Pre- and post-natal exposure to antibiotics and the development of eczema, recurrent wheezing and atopic sensitization in children up to the age of 4 years.

BACKGROUND: Little data are available on the relationship between indirect antibiotic exposure of the child in utero or during lactation and allergic diseases. On the other hand, several studies have been conducted on the association with direct post-natal antibiotic exposure, but the results are conflicting. OBJECTIVE: The aim of this study was to investigate pre- and post-natal antibiotic exposure and the subsequent development of eczema, recurrent wheeze and atopic sensitization in children up to the age of 4 years. METHODS: We conducted an aetiologic study in 773 children based on a prospective birth cohort project in which environmental and health information were collected using questionnaires. Antibiotic exposure was assessed as maternal antibiotic intake during pregnancy and during lactation and as medication intake of the child. The chronology of exposures and outcomes was taken into account during the data processing. At the age of 1 and 4 years, a blood sample was taken for the quantification of specific IgE. RESULTS: Prenatal antibiotic exposure was significantly positively associated with eczema, whereas no association was found with recurrent wheeze and atopic sensitization. We found a positive, although statistically not significant, association between antibiotic exposure through breastfeeding and recurrent wheeze. Neither eczema nor atopic sensitization was significantly associated with antibiotic exposure through breastfeeding. Finally, we observed a negative association between the use of antibiotics in the first year of life and eczema and atopic sensitization, and also between antibiotic use after the first year of life and recurrent wheeze, eczema and atopic sensitization. CONCLUSION: Indirect exposure to antibiotics (in utero and during lactation) increases the risk for allergic symptoms in children, while direct exposure to antibiotics appears to be protective. The biological mechanisms underlying these findings still need to be elucidated.

Detection of recurrence in patients with clinical stage I nonseminomatous testicular germ cell tumors and consequences for further follow-up: a single-center 10-year experience.

PURPOSE: A wait-and-see policy for patients with stage I nonseminomatous testicular germ cell tumors (NSTGCT) was evaluated in a prospective study. The frequency and time of recurrence, detection of recurrence, and presence of unfavorable prognostic factors were investigated. PATIENTS AND METHODS: During the period 1982 to 1992, 154 patients with stage I NSTGCT (median age, 29 years) underwent orchidectomy and were monitored at follow-up evaluation with physical examinations, alfafetoprotein (AFP) and beta-human choriogonadotropin (hCG) levels, chest x-rays (CXR), and computed tomographic (CT) scans of the abdomen and chest. Multivariate logistic regression analyses were performed to identify prognostic factors. RESULTS: During a median follow-up period of 7 years (range, 2 to 12), recurrence was found in 42 patients (27.3%). All cases of recurrence were detected within 2 years, 90% in the first year after orchidectomy. In 29 patients (69.0%), recurrence was detected in the abdominal lymph nodes. Nine patients (21.4%) had metastases in the retroperitoneum and mediastinum and/or lungs, and four patients (9.6%) had metastases only in the mediastinum or lungs. The majority of recurrences (97.6%) were detected by tumor markers and CT scans. Recurrence was related to the presence of vascular invasion, embryonal carcinoma (E), elevated preoperative hCG level, and absence of mature teratoma (M). Only vascular invasion was an independent risk factor. After polychemotherapy treatment for recurrence, the survival rate for the total group was 98.7%. CONCLUSION: The wait-and-see policy is a reliable method for follow-up monitoring of patients with stage I NSTGCT. Even in patients with unfavorable prognostic factors, it is justified to await the possible appearance of metastases. For the future, it is recommended that CXR be omitted from the schedule, and it might be feasible to discontinue follow-up evaluations after 5 years.

Complications of venous access ports in 132 patients with disseminated testicular cancer treated with polychemotherapy.

PURPOSE: Venous access ports (VAPs) can be used to administer polychemotherapy to patients with malignancies. The purpose of this study was to evaluate perioperative and late complications related to VAP implantations and to analyze factors that may predict the development of complications. PATIENTS AND METHODS: During the period 1983 to 1994, 135 VAPs were implanted in 132 patients with disseminated testicular tumors. In a retrospective study, the perioperative and late complications were recorded in this homogeneous patient group. Multivariate analysis was performed to detect factors that may predict the development of complications. RESULTS: The median age of the patients was 28 years (range, 16 to 55). Perioperative complications were recorded in five patients (3.7%): pneumothorax in two (1.5%), blood loss in two (1.5%), and mediastinal bleeding in one (0.7%). The ports remained in situ for a total of 55,247 days (median, 413; range, 7 to 1,607). In 31 patients (23%), 42 late complications developed (31%): system obstruction in 13 (9.6%), thrombosis in 11 (8.1%), infection in six (4.4%), catheter defect in six (4.4%), extravasation in four (3.0%), and local skin necrosis in two (1.5%). Late complications were significantly more common in patients who had received chemotherapy before VAP implantation (P < .001). Univariate analysis showed that there were significantly more complications after VAP implantation under local anesthesia than under general anesthesia (P < .05). CONCLUSION: Polychemotherapy could be administered in an adequate manner using a VAP. Complications occurred in 26.7% of a homogeneous group of patients who received a VAP implantation for polychemotherapy for disseminated testicular cancer. Chemotherapy treatment before VAP implantation was the only independent risk factor for late complications.

Sexual dysfunction in nonseminoma testicular cancer patients is related to chemotherapy-induced angiopathy.

PURPOSE: To establish the prevalence of sexual dysfunctions after different treatment modalities for nonseminomatous testicular germ cell tumor (NSTGCT) and to investigate whether treatment-induced angiopathy and neuropathy is related to sexual dysfunction. PATIENTS AND METHODS: A questionnaire assessing sexual dysfunction was sent to 255 NSTGCT survivors. Polychemotherapy (PCT) regimens (cisplatin, vinblastine, and bleomycin [PVB], vinblastine substituted by etoposide [BEP], or cisplatin substituted by carboplatin [CEB], etoposide combined with cisplatin [EP], or with ifosfamide and cisplatin [VIP] were compared regarding treatment-induced angiopathy and neuropathy. Sexual dysfunctions were related to Raynaud's phenomenon and acral paresthesia. RESULTS: Among the 215 responders, 56 (26%) had been treated by orchidectomy and surveillance, 42 (19.6%) by PCT, and 117 (54.4%) by PCT and resection of residual retroperitoneal tumor mass (RRRTM). Overall, loss of libido was reported by 19.1%, decreased arousal by 11.2%, erectile dysfunction by 12.1%, decreased intensity of orgasm by 20%, and ejaculatory problems by 28%. Patients treated with PVB suffered more often from Raynaud's phenomenon compared with those treated with other regimens (40.4% v 29%; P < .05) and from paresthesia (31.6% v 14.7%; P < .05). Patients with Raynaud's phenomenon had more often erectile dysfunction (28.8%) compared with those without (8.4%) (P < .05). CONCLUSION: Compared with orchidectomy alone, PCT, with or without RRRTM, induced more often posttreatment sexual dysfunction. Compared with other chemotherapeutic regimens, signs of angiopathy and neuropathy were most prevalent in those treated with PVB. Erectile dysfunction was related to the chemotherapy-induced Raynaud's phenomenon but not to acral paresthesia.

Lung function measures and their relationship to respiratory symptoms in 7- and 8-year-old children.

Abnormal pulmonary function in childhood is a well-known risk factor for lung function impairment in adult life. It is therefore of clinical interest to recognize lower pulmonary function in childhood. We investigated the association between asthma-like respiratory symptoms and the lung function parameters FVC, FEV1, and FEF(25-75) in a population-based sample of 402 schoolchildren, aged 7 and 8 years, using linear regression analyses. Without accounting for other respiratory symptoms, wheeze, exercise-induced wheeze, chronic cough, and history of wheezy bronchitis or lower respiratory infections in early childhood were significantly associated with reduced lung function. After stepwise elimination of symptoms from the regression models, only exercise-induced wheeze (FEV1, -15%pred, FEF(25-75), -21%pred) and a history of chronic cough (FEV1, -5%pred; FEF(25-75), -11%pred) remained significant predictors of decreased lung function. After adjustment for different variability, no significant differences were seen between the effects of symptoms on the flow measurements FEV1 and FEF(25-75). We conclude that children who report exercise-induced wheeze and/or chronic cough may have a considerable deficit in lung function at early school age.

Changes in respiratory and allergic symptoms in schoolchildren from 1996 to 2002, results from the ISAAC surveys in Antwerp (Belgium).

Two cross sectional surveys (1995/1996 and 2001/2002) were carried out according to the ISAAC protocol among 6-7 and 13-14 year old schoolchildren in Antwerp, Belgium. A total of 8244 children participated in 1996 and 8159 children in 2002. No significant differences in current prevalence of asthma and asthma medication was found in 6-7 year olds and 13-14 year old girls. Significantly less asthma and asthma medication was reported by 13-14 year old boys in 2002. Symptoms of wheeze had lower occurrence in all groups in 2002, which was significant for older age group. Current prevalence of rash was significantly higher in the 6-7 year olds in 2002. No such increase was found for rash in the older age groups but they reported significantly more rhinitis. No differences were found between urban and suburban Antwerp in either survey. No clear changes in the occurrence of asthma were found for school children in Antwerp while wheeze was reported less in 2002 compared to 1996. Allergic disorders had higher occurrences in schoolchildren in 2002.

Distribution of total serum IgE and specific IgE to common aeroallergens by sex and age, and their relationship to each other in a random sample of the Dutch general population aged 20-70 years. Dutch ECRHS Group, European Community Respiratory Health Study.

To describe the distribution of serum total IgE and specific IgE to common aeroallergens by sex and age and to study their relationship to each other, we measured serum total IgE and specific IgE (CAP) to house-dust mite, timothy grass, cat, birch, and Cladosporium in a random sample of 2496 subjects, aged 20-70 years from the Dutch general population. We found that total IgE was higher in men, independently of smoking, and that total IgE had no relationship with age after adjustment for specific IgE and smoking in linear regression analysis. At least one positive specific IgE test was found in 32% in both sexes. Men had higher prevalences of specific IgE to house-dust mite and lower prevalences of specific IgE to birch than women. The proportion with positive specific IgE decreased with age. The mean total IgE increased with the number of positive specific IgE tests. Thus, total IgE is higher in men and has no relationship with age if specific IgE is taken into account. The prevalences of specific IgE to aeroallergens are high and decrease with increasing age. We suggest that sex differences in total IgE should be considered when using total IgE.

Association of skin test reactivity, specific IgE, total IgE, and eosinophils with nasal symptoms in a community-based population study. The Dutch ECRHS Group.

BACKGROUND: Skin prick tests and measurement of specific IgE are important markers of the possible causes of disorders of the upper respiratory tract. OBJECTIVE: In this study we investigated the association of skin test reactivity and specific IgE positivity to five common aeroallergens separately and of total serum IgE and eosinophil count with nasal allergy symptoms in a random sample of the adult population in the Netherlands. METHODS: A cross-sectional study was carried out in a sample of 2167 subjects, aged 20 to 70 years, stratified by age and gender. Nasal allergy symptoms were differentiated into three categories: symptoms after exposure to indoor allergens only, symptoms after exposure to outdoor allergens only, and symptoms after exposure to both indoor and outdoor allergens. Associations were investigated by multiple logistic regression analyses with adjustment for area of residence, gender, age, and smoking status. RESULTS: Skin test and specific IgE reactivity to indoor and outdoor allergens were significantly related to their corresponding nasal symptom groups. Odd ratios increased with increasing number of positive skin test results or increasing levels of specific IgE to allergens in all three nasal symptom groups. For each allergen, a positive skin test result together with a positive specific IgE measurement were the strongest predictors of nasal symptoms. Sensitization to house dust mite was the most prevalent in our study population, whereas the association of skin test reactivity and specific IgE positivity with nasal symptoms was strongest for cat allergen. Skin test and specific IgE reactivity to Cladosporium species were not significantly related to the prevalence of nasal symptoms. Total serum IgE was related to nasal symptoms only in subjects who reported symptoms in response to both indoor and outdoor allergens and only at high levels of IgE. Eosinophil count was associated with nasal symptoms in all nasal symptom groups. CONCLUSION: Our findings confirm the close relationship of skin test positivity with reported symptoms of nasal allergy in a general population. Specific IgE positivity also shows a close relationship with nasal symptoms in response to allergen exposure in a general population. Skin testing and specific IgE measurement may be considered complementary to one another in diagnosing allergic rhinitis. Total IgE may be considered an indicator of greater dysregulation of the immune system in atopic allergy. Eosinophil count is associated with nasal symptoms, regardless of type and extent of nasal symptoms.

Occupational risk factors of lung cancer: a hospital based case-control study.

OBJECTIVES: To investigate the relation between lung cancer and exposure to occupational carcinogens in a highly industrialised region in western Europe. METHODS: In a case-control study 478 cases and 536 controls, recruited from 10 hospitals in the Antwerp region, were interviewed. Cases were male patients with histologically confirmed lung cancer; controls were male patients without cancer or primary lung diseases. Data were collected by questionnaires to obtain information on occupations, exposures, and smoking history. Job titles were coded with the Office of Populations, Censuses and Surveys industrial classification. Exposure was assessed by self report and by job-task exposure matrix. Exposure odds ratios were calculated with logistic regression analysis adjusted for age, smoking history, and marital and socio-economic status. RESULTS: A job history in the categories manufacturing of transport equipment other than automobiles (for example, shipyard workers), transport support services (for example, dockers), and manufacturing of metal goods (for example, welders) was significantly associated with lung cancer (odds ratios (ORs) 2.3, 1.6, and 1.6 respectively). These associations were independent of smoking, education, civil, and economic status. Self reported exposure to potential carcinogens did not show significant associations with lung cancer, probably due to nondifferential misclassification. When assessed by job-task exposure matrix, exposure to molybdenum, mineral oils, and chromium were significantly associated with lung cancer. A strong association existed between smoking and lung cancer: OR of ex-smokers 4.2, OR of current smokers 14.5 v non-smokers. However, smoking did not confound the relation between occupational exposure and lung cancer. CONCLUSIONS: The study has shown a significant excess risk of lung cancer among workers in manufacturing of metal goods, manufacturing of transport equipment (other than automobiles), and transport support services. Assessment of exposure to specific carcinogens resulted in significant associations of chromium, mineral oils, and molybdenum with lung cancer. This study is, to our knowledge, the first study reporting a significant association between occupational exposure to molybdenum and lung cancer.

Does the use of antibiotics in early childhood increase the risk of asthma and allergic disease?

BACKGROUND: One of the mechanisms evoked to explain the increasing prevalences of asthma and allergy, in particular among children, is the 'Western lifestyle' or 'hygiene' hypothesis. As early childhood infections are assumed to hold a protective effect on the development of asthma and allergies, the use of antibiotics at that sensitive age may lead to an increased risk of asthma and allergy. OBJECTIVE: The aim of this study is to investigate the association between the use of antibiotics in the first year of life and the subsequent development of asthma and allergic disorders. METHODS: In a population-based sample of 7-and-8-year-old children questionnaire and skin prick test data were collected from 1206 and 675 subjects, respectively. Prevalence rates of asthma, allergic disorders and skin test positivity were compared between children with and without early life use of antibiotics, taking into account other possible risk factors including early respiratory infections. The effect of genetic predisposition was investigated by stratified analyses of children with and without parental hay fever. RESULTS: The use of antibiotics during the first year of life was significantly associated with asthma (OR = 1.7, 95% CI 1.0-3.1), hay fever (OR = 2.3, 95% CI 1.3-3.8) and eczema (OR = 1.3, 95% CI 1.0-1.8). No significant relationship was found with skin test positivity (OR = 1.1, 95% CI 0.7-1.7). After stratification for the presence of parental hay fever, children without parental hay fever did not show any significant associations between antibiotics use and asthma or allergy, whereas in children with parental hay fever the use of antibiotics was significantly related with asthma (OR = 2.3, 95% CI 1.1-5.1), hay fever (OR = 2.8, 95% CI 1.5-5.1) and eczema (OR = 1.6, 95% CI 1.0-2.6), and of borderline statistical significance with skin test positivity (OR = 1.6, 95% CI 0.9-3.0). CONCLUSION: Early childhood use of antibiotics is associated with an increased risk of developing asthma and allergic disorders in children who are predisposed to atopic immune responses. These findings support recent immunological understanding of the maturation of the immune system.

Importance of a new tumor marker TRA-1-60 in the follow-up of patients with clinical stage I nonseminomatous testicular germ cell tumors.

BACKGROUND: TRA-1-60 is a new tumor marker for embryonal carcinoma-positive nonseminomatous testicular germ cell tumors (NSTGCT). Upper normal reference value (RV) and serum half-life (t1/2) were determined. The value was determined in the follow-up of 154 patients with stage I NSTGCT. METHODS: TRA-1-60 was measured in normal controls (n = 100) to determine RV and in patients without recurrence for t1/2. In all patients, TRA-1-60 was determined at the time of orchidectomy. In 42 patients with recurrence, values were also evaluated 1 month before and at the time of computed tomography-confirmed recurrence. Predictive values and survival probability were examined and compared with values for alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG). RESULTS: RV was 230 U/ml and t1/2 9.5 days. Elevated TRA-1-60 at the time of orchidectomy was not associated with recurrence. One month before recurrence, 21 of 42 patients had elevated TRA-1-60 levels (50%); 10 were negative for both AFP and hCG. At the time of recurrence, 24 patients had elevated TRA-1-60 levels (57.1%): 9 were negative for AFP/hCG. Patients with TRA-1-60 levels of > 500 U/ml had a poorer recurrence-free survival probability (p = 0.015). CONCLUSIONS: TRA-1-60 is useful in the follow-up of stage 1 NSTGCT. The combination of AFP, hCG, and TRA-1-60 may improve the early detection of recurrence.

Cisplatin-based chemotherapy changes the incidence of bilateral testicular cancer.

BACKGROUND: The introduction of cisplatin-based chemotherapy has remarkably increased the survival of testicular cancer patients. With this success, the concern for a contralateral testicular tumor has increased. The aim of this study was to investigate whether the risk for contralateral testicular tumor development was influenced by cisplatin-based chemotherapy. METHODS: The incidence of a contralateral testicular tumor among 365 consecutive patients with a nonseminoma testicular tumor, diagnosed in the period 1980 and 1995, was established and related to previous therapy. RESULTS: Eleven of 365 men (3%) developed a contralateral testicular tumor. After a total of 2403 person-years at risk, 4 of 225 chemotherapy-treated patients (1.8%) developed a contralateral testicular tumor, and 7 of 140 patients (5%) treated with orchidectomy alone developed a contralateral tumor. In comparison to this surveillance subgroup, patients previously treated with chemotherapy have a relative risk of 0.30 to develop a second testicular tumor. CONCLUSIONS: In Dutch men with a nonseminoma testicular tumor, the incidence of a contralateral testicular tumor is 3%, which is 60-fold the expected incidence rate of testicular cancer. A three times lower incidence rate of a contralateral testicular tumor was found in the chemotherapy subgroup compared with those on surveillance. This supports the hypothesis that cisplatin-based chemotherapy may eradicate carcinoma in situ or early testicular cancer.

Complications of the post-chemotherapy resection of retroperitoneal residual tumour mass in patients with non-seminomatous testicular germ cell tumours.

OBJECTIVE: To evaluate the resection of the retroperitoneal residual tumour mass (RRTM) for histological examination after chemotherapy in patients with disseminated non-seminomatous testicular germ cell tumours (NSTGCTs), with particular attention to surgical morbidity. PATIENTS AND METHODS: From 1979 to 1995, 112 patients (mean age 28 years, range 16-53) with NSTGCT had residual disease after chemotherapy for which surgical evaluation was indicated; the histology of the residual tumour and the surgical complications were assessed. Possible associations between the occurrence of surgical complications and the age of the patient, size of the residual tumour, operative duration, previous laparotomy and pathological findings were evaluated. RESULTS: The median size of the residual tumour was 4 cm (range 0-18); histological examination revealed viable tumour in 9%, mature teratoma in 44% and necrosis/fibrosis in 44% of the patients. In three patients (2.8%) no residual tumour mass was found at laparotomy. There were 26 complications in 20 patients (18%); urinary tract infection was the most common, occurring in nine patients (8%). One patient died during the induction of anaesthesia. There were no significant relationships between the occurrence of complications and age, size of the residual tumour, operative duration, previous laparotomy or pathological findings. CONCLUSION: The resection of RRTM after polychemotherapy treatment for disseminated NSTGCT is a safe surgical procedure, with low treatment morbidity consisting mainly of urinary tract infection. Knowledge of the potential complications may help to prevent morbidity. However, the surgical evaluation of the ultimate effect of polychemotherapy remains the gold standard.

Sexual functioning after multimodality treatment for disseminated nonseminomatous testicular germ cell tumor.

PURPOSE: We determined sexual functioning after chemotherapy for disseminated nonseminomatous testicular germ cell tumor, and evaluated the impact of resection of post-chemotherapy residual retroperitoneal tumor. MATERIALS AND METHODS: A total of 155 consecutive patients treated with chemotherapy for disseminated nonseminomatous testicular germ cell tumor (between 1980 and 1994) was questioned about their sexual functioning. The patients were divided in 2 subgroups: patients treated with or without resection of post-chemotherapy residual retroperitoneal tumor. Volume and location (divided into left para-aortal or right paracaval/interaortacaval) of the resected tumor were related to absence of ejaculation as well as decreased semen amount. In addition, libido, arousal, erection and orgasm were related to ejaculatory dysfunction. RESULTS: A total of 43 patients (27.7%) was treated with chemotherapy only and 112 (72.3%) had additional resection of post-chemotherapy residual retroperitoneal tumor mass. Overall, 22.4% reported loss of libido, 14.1% decreased arousal, 16% erectile dysfunction, 23.1% decreased orgasmic intensity, 17.4% decreased semen amount and 18.7% complete absence of antegrade ejaculation. With exception of absence of ejaculation, sexual dysfunctions were reported in similar frequencies in both treatment subgroups. In the resection of post-chemotherapy residual retroperitoneal tumor subgroup, 25.9% of the patients had complete absence of ejaculation. The other sexual dysfunctions were related neither to decreased semen amount nor to complete absence of ejaculation. The mean volume of resected tumor was higher (95 cm.3) in patients with absence of ejaculation than in those without (40 cm.3), and patients with right paracaval/interaortacaval tumor (20 of 58, 34.5%) reported more often absence of ejaculation than those with left para-aortal tumor (9 of 54, 16.7%). CONCLUSIONS: In patients treated for disseminated nonseminomatous testicular germ cell tumor, post-chemotherapy sexual morbidity cannot be neglected. Except for loss of antegrade ejaculation, sexual dysfunctions are not related to resection of post-chemotherapy residual retroperitoneal mass. A high volume of tumor and a right paracaval/interaortacaval location predispose to loss of antegrade ejaculation.

Objective and subjective effects of treatment for testicular cancer on sexual function.

OBJECTIVE: To determine whether the treatment of patients with testicular cancer, using cisplatin combined with etoposide and bleomycin (BEP) after orchidectomy in those with disseminated disease, causes changes in sex hormones and penile vascularization, possibly related to sexual dysfunction. PATIENTS AND METHODS: Ten patients treated with BEP were compared with 11 undergoing orchidectomy alone followed by surveillance. Sex hormone levels were analysed and cavernosal artery duplex ultrasonography performed before orchidectomy and at 6 and 12 months afterward. Patients were questioned about their sexual function. After 1 year, a visual erotic stimulation (VES) test was performed to assess penile rigidity. RESULTS: In contrast to the surveillance group, BEP-treated patients had higher follicle-stimulating hormone (4.6 vs 26.5 U/L) and luteinizing hormone (1.4 vs 8.2 U/L) levels, and lower testosterone levels (21.1 vs 14.7 nmol/L) at 6 months than at baseline. At 1 year, most patients had compensated hypergonadotrophic eugonadism, but Leydig cell function had recovered. Changes in cavernosal artery peak flow velocities induced by local injection with papaverine/phentolamine showed no difference between the groups before and 6 months after orchidectomy. Loss of libido and erectile dysfunction were reported more frequently by BEP-treated patients. However, 1 year after treatment, most reported a satisfying sex life and VES resulted in a rigid erection in nearly all patients. The reported erectile dysfunction could not be explained by changes in plasma testosterone levels or diminished blood flow velocities. CONCLUSIONS: After being diagnosed with testicular cancer, sexual morbidity is considerable, but within 1 year some improvement may be expected. BEP induces transient testicular dysfunction but this recovers. Although BEP is related to symptoms of angiopathy, cavernosal blood flow seems to be unaffected. These findings and the normal VES-evoked penile rigidity suggest that sexual dysfunction is more psychological than organically induced by BEP.