Evidence on methylphenidate in children and adolescents with ADHD is in fact of 'very low quality'.

Banaschewski and colleagues from the European Attention Deficit Hyperactivity Disorder (ADHD) guideline group make a number of critical comments regarding our systematic review on methylphenidate for children and adolescents with ADHD. In this article, we present our views, showing that our trial selection was not flawed and was undertaken with scientific justification. Similarly, our data collection and interpretation was systematic and correct. We have followed a sound methodology for assessing risk of bias and our conclusions are not misleading. We acknowledge that different researchers might make risk of bias judgments at higher or lower thresholds, but we have been consistent and transparent in applying our pre-defined and per reviewed protocol. Although we made minor errors, we demonstrate that the effects are negligible and not affecting our conclusions. We are happy to correct such errors and to engage in debate on methodological and ethical issues. In terms of clinical implications, we are advocating that clinicians, patients and their relatives should weight carefully risks and benefits of methylphenidate. Clinical experience seems to suggest that there are people who benefit from this medication. Our systematic review does, however, raise questions regarding the overall quality of the methylphenidate trials.

Vibrationally resolved photoabsorption spectroscopy of red fluorescent protein chromophore anions.

Photoabsorption studies of red fluorescent protein chromophore anions have been performed at the ELISA electrostatic heavy-ion storage ring. The broad absorption band due to electronic excitation of the chromophores is tuned to a longer wavelength (redshifted) by extending the electronic conjugation of the molecule. A clear vibrational progression is resolved with E(vib) approximately 380 and 520 cm(-1) for two different forms of the chromophore. The vibrational modes correspond to collective motions of the entire molecular structure. It is argued that the excited electronic state has an equilibrium configuration far from that of the electronic ground state, i.e., poor Franck Condon overlap.

Pink and blue collar jobs: children's judgments of job status and job aspirations in relation to sex of worker.

Past work shows that even young children know that occupations are differentially linked to men and women in our society. In our research, we studied whether 6- and 11-year-old children's (a) beliefs about job status and (b) job interests would be affected by the gendered nature of jobs. When asked about familiar occupations, children gave higher status ratings to masculine jobs and expressed greater interest in jobs culturally associated with their own sex. To circumvent the extant confounds between job gender and job status in our culture, we also developed a new methodology in which novel jobs were portrayed with either male or female workers. Older children rated novel jobs portrayed with male workers as having higher status than the identical jobs portrayed with female workers. Portrayal sex had no effect on children's own interests in these novel jobs at either age. Methodological, theoretical, and educational issues are discussed in relation to sex-role development and vocational aspirations.

Behavioural effects in female rats of postnatal exposure to sub-toxic doses of polychlorinated biphenyl congener 153.

Polychlorinated biphenyls (PCBs) are widespread environmental contaminants that are also present in human tissues and breast milk. Behavioural disturbances have been reported in both children and animals exposed perinatally to PCBs. The present study assessed the behavioural consequences in female rats of postnatal exposure to the di-ortho-substituted 2,2',4,4',5,5'-hexachlorobiphenyl (IUPAC no. 153), which is one of the PCB congeners most frequently detected in human milk. The different groups of mothers were dosed via gavage with 5 mg/kg bodyweight of PCB 153 in corn oil or 5 ml/kg bodyweight corn oil vehicle every second day from day 3 to day 13 after delivery. The exposure did not affect the bodyweight of the dams nor the physical development of the pups. Operant behavioural testing of the female offspring by two different schedules of reinforcement was performed. First, the animals were tested by a multiple schedule with two components: fixed interval (FI) and extinction (EXT), which has proved sensitive in revealing changes in activity level. There were no statistically significant differences in frequency or interresponse times of lever pressing between the PCB-exposed female rats and the controls. These results were in contrast to a previous, analogous study where PCB 153 produced an increased frequency of lever presses during the FI in male rats, indicating a sex-specific behavioural effect of PCB 153. The female offspring was also tested by a conjunctive schedule with two components: variable interval (VI) and differential reinforcement of low rate (DRL). This schedule revealed slower acquisition of time discrimination in the PCB 153-exposed females as compared with the controls. The VI-DRL results showed that PCB 153 may also produce long-lasting behavioural effects in female rats following postnatal exposure through the mother's milk.

Effects of ginseng treatment on neutrophil chemiluminescence and immunoglobulin G subclasses in a rat model of chronic Pseudomonas aeruginosa pneumonia.

Chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients is almost impossible to eradicate with antibiotic treatment. In the present study, the effects of treatment with the Chinese herbal medicine ginseng on blood polymorphonuclear leukocyte (PMN) chemiluminescence and serum specific antibody responses were studied in a rat model of chronic P. aeruginosa pneumonia mimicking CF. An aqueous extract of ginseng was administered by subcutaneous injection at a dosage of 25 mg/kg of body weight/day for 2 weeks. Saline was used as a control. Two weeks after the start of ginseng treatment, significantly increased PMN chemiluminescence (P

Immunohistochemical diagnosis of systemic bovine zygomycosis by murine monoclonal antibodies.

Murine monoclonal antibodies (Mabs) against water-soluble somatic antigens (WSSA) and the wall fraction (WF) from Rhizopus arrhizus (Rhizopus oryzae) were produced in vitro by fusion of splenocytes from immunized BALB/c mice with mouse myeloma X63-Ag 8.653 cells. Supernatants reacting only with homologous antigens in an enzyme-linked immunosorbent assay were subsequently screened for reactivity with homologous fungi in immunohistochemical techniques. All four Mabs raised against the WF of A. arrhizus failed to react on tissues. However, four of the Mabs raised against the WSSA of R. arrhizus (Mab-WSSA-RA-1 through Mab-WSSA-RA-4) revealed a high homologous reactivity on tissues and the cross-reactivity of these were subsequently evaluated on tissues containing other members of the family Mucoraceae and other unrelated fungi. On tissues and on immunoblots all four Mabs reacted identically and specifically with members of the family Mucoraceae, i.e., Absidia corymbifera, R. arrhizus, and Rhizomucor pusillus. The Mabs were all isotyped as IgM antibodies, were nonprecipitating, and reacted with homologous antigens with molecular masses from I4 to 110 kDa. With WSSA from A. corymbifera and R. pusillus the four Mabs were bound to antigens from 14 to 52 kDa and from 20 to 28 kDa, respectively. The diagnosis of 145 bovine lesions obtained by one of the specific Mabs (Mab-WSSA-RA-1) were compared to results obtained by heterologously absorbed polyclonal antibodies. In most lesions (n = 140 [approximately 97%]) the Mab and the polyclonal antibodies reacted in a similar pattern, i.e., positively for zygomycosis in 89 lesions, negatively in 41 aspergillosis lesions, and negatively in 10 undiagnosed lesions. Hyphae within two of four lesions in lymph nodes, which were not stained by the polyclonal antibodies, reacted with the specific Mab. However, in another three lesions of lymph nodes stained by the polyclonal antibodies no reactivity was seen with the Mab-WSSA-RA-1. The immunoreactivity of the Mabs (Mab-WSSA-RA-1 through Mab-WSSA-RA-4) raised against WSSA of R. arrhizus justify their application for the in situ diagnosis of systemic bovine zygomycosis.

Development of murine monoclonal antibodies for the immunohistochemical diagnosis of systemic bovine aspergillosis.

Murine monoclonal antibodies (MAbs) against water-soluble somatic antigens (WSSA) and the wall fraction (WF) from Aspergillus fumigatus were produced by fusion of splenocytes from immunized BALB/c mice with mouse myeloma X63-Ag 8.653 cells. The supernatants of in vitro cultured hybridomas were initially screened for reactivity with the WSSA and the WF from A. fumigatus and WSSA of other fungi in an enzyme-linked immunosorbent assay (ELISA). Supernatants reacting only with A. fumigatus antigens were subsequently screened for homologous and heterologous reactivity with immunohistochemical techniques using formalin-fixed, paraffin-embedded tissues from experimentally infected mice. Because of a high immunohistochemical reactivity with homologous fungi, 4 MAbs raised against A. fumigatus WSSA and WF were selected for a further evaluation of cross-reactivity (diagnostic specificity) in immunohistochemical and immunoblotting assays. In immunohistochemical assays, all MAbs raised against WSSA cross-reacted heavily with a number of other fungal species. All 4 MAbs (MAb-WF-AF-1-4) raised against the WF reacted strongly with hyphae of Aspergillus spp.; hyphae of Scedosporium apiospermum were also strongly labeled by MAb-WF-AF-3 and -4. The 2 specifically reacting MAbs (MAb-WF-AF-1 and -2) were of the IgM biotype and were precipitating, and in immunoblotting experiments both bound to a 106-kD antigen of the WF, whereas they did not bind to WSSA of A. fumigatus. One of the 2 aspergillosis-specific MAbs (MAb-WF-AF-1) was used to screen 145 mycotic lesions of cattle. The diagnoses on bovine lesions obtained by MAb-WF-AF-1 were compared with results based on reactivity with heterologously absorbed polyclonal antibodies and, for some lesions, to culture results. In the vast majority of lesions (n = 133), the MAb-WF-AF-1 and the polyclonal anti-Aspergillus antibodies reacted in a similar pattern, i.e., positively in 41 aspergillosis lesions and negatively in 92 zygomycotic lesions. Hyphae in 3 of 12 lesions that were not stained by the polyclonal antibodies reacted with the specific MAb-WF-AF-1; i.e., aspergillosis was diagnosed. The characteristics of the 2 MAbs (MAb-WF-AF-1 and -2) raised against the WF of A. fumigatus in ELISA and immunoblotting and immunohistochemical assays justify their application for the in situ diagnosis of systemic aspergillosis of cattle.

A retrospective study of bovine abortions associated with Bacillus licheniformis.

A retrospective study of bovine abortions associated with Bacillus licheniformis is described. The material consisted of 2445 bovine abortions submitted for diagnostics from 1986 through 1993. Initially, B. licheniformis had been isolated from 81 cases. Sections of these cases were re-examined microscopically and immunohistochemically by a PAP technique using a primary antibody against B. licheniformis. Of these abortions, 47 were most likely associated with B. licheniformis as tissue lesions with immunostained bacteria were present in these. In the remaining cases the diagnosis may not have been established due to the lack of sufficient materials, or the isolation of the bacterium was considered to be a result of contamination. In four cases concomitant infections with B. licheniformis and bovine virus diarrhoea virus were present. Abortions caused by B. licheniformis were predominantly seen during the winter months and in late pregnancy. The most common lesions were necrotizing placentitis followed by fetal multifocal suppurative bronchopneumonia. Immunohistochemically, B. licheniformis was demonstrated in association with tissue lesions and intracellularly in trophoblasts. The pattern of bacterial isolations, especially from the placenta, lungs, and abomasal contents, combined with the histological findings points to B. licheniformis abortions as being of haematogenous origin with subsequent transplacental spread to the fetus.

Sensitivity, specificity and predictive value of blood cultures from cattle clinically suspected of bacterial endocarditis.

This study investigated the number of blood culture-positive cattle among 215 animals clinically suspected of having bacterial endocarditis. For animals that were necropsied, the sensitivity, specificity and predictive value of the diagnosis of endocarditis were calculated on the basis of the isolation of the causative bacteria from blood. Furthermore, it was investigated whether the glutaraldehyde coagulation time, total leucocyte count, per cent neutrophil granulocytes, pulse rate and duration of disease could help to discriminate endocarditis from other diseases. Among 138 animals necropsied the sensitivity, specificity and predictive value of blood cultivation were 70.7 per cent, 93.8 per cent and 89.1 per cent, respectively. None of the other measurements could be used to discriminate between endocarditis and non-endocarditis cases.

Enzyme immunohistochemistry with mono- and polyclonal antibodies in the pathological diagnosis of systemic bovine mycoses.

To improve the immunohistopathological diagnosis of systemic bovine mycoses, we have evaluated the utility of antifungal polyclonal and monoclonal antibodies, and peroxidase and alkaline phosphatase staining techniques. A rabbit polyclonal antibody to mannan from Candida albicans was specific for candidosis. The diagnosis of aspergillosis was accomplished using a rat monoclonal antibody to the galactofuran side chains of Aspergillus galactomannan. A murine monoclonal antibody reacting with weakly Con-A binding 41 and 46 kDa somatic antigens from Absidia corymbifera was used for immunostaining of zygomycetic hyphae. Peroxidase antiperoxidase (PAP) and alkaline phosphatase antialkaline phosphatase (APAAP) complexes were visualized using aminoethylcarbazole and fast red substrates. A green staining of PAP reactions with dioctyl sulfosuccinate sodium and 3,3',5,5'-tetramethylbenzidine (DONS/TMB) was effective for the demonstration of fungi in dual and triple infections. Tissue sections of experimentally infected mice were used to determine the sensitivity and specificity of the antibodies. Tissues obtained from 161 bovine mycotic lesions previously studied by indirect immunofluorescence staining were further evaluated using the three antibodies. In all of 45 lesions solely affected by aspergillosis and in three solely affected by candidosis the diagnoses were confirmed by the new evaluation. In 85 of 96 cases of single infections with zygomycetes the diagnosis was confirmed, while none of the antibodies reacted with fungal elements in the remaining 11 lesions. Aspergillus hyphae were detected in all three lesions with dual aspergillosis and zygomycosis, whereas zygomycetic material was confirmed in only two of these cases. A mixed infection of candidosis and zygomycosis in a lymph node was confirmed too. In 13 cases in which a diagnosis had not hitherto been obtained, aspergillosis and zygomycosis were recorded each in three cases.

Abortion and calf mortality in Danish cattle herds.

The aetiology of abortions and calf mortality in 65 Danish cattle herds consisting of both dairy and beef breeds during a 1-year period is described. All observed aborted foetuses, still-born calves, and calves dying before 6 months of age were necropsied, and relevant microbiological examinations were performed. A total of 240 calves and 66 abortions were submitted corresponding to a calf mortality rate of 7%. The abortion frequency could not be calculated. 43% of the calves died at day 0, while 22% were aborted, 15% died during the first week of life, 9% died from 1 to 4 weeks of age, and 11% died at the age of 1 to 6 months. The most common cause was neonatal pulmonic atelectasis (stillbirth) followed by foetal infections, pneumonia, and septicaemia.

Bovine mycotic abortion--a comparative study of diagnostic methods.

The agreement between three diagnostic methods (mycology, morphology, and immunofluorescence staining) was compared two by two in elucidating the aetiological diagnosis in 52 cases of bovine mycotic abortion. Agreement between the three methods was expressed by the kappa coefficient (kappa), and ranked as follows: mycology and immunofluorescence staining (kappa = 0.48); morphology and immunofluorescence staining (kappa = 0.40); mycology and morphology (kappa = 0.28). A. fumigatus was confirmed to be the main cause of bovine mycotic abortion with members of the zygomycetes (order Mucorales) being the second most important group. In two aborted placentas a Candida species was found to be the cause of mycotic placentitis.

[Malignant melanoma--a warning. How to reduce mortality?]. / Malignt melanom--et varsko. Hvordan redusere dødeligheten?

Incidence of malignant melanoma of the skin has risen rapidly during the last decades. Mortality rates are also rising, although not so much as incidence rates. There is strong evidence that exposure to sunlight is a major factor in the etiology of melanomas. There appears to be no direct cumulative dose-response relationship, except in the case of lentigo maligna melanoma. Episodes of sunburn among children and young individuals seem to be more important as an etiologic factor for melanoma than chronic exposure to the sun. Very high risk of melanoma exists in persons with dysplastic nevus syndrome. Persons with giant congenital nevi are also at increased risk. However, many melanomas arise de novo. It is our intention to reduce mortality by screening families at risk, by early detection and treatment of melanomas, and by education.

Monitoring middle ear pressure by tympanometry. A study of middle ear pressure variation through seven hours.

The aim of this investigation was to monitor fluctuations in middle ear pressure, to study tympanometric signs of Eustachian tube functioning and to assess the validity of the tympanometric readings. In 20 patients with a low initial middle ear pressure (-150 daPa or lower) and 5 normals, impedance tympanometry was performed every 3 min through 7 h. Median pressure for the patients was -150 daPa (range 100 to -400 daPa) and for the normals 0 daPa (range 50 to -50 daPa). A remarkable pressure increase was seen after changing the body position to the supine. The patients were arranged into three groups according to the lowest middle ear pressure registered. Median pressures for the groups were running at a rather constant level. However, the individual pressure fluctuations in many patients were so great that a single tympanometric reading has to be considered unreliable when selecting patients for insertion of ventilation tubes. Thirteen patients never equalized their negative middle ear pressure, indicating that their Eustachian tube did not open during the test period. In spite of this the pressure did not decrease to lower values, indicating that maintaining a relative constant middle ear pressure is independent of opening of the Eustachian tube.

A 24-week multicenter double-blind study of doxazosin and hydrochlorothiazide in patients with mild to moderate essential hypertension.

The new alpha1-adrenoceptor antagonist, doxazosin (DOX), was compared with hydrochlorothiazide (HCTZ), both drugs administered once daily, in a randomized double-blind study including 115 patients. The mean final daily doses used were DOX, 10.8 mg; HCTZ, 89.1 mg. There were no statistically significant differences between treatment groups for blood pressure (BP) changes except that HCTZ produced a significantly greater fall (p = 0.04) in supine systolic BP than DOX. The statistically significant mean differences in changes in lipid parameters (total cholesterol and total triglycerides) were in favour of DOX. The number of patients reporting side-effects were DOX, 27/57; HCTZ, 29/53, with two DOX- and five HCTZ-treated patients withdrawn due to side-effects. In the HCTZ-treated group, laboratory serum tests indicated 11 patients with abnormally low potassium and seven with abnormally high uric acid concentrations. The overall results suggest a benefit-to-risk ratio in favour of DOX.

A case of guttural pouch mycosis in a horse.

A case of guttural pouch mycosis in an 11-year-old horse is described. The fungus isolated was identified as Emericella nidulans. Housing under bad hygienic conditions without ventilation for three years might have been a predisposing factor.

Bovine mycotic abortion in Denmark.

A survey is given of the occurrence of mycotic infections associated with abortion in Danish cattle. During a period of six years a total of 748 samples of placenta material were examined. Mycotic abortion was demonstrated in 101 cases (14%). The case rate was significantly higher (21%) during the winter months from December through February than during the rest of the year (10%). Abortions occurred as from the 135th day of pregnancy, with maximum in the eighth month, where 45% of all cases were observed. A. fumigatus was demonstrated in 77 cases, Mucor spp. in 11 cases, Absidia spp. in 5 cases, and a mixed infection with A. fumigatus and Mucor spp. in 3 cases. In 5 cases the fungi were demonstrated by microscopic and histological examination, but not by culture. The annual occurrence of mycotic abortion varied from 10% to 24% of cases of abortion examined. The latter figure was recorded in a year following a particularly heavy rainfall in the month of June.

Bovine cryptosporidiosis in Denmark. 2. Cryptosporidia associated with neonatal calf diarrhea.

In recent years cryptosporidia have often been identified in diarrheic calves of under one month old, either as the sole pathogenic agent or in combination with other diarrhea-causing infectious agents. In 203 cases of bovine cryptosporidiosis, recorded over a period of two years, cryptosporidia were present in such great numbers that they would seem to be of causal significance. The calves were from three days to five weeks old. In 111 cases (55%) a monoinfection with cryptosporidia occurred, while in the rest of the cases mixed infections with other agents associated with calf diarrhea were demonstrated, especially rotavirus (61 cases) and coronavirus (32 cases); in addition, mixed infections with ETEC (four cases), septicaemic E. coli (two cases), salmonellosis (11 cases), and BVD and coccidiosis (one case each) were seen. In 87 (10%) of 849 4-21-day-old dead calves a massive occurrence of cryptosporidia was demonstrated. Extreme emaciation was noted in 36 of 122 autopsied calves. Most of these calves were more than 14 days old, and mono-infection with cryptosporidia was demonstrated in two thirds of them. In younger calves, more acute cases of cryptosporidiosis were commoner, often in connection with concomitant infections with rota- or coronavirus.