Age-specific patterns of unsatisfactory results for conventional Pap smears and liquid-based cytology: data from two randomised clinical trials.

OBJECTIVE: To investigate the rate of unsatisfactory cervical cell samples in liquid-based cytology (LBC) versus conventional cytology (CC) by age. DESIGN: Randomised clinical trials. SETTING: Population-based cervical cancer screening in the Netherlands and Italy. POPULATION: Asymptomatic women invited for screening enrolled in two randomised trials: Netherlands ThinPrep versus conventional cytology (NETHCON; 39 010 CC, 46 064 LBC) and New Technologies in Cervical Cancer Screening (NTCC; 22 771 CC, 22 403 LBC). METHODS: Comparison of categorical variables using Pearson's chi-square test, logistic regression and trend tests. MAIN OUTCOME MEASURES: Proportion of unsatisfactory samples, ratio of LBC versus CC, and variation by 5-year group. RESULTS: In NETHCON, a lower percentage of LBC samples were judged to be unsatisfactory compared with CC samples (0.33 versus 1.11%). There was no significant trend in unsatisfactory results by age group for conventional cytology (P(trend) = 0.54), but there was a trend towards an increasing percentage of unsatisfactory results with increasing age for LBC (P(trend) < 0.001). In NTCC, a lower percentage of LBC samples were judged to be unsatisfactory compared with conventional cytology (2.59 versus 4.10%). There was a decrease in the unsatisfactory results by age group with conventional cytology (P(trend) < 0.001) and with LBC (P(trend) = 0.01), although the latter trend arose from the 55-60-years age group (P(trend) = 0.62 when excluding this group). CONCLUSIONS: The clinical trial in which the results were collected and the cytologic method used were the most important determinants of unsatisfactory cytology. In all situations, the proportion of unsatisfactory samples was lower in LBC compared with CC. The effects of age depended on the criteria used to define unsatisfactory results.

European guidelines for quality assurance in cervical cancer screening: recommendations for cervical cytology terminology.

There are many different systems of cytology classification used in the member states of the European Union (EU) and many different languages. The following short annexe to Chapter 3 of the European Guidelines for Quality Assurance in Cervical Cancer Screening provides a framework that will allow different terminologies and languages to be translated into standard terminology based on the Bethesda system (TBS) for cytology while retaining the cervical intraepithelial neoplasia (CIN) classification for histology. This approach has followed extensive consultation with representatives of many countries and professional groups as well as a discussion forum published in Cytopathology (2005;16:113). This article will describe the reporting of specimen adequacy, which is dealt with in more detail elsewhere in Chapter 3 of the guidelines, the optional general categorization recommended in TBS, the interpretation/cytology result and other comments that may be made on reports such as concurrent human papillomavirus testing and the use of automation review and recommendations for management. The main categories in TBS will be described in the context of CIN, dyskaryosis and dysplasia terminologies so that all may be translated into the same framework. These guidelines should allow European countries to adapt their terminology in such a way as to make their screening programmes comparable with each other as well as with programmes elsewhere in the world.

European guidelines for quality assurance in cervical cancer screening: recommendations for collecting samples for conventional and liquid-based cytology.

The current paper presents an annex in the second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening. It provides guidance on how to make a satisfactory conventional Pap smear or a liquid-based cytology (LBC) sample. Practitioners taking samples for cytology should first explain to the woman the purpose, the procedure and how the result will be communicated. Three sampling methods are considered as acceptable for preparing conventional Pap smears: (i) the cervical broom; (ii) the combination of a spatula and an endocervical brush; and (iii) the extended tip spatula. Smear takers should take care to sample the entire circumference of the transformation zone, to quickly spread the cellular material over a glass slide, and to fix the preparation within a few seconds to avoid drying artefacts. According to local guidelines, one of these three methods may be preferred. Sampling with a cotton tip applicator is inappropriate. Similar procedures should be followed for sampling cells for LBC, but only plastic devices may be used. The collected cells should be quickly transferred into a vial with fixative liquid according to the instructions of the manufacturer of the LBC system. Subsequently, the slide or vial and the completed request form are sent to the laboratory for cytological interpretation.

European guidelines for quality assurance in cervical cancer screening: recommendations for cytology laboratories.

The quality of a cervical cytology laboratory depends on adequate handling and staining of the samples, screening and interpretation of the slides and reporting of the results. These guidelines give an overview of procedures recommended in Europe to manage the balance between best patient care possible, laboratory quality assurance and cost effectiveness and will be published as a chapter 4 in the European Guidelines for Quality Assurance in Cervical Cancer Screening. The laboratory guidelines include protocols for personnel and organisation, material requirements, handling and analysing cervical samples, recording of results, quality management and communication. The section on quality management is comprehensive and includes protocols for all aspects of internal and external quality assurance. The guidelines are extensively referenced and as far as possible the recommendations are evidence-based.

Hamilton's rule, imprinting and parent-offspring conflict over seed mass in partially selfing plants.

When genes in the offspring control the provisioning of the seed, the optimal seed size can be calculated exactly by applying Hamilton's rule. When seed size is a compromise between mother and offspring, we predict that outcrossing plant species produce larger seeds than selfers. This trend was found in the British flora and in a number of well-studied plant families. The analysis was extended to imprinting, a conditional strategy in which a gene in the offspring takes more resources when derived from the father than from the mother. The conditions for imprinting to be selected were rather restrictive. The analysis is relevant for the current debate about the evolution of imprinting in Arabidopsis thaliana.

Interstitial pneumonia and hepatitis caused by minocycline.

A 28-year-old patient is described who presented with progressive dyspnoea and jaundice due to interstitial pneumonia and hepatitis. The most likely cause is a drug-related reaction to minocycline. We discuss the different kinds of drug-related reactions that are most likely involved.

Heritability of nectar production in Echium vulgare.

Heritabilities of nectar production in the wild species Echium vulgare were estimated as realised heritability under controlled and field conditions. The nectar production of offspring from high- and low-nectar-producing parents was significantly different in both controlled and field conditions, indicating that nectar production is in part genetically determined. The present study is the first one to report a genetic component of variation of nectar production in a wild plant species in the field. Heritability estimated under controlled conditions was 0.13 and therewith less than the heritability estimated under field conditions, which amounted to 0.26. Offspring of high-nectar-producing plants produced comparable amounts of nectar in the growth chamber (1.28 microl) and in the field (1.22 microl). In contrast, the nectar production of offspring of low-nectar-producing plants was significantly higher in the growth chamber (0.95 microl) than in the field (0.55 microl), indicating a genotype by environment interaction. The level of heritability of nectar production was dependent on the environment. Under less favourable conditions, like those in the field, heritability of nectar production increased. Nectar production was not correlated with any of the vegetative or reproductive traits measured, and hence no costs of nectar production could be detected. Results obtained stress the importance of field measurements in determining heritabilities.

Cerebriform intradermal naevus (a rare form of secondary cutis verticis gyrata).

BACKGROUND: Acquired cerebriform intradermal naevus (CIN) is a rare form of pseudo cutis verticis gyrata. CASE REPORT: A case of acquired CIN of the scalp in a 46-year-old male patient is presented. The clinical and histopathological presentations of CIN are described and the therapeutic possibilities are discussed. CONCLUSIONS: In each individual case the physician must decide whether to do surgery or follow a wait-and-see policy. There is little risk of malignant change of CIN, and surgical excision of such lesions often involves evident mutilation.

Selective seed abortion increases offspring survival in Cynoglossum officinale (Boraginaceae).

Selective embryo abortion is one of the evolutionary explanations for the surplus of ovules found in many plant species. To manipulate the level of embryo abortion, we removed ovules and applied nutrients to plants of Cynoglossum officinale (Boraginaceae) after they started to flower. From these two treatments and a control series, seeds were collected, germinated, and transplanted in the field to assess the quality of the resulting offspring. Nutrient addition did not increase the number of seeds per flower significantly. Fewer embryos were aborted in the ovule removal treatment. The seeds produced in the ovule removal treatment had a significantly greater mass and significantly lower survival than the offspring from the control group. This difference in survival indicates that offspring of lower quality are selectively aborted in the control group. Offspring from the nutrient addition treatment survived longer. The offspring of the treatments did not differ significantly from the control group in growth. Simple mathematical calculations, based on the differences in offspring quality that we found, indicate that the selective abortion hypothesis can be an important factor explaining the advantage of the "surplus production" of ovules.

Malabsorption syndrome in a patient of Mediterranean origin; immunoproliferative small intestinal disease.

We describe a 30-year-old woman of Turkish descent presenting with abdominal pain and signs of malabsorption. The cause of her complaints turned out to be immunoproliferative small intestinal disease which is a very uncommon disorder in our geographical region. We discuss the differential diagnosis of this disease and the therapeutical options.

Is there a common etiology for the rising incidence of and decreasing survival with adenocarcinoma of the lung?

We studied possible explanations for the deteriorating survival for adenocarcinoma of the lung between 1975 and 1994 in relation with trends in incidence. The proportion of adenocarcinoma among men has been increasing since 1975 and for those born after 1920, while survival has decreased since 1975 and for those born since 1930. Among women, both the proportion of adenocarcinoma and survival have remained more or less constant. The rising incidence and the decreasing survival may both be related to changes in tobacco use, the increased use of low-tar filter cigarettes since the 1960s being the most likely candidate.

Increased but low incidence and poor survival of malignant mesothelioma in the southeastern part of The Netherlands since 1970: a population-based study.

Changes in the incidence and survival rates for malignant mesothelioma in the southeastern part of The Netherlands since 1970 were investigated, using data from the Eindhoven Cancer Registry (ECR). The exposure to asbestos in this area is presumed to be limited. Most of the mesotheliomas occurred in the pleura, where there were 119 (88%) against 15 (11%) in the peritoneum and two in the tunica vaginalis testis. Compared to other European countries, the incidence rate for the southeastern part of The Netherlands was fairly low in the second half of the 1980s. Between 1975 and 1994 the age-adjusted incidence rates (ESR) for pleural mesothelioma increased twofold (from 10 to 19 per one million person-years among men and from 2.4 to 3.8 among women). The rate for peritoneal mesothelioma remained constant. The overall relative 0.5-, 1-, and 3-year survival rates remained 68, 42, and 8%, respectively. The fourfold higher incidence rate for men compared with women reflects the fact that mesothelioma is mainly an occupational disease. In view of presumed limited exposure to asbestos and small geographical variation, the incidence of mesothelioma in the southeastern part of The Netherlands will probably remain low, despite an increase in the past decades.

Direct and indirect estimates of the selfing rate in small and large individuals of the bumblebee pollinated Cynoglossum officinale L (Boraginaceae).

We measured the relationship between selfing rates and flower number in an experimental population of bumblebee pollinated Cynoglossum officinale, with plants differing in flower number. Results were compared with the prediction of a model based on pollen dynamics and pollinator behaviour. The selfing rate, as measured by multilocus oligonucleotide DNA fingerprinting, increased with flower number and ranged from 0% to 70%. Flowers on large plants received an equal number of visits from bumblebees as flowers on small plants. On large plants more flowers in a row were visited, inducing geitonogamy. The overall relationship between selfing rate and number of flowers can be explained by pollen dynamics and pollinator behaviour without invoking postpollination processes such as differential pollen tube growth and abortion.

Improvement and plateau in survival of small-cell lung cancer since 1975: a population-based study.

BACKGROUND: Cytotoxic therapy appears to have improved short-term survival for patients with small-cell lung cancer, but little is known about the results for unselected patients and trends in long-term survival. PATIENTS AND METHODS: One thousand seven hundred ninety-six patients with small-cell lung cancer diagnosed between 1975 and 1994 in southeastern Netherlands. We studied treatment policy for and survival of unselected patients since 1975, when cytotoxic therapy emerged. RESULTS: The proportion patients receiving chemotherapy, with or without irradiation, almost tripled from 30% to 82% for patients younger than 70 years of age and from 15% to 56% for those over 70, whereas the proportion receiving only radiotherapy decreased from 36% to 5% in both age groups. The short-term (< 2 year) survival rate improved markedly between 1975 and 1989, especially for patients younger than 70 (median survival increased from five to 10 months). Two-year survival remained poor (8%). Two percent of all patients younger than 70 years at diagnosis survived for at least eight years, but these patients still represent an excess five-year mortality of 39%. CONCLUSIONS: In southeastern Netherlands short-term survival of patients with small-cell lung cancer improved markedly up to the end of the 1980s, but a major impact on cure rates has not been achieved.

Divergent changes in survival for histological types of non-small-cell lung cancer in the southeastern area of The Netherlands since 1975.

We studied the incidence and survival rates for the histological subtypes of non-small-cell lung cancer, using data from the Eindhoven Cancer Registry over the period 1975-94. The proportions with adenocarcinoma and large-cell undifferentiated carcinoma increased from 11% to 21% and from 11% to 15%, respectively, while those with squamous cell carcinoma decreased from 78% to 62%. The increase in the proportion with adenocarcinoma was only found among men. Although the overall prognosis for patients with non-small-cell lung cancer has remained unchanged, there have been divergent changes between morphological subtypes. Relative 1- and 5-year survival rates for squamous cell carcinoma have improved slightly from 48% to 51% and from 14% to 16%, respectively, because of an increase in the proportion with localized tumours, while relative 1- and 5-year survival rates for adenocarcinoma have decreased from 59% to 45% and from 28% to 18%, respectively, because of a decrease in localized tumours. The proportion with localized tumours and the relative 1-year survival for large-cell undifferentiated carcinoma (about 18% and 30% respectively) were markedly lower. The divergent trends could partly be explained by changes in the histological classification of tumours, but changes in patterns of risk and biological behaviour of adenocarcinoma cannot be excluded.

Sex and size in cosexual plants.

There are conceptual and practical difficulties in measuring the exact shape of fitness-gain curves and sex allocation, and these hamper empirical testing of some of the basic predictions of sex allocation theory for plants. Nevertheless, our knowledge of the processes that shape fitness-gain curves allows us to formulate hypotheses to test predictions of sex allocation theory. One such hypothesis is that plants adjust their gender according to size. The connection between plant size and gender was generally thought to be weak. Recent data, however, suggest that size-dependent sex allocation (SDS) is a common phenomenon in hermaphrodites and other cosexual plants.

Endometrial thickness assessed by transvaginal ultrasound insufficiently predicts occurrence of hyperplasia during unopposed oestrogen use.

In the present study, unopposed oestrogens were given to 184 non-hysterectomized women, for a duration varying from four weeks to 24 months, while the endometrial responses were monitored by transvaginal sonography (TVS) and backed up by endometrial sampling (conducted when the endometrial thickness reached 8 mm (double layer) or more, vaginal bleeding occurred during oestrogen administration, or after one year of unopposed oestrogen use). In cases where the endometrial thickness reached 8 mm or more, progestogens were administered for 12 days. In 64% of the women, administration of progestogen could be postponed until at least the fourth month of treatment under the pre-defined decision criteria. Eleven percent of the patients used oestrogens continuously during the two year study period, without any need of additional progestogen. In total, 338 endometrial biopsies were performed; 16 cases of hyperplasia were detected. In three cases, the corresponding endometrial thickness was below 8 mm (in one case, 5 mm). Endometrial thickness could not consistently predict occurrence of hyperplasia. In eight cases, hyperplasia occurred within 4 months of treatment, and in four cases, within only 2 months (of which only one case could possibly be attributed to previous hormone use and none to endogenous oestrogen production). The rapid occurrence of hyperplasia should be taken into account in studies of quarterly progestogen administration with hormone replacement therapy. It is concluded that postponement of progestogen administration with hormone replacement therapy under guidance of TVS only (without biopsies) would not be adequately safe to be recommended for clinical practice.

[Opportunistic lung infections in patients with chronic obstructive lung disease; a side effect of inhalation corticosteroids?]. / Opportunistische longinfecties bij patiënten met chronische obstructieve longziekte; een bijwerking van inhalatiecorticosteroïden?

In four patients, men of 64, 66 and 69 years old and a woman of 65 years, who suffered from chronic obstructive pulmonary disease (COPD) and used inhalation corticosteroids in a relatively high dose (800-1600 micrograms of budesonide per day), a pulmonary infection was diagnosed caused by Mycobacterium malmoense (the first two patients) and Aspergillus (the other two) respectively. Inhalation corticosteroids are of great importance in the treatment of asthmatic patients. Their place in the treatment of patients with COPD is much less clear. The patients did not have an immunological deficiency or anatomical pulmonary or bronchial deformation which could have explained the occurrence of these infections. The high dosages of inhalation corticosteroids may have been involved in the cause of these infections by suppressing the T-cell response locally. In view of this, longterm inhalation corticosteroid treatment should be prescribed in COPD patients only if the efficacy of the medication has been proved in the individual patient involved.