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Biomedical subjects

G K Kiroff

Publications and source records attributed to G K Kiroff.

At least 19 recordsLinked to original sources

Comparative study on acute pancreatitis management.

BACKGROUND: Guidelines have been published regarding the management of acute pancreatitis by the British Society of Gastroenterology (BSG). The aim of the present paper is to compare the management of patients with acute pancreatitis in a tertiary referral medical centre and a regional health centre in Australia during 2001, evaluate compliance with the published BSG guidelines, and compare our data with those of a similar UK study. METHODS: Patients with a primary diagnosis of acute pancreatitis were identified retrospectively. Eighty-four admissions from the Austin Hospital (AH), a tertiary referral centre, and 83 from The Geelong Hospital (TGH), a regional health centre, were treated in these two hospitals. The histories were collected and examined for compliance with the guidelines recommended by the BSG. We compared our data with the data from the two UK hospitals in a previous study. RESULTS: Only 38% of patients from these two centres had all the investigations performed for severity stratification as recommended by BSG. In other respects, AH and TGH managed these patients with acute pancreatitis according to the recommendations. The overall mortality rate from acute pancreatitis was 3.0%, and within the group of severe acute pancreatitis the mortality rate was 22.7%. 65.5% of patients from AH with gallstone related acute pancreatitis had a cholecystectomy or sphincterotomy and extraction of gallstones within 4 weeks of presentation. There were five re-admissions to AH in 2001 due to non-operated gallstone-related acute pancreatitis. In contrast, 84.3% of patients from TGH had definitive treatment within 4 weeks and there were three re-admissions to TGH. CONCLUSION: Overall, both a tertiary referral centre and smaller regional hospital in Australia managed acute pancreatitis according to recently published BSG guidelines. The guidelines emphasized the importance of expertise in hepatopancreatobiliary surgery, availability of intensive care unit/high dependency unit and dynamic CT scanning. The recommendations for definitive treatment of patients with gallstone-related pancreatitis within 4 weeks of presentation reduced the morbidity and mortality in this group. Although compliance with the guidelines on investigation for severity stratification of acute pancreatitis was poor, this lack of formal severity assessment did not appear to influence the outcome.

Acute Disease↗

Ablation of Barrett's epithelium: the promise and the problems.

The incidence of adenocarcinoma of the esophagus has increased dramatically over recent years. Because Barrett's epithelium is recognized as a risk factor for adenocarcinoma there is an interest in reversing this metaplasia. A number of endoscopic methods of destruction of esophageal columnar epithelium have been described. The purpose of this article is to review the currently available methods of managing Barrett's epithelium with particular reference to the role of ablative therapy in reducing the risk of adenocarcinoma.

Barrett Esophagus↗

Publication bias in presentations to the Annual Scientific Congress.

BACKGROUND: Free papers presented to the Annual Scientific Congress (ASC) of the Royal Australasian College of Surgeons (RACS) were reviewed for the years 1994, 1995 and 1996. Reports were examined for evidence of publication bias. METHODS: Suitable free papers were identified from the proceedings of the meetings and authors were contacted to obtain information about the research reported and any publications resulting from it. RESULTS: Responses were obtained from 302 of 576 presentations considered suitable. A total of 55% of responding authors reported publication of their paper. Basic science papers were most likely to be published. There was a significant bias in favour of publication of positive results (98 of 139 positive vs 76 of 159 inconclusive or negative reports; P < 0.01). Retrospective data were as likely to be published as prospective (51% and 57%, respectively). Reports describing studies of high-level evidence were more likely to be published in journals with a high impact factor. CONCLUSION: The ASC is a comprehensive meeting that attracts a wide range of free papers from most sections of the RACS. There appears to be no evidence of bias in selection of papers for inclusion in the meeting but there is bias in the subsequent publication, which favours positive reports.

Australia↗

Minimal residual marrow disease: detection and significance of isolated tumour cells in bone marrow.

BACKGROUND: Detection of malignant cells in bone marrow and peripheral blood of patients with solid tumours at the time of surgery is increasingly emerging as a prognostic factor for disease progression and a way of monitoring adjuvant therapies. Furthermore, isolation and characterization of these cells provide insight into the early metastatic process, with potential therapeutic implications. This article reviews the current knowledge about the clinical significance of minimal residual marrow disease (MRMD) and its methods of detection, outlining some of their specific technical problems. METHODS: A comprehensive review of articles cited in the largest medical databases was conducted. RESULTS: The sensitivity of the methods of detecting MRMD has improved substantially in the past decade, resulting in higher detection rates. In many solid tumours MRMD has been found to correlate with disease-free and overall survival; however, the importance of this as an independent prognostic variable remains contentious. CONCLUSIONS: There is a need for a standardized approach to the detection of these cells before they become integrated into the current staging systems. The challenge remains to establish which of these tumour cells have the capacity to progress and develop metastatic disease, what are the early genetic and molecular mechanisms underlying this process and to apply novel, better targeted therapies against them.

Bone Marrow↗

The introduction of patient-controlled analgesia into an isolated rural hospital.

This study investigated the feasibility of using patient-controlled analgesia (PCA) effectively in a small 70 bed isolated rural hospital. The first 50 patients to use a Bard PCA 1, in the Port Lincoln Hospital, South Australia, were studied. The patients consumed morphine at a mean rate of 1.24 mg/h and used PCA for a mean of 48 h. Thirty-eight per cent of patients required treatment for nausea and other complications which is similar to the rate of those in other published series. Visual analogue pain scores showed excellent pain control, generally without evidence of oversedation; however, there was one episode of respiratory depression. Seventy-eight per cent of patients reported that their pain was relieved most or all of the time. The study demonstrated that a PCA service provided by nursing staff, the GP anaesthetist and rural surgeons is feasible in an isolated rural hospital.

Adult↗

Cervical or thoracic anastomosis for esophagectomy for carcinoma.

A prospective trial was conducted to compare intrathoracic and cervical anastomoses after esophagectomy for squamous cell carcinoma of the middle or lower one-third of the esophagus. One hundred and twenty-three patients were randomized to have either a cervical or thoracic anastomosis. Thirty-one patients were subsequently excluded either because esophagectomy was performed without thoracotomy or the tumor was unresectable or because the randomization protocol was not complied with. Transfusion requirements and operating time were similar for the 49 patients having esophagectomy by way of the laparotomy and right thoracotomy (TA) and the 43 patients who underwent laparotomy, right thoracotomy and cervicotomy (CA). Forty-three per cent of the CA and 49 per cent of the TA patients had involved lymph nodes. An esophagectomy incorporating a cervical anastomosis resulted in a significantly greater margin of macroscopically normal esophagus above the tumor (median of 4.0 versus 1.5 centimeters for TA). A leak was significantly more frequent after cervical anastomosis (26 per cent) than thoracic (4 per cent) (p less than 0.002). Respiratory complications were more frequent with a thoracic anastomosis, but this was not statistically significant. Thirty day mortality rates were similar for the two groups: 14.3 per cent, TA, and 9.3 per cent, CA (p = N.S.). Postoperative strictures occurred in 14 per cent of TA and 23 per cent of CA patients and were most common after an anastomotic leak. The survival patterns of the two groups were similar. The median survival time for CA patients was 23 months and for TA, 20 months. Excluding hospital mortality, 47 per cent of patients were alive at two years and 30 per cent at 40 months. Survival was related to extent of disease. The greater length of tumor-free esophagus removed with a cervical anastomosis did not result in an improved long term survival period, but was associated with a significantly higher incidence of anastomotic fistula.

Aged↗

Bile salt-induced injury of rabbit oesophageal mucosa measured by hydrogen ion disappearance.

Oesophageal injury secondary to gastro-oesophageal reflux is unlikely to be due to the effects of hydrochloric acid alone. The present authors have investigated the development of acid and bile salt-induced oesophageal mucosal injury in a rabbit model. Solutions of hydrochloric acid and sodium taurocholate (ST) were perfused through an isolated oesophageal preparation and mucosal injury was determined by measuring the rate of H+ disappearance. Perfusion with acid alone in concentrations up to 10 mmol/l did not affect the H+ disappearance rate. Addition of 1 mmol/l ST to an acid perfusate resulted in loss of H+ from the system. The increase in H+ disappearance rate was associated with loss of ST from the perfusate. Sodium taurocholate was only lost from the system when in an acid medium. Increased rate of H+ disappearance occurred even after the bile salt had been washed out of the perfused oesophagus. The mechanism of bile salt-induced mucosal injury was unlikely to be due to mucosal disruption secondary to micelle formation since the critical micellar concentration of taurocholate was found to be greater than that used in the perfusate. These findings indicate that bile salts may be an important factor in hydrochloric acid-related damage to oesophageal mucosa, by acting through mechanisms unrelated to micelle formation.

Animals↗

Morphological changes caused by exposure of rabbit oesophageal mucosa to hydrochloric acid and sodium taurocholate.

The present authors have studied the light and electron microscopic changes in rabbit oesophageal mucosa which has been exposed to solutions of hydrochloric acid and sodium taurocholate (ST). In an in vivo model the oesophagus was perfused with saline, acid (0.1-40 mmol/l of H+) or taurocholate (0.1-1.0 mmol/l at pH 2.0 or 1.0 mmol/l at neutral pH). At the end of each perfusion experiment the oesophagus was removed and assessed by the naked eye, light and electron microscopy. Some desquamation of superficial stratum corneum cells occurred in all specimens perfused for 5 h. Injury was more evident to the stratum spinosum and basal cell layers. Damage was more severe in the bile salt plus acid perfused specimens, varying between margination of nuclear chromatin in the basal cells to complete necrosis and separation of the overlying layers. Taurocholate in neutral solution did not damage the oesophageal epithelium. Electron microscopy revealed that damage to cells in the basal layers and stratum granulosum occurred within 30 min of exposure to acidified taurocholate, this damage increasing with time. It is concluded that taurocholate is able to damage oesophageal mucosa, that the damage first occurs in the deeper layers of the oesophageal mucosa and that the damage may occur in the absence of gross or light microscopic changes in the mucosa.

Animals↗

Peripheral blood leucocyte subpopulations in patients splenectomized for trauma.

Monoclonal antibodies were used to type leucocyte subpopulations in peripheral blood mononuclear leucocytes (MNL) from patients who had had spleens removed following trauma. The proportion of OKT3+ (T) cell and OKT4+ ('T helper/inducer') cell was significantly decreased in splenectomized subjects. While a decrease was also observed for the OKT8+ ('T suppressor/cytotoxic') cells, this was not significant. The ratio of OKT4+/OKT8+ cells was significantly decreased in the splenectomized group. Interestingly, the absolute numbers of OKT3+, OKT4+ and OKT8+ cells were increased. The % of B lymphocytes (identified as Ig+ and FMC1+ cells) was significantly increased in patients. The proportion of MHC Class II+ cells (FMC4+) was also increased although not significantly. A marked increase in % of monocytes (FMC33+) was observed in patients. The changes in proportion of regulatory T cells and monocytes may in part explain the depressed mitogen responses of MNL from splenectomized subjects.

Adult↗

Heterotopic autologous splenic grafts in rat. Morphological studies.

Splenic grafts autotransplanted at splenectomy into the omentum of 23 Porton strain rats were compared with spleens from 10 sham-operated controls. Six months after transplantation, the grafts weighed between 81 to 545 mg (median 166 mg) compared to control spleens which weighed 775 to 1,250 mg (median 995 g). Histoquantitation of the grafts revealed marked reduction of the splenic white pulp when compared to control spleens. Morphological examination showed not only a reduction of lymphocytes but also a striking architectural abnormality in all grafts. In 2 of the transplants, no lymphoid aggregates were observed; small subcapsular collections were present in 7, while in 8, isolated perivascular aggregates of lymphocytes with poorly formed marginal zones were observed. Only 6 transplanted spleens showed linkage of adjacent lymphoid aggregates but the number and size of these aggregates were clearly less than normal. These findings indicate that autotransplanted splenic tissue in rats does not regain histological normality. The implications of these observations for autotransplantation in splenectomized patients are discussed.

Animals↗

Elevated natural killer (NK) cytotoxicity of mononuclear leucocytes from splenectomized patients: increase in Leu-7+ and Leu-11+ leucocytes.

The natural killer (NK) cell cytotoxic activity (against K562 targets) of peripheral blood mononuclear leucocytes (MNL) from patients splenectomized for trauma was examined. The data were fitted to a mathematical model from which the values for maximal cytotoxicity, and the number of MNL required to achieve 25% cytotoxicity (LD25-, were computed. The results showed that the NK cell cytotoxicity of MNL from splenectomized patients was significantly elevated at all effector/target cell ratios tested (1:1 to 100:1), compared to normal subjects. In the splenectomized group there was a significant increase in the maximal cytotoxicity and a significant reduction in the LD25. Flow cytofluorometry studies revealed an increase in percentage and absolute numbers of cells bearing Leu-7 or the Leu-11 antigens in MNL of splenectomized patients. We found that there was a significant correlation between the percentage of Leu-11+ cells and the NK cytotoxicity (both maximal and LD25) but not between Leu-7+ and these parameters, for both the controls and splenectomized subjects. This suggests that the increased NK cytotoxicity by the MNL of splenectomized patients may be due wholly or partly to an increase in the proportion of cells expressing the Leu-11+ antigens.

Adult↗

Domperidone, metoclopramide, and placebo. All give symptomatic improvement in gastroesophageal reflux.

A double-blind crossover study was conducted of two gastric prokinetic drugs in 23 patients with gastroesophageal reflux. Patients were divided into two groups on the basis of a dual-isotope mixed-meal study of their gastric emptying (GE). Group I had normal GE and group II delayed GE. Nine gastrointestinal symptoms were assessed for frequency and severity before treatment. The trial had three 1-month treatment periods using metoclopramide 10 mg q.i.d., domperidone 20 mg q.i.d., or placebo on a random basis. Symptoms were reassessed at the end of each month. Taken as a whole, the group showed a significant symptomatic response in all three treatment periods (p less than 0.0001), but patients with delayed or normal GE did not differ significantly in their symptomatic response. Eleven patients complained of side effects with metoclopramide and three stopped therapy before the 1-month course was completed. Two patients described side effects with domperidone, including one woman with galactorrhea after 36 h of treatment. Three patients on placebo also complained of important side effects. We conclude that a significant placebo effect is present in the treatment of gastroesophageal reflux. No significant difference was demonstrated in symptomatic improvement between placebo, domperidone, and metoclopramide in this study.

Adult↗

Elevated natural killer (NK) cell activity: a possible role in resistance to infection and malignancy in immunodeficient splenectomized patients.

Splenectomized patients, who have had their spleens removed following trauma, have immune deficiencies. However, the risk of infection (with one exception--septicaemia caused mainly by Streptococcus pneumoniae) and malignancy in these patients appears to be comparable to that of healthy individuals. We propose that a compensatory increase in the activity of effector cells, such as natural killer cells (NK) and macrophages, may protect against infection and malignant diseases in splenectomized individuals.

Adolescent↗