Increased risk of preterm delivery and pre-eclampsia in women with polycystic ovary syndrome and hyperandrogenaemia.

OBJECTIVE: To study the risk of adverse pregnancy outcomes in women with polycystic ovary syndrome (PCOS), and to examine the role of hyperandrogenaemia. DESIGN: Cohort study. SETTING: Singleton pregnancies in women with PCOS identified at a private fertility clinic during 1997-2010 and a background population including all singleton deliveries at Hvidovre Hospital, Denmark, in 2005. POPULATION: A cohort of 459 women with PCOS and a background population of 5409 women. METHODS: Obstetric outcomes were extracted from national Danish registries and odds ratios (ORs) were calculated by multiple logistic regression analysis, adjusting for age, parity, and body mass index. MAIN OUTCOME MEASURES: Risk of pre-eclampsia, preterm delivery, and small for gestational age offspring in the entire PCOS population and in a subsample with hyperandrogenaemia. RESULTS: Women with PCOS had an increased risk of preterm delivery <37 weeks of gestation (OR 2.28; 95% confidence interval, 95% CI, 1.51-3.45; P < 0.0001). The elevated risk was confined to hyperandrogenic women with PCOS: preterm delivery before 37 weeks of gestation (OR 2.78; 95% CI 1.62-4.77; P < 0.0001), and was not seen in normoandrogenic women with PCOS (OR 1.35; 95% CI 0.54-3.39; P = 0.52). The overall risk of pre-eclampsia was not elevated (OR 1.69; 95% CI 0.99-2.88; P = 0.05) compared with the background population, but was significantly increased in the hyperandrogenic subsample (OR 2.41; 95% CI 1.26-4.58; P < 0.001). The risk of small for gestational age offspring was similar in all groups. CONCLUSION: Women with PCOS had an increased risk of preterm delivery compared with the background population. The increased risk was confined to hyperandrogenic women with PCOS who had a two-fold increased risk of preterm delivery and pre-eclampsia.

Acute monocytic or myelomonocytic leukemia with balanced chromosome translocations to band 11q23 after therapy with 4-epi-doxorubicin and cisplatin or cyclophosphamide for breast cancer.

PURPOSE: To report five cases of acute monocytic or myelomonocytic leukemia after chemotherapy with 4-epidoxorubicin for breast cancer and to evaluate the risk of leukemia after the use of this drug. PATIENTS AND METHODS: One hundred fifty-seven patients with advanced breast cancer were randomized to either 4-epi-doxorubicin plus cisplatin or 4-epi-doxorubicin alone. An additional 203 patients were treated prospectively with 4-epi-doxorubicin alone. All were observed closely for leukemic complications. RESULTS: Three patients from the randomized study developed leukemia; all were in the subgroup of 74 patients who received 4-epi-doxorubicin plus cisplatin, whereas no leukemia was observed among the remaining 83 patients in the randomized study or among the additional 203 patients who were treated prospectively with 4-epi-doxorubicin alone (P = .023, log-rank test). In the subgroup of 74 patients who were treated with 4-epi-doxorubicin plus cisplatin, the cumulative risk of leukemia was 16.0% +/- 9.9% (mean +/- SE) 33 months after the start of therapy; the relative risk was 668 (95% confidence interval [Cl], 138 to 1,953). Two other cases of acute monocytic and myelomonocytic leukemia were observed after 4-epi-doxorubicin plus alkylating agents were administered for breast cancer. Three of five cases of leukemia presented balanced translocations to chromosome band 11q23 and two, loss of a whole chromosome no. 7 or its long arm. CONCLUSIONS: 4-epi-doxorubicin is leukemogenic, and the leukemias are often acute monocytic or myelomonocytic with balanced chromosome translocations to band 11q23, such as in the leukemias after therapy with the epipodophyllotoxins. Furthermore, our results suggest a synergistic effect in leukemogenesis between 4-epi-doxorubicin targeting DNA-topoisomerase II and directly genotoxic drugs such as cisplatin or alkylating agents.

Therapy-related myelodysplasia and acute myeloid leukemia. Cytogenetic characteristics of 115 consecutive cases and risk in seven cohorts of patients treated intensively for malignant diseases in the Copenhagen series.

Therapy-related acute myeloid leukemia (t-AML), often presenting as myelodysplasia (t-MDS), has become the most serious long-term complication of cancer therapy and offers a unique opportunity to study chemical leukemogenesis. Seven cohorts of patients treated for six different types of primary tumor have been followed closely for leukemic complications, and 115 consecutive patients with t-MDS or t-AML, including 45 cases from the cohorts, have been investigated cytogenetically at our institutions during the past 16 years. In patients primarily treated with alkylating agents, the risk of t-MDS and t-AML increased by approximately 1% per year from 2 to at least 8 years after start of treatment. In most cases, the disease presented as t-MDS with loss of a whole chromosome 5 or 7, or various parts of their long arms, and the leukemias were of FAB-subtypes M1, M2, or M4. In patients treated with drugs targeting at DNA-topoisomerase II, such as etoposide, doxorubicin, 4-epidoxorubicin, or mitoxantrone combined with drugs reacting directly with DNA, such as cisplatin or alkylating agents, the risk of leukemia increased much more steeply from only one year after start of therapy. These early onset cases often presented as overt leukemia of FAB-subtypes M4 or M5 with balanced translocations to chromosome bands 11q23 and 21q22, whereas later onset cases often shared characteristics with cases observed after therapy with alkylating agents alone. Both alkylation of DNA and poisoning of DNA-topoisomerase II may result in development of t-AML with different clinical and cytogenetic characteristics. There may be a synergistic leukemogenic effect between the two types of drug, and in patients with germ cell tumors treated with etoposide, cisplatin and bleomycin, reassessment suggested the risk of leukemia to increase exponentially with increasing doses of cisplatin and etoposide.

Human monocyte function in vitro: influence of conditions during transport of blood from patient to laboratory.

Monocyte functional tests were carried out on samples of peripheral human blood which had been subjected to 4 different conditions of transport and temperature. There was no difference in cell viability or pinocytic, phagocytic and chemotactic activity of monocytes isolated from blood exposed to these different conditions. However, the yield of monocytes obtained after metrizoate/polysucrose centrifugation was very low when blood samples in transit were kept for 2 h at 0--4 degrees C. It is concluded that a period of transport up to 24 h is acceptable, provided the temperature of the blood sample is kept between 15 and 25 degrees C.

Phagocytosis and killing of Escherichia coli X43 by individual resident mouse peritoneal macrophages assessed by an autoradiographic technique.

An autoradiographic technique for the determination of viable bacteria in individual cells is described, based on the incorporation of [3H]thymidine into the DNA of viable Escherichia coli X43, following phagocytosis by resident mouse peritoneal macrophages. The results of the autoradiographic technique were in overall agreement with viable colony counts. Investigation of the killing of E. coli X43 with the autoradiographic technique showed that the percentage viable bacteria tended to be the same irrespective of the number of bacteria ingested per macrophage, although there was a definite correlation between the numbers phagocytosed and the percentage killed in some of the experiments.

Ability of rosetting or non-rosetting individual control and inflammatory macrophages to kill Escherichia coli X43 intracellularly.

An autoradiographic method combined with a rosette technique was used to assess the bactericidal activity of individual control and inflammatory peritoneal macrophages (PM phi) in the presence or absence of expression of Fc receptor for IgG (FcR). There was a lack of FcR reactivity in a certain percentage of both categories of PM phi exposed to E. coli X43, a bacterium which is readily phagocytosed in the presence of specific antibody. Both rosetting and non-rosetting PM phi were capable of phagocytosing E. coli X43, but inflammatory PM phi showed a marked reduction in their capacity to ingest these bacteria compared with control PM phi. Once ingested the E. coli X43 were killed equally well by non-rosetting and rosetting control and inflammatory PM phi.

Comparison of detection speed and yield in agitated and non-agitated aerobic blood culture bottles.

The influence of agitation on detection speed and yield was evaluated in 7,033 paired, identical aerobic blood culture bottles (Media Department, Statens Seruminstitut, Copenhagen, Denmark). One bottle was agitated and the other was incubated stationary. Of a total of 943 organisms isolated in aerobic blood culture bottles, 74% were clinically significant. No difference in the total yield of significant organisms was observed between agitated and non-agitated bottles. In the evaluation of detection speed, only cultures where organisms were isolated from both bottles, but at different times, were included, to ensure that no other factors influenced the result. Staphylococci, Pseudomonas spp., and Candida spp. were detected significantly faster in agitated bottles, on average 0.5-1 day earlier (p < 0.05), and in the majority of the cases within the first incubation day. These species are frequently found and are important causes of severe generalized infections, especially in immunocompromised patients, where early detection is of great importance. The detection principle in agitated bottles in our system, darkening of blood, proved to be an easy, reliable, and fast method to detect positive aerobic blood cultures, which could probably lead to increased automation.

In vitro cytotoxic effect of alpha-hemolytic Escherichia coli on human blood granulocytes. Correlation with size of alpha-hemolysin production.

The correlation of the in vitro cytotoxic effect of 107 alpha-hemolytic strains of Escherichia coli with various other bacterial characteristics was investigated. Damage to human blood granulocytes in the presence of fresh or heated autologous plasma was quantified by measuring the release of chromium-51 from labelled cells. 95 strains had a cytotoxic effect which was equal in the presence of fresh or heated plasma, whereas 12 strains showed an effect which was reduced in fresh compared with heated plasma. The cytotoxic effect increased as the number of bacteria per granulocyte was increased. The average size of the alpha-hemolysin production of the strains was 185 HU50/ml ranging from 3-2519HU50/ml. The cytotoxic effect of the strains was directly correlated with the size of the alpha-hemolysin production. The cytotoxic effect was not correlated with the O-antigen serotype or the type of infection from which the strains were derived. These results indicate that the ability to produce alpha-hemolysin is the bacterial characteristic which is of decisive importance for the cytotoxicity of alpha-hemolytic E. coli towards human blood granulocytes.

Rate-limiting components and reaction steps in complement-mediated haemolysis.

The aims of this study were to identify the rate-limiting components and reaction steps in the integrated activation sequence of the alternative (AP) and classical (CP) pathways of the complement (C) system. In an initial correlation analysis we found that the haemolysis rate in AP was correlated with the concentrations of C5 and IgM. In CP, the haemolysis rate was correlated with the concentrations of C2-C6, factors I and B, and IgM. In order to identify the rate-limiting components, we added single, purified C components and IgM to pooled, normal human serum and measured the resultant change in the haemolysis rate. We found that a large number of different components, rather than a single one, were rate-limiting in AP and CP. In reconstitution experiments we found that in CP the rate-limiting reaction steps are the activation of C4 and C2. In AP we cannot identify the rate-limiting step precisely, but can only state that it is at the C3 activation step or earlier.

Epidemiology of pertussis in Denmark: the impact of herd immunity.

BACKGROUND: An evaluation is presented of the Danish pertussis immunization programme, which consists of three injections of plain whole-cell pertussis vaccine given alone at ages 5 weeks, 9 weeks, and 10 months. DATA: The incidence of pertussis in vaccinated and unvaccinated children since the start of vaccination was obtained from the notification system for infectious diseases. Data for vaccination coverage were obtained from the National Social Security. The data for 1980-1986 were supplemented with data from culture-verified cases and hospitalized cases. RESULTS: Compared with other countries using four injections, incidence rates in Denmark are high, especially in pre-school years, leaving infants at a relatively high risk for contracting pertussis from siblings. However, compared with the era before general vaccination, the incidence of pertussis has fallen to one-sixteenth of its former levels. Today, only one in 20 vaccinated, and one in six unvaccinated children develop pertussis before the age of 15 years. This considerable fall, which has also occurred among unvaccinated children, is used to elucidate the importance of herd immunity, which, with the relatively high vaccination coverage in Denmark, was found to play a major role. CONCLUSIONS: The importance of herd immunity is stressed, and it is recommended that a fourth injection of pertussis vaccine is introduced to bring incidence rates down to the very low values found in countries with more intensive vaccination programmes.

Models for prediction of the frequency of toxoplasmosis in pregnancy in situations of changing infection rates.

BACKGROUND: Estimation of the number of women infected during pregnancy with Toxoplasma gondii from seroconversion or seroprevalence data meets with various difficulties. Because of the high risk of transmission of the infection to the fetus such infections are however a major concern in pregnancy-related health planning. METHODS: The expected annual percentage of pregnant women infected with Toxoplasma was calculated using models with varying assumptions with regard to the infection rate, assumed to be independent of age but dependent on calendar time. Three situations were studied: a stable situation, a sudden fall in the infection rate and a gradually declining (slower or faster) infection rate over the lifetime of the pregnant women. RESULTS: With a constant infection rate, a maximum number of affected pregnancies occurs at a yearly infection rate of 4%. In countries with a strongly decreasing annual infection rate, estimates based on data on the relation between age and seropositivity related to only one period of time tend to overestimate the number of affected pregnancies by as much as 60%. CONCLUSIONS: In countries in transition from high to low infection rates, it is likely that the influence of decreasing immunity will, at least temporarily, more than outweigh the influence of the falling infection rates, resulting in a higher number of infected pregnant women. The models used can also describe situations with age-dependent variation in the infection rate, and may well apply to other infectious diseases relevant to pregnancy.

Bladder management and urinary tract infections in Danish hospitals, nursing homes, and home care: a national prevalence study.

OBJECTIVE: To establish the prevalence of urinary tract infection in patients undergoing various forms of bladder management. DESIGN: A nationwide descriptive point-prevalence survey with logistic regression analysis of the data relating infection to bladder management. SETTING: Fifteen hospitals, 21 nursing homes, and 13 home care districts throughout Denmark. PATIENTS: Information was collected on 3,665 patients. On the day of the study, 349 patients had indwelling catheters and 1,150 were using external urine drainage systems (condoms or diapers) for bladder management. RESULTS: The prevalence of urinary tract infections in catheterized patients and those using external drainage systems was 13.2% and 8.1%, respectively. The prevalence of hospital-acquired urinary tract infection (4.2%) had not changed from that reported in 1978. The proportion of these infections related to the indwelling catheter, however, had reduced from 66% to 30%. Logistic regression analysis confirmed that, when corrected for the patient-related confounders (female gender, age > 60 years, incontinence, immobility, and stay in hospital for longer than 15 days), condoms (odds ratio [OR], 5.94; 95% confidence interval [CI95], 2.8 to 12.5), indwelling catheters (OR, 3.3; CI95, 2.3 to 4.8), and diapers (OR, 1.5; CI95, 1.1 to 2.1) were significantly (P < .001, P < .001, and P = .008, respectively) related to infection. CONCLUSIONS: Prevalence surveys have revealed that over the period 1978 to 1991, during which efforts have been made to restrict the use of indwelling catheters and to encourage the care of catheterized patients according to guidelines recommended by the Danish National Centre for Hospital Hygiene, the percentage of hospital-acquired urinary tract infections associated with indwelling catheters has been halved. External urine drainage systems, however, have emerged as significant risk factors for urinary tract infection.

A multicenter questionnaire investigation of attitudes toward hand hygiene, assessed by the staff in fifteen hospitals in Denmark and Norway.

A questionnaire survey was carried out anonymously among 2557 health care workers in Denmark and Norway to identify and quantify factors that affect the handwashing behavior of physicians, nurses, and other staff groups who perform direct patient care. For number of daily patient contacts physicians reported significantly fewer instances of hand hygiene (HH) per day than did those in other medical professions. Male physicians reported significantly fewer HH per day than did their female colleagues. Significant differences were found among staff groups in emphasis on factors motivating and discouraging HH. The main motivating factor for all groups, however, was an awareness that HH is important for the prevention of infection. Skin problems from frequent handwashing and the use of agents that irritate and dry the skin were the main reasons for disinclination toward HH. The number of points given to these statements correlated well with the stated frequency of HH in staff groups with relatively many (9 to 24) patient contacts per day. Many studies have revealed low standards of HH in health care settings. Whenever HH is taught, the significance of HH for the prevention of infection is always stressed. The participants in this survey were well aware of this significance, but there is still a discrepancy between theory and practice. Goal-specific strategies to improve HH practices would probably be more effective if more were done to minimize the factors that health care workers find detrimental to HH. Continual evaluation of the possibly detrimental effects of current hand washing agents should also be carried out.

Infant BCG vaccination study in Lithuania.

SETTING: Infants identified in maternity hospitals in Vilnius, Lithuania. OBJECTIVES: To test the capacity of the BCG vaccine, Danish strain 1331 (Danish vaccine), to induce tuberculin reactivity and scar formation in neonates compared to the WHO International Reference Preparation of BCG (IRP vaccine), and to study the effect of dose and of age at vaccination. DESIGN: A randomized four-armed study: 1) normal dose, 0.05 ml Danish vaccine given to neonates at birth, 2) half the normal dose of Danish vaccine given at birth, 3) IRP vaccine given at birth at normal infant dose, and 4) the normal infant dose of Danish vaccine given at 3 months of age. RESULTS: Larger tuberculin reactions, as well as an increased frequency and larger scars, were seen when Danish vaccine was given at 3 months of age in comparison to neonatal vaccination. Halving the dose resulted in smaller reactions, but the difference was not significant. The IRP vaccine resulted in borderline significantly larger reactions in comparison to the Danish vaccine. The number of infants receiving very early vaccination (0-2 days) was not evenly distributed in all groups, however, which is believed to explain the observed difference.

Use of gloves and handwashing behaviour among health care workers in intensive care units. A multicentre investigation in four hospitals in Denmark and Norway.

Glove use and handwashing frequencies (HW) were observed in intensive care units (ICU) in two university hospitals in Denmark and two in Norway. The study included a total of 1632 patient procedures performed by 325 persons. Handwashing (HW) has become an important part of general barrier precautions. Earlier studies have shown that health care workers (HCW) far too often neglect to wash their hands after patient procedures when handwashing is strongly recommended. Despite earlier claims that increased glove use in hospitals would discourage handwashing, our results showed that HCW washed their hands more often after glove use (57%) than when gloves had not been used (40%). This significant difference in HW frequency was also noted when similar procedures were carried out by HCW with or without gloves. This might be a matter of personal discomfort after wearing gloves, but could also be due to differences in awareness of hygienic aspects of patient care. In the two countries gloves were used on average at 17% of the procedures, but were not used appropriately for dirty procedures. The results of this study indicate that more effective methods for the implementation of appropriate glove use and HW should be emphasized.

Management of urinary bladder function in Danish hospitals, nursing homes and home care.

The purpose of this study was to determine the prevalence of the various devices used for bladder function management in Denmark and to assess the scope for the use of alternatives to the indwelling urethral catheter. Data were collected on 1581 hospital patients, 1341 nursing home residents and 743 patients receiving home care. The sample populations were characterized by age, sex and independence in the activities of daily living. The prevalence of indwelling catheters in the three groups of patients was 13.2%, 4.9% and 3.9%, respectively. The equivalent figures for condom drainage systems were 1.5%, 0.8% and 1.2%, and for napkins 10.1%, 52.1% and 34.1%. Comparison of the results from this survey with earlier data indicates that over the period 1980-1991 (during which efforts have been made in Denmark to restrict indwelling bladder catheterization and encourage the use of alternative devices) there has been a reduction in the prevalence of indwelling catheters in hospital medical wards from 13.7% to 6.6%. Examination of the reasons for catheterization revealed that the proportions of patients catheterized because of incontinence were 14% in hospitals, 31% in nursing homes and 33% in home care. There is clearly a need to continue the educational efforts to inform staff of the infection risks and complications associated with indwelling catheters and persuade them of the advantages of the alternative techniques for care of the incontinent patient.

A comparison of the effects of preoperative whole-body bathing with detergent alone and with detergent containing chlorhexidine gluconate on the frequency of wound infections after clean surgery. The European Working Party on Control of Hospital Infections.

In a prospective, randomized, double-blind, placebo-controlled study involving 27 surgical units in six European countries, the effect of preoperative whole-body bathing on two occasions with a detergent containing chlorhexidine (CHX+) on the incidence of wound infection in elective, clean surgery was compared with two bathings with a detergent without chlorhexidine (CHX-). In the CHX+ group 2.62% of 1413 patients and in the CHX- group 2.36% of 1400 patients subsequently became infected. The infection rate in the CHX+ group was 1.11 times that in the CHX- group with 95% confidence limits ranging between 0.69 and 1.82. Consequently, bathing patients twice preoperatively with chlorhexidine-detergent did not reduce the incidence of infection of clean wounds.

Bacteraemia in surgical patients with intravenous devices: a European multicentre incidence study. The European Working Party on Control of Hospital Infections.

A survey of the incidence of bacteraemia and the use of intravenous (IV) devices among 10,616 surgical patients was performed in 42 hospitals in eight countries. It was found that 63 per cent of the patients surveyed had an IV device inserted at some time during their hospital stay, with national variations between 40 and 99 per cent. The incidence of device-related thrombophlebitis was 10.3 per cent, with national variations between 7.8 and 28.4. Among the surgical patients not given IV therapy, 1.5/1000 had a bacteraemia, 0.5/1000 of them hospital-acquired. The corresponding figures for patients with a peripheral but no central IV device were 6.9 and 3.7, and for patients with a central venous catheter (CVC) 59.0 and 44.8, respectively. Even though there was a strong correlation between the incidence of bacteraemia and certain diagnoses there was also an independent correlation between it and CVCs or peripheral IV lines. No correlation was demonstrated between the number of catheter days per site for patients with a peripheral IV device, and hospital-acquired bacteraemia. This may be due to the low mean number of catheter days per site that was observed. There was a large and not easily explained national variation in the incidence of bacteraemia in patients with CVCs of between 16 and 108/1000.

Urinary-tract infection and bacteraemia in hospitalized medical patients--a European multicentre prevalence survey on nosocomial infection.

A co-ordinated survey of 3899 medical patients in 169 wards, performed simultaneously in eight countries, showed a point-prevalence of urinary-tract infection (UTI) and bacteraemia of 12.6 and 1.6 per cent, respectively. One-half of the infections were acquired after the patients' admission. The bacteriological patterns of hospital- vs community-acquired infections were different, but showed no unexpected features. Antibiotic treatment was recorded in 22.3 per cent of the patients in this study, urinary-tract disinfectants, sulphonamides or penicillins being used in 95 per cent of those treated for UTI. The overall prevalence of urinary-tract drainage was 11.0 per cent with no significant difference between the two sexes. At ward level the rate of catheterized patients varied from below 5 per cent to more than 25 per cent, indicating--besides variations in the ward populations--differences in policies. The association between nosocomial UTI and the presence of an indwelling catheter and/or female sex was confirmed, while high age appeared to be a secondary risk factor among catheterized patients. The prevalence of nosocomial bacteraemia in patients with UTI was five times higher than in those without urinary-tract involvement, and a significant part of the nosocomial cases of both UTI and bacteraemia was clearly device-related. Guidelines for the use of indwelling catheters should be restrictive and provide for prompt removal. When introduced and followed they will effectively reduce nosocomial UTI and bacteraemia.

Differential antibody response of Gambian donors to soluble Plasmodium falciparum antigens.

A seroepidemiological and clinical study was performed in an area of West Africa (The Gambia) where Plasmodium falciparum is endemic with seasonal transmission. Plasma samples were tested by intermediate gel immunoelectrophoresis for antibodies against 7 soluble P. falciparum antigens. There were marked differences in the age-related pattern of antibody response to the different antigens. Antibodies to 4 of the antigens were acquired slowly with a maximum prevalence reached after 25-35 years of age. Antibodies against the 3 remaining antigens, including the endotoxin-like antigen, Ag7, were acquired earlier with a plateau of maximum prevalence reached after 5-11 years, i.e. at the time when morbidity due to malaria decreased. Children who had not appeared to be infected with malaria during the preceding transmission season had lower levels of antibodies to soluble antigens than did children who had had a documented attack of clinical malaria or parasitaemia. There was no difference in antibody profiles to soluble antigens between children with sickle cell trait and children with normal haemoglobin.