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Biomedical subjects

T Sigsgaard

Publications and source records attributed to T Sigsgaard.

At least 37 records · Page 2Linked to original sources
PubMed2000

Antiemetic efficacy of combination therapy with granisetron plus prednisolone plus the dopamine D2 antagonist metopimazine during multiple cycles of moderately emetogenic chemotherapy in patients refractory to previous antiemetic therapy.

Effective antiemetic treatment of patients who have previously experienced chemotherapy-induced nausea and vomiting is difficult. The aim of this study was to evaluate the antiemetic efficacy of a single intravenous dose of granisetron plus a 3-day oral treatment with prednisolone 25 mg once a day plus metopimazine 30 mg four times a day in patients refractory to previous antiemetic treatment with granisetron or with prednisolone plus metopimazine. The study population was made up of 25 consecutive women with stage I or II breast cancer, who were treated with multiple cycles of adjuvant cyclophosphamide, fluorouracil plus methotrexate or cyclophosphamide, epirubicin plus fluorouracil given i.v. every 3 weeks. Patients received the three-drug combination of antiemetics during a total of 113 cycles of chemotherapy. No emetic episodes were reported in 88.9% cycles on day 1, in 94.7% cycles on days 2 through 5 and in 85.8% cycles on days 1 through 5 after chemotherapy. No nausea was reported in 43.4% cycles on day 1, in 49.6% cycles on days 2 through 5 and in 34.5% cycles on days 1 through 5. Nineteen patients (76.0%) completed the scheduled nine cycles of chemotherapy, 1 being withdrawn because of > or =5 emetic episodes and 5, because they were not satisfied with the antiemetic treatment. The treatment was well tolerated. In conclusion, granisetron plus prednisolone plus metopimazine is a highly effective antiemetic treatment in patients receiving moderately emetogenic chemotherapy refractory to antiemetic therapy with granisetron or prednisolone plus metopimazine.

Adult↗
PubMed2000

S and Z alpha1-antitrypsin alleles are risk factors for bronchial hyperresponsiveness in young farmers: an example of gene/environment interaction.

Several studies have found an association between the rare Pi-alleles and asthma or bronchial hyperresponsiveness (BHR). This study deals with the effect of Pi-type on BHR among 2,308 young Danish people living in rural areas with a mean +/- SD age of 19.7+/-2.4 yrs. Interviews, pulmonary function testing, bronchial histamine provocation and skin-prick tests were performed. Serum alpha1-antitrypsin levels were determined and phenotyping was performed by means of isoelectric focusing and the subjects categorized into four groups: 1) MM and MX; 2) MS; 3) MZ; and 4) rare, i.e. SZ, SS and ZZ. Among the farmers, a significant positive trend for sensitization towards house dust mites was found, ranging from 12% in the MM group to 22% in the rare Pi-group. A positive test for trend was found within the Pi-groups in a one-sided test for doctor-diagnosed asthma with a peak prevalence of 40% for these symptoms among smokers in the rare Pi-group. On multiple logistic regression analysis, an increased odds ratio (OR) for BHR was found among farming school attendants with the rare Pi-alleles. The OR (95% confidence interval) was 1.71 (0.84-3.49) for MS, 1.93 (1.10-3.39) for MZ and 4.34 (1.19-15.8) for the rare Pi-group. Such a relationship was not found among the conscripts. These results show that a gene/environment interaction may exist between the farming occupation and the rare Pi-alleles, leading to a higher proportion of bronchial hyperresponsiveness related to the rare Pi-alleles in farming school attendants, in contrast to what is found among other young people living in rural areas.

Adult↗
PubMed2000

Cytokine release from the nasal mucosa and whole blood after experimental exposures to organic dusts.

The aim of this study was to assess the cytokine response after nasal exposure to organic dusts. In a double blinded, crossover study five garbage workers with occupational airway symptoms and five healthy garbage workers were intranasally exposed to endotoxin (lipopolysaccharide LPS), beta-1,3-D-glucan (GLU), Aspergillus sp., compost or the saline dilute for 15 min. Nasal cavity volume and nasal lavage (NAL) were performed at baseline and 3, 6, 11 h postexposure. NAL was analysed with differential cell counts, cysteinyl-leukotrienes, tumour necrosis factor alpha, interleukin (IL)-1beta, IL-6 and IL-8. A whole blood assay on cytokine-release was performed with LPS and GLU. NAL cytokines neutrophils, lymphocytes and albumin increased significantly at 6 h after LPS exposure. GLU induced an increase in albumin and a slight increase in IL-1beta 6-11 h post exposure. In the WBA a significant increase in all cytokines after exposure to LPS as well as GLU was found. Significantly more cells were seen in NAL of the control group 6 h post LPS exposure. In conclusion lipopolysaccharide is the most potent inducer of inflammation in the nasal mucosa whereas compost and beta-1,3-D-glucan only induce minor changes. This reaction to lipopolysaccharide is attenuated in workers with occupational airway symptoms. In whole blood assay, however, beta-1,3-D-glucan also induces cytokine release, indicating a different protective effect of the nasal mucosa towards lipopolysaccharide and beta-1,3-D-glucan.

Allergens↗
PubMed2000

The shape of the maximum expiratory flow-volume curve reflects exposure in farming.

The objective of the study was to examine the effect of farming exposure, respiratory symptoms and smoking on the shape of the MEFV-curve in 1,691 male farming students and 407 male controls and to relate the slope ratio with FEV(1) and FEV(1) /FVC. Each subject underwent a medical interview and the slope ratios from the MEFV-curve at 75 (SR75), 50 (SR50) and 25 (SR25) %FVC together with FEV1 and FVC were recorded. Histamine bronchial reactivity (Yan method) was measured and skin prick test with inhalant allergens was performed. In smokers, SR75 increased with increasing exposure to: general farming, swine and dairy cattle (p< or =0.020). SR50 increased with increasing exposure to farming (p=0.015). In non-smokers, SR25 increased with increasing exposure to swine and dairy cattle (p=0. 021) and increased SR25 was associated with sensitisation to house dust mite (p=0.017). Data revealed an interaction between smoking and exposure to farming. FEV(1) and FEV(1)/FVC was not associated with farming exposure or production animals. FEV1 and FEV(1)/FVC (p< or =0.003) were lower among subjects wi bronchial hyperresponsiveness and asthma (FEV(1) and asthma only in smokers). SR75 (p=0.037) and SR50 (p=0.024) were increased in subjects with asthma and SR75 was increased in subjects with bronchial hyperresponsiveness, but only in smokers (p=0.002). In conclusion, exposure to farming seems to influence the shape of the MEFV-curve and there are indications of interaction between exposure to organic dust and smoking. These changes are seen only in the slope ratios and not in FEV(1) and FEV(1)/FVC. However, FEV(1) and FEV(1)/FVC are superior to slope ratios in differentiating healthy subjects from those with respiratory symptoms.

Agricultural Workers' Diseases↗
PubMed1999

Granisetron compared with prednisolone plus metopimazine as anti-emetic prophylaxis during multiple cycles of moderately emetogenic chemotherapy.

This randomized, double-blind, double-dummy parallel study compared the anti-emetic efficacy and tolerability of the serotonin antagonist granisetron with prednisolone plus the dopamine D2 antagonist metopimazine during nine cycles of moderately emetogenic chemotherapy. Chemotherapy naive women with stage I or II breast cancer scheduled to intravenous cyclophosphamide, fluorouracil and methotrexate or cyclophosphamide, epirubicin and fluorouracil every 3 weeks were included. Patients received a single intravenous dose of granisetron 3 mg or a 3-day oral treatment with prednisolone 25 mg once a day plus metopimazine 30 mg four times a day. A total of 223 women were enrolled and 218 patients (97.8%) were evaluable for efficacy. Granisetron (n = 109) was superior to prednisolone plus metopimazine (n = 109) in the prophylaxis of acute nausea and vomiting during the first cycle of chemotherapy (P < 0.001) and prednisolone plus metopimazine was superior on days 2-5 (P = 0.002). Overall, granisetron was superior on days 1-5 (P = 0.009). The median number of cycles completed with granisetron was five (95% confidence interval 4-6) compared with two (95% confidence interval 2-2) for prednisolone plus metopimazine (P = 0.0019). Constipation and rash were reported more frequently with granisetron (P < 0.001 and P = 0.043 respectively) and palpitations more frequently with prednisolone plus metopimazine (P = 0.015). In conclusion, the number of cycles completed with granisetron was significantly higher than the number completed with prednisolone plus metopimazine, but the anti-emetic efficacy of both treatments declined during multiple cycles of moderately emetogenic chemotherapy.

Adult↗
PubMed1999

Genetic and environmental influence on asthma: a population-based study of 11,688 Danish twin pairs.

The aim of this study was to estimate the relative influence of genetic and environmental factors on the aetiology of asthma. The classic twin study design was used to analyse data on self-reported asthma obtained by a questionnaire mailed to 34,076 individuals, aged 12-41 yrs and originating from the Danish Twin Register. The cumulative incidence of asthma was 6.2% in the pooled sample. The data showed a decreasing cumulative incidence with age for males, but no sex or zygosity difference was observed. Substantially higher concordance rates, odds ratios and correlations for asthma were estimated in the monozygotic than in the dizygotic twins. Using biometric modelling, a model including additive genetic and nonshared environmental effects provided the best overall fit to the data. According to this model, 73% of the variation in liability to asthma was explained by genetic factors. No sex difference or age-dependency in the magnitude of genetic effects was observed. The biometric analysis emphasized a major influence of genetic factors in the aetiology of asthma. However, a substantial part of the variation in liability to asthma is due to the impact of environmental factors specific to the individual. There is no evidence for a substantial impact of genetic dominance or the shared environment.

Adolescent↗
PubMed1999

Lung status in young Danish rurals: the effect of farming exposure on asthma-like symptoms and lung function.

The aim of this study was to assess the prevalence of asthma (self-reported) and relate this to lung function and factors associated with asthma in young farmers. Two hundred and ten female and 1,691 male farming students together with 407 males controls were studied. Each subject underwent a medical interview; forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were recorded using a dry wedge spirometer. Histamine bronchial reactivity was measured using the Yan method. Skin prick testing was performed using inhalant allergens. Nonsmokers had lower prevalence of asthma (5.4-10.8%) than smokers (11.3-21.0%) (p<0.05). Females reported symptoms of asthma nearly twice as often as males. Sex, smoking and a family history of asthma/allergy were significantly associated with asthma. Controls had higher standardized FEV1 and FVC residuals than male students, both nonsmokers (0.21 and 0.24) versus (-0.06 and -0.05) and smokers (0.29 and 0.33) versus (-0.11 and 0.13) (p<0.032). Bronchial hyperresponsiveness, asthma, siblings with allergy and working with cattle (controls only) were significantly associated with reduced lung function. In conclusion, the prevalence of asthma was significantly related to smoking, female sex, family history of asthma and allergy. Whilst bronchial hyperresponsiveness was associated with reduced lung function and lung function was slightly reduced in the male farming students, there was no association found between occupational farming exposure and either lung symptoms or lung function.

Adolescent↗
PubMed1999

Health hazards to waste management workers in Denmark.

This paper deals with the Danish investigations of garbage recycling workers (GRW) in the beginning of the 90ties. The studies are summarized here showing a wide range of symptoms and diseases, from occupational asthma to gastrointestinal and skin symptoms. From the Danish experiences it seems that under normal circumstances with a good hygiene and use of the proper protective equipment by an educated work force, garbage handling induces a small but significant risk of occupational asthma. The majority of the asthma cases we have experienced in Denmark have been due to a poor perception of the risks related to organic dust exposure. However, there is still an increased prevalence of respiratory symptoms such as chest tightness and toxic alveolitis. Furthermore gastrointestinal and skin symptoms are more frequent among GRW compared to other blue-collar workers.

Adult↗
PubMed1997

Dose-finding study of oral metopimazine.

A few studies indicate a dose-response effect of the antiemetic metopimazine. The aim of this study was therefore to investigate the tolerability of increasing doses of metopimazine given orally every 4 h for eleven doses. The dose levels 20 mg, 30 mg, 40 mg, 50 mg and 60 mg were studied in 36 patients completing 46 cycles of chemotherapy. Serum concentrations of metopimazine and the acid metabolite AMPZ were measured by HPLC in 13 patients (15 cycles). The dose-limiting toxicity was moderate to severe dizziness caused by orthostatic hypotension as seen in 0, 0, 17%, 42% and 50% of patients at the respective dose levels. Other side effects were few and mild, and only a single possible extrapyramidal adverse event was observed in a patient at the 60-mg dose. High serum concentrations were not predictive for toxicity, as found on comparison of patients with and without symptoms, but in individual patients symptoms were seen at the time of Cmax. We found that metopimazine was safe with a dosage of 30 mg x 6. This dose is four times higher than that previously recommended for antiemetic use.

Administration, Oral↗
PubMed1997

Spirometry with a Fleisch pneumotachograph: upstream heat exchanger replaces heating requirement.

The exact temperature of the head of an unheated Fleisch pneumotachograph (PT) during recording is not known, and variation in its temperature may lead to errors in measuring spirometric indexes. We measured PT head temperature during blows from five normal subjects, recorded by using a PT with and without an upstream heat exchanger to condition the air to the ambient temperature that was set in a climate chamber. Group mean (+/- SD) temperature of a thermocouple (TC) placed inside the PT head was 11.8 +/- 1.9 degrees C with 7 degrees C ambient, 25.4 +/- 1.3 degrees C at 23 degrees C, and was 37.2 +/- 0.3 degrees C at 37 degrees C. The between-subject range of temperature for this TC was 7.5 degrees at 7 degrees C, 5.5 degrees at 23 degrees C, and 1.1 degrees at 37 degrees C. The mean within-subject within-blow variation of temperature for this TC was 10.0 degrees and 3.3 degrees C for ambient of 7 degrees and 23 degrees C, respectively. At the usual ambient temperature in a laboratory, these differences in temperature lead to a 3.6% between-subject bias in recording, and the within-subject differences lead to 2.6% underreading of peak expiratory flow and a 0.5% overreading later in the blow, which makes ATPS-to-BTPS correction erroneous or difficult to perform. With the use of an upstream heat exchanger, the group mean temperature was 8.7 +/- 0.4 degrees, 23.2 +/- 0.2 degrees, and 37.1 +/- 0.2 degrees C at the three ambient temperatures, respectively, and the within-subject within-blow variation was reduced to < 1 degrees C. A heat exchanger placed upstream of the PT satisfactorily conditioned expired air to the ambient temperature and removed the error.

Adult↗
PubMed1997

Randomized, double-blind comparison of ondansetron versus ondansetron plus metopimazine as antiemetic prophylaxis during platinum-based chemotherapy in patients with cancer.

PURPOSE: To investigate the antiemetic effect and tolerability of the 5-hydroxytryptamine3(5-HT3) antagonist ondansetron plus the dopamine D2 antagonist metopimazine versus ondansetron alone in patients receiving platinum-based chemotherapy. PATIENTS AND METHODS: One hundred eleven chemotherapy-naive patients who were scheduled to receive two consecutive courses of platinum-based chemotherapy were randomized between ondansetron 8 mg intravenously (IV) followed by 8 mg orally twice a day plus metopimazine 35 mg/m2 as a 24-hour continuous infusion followed by 30 mg orally four times a day for 4 days, or ondansetron plus placebo. The study used a double-blind, crossover, placebo-controlled design. RESULTS: Ninety-four patients completed the crossover. Complete response (CR; no emetic episodes) was obtained on day 1 in 77.7% of the patients who received the combination versus 50.0% of those who received ondansetron alone (P = .00002), and in 51.7% versus 31.0% on days 2 to 6 (P = .0009). The overall CR (days 1 to 6) was 48.9% versus 25.3% (P = .0002). Additionally, significantly less nausea was observed with the combination on day 1 (P = .0002), days 2 to 6 (P = .0001), and days 1 to 6 (P = .00004). Patient preference was 63.6% for the combination and 13.6% for ondansetron alone; 22.7% expressed no treatment preference (P < .0001; therapeutic gain 50.0%; 95% confidence interval [CI], 31.6% to 68.4%). Adverse reactions were mild and without significant differences between the two treatments. CONCLUSION: Metopimazine plus ondansetron was significantly superior to ondansetron alone, concerning all efficacy parameters assessed, in patients who received platinum-based chemotherapy.

Adult↗
PubMed1997

Arylamine N-acetyltransferase 1 (NAT1) and 2 (NAT2) polymorphisms in susceptibility to bladder cancer: the influence of smoking.

Aromatic amines are involved in the etiology of bladder cancer. These compounds are acetylated by N-acetyltransferase 1 (NAT1) and 2 (NAT2), and epidemiological studies have shown that the slow NAT2 acetylator phenotype is associated with increased risk of bladder cancer and may be associated with decreased risk of colorectal cancer. By using PCR-RFLP analyses to identify three known slow acetylator alleles (M1, M2, and M3) and the wild-type, or fast, allele, the NAT2 genotypes were determined. No association between the NAT2 slow acetylator genotype and bladder cancer was found either by crude analyses [odds ratio (OR), 1.32; 95% confidence interval (CI), 0.91-1.92) or by logistic regression analyses adjusted for age, gender, and smoking exposure (OR, 1.22; 95% CI, 0.92-1.62). A similar observation was made when the cases were divided into incident and surviving cases. Dividing the cases by pathological classification (benign or malignant) did not alter this finding. Likewise, analyses of the NAT1 and glutathione S-transferase mu 1 (GSTM1) genotypes showed no associations between the NAT1 or GSTM1 genotypes and bladder cancer risk. However, restricting the analysis to people exposed to potential bladder carcinogens (i.e., smokers) among cases and controls, a small but significant association between the slow acetylator genotype and bladder cancer risk was revealed among all cases with malignant tumors (OR, 1.35; 95% CI, 1.02-1.80) and among incident cases with malignant tumors (OR, 1.50; 95% CI, 1.04-2.16). The allele frequencies in the group consisting of smokers showed an overrepresentation of the NAT2 M1 (NAT2*5) allele in the incident case group. The NAT1 and GSTM1 genotypes were not associated with increased risk of bladder cancer among smokers. Analyses of genetic combinations of NAT1/NAT2 as potential risk factors for bladder cancer seem to indicate that the normal NAT1/fast NAT2 genotype may be a protective genotype compared with the other genotype combinations. Analyses of genetic combinations of NAT2/GSTM1 did not reveal any combination of NAT2 and GSTM1 genotypes associated with increased bladder cancer risk.

Aged↗
PubMed1996

Exposure to urban and rural air pollution: DNA and protein adducts and effect of glutathione-S-transferase genotype on adduct levels.

Ambient air in urban areas is polluted by agents suspected of causing cancer in humans. A number of epidemiological studies have revealed an increased cancer risk in urban communities, especially in lung cancer. The relative risk have been estimated to be in the order of 1.5. The objective of this study was to evaluate differences in genotoxic exposure through air pollution in urban and rural areas using DNA and protein adducts as biomarkers. Another objective was to investigate whether the GSTM1 genotype has any effect on adduct level. The analyses included 32P postlabelling of DNA adducts in lymphocytes, enzyme-linked immunosorbent assay for measuring benzo[a]pyrene protein adducts and polymerase chain reaction amplification of the GSTM1 genotype. The study was a cross-sectional study of non-smoking, healthy males from rural and urban Danish areas and from Athens, Greece. All individuals in the study were healthy, non-smoking males. The Danish urban group included 74 university students, the rural group 29 students from agricultural colleges and the Greek group 17 individuals. Adduct levels differed significantly in the three groups with median levels of 0.152 fmol/micrograms DNA (rural), 0.205 fmol/micrograms (urban) and 0.285 fmol/micrograms (Athens). The adduct patterns showed some identical spots, but also specific adducts. Here we report increasing DNA adduct levels comparing residents in rural, small urban and large urban residential areas; we found no influence of GSTM1 genotype on DNA or protein adduct levels in non-smokers exposed to low levels of air pollution.

Adult↗
PubMed1996

Glutathione S-transferase mu as a risk factor in bladder tumours.

Glutathione transferases are involved in the detoxification of many zenobiotica involved in the etiology of cancer. To investigate the role of the glutathione S-transferase M1 deletion (GSTM1*0/0) in bladder carcinogenesis, the polymerase chain reaction was used to determine the GSTM1 genotypes of cancer patients (n = 234) and hospital controls (n = 202). Overall, the proportion of GSTM1*0/0 in the case group was 57%, compared to 50% in the control group giving an odds ratio (OR) of 1.33, (0.91-1.94; 95% confidence interval (CI)). Dividing the bladder cancer group into incident (n = 87) and surviving case groups (n = 147), a modest association between the GSTM1*0/0 genotype and bladder cancer was found in the surviving group, whereas, in the incident group no association was found. Logistic regression analysis of the incident cases, adjusting for age, gender, and cigarette smoking, revealed ORs of 1.12 (0.61-2.08) and 0.74 (0.33-1.73) for the malignant and benign tumours, respectively. The corresponding adjusted ORs for the surviving cases were 1.81 (1.04-3.13) for benign and 1.43 (0.80-2.56) for malignant tumours. Thus, in this study, the GSTM1 deletion is not a risk factor for the development of bladder cancer, but may be related to the survival of the bladder cancer patients. This finding is very important for the design of case-control studies in general, and for the interpretation of existing data.

Aged↗
PubMed1996

Peak expiratory flow and the resistance of the mini-wright peak flow meter.

The purpose of this study was to examine whether the resistance of the peak flow meter influences its recordings. One hundred and twelve subjects, (healthy nonsmokers and smokers and subjects with lung diseases) performed three or more peak expiratory flow (PEF) manoeuvres through a Fleisch pneumotachograph with and without a mini-Wright peak flow meter added in random order as a resistance in series. The results were as follows. In comparison with a pneumotachograph alone, peak flow measured with an added mini-Wright meter had a smaller within-test variation, defined as the difference between the highest and second highest values of PEF in a series of blows. The mean (SE) variation was 14 (1.3) L.min-1 and 19 (1.5) L.min-1 with and without meter added, respectively. In comparison with the pneumotachograph alone, the addition of the mini-Wright meter caused PEF to be underread, especially at high flows. The difference (PEF with meter minus PEF without meter) = -0.064 (average PEF) -8 L.min-1; R2 = 0.13. The mean difference was -7.8 (1.1) %, and increased numerically for a given PEF, when maximal expiratory flow when 75% forced vital capacity remains to be exhaled (MEF75%FVC) decreased. The reproducibility criteria for repeated measurements of peak flow are more appropriately set at 30 L.min-1 than the commonly used 20 L.min-1, because a within-test variation of less than 30 L.min-1 was achieved in 76% of the subjects without PEF meter inserted and in 88% with meter inserted, with no difference between healthy untrained subjects and patients. The resistance of the peak expiratory flow meter causes less variation in recordings but reduces peak expiratory flow, especially at high values and when the peak is large as compared with the rest of the maximal expiratory flow-volume curve.

Adolescent↗
PubMed1996

Urinary 1-hydroxypyrene, a PAH biomarker in foundry workers.

Exposure to PAH in foundry workers has been studied by urinary 1-hydroxypyrene (HPU) levels, quantitatively measured by reversed phase HPLC. Seventy male foundry workers and 68 matched controls were investigated. Polycyclic aromatic hydrocarbon (PAH) exposure was defined by 17 breathing zone hygienic samples, consisting of 16 selected PAH compounds. Mean total PAH concentration (SD) was 10.40 (4.04) mu g/m3. A multiple regression model of tobacco consumption, age, airborne PAH-exposure and foundry work on log HPU showed a significant correlation, p < 0.001, r2 = 0.69. Only foundry work (p < 0.0001) and airborne PAH exposure (p = 0.0478) contributed significantly to the model. These data suggest that HPU is a sensitive biomarker for low-dose PAH exposure.

Adult↗
PubMed1994

Lung function changes among recycling workers exposed to organic dust.

This study examines the workshift changes in lung function among 99 recycling workers, and correlates these findings with measurements of total dust and endotoxins. Exposure to organic dust caused a fall in FEV1 over the workshift, and this was significantly associated with the exposure to organic dust. No significant association was found between endotoxin exposure and lung function decrements. This lack of association could be due to the low concentrations of endotoxins to which the workers were exposed, as no workers were exposed to more than 100 ng/m3.

Dust↗