A case of familial tumoral calcinosis/hyperostosis-hyperphosphatemia syndrome due to a compound heterozygous mutation in GALNT3 demonstrating new phenotypic features.

SUMMARY: A new case of familial tumoral calcinosis (FTC)/hyperostosis-hyperphosphatemia syndrome (HHS) due to a novel compound heterozygous mutation in N-acetylgalactosaminyltransferase 3 (GALNT3) and with new phenotypic findings is presented. The response in serum phosphate and fibroblast growth factor 23 (FGF23) to medical treatment is detailed. This case expands the genotype and phenotype of FTC/HHS and gives insight into its treatment and pathophysiology. INTRODUCTION: FTC and HHS are caused by mutations in FGF23, GALNT3, or KLOTHO. They are characterized by hyperphosphatemia, increased phosphate reabsorption, and elevated or inappropriately normal serum 1,25-dihydroxyvitamin D(3) (1,25-D(3)); FTC is associated with calcific masses, and HHS with diaphyseal hyperostosis. METHODS: A 36-year-old woman presented with abnormal dental X-rays at age 12 and was hyperphosphatemic at 22. She underwent radiographic, biochemical and genetic testing, and medical treatment. RESULTS: Serum phosphorus was 7.3 mg/dL (2.5-4.8), TmP/GFR 6.99 mg/100 mL (2.97-4.45), 1,25-D(3) 35 pg/mL (22-67). Radiographs revealed tooth anomalies, thyroid cartilage calcification, calcific masses in vertebral spaces, calcification of the interstitial septa of the soft tissue in the lower extremities, and cortical thickening of the long bones. Her total hip Z score was 1.9. C-terminus serum FGF23 was 1,210 RU/mL (20-108), but intact FGF23 was 7.4 pg/mL (10-50). DNA sequencing determined she was a compound heterozygote for mutations in GALNT3. Treatment with niacinamide and acetazolamide decreased TmP/GFR and serum phosphate, which was paralleled by a decrease in serum C-terminus FGF23. CONCLUSIONS: This case broadens the spectrum of phenotypic and genotypic features of FTC/HHS and suggests treatments to decrease renal phosphate reabsorption in the setting of a low intact FGF23.

Pain in fibrous dysplasia of bone: age-related changes and the anatomical distribution of skeletal lesions.

UNLABELLED: To determine the prevalence, distribution, age-related changes and treatment of pain in fibrous dysplasia, we studied 78 children and adults. Pain was common, more prevalent and intense in adults, sometimes requiring narcotic analgesia. It was often untreated, especially in children, and surprisingly severity did not correlate with skeletal disease burden. INTRODUCTION: Pain is common in fibrous dysplasia (FD), but relatively unstudied. We studied a well-characterized population of patients with a spectrum of disease. METHODS: Thirty-five children (16 male, 19 female, mean age 11.4 (range 5-18)) and 43 adults (15 male, 28 female, 23-62 yrs, mean age 40.3 (range 23-62)) were studied. Bone scans were used to identify the location and extent of disease. The Brief Pain Inventory was used to determine severity. RESULTS: Pain at sites of FD was common, reported by 67% of the population, but more prevalent and severe in the adult group than the children (81% and 49%, respectively p < 0.005, severity 4.1/10, and 2.8/10, respectively, p < 0.01). Surprisingly, there was no correlation between pain severity and skeletal disease burden. Children were more likely than adults to be untreated for pain (44% vs. 26%). CONCLUSIONS: Pain, which was sometimes severe, was common in subjects with FD. It was often un- or under-treated, especially in children. The prevalence and severity of pain was greater in the adult group, but unrelated to the burden of FD.

Age-related changes in the normal sagittal relationship between globe and orbit.

PURPOSE: To establish the pattern of change in globe protrusion with advancing age. The findings contribute to our understanding of orbital ageing, and are useful in the longitudinal assessment of patients with orbital disease, craniofacial abnormalities and trauma. METHODS: Ocular protrusion from the lateral orbital rim to the corneal apex was measured in 653 Caucasians aged 21-80 years. Healthy subjects only were included in the study excluding those with ocular or orbital diseases. Measurements were taken using a single instrument and observer. Data were analysed for both sexes and each eye separately. RESULTS: The mean exophthalmometry reading in both sexes (318 female and 335 male) was 19+/-2mm. Ninety-eight percent of readings between the two eyes were within 1mm of each other and no subject had greater than 2mm of asymmetry. In all groups there was a negative linear correlation between ocular protrusion and age. This correlation was found to be highly statistically significant in all groups (r=0.56-0.65, p<0.0001). There was no statistically significant difference between change in ocular protrusion with age between the left and right eye for females or males. This study demonstrates a strong association between ocular protrusion and age in a Caucasian population. This association is an almost linear reduction in ocular protrusion with increasing age between the ages of 31 and 80. Asymmetry in ocular protrusion between the two eyes does not develop with increasing age.

Children's use of phonology to infer grammatical class in vocabulary learning.

Prior studies of the relationship between phonological information and grammatical category assignment have focused on whether these relationships exist and whether people have learned them. This study investigates whether these relationships affect preschool children's vocabulary acquisition in a laboratory setting. Child participants learned 12 vocabulary words (6 nouns and 6 verbs) under three conditions, in which, (1) the syllable number/grammatical category relationship matched English, (2) the syllable number/grammatical category relationship was opposite to English, or (3) there was no relationship between syllable number and grammatical category. In the initial presentation of the words, children assumed that the novel words matched the pattern found in English. When the syllable number/grammatical category pattern matched that of English, the children learned more of the words. Phonological information also predicted error patterns. These results suggest that any account of vocabulary acquisition should consider the role of phonological information.

Evaluation of fiscal and treatment outcomes in major joint replacement.

The market demand for major arthroplasty procedures is increasing. This descriptive comparative study was conducted to examine clinical and fiscal outcomes in total joint arthroplasty patients discharged either to home or to a subacute unit. The post-acute care setting was self-selected by patients after information was provided on both options. The Self-Administered Joint Rating Questionnaire served as the primary data collection tool. Age, health status, and living alone were significant factors in post-acute care site selection. Although there were no significant differences in clinical outcomes between the two groups, overall costs were substantially different. Opportunities to maintain outcome status, while reducing total costs, in the subacute group are discussed.

Clinical skills assessment.

BACKGROUND: From September 1996, all GP registrars completing vocational training in the United Kingdom must demonstrate competence by means of a four-part assessment procedure. AIM: To look at the accuracy of one of the components of vocational training: the trainer's report. METHOD: Seventy-five registrars completing their general practice training at the end of July 1997 were invited to take part in a practical skills workshop. Eight stations were designed to test practical skills and diagnostic interpretations that were included in the trainer's report, and a clinical vignette accompanied each task. The marking schedule used was developed from the minimum standards required in the trainer's report. Twenty-nine registrars (38%) took part in the workshop. RESULTS: Only one registrar passed all eight stations. The maximum number of stations failed by any one individual was five and this doctor was the only one of the sample to ultimately fail summative assessment. The majority of registrars failed by being unable to interpret clinical findings. Twenty-five registrars (86%) responded to the follow-up questionnaire. Of these, only six felt that the stations were unrealistic. All but two registrars had spent at least six months in their hospital training doing obstetrics and gynaecology but, in spite of this, only 31% of registrars were above minimum competence for vaginal and speculum examination. CONCLUSION: With one exception, registrars passed all aspects of the trainer's report. Discrepancy was found between the trainer's report and the doctor's ability to carry out clinical procedures. There is an assumption that many of these clinical skills are being taught and assessed at undergraduate level and during the hospital component, but this cannot be taken for granted. Doubt must also be cast on whether the trainers are using the trainer's report appropriately, and whether this is a valid and reliable tool to identify skills deficient in registrars for summative assessment.

Total joint arthroplasty: a comparison of postacute settings on patient functional outcomes.

PURPOSE: This descriptive comparative study was conducted to examine functional outcomes of total joint arthroplasty patients discharged to subacute rehabilitation programs compared with those of patients discharged directly home with home physical therapy follow-up. SAMPLE: This study used a convenience sample of 96 patients having total joint arthroplasty performed by one physician within one institution. The postacute care setting was self-selected by the patients after information was provided on both options. METHODS: A patient self-evaluation questionnaire was administered preoperatively and at 1 month and 3 months after surgery. A total functional score was obtained by combining the four subscores of the questionnaire/tool: subjective, pain, walking, and activities of daily living. Quantitative data on length of stay and cost were collected for each rehabilitative site. FINDING: All patients improved significantly over time in all subscores and in total score. There was no statistically significant difference in scores between the home and the subacute group. There was a significant difference in the mean total cost of the joint replacement for the subjects who went to the subacute unit ($24,144) compared to those who went directly home ($16,918). The groups were significantly different demographically, with the subacute group being older (age > 72), and likely to have comorbidities and to live alone. CONCLUSION: The majority of total joint replacement patients can achieve acceptable functional outcomes in a reasonable length of time at home with physical therapy supervision. Rehabilitation in a subacute facility may be most useful for the elderly patient with comorbidities, particularly those who live alone.

Orthographic cues to lexical stress: effects on naming and lexical decision.

Words whose spellings represent regular phonemic patterns, such as mint, show advantages in naming and lexical decision tasks over words, such as pint, that have exceptional relations between orthographic and phonemic patterns. We have extended such phenomena to the domain of lexical stress, by showing that disyllabic words whose spellings are consistent with their stress are easier to process than words whose spellings are misleading about stress. Such words are named more quickly and are pronounced with incorrect stress less often (Experiment 1). They are also classified more quickly and accurately in lexical decision tasks (Experiments 2 and 3). These results indicate that literate speakers have learned orthographic correlates to lexical stress in English. In addition, the similarities between results in the phonemic and prosodic domains indicate that models of reading developed for the former could be extended to the latter area.

Rule- and idiosyncratically derived denominal verbs: effects on language production and comprehension.

A distinction is drawn between two classes of denominal verbs, and four experiments examine the effects of this distinction on the production and comprehension of denominalizations. Rule-derived (RD) denominals are formed from nouns belonging to semantic categories whose members share the same meaning when they are used as verbs. For instance, denominal verbs formed from vehicles generally mean "to travel/convey by x," where x represents the specific vehicle. In contrast, idiosyncratically derived (ID) denominals are drawn from categories whose members possess diverse meanings when they are used as verbs. Thus, to fish means "to try to catch fish," whereas to dog means "to chase tirelessly." Because the verb meanings of rule-derived terms are relatively predictable, they might be more easily produced and understood. Experiments 1 and 2 show that speakers are more likely to select RD terms for denominalization and are faster at creating denominal uses for RD terms. Experiments 3 and 4 show that RD denominals are rated as easier to understand than ID denominals, and that they are interpreted more uniformly across readers. The Discussion considers pragmatic accounts of the results, the theoretical basis for the distinction between RD and ID terms, and the more general point that experimental methods can be used to study creative uses of language.

Motivation of general practitioners attending postgraduate education.

BACKGROUND: The 1990 Contract encouraged general practitioners to participate in continuing medical education by providing a financial incentive. AIM: The study was designed: to determine the motivation of general practitioners attending education events; and to compare motivation and reasons for attendance pre- and post-Contract at commercial and non-commercial meetings, and at the different educational categories of Disease Management (DM), Health Promotion (HP) and Service Management (SM). METHOD: Two structured questionnaires were used. The first was sent to all general practitioners in the West of Scotland and asked about motivation pre-1990 Contract and the second, post-Contract, looked at motivation and reasons for attending a course as part of post course assessment. This latter was part of a much larger study evaluating continuing medical education. RESULTS: A total of 1161 practitioners responded to questionnaire I and 552 general practitioners attended 27 randomly selected postgraduate meetings. Finance was a motivator in 3.8% pre-Contract, and this increased to 33.3% post-Contract and was the most commonly stated reason for attendance in 81.3%. Financial incentive had the biggest influence on those attending HP sessions (91.5%), then SM (87.2%) and finally DM (78.6% (chi 2 = 8.68; P < or = 0.013). It was also important to 73% attending drug-company-sponsored meetings compared with 83.7% going to non-commercial ones. Interest was a good motivator both pre- and post-Contract, but more so for DM than other categories and drug company as opposed to non-commercial meetings (chi 2 = 9.4; P < 0.002). Lack of knowledge became a less-important motivator post-Contract, and doctors felt least knowledgeable in SM (62.2%), as opposed to DM (57.9%) and HP (23.6%) (chi 2 = 38.8; P < 0.001, with each differing significantly from both others). Doctors found the topics provided by the pharmaceutical companies more interesting (chi 2 = 9.4; P < 0.002) and the hospitality provided more alluring than scheme meetings (chi 2 = 28.6; P < 0.001). CONCLUSIONS: Finance has a major effect on attendance at postgraduate meetings but may not be a good incentive for learning. Planning for education must take into account the different motivational factors for the different categories. Reasons for attending commercial meetings differ from non-commercial ones and these events should be closely monitored.

General practitioners' views on continuing medical education.

BACKGROUND: The 1990 contract for general practitioners altered the provision of continuing medical education. AIM: This study set out to examine doctors' experiences of postgraduate education before and after the contract and their preferences for the provision of postgraduate education. METHOD: In 1991 a structured questionnaire was sent to 1959 doctors registered on the database held by the west of Scotland postgraduate office. RESULTS: An 82% response rate was obtained. Eighty eight questionnaires had to be excluded. Of 1523 respondents, 74% were entitled to study leave under the terms of their practice agreement, an increase of 15% since the introduction of the contract. When attending courses 11% reported that they always employed a locum (32% occasionally). Those who did so were more likely to be general practitioners in rural areas than in urban or mixed areas. Almost all respondents (1485, 98%) had participated in postgraduate education since April 1990. Lectures remained popular (47% of respondents indicated it was their preferred or most preferred choice) while distance learning and practice based learning were least preferred. Evening meetings and afternoon meetings were the most popular, and Wednesday and Thursday were reported to be the most suitable days for educational meetings. CONCLUSION: Organizing education for a large number of people is difficult, but individuals' preferences and difficulties have emerged which must be taken into account when doing so. In terms of attendance, postgraduate education seems to have been a success although its value in influencing quality of care is more doubtful. Perhaps the development of personal education plans may make learning more useful and relevant.

Demographic characteristics of general practitioners attending educational meetings.

There are many factors which influence general practitioners' behaviour with regard to attendance at education meetings. The demographic characteristics of general practitioners in the west of Scotland attending educational meetings were studied over a two year period. A total of 1672 doctors had attended sufficient sessions to claim their postgraduate education allowance and of these 1551 (93%) responded to the questionnaire. Overall attendance at meetings did not vary between age groups, but older doctors (those born before 1935) attended the highest mean number of education sessions on disease management and the lowest mean number on service management and health promotion. Doctors in rural areas attended fewer meetings than those in urban areas with the largest difference in the disease management category. Doctors from smaller practices attended significantly fewer sessions on service management than those from larger practices. There was no difference between sexes regarding the mean total number of education sessions attended but men attended significantly more sessions on service management and women attended more on health promotion. Full-time doctors attended more service management sessions than part-time doctors. Those who were widowed or divorced attended fewer sessions in total, the differences being greatest in service management and health promotion. Multiple regression analysis showed that location of practice, whether working full time or part time and marital status had a small but statistically significant bearing on overall attendance at meetings. Although the differences are small, these factors should be noted by education providers, negotiators and government.

Who are the providers of postgraduate medical education?

The view, background and motivation of providers of medical education was studied using a structured questionnaire which was sent to all those who organized courses for the Postgraduate Education Allowance in the West of Scotland. Two hundred and twenty-five replies were received from 254 course providers, giving an 88.6% response rate; 51.8% of course providers were general practitioners, 24.1% hospital consultants, 2% were from the pharmaceutical industry, 3.6% from commercial companies, 2.6% health board administrators, 1% general practitioners also running commercial companies, 14.9% others. Only 29.3% had training for organizing courses, although 68.7% thought special training was important. 43% used a combination of GPs and hospital consultants at their courses and a considerable number continued to organize lecture style courses. 32.8% used pre-course material and 50.7% used post-course assessment. 21.5% of providers had to provide their own secretarial back-up. The provision of continuing medical education is haphazard. The new contract has increased the amount of education available without addressing the needs of the providers. Proper training, planning and evaluation of courses, adequate funding, protected time and good secretarial back-up are required for good, meaningful and relevant continuing medical education.

Word and world order: semantic, phonological, and metrical determinants of serial position.

Animacy, word length, and prosody have all been accorded prominent roles in explanations for word order variations in language use. We examined the sequencing effects of these factors in two types of tasks. In recall tasks designed to simulate language production, we found selective effects of animacy. Animate nouns tended to appear as subjects in transitive sentences, but showed no special affinity for initial position in conjunctions within sentences, but showed no special affinity for initial position in conjunctions within sentences, suggesting a stronger involvement of animacy in grammatical role assignment than in word ordering. Word length had no significant impact: Shorter words did not appear earlier than longer words within sentences or within isolated conjunctions of nouns. Prosody had a weak effect on word order in isolated conjunctions, favoring sequences with alternating rhythm, but only in the absence of an animacy contrast. These results tend to confirm a hypothesized role for conceptual (meaning-based) accessibility in grammatical role assignment and to disconfirm a hypothesized role for lexical (form-based) accessibility in word ordering. In a judgment task, forms with animate nouns early were preferred across all constructions, and forms with short words early were often preferred both in sentences and in conjunctions. The findings suggest a possible asymmetry between comprehension and production in functional accounts of word order variations.

Memory biases in left versus right implied motion.

People remember moving objects as having moved farther along in their path of motion than is actually the case; this is known as representational momentum (RM). Some authors have argued that RM is an internalization of environmental properties such as physical momentum and gravity. Five experiments demonstrated that a similar memory bias could not have been learned from the environment. For right-handed S, objects apparently moving to the right engendered a larger memory bias in the direction of motion than did those moving to the left. This effect, clearly not derived from real-world lateral asymmetries, was relatively insensitive to changes in apparent velocity and the type of object used, and it may be confined to objects in the left half of visual space. The left-right effect may be an intrinsic property of the visual operating system, which may in turn have affected certain cultural conventions of left and right in art and other domains.

Using sound to solve syntactic problems: the role of phonology in grammatical category assignments.

One ubiquitous problem in language processing involves the assignment of words to the correct grammatical category, such as noun or verb. In general, semantic and syntactic cues have been cited as the principal information for grammatical category assignment, to the neglect of possible phonological cues. This neglect is unwarranted, and the following claims are made: (a) Numerous correlations between phonology and grammatical class exist, (b) some of these correlations are large and can pervade the entire lexicon of a language and hence can involve thousands of words, (c) experiments have repeatedly found that adults and children have learned these correlations, and (d) explanations for how these correlations arose can be proposed and evaluated. Implications of these phenomena for language representation and processing are discussed.

An analysis of the trainee year in general practice.

A survey of 12,425 trainee consultations is reported. Chronic illness only constituted 19.4% of their workload. The greatest number of consultations occurred with younger patients in the 20-30 age group. Only a small proportion of consultations involved anticipatory care and health education (0.3% and 1.1% of total workload respectively). Women patients showed a strong preference to consult a female doctor with twice as many seeing a lady trainee in preference to a male doctor. The study has implications for teaching and learning during the trainee year in general practice.

Representational momentum in memory for pitch.

When a visual pattern is displayed at successively different orientations such that a rotation or translation is implied, an observer's memory for the final position is displaced forward. This phenomenon of representational momentum shares some similarities with physical momentum. For instance, the amount of memory shift is proportional to the implied velocity of the inducing display; representational momentum is specifically proportional to the final, not the average, velocity; representational momentum follows a continuous stopping function for the first 250 ms or so of the retention interval. In a previous paper (Kelly & Freyd, 1987) we demonstrated a forward memory asymmetry using implied changes in pitch, for subjects without formal musical training. In the current paper we replicate our earlier finding and show that the forward memory asymmetry occurs for subjects with formal musical training as well (Experiment 1). We then show the structural similarity between representational momentum in memory for pitch with previous reports of parametric effects using visual stimuli. We report a velocity effect for auditory momentum (Experiment 2), we demonstrate specifically that the velocity effect depends on the implied acceleration (Experiment 3), and we show that the stopping function for auditory momentum is qualitatively the same as that for visual momentum (Experiment 4). We consider the implications of these results for theories of mental representation.