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Biomedical subjects

M Bilous

Publications and source records attributed to M Bilous.

35 records · Page 2Linked to original sources

Interferon alfa for chronic active hepatitis B. Long term follow-up of 62 patients: outcomes and predictors of response.

OBJECTIVE: To evaluate the response to treatment with interferon alfa and the long term outcome of patients with chronic active hepatitis B. METHODS: Sixty-two patients with chronic active hepatitis B (43 males, 19 females; age range, 10-67 years) who were treated with interferon alfa at Westmead Hospital between 1984 and 1992 were followed up (mean period of follow-up, 44 months). Thirty-nine patients were treated with interferon alfa-2a and 23 with interferon alfa-2b for a mean of 22.5 weeks. Interferon was given three times a week with a dose range of 3-21 million U. We evaluated pretreatment predictors of response (patient's age, sex, ethnic origin, presence of cirrhosis, serum levels of alanine aminotransferase [ALT] and hepatitis B virus DNA [HBV-DNA]) and the effect of dose and type of interferon. RESULTS: Nine patients had a complete response to treatment with interferon alfa (loss of hepatitis B surface antigen), 26 had a partial response (permanently HBV-DNA negative, hepatitis B e antigen to anti-hepatitis Be seroconversion), eight had a transient response and 19 had no response. All patients with a complete response had normal ALT levels at last follow-up. Histological evidence of hepatic inflammation was significantly reduced in responders. A high pretreatment ALT level and a low HBV-DNA titre were both positive predictors of a favourable response. We found no significant difference in the response to different types of interferon or to high or low dose regimens, or in the responses of patients with cirrhosis. CONCLUSION: Treatment with interferon alfa was associated with prolonged suppression of HBV replication in over half these patients and 14% appear to have been cured of the infection. Suppression of HBV replication is associated with sustained abatement of liver disease.

Adult↗

Adequacy of histopathology reports for breast cancer in New South Wales.

To assess the adequacy of diagnostic histopathology reports for breast cancer in New South Wales (NSW) and the Australian Capital Territory (ACT), a cross-sectional survey of diagnostic histopathology reports was carried out on a random sample (n = 1000) of NSW and ACT women diagnosed with breast cancer in 1992 and notified to the NSW Central Cancer Registry. A single pathologist with expertise in breast cancer reviewed the reports, from laboratories in public and private sectors, against a checklist enumerating basic features considered useful for decision making by surgeons and/or medical and radiation oncologists. While information was provided by almost all reports on histological classification (94%), size of tumor (93%) and involvement of lymph nodes (99.8%), this was not so for tumor resection/biopsy margin (77%), histological grade (69%), nuclear grade (23%), mitotic rate (11%) and the presence or absence of lymphatic (34%) or vascular (24%) invasion. Pathologists from teaching hospitals and those who reported on more than 10 cases in the sample were more likely to provide relevant information. Many diagnostic histopathology reports for breast cancer did not fulfil the requirements for a satisfactory report, established prognostic and predictive features frequently being omitted. The uniform use by pathologists of a carefully designed checklist could ensure that standard information is provided for every breast cancer, thereby facilitating choice of therapy for all patients.

Breast Neoplasms↗

Coinfection with hepatitis B and C or B, C and delta viruses results in severe chronic liver disease and responds poorly to interferon-alpha treatment.

Chronic coinfection with the hepatitis B (HBV) and hepatitis delta (HDV) viruses is known to cause severe liver disease, but the importance of coinfection with hepatitis C virus (HCV) and HBV has not been well documented. In the present study, the clinical and pathological severity of liver disease among patients with hepatitis resulting from multiple viruses was examined and an open trial of the efficacy of interferon-alpha 2b (IFN-alpha) treatment was conducted. Nineteen patients with chronic HBV and HCV infection and 17 with HBV, HCV and HDV infection were studied; 12 in each group underwent liver biopsy. For each coinfected patient, two patients infected with HCV alone were selected as controls, and these were matched for age and risk factor and were estimated to have been infected for a similar duration. Coinfection with HBV and HCV or HBV, HCV and HDV was associated with more severe liver disease than HCV alone (P < 0.01); total Scheuer score, portal and lobular inflammation and fibrosis were all worse in coinfected subjects. Eight patients with chronic HBV and HCV were treated with recombinant IFN-alpha 2b [3 million units (MU), thrice weekly for 6 months]. Liver function tests normalized in two patients and one lost hepatitis B surface antigen (HBsAg). Seven patients with hepatitis B, C and delta coinfection were treated with the same regimen and only one normalized serum alanine aminotransferase (ALT) during (and after) treatment. It is concluded that coinfection with multiple hepatitis viruses is associated with histologically more severe liver disease than HCV alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Excess iodine induces the expression of thyroid solid cell nests in lymphocytic thyroiditis-prone BB/W rats.

Previous epidemiological studies have suggested that lymphocytic thyroiditis and/or an increased iodine intake may be risk factors for the development of thyroid cancer. We previously reported that excess iodine accelerated the development of thyroid lymphocytic infiltration (LI) in the autoimmune BB/W rat model. We also found that excess iodine increased thyroid cell proliferation in a disordered manner. The present study was designed to further explore these observations and to address the question as to whether excess iodine under certain conditions predisposes the thyroid gland to neoplasia. To test this hypothesis, the lymphocytic thyroiditis-prone BB/W rat was exposed to excess iodine in drinking water. Ten BB/W rats at 4 weeks of age were given iodine water (NaI 0.05%) for 10 weeks, whilst another 10 BB/W rats were given tap water and served as controls. Eighteen normal Wistar rats were also divided into excess iodine and control groups, served as a comparison to the BB/W rats. We found that an excess iodine intake accelerated the development of LI in the BB/W rat. Severe LI was usually accompanied by prominent thyroid cell proliferation, evident as numerous microfollicles and cell masses, not forming normal thyroid follicles. Numerous lymphocytes and plasma cells often encroached on these areas of increased cellular proliferation. The surprising feature, and a possible indicator of activated thyroid cell proliferation, was the high incidence of thyroid solid cell nest-like lesions (SCN) in the iodine treated BB/W rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Comparison of fluoropolymer passivated Dacron and polytetrafluoroethylene grafts in a sheep model.

The search for an optimal prosthetic vascular graft suitable for small vessels continues. The aim of this study was to compare a fluoropolymer passivated Dacron graft with a standard polytetrafluoroethylene graft. A sheep animal model was used. Under general anaesthesia a 5-cm length of 5-mm diameter graft was interposed into the left carotid artery. After an interval of 1, 2 or 3 months the sheep were reanaesthetized and a carotid angiogram performed before harvesting the graft. Graft patency was assessed by macroscopic inspection, angiography and histological examination. Overall, four of eight polytetrafluoroethylene grafts and three of ten fluoropolymer passivated Dacron grafts remained patent with similar patency rates at 1, 2 and 3 months. Histological examination of all available grafts showed evidence of fibrointimal hyperplasia. All but one of the occluded grafts had fibrointimal hyperplasia.

Anastomosis, Surgical↗

Effect of an omental wrap on the healing and vascularity of compromised intestinal anastomoses.

Adult Wistar rats were used to investigate the ability of an omental wrap to limit leakage from compromised intestinal anastomoses. Under ketamine anesthesia, a section of small bowel was divided and then reanastomosed using a "control" anastomosis, a "deficient" anastomosis, or an "ischemic" anastomosis, plus or minus the addition of a wrap of omentum. Initially 10 rats were randomly assigned to each group. Nineteen of the 20 rats with unwrapped compromised anastomoses died within six weeks, compared with five deaths in the rats protected by an omental wrap (Fisher's exact test; P less than 0.01). The experiment was then repeated with a sample of rats from each anastomotic group being sacrificed for histologic examination on days 2 to 7, 10, 14, and 42. At the time of sacrifice a dye was injected into the omental vasculature to determine its contribution to the healing anastomosis. An anastomosis could be demonstrated between omental and bowel wall vessels by the third postoperative day. At one week the infarcted bowel edges were being resorbed and the omentum formed a fibrotic cylinder aligning the separated ends of bowel wall. At six weeks the scar became more contracted and the bowel mucosa had started to grow onto its luminal surface. It is concluded from this study that the omental wrap is protective to a compromised anastomosis by providing a biologically viable plug to prevent early leakage and a source of granulation tissue and neovasculature for later wound repair.

Anastomosis, Surgical↗

Immunocytochemistry and in situ hybridisation of epidermal growth factor receptor and relation to prognostic factors in breast cancer.

The breast tumour distribution of epidermal growth factor receptor (EGFR) was studied in 193 patients with primary breast cancer by immunocytochemistry on frozen sections. EGFR was correlated (P = 0.0009) with growth fraction assessed by Ki-67, and negatively correlated with oestrogen receptor (ER, P = 0.0001) and progesterone receptor (PR, P = 0.0001) status. In 47 patients, in-situ hybridisation for EGFR mRNA showed good agreement with the immunocytochemically assessed EGFR protein. There were, however, several tumours in which EGFR mRNA could be detected in the absence of EGFR protein and there were differences between the ER and PR status of those tumours in which translation of EGFR mRNA was not seen. The cause of these differences is unclear, but these findings may represent a clue as to the differential control of breast cancer cell receptors.

Adult↗

Can the response to interferon treatment be predicted in patients with chronic active hepatitis C?

Twenty-one of 40 patients with chronic non-A, non-B hepatitis (37 anti-HCV positive) were randomised to receive interferon alpha 2b (3 million units subcutaneously thrice weekly for 24 weeks) and then to be observed for six months. Among the other 19 patients (controls) randomised to be observed without treatment for 12 months, eight have subsequently been treated with interferon for six months. One treated patient and three controls were lost to follow-up. A return to normal serum alanine aminotransferase levels which lasted until the end of the treatment period occurred in 18 (64%) of the 28 patients given interferon (and in 13 of 21 (62%) randomised to treatment), but only in one of the 16 untreated controls (p less than 0.001). Multivariant analysis indicated that, compared with the ten nonresponders, the 18 patients who responded to interferon were more likely to have acquired infection by intravenous drug abuse than by blood transfusion (p less than 0.05), and were more likely to have histologically less severe chronic liver disease (p less than 0.01). Thus, all 13 patients with less severe liver disease histologically responded to interferon, but only five of 15 patients with cirrhosis or bridging fibrosis responded. Among 17 responders followed for more than four months, five (28%) are still in remission a median of 13 months (range four months to 24 months) after stopping interferon. The characteristics which favoured a response during treatment also appeared to distinguish those who experienced sustained post-treatment remission.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Randomised controlled trial of recombinant human interferon -alpha A for chronic active hepatitis B.

The efficacy of interferon treatment for Australian patients with chronic active hepatitis B (CAH-B) was assessed by a three-centre randomised controlled trial in Sydney and Brisbane. Thirty patients (29 with histologically-proven CAH-B with and without cirrhosis and one with chronic persistent hepatitis) were allocated to receive either thrice weekly intramuscular injections of recombinant human leucocyte interferon -alpha A (either 2.5, 5.0 or 10.0 million units/m2) for six months followed by 12 months of observation, or to be observed for 18 months without active treatment. Three of 23 treated patients but none of seven controls underwent clinical, biochemical and histological resolution of their disease with loss of HBsAg, HBeAg and HBV-DNA from serum. An additional six treated and two control patients underwent a sustained partial remission of their disease. This was characterised by resolution of symptoms and serum aminotransferase abnormalities in association with seroconversion from HBeAg positive to negative, loss of HBV-DNA from serum but persistent hepatitis B surface antigenaemia. In such patients, there was significant improvement in histological appearances but some necroinflammatory activity remained and fibrosis was unchanged. Although total response rates were similar in treated and control subjects, they appeared to occur earlier after interferon treatment. Treatment with interferon was associated with predictable but minor side effects that usually did not necessitate dose reduction and rarely compromised the patient's life style. Interferon is thus a feasible treatment for CAH-B. Complete responses occurred only in treated patients and partial responses appeared to occur earlier in treated than in untreated patients. However, differences in the partial response rate at 18 months were not significant and seroconversion from HBeAg positive to negative was not associated with complete histological resolution of disease activity. Hence, while interferon is a promising agent for treatment of CAH-B, efforts must continue to define more optimal treatment regimes and to identify those patients most likely to respond to this agent.

Adult↗

Chronic non-A, non-B hepatitis: lack of correlation between biochemical and morphological activity, and effects of immunosuppressive therapy on disease progression.

A study was made of 52 patients considered to probably have chronic non-A, non-B hepatitis who were seen during an eight-year period at Westmead Hospital, Sydney. The patients were followed for a median of 28 months to assess the natural history of the disease and, in a small number of patients, the effect of immunosuppressive therapy on disease progression was examined. In 94% of cases, infection appeared to have been acquired by a parenteral route; the remainder were sporadic infections. Fifty-six per cent of the patients had mild constitutional symptoms and the remainder were asymptomatic. Similarly, 54% of patients had no signs of chronic liver disease and none exhibited signs of hepatic decompensation. Liver biopsies were performed in 42 patients; chronic active hepatitis with or without cirrhosis was present in 90%. However, neither the presence of symptoms nor the degree of biochemical abnormality were predictive of disease severity as determined histologically. Among eight patients treated with corticosteroids (with or without azathioprine), six underwent follow-up liver biopsy. Quantitative analysis of inflammatory and fibrotic changes indicated significant (p less than 0.01) progression of histological severity during a median 33 months (range 7-98 months) between biopsies with cirrhosis developing in four instances. In contrast, among the seven untreated patients rebiopsied after a median of 16.0 months (range 11-37 months) there was no overall change in histological severity and only one patient developed cirrhosis. it is concluded that histological assessment is required in all patients suspected of having chronic non-A, non-B hepatitis as other means of assessment are unreliable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Fat necrosis of the breast following lumpectomy and radiation therapy for early breast cancer.

Between January 1980 and December 1985, 121 patients with early breast cancer were treated in the Department of Radiation Oncology at Westmead Hospital by external beam irradiation and an iridium wire boost following "lumpectomy". After a median follow-up of 26 months, 14 patients have developed recurrent masses in the treated breast. In four, recurrent carcinoma was strongly suspected and subsequently confirmed by fine needle aspiration biopsy, but in only two was a subsequent salvage mastectomy possible. The remaining 10 patients developed a nodule which was usually tender. With three exceptions, the nodule was at the primary tumour site and developed 4-43 months after treatment. In seven, tumour recurrence was suspected but not confirmed by biopsy and the other three were accepted as having post-treatment "radiation fibrosis". Excision biopsy was undertaken in eight of the 10 patients. Another patient underwent partial mastectomy for presumed local recurrence. The histological appearance in all cases was similar, with areas of fat necrosis and fibrosis with atypical stromal fibroblasts. Suture material was present microscopically in eight patients and was noted macroscopically (that is, by mammogram) in the one patient who did not undergo surgery. This complication is most likely caused by a combination of surgical and radiation factors. The difficulty in management is differentiation between tumour recurrence and a benign condition.

Brachytherapy↗

Altered hepatic calcium homeostasis in guinea pigs with halothane-induced hepatotoxicity.

Exposure of guinea pigs to 1% halothane in air for 4 hr resulted in extensive centrizonal hepatic necrosis in 70% of animals examined 2 to 3 days later. In contrast, confluent hepatic necrotic lesions were not present in animals studied 24 hr after halothane exposure; only microvascular fatty change of hepatocytes with occasional necrotic cells was observed at that time (in 84% of animals). This delayed onset of lesion development afforded the opportunity to study microsomal membrane composition and indices of Ca++ homeostasis before and after the onset of halothane-induced hepatic necrosis. Hepatic microsomal cytochrome P-450 levels were unaltered 24 hr after halothane exposure, but fell to approximately 50% of control values at 72 hr. This indicates that such changes were most likely the result of hepatocellular necrosis. Microsomal lipid composition, including the relative proportions of individual phospholipids, was unaltered during halothane-induced hepatotoxicity. In contrast, microsomal Ca++ sequestration, as assessed by 45Ca uptake, was reduced 24 hr after halothane exposure compared with controls (2.76 +/- 1.32 nmol/mg of protein per min, vs. 6.63 +/- 2.88 nmol/mg of protein per min, P less than .001). This early change in microsomal Ca++ uptake was associated with a 10-fold increase in total hepatic Ca++ content at 24 hr. Subsequent changes in hepatic Ca++ content were proportionate to the severity of liver necrosis. The observation that abnormalities of hepatic Ca++ homeostasis antedate the presence of liver cell necrosis is consistent with a role for altered Ca++ fluxes in the mechanism of halothane-induced liver injury.

Alanine Transaminase↗

Breast cancer metastases masquerading as primary gastric carcinoma.

Three patients are described in whom primary gastric carcinoma of the limits plastica type was initially diagnosed. All three patients had been treated for breast carcinoma; in two the disease had been bilateral, and in two the gastric tumour was the first manifestation of relapse of that patient's breast carcinoma. The three cases are examples of a pattern of spread particularly likely to occur in infiltrating lobular carcinoma of the breast. The importance of recognizing this is paramount if appropriate therapy is to be given. One of the patients has had an excellent remission on Tamoxifen, another may be showing some response, and the third has commenced treatment with Medroxyprogesterone acetate.

Aged↗

Ductal carcinoma in situ. Part I: Definition and diagnosis.

The frequency of diagnosis of ductal carcinoma in situ (DCIS) has increased in Australia, largely because of the national screening programme. Ductal carcinoma in situ presents a dilemma because of problems with its diagnosis and variations in reporting pathological and radiological findings, making it difficult to define optimal treatment and communicate information in a way that helps the patient understand the problems and make decisions. There is considerable inter-observer variation, particularly in differentiating low-grade DCIS from ductal hyperplasia, with or without atypia, but pathologists who participate in regular pathological review sessions vary less in their opinions. Mammography remains the main investigative tool for DCIS and the American College of Radiology has recommended standardized reports. A team approach is required for the removal and diagnosis of possible DCIS. Although the team may be best co-located in the one facility, this is not practical in many community hospital settings which lack on-site radiology and pathology services. The decision about how much breast tissue to remove will need to be made for each patient and depends on the size of the microcalcification and how suspicious the mammogram is for DCIS. We recommend the use of synoptic reports for DCIS, and we document the minimum factors that should be reported by pathologists. The evaluation and management of DCIS by a multidisciplinary team will allow the patient access to information required to make often difficult treatment decisions. In this paper, we review the literature about the natural history, pathology, cytology and radiology of DCIS and document the 20 critical steps required for the diagnosis of impalpable, mammographic microcalcifications suspected to be DCIS.

Biopsy↗