Clinical evaluation of the HemoSonic monitor in cardiac surgical patients in the ICU.

The HemoSonic monitor (HemoSonic 100, Arrow International, Reading, PA, U.S.A.) is a minimally invasive device to determine cardiac output by means of M-mode and pulsed Doppler ultrasound. We evaluated the HemoSonic monitor by comparing its output to paired measurements obtained by the standard thermodilution technique in patients who had recently undergone cardiac surgery. Forty-seven paired measurements were carried out in 13 patients. The correlation between the two methods was very good with a correlation coefficient of 0.81. Comparison of the two techniques using the method described by Bland and Altman showed a mean of the differences of -0.23. The limits of agreement were -2.35 to 1.89. There was a reduced correlation between techniques at higher values of cardiac output. We concluded that the HemoSonic monitor has a place in intensive care monitoring, with good correlation with cardiac output measured by the thermodilution technique. It appears to be less suitable for use in patients with a high cardiac output state. The oesophageal probe is moderately difficult for patients to tolerate and is only appropriate for use in sedated patients. The accuracy of the device is somewhat operator-dependent.

Trends in cigarette smoking in 36 populations from the early 1980s to the mid-1990s: findings from the WHO MONICA Project.

OBJECTIVES: This report analyzes cigarette smoking over 10 years in populations in the World Health Organization (WHO) MONICA Project (to monitor trends and determinants of cardiovascular disease). METHODS: Over 300,000 randomly selected subjects aged 25 to 64 years participated in surveys conducted in geographically defined populations. RESULTS: For men, smoking prevalence decreased by more than 5% in 16 of the 36 study populations, remained static in most others, but increased in Beijing. Where prevalence decreased, this was largely due to higher proportions of never smokers in the younger age groups rather than to smokers quitting. Among women, smoking prevalence increased by more than 5% in 6 populations and decreased by more than 5% in 9 populations. For women, smoking tended to increase in populations with low prevalence and decrease in populations with higher prevalence; for men, the reverse pattern was observed. CONCLUSIONS: These data illustrate the evolution of the smoking epidemic in populations and provide the basis for targeted public health interventions to support the WHO priority for tobacco control.

Prior calcium channel blockade and short-term survival following acute myocardial infarction.

There is concern over the safety of calcium channel blockers (CCBs) in acute coronary disease. We sought to determine if patients taking calcium channel blockers (CCBs) at the time of admission with acute myocardial infarction (AMI) had a higher case-fatality compared with those taking beta-blockers or neither medication. Clinical and drug treatment variables at the time of hospital admission predictive of survival at 28 days were examined in a community-based registry of patients aged under 65 years admitted to hospital for suspected AMI in Perth, Australia, between 1984 and 1993. Among 7766 patients, 1291 (16.6%) were taking a CCB and 1259 (16.2%) a betablocker alone at hospital admission. Patients taking CCBs had a worse clinical profile than those taking a beta-blocker alone or neither drug (control group), and a higher unadjusted 28-day mortality (17.6% versus 9.3% and 11.1% respectively, both P < 0.001). There was no significant heterogeneity with respect to mortality between nifedipine, diltiazem, or verapamil when used alone, or with a beta-blocker. After adjustment for factors predictive of death at 28 days, patients taking a CCB were found not to have an excess chance of death compared with the control group (odds ratio [OR] 1.06, 95% confidence interval [CI]; 0.87, 1.30), whereas those taking a beta-blocker alone had a lower odds of death (OR 0.75, 95% CI; 0.59, 0.94). These results indicate that established calcium channel blockade is not associated with an excess risk of death following AMI once other differences between patients are taken into account, but neither does it have the survival advantage seen with prior beta-blocker therapy.

Screening for abdominal aortic aneurysm: lessons from a population-based study.

OBJECTIVES: To test the acceptability of screening and to identify modifiable risk factors for abdominal aortic aneurysm (AAA) in men. DESIGN: A trial of ultrasound screening for AAA in a population-based random sample of men aged 65-83 years, and a cross-sectional case-control comparison of men in the same sample. PARTICIPANTS: 12,203 men who had an ultrasound examination of their abdominal aorta, and completed a questionnaire covering demographic, behavioural and medical factors. MAIN OUTCOME MEASURES: Prevalence of AAA, and independent associations of AAA with demographic, medical and lifestyle factors. RESULTS: Invitations to screening produced a corrected response of 70.5%. The prevalence of AAAs (> 30 mm) rose from 4.8% in men aged 65-69 years to 10.8% in those aged 80-83 years. The overall prevalence of large (> 50 mm) aneurysms was 0.69%. In a multivariate logistic model Mediterranean-born men had a 40% lower risk of AAA (> 30 mm) compared with men born in Australia (odds ratio [OR], 0.6; 95% CI, 0.4-0.8), while ex-smokers had a significantly increased risk of AAA (OR, 2.3; 95% CI, 1.9-2.8), and current smokers had even higher risks. AAA was significantly associated with established coronary and peripheral arterial disease and a waist:hip ratio greater than 0.9; men who regularly undertook vigorous exercise had a lower risk (OR, 0.8; 95% CI, 0.7-1.0). CONCLUSION: Ultrasound screening for AAA is acceptable to men in the likely target population. AAA shares some but not all of the risk factors for occlusive vascular disease, but the scope for primary prevention of AAA in later life is limited.

Chinese attitudes to institutional care of their aged. A study of members from the Chung Wah Association, Western Australia.

OBJECTIVE: To examine Chinese attitudes to institutional care of their aged and to identify the factors that influence these attitudes. METHOD: A cross sectional survey of 815 randomly selected members of the Chung Wah Association, Western Australia was undertaken in 1997 using a mailed self administered questionnaire. The survey instrument was developed through a literature review, interviews and pilot testings and consisted of categorical and noncategorical items. The data were analysed using the SAS (V 6.12) software package. Factor analysis, logistic regression and Chi-square analysis were used on the data. The statistical significance level was set at p < or = 0.05. RESULTS: A total of 431 (53%) completed responses were received. The study showed that 86% of the respondents agreed that the disabled elderly should be institutionalised. Age contributed mainly to the respondents' attitudes to institutionalising the disabled elderly, while the respondents' sex, education, occupation, country of origin and length of residence in Australia did not. Social responsibilities together with the health factors of the elderly had important effects on these attitudes. About 55% of respondents agreed that their Chinese culture influenced their attitude. Only 21% of the respondents agreed that the nondisabled elderly should be institutionalised, 54% disagreed, while 24% remained neutral. Respondents who were likely to institutionalise their disabled elderly were also unlikely to live with their children when they became disabled. A majority of respondents were in favour of government funding of institutions and care givers of the elderly. CONCLUSION: The study provided several important observations and information for health planners and general practitioners to identify the aged at risk of institutionalisation and make arrangements for community support for effected families so that the aged can be encouraged to remain with their families.

Design of the multicenter Australian study of epidural anesthesia and analgesia in major surgery: the MASTER trial.

The Multicenter Australian Study of Epidural Anesthesia and Analgesia in Major Surgery (The MASTER Trial) was designed to evaluate the possible benefit of epidural block in improving outcome in high-risk patients. The trial began in 1995 and is scheduled to reach the planned sample size of 900 during 2001. This paper describes the trial design and presents data comparing 455 patients randomized in 21 institutions in Australia, Hong Kong, and Malaysia, with 237 patients from the same hospitals who were eligible but not randomized. Nine categories of high-risk patients were defined as entry criteria for the trial. Protocols for ethical review, informed consent, randomization, clinical anesthesia and analgesia, and perioperative management were determined following extensive consultation with anesthesiologists throughout Australia. Clinical and research information was collected in participating hospitals by research staff who may not have been blind to allocation. Decisions about the presence or absence of endpoints were made primarily by a computer algorithm, supplemented by blinded clinical experts. Without unblinding the trial, comparison of eligibility criteria and incidence of endpoints between randomized and nonrandomized patients showed only small differences. We conclude that there is no strong evidence of important demographic or clinical differences between randomized and nonrandomized patients eligible for the MASTER Trial. Thus, the trial results are likely to be broadly generalizable.

The effect of mammographic screening on invasive breast cancer in Western Australia.

OBJECTIVE: To determine whether mammographic screening has affected the presentation of invasive breast cancer in Western Australia. DESIGN: Population-based reviews of the presentation of all invasive breast cancers diagnosed in Western Australia in 1989 and 1994. SETTING: Western Australia (population 1.8 million). Active recruitment of women aged 50-69 years for mammographic screening began in 1989. MAIN OUTCOME MEASURES: Size and stage of invasive breast cancers at diagnosis. RESULTS: From 1989 to 1994, the age-standardised incidence rose from 109 to 123 per 100,000 woman-years, based on 584 and 750 cases, respectively. The proportion of all invasive breast cancers detected as a result of a mammogram increased from 9.2% in 1989 to 34.5% in 1994. Among the cases where relevant information was recorded, the proportion of "impalpable" tumours increased from 7.7% in 1989 to 27.6% in 1994, and the average size of palpable tumours fell. There was an unexpected increase in the proportion of tumors that were negative on assays for oestrogen and progesterone receptors. CONCLUSIONS: A relatively simple and inexpensive clinical review has boosted confidence that the outlay of public monies required to establish and conduct screening in Australia appears likely to yield the reductions in mortality from breast cancer that would be predicted on the basis of the earlier controlled trials of mammography.

Finding bile duct injuries using record linkage: a validated study of complications following cholecystectomy.

Laparoscopic cholecystectomy was introduced to Western Australia in 1991 and has become the method of choice for this procedure, although there are concerns about complications, particularly bile duct injuries. Previous studies have investigated this problem but have not confirmed the accuracy of coded information. We used Record Linkage to link operative admissions to subsequent admissions for all people who underwent cholecystectomy between 1988 and 1994. Using ICD9-CM discharge codes, we identified patients with an associated complication. We validated these patients' medical notes to obtain the proportion of complications in the period encompassing the introduction of laparoscopic cholecystectomy. We found 48 bile duct injuries in 413 patients. Of these 43% were found using complication codes on the operative admission, 79% using linked records of subsequent admissions, and 90% by adding lists of complicated cases from the three teaching hospitals. Any epidemiological research that uses surgical complication codes from operative admissions, particularly in the absence of a specific ICD9-CM code, will lead to significantly underestimating the prevalence of complications. By using record linkage, and validating medical records, we captured a significant proportion of complications.

Arrhythmias and mortality after myocardial infarction in diabetic patients. Relationship to diabetes treatment.

OBJECTIVE: To assess the relationship between clinical course after acute myocardial infarction (AMI) and diabetes treatment. RESEARCH DESIGN AND METHODS: Retrospective analysis of data from all patients aged 25-64 years admitted to hospitals in Perth, Australia, between 1985 and 1993 with AMI diagnosed according to the International Classification of Diseases (9th revision) criteria was conducted. Short- (28-day) and long-term survival and complications in diabetic and nondiabetic patients were compared. For diabetic patients, 28-day survival, dysrhythmias, heart block, and pulmonary edema were treated as outcomes, and factors related to each were assessed using multiple logistic regression. Diabetes treatment was added to the model to assess its significance. Long-term survival was compared by means of a Cox proportional hazards model. RESULTS: Of 5,715 patients, 745 (12.9%) were diabetic. Mortality at 28 days was 12.0 and 28.1% for nondiabetic and diabetic patients, respectively (P < 0.001); there were no significant drug effects in the diabetic group. Ventricular fibrillation in diabetic patients taking glibenclamide (11.8%) was similar to that of nondiabetic patients (11.0%) but was lower than that for those patients taking either gliclazide (18.0%; 0.1 > P > 0.05) or insulin (22.8%; P < 0.05). There were no other treatment-related differences in acute complications. Long-term survival in diabetic patients was reduced in those taking digitalis and/or diuretics but type of diabetes treatment at discharge had no significant association with outcome. CONCLUSIONS: These results do not suggest that ischemic heart disease should influence the choice of diabetes treatment regimen in general or of sulfonylurea drug in particular.

Prognostic factors in elective aortic reconstructive surgery.

BACKGROUND: The present study was carried out to determine the risk factors associated with peri-operative mortality and long-term survival in patients undergoing abdominal aortic reconstructive surgery (ARS). METHODS: A retrospective review was performed of the case notes of all patients having ARS at a university teaching hospital during a 5.5-year period, and their details entered onto a pro forma. RESULTS: A total of 252 patients underwent ARS between July 1989 and December 1994. The peri-operative mortality was 7.5%. The most frequent adverse events were cardiac events, accounting for 8 (42%) of the peri-operative deaths. The risk of a peri-operative cerebrovascular accident was low (n = 3, 1.2%) as was the risk of peri-operative renal failure requiring dialysis (n = 3, 1.2%). Factors independently linked to increased peri-operative mortality included moderate-to-severe hypertension (P = 0.05, odds ratio = 3.54), those with renal impairment (P = 0.05, odds ratio = 2.69), and blood transfusion requirements (P < 0.001, odds ratio = 1.26). Long-term survival was independently shortened by occlusive disease (P = 0.004, hazard ratio = 2.78) and ischaemic heart disease (P < 0.001, hazard ratio = 3.58). CONCLUSIONS: The risks of ARS were significantly increased in patients with severe hypertension, those with renal impairment and those requiring blood transfusion. Long-term survival was shortened for those patients with occlusive aortic disease and ischaemic heart disease. These risk factors should be carefully assessed in each patient before performing elective ARS.

Dipyridamole thallium-201 scintigraphy for early risk stratification of patients after uncomplicated myocardial infarction.

OBJECTIVE: To determine the safety and prognostic value of dipyridamole thallium-201 scintigraphy performed in patients within three to five days of acute myocardial infarction, including those receiving thrombolytic treatment. DESIGN: A prospective study of dipyridamole thallium-201 scintigraphy in patients early after acute myocardial infarction. SETTING: University hospital. PATIENTS: 200 patients who were clinically uncomplicated at day 3 after infarction, 92 (46%) of whom had received thrombolysis. MAIN OUTCOME MEASURES: Incidence of cardiac death, non-fatal reinfarction, readmission to hospital for unstable angina, or non-elective revascularisation procedure within six months' follow up. RESULTS: No patient had a serious complication from the dipyridamole study. At six month follow up, 55 patients (28%) had suffered a defined cardiac event. Patients who received thrombolysis had the same extent of thallium-201 redistribution and the same occurrence of subsequent cardiac events as those not receiving thrombolysis. Patients who subsequently had an event had more myocardial segments showing thallium-201 redistribution than event free patients: 2.7 (SD 1.9) v 1.2 (1.4), respectively (p < 0.001). Among all clinical and scintigraphic variables, multivariate analysis identified the extent of thallium-201 redistribution as the only independent predictor of outcome (p < 0.001). Among 63 patients (32%) of the study cohort who showed more than two myocardial segments with thallium-201 redistribution, the adjusted risk ratio for a cardiac event was 7.5 (95% confidence interval 2.9 to 19.1) compared with patients without any redistribution. CONCLUSIONS: Dipyridamole thallium-201 scintigraphy can be performed safely within a few days of the event in patients with uncomplicated myocardial infarction, including those who received thrombolysis, and can identify a subgroup of patients at high risk of future ischaemic events.

Breast cancer in Western Australia in 1989. V: Outcome at 5 years after diagnosis.

BACKGROUND: A follow-up study was undertaken of all Western Australian women who had a new diagnosis of breast cancer during 1989. The aims were to determine survival, frequency of recurrence and quality of life (QoL) of Western Australian women 5 years after a diagnosis of breast cancer; to determine reasons for choice or rejection of reconstructive surgery in those women treated by mastectomy, and to determine if the choice of lumpectomy or mastectomy affects subsequent QoL. METHODS: The vital status as at 1st June 1994 of all 692 women who had a new diagnosis of breast cancer in 1989 was ascertained by electronic linkage to official mortality registrations. A subsample of 215 survivors who had originally been treated by the nine surgeons who had managed 20 or more cases each was sent a reply-paid postal questionnaire asking about follow-up treatment since diagnosis, recurrence of disease, current QoL and attitudes to, and use of, reconstructive surgery. RESULTS: The overall survival rate at 5 years was 80.8% (85.9% and 78.8% for Stage I and II, respectively). Cumulative mortality was 35% lower among the third of patients treated by the nine most active surgeons (14% vs 22%, P < 0.02), but this may be subject to referral bias. The subsample was representative of all surviving cases except for being an average of 2.7 years younger at diagnosis (mean ages 55.2 and 57.9 years). The response rate of the subsample to the postal questionnaire was 78%. Of women who had had a mastectomy, 40% had considered having a reconstruction, but only nine (11%) had undergone this operation. Median QoL on the Rosser scale (maximum = 1.0) was 0.9. QoL was worse for the 23% of patients with a recurrence of breast cancer. Patients treated by breast-conserving surgery showed a trend toward a better QoL compared with those treated by mastectomy. CONCLUSION: At 5 years after the diagnosis of breast cancer, one in five women had died and an estimated one in four of the survivors had recurrent disease. Quality of life in the remaining patients, half of whom had undergone adjuvant treatment, was very good. These are important baseline data against which to judge the impact of mammographic screening.

Stereotactic 14 gauge core-biopsy of the breast: results from 101 patients.

BACKGROUND: Along with fine needle aspiration (FNA) cytology, core-biopsy has become an integral part of the assessment of mammographically detected breast lesions. METHODS: A series of stereotactic large-core-biopsies of mammographically detected breast lesions was studied to assess the accuracy and limitations of the technique in diagnosing malignancy and in giving specific benign diagnoses, and its use in determining surgical management. RESULTS: Eighty per cent of carcinomas were diagnosed as malignant (absolute sensitivity). In 88.8% of the cancers, the core-biopsy was classified as malignant, suspicious or atypical/indeterminate (complete sensitivity), and in 72% of the invasive carcinomas, invasive tumour was present in the core. The technique was more successful for invasive carcinomas than for ductal carcinoma in situ (DCIS) (absolute sensitivity 86.1 and 55.5, respectively; P = 0.28) and for malignant mass lesions than for a mass with associated microcalcifications or for pure microcalcifications (absolute sensitivity 91, 71 and 66.6%, respectively; P = 0.19). In five of the 45 cancers (11.1%), no tumour tissue was present in the core, but all were excised after mammographic review and no delays in diagnosis have been experienced to date. The benign to malignant ratio for excised lesions was 0.11:1. Of the benign lesions, a specific diagnosis was given in 49% (calcifications in the core in a background of fibrocystic change, or postoperative scarring, or fibro-adenoma); the remainder showed non-specific benign findings. All patients where invasive carcinoma was diagnosed in the core underwent axillary clearance and wide local excision or mastectomy at their first operation. CONCLUSIONS: This technique can markedly reduce the number of benign lesions needing open biopsy, and provide information allowing definitive management of most carcinomas at the first operation. The accuracy of core-biopsy was lower in DCIS/microcalcification lesions; extra core samples or a combination of FNA and core-biopsy may be of value in these cases.

Trends in the home management of non-fatal acute myocardial infarction in Perth, Western Australia between 1984 and 1993.

BACKGROUND: Trends in the incidence of acute myocardial infarction (AMI) that are based on admissions to hospital would be misleading if the proportion of non-fatal infarctions treated at home changed over time. AIM: To estimate trends in the management at home of cases of non-fatal AMI in Perth between 1984 and 1993 in order to determine if the number of such cases has remained consistently small and can be neglected in studies of the incidence of AMI. METHODS: In 1989, 251 general practitioners in Perth responded to a postal questionnaire asking about management of cases of AMI at home in the preceding 12 months. In 1993, 288 general practitioners and 174 physicians responded to the same questionnaire. RESULTS: We estimate that 1.5% of all patients less than 65 years of age diagnosed with non-fatal AMI were managed at home in 1989. The corresponding figure for 1993 was 4.1%. A previous study in Perth in 1984 found that 3.9% of cases of non-fatal AMI in patients less than 65 years of age were managed at home. CONCLUSION: The management at home of cases of non-fatal AMI in people of working age in Perth has remained at a negligible level from 1984 to 1993. Thus a register based on admissions to hospital for AMI will accurately reflect trends in AMI in people of working age.

Breast cancer in Western Australia in 1989: IV. Summary of histopathological assessment in 655 cases.

This study was part of a population-based survey of all cases of breast cancer diagnosed in Western Australia in 1989. The paper concerns histopathology reporting by pathologists in 655 cases of carcinoma of the breast in that year, before the introduction of mammographic screening programmes. Pathological features of the neoplasms are documented, and the extent to which information known to be of clinical or prognostic importance was included in the reports is analysed. 96.5% of all pathology reports included information on breast cancer subtype and, in 98.6% of cases with axillary dissection, the number of lymph nodes dissected, and the number containing metastatic tumor was stated. In 83.7% of cases of invasive carcinoma exact tumor dimensions were recorded. In 44.9% of cases histological grade was recorded, and information about excision margins was present in 60% of reports overall. The reporting of pathological features in many instances was limited by the way in which the specimen was handled prior to reception. At the time of the study, views about the importance of many aspects of histological assessment were still evolving. Even now, for example, consensus is still being reached on the value of histological grading in predicting prognosis and whether reliable histological assessment of such factors as extent of DCIS and completeness of excision of DCIS is possible. The introduction of mammographic screening since 1989 has provided a focus for wider discussion about the value of histological information in prognostication and patient management. A case is made to support the use of "check lists" for surgical pathology reports in cases of breast cancer.

Breast cancer in Western Australia in 1989: III. Accuracy of FNA cytology in diagnosis.

A population-based study of all cases of breast cancer diagnosed in Western Australia (WA) in 1989 revealed 701 cases of cancer in 692 women. Three hundred and ninety-six (56.5%) of these cancers had fine needle aspiration (FNA) cytology. Forty-three cases were managed non-surgically, on the basis of an FNA diagnosis and without histologic follow up. Of the cases with histological follow-up, 73% received an unequivocal diagnosis of malignancy by FNA, and abnormal cells (atypical, suspicious or malignant diagnoses) were reported in 94.2%. Of the cases, 3.2% were reported as benign and in 2.6% the samples taken were unsatisfactory. There were no false positive cytological diagnoses of malignancy. This study is the first to examine the results of FNA diagnosis of breast cancer from a medical community as a whole, rather than for individual or specialist units; the accuracy of diagnosis was similar for different pathology practices including public and private sector laboratories. Lower absolute sensitivity (the proportion of cases given an unequivocal diagnosis of malignancy) was seen in very small and very large tumours, pure duct carcinoma in situ (DCIS), and invasive lobular carcinoma. False negative rates (the proportion of cases given a benign cytological diagnosis) were very low for all laboratories (0-4.5%) and for all types of carcinoma, and the proportion of unsatisfactory samples was exceptionally low for all laboratories (0-4.5%). The overall figures for accuracy are similar to those reported from other centres in Australasia and overseas, and confirm the effective use of FNA cytology throughout the clinical and pathology community in WA.

Early identification of patients at low risk of death after myocardial infarction and potentially suitable for early hospital discharge.

OBJECTIVES: To find (a) whether data available shortly after admission for acute myocardial infarction can provide a reliable prognostic indicator of survival at 28 days, and (b) whether such an indicator might be used to identify patients at low risk of death and suitable for early discharge. DESIGN: Retrospective analysis of data collected on patients admitted to a coronary care unit for acute myocardial infarction. A validation sample was selected at random from these patients. SETTING: Coronary care units in Perth, Western Australia. SUBJECTS: 6746 patients aged under 65 and resident in the Perth Statistical Division who during 1984-92 were admitted to a coronary care unit with symptoms of myocardial infarction. MAIN OUTCOME MEASURES: Sensitivity and specificity of several models for predicting survival at 28 days after myocardial infarction, and detailed performance characteristics of a particular model. RESULTS: Patients with a pulse rate of 100 beats/min or less, aged 60 or under, and with symptoms typical of myocardial infarction, no past history of myocardial infarction or diabetes, and no significant Q wave in the admission electrocardiogram had a very high chance of survival at 28 days (99.2%). These patients made up one third of all patients studied. CONCLUSION: The prognostic index identifies patients very soon after admission who are at low risk of death and potentially eligible for early discharge from hospital or the coronary care unit. Computing the index does not need complex cardiac investigations.

Cellular electrophysiology of WAY-123,398, a new class III antiarrhythmic agent: specificity of IK block and lack of reverse use dependence in cat ventricular myocytes.

OBJECTIVE: The objectives were (a) to evaluate the effects of WAY-123,398, a new class III antiarrhythmic agent, on the action potential of canine Purkinje fibres in comparison with dofetilide, E-4031, and dl-sotalol, and (b) to characterise the mechanism of the class III action by studying its effects on several ionic currents in isolated cat myocytes. METHODS: Transmembrane potentials in Purkinje fibres were studied with standard microelectrodes filled with 3M KCl. Myocytes were isolated by enzymatic disaggregation with collagenase and current recordings were obtained by voltage clamp with either the nystatin perforated patch technique or the usual whole cell configuration. RESULTS: WAY-123,398 prolonged action potential duration (APD) in Purkinje fibres and in cat ventricular myocytes without altering other variables of the action potential; in Purkinje fibres the concentration producing a 20% prolongation of APD-60 mV at a basic cycle length of 1000 ms was 0.2 microM. After depolarising voltage steps, the delayed rectifier (IK) peak tail currents in cat myocytes were blocked with IC50 = 0.1 microM. The block was unaffected by varying the duration (200 to 500 ms) or the frequency (0.4 to 2.5 Hz) of the depolarising steps. A much higher concentration of WAY-123,398 (10 microM) did not have effects on the L type Ca current (ICa-L), and on the inward rectifier (IK1) and transient outward (I(to)) K currents. CONCLUSIONS: The results indicate that WAY-123,398 is an effective and specific class III agent devoid of class I activity, and suggest that WAY-123,398 prolongs cardiac repolarisation by specifically blocking the delayed rectifier current (IK). The block was unchanged over a range of frequencies and duration of depolarisation, showing no evidence of "reverse use dependence" of block.

Breast cancer in Western Australia in 1989. I. Presentation.

This study was designed as a population-based study of all cases of breast cancer diagnosed in Western Australia (WA) in 1989. Cases were identified from the State Cancer Registry and from computerized hospital inpatient records. Data were obtained from the records of surgeons and oncologists managing the patients, hospital medical records, and pathology and cytology reports. A total of 701 histologically proven tumours were documented in 692 women. Of these 6.8% were not known to the State Cancer Registry. Two-thirds (68%) of tumours were first detected by the woman herself, 11% were found by a doctor and 11% were detected by mammographic screening. Stage I tumours accounted for 40% of tumours and Stage II 39%. The estimated lifetime risk of a WA woman developing at least one malignant breast tumour is 10%. Passive surveillance based upon a legal obligation on doctors to notify cases of cancer may be resulting in a significant under-estimation of the incidence of cancer in WA. Mammographic screening played only a small role in the detection of breast cancer in WA in 1989, but its contribution and the proportion of stage I tumours should both increase as a population-based mammographic screening programme is established. This survey will provide a yardstick against which changes can be measured. Eighty-four per cent of tumours presently occur in women who would have access to mammographic screening although only 44% occur in the 50-69 age bracket that is to be actively recruited. The lifetime risk of breast cancer in WA women is greater than has been appreciated previously.

Breast cancer in Western Australia in 1989. II. Diagnosis and primary management.

This study was designed as a population-based study of all cases of breast cancer diagnosed in Western Australia (WA) in 1989. Cases were identified from the State Cancer Registry and from computerized hospital inpatient records. Data were obtained from the records of surgeons and oncologists managing the patients, hospital medical records and pathology and cytology reports. A total of 701 tumours in 692 women were treated by 105 different surgeons of whom 25 saw 10 or more cases. Over 70% were proven by cytology or biopsy within 2 weeks of presentation to a doctor. The first diagnostic investigation was fine needle aspiration in 45%, open biopsy in 28% and diagnostic mammogram in 24.4%. A definitive procedure involving breast conservation was performed in 31.3% of patients with operable tumours; 35.6% of those under 50 years of age. If axillary dissection or sampling was part of such treatment, 93.5% of those under 50 years and 75% of those 50 years and over had radiotherapy to the residual breast. Although less than one-third of patients were referred to a medical oncologist almost a half had adjuvant systemic therapy (92% of node positive and 23% of node negative patients). Tamoxifen was prescribed as part of adjuvant therapy in 93% of those over 50 years and cyclophosphamide, methotrexate and 5-fluorouracil in 71% of those under 50 years. Less than 10% of patients treated with mastectomy and axillary dissection had postoperative radiotherapy to the chest wall and drainage areas. The patterns of care of patients with breast cancer in WA prior to the introduction of population-based mammographic screening have been established.(ABSTRACT TRUNCATED AT 250 WORDS)