Monitoring dendritic cells in clinical practice using a new whole blood single-platform TruCOUNT assay.

Dendritic cells (DC) from distinct DC subsets are essential contributors to normal human immune responses. Despite this, reliable assays that enable DC to be counted precisely have been slow to evolve. We have now developed a new single-platform flow cytometric assay based on TruCOUNT beads and the whole blood "Lyse/No-Wash" protocol that allows precise counting of the CD14(-) blood DC subsets: CD11c(+)CD16(-) DC, CD11c(+)CD16(+) DC, CD123(hi) DC, CD1c(+) DC and BDCA-3(+) DC. This assay requires 50 microl of whole blood; does not rely on a hematology blood analyser for the absolute DC counts; allows DC counting in EDTA samples 24 h after collection; and is suitable for cord blood and peripheral blood. The data is highly reproducible with intra-assay and inter-assay coefficients of variation less than 3% and 11%, respectively. This assay does not produce the DC-T lymphocyte conjugates that result in DC counting abnormalities in conventional gradient-density separation procedures. Using the TruCOUNT assay, we established that absolute blood DC counts reduce with age in healthy individuals. In preliminary studies, we found a significantly lower absolute blood CD11c(+)CD16(+) DC count in stage III/IV versus stage I/II breast carcinoma patients and a lower absolute blood CD123(hi) DC count in multiple myeloma patients, compared to age-matched controls. These data indicate that scientific progress in DC counting technology will lead to the global standardization of DC counting and allow clinically meaningful data to be obtained.

Surgical and physical stress increases circulating blood dendritic cell counts independently of monocyte counts.

Dendritic cells (DCs) are specialized antigen-presenting cells that have the unique ability to initiate a primary immune response. The effect of physiologic stress on circulating blood DCs has thus far not been studied. In this study, we applied a recently developed method of counting blood DCs to test the hypothesis that significant stress to the body such as surgery and exercise might induce measurable changes in the DC numbers, subsets, phenotype, and function. Twenty-six patients scheduled for elective laparoscopic cholecystectomy, 4 for elective hysterectomy, 56 controls, and 5 volunteers who underwent a stress exercise test were enrolled in the study. Absolute DC counts increased acutely (71.7% +/- 11% [SEM], P =.0001) in response to the stress of surgery and dropped below preoperative levels (-25% +/- 14% [SEM], P =.05) on days 2-3. The perioperative DC subset balance remained constant. Interestingly, DC counts changed independently of monocyte counts. Exercise also induced a rise in DC counts but coincidentally with monocyte counts. Surprisingly, no phenotypic or functional activation of DCs was seen in either stress situations in vivo. DCs are rapidly mobilized into the circulation in response to surgical and exercise stress, which may serve to prepare the host's immune defenses against trauma. The independent regulation of the DC and monocyte counts reinforces the distinction between these 2 cell populations.

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.

Complications of cholecystectomy: risks of the laparoscopic approach and protective effects of operative cholangiography: a population-based study.

BACKGROUND: Previous studies suggest that laparoscopic cholecystectomy (LC) is associated with an increased risk of intraoperative injury involving the bile ducts, bowel, and vascular structures compared with open cholecystectomy (OC). Population-based studies are required to estimate the magnitude of the increased risk, to determine whether this is changing over time, and to identify ways by which this might be reduced. METHODS: Suspected cases of intraoperative injury associated with cholecystectomy in Western Australia in the period 1988 to 1994 were identified from routinely collected hospital statistical records and lists of persons undergoing postoperative endoscopic retrograde cholangiopancreatography. The case records of suspect cases were reviewed to confirm the nature and site of injury. Ordinal logistic regression was used to estimate the risk of injury associated with LC compared with OC after adjusting for confounding factors. RESULTS: After the introduction of LC in 1991, the proportion of all cholecystectomy cases with intraoperative injury increased from 0.67% in 1988-90 to 1.33% in 1993-94. Similar relative increases were observed in bile duct injuries, major bile leaks, and other injuries to bowel or vascular structures. Increases in intraoperative injury were observed in both LC and OC. After adjustment for age, gender, hospital type, severity of disease, intraoperative cholangiography, and calendar period, the odds ratio for intraoperative injury in LC compared with OC was 1.79. Operative cholangiography significantly reduced the risk of injury. CONCLUSION: Operative cholangiography has a protective effect for complications of cholecystectomy. Compared with OC, LC carries a nearly twofold higher risk of major bile, vascular, and bowel complications. Further study is required to determine the extent to which potentially preventable factors contribute to this risk.

Misclassification of social disadvantage based on geographical areas: comparison of postcode and collector's district analyses.

BACKGROUND: Analysis of socioeconomic status (SES), defined on the basis of geographical area, will always be subject to misclassification of individuals. We studied the relationship between SES and selected health-related measures when SES was defined firstly on the basis of postcode and secondly on the basis of the smaller spatial area of collector's district (CD). METHOD: A Census population of 1.4 million was used to investigate the misclassification of individuals to SES group using postcode as opposed to CD. A field survey of 1000 respondents and a mortality register of 1756 deaths were used to compare the relationship between SES and certain outcome variables, when SES group was assigned using postcode and CD. Misclassification probability matrices were used to try to adjust the postcode-based results to approximate CD-based results. RESULTS: The Census data showed that nearly 50% of residents were misclassified into SES groups by the postcode-based system compared with a CD-based system. In comparing the most socially disadvantaged group with the least disadvantaged group, the postcode analysis underestimated the absolute effects of SES by 58% for the increased prevalence of smoking, by 19% for the reduced prevalence of participation in junior sporting clubs and by 13% for the increased mortality rate at ages 0-64 years. Adjustment of postcode-based results using misclassification matrices proved fruitless due to differential misclassification and technical difficulties. CONCLUSIONS: Misclassification of individuals to SES groups on the basis of postcode has caused an underestimation of the true relationship between SES and health-related measures. A reduction of this misclassification by using smaller spatial areas, such as CD or census enumeration districts, will provide improved validity in estimating the true relationship.

Changing patterns of medical treatment in acute myocardial infarction. Observations from the Perth MONICA Project 1984-1990.

TYPE OF STUDY: Descriptive study of trends in the drug therapy for acute myocardial infarction. SETTING: Population-based register of acute coronary events compiled for the years 1984 to 1990 in the course of the Perth MONICA project. CASES: 5294 cases meeting clinical criteria for acute myocardial infarction. RESULTS: Striking changes were seen in the use of aspirin before admission to hospital (from 4% to 18%). During the stay in hospital the use of beta-blockers increased steadily from 52% to 76%, while the use of aspirin increased 3.5-fold from 25% to 88% and the use of streptokinase increased 13.5-fold from 2.4% to 32.4%. The proportion of patients prescribed beta-blockers on discharge from hospital increased from 46% to 65% and that for aspirin rose from 16% to 83%. There were also major relative increases in the use of lipid-lowering agents and declines in the use of antiarrhythmic drugs. CONCLUSION: These trends in the pharmacological management of myocardial infarction mirror the emerging evidence from clinical trials, although the increases in the use of certain types of drugs antedated publication of the results of major randomised studies. The changes in therapy would partly explain observed improvements in case fatality and may have contributed to the decline in coronary mortality observed in the Perth community.

Mortality from coronary heart disease and incidence of acute myocardial infarction in Auckland, Newcastle and Perth.

OBJECTIVE: To confirm the existence of regional differences in coronary death rates in Australia and New Zealand and to determine whether or not these are associated with parallel differences in the incidence of acute myocardial infarction. DESIGN: Descriptive epidemiological study. SETTING: Community based study. SUBJECTS: Residents of Auckland, Newcastle and Perth aged 25-64 years admitted to hospital for acute myocardial infarction or dying from coronary heart disease between 1983 and 1987. MAIN OUTCOME MEASURES: Definite acute myocardial infarction or coronary death classified according to the criteria of the World Health Organization MONICA project. RESULTS: This study confirms the marked variation, evident from official statistics, in mortality rates from ischaemic heart disease between Newcastle (high), Auckland and Perth (low). A different pattern is observed for the incidence of acute myocardial infarction and there are also obvious differences between centres in the case fatality ratios for all acute coronary events combined. Newcastle has the highest rate for all coronary events, particularly in women. Auckland is characterised by substantially higher case fatality ratios compared with the two Australian cities. This is due especially to higher rates of coronary death outside hospital. Perth, which has the lowest mortality rates and case fatality ratios in both men and women, has rates for admission to hospital for acute myocardial infarction and all cases of ischaemic heart disease that are disproportionately high in relation to the corresponding mortality rates. CONCLUSION: The differences in case fatality ratios between these three centres are not readily explained by artefacts related to enumeration or classification. Rather, they are most likely related to differences in the natural history of ischaemic heart disease in the three populations. Differences in medical management may also contribute to the substantial variation in mortality rates.

Prevalence of abdominal aortic aneurysm in Western Australia.

The prevalence of abdominal aortic aneurysm (AAA) in Western Australia was studied using health department mortality data. Age-standardized and age-specific mortality rates related to the disease were calculated for the period 1980-88. The mortality rate has risen by 36 per cent for men and 24 per cent for women. Most of this rise was due to an increase in non-hospital and emergency admission hospital deaths. The number of elective and emergency operations has also risen. Despite two decades of elective surgery, the mortality rate for AAA continues to rise. This rise is highly suggestive of an increasing prevalence. This contrasts with the decline in deaths from other manifestations of arteriosclerosis and provides support for a policy of screening for aneurysm.

Mortality from asthma in Western Australia.

From a cohort of all 5760 male and 4979 female patients who were admitted to WA hospitals and were discharged with a diagnosis of asthma between 1976 and 1980, 265 deaths in men and 189 deaths in women were identified by the end of 1982. The standardized mortality ratio (SMR) for all causes of death for this cohort was 1.6 for men (P less than 0.001) and 1.7 for women (P less than 0.001). Both sexes showed a significant increase in deaths that were attributable to asthma (SMR, 57.9), chronic airflow obstruction (SMR, 9.3) and ischaemic heart disease (SMR, 1.3). The excess death rates for asthma were observed in all age groups, but those for chronic airflow obstruction and ischaemic heart disease were present in older age groups only. These findings indicate that asthma remains a potentially fatal disease in the Australian community. The excess mortality ratios for chronic airflow obstruction that were observed in patients who were admitted to hospital with asthma also suggest that asthma may result in irreversible airflow obstruction.

Sub-national differentials in New Zealand fertility, 1971-76.

PIP: The study objectives were to examine subnational differentials in New Zealand fertility during 1971-76 and to investigate whether or not the general fertility decline in New Zealand over the 1971-76 period was characterized by distinctive regional patterns. 2 fertility measures provided the statistical basis for this fertility analysis: the age specific fertility rate and the total fertility rate. Age spcific fertility rates (ASFR) were calculated from live births registered during the calendar years 1971 and 1976, classified by age group and usual residence of mother, and total female populations in the appropriate age groups as enumerated at the 1971 and 1976 Censuses of Population and Dwellings. Between 1971-76 the total fertility rate dropped from 3.18-2.27 children/woman. In relative terms the fertility decline in New Zealand during 1971-76 (29%) was substantially greater than that during the preceding 5-year period (7%). There were essential differences in the demographic composition and population growth patterns of the North and the South Islands. The North Island is more urbanized, has the country's major commercial and industrial centers, and though smaller in area size contains over 70% of the country's population. It attracts the bulk of external immigrants and gains from the net interisland movement of population. It is most likely for these reasons that throughout the 20th century the North Island has supported a much higher rate of population growth than the South Island. In relative terms, the decline in fertility during 1971-76 was fractionally lower in the North Island, 28.1% against 30.0% in the South Island. Consequently, the North South differential in the total fertility rate widened from 7% in 1971 to 10% in 1976, with the South Island experiencing almost "replacement level" fertility in 1976. These trends confirm the widening North South gap in average family size indicated by the 1971 Census data on children ever born to ever married women. Among the individual 19 Regions, the declines in total fertility rates during the 1971-76 period ranged from less than 25% in Waikato, Taranaki, and Aorangi to over 34% in Otago. With the exception of Aorangi, none of the 7 South Island Regions recorded a fertility decline of less than 28%. In 3 Regions it was over 30%. Among the 12 North Island Regions only 2 (Auckland and Manawatu) experienced such relatively large falls in fertility. The larger and more urbanized regions have experienced generally lower fertility than the smaller and less urbanized ones; the fertility rates in nonurban areas significantly exceed those prevalent in the main urban areas. At ages 25 and older, in percentage terms, the 1971-76 decline in fertility for the total population varied directly with age; the fertility rate for the 25-29 age group fell by 24.0%, that for the 40-44 year group fell by 51.4%.^ieng