Familial Cervical Cancer: Case Reports,Review and Clinical Implications

We report three Dutch families with familial clustering of (pre)neoplastic cervical disease, review the literature on familial risks of cervical intraepithelial neoplasia (CIN) and cervical cancer, and discuss possible practical guidelines for women with a family history of cervical cancer. Daughters and sisters of women with cervical cancer have been reported to have a relative risk of 1.5-2.3 to develop this type of cancer. From a practical clinical point of view, we suggest that as in women with an increased non-genetic risk to develop cervical cancer (e.g. because of immunosuppressive therapy) increased surveillance to detect this tumour should be considered in women with an increased risk based on family history. Cessation of smoking should be advised. As the use of condoms at least prevents HPV re-infection its use can be recommended as a way to lower the cervical cancer risk. Future studies to determine the genetic contribution to the development of cervical cancer should include the paternal family history of cancer and, because genetic predisposition might express itself as a higher risk to develop precursors of cervical cancer, carcinoma in situ and CIN grade II-III.     

Human immunodeficiency virus infection in children hospitalised with tuberculosis

The impact of HIV infection on clinical presentation and outcome of tuberculosis (TB) was studied in children hospitalised at the Brooklyn Hospital for Chest Diseases (BCH), Cape Town over the 2-year period January 1998 to December 1999. Clinical data were extracted from a prospectively compiled patient register. Of 261 children with TB, 114 (median age 24 mths) were not HIV-infected and 36 (median age 23 mths) were HIV-infected. The HIV status of 111 children (median age 37 mths) was not determined. Pulmonary TB with or without extrapulmonary TB occurred in 97 (85%) children who were not HIV-infected, 35 (97%) HIV-infected children and 87 (78%) of those not tested (p = 0.025). A tuberculin reaction > or = 15 mm was elicited in ten (31%) of 32 HIV-infected children, 76 (72%) of 106 non-HIV-infected and 62 (71%) of those not tested (p < 0.001). Mycobacterium tuberculosis was cultured from 116 (49%) of 238 children and drug sensitivity was evaluated in 79. Nine isolates (11%) were resistant to isoniazid (INH) and 11 (14%) to INH and rifampicin (RMP). Two HIV-infected children treated previously in BCH for drug-sensitive TB were re-admitted with INH and RMP resistance. Two (2%) non-HIV-infected children, six (17%) HIV-infected children and one (1%) child with undetermined HIV status died (p < 0.001).     

Beta-cell capacity and insulin sensitivity in prepubertal children born small for gestational age: influence of body size during childhood

Insulin secretion and sensitivity was studied in 28 prepubertal children born small for gestational age (SGA) and in 22 prepubertal children born appropriate for gestational age (AGA). The effect of body size during childhood was also assessed. Insulin sensitivity was measured using the hyperinsulinemic-euglycemic clamp (M value), and beta-cell function was studied with the hyperglycemic clamp plus arginine. First-phase insulin response (FIR) was used to calculate the disposition index (FIR x M value). Arginine-stimulated second-phase insulin response was used as a measure of beta-cell capacity. DeltaBMI(0-1 year), DeltaBMI(0-2 years), and DeltaBMI(2-9 years) were classified in tertiles. SGA children were less insulin sensitive than AGA children (P = 0.009). beta-Cell capacity and disposition indexes were similar in the two groups. In SGA children, M values were lower in the tertile with the highest DeltaBMI(2-9 years) than in the tertile with the lowest DeltaBMI(2-9 years) (P = 0.01). No association between DeltaBMI(0-2 years) and decreased insulin sensitivity was found. In conclusion, prepubertal SGA children show decreased insulin sensitivity rather than decreased beta-cell capacity. Interventions to improve fetal growth and prevent overweight after the second year of life appear to be important factors in the prevention of type 2 diabetes in children born SGA.     

Use and Evaluation of an Individually Tailored Website for Counselees Prior to Breast Cancer Genetic Counseling

This article explores the use and evaluation of a pre-visit website which aims to prepare counselees who are the first in their family to request breast cancer genetic counseling. This website E-info gene^ca provides computer-tailored information and a blank question prompt sheet (QPS) on which counselees can formulate their questions for the consultation. The objectives of this study are: first, to assess which factors influence the use of E-info gene^ca, including the duration of site and page views, the influence of topic sequence in the menu bar on the sequence of page views, and the relation between website use and the use of the QPS; second, to explore counselees’ evaluations of E-info gene^ca and relations with counselee characteristics. User statistics were analyzed to describe duration of site and page views. Multivariate analyses were used to predict duration of web and page views, sequence of page views, QPS use, and site evaluations. Independent variables were sociodemographic background, disease status, psychological functioning, and information needs. All 101 counselees who were provided with a login accessed the website and spent, on average, 21 min viewing the website. Counselees affected with breast cancer spent more time on the website than unaffected counselees. Half of all page views were within the sequence of topics in the menu and older counselees, and those who made less use of the internet more often navigated according to the menu sequence than others. Having viewed information about why it is important to ask questions increased QPS use. Counselees who had higher information needs considered the information more helpful. This hospital-provided website for breast cancer genetic counselees was accessible and was evaluated positively, even concerning older counselees and those who had not searched the internet for information about hereditary cancer. Counselees might navigate hospital-provided websites more in line with the sequence of topics in the menu bar, than generally accessible health websites.     

Longitudinal echocardiographic follow-up in children with congenital complete atrioventricular block

BACKGROUND: Due to a low heart rate (HR) in children with congenital complete atrioventricular block (CCAVB), a larger stroke volume of the left ventricle (LV) may be expected. If so, end-diastolic (LVEDD) and end-systolic (LVESD) diameters may be enlarged and even dilated cardiomyopathy (DCM) may occur. The aim of this study was to answer the question if children with CCAVB develop LV dilatation. Furthermore, we investigated whether LV dilatation would decrease after pacing. METHODS: We longitudinally evaluated echocardiographic data (LVEDD, LVESD, shortening fraction [SF]) in 36 children with CCAVB. Age at the first visit was 2.5 +/- 3.3 years (mean +/- SD); follow-up 10.6 +/- 7.3 years. RESULTS: Three children had DCM, already at 1st visit. LVEDD and LVESD Z scores in all children with CCAVB were larger than in normal controls (LVEDD Z score 1.38 +/- 1.80; LVESD Z score 0.64 +/- 1.35). Both Z scores were larger when HR was lower. Both Z scores increased over time in children who met criteria for pacing, but did not change in non-paced children. Physiologic pacing decreased both Z scores. SF of all children was normal and remained normal during follow-up (0.39 +/- 0.05 1st visit vs 0.39 +/- 0.06 last visit). CONCLUSIONS: We conclude that children with CCAVB have LV dilatation, which is progressive in children who met criteria for pacing. LV dilatation regressed by physiologic pacing. LV dilatation was larger when HR was lower. SF does not deteriorate over time. DCM occurs early in the disease and does not develop during childhood, not even in children with LV dilatation.     

Opening the black box: the patient mix of GP trainees

Background

The variety of health problems (patient mix) that medical trainees encounter is presumed to be sufficient to masterthe required competencies.

Aim

To describe the patient mix of GP trainees, to study differences in patient mix between first-year and third-year GP trainees, and to investigate differences in exposure to sex-specific diseases between male and female trainees.

Design and setting

Prospective cohort study in Dutch primary care.

Method

During a 6-month period, aggregated data about International Classification of Primary Care diagnosis codes, and data on the sex and age of all contacts were collected from the electronic patient record (EPR) system.

Results

Seventy-three trainees participated in this study. The mean coding percentage was 86% and the mean number of face-to-face consultations per trimester was 450.0 in the first year and 485.4 in the third year, indicating greater variance in the number of patient contacts among third-year trainees. Diseases seen most frequently were: musculoskeletal (mean per trimester = 89.2 in the first year/91.0 in the third year), respiratory (98.2/92.7) and skin diseases (89.5/96.0). Least often seen were diseases of the blood and blood-forming organs (5.3/7.2), male genital disorders (6.1/7.1), and social problems (4.3/4.2). The mean number of chronic diseases seen per trimester was 48.0 for first-year trainees and 62.4 for third-year trainees. Female trainees saw an average of 39.8 female conditions per trimester — twice as many as male trainees (mean = 21.3).

Conclusion

Considerable variation exists trainees in the number of patient contacts. Differences in patient mix between first- and third-year trainees seem at least partly related to year-specific learning objectives. The use of an EPR-derived educational instrument provides insight into the trainees'' patient mix at both the group and the individual level. This offers opportunities for GP trainers, trainees, and curriculum designers to optimise learning when exposure may be low.     

Open-access transvaginal sonography in women of reproductive age with abnormal vaginal bleeding: a descriptive study in general practice

Background

Diagnostic ultrasonography is used by GPs in approximately 10% of patients of reproductive age with abnormal vaginal bleeding. Transvaginal sonography is recommended as a first-line diagnostic instrument for assessing uterine pathology.

Aim

To assess if findings resulting from openaccess sonography were in agreement with the GPs’ working hypotheses and if these findings contributed to GPs’ management.

Design and setting

Prospective observational cohort study of GPs working in the health district of the Academic Medical Center, Amsterdam and their patients consulting with abnormal vaginal bleeding.

Method

Data on patients’ history, GPs’ primary working hypotheses, and intended management were recorded. After sonography, GPs recorded their actual management.

Results

A total of 122 patients were included by 18 GPs from June 2003 to December 2004. Data from 89 patients were available for analysis. The GPs’ working hypotheses implied ‘no structural pathology’ in 65/89 patients, and ‘fibroids’ in 24/89 patients. Sonographic findings were confirmed in 50/65 patients where ‘no structural pathology’, and in 14/24 of those where ‘fibroids’ were expected. Initially, GPs had intended to refer nine patients to a gynaecologist. Actual management after sonographic assessment was watchful waiting or drug therapy in 57/89 patients. Eighty-nine per cent of these patients had normal sonographic findings. The actual referral rate rose to 27/89 patients. In 17 referred patients, sonographic findings were suggestive of intracavitary abnormalities.

Conclusion

Open-access sonography contributed to more accurate diagnoses and improved GPs’ management of women with abnormal vaginal bleeding.     

Differential effect of drug interference in immunogenicity assays

The presence of anti-drug antibodies (ADA) in adalimumab-treated patients is associated with reduced serum adalimumab levels and a lower clinical response. Currently, there is no standard for measurement of anti-drug antibodies and many factors influence the results. Consequently, the incidence of ADA as reported in different studies varies considerably. Here we investigated the differential effect of drug interference in two common types of assays used to measure anti-adalimumab: an antigen binding test (ABT) and a more often-used bridging elisa. We measured ADA to adalimumab in a cohort of 216 rheumatoid arthritis patients treated with adalimumab for 28 weeks. Only 15 samples (7%) were positive in the bridging elisa, compared to 29 (13%) in the ABT, despite the fact that the bridging elisa was the most sensitive assay. Furthermore, in an ABT specific for IgG4, 48 samples (22%) were found positive. The bridging elisa was found to detect only the bivalent form of (drug-specific) IgG4, resulting in an underestimation of ADA levels. However, the predominant reason for the different outcomes of these assays was a differential susceptibility to drug interference. In particular, the bridging elisa only detected ADA in the absence of detectable amounts of circulating adalimumab and is therefore not suited for measurement of ADA in complex with the drug. In summary, we showed that a bridging elisa is susceptible to drug interference and typically measures ADA only in absence of detectable drug levels.