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A comparison of oral midazolam, nitrazepam and placebo in young and elderly subjects.

Twelve young and twelve elderly subjects received a single dose orally of midazolam 15 mg, nitrazepam 5 mg and placebo in a double-blind, crossover comparison. Midazolam acted rapidly, producing a deep sleep at 1 h in fifteen subjects compared to two after Nitrazepam and none after placebo. No comparison of psychomotor tests was possible at this time, but such tests showed that there was no detectable subjective or objective psychomotor impairment at 4 h postdose with either drug. However, the EEG scores strongly suggested that volunteers were more sleepy at 8 h after nitrazepam in comparison to placebo or midazolam. Both groups appeared to handle the drug in a similar manner, there being no significant differences between the groups in the plasma concentration time curves of nitrazepam, or midazolam. The elderly had higher concentrations of alpha-hydroxymidazolam. This accounted for a small proportion of the total plasma benzodiazepine concentration, and the mean area under the curve for midazolam and metabolite was not significantly different in the old from that in the young.

Adult↗

Prosocial behavior in hyperactive boys: effects of stimulant medication and comparison with normal boys.

To clarify the effects of stimulant medication on hyperactive (ADHD) children's prosocial as well as aversive behaviors toward peers, 19 hyperactive boys, aged 7-12, were observed as they acted as "leaders" for groups of 2-4 unfamiliar younger children. In a double-blind crossover design, subjects were observed twice, once on placebo and again on a moderate (0.6 mg/kg) dose of methylphenidate (Ritalin). Thirteen comparison boys, without problems in attention and behavior, were also observed in the same leader roles. Relative to comparison boys, hyperactive boys on placebo were more socially engaged, used more aversive leadership techniques, and were rated as less likable by the younger children in their groups. Aversive social behaviors were the strongest predictors of being disliked by the younger children. No differences were found between comparison and unmedicated hyperactive boys for any aspect of prosocial behavior. Stimulant medication had a general dampening effect on social behavior, significantly reducing social engagement and increasing (mild) dysphoria relative to the placebo condition. The implications of these findings for understanding and treating the peer relationship difficulties of hyperactive children are discussed.

Attention Deficit Disorder with Hyperactivity↗

Monoamine oxidase-B inhibition: a comparison of in vivo and ex vivo measures of reversible effects.

A behavioural test involving potentiation of the effects of an acute injection of beta-phenylethylamine (10 mg kg-1 i.p.) was used to assess the time-course of type-B MAO inhibition after administration of (--)deprenyl (5 mg kg-1 i.p.) and of MD 240928 (20 mg kg-1 i.p.) respectively. Potentiation of the effects of beta-phenylethylamine was observed 1 h after injection of (-)deprenyl or MD 240928. This effect was still evident 120 h after administration of (-)deprenyl but not 24 h after administration of MD 240928. Comparisons of ex vivo estimates of MAO activity yielded a corresponding time-course for the recovery of this enzyme. The extent of MAO inhibition required for potentiation of the effects of beta-phenylethylamine was inferred from a comparison of the behavioural test results and the ex vivo MAO activity observed after (-)deprenyl administration. These comparisons indicate a significant underestimation of MD 240928-induced MAO inhibition using ex vivo measures. This underestimation is interpreted as evidence for dilution effects in the ex vivo assay of MAO inhibition. The potentiation of effects of beta-phenylethylamine under the present conditions is proposed as a useful and simple test for effects of reversible type-B MAO inhibitors.

Animals↗

What they want and what they get: the social goals of boys with ADHD and comparison boys.

Twenty-seven boys diagnosed with attention-deficit hyperactivity disorder (ADHD) and 18 comparison boys participated in a competitive tetradic interaction task. Boys were individually interviewed before the game about their goals for the interaction, and adult observers inferred boys' social goals from videotapes of the interaction. Social acceptance was determined by combining positive and negative sociometric nominations collected through individual interviews at the end of the summer research program in which the interaction was held. In their self-reports, ADHD-high aggressive boys prioritized trouble-seeking and fun at the expense of rules to a greater extent than did both ADHD-low aggressive and comparison boys. Observers judged ADHD-high aggressive boys to seek attention more strongly and seek fairness less strongly than of the other two groups. Self-reported goals of defiance and cooperation predicted boys' end-of-program social standing, even with interactional behaviors and subgroup status controlled statistically. Observer-inferred goals were differentially associated with social acceptance for ADHD and comparison boys, suggesting discontinuities in peer interaction processes. Differentiation of goals from behavior and the integral role of children's goals in peer acceptance are discussed.

Aggression↗

Comparison of individual surgeon's performance. Risk-adjusted analysis with POSSUM scoring system.

UNLABELLED: Comparison of outcome after colorectal resection among different surgeons is difficult. Crude rates of morbidity and mortality can be misleading because such rates make no allowance for differences in case mix and fitness of patients. AIM: The aim of this study was to compare outcome among five surgeons by means of the simple, well-validated scoring system POSSUM for risk-adjusted analysis. METHODS: A total of 438 patients were studied prospectively. Each patient underwent colorectal resection by one of the five surgeons. Demographic details, operative procedure, and postoperative course were recorded, and physiologic and operative severity scores were determined. Risk of morbidity and mortality was calculated for each patient. RESULTS: Incidence of morbidity varied sharply among the five surgeons, from 13.6 to 30.6 percent, and the 30-day mortality varied from 4.5 to 6.9 percent. However, application of POSSUM to allow risk-adjusted analysis of the data demonstrated that the incidence of morbidity and mortality predicted by POSSUM based on patients physiologic and operative risks factors was very similar to the observed outcome for each surgeon. CONCLUSION: Direct comparison of individual surgeon's performance based on crude rates of morbidity and mortality can be misleading. Risk-adjusted analysis allows more meaningful comparison.

Aged↗

Comparison of three actin-coding sequences in the mouse; evolutionary relationships between the actin genes of warm-blooded vertebrates.

We have determined the sequences of three recombinant cDNAs complementary to different mouse actin mRNAs that contain more than 90% of the coding sequences and complete or partial 3' untranslated regions (3'UTRs): pAM 91, complementary to the actin mRNA expressed in adult skeletal muscle (alpha sk actin); pAF 81, complementary to an actin mRNA that is accumulated in fetal skeletal muscle and is the major transcript in adult cardiac muscle (alpha c actin); and pAL 41, identified as complementary to a beta nonmuscle actin mRNA on the basis of its 3'UTR sequence. As in other species, the protein sequences of these isoforms are highly (greater than 93%) conserved, but the three mRNAs show significant divergence (13.8-16.5%) at silent nucleotide positions in their coding regions. A nucleotide region located toward the 5' end shows significantly less divergence (5.6-8.7%) among the three mouse actin mRNAs; a second region, near the 3' end, also shows less divergence (6.9%), in this case between the mouse beta and alpha sk actin mRNAs. We propose that recombinational events between actin sequences may have homogenized these regions. Such events distort the calculated evolutionary distances between sequences within a species. Codon usage in the three actin mRNAs is clearly different, and indicates that there is no strict relation between the tissue type, and hence the tRNA precursor pool, and codon usage in these and other muscle mRNAs examined. Analysis of codon usage in these coding sequences in different vertebrate species indicates two tendencies: increases in bias toward the use of G and C in the third codon position in paralogous comparisons (in the order alpha c less than beta less than alpha sk), and in orthologous comparisons (in the order chicken less than rodent less than man). Comparison of actin-coding sequences between species was carried out using the Perler method of analysis. As one moves backward in time, changes at silent sites first accumulate rapidly, then begin to saturate after -(30-40) million years (MY), and actually decrease between -400 and -500 MY. Replacements or silent substitutions therefore cannot be used as evolutionary clocks for these sequences over long periods. Other phenomena, such as gene conversion or isochore compartmentalization, probably distort the estimated divergence time.

Actins↗

The concept of major depression. I. Descriptive comparison of six competing operational definitions including ICD-10 and DSM-III-R.

All operationalized diagnostic systems contain a diagnostic category, which corresponds to the concept of major depression. Yet, these corresponding definitions are not identical. Up to now, no comprehensive comparisons of the competing diagnoses have been published. We will therefore present a series of studies, describing six different operational definitions of major depression according to their content and construction and empirically comparing them in large inpatient and outpatient samples. This first paper presents a descriptive comparison of the definitions given in the Feighner Diagnostic Criteria, the Research Diagnostic Criteria, the Diagnostic and Statistical Manual of Mental Disorders, third edition and third edition, revised, and in two developmental drafts of the ICD-10 diagnostic criteria for research (draft April 1987-I87; draft April 1989-I89). The descriptive comparison will demonstrate that there are many similarities, especially concerning the symptom-criteria of major depression. Classificatory relevance could only be assumed for those differences found for cut-offs, for time criteria and especially for exclusion criteria. Whether these differences are negligible and whether patients classified by different diagnostic systems are really comparable will be examined in subsequent publications.

Depressive Disorder↗

Poisson, compound Poisson and process approximations for testing statistical significance in sequence comparisons.

DNA and protein sequence comparisons are performed by a number of computational algorithms. Most of these algorithms search for the alignment of two sequences that optimizes some alignment score. It is an important problem to assess the statistical significance of a given score. In this paper we use newly developed methods for Poisson approximation to derive estimates of the statistical significance of k-word matches on a diagonal of a sequence comparison. We require at least q of the k letters of the words to match where 0 less than q less than or equal to k. The distribution of the number of matches on a diagonal is approximated as well as the distribution of the order statistics of the sizes of clumps of matches on the diagonal. These methods provide an easily computed approximation of the distribution of the longest exact matching word between sequences. The methods are validated using comparisons of vertebrate and E. coli protein sequences. In addition, we compare two HLA class II transplantation antigens by this method and contrast the results with a dynamic programming approach. Several open problems are outlined in the last section.

Algorithms↗

Comparison of in vivo 1H MRS of human brain tumours with 1H HR-MAS spectroscopy of intact biopsy samples in vitro.

High resolution magic angle spinning (MAS) 1H nuclear magnetic resonance (NMR) spectroscopy has been employed to study intact human brain tumour tissue and comparison with the corresponding in vivo spectrum has been made. Two dimensional 1H MAS-NMR measurements, including J-resolved and homonuclear shift correlation spectra, were obtained to aid metabolite signal assignment. MAS gave greatly improved line-shape and reduced line-width in comparison to conventional high resolution in vivo 1H MRS of intact tissue, permitting the simultaneous detection of cellular lipids and metabolites. The technique provides the most direct method for comparison of in vivo spectra with high resolution spectra in vitro and hence allows more reliable peak assignment of in vivo 1H MRS spectra.

Astrocytoma↗

Structural comparison of 26S rRNA-binding ribosomal protein L25 from two different yeast strains and the equivalent proteins from three eubacteria and two chloroplasts.

The sequences of Saccharomyces carlsbergensis ribosomal protein (r-protein) SL25* and its equivalents from Candida utilis (CL25), Escherichia coli (EL23), Bacillus stearothermophilus (BL23), Mycoplasma capricolum (ML23), Marchantia polymorpha chloroplasts (McpL23), and Nicotiana tabacum chloroplasts (NcpL23) were examined using a computer program that evaluates the extent of sequence similarity by calculating correlation coefficients for each pair of residues in two proteins from a number of physical properties of individual amino acids. Comparison matrices demonstrate that the prokaryotic sequences (including McpL23 and NcpL23) can be aligned unambiguously by introducing small internal deletions/insertions at three specific positions. A similar comparison brought to light a clear evolutionary relationship between the prokaryotic and the yeast proteins despite the fact that visual inspection of these sequences revealed only limited similarity. The alignment deduced from this comparison shows the two yeast r-proteins to have acquired a long (50-60 amino acids) N-terminal extension as well as a 13-amino acid-long deletion near the C-terminus. The significance of these findings in terms of the evolution of r-proteins in general and the biological function of various parts of the SL25 protein in particular is discussed.

Amino Acid Sequence↗

A thermoluminescent dosimetry postal dose inter-comparison of radiation therapy centres in Malaysia.

A thermoluminescent dosimetry (TLD) postal dose inter-comparison was carried out amongst radiotherapy centres in Malaysia. The aim of this TLD inter-comparison was to compare the uniformity involved in the measurement of absorbed dose among the participating centres. A set of 5 TLD chips placed within acrylic trays were mailed to all participating centres for irradiation to an absorbed dose to water of 2 Gy. Measurements were made for 6 MV and 60Co photon beams. Results show an agreement of +/- 5% for all but three radiotherapy centres. The ratios of the TLD readings to that of the reference centre are comparable with other national/regional dose inter-comparisons. The importance of a proper ongoing quality assurance program is essential in maintaining the consistency and uniformity of doses delivered.

Equipment Failure Analysis↗

A comparison of Australian and Canadian calibration coefficients for air kerma and absorbed dose to water for 60Co gamma radiation.

Australian and Canadian calibration coefficients for air kerma and absorbed dose to water for 60Co gamma radiation have been compared using transfer standard ionization chambers of types NE 2561 and NE 2611A. Whilst the primary standards of air kerma are similar, both being thick-walled graphite cavity chambers but employing different methods to evaluate the Awall correction, the primary standards of absorbed dose to water are quite different. The Australian standard is based on measurements made with a graphite calorimeter, whereas the Canadian standard uses a sealed water calorimeter. The comparison result, expressed as a ratio of calibration coefficients R=N(ARPANSA)/N(NRC), is 1.0006 with a combined standard uncertainty of 0.35% for the air kerma standards and 1.0052 with a combined standard uncertainty of 0.47% for the absorbed dose to water standards. This demonstrates the agreement of the Australian and Canadian radiation dosimetry standards. The results are also consistent with independent comparisons of each laboratory with the BIPM reference standards. A 'trilateral' analysis confirms the present determination of the relationship between the standards, within the 0.09% random component of the combined standard uncertainty for the three comparisons.

Absorption↗

Biometrical evaluation of bioequivalence trials using a bootstrap individual direct curve comparison method.

Bioequivalence of two medicinal, or veterinary, products is established by comparing the mean of bioavailability measures, such as AUC and Cmax, following administration of the test (T) and reference (R) products. However, the use of these parameters has several drawbacks, e.g. they do not take into consideration the overall pharmacokinetic profile shape. Therefore, concerns have been raised regarding their appropriateness for assessment of bioequivalence. To overcome the limitations of these bioequivalence parameters, direct curve comparison metrics methods were recently proposed on an average basis. In this paper, an individual based direct curve comparison method for assessing bioequivalence is proposed. The bioequivalence of T and R in each subject is evaluated by a new curve comparison metrics delta. The metrics delta is the absolute sum of the difference between two curves. The significance of the metrics for each subject is assessed by bootstrapping. An overall bioequivalence of T and R may be considered if less than 25% of the subjects show statistically different profiles.

Area Under Curve↗

Comparison of protein structures using 3D profile alignment.

A novel method for protein structure comparison using 3D profile alignment is presented. The 3D profile is a position-dependent scoring matrix derived from three-dimensional structures and is basically used to estimate sequence-structure compatibility for prediction of protein structure. Our idea is to compare two 3D profiles using a dynamic programming algorithm to obtain optimal alignment and a similarity score between them. When the 3D profile of hemoglobin was compared with each of the profiles in the library, which contained 325 profiles of representative structures, all the profiles of other globins were detected with relatively high scores, and proteins in the same structural class followed the globins. Exhaustive comparison of 3D profiles in the library was also performed to depict protein relatedness in the structure space. Using multidimensional scaling, a planar projection of points in the protein structure space revealed an overall grouping in terms of structural classes, i.e., all-alpha, all-beta, alpha/beta, and alpha+beta. These results differ in implication from those obtained by the conventional structure-structure comparison method. Differences are discussed with respect to the structural divergence of proteins in the course of molecular evolution.

Algorithms↗

Estimating the transition/transversion ratio from independent pairwise comparisons with an assumed phylogeny.

A method is presented for estimating the transition/transversion ratio (TI/TV), based on phylogenetically independent comparisons. TI/TV is a parameter of some models used in phylogeny estimation intended to reflect the fact that nucleotide substitutions are not all equally likely. Previous attempts to estimate TI/TV have commonly faced three problems: (1) few taxa; (2) nonindependence among pairwise comparisons; and (3) multiple hits make the apparent TI/TV between two sequences decrease over time since their divergence, giving a misleading impression of relative substitution probabilities. We have made use of the time dependency, modeling how the observed TI/TV changes over time and extrapolating to estimate the "instantaneous" TI/TV-the relevant parameter for phylogenetic inference. To illustrate our method, TI/TV was estimated for two mammalian mitochondrial genes. For 26 pairs of cytochrome b sequences, the estimate of TI/TV was 5.5; 16 pairs of 12s rRNA yielded an estimate of 9.5. These estimates are higher than those given by the maximum likelihood method and than those obtained by averaging all possible pairwise comparisons (with or without a two-parameter correction for multiple substitutions). We discuss strengths, weaknesses, and further uses of our method.

Animals↗

The complete mitochondrial DNA sequence of the domestic sheep (Ovis aries) and comparison with the other major ovine haplotype.

The complete mitochondrial DNA (mtDNA) molecule of the domestic sheep, Ovis aries, was sequenced, together with part of the mtDNA of a specimen representing the other major O. aries haplotype group. The length of the complete ovine mtDNA presented is 16,616 nucleotides (nt). This length is not absolute, however, due to heteroplasmy caused by the occurrence of different numbers of a 75-nt-long tandem repeat in the control region. The sequence data were included in analyses of intraspecific ovine molecular differences, molecular comparisons with bovine mtDNAs, and phylogenetic analyses based on complete mtDNAs. The comparisons with bovine mtDNAs were based on the central domains of the ovine control regions, representing both major ovine haplotype groups, and the corresponding domains of Bos taurus and B. indicus. The comparisons showed that the difference between the bovids was 1.4 times greater than the intraspecific ovine difference. These findings suggest that the strains of wild sheep from which domestic sheep originated were more closely related than were the B. primigenius subspecies which gave rise to B. indicus and B. taurus cattle. Datings based on complete mtDNAs suggest that the bovine and ovine lineages diverged about 30 million years before present. This dating is considerably earlier than that proposed previously.

Animals↗

The comparison of reliabilities in dental imaging methods.

OBJECTIVES: Common practice in the statistical comparison of imaging instruments with limited reproducibility consists in the separate estimation of the instrument's reliabilities. However, as soon as one of the imaging methods is subject to item-specific bias (which has to be expected in many dentomaxillofacial imaging procedures), this approach will end in severe errors in reliability computation and in corresponding erroneous clinical conclusions. This paper seeks to point out these effects and to illustrate a more appropriate model for the comparison of instrumental reliabilities. METHODS: A standard reliability model was adjusted for item-specific bias and illustrated by the comparison of twice repeated planimetric cephalometry versus twice repeated noninvasive orthodontic video imaging (based on the Digigraph 100 device) in 50 children; the anterior cranial base length was used for illustration. RESULTS: The proposed model revealed pronounced inferiority of the video-based imaging system concerning its reliability compared with the X-ray based standard. Analysis using separate estimation of the two reliabilities would result in the reverse conclusion and thus falsely establish video imaging, which is in fact less reliable, as a superior diagnostic method. CONCLUSION: The reliabilities of dentomaxillofacial imaging methods have to be adjusted for potential item-specific bias to avoid the erroneous conclusion of the superiority of a diagnostic innovation.

Adolescent↗

[Topical treatment of atopic dermatitis with Hypericum cream. A randomised, placebo-controlled, double-blind half-side comparison study].

BACKGROUND: Recent investigations suggest an anti-inflammatory and antibacterial effect of hyperforin, which is a major constituent of Hypericum perforatum L. (Saint John's wort). OBJECTIVE: In a half-side comparison study we assessed the efficacy of a cream containing Hypericum extract standardized to 1.5% hyperforin (verum) in comparison to the corresponding vehicle (placebo) for the treatment of subacute atopic dermatitis. The study design was a prospective randomized placebo-controlled double-blind single center study. METHODS: In twenty one patients suffering from mild to moderate atopic dermatitis (mean SCORAD 44.5) the treatment with verum or placebo was randomly allocated to the left or right site of the body, respectively. The patients were treated twice daily over a period of four weeks. Eighteen patients completed the study. The severity of the skin lesions on the left and right site was determined by means of a modified SCORAD-index (primary endpoint). RESULTS: The intensity of the eczematous lesions improved on both sites of treatment. However, the Hypericum cream was significantly superior to the vehicle at all clinical visits (days 7, 14, 28) (p<0.05). Skin colonization with Staphylococcus aureus was reduced by both verum and placebo, showing a trend to better antibacterial activity of the Hypericum cream (p=0.064). Skin tolerance and cosmetic acceptability was good or excellent with both the Hypericum cream and the vehicle (secondary endpoints). CONCLUSION: Hypericum cream was significantly superior to its vehicle in the topical treatment of mild to moderate atopic dermatitis. The therapeutic efficacy of the Hypericum cream should be evaluated in further studies with larger patient cohorts, in comparison to standard therapeutic agents (i.e. corticosteroids).

Adolescent↗