P=0.03). The baseline error rates at the other hospitals ranged from 25% to 46%, but the control hospital did not show a significant change in error rate over the same study period ( P=0.66). A post-hoc review suggested that liquid preparations were more difficult to prescribe correctly, which in part accounted for the differences in error rate between hospitals. CONCLUSIONS: Academic detailing appears to be a useful method of reducing erroneous hospital prescriptions; and, to our knowledge, this is a novel finding.

Analgesics, Opioid↗

Insurance and the risk of ruptured appendix in the adult.

BACKGROUND: Disparities in medical care related to the insurance status of patients have been reported. A retrospective analysis was performed to examine the insurance-related differences in the risk of appendiceal perforation in the Prince of Wales Hospital (POWH), New South Wales. METHODS: Computerized data of 1179 patient years who had a diagnosis of appendicitis and were admitted to the POWH over the preceding 10 years were examined. The outcome measure was appendiceal perforation. Patient variables examined were insurance status, sex, age, and socio-economic status (SES). Three hundred patients over the same period were identified who had an appendicectomy but not appendicitis. Multiple logistic regression and Fisher's exact test were used for statistical analysis. RESULTS: The overall perforation rate in 1179 patients was 17%. The only factor that was related to an increased risk of perforation was age over 50 years (odds ratio (OR) 1.57; 95% confidence interval (CI) 1.04-2.53). Sex, insurance status or SES were not associated with a higher risk of perforation. The overall rate of negative appendicectomy was 20% (300 of 1479 patients), and the rate was higher in the uninsured patients (22 vs 17%, P = 0.014, Fisher's exact test). CONCLUSIONS: Lack of health insurance was not associated with an increased incidence of appendiceal perforation at the POWH. Age over 50 years was identified as the only risk factor for appendiceal perforation. The lower negative appendicectomy rate in the insured group may be because of better diagnostic ability of consultants compared to registrars.

Acute Disease↗

The validity of surgical wound infection as a clinical indicator in Australia.

BACKGROUND: Evidence-based medicine and measurement of outcome have become the foremost strategy of departments of health and quality care in Australia in the 1990s. The Australian Council of Healthcare Standards, (ACHS), formed in 1974, has introduced a Clinical Indicators Programme which monitors a number of clinical outcomes, including rates of specific nosocomial infections. It is the only formal system in Australia which attempts to monitor nosocomial infection in hospitals, and the ACHS acknowledges that the data provided to them are collected using a variety of sources and definitions. METHODS: The present study discusses the validity of the present definitions of nosocomial surgical wound infection used for accreditation, how validity may be improved and the attempts by some international systems to improve their own data. RESULTS: The ACHS definitions of nosocomial surgical wound infection lack validity, and the rates provided lack generalizability. Several international surveillance systems have resources in place to provide members with standardized training for practitioners, and support for methodology, data analysis and reporting, which assists in improving the quality of the data collected. CONCLUSION: It is our belief that the validity of surgical wound infections will be improved by adoption of National Nosocomial Infection Surveillance (NNIS) definitions, stratification of surgical wound infections by anatomical site of infection for sentinel procedures. The ACHS system must adopt the proposed changes if the rates are to be used as a local and national indicator.

Australia↗

Methods of replacing blocked hepatic artery catheters.

BACKGROUND: Regional chemotherapy using hepatic artery catheters is one method of treating patients with colorectal liver metastases. A problem arises when the catheter occludes in patients who are responding to treatment. This report describes experience of replacing occluded hepatic artery catheters. METHODS: Some 108 patients with colorectal liver metastases had hepatic arterial catheters surgically implanted for regional chemotherapy. The catheter occluded in 17 patients at a time when they were responding to treatment. Twelve catheters were replaced, of which seven were inserted retrogradely into the splenic artery, four were anastomosed end to side to the common hepatic artery via a saphenous vein graft and one was replaced in the patent gastroduodenal artery. RESULTS: The mean duration of catheter survival when a saphenous vein graft was used was 9.6 months compared with 2.5 months following retrograde insertion into the splenic artery. CONCLUSION: Replacement of hepatic artery catheters is possible and may be of benefit in patients whose catheters fail while they are responding to treatment. The use of a saphenous vein graft appears to be a more anatomical and therefore preferable method of replacement than retrograde splenic artery cannulation.

Catheters, Indwelling↗

Some examples of the analysis of complex samples by micellar electrokinetic capillary chromatography with photodiode array detection.

The use of micellar electrokinetic capillary chromatography with photodiode array detection to assist in identifying the minor components in crude morphine, poppy straw and opium preparations, for the analysis of synthetic colours and other food additives in cordials and confectionery and for the identification of the ring substituted amphetamine derivative methylenedioxyethylamphetamine in illicit drug samples is demonstrated.

3,4-Methylenedioxyamphetamine↗

Spontaneous Clostridium septicum myonecrosis in congenital neutropaenia.

Spontaneous Clostridium septicum myonecrosis is an uncommon disorder that has been described in association with malignancy, immunosuppression and neutropaenia. Typical clostridial myonecrosis develops without a visible portal of entry and mortality is high. The pathogenesis is not completely understood but the clostridia may gain access to the circulation via areas of ileo-caecal ulceration secondary to enterocolitis, antibiotics or neoplasms. A 5 year old boy with congenital neutropaenia presented with spontaneous Clostridium septicum myonecrosis in the thigh. Limb salvage was achieved using antibiotics, hyberbaric oxygenation and selective debridement. The portal of entry may have been the gastrointestinal tract as colonic ulceration may occur in neutropaenia, and pre-morbid clindamycin administration may have encouraged overgrowth of colonic clostridia.

Anti-Bacterial Agents↗