Frequency of non-histologically diagnosed basal cell carcinomas in daily Dutch practice.

BACKGROUND: Population-based basal cell carcinoma (BCC) incidences are based on cancer registry data; however, these only include histologically diagnosed tumours. OBJECTIVES: First, to investigate the number of subsequent non-histologically diagnosed BCC(s) in patients with a first histologically diagnosed BCC in 2004. Secondly, to observe differences in tumour characteristics between subsequent histologically and subsequent non-histologically diagnosed BCC(s). METHODS: All patients, from four hospitals located in the serving area of the Eindhoven Cancer Registry, with a first histologically diagnosed BCC in 2004 (n = 1290) were selected. A linkage was made with PALGA, the nationwide network and registry of histo- and cytopathology, to obtain pathology reports of subsequent histologically diagnosed BCC(s) up to 1 November 2010. Patient records were extracted from the participating dermatology departments and reviewed up to 1 November 2010 to identify non-histologically diagnosed BCC(s). RESULTS: Overall, 33.2% of the 1089 followed up patients developed subsequent histologically and/or non-histologically diagnosed BCCs. In total, 1974 BCCs were observed of which 1833 were histologically and 141 were non-histologically diagnosed BCCs. The distribution of tumour site and subtype differed significantly between subsequent histologically and subsequent non-histologically diagnosed BCCs. CONCLUSIONS: The total burden of BCC is underestimated by the absence of data on the occurrence of non-histologically diagnosed BCCs in daily dermatological practice. It is pivotal for Dutch healthcare policy makers to acknowledge this to make accurate BCC-related cost estimates.

Identification of a mutation associated with erythromycin resistance in Bordetella pertussis: implications for surveillance of antimicrobial resistance.

Erythromycin treatment failures and in vitro resistance of Bordetella pertussis have been reported on several occasions in the past few years, but the mechanism of resistance has not been described. One potential mechanism, genetic modification of the erythromycin-binding site on the 23S rRNA of the 50S ribosomal subunit, has been observed in other bacteria. To explore this possibility, we amplified the portion of the 23S rRNA gene encoding the central loop of domain V. DNA sequencing and restriction fragment length polymorphism of the PCR products showed that each of the four erythromycin-resistant B. pertussis strains tested contained an A-to-G transition mutation at position 2058 (Escherichia coli numbering) of the 23S rRNA gene. The mutation was not found in seven erythromycin-susceptible isolates tested. Two of the resistant isolates were heterozygous, containing at least one mutant copy and one wild-type copy of the 23S rRNA gene. These results indicate that erythromycin resistance in these strains is likely due to a mutation of the erythromycin-binding site in the 23S rRNA gene. Identification of the resistance mechanism will facilitate development of molecular susceptibility testing methods that can be used directly on clinical specimens in the absence of an isolate.

Bordetella pertussis isolates with a heterogeneous phenotype for erythromycin resistance.

Erythromycin is currently being used for both prophylaxis and treatment of pertussis infections. Erythromycin resistance was first recognized in Bordetella pertussis in Arizona in 1994, and since then, three additional resistant isolates have been identified in the United States. To better assess the potential public health impact of erythromycin-resistant B. pertussis, we used the disk diffusion assay to evaluate the frequency of erythromycin resistance among 1,030 recently circulating U.S. isolates and found the rate of occurrence to be <1%. We also describe a novel heterogeneous phenotype, with erythromycin-resistant colonies appearing only after a 7-day incubation period. To optimize patient management, we recommend that clinicians be alert to potential treatment failures and that laboratorians use a 7-day incubation period when screening for resistance. Our ongoing national surveillance will continue to monitor for resistant B. pertussis isolates and their potential association with changing pertussis epidemiology.

Molecular epidemiology of Bordetella pertussis by pulsed-field gel electrophoresis profile: Cincinnati, 1989-1996.

Reported cases of pertussis have increased in the United States, with peaks occurring every few years. Bordetella pertussis isolates collected in Cincinnati from 1989 to 1996 were analyzed with pulsed-field gel electrophoresis (PFGE), to evaluate trends. Among 496 isolates, 30 PFGE profiles were identified; 32% were CYXXI-010, the profile that predominated each year. Eighteen profiles (198 strains) were identified in 1989-1992, 20 profiles (197 strains) were identified during the 1993 epidemic, and 11 profiles (101 strains) were identified in 1994-1996. From 1989 to 1996, among 42 patients, isolates from household members in 17 (89%) of 19 households had concordant PFGE profiles. There was no association between PFGE profile and seasonality, age, and hospitalization or pneumonia in infants <1 year old. The 1993 epidemic was associated primarily with an increased prevalence of PFGE profiles that circulated before and after 1993, which suggests that the epidemic was due to factors other than the emergence of a novel B. pertussis strain.

Real-time PCR assay targeting IS481 of Bordetella pertussis and molecular basis for detecting Bordetella holmesii.

Detection of Bordetella holmesii by a real-time PCR assay targeting IS481 of Bordetella pertussis is reported. Sequencing of IS481-specific PCR products from B. pertussis and B. holmesii isolates revealed sequence homology. Restriction fragment length polymorphism demonstrated a low copy number of IS481-like sequences in B. holmesii. These results, and culture of B. holmesii from patients with cough, suggest that the specificity and predictive value of IS481-based PCR assays for pertussis may be compromised.

Polymorphism in Bordetella pertussis pertactin and pertussis toxin virulence factors in the United States, 1935-1999.

To elucidate the potential role of the etiologic agent in recent increases of pertussis incidence in the United States, we studied the polymorphism in pertactin and pertussis toxin, which are Bordetella pertussis proteins important for pathogenesis and immunity. We sequenced regions of their genes (prn and ptx) in 152 B. pertussis strains isolated from 1935 through 1999 and identified 2 prn sequences: prn1 (old), observed continuously since 1935, and prn2 (new), not recognized until 1981 but seen in 97% of tested isolates in 1999. There were 3 ptx S1 subunit sequences: ptxS1D (old) was identified in 3 strains (1935 and 1939); ptxS1B (old) represented 87% of the strains recovered during 1935-1974; and ptxS1A (new) was the most prevalent during 1975-1987 and 1989-1999 (64% and 78%, respectively). Potential association between vaccination and the observed shift from old to new types requires further study. Our results provide the basis for prospectively monitoring for changes among circulating B. pertussis that might have epidemiologic relevance.

Molecular epidemiology of Bordetella pertussis by DNA fingerprinting with pulsed-filled gel electrophoresis, 1989-1996

Pertussis is an endemic disease in the United States of America, with epidemics occurring every three to four years. In Cincinnati, Bordetella pertussis isolates collected from 1989 to 1996 were analysed by genomic subtyping with pulsed-field gel electrophoresis (PFGE) to evaluate the B pertussis population before, during and after a large epidemic of epidemiologically relevant changes. Among the 496 B pertussis isolates, 31 PFGE profiles were identified; 32 percent of isolates were CYXXI-010 and this profile predominated in each year. Nineteen, 20 and 12 PFGE profiles were identified in the pre-epidemic period (n=198), during the epidemic (n = 197) and in the post-epidemic period (n = 101), resulting in genotypic diversities of 0.82, 0.83 and 0.76 respectively. From 1989 to 1996, among 19 households clusters of 42 patients, 17 (89 percent) households had concordant PFGE profiles among isolates from household members. There was no association between PFGE type and seasonality, age, hospitalisation or pneumonia in infants. The 1993 epidemic was primarily associated with increased prevalence of B pertussis PFGE profiles that circulated before and after the epidemic, suggesting increased susceptibility to pertussis rather than a novel strain as a cause of the outbreak.(Au)

Evidence for transmission of pertussis in schools, Massachusetts, 1996: epidemiologic data supported by pulsed-field gel electrophoresis studies.

In 1996, 18 of 20 pertussis outbreaks reported in Massachusetts occurred in schools. Pertussis surveillance data were reviewed and a retrospective cohort study was conducted in a high school that experienced an outbreak. Bordetella pertussis isolates from 9 school cases and from 58 cases statewide were examined by use of pulsed-field gel electrophoresis (PFGE). Statewide incidence rates were highest among children aged <1 year, 10-14 years, and 15-19 years (106, 117, and 104 cases per 100,000, respectively). Among 34 confirmed and 20 probable cases at the school, 61% had cough onset within 8 weeks of school opening. Five different PFGE types were identified among the 58 B. pertussis isolates from throughout the state. All 9 isolates from the affected high school were the same PFGE type. School-aged children may play an important role in pertussis epidemics. Consideration should be given to use of acellular pertussis vaccines among school-aged children.

A uniform histological cluster scheme for ICD-O-coded primary central nervous system tumors.

Comparability of population-based measures of risk and prognosis for primary central nervous system (CNS) tumors, which exhibit marked histological diversity, may be hampered by differences in detection and case ascertainment and by the lack of unequivocal and uniform histological criteria for pathological diagnoses. Furthermore, many cancer registries do not include benign tumors as defined by the International Classification of Diseases for Oncology (ICD-O), such as meningiomas, schwannomas and pituitary adenomas. We propose both a detailed and a rough uniform histological cluster scheme for data coded according to the first or second edition of the ICD-O, published in 1976 and 1990, respectively. Primary CNS tumors, typed and graded according to (modified) classification systems of Bailey and Cushing, Kernohan, Ringertz, the WHO and Daumas-Duport, are clustered as clinically relevant entities on the basis of the second edition of the WHO classification system, published in 1993. The proposed scheme identifies some of the (potential) pitfalls in the descriptive epidemiology of CNS tumors and may facilitate temporal and geographical comparability of population-based data.

Incidence of primary central nervous system cancers in South and East Netherlands in 1989-1994.

About 2,000 patients with primary CNS cancers, as defined by the ICD-O, were registered in four adjacent cancer registries in South and East Netherlands in 1989-1994, covering a population of more than 5 million people. About 85% of the patients were registered through pathological laboratories, concentrated in four centers for neurosurgery. Patients with a clinical-radiological diagnosis only (about 50% in the age-group of 75 years and older) were mainly identified through medical records of hospitalized patients. World-standardized incidence rates of 6.5 and 4.4 per 100,000 person-years for males and females, respectively, were similar to those reported in other European cancer registries. Eighty-five percent of histologically verified primary CNS cancers were of glial origin, 6% were lymphomas and 4% embryonal tumors. Gliomas were mainly of astrocytic (about 85%) and oligodendroglial or mixed type (about 10%). Without additional review most astrocytic tumors could be classified into high-grade (70-75%) and low-grade astrocytomas (20-25%). Different grading systems were used for gliomas, but the dichotomy of astrocytomas according to differentiation grade seemed to correspond well with the definition of the WHO. Age-specific incidence rates for low-grade astrocytomas were remarkably constant. The incidence of high-grade astrocytomas increased sharply with age and declined after the age of 70, whereas the incidence of clinically diagnosed tumors continued to increase. Male/females-ratios were relatively high for these tumor types (1. 6-1.7). We conclude that the registration of primary CNS cancers in the Netherlands may be almost complete and valid for gliomas, embryonal tumors and lymphomas.

Incidence of primary cancer of the central nervous system in southeastern Netherlands during the period 1980-94. Specialists in neuro-oncology in southeastern Netherlands.

OBJECTIVES: Substantial increases in incidence and mortality rates for primary brain tumors have been reported in many, but not all, countries over the past several decades. We analyzed incidence rates for (potential) primary malignant central nervous system (CNS) tumors in an area (southeastern Netherlands) and during a period (1980-94) in which access to healthcare was good and computerized tomography (CT) was available. METHODS: Data were obtained from the Eindhoven and Maastricht cancer registries, representing a population of 936,000 and 847,000 inhabitants, respectively. Cases were identified of primary CNS tumors (ICD-0 codes 191, 192, excluding lymphomas) and brain metastases from an unknown primary site (code 199) and data on mortality according to gender and region were provided by Statistics Netherlands. RESULTS: Incidence rates in three-year periods of primary CNS cancer remained stable, also for patients aged 60 years and older. Mortality/incidence ratios ranged from 0.6 to 0.9. Although more CNS cancers were histologically verified in recent years, especially in the Eindhoven region, changes in diagnosis probably did not influence the overall trend of primary CNS cancer. CONCLUSIONS: Major changes in the incidence of the most common types of primary CNS cancers (i.e., high-grade astrocytomas) were unlikely in southeastern Netherlands.

Survival rates for primary malignant brain tumours in Europe. EUROCARE Working Group.

In the framework of EUROCARE, a concerted action between 45 population-based cancer registries, in 17 European countries, survival of patients with primary malignant brain tumours was investigated. Survival analysis was carried out on 16,268 patients diagnosed between 1985 and 1989 and followed-up for at least 5 years. The mean European age-standardised 5-year relative survival was 17% in men and 20% in women, with minimal intercountry variations, except for markedly lower rates in Scotland, Estonia and Poland. The age-specific analysis showed a relatively uniform survival in patients aged more than 65 years at diagnosis, but there were more marked intercountry differences in younger patients. In the 15-44 year age group (25% of the total study population) 5-year relative survival ranged between 55% (Finland and Sweden) and 27% (Poland). Generally, survival decreased with increasing age at diagnosis. The analysis of a temporal trend in survival was carried out on a subset of registries with available data from 1978-1989. Overall, there was an increase in survival over the considered study period, mostly confined to 1-year survival, suggesting that it was mostly related to improved diagnostic techniques. The most important survival increase occurred in the younger patients, both for 1- and 5-year survival, suggesting that younger patients have less biologically aggressive tumours, benefiting from the combined effect of diagnostic accuracy and effective therapies. The most marked survival increase was seen in England and Denmark, countries with low survival rates at the beginning of the study period, whereas in Finland and Germany, where survival was relatively high to begin with, no important temporal trend was seen.

A randomized double-blind trial comparing a two-component acellular to a whole-cell pertussis vaccine in Senegal.

A randomized, double-blind trial comparing a diphtheria-tetanus-acellular pertussis vaccine (DTaP) (pertussis toxoid and filamentous hemagglutinin) with a whole-cell vaccine (DTwP) was conducted. A case-contact study was nested in the trial to estimate absolute efficacy. From 1990 through 1994, 4181 children were randomized to receive one of the vaccines at 2, 4, and 6 months. Severe adverse events were monitored weekly during two visits after vaccination. Fewer serious adverse events were observed after DTaP. Surveillance for cough illnesses persisting more than 7 days, in children under 15 years of age, was made by weekly home visits. Examining physicians, blind to vaccination status, took samples for culture and serologic testing. Pertussis was defined as 21 or more days of cough confirmed by culture, serology, or contact with a culture-confirmed person. Beginning 28 days after the third vaccine dose, the overall ratio of pertussis incidence in the DTaP group relative to the DTwP group (RRac/wc) was 1.54 (95% CI, 1.23-1.93). In children younger than 18 months of age, RRac/wc was 1.16 (95% CI, 0.77-1.73) and 1.76 (95% CI, 1.33-2.33) in children older than 18 months, which suggests a shorter duration of protection with the acellular vaccine (P = 0.090). Absolute efficacy estimates derived from the case-contact study confirmed the lower protection afforded by the acellular vaccine compared with the whole-cell vaccine: 31% (95% CI, 7-49) versus 55% against the protocol case definition, and 85% (95% CI, 66-93) versus 96% for the more severe WHO case definition. Although vaccination with DTaP provided a lower degree of protection than the highly effective DTwP, this difference was less prominent before 18 months of age, the customary age for a fourth dose. The safer DTaP vaccine may prove a valuable substitute for whole-cell vaccines when used in a schedule that includes a booster-dose.

A Bordetella pertussis fepA homologue required for utilization of exogenous ferric enterobactin.

The bfeA (Bordetella ferric enterobactin) receptor gene was cloned from a Bordetella pertussis chromosomal library by using a screen in Escherichia coli to detect iron-repressed genes encoding exported proteins translationally fused to the E. coli phoA gene. The bfeA gene encoded a protein with a molecular mass of approximately 80 kDa and about 50% amino acid sequence identity to both the fepA- and pfeA-encoded enterobactin receptors of E. coli and Pseudomonas aeruginosa, respectively. Enterobactin prepared from iron-starved E. coli cultures supported growth of B. pertussis and Bordetella bronchiseptica in the presence of the iron chelator ethylenediamine-di-(o-hydroxyphenylacetic acid) (EDDA). Expression of the bfeA gene was induced by low iron availability, and iron-regulated expression appeared to be dependent upon the presence of the sequence contained within 370 bp upstream of the bfeA structural gene. An internal fragment of the bfeA structural gene and flanking regions were shown by Southern analysis to be highly conserved among Bordetella species. Insertional inactivation of bfeA in both B. pertussis and B. bronchiseptica greatly impaired their ability to grow in the presence of enterobactin and EDDA. These findings suggest that enterobactin produced by other respiratory flora could aid in the colonization of the respiratory tract by Bordetella species.

Analysis of Bordetella pertussis isolates from an epidemic by pulsed-field gel electrophoresis.

We examined genetic variation among 78 clinical isolates of Bordetella pertussis, including 54 strains recovered during a 1986 pertussis epidemic. A total of 16 pulsed-field gel electrophoresis (PFGE) profiles, generated with each of three different enzymes (XbaI, SpeI, and DraI), were obtained from the epidemic and sporadic isolates included in the study. Indistinguishable profiles were seen among strains unrelated temporally or geographically, as well as among strains isolated sporadically from the same geographic areas. All isolates from the epidemic had indistinguishable PFGE profiles. The PFGE pattern of the epidemic strains was shared with only 1 of 25 strains isolated independently of the outbreak. This isolate was cultured from a specimen from a laboratory scientist who had been working with the epidemic strains, further implicating the usefulness of PFGE for the epidemiologic study of clinical strains of B. pertussis. Differences in PFGE profiles for single epidemic strains occurred occasionally upon repeated passage on agar medium, suggesting that subculturing of initial isolates should be minimized before pulsed-field analysis.

Cancer incidence in The Netherlands in 1989 and 1990: first results of the nationwide Netherlands cancer registry. Coordinating Committee for Regional Cancer Registries.

The first results are presented of the newly established Netherlands Cancer Registry, which covers the whole Dutch population (approximately 15 million people). The registry receives data on incident cancer cases from nine autonomous regional cancer registries. Notification occurs primarily through the national registry of all pathology and haematology departments, with additional reporting by medical records' departments of all hospitals. Data on cancer patients are abstracted directly from the medical records by trained registration clerks. In the years 1989-1990, the most common cancer sites among males were cancers of the lung, prostate and colon. For females, breast cancer ranked first, followed by cancer of the colon and lung. A comparison with age-adjusted (world standard population) incidence rates reported by other western cancer registries showed a relatively high incidence of lung cancer among males (72.9 per 100,000) and breast cancer among females (76.2 per 100,000). Through its near completeness and the high quality of the registered data, the Netherlands Cancer Registry offers excellent opportunities for epidemiological and clinical research.

Pertussis infection among adults during the 1993 outbreak in Chicago.

To evaluate the role of adults in the transmission of pertussis during an epidemic, persons presenting with unexplained cough to ambulatory care clinics were evaluated for evidence of pertussis infection. Nasopharyngeal specimens for culture and serum samples for IgG and IgA antibodies to filamentous hemagglutinin and pertussis toxin antigens of Bordetella pertussis were obtained. Thirty-eight adults were enrolled in the study; 10 (26%) had serologic evidence of B. pertussis infection. Clinical findings were not significantly different among persons with and without evidence of pertussis infection. Pertussis should be considered in the differential diagnosis of persistent cough in all age groups. Future use of new acellular pertussis vaccines in adults may substantially impact the control of the infection.

Cloning and initial characterization of the Bordetella pertussis fur gene.

In several Gram-negative pathogens the fur (ferric uptake regulator) gene product controls the expression of many genes involved in iron uptake and virulence. To facilitate the study of iron-regulated gene expression in Bordetella pertussis, we cloned the fur gene from this organism. The B. pertussis fur gene product was 54% identical to the Escherichia coli Fur and complemented two E. coli fur mutants. As with the E. coli fur gene, sequences upstream of the B. pertussis fur were homologous to the consensus Fur-binding site and to the consensus catabolite activator protein binding site.

Concurrent outbreaks of pertussis and Mycoplasma pneumoniae infection: clinical and epidemiological characteristics of illnesses manifested by cough.

Concurrent outbreaks of illnesses that were manifested by cough and that were suspected to be due to Bordetella pertussis and Mycoplasma pneumoniae infection were investigated in a midwestern town in Illinois. Three studies were conducted: questionnaires on the clinical and epidemiological characteristics of illness were administered to patients; serological tests were performed to confirm the presence of each pathogen and to develop case definitions for each illness; and case definitions were applied to responses to a mail-in questionnaire for estimating the magnitude of both outbreaks. In 135 cases of suspected pertussis and 42 cases of suspected mycoplasmal infection, subjects had a cough for > or = 14 days (the pertussis outbreak case definition). Among 20 laboratory-confirmed cases, a cough for > or = 14 days had a specificity of 20% for pertussis, and a cough for > or = 28 days plus whoop and/or vomiting had a specificity of 90% for pertussis. Six hundred-seventeen pertussis cases per 100,000 population and 1,179 cases of M. pneumoniae infection per 100,000 population occurred. In this setting, the standard outbreak case definition for pertussis lacked adequate specificity to distinguish pertussis from mycoplasmal infection. The magnitude of each outbreak was greater than the number of reported cases suggested.

Close coupling results for inelastic collisions of NH3 and Ar. A stringent test of a spectroscopic potential.

We have calculated state-to-state total cross sections for rotational excitation and inversion of NH3 by collisions with Ar using the close coupling method. The Ar-NH3 interaction potential has been obtained from a fit to the spectrum of this van der Waals molecule. The calculated cross sections agree to within about 30% with the measured values; the estimated error in the latter is 10% to 20%.