A little-known aspect of Arthur Conan Doyle (1859-1930): the call of India and a debt to Walter Scott (1771-1832).

This paper recalls the early life of Dr Arthur Conan Doyle when his writing centred briefly on India. The significance of a young female skeleton given to the museum of the Royal College of Surgeons of Edinburgh in 1879 is reviewed. Morphometric and genetic evidence is provided to show that the skeleton originated in the Andaman Islands. It is suggested that Doyle saw it during his undergraduate or early postgraduate years, leading him to introduce an Andaman Islander into his novel The Sign of the Four, published in 1890. Like his inspiring predecessor Walter Scott, Doyle wrote of India but did not visit the country: both authors learned indirectly of the Indian Raj and the Indian Medical Service. Doyle knew of the convict colony established after the Sepoy Mutiny of 1857 at Port Blair, capital of the Andamans, but the reason he chose an Islander to commit murder in London has, until now, remained contentious.

The micro-assay of the disaccharide isomers of chondroitin sulphate.

Connective tissue extracts containing the 4- and 6-sulphated isomers of chondroitin sulphate can be measured at the microgram level (approximately 10 microgram) using colorimetric assays. The chondroitin sulphates are depolymerised to disaccharides using chondroitin ABC lyase (EC 4.2.2.4). The 4- and 6-sulphated disaccharides after treatment with acid periodate are determined using a thiobarbituric acid procedure. An alkaline borate p-dimethylaminobenzaldehyde reaction is used to measure 6-sulphated disaccharide, the 4-sulphated disaccharide not forming a chromogen. Unsulphated disaccharide causes interference in both assays and if present is separated prior to assay using paper electrophoresis fractionation.

Pharmacotherapy of borderline personality disorder. Alprazolam, carbamazepine, trifluoperazine, and tranylcypromine.

Sixteen female outpatients with borderline personality disorder and prominent behavioral dyscontrol, but without a current episode of major depression, were studied in a double-blind, crossover trial of placebo and the following four active medications: alprazolam (average dose, 4.7 mg/d); carbamazepine (average dose, 820 mg/d); trifluoperazine hydrochloride (average dose, 7.8 mg/d); and tranylcypromine sulfate (average dose, 40 mg/d). Each trial was designed to last six weeks. Tranylcypromine and carbamazepine trials had the highest completion rates. Physicians rated patients as significantly improved relative to placebo while receiving tranylcypromine and carbamazepine. Patients rated themselves as significantly improved relative to placebo only while receiving tranylcypromine. Patients who tolerated a full trial of trifluoperazine showed improvement, those receiving carbamazepine demonstrated a marked decrease in the severity of behavioral dyscontrol, and those receiving alprazolam had an increase in the severity of the episodes of serious dyscontrol. As an adjunct to psychotherapy, pharmacotherapy can produce modest but clinically important improvement in the mood and behavior of patients with borderline personality disorder. As a research tool, patterns of pharmacological response may provide clues to biological mechanisms underlying dysphoria and behavioral dyscontrol.

CSF metabolites in borderline personality disorder compared with normal controls.

Cerebrospinal metabolites were measured in 17 patients with borderline personality disorder and 17 normal controls. There were no significant differences between the two groups in levels of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), or 3-methoxy-4-hydroxyphenylglycol (MHPG). Within the borderline group, lower levels of CSF 5-HIAA were significantly associated with a history of genuine suicide attempts, but were not associated with violence, self-mutilation, or with the presence of major depression. Thus, CSF 5-HIAA levels are not distinctively low in a diagnostic group characterized by impulsivity and suicidal behavior, but within that group may be associated with genuine suicide attempts.

Alprazolam-induced dyscontrol in borderline personality disorder.

The authors report a significant increase in dyscontrol in patients with borderline personality disorder who were taking alprazolam during a double-blind, placebo-controlled crossover study. They suggest that caution be used in prescribing alprazolam to patients with similar histories.

Positive effects of carbamazepine on behavioral dyscontrol in borderline personality disorder.

In a double-blind crossover trial, carbamazepine, an anticonvulsant with primary effects on subcortical limbic structures, decreased the severity of behavioral dyscontrol in 11 women with borderline personality disorder significantly more than placebo. The authors emphasize the preliminary nature of their findings and discuss alternative hypotheses regarding mechanisms by which carbamazepine might influence behavioral dyscontrol.

Dysphoria associated with methylphenidate infusion in borderline personality disorder.

Two patients with borderline personality disorder experienced dramatic dysphoric episodes after acute administration of intravenous methylphenidate in a double-blind manner. These dysphoric episodes were similar to those which occurred spontaneously under conditions of psychological stress. Case histories and the behavioral and cardiovascular effects of the infusions are described. The pharmacology of methylphenidate is discussed in order to elucidate possible mechanisms mediating the observed responses to this drug.

Neuropsychological testing of patients with borderline personality disorder.

OBJECTIVE AND METHOD: This study examined whether a battery of neuropsychological tests could detect cognitive deficits--particularly in the areas of perception, learning, and memory--in patients with borderline personality disorder. The test battery was completed by 16 research outpatients with borderline personality disorder, typified by behavioral dyscontrol and diagnosed according to DSM-III-R criteria and the Diagnostic Interview for Borderline Patients. A comparison group of 16 normal volunteers also completed the test battery. RESULTS: The performance of the borderline patients was significantly impaired in comparison with that of the normal group on memory tests requiring uncued recall of complex, recently learned material. Cues given on an auditory memory task partially corrected that deficit. The patients' performance was also significantly impaired on several visual perceptual tests. These deficits do not appear to have been attributable to attentional problems, psychomotor impairment, current major depression, or history of alcohol abuse. CONCLUSIONS: The observed difficulties in separating essential from extraneous visual information and in recalling complex material may be relevant in understanding some of the clinical features of borderline personality disorder. The observed memory improvement resulting from cueing suggests specific strategies that may be used to aid patients' recall of complex material.

Mood variability: a study of four groups.

OBJECTIVE: The authors' goal was to determine whether self-rated patterns of mood regulation differed among patients with major depression, patients with borderline personality disorder, patients with premenstrual syndrome (PMS), and normal subjects. METHOD: Fourteen days of morning and evening mood self-ratings on a visual analog scale were analyzed for 65 female subjects (10 with major depression, 16 with borderline personality disorder, 15 with PMS, and 24 without psychiatric diagnoses). For each individual, the mean and standard deviation of morning and evening ratings, the mean absolute change in mood from one day to the next, and the change from morning to evening were determined. RESULTS: The four groups differed significantly on every measure of mood and mood variability except diurnal variation. As expected, the group with major depression had the lowest global ratings and a low degree of variability. The group with borderline personality disorder was less depressed than the group with major depression and showed a high degree of mood variability. Autocorrelation analysis suggested that mood ratings in borderline personality disorder vary randomly from one day to the next. The mood variability over the 14 days of the patients with PMS was significantly greater than that of normal subjects. CONCLUSIONS: The visual analog scale can capture patterns of mood and mood variability thought to be typical of these diagnostic groups. Mood disorders differ not only in the degree of abnormal mood but also in the pattern of mood variability, suggesting that mechanisms regulating mood stability may differ from those regulating overall mood state.

Histopathology and the future.

A plea is made for a revolution in diagnostic histopathology. In the present account a brief analysis is given of the drawbacks to existing methods used in the histopathological laboratory and suggestions are made for research in those methods which could lead to progress in the speed and sensitivity of diagnosis and to great economies in histopathological practice. The abolition or replacement of certain techniques used at present is proposed.

Preparation of unfixed undemineralized bone sections: the Bright bone cryostat.

A bone cryostat is described with which cold sections of unfixed, undemineralized calcified tissue can be prepared. The bone cryostat is suitable for the preparation of the sections required for the histochemical and immunofluorescent study of bone, for electron microprobe analysis, and for bone and joint autoradiography with soluble compounds.

Advances in the microscopy of osteoarthritis.

This review describes recent contributions made by microscopy to the understanding of osteoarthritis, a clinical syndrome the pathological features of which are well defined by classical white light microscopy. The fluorescence and reflected light, conventional and scanning optical microscopy of excised osteoarthritic tissue preparations, from human and animal sources, has enabled the identification of cell proteins such as S100, of matrix components such as the proteoglycans and collagens, and of adhesion molecules including fibronectin, the integrins and tenascin. Comparable microscopic studies have been made of cell and tissue culture preparations of osteoarthritic cartilage and synovium. Scanning optical microscopy also allows the rapid measurement, in hydrated osteoarthritic tissues, of cell density, cell size, surface roughness and other parameters. The importance of water in sustaining the physical attributes of cartilage is accepted and new forms of electron microscopy can play important parts in the study of unfixed osteoarthritic cartilage. These methods include the low temperature scanning electron microscopy and electron probe x-ray microanalysis of hydrated bulk material and the high resolution transmission electron microscopy of low temperature replicas of cartilage surfaces. Understanding of osteoarthritis has been facilitated by these advances and will continue to be enhanced as new techniques of microscopy evolve.

Neuroendocrine effects of limbic activation by electrical, spontaneous, and pharmacological modes: relevance to the pathophysiology of affective dysregulation in psychiatric disorders.

1. Literature is reviewed that implicates various limbic structures (particularly amygdala and hippocampus) in the modulation of stress-associated neuroendocrine systems. 2. Procaine and related local anesthetics may show a selective proclivity for activating limbic structures. 3. Procaine stimulates ACTH-cortisol and prolactin, but not growth hormone secretion. This pattern is most comparable to that elicited by stimuli which act bilaterally on temporal lobe and limbic areas. 4. Procaine may be a useful agent for helping to elucidate the anatomic and physiologic basis for mood, endocrine, and cognitive dysregulation associated with stress and affective disorders. 5. The endocrine concomitants of limbic activation may have relevance to the course and symptom complex of affective disorders and related psychiatric conditions.

Suicidal and parasuicidal behavior in borderline personality disorder.

One of the most perplexing and dangerous aspects of borderline personality disorder is the wide array of suicidal and parasuicidal behaviors. Close phenomenologic evaluation of these behaviors reveals that they can be differentiated into various subcategories. Approaching these behaviors with a biologic perspective may prove helpful in elucidating the underlying etiologies and therapeutic approaches.

Synovitis after surgical division of the anterior cruciate ligament of the dog.

The synovial reaction to the surgical division of an anterior cruciate ligament in inbred beagle dogs, was studied. The left ligaments of 16 animals were divided by a 'blind' technique: the right stifle joints were also explored under aseptic conditions but the cruciate ligaments were not cut. Operation was followed by the formation of a blood-stained sterile effusion and by acute synovitis, sustained on the left, transient on the right. The effusion gradually diminished, becoming serous, but haemosiderin remained within subsynoviocytic macrophages for at least 84 days and lymphocytic foci and synovial cell hyperplasia persisted for similar times. It is suggested that interpretation of the cartilage changes in this cruciate ligament division model of osteoarthrosis should take account of the extent and duration of the post-operative inflammation.

In vitro measurement of articular cartilage deformations in the intact human hip joint under load.

Using a new roentgenographic technique for measuring cartilage deformation in intact joint specimens, twenty-eight normal human hip joints from subjects twenty-five to eighty-five years old were loaded with a force of five times body weight in a testing machine. The initial unloaded thickness of the articular cartilage of the femoral head and the changes in thickness of this cartilage under load were measured roentgenographically at seven to twelve sites on each femoral head. These measurements showed that the deformations of femiral-head articular cartilage under load in the intact joint are non-uniform and increase greatly with age. In twelve specimens measurements were also made of the increase in cartilage deformation with time when the load of five times body weight was maintained on the joint. A single osteoarthrotic joint was also studied. The experimental findings imply changes in the fundamental mechanical properties of the cartilage with age, which probably result from age-related alterations in cartilage microstructure and chemical composition.

Cerebral structure in borderline personality disorder.

Computed tomographic (CT) scans of brains of patients with borderline personality disorder and normal volunteers were analyzed for ventricle-brain ratios, third ventricular size, and evidence of frontal lobe atrophy. There were no significant differences between the two groups on any of these measures except for a narrower third ventricle in borderline patients, which could be accounted for by the narrower third ventricle observed in female subjects overall. While borderline patients may show signs of subtle neurological dysfunction, they do not show evidence of structural brain pathology.

Improvement in attitudes toward the elderly following traditional and geriatric mock clinics for physical therapy students.

The purpose of this study was to determine whether the attitudes of students in a physical therapy education program toward the elderly could be influenced positively by (1) having classroom discussion led by an individual with expertise in geriatrics and (2) having only individuals aged 65 years or older participate in a specially designed geriatric mock clinic (GMC). Subjects were 47 first-year students divided into a control group (n = 24) and an experimental group (n = 23). Students in the control group participated in two 4-week clinical rotations. Students in the experimental group participated in one 5-week clinical rotation and in one 3-week GMC. Students in both groups were given a pretest and a posttest administration of the Kogan Old People Scale to assess their attitudes toward the elderly. No significant difference was found between the two groups' overall attitude scores on the pretest or the posttest results. Overall, positive attitude scores increased significantly for both groups, although the increase was greater for the experimental group than for the control group. Negative attitude scores decreased significantly for the experimental group, but did not change for the control group. We concluded that both traditional clinical rotations and a specially designed GMC influenced the students positively. Suggestions have been made for the Clinical Instructor who wishes to influence physical therapy students' attitudes to meet the increasing needs of the elderly patient population.

Mandatory continuing education or periodic reexamination?

A descriptive study of physical therapists located primarily in the southeastern United States was undertaken to determine their opinions concerning mandatory continuing education or reexamination for license renewal. A majority of the 1,187 respondents favored continuing education rather than reexamination. Of those favoring continuing education, a majority prefer a yearly minimum requirement of at least 10 hours, a three-year review cycle, a sharing of costs by therapists and employers, provision of courses by the national association, approval of courses by the district or state association, and awarding of credit for demonstrated improved performance at the course. Of those favoring periodic reexamination, a majority preferred a five-year cycle, self-assessment methods available prior to reexamination, a sharing of costs by therapists and government, and an oral examination that the national association would compose but academic institutions administer. Both groups favor probationary status for noncompliance. Based on the findings, some implications for adoption and implementation of either system for the physical therapy profession are discussed.

Improving physical therapy students' clinical problem-solving skills: an analytical questioning model.

The purpose of this study was to assess the effectiveness of a model for teaching problem-solving skills to first-year physical therapy students using the Watson-Glaser Critical Thinking Appraisal (CTA) and participant feedback. We used a pretest-posttest control group design. Subjects were 31 first-year physical therapy students divided into a Control Group (n = 15) and an Experimental Group (n = 16). Students in the Experimental Group used the problem-solving model during a four-week clerkship. No difference was found between the Experimental and Control Groups' performance on the CTA. Subjectively, students in the Experimental Group and their Clinical Instructors found the model to be an effective tool that aided students' understanding of patient assessment and treatment program planning. The need for an objective assessment tool of problem-solving models in physical therapy is discussed.