Biphasic solitary fibrous tumour: a report of two cases with epithelioid features.

We present two cases of solitary fibrous tumour (SFT) showing biphasic morphology with a spectrum of malignant epithelioid components. Slides prepared from formalin-fixed and paraffin-embedded tissue from both cases were stained with haematoxylin and eosin and by immunohistochemistry. Interphase fluorescent in situ hybridisation studies were performed in both cases using paraffin-embedded tissue to look for the t(X;18) translocation, thereby to exclude synovial sarcoma. Both cases showed biphasic morphology with some areas having typical benign spindled SFT morphology (including CD34 expression) and other areas having a malignant epithelioid appearance. In one of the cases, the epithelioid area, which was well circumscribed and showed packeting of cell groups, demonstrated expression of cytokeratin and epithelial cadherin but not of CD34. In the second case, the immunophenotype of the epithelioid component was similar to that of the benign SFT component. These findings suggest that epithelioid change in SFT shows a range of differentiation at one end, similar to that of a standard SFT, and at the other end, possibly acquiring epithelial characteristics.

Piperazinylpyrazines with central serotoninmimetic activity.

A series of 2-(1-piperazinyl)pyrazines was synthesized and evaluated for central serotonin-like activity. The most interesting member of the series, 6-chloro-2(1-piperazinyl)pyrazine (3a), had pharmacological properties characteristic of potent central serotoninmimetic activity and only weak peripheral serotoninmimetic action. Structural similarities between 3a and serotonin are discussed.

2-Mercaptoacetamidines as gastric antisecretory agents.

A series of N-substituted 2-mercaptoacetamidines was synthesized and evaluated for gastric antisecretory activity in dogs stimulated with gastrin tetrapeptide. The most potent analogues showed 80--95% inhibition of acid secretion after an oral dose of 8 mg/kg. Thus, these compounds represent a new structural type having significant antisecretory activity. Disulfides had essentially the same antisecretory potency as the corresponding mercaptoacetamidines, indicating a metabolic interconversion. Alkylation of the mercapto group decreased potency. Higher carboxamidine homologues such as 2- and 3-mercaptopropionamidines had very low activity. Hydroxyacetamidines and mercaptoacetamides also had low potency. Side effects observed with this series of compounds included emesis, tachycardia, and gastric bleeding.

Piperazinylquinoxalines with central serotoninmimetic activity.

Regioselective syntheses of substituted 2-chloroquinoxalines and derived 2-(1-piperazinyl)quinoxalines are described. Selectivity in regards to serotonin reuptake blocking and serotoninmimetic activities of the piperazinylquinoxalines is reported. In general, introduction of a 6-substituent into the piperazinylquinoxaline enhanced serotonin reuptake blocking activity and diminished serotoninmimetic activity. Unsubstituted and 3-hydroxypiperazinylquinoxalines had primarily serotoninmimetic activity.

Synthesis and stereospecific antipsychotic activity of (-)-1-cyclopropylmethyl-4-(3-trifluoromethylthio-5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine.

The synthesis and resolution of 3-iodocyproheptadine [(+/-)-5a] and 1-cyclopropylmethyl-4-(3-iodo-5H-dibenzo-[a,d]cyclohepten-5-ylidene)piperidine [(+/-)-5b] are described. The resulting atropisomers undergo reaction with trifluoromethylthiocopper to give optically active products without extensive racemization. In this manner, optically pure (+)- and (-)-3-trifluoromethylthiocyproheptadine [(+)-6a and (-)-6a, respectively] and (+)- and (-)-1-cyclopropylmethyl-4-(3-trifluoromethylthio-5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine [(+)-6b and (-)-6b, respectively] have been prepared. The influence of a chiral europium shift reagent on the proton and fluorine resonance signals as a diagnostic tool for the determination of the optical purities of these atropisomers is discussed. The four compounds, (+)-6a, (-)-6a, (+)-6b, and (-)-6b, were studied in squirrel monkeys for their ability to block conditioned avoidance responding. All of the antiavoidance activity was found to reside solely in the levorotatory compounds (-)-6a and (-)-6b. Further comparison of the enantiomers (-)-6b and (+)-6b showed that the ability to antagonize apomorphine-induced stereotyped behavior is confined to the levorotatory isomer (-)-6b while weak central anticholinergic activity resides solely in the dextrorotatory isomer (+)-6b. Neither (-)-6b has significant peripheral anticholinergic activity.

Comparison of the effects of timolol and other adrenergic agents on intraocular pressure in the rabbit.

The effect of timolol, propranolol, epinephrine, and isoproterenol on intraocular pressure (IOP) (measured by tonometry) were compared after topical administration in conscious rabbits. Epinephrine and isoproterenol decreased IOP in normotensive rabbits, whereas propranolol had no effect. Timolol produced only a slight and inconsistent lowering of IOP in normotensive rabbits. All four agents reduced IOP elevated by an oral water load; the adrenergic agonists were substantially more active than the two beta-adrenergic blocking agents. In alpha-chymotrypsin-induced ocular hypertension, epinephrine, isoproterenol, and timolol were essentially equally effective, whereas propranolol exhibited only weak activity. In this latter model, timolol did not lose its effectiveness after multiple instillations (three/day) over an 8-day period. The concentration of timolol in the acqueous humor after topical application of effective hypotensive doses was relatively high as compared to that found in plasma. In addition, topical doses of timolol required to lower IOP were considerably greater than those needed to reduce or block the ocular hypotensive activity of isoproterenol. The mode of action and therapeutic implications of beta-adrenergic blocking agents in glaucoma are discussed.

Studies on L-640,035: a novel antagonist of contractile prostanoids in the lung.

The effects of L-640,035 (3-hydroxymethyl-dibenzo [b,f] thiepin-5,5-dioxide) have been studied on pulmonary smooth muscle contraction in vitro and in vivo. When studied in vitro on guinea-pig tracheal chains, L-640,035 produced significant shifts in the dose-response curves to a prostaglandin (PG) endoperoxide analogue (U-44069) (pA2 7.0), PGF2 alpha (pA2 5.9) and PGD2 (pA2 6.5). L-640,035 produced no significant shift in the dose-response curves to leukotriene D4 or histamine and produced a small but statistically significant shift in the dose-response curve to 5-hydroxytryptamine (5-HT) (pA2 5.2). With the exception of PGF2 alpha, Schild analysis did not in general indicate competitive inhibition. The main metabolite of L-640,035, L-636,499, also produced significant parallel shifts in the dose-response curves to U-44069 (pA2 6.0) and PGF2 alpha (pA2 6.0), but with some reduction in the maximal contraction. When L-640,035 was administered intravenously to guinea-pigs, significant inhibition of increases in pulmonary resistance or insufflation pressure induced by U-44069 (ED50 0.16 mg kg-1), leukotriene D4 (ED50 0.25 mg kg-1) and 5-HT (ED50 3.4 mg kg-1) but not histamine (ED50 greater than 10 mg kg-1) was observed. When L-640,035 was administered intravenously to dogs a significant inhibition of increases in pulmonary resistance induced by U-44069 (ED50 0.85 mg kg-1) but not histamine (ED50 greater than 30 mg kg-1) was observed. 5 When L-640,035 was administered by the intraduodenal route to dogs at doses of 3 and 10 mg kg- significant inhibition of increases in pulmonary resistance induced by sodium arachidonate (3 mgkg1 i.v.) was observed with a duration of action of > 255 min. 6 It is concluded that L-640,035 is a novel, relatively selective, and orally active antagonist of the actions of contractile prostanoids on pulmonary smooth muscle.

The anticonvulsant action of methazolamide in mice: antagonism by various inhibitors of dopamine beta-hydroxylase.

The dopamine beta-hydroxylase inhibitors, FLA-63 and picolinic acid, antagonized the anticonvulsant action of methazolamine in mice; disulfiram and pyrimidinethiol were inactive. FLA-63 and picolinic acid, but not disulfiram or pyrimidinethiol prevented pheniprazine restoration of the anticonvulsant action of methazolamide in reserpinized mice. The present findings clearly demonstrate that differences exist among inhibitors of dopamine beta-hydroxylase regarding their ability to antagonize the anticonvulsant action of methazolamide under various test conditions.

Neural tube defects in Victoria, Australia: potential contributing factors and public health implications.

OBJECTIVES: To measure population prevalence and determine potential predictors of neural tube defects. METHOD: Analysis of all births reported to a mandated collection of perinatal data, and terminations prior to 20 weeks' gestation that have been reported to a data collection of birth defects in Victoria from 1983 to 1997. Prevalence at birth and risk ratios of infant and maternal characteristics associated with neural tube defects were calculated. RESULTS: Prevalence of spina bifida has remained steady for 15 years and was 8.8/10,000 in 1997. Anencephaly increased to 7.9/10,000 in 1997. After exclusion of pregnancy terminations, the 1997 birth prevalence was 4.5/10,000 for spina bifida and 2.4/10,000 for anencephaly. Neural tube defects are identified in 1 in 1600 fetuses, the risk being significantly higher for epileptic women (Adjusted Odds Ratio (AOR) = 3.70, 95% CI 2.25-6.07), multiple births (AOR = 4.56, 95% CI 3.46-6.02), teenage mothers (AOR = 1.47, 95% CI 1.09-2.00) compared with those aged 25-29, and women with three or more previous pregnancies (AOR = 1.40, 95% CI 1.10-1.78). The risk was lower for women of East Asian (AOR = 0.70, 95% CI 0.49-1.00) and Middle Eastern origin (AOR = 0.60, 95% CI 0.35-1.02) and these differences were approaching statistical significance. CONCLUSION: Total prevalence of neural tube defects did not decline up to 1997. IMPLICATIONS: It is unlikely that targeting 'at risk' groups identified in this study would make a difference to neural tube defect incidence. However, consideration could be given to identifying larger 'at risk' groups such as those with homocysteine metabolism defects.

Evolution of the Emergency Management of Severe Burns (EMSB) course in the UK.

The principle of the 'golden hour' is now well established and forms the basis of a growing number of instructional courses teaching a systematic approach to the management of major trauma. In April 1997, the EMSB course, developed by the Australian and New Zealand Burn Association, was adopted by the British Burn Association to meet the needs of health professionals dealing with major burn injuries in this country. The experience of the first 13 courses following the introduction of EMSB is discussed and the course is recommended as a requirement for the training of UK plastic surgeons and plastic surgery nurses.

Vinylpyridine: an unusual cause of a chemical burn.

A case of a chemical burn following cutaneous exposure to vinylpyridine is presented. This unusual injury was distinguished by the delay in onset of pain and erythema, followed by gradual resolution leaving patchy skin discolouration. The properties of vinylpyridine are outlined. This case illustrates the dangers of long-term chemical storage and the importance of proper disposal.

Congenital skin loss following Nd:YAG placental photocoagulation.

This is the first reported case of congenital skin loss following endoscopic placental laser coagulation, a new technique for the ante-natal treatment of twin-twin transfusion syndrome. The skin defect healed rapidly after birth with dressings alone, mimicking the spontaneous re-epithelialisation of a minor burn wound or aplasia cutis congenita.

Correspondences among parent, teacher, and student perceptions of adolescents' learning disabilities.

A group of 26 adolescents with learning disabilities (Grades 9 through 12), their parents, and their special education teachers were asked to rate the students' skills in each of 21 specific areas covering general ability, oral language, reading, written language, math, study skills, motivation, social skills, attention, and nonverbal skills. Correspondences in the absolute and relative ratings of parents, teachers, and students across the 21 skill areas were examined. The parents' ratings were consistent with those of the teachers in 16 areas and significantly lower than the teachers in 5 areas. The students' ratings were generally higher than those of their parents and teachers. The student-teacher differences were significant in 6 areas, whereas the student-parent differences were significant in 11 areas. Although generally lower in absolute terms than the ratings of their children, the parents' relative ratings were strikingly parallel to their children's ratings across skill areas (r = 80). Differences in the reference groups used for the ratings did not seem to account for the discrepant ratings. Possible implications of the differing perceptions of students' learning disabilities for students' self-esteem and academic progress are discussed.

The metaphor of scaffolding: its utility for the field of learning disabilities.

Over the past 20 years, an increasing number of psychologists and educators have used the notion of scaffolding as a metaphor for the process by which adults (and more knowledgeable peers) guide children's learning and development. The purpose of the present article is to provide a critical analysis of the scaffolding metaphor, with particular emphasis on its applications to the case of atypical learners. In the initial sections of the article, the origins and early applications of the metaphor are sketched. With this as background, criticisms of the metaphor raised by others are reviewed, and a proposal for an enriched version of the metaphor is presented. At the heart of the proposed revision is an emphasis on the communicational dynamics and conceptual reorganization involved in adult-child interactions. With an enriched metaphor as a frame, the next section reviews applications of the scaffolding metaphor to the study of parent-child interactions and teacher-student instructional activities involving children with learning disabilities. The strengths and limitations of this work are evaluated, and proposals are made for how to reap further benefits from applications of the scaffolding metaphor to analyses of the development and instruction of children with learning disabilities.

Individual differences in the self-image of adolescents with learning disabilities: the roles of severity, time of diagnosis, and parental perceptions.

The self-images of 49 adolescents with learning disabilities (Grades 9 through 12, mean age = 15.9) and 49 normally achieving peers (Grades 9 through 12, mean age = 16.0) were compared using the Offer Self-Image Questionnaire (OSIQ). The group with LD scored significantly lower than the comparison group on 4 of the 10 OSIQ scales. Later-diagnosed adolescents with LD scored significantly higher than early-diagnosed adolescents on two of the scales. Severity of the learning disability was not found to be related to self-image scores. In a second study, parental perceptions of the self-images of 28 of the 49 students with LD were studied by administering the Offer Parent-Adolescent Questionnaire (OPAQ) and an informal questionnaire to their parents. On 6 of the 10 OPAQ scales, parents perceived their children as having a lower self-image than the adolescents themselves reported. Significant but moderate relationships were found between parents' perceptions and adolescent self-image scores. Results of the two studies are interpreted in terms of a multidimensional conception of self-image that considers factors inherent to the individual as well as interpersonal and institutional factors.

Reducing non-attendance at outpatient clinics.

Outpatient non-attendance is a common source of inefficiency in a health service, wasting time and resources and potentially lengthening waiting lists. A prospective audit of plastic surgery outpatient clinics was conducted during the six months from January to June 1997, to determine the clinical and demographic profile of non-attenders. Of 6095 appointments 16% were not kept. Using the demographic information, we changed our follow-up guidelines to reflect risk factors for multiple non-attendances, and a self-referral clinic was introduced to replace routine follow-up for high risk non-attenders. After these changes, a second audit in the same six months of 1998 revealed a non-attendance rate of 11%--i.e. 30% lower than before. Many follow-up appointments are sent inappropriately to patients who do not want further attention. This study, indicating how risk factor analysis can identify a group of patients who are unlikely to attend again after one missed appointment, may be a useful model for the reduction of outpatient non-attendance in other specialties.

Indoor radon maps of the United States.

A recently published compilation of average radon levels in 1,729 U.S. counties with standard errors of approximately 20% is used to generate maps exhibiting these results and showing correlations over multicounty areas. Several large areas and numerous smaller areas with high radon levels are identified.

Two semi-automatic elutriators for extracting nematodes and certain fungi from soil.

Two efficient, semi-automatic elutriators for assaying soil samples for nematodes are described. The first apparatus is a four-unit elutriator which combines conventional extraction methods with the following major features: automatic mixing of 500- to 1,500-cm(3) soil samples with water (+/- air); "turbinate" sample splitters from which fractions of 1/15 or greater are passed onto 26- or 38-microm sieves for collection of larvae and adult nematodes; the capacity for collecting roots, intact egg masses, and cysts on 250-425-microm sieves; and a variable speed motorized sieve-shaker. Nematodes, after being collected on 38-microm sieves, are separated from debris by centrifugation or by Baermann trays. Secondary features include: air cylinders, solenoid valves, and time clock for automatic dumping residual soil and water; relay-controlled coarse spray nozzles activated for 5 sec every 30 sec for washing nematodes through 250-425-mum sieves; adjustable rates of water amt air flow, and tinting. The second type of elutriator operates on similar principles but costs less to construct. It requires somewhat more operator participation; sieve spraying is carried out by the operator, anti elutriators are dumped manually. Both elutriators also show promise for monitoring populations of certain other soil microorganisms.