Amrinone versus dopamine-nitroglycerin after reconstructive surgery for complete atrioventricular septal defect

To compare the effectiveness and safety of amrinone and a combination of dopamine and nitroglycerin in infants after reconstructive surgery for congenital heart disease. A prospective, randomized, double-blind study. Pediatric intensive care unit in a university hospital. Thirty-two infants with complete atrioventricular septal defect. Amrinone loading dose, 2 mg/kg, followed by a maintenance infusion, 7.5 μg/kg/min, was given to 17 infants before separation from cardiopulmonary bypass. The remaining 15 patients received a combination of dopamine, 5 μg/kg/min, and nitroglycerin, 1 μg/kg/min. The circulatory state of the patients was evaluated from 4 to 18 hours after cardiopulmonary bypass. The systemic blood flow index, calculated using the Fick principle, was higher in the amrinone group (2.5 ± 0.7 L/min/m²) compared with the dopamine-nitroglycerin group (2.0 ± 0.6 L/min/m², mean ± SD). The pulmonary blood flow index in the amrinone group was higher (2.9 ± 0.6 L/min/m²) than in the dopaminenitroglycerin group (2.2 ± 0.6 L/min/m²); no significant difference was noted in the mean pulmonary artery pressure. The oxygen extraction ratio was higher in the dopamine-nitroglycerin group (0.41 ± 0.07) compared with the amrinone group (0.34 ± 0.08). Despite lower platelet counts in the amrinone group, no hemorrhagic complications were seen in any patient. With this dosage regimen, amrinone provides a higher cardiac output, more favorable oxygen dynamics, and lower pulmonary vascular resistance than dopamine and nitroglycerin.     

Concurrent LOH at multiple loci in human malignant mesothelioma with preferential loss of NF2 gene region

Human malignant mesothelioma (MM) is a highly aggressive neoplasm related to occupational asbestos exposure and characterised by a long latency period between the exposure and onset of disease. Previous studies indicate that losses at different genomic regions are present in MM. We examined allele loss at three known tumour suppressor gene regions (22q/NF2 gene, 9p/p16 gene, and 3p/FHIT gene) and at two other frequently deleted areas (14q and 6q) in MM. Loss of heterozygosity (LOH) was investigated in cell cultures and primary tumours with several highly polymorphic markers for each site. To study if LOH of the NF2 gene is a consistent feature in MM, we performed a more detailed analysis of chromosome 22q that included a NF2 marker (NF2CA3). We observed a high frequency of LOH occurring simultaneously at multiple loci. In particular, 100% of the cultured MM cells exhibited LOH at the NF2 gene region. From the other chromosomal sites analysed, recurrent allele loss was detected at 9p (5/7; 71%), 3p (4/7; 57%), 14q (3/7; 43%), and 6q (3/7; 43%). Of the 32 tumours, even those trimmed to exclude normal tissue, few showed LOH, suggesting consielment by normal cells within MM tumours, whereas tumour cells in primary cultures showed LOH already in passages 1-2. In conclusion, our present LOH data indicate that MM cells exhibit allele losses at multiple tumour suppressor gene sites concurrently, involving NF2 gene preferentially. This supports the view that the accumulation of multiple genetic hits is characteristic to malignant transformation of MM cells.     

Effects of commercial chlorophenolate, 2,3,7,8-TCDD,and pure phenoxyacetic acids on hepatic peroxisome proliferation,xenobiotic metabolism and sister chromatid exchange in the rat

The induction of hepatic peroxisome proliferation and drug metabolizing enzymes and of sister chromatid exchange (SCE) in lymphocytes was studied in male Han/Wistar rats after exposing them for 2 weeks to a commercial chlorophenolate formulation (Ky-5) (100mg/kg/ day), to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD; 0.05–5 g/kg/wk) and to the pure phenoxyacetic acids, 2,4-dichlorophenoxyacetic acid (2,4-D; 100 mg/kg/day) and 2-chloro-4-methylphenoxyacetic acid (MCPA; 100 mg/kg/day). The chlorophenolate formulation and pure 2,4-D and MCPA caused significant increases in the number of peroxisomes in liver cells, although the average size of peroxisomes was not affected, whereas the effect of even the highest dose of 2,3,7,8-TCDD remained small. This finding indicates that dioxin impurities do not account for the peroxisome proliferation induced by chlorophenolate. The relative weight of the liver increased significantly in rats treated with the chlorophenolate formulation and with 2,3,7,8-TCDD (5.0 and 0.5 g/kg). The pattern of induction of xenobiotic metabolizing enzymes showed some differences between chlorophenolate treatment and 2,3,7,8-TCDD treatment. Furthermore, the effects of pure phenoxyacetic acids were different from that seen with chlorophenolate and 2,3,7,8-TCDD. The highest dose of 2,3,7,8-TCDD increased the frequency of SCE in circulating lymphocytes slightly, but significantly.     

Hypolipidemia and peroxisome proliferation induced by phenoxyacetic acid herbicides in rats

Male Wistar rats were treated daily by gavage with two phenoxy herbicides, 2,4-dichlorophenoxyacetic acid (2,4-D)(100-200 mg/kg body wt) and 4-chloro-2-methylphenoxyacetic acid (MCPA) (100-200 mg/kg body wt), and with the chemically different glyphosate N-phosphonomethyl glycine (300 mg/kg body wt) 5 days per week for 2 weeks. A hypolipidemic drug, clofibrate [ethyl-2-(4-chlorophenoxy)-2-methylpropionate], which is structurally related to phenoxy acids, was used as a positive control (200 mg/kg body wt). 2,4-D and MCPA had several effects similar to those of clofibrate: all three compounds induced proliferation of hepatic peroxisomes, decreased serum lipid levels, and increased hepatic carnitine acetyltransferase and catalase activities. 2,4-D and MCPA, but not clofibrate, decreased lipoprotein lipase activity in the adipose tissue to about a third of the control value but did not change the lipoprotein lipase activity in the heart muscle. The data suggest that these compounds cause hypolipidemia not by enhancing the storage of peripheral lipids in adipose tissue but by preferentially increasing lipid utilization in the liver. Glyphosate caused no peroxisome proliferation or hypolipidemia, suggesting that these effects are associated with the structural similarity between phenoxy acid herbicides and clofibrate.     

Age- and Sex-related Differences in Rat Liver Microsomal Enzymes and their Inducibility by Toluene

Abstract: In the liver microsomes of toluene-treated and control Sprague-Dawley rats (n=148, males and females aged 13–93 days), the contents of cytochrome P-450 and b₅ and the activities of NADPH – cytochrome c reductase and four monooxygenases were studied. In male control rats, cytochrome contents and NADPH – cytochrome c reductase, aminopyrine N-demethylase and aniline hydroxylase activities increased to the age of one month, and after a slight decrease in cytochrome concentrations, the average adult level was reached by the age of two months. Aniline hydroxylase and 7-ethoxycoumarine O-deethylase activities decreased to about half at the same age period. In control female rats, the activities of aminopyrine N-demethylase and aniline hydroxylase decreased after the age of one month, and they remained at a considerably lower level in adult females than in males. The sex-dependence of other enzymes was negligible. Toluene induction was already well developed in the youngest age group of both sexes; in most cases the induced enzyme levels in young rats were as high or higher than in adults. In adult female rats, toluene induction of all enzymes was weaker than in males. In male rats, the toluene-induced level of aniline hydroxylase and 7-ethoxycoumarine O-deethylase showed deep minima at the age of 43–53 days, at the puberty of rats.     

An extensive pattern of atypical neural speech-sound discrimination in newborns at risk of dyslexia

ObjectiveIdentifying early signs of developmental dyslexia, associated with deficient speech-sound processing, is paramount to establish early interventions. We aimed to find early speech-sound processing deficiencies in dyslexia, expecting diminished and atypically lateralized event-related potentials (ERP) and mismatch responses (MMR) in newborns at dyslexia risk.MethodsERPs were recorded to a pseudoword and its variants (vowel-duration, vowel-identity, and syllable-frequency changes) from 88 newborns at high or no familial risk. The response significance was tested, and group, laterality, and frontality effects were assessed with repeated-measures ANOVA.ResultsAn early positive and right-lateralized ERP component was elicited by standard pseudowords in both groups, the response amplitude not differing between groups. Early negative MMRs were absent in the at-risk group, and MMRs to duration changes diminished compared to controls. MMRs to vowel changes had significant laterality × group interactions resulting from right-lateralized MMRs in controls.ConclusionsThe MMRs of high-risk infants were absent or diminished, and morphologically atypical, suggesting atypical neural speech-sound discrimination.SignificanceThis atypical neural basis for speech discrimination may contribute to impaired language development, potentially leading to future reading problems.     

Contact sensitization to 4,4'-diaminodiphenylmethane and to isocyanates among general dermatology patients

Background:  Diisocyanates and 4,4'-diaminodiphenylmethane (MDA) are industrial sensitizers. Occupational asthma is a risk among workers exposed to diisocyanates. Exposure may also lead to contact sensitization and allergic contact dermatitis.
Objective:  The aim of this study was to determine the occurrence of contact sensitization to MDA and to diisocyanates among general dermatology patients.
Patients and methods:  Patch testing with MDA was carried out in 1595 patients. Diphenylmethane-4,4'-diisocyanate (MDI) and toluene-2,4-diisocyanate (TDI) were tested in 1023 patients and isophorone diisocyanate (IPDI) and 1,6-hexamethylene diisocyanate (HDI) in 433 patients. The clinical data and sources of exposure are analysed.
Results:  MDA reactions were seen in 17 (1.1%) patients and MDI reactions in 4 patients. Six MDA-positive patients reacted to p -phenylenediamine and two to epoxy chemicals. 5/10 of the TDI reactions were seen concurrently with reactions to MDI, MDA, HDI, or to IPDI. IPDI reactions were seen in eight patients and HDI reactions in two patients. Possible sources of exposure were traced in most patients, although the association with the current dermatitis was not apparent in all cases.
Conclusion:  (Di)isocyanates may induce contact sensitization with or without allergic contact dermatitis.     

Early detection of skin cancer as public health policy: comparison of campaign and routine activity

OBJECTIVE: The objective of this study was to evaluate the early detection of skin cancer, with emphasis on comparison of campaign (short high-intensity periods) and routine (continuous low-intensity) activity. METHODS: The study population consisted of 5903 campaign and 4284 routine attenders visiting a nurse at the Pirkanmaa Cancer Society between January 1, 1991, and December 31, 2000. Skin cancers were identified from the Finnish Cancer Registry. The performance of the program was evaluated in terms of sensitivity, specificity, positive and negative predictive values. RESULTS: A single lesion was more frequently examined during campaigns whereas a partial or total body were examined less frequently (p<0.001). Attenders received referral for removal of a lesion more frequently in routine activity (52% vs. 20% p<0.001), regardless of extent of the examination. The cumulative incidence of skin cancer within 24 months was 3.2% for routine and 1.6% for campaign attenders (p<0.001). Sensitivity was higher (82% vs. 59%, p<0.001), while specificity was lower (49% vs. 79%, p<0.001) for routine activity. CONCLUSIONS: Even though neither approach appears optimal, scheduled appointments with adequate time allocation per subject provided a lower threshold for detection and a higher yield of skin cancers compared to high-intensity campaigns.     

Nickel sensitization in orthodontically treated and non-treated female adolescents

Background. The importance of the nickel exposure from fixed orthodontic appliances is under continuous discussion. Objectives. Our aim was to investigate nickel allergy and the risk of nickel sensitization among female adolescents during orthodontic treatment with fixed appliances as compared with non‐treated female adolescents. Subjects and methods. Female patients starting or with ongoing orthodontic treatment (n = 30) and young females without a history of orthodontic treatment (n = 140) were studied. Patch testing with 5% nickel sulfate was carried out twice on each participant with an approximately 1‐year interval. The subjects completed a questionnaire before the first testing. Results. None of the 7 orthodontic patients with a positive patch test reaction to nickel had any clinically visible intraoral allergic symptoms during their treatment. No significant difference was seen in the occurrence of positive nickel reactions in regard to orthodontic treatment, or between the first and second tests. In the treatment group, 2 patients changed from nickel‐positive to nickel‐negative during the observation period, and one patient showed an opposite change. The quantity and course of changes in the repeated nickel patch test reactions did not differ significantly between the subjects with and without orthodontic treatment experience. Conclusions. Nickel sensitization from orthodontic appliances is improbable, but nickel sensitization may develop also during orthodontic treatment.     

A double-blind placebo-controlled study to evaluate endometrial safety and gynaecological symptoms in women treated for up to 5 years with tamoxifen or placebo – A substudy for IBIS I Breast Cancer Prevention Trial

Aims of the studyThis prospective study was performed to investigate the effects of 5-year’s use of tamoxifen in preventive setting on endometrium and gynaecological symptoms.Material and methodsAltogether 96 women were treated either with tamoxifen (TAM, n = 45) or placebo (PLA, n = 51) for up to 5 years in a randomised, double-blind IBIS I breast cancer prevention trial, clinically followed-up for an additional year and for the occurrence of malignancies at least 9 years between 2/1995 and 7/2009 in Finland. The gynaecological follow-up with trans-vaginal ultrasound and endometrial biopsies were performed at baseline, at 2.5 and 5 years and at the 6 years follow-up visit.ResultsWomen in the TAM group discontinued the treatment significantly more often (44% versus 22%; p = 0.017) and earlier (at 15 versus 30 months; p = 0.044), than those in the PLA group. In postmenopausal women the median endometrial thickness was significantly increased at five years in the TAM group (median 4.3 versus 2.0 mm, p = 0.011), but there was no difference between the groups at one year after the treatment. There were also statistically significantly more referrals to hospitals due to gynaecological findings in the TAM group (risk rates (RR) 3.15; 95% confidence intervals (CI) 1.12–10.10), but no differences in hysterectomy rates or other serious adverse event rates were observed.ConclusionsThe discontinuation rate in the TAM group was high, and the discontinuations also occurred early. Even though there were significantly more non-serious gynaecological events during the TAM treatment, routine gynaecological follow-up cannot be recommended.