T-Cell receptor αβ and γδ T cells in rat and human skin — are they equivalent?

In the not-so-distant past the skin was generally viewed as a passive target for immune-mediated injury. Over the last decade, however, concepts of a previously unrecognized role for the skin have unfolded, whereby resident bone marrow-derived leukocytes (e.g. Langerhans cells and T cells) initiate and regulate the immune responses that protect it. Their combination with other immunomodulatory resident cells (e.g. keratinocytes, melanocytes, endothelial cells, fibroblasts) led to the idea that the skin may function as a self-sustaining lymphoid tissue. Although T lymphocytes or, at least, certain subpopulations thereof have the general propensity to populate epithelial tissues, there exist major species differences regarding the phenotype of intraepidermal T cells. The purpose of this review is to fill gaps in our understanding of the relationship of rodent skin T cells to T cells identified in human skin and the normal physiologic and pathologic role(s) of these cells.     

Abnormal Digital Pressure Measurements in Diabetic Neuropathic Foot Ulceration

The diabetic neuropathic ulcer is typically slow to heal and recurrent. Macrovascular insufficiency is usually excluded as foot pulses are present and ankle:brachial pressure ratios are not decreased. These assessments cannot however exclude more distal vascular disease. Digital pressure measurements enable a reliable assessment of the distal peripheral vascular status to be made. The aim of this study was therefore to use toe pressures to assess the contribution of distal ischaemia in the pathogenesis of the neuropathic ulcer. Sixteen diabetic patients with recurrent neuropathic foot ulceration had their toe pressures compared to 10 neuropathic patients without a history of foot ulceration, 10 diabetic control subjects, and 11 normal subjects. Four non-diabetic patients with neuropathy and foot ulceration were also assessed. All subjects had ankle:brachial pressure indices ≧ 1. Toe pressure was assessed using laser Doppler flowmetry to record the return of skin blood flow. The toe:brachial pressure index (TBI) was then calculated. The diabetic patients with a history of recurrent neuropathic ulceration, had the lowest mean TBI, 0.63 ± 0.14 (SD), compared to the non-ulcerated diabetic neuropathy patients, the diabetic control subjects, and the normal subjects. 0.84 ± 0.11, 0.82 ± 0.1, and 0.81 ± 0.07, p < 0.01, respectively. Three of the four non-diabetic patients with neuropathic foot ulceration also had an abnormally low TBI. Reduced toe pressure measurements are thus found to be associated with neuropathic foot ulceration. The contribution of distal ischaemia in the pathogenesis of the diabetic neuropathic foot ulcer needs to be evaluated. One hundred and eight non-insulin-dependent diabetic patients who had been tested for autonomic dysfunction in 1984/85 were re-evaluated 5 years later. Autonomic function was assessed by means of four cardiovascular tests (heart rate variation during deep breathing and standing, and blood pressure variation after standing and sustained handgrip). Eighteen subjects were lost to follow-up; in the 90 patients who completed the study, both the deep breathing and the handgrip test significantly worsened (respectively from 13.7 ± 7.8 to 11.6 ± 6.3 beats min^?1 p < 0.01, and from 16.9 ± 8.2 to 12.7 ± 7.1 mmHg, p < 0.001), whereas both the 30:15 ratio and the variation of blood pressure on standing did not change. The impairment of a comprehensive evaluation score (from 2.5 ± 1.7 to 3.0 ± 1.5; p < 0.05) also confirmed the gradual deterioration of autonomic function over the study period.     

Mapping the Von Hippel -- Lindau disease tumour suppressor gene: identification of germline deletions by pulsed field gel electrophoresis

Von Hlppel—Lindau (VHL) disease is a dominantly Inheritedfamillal cancer syndrome In which affected individuals havea greatly increased predisposition to the development of haemangloblastomasof the central nervous system and retina, renal cell carcinomaand phaeochromocytoma. The VHL gene has been mapped to chromosome3p25 -p26 by genetic linkage studies and we have previouslydemonstrated that the VHL gene is tightly linked to the D3S601locus (Zmax = 18.86 at     

Normalization of the blood lactate profile in athletes

The power output-blood lactate or velocity-blood lactate relationship, the lactate "profile", is a widely used method for the evaluation of athletes. Recent observations have suggested a shift in the blood lactate profile when athletes are fatigued, as at training camps. This study was designed to determine whether the blood lactate profile could be corrected for progressive muscle glycogen depletion by normalizing for the peak exercise blood lactate concentration. Ten well-trained subjects performed incremental cycle ergometer exercise followed by supramaximal exercise (Wingate test) following 3 days of usual and 3 days of heavier than usual training. Following heavier than usual training, blood lactate accumulation was reduced during submaximal exercise such that the power output associated with a lactate concentration of 4 mM was significantly increased (3.08 vs 3.51 W/kg). The maximal blood lactate concentration was also reduced (14.8 vs 12.7 mM) although average supramaximal power output was unchanged (9.03 vs 8.92 W/kg). When the submaximal blood lactate concentrations were normalized for the maximal blood lactate concentration, there were no significant differences in the power output associated with 20% (2.6 vs 2.7 W/kg), 25% (3.1 vs 3.2 W/kg), or 30% (3.3 vs 3.5 W/kg) of maximal lactate. The results suggest that normalization based on peak exercise blood lactate may be a useful strategy for circumventing one of the primary practical barriers to the use of the blood lactate profile in athletes.     

Clinical teaching roles of athletic trainers

Studies of clinical teaching roles have not appeared in the athletic training literature. The purposes of this study were to: 1) describe clinical teaching roles of Midwest ATCs, and 2) determine the effect of educational preparation on teaching activities and opinions of ATCs. A three-part questionnaire was returned by 154 ATCs (78%) in NATA District 5. The questionnaire included demographic, teaching, and opinion items. More than 50% of the ATCs were teacher-certified and the majority had a master's or higher degree. Most ATCs clinically supervised between one to eight students who received clinical instruction about 20 hours weekly. The ATCs who taught clinically either presented information or directed tasks from five to six Role Delineation Domains. They used three or more teaching methods and six or more audiovisual aids with their presentations. The ATCs saw the importance of clinical education and the responsibility to present clinical information, and expressed positive opinions about academic preparation for clinical teaching. Those with teaching degrees felt more prepared to teach (p<.05) than did nonteachers. Teachers conducted clinical teaching activities similar to nonteachers. We concluded that less experienced athletic trainers feel educationally prepared and enjoy clinical teaching as much as their more experienced peers. The ATCs with a teaching background presented a broader content through more mature teaching methods than did nonteachers. It appeared that adequate preparation for teaching and the attainment of an advanced degree may inspire confidence in clinical teaching. These attributes may become important characteristics to look for when recruiting clinical instructors.     

Correlation of manual dexterity and comprehension with oral hygiene and periodontal status in mentally handicapped adults

Although there is relatively little information concerning the oral health of handicapped adults there is increasing evidence to suggest that their oral condition, particularly periodontal health, is poor. The present investigation involved assessment of 382 handicapped patients attending four different Adult Training Centres in Birmingham. The caries status, oral hygiene, and periodontal conditions were evaluated and the Community Periodontal Index of Treatment Need (CPITN) was calculated. In order to assess the manual dexterity and the comprehension of the trainees a standard test was devised. This consisted of timing each participant in carrying out simple instructions to pick up and position certain common objects. The results indicated high levels of plaque, calculus, and bleeding with a mean CPITN of 7.43. The mean time taken for the manual dexterity and comprehension test was 23.9 seconds with a range from 10 to 80 seconds, S.E.+/- 1.33. This compares with results from 34 "normal" adults of a mean time of 8.2 seconds +/- 1.8 with a range of 6 to 12 seconds. There was no significant correlation between the Manual Dexterity and Comprehension scores and the periodontal indices in the handicapped adults.     

The pharmacokinetics and toxicity of the anthrapyrazole anti-cancer drug CI-941 in the mouse: a guide for rational dose escalation in patients

Summary CI-941 is a new synthetic DNA-binding agent selected for phase I clinical evaluation. The drug has broad-spectrum antitumour activity against a number of murine tumours and, in contrast to doxorubicin, is unlikely to induce cardiotoxicity by a free-radical-mediated mechanism. In this study the toxicity and pharmacokinetics of CI-941 were studied in the mouse to enable the implementation of a pharmacokinetically guided dose-escalation strategy in patients. Following a single i.v. bolus injection in mice, CI-941 induced dose-dependent leukopenia. The white blood cell counts were suppressed on day 3 by 18%, 50% and 65% of control, at doses of 10, 15 and 20 mg/kg CI-941, respectively. Other toxicities such as weight loss, alopecia, diarrhoea and convulsions were observed at doses >20 mg/kg. Lethality studies in female Balb-c mice resulted in an LD₁₀ value of 20 mg/kg (95% confidence limits; range, 19–21 mg/kg) and an LD₅₀ value of 22 mg/kg (95% confidence limits; range, 21–23 mg/kg). The pharmacokinetics of CI-941 were studied at four dose levels from 1/10 of the LD₁₀ to the LD₁₀ (20 mg/kg). The drug was rapidly cleared from the plasma (250–400 ml/min per kg) at a rate approaching the cardiac output of mice, displaying triphasic plasma pharmacokinetics. The area under the plasma CI-941 concentration vs time curve (AUC) was linear with respect to the dose, up to and including 15 mg/kg (AUC=110 M x min at 15 mg/kg), but became non-linear at 20 mg/kg (AUC=277 M x min). Despite 80%–84% plasma protein binding, CI-941 was rapidly and extensively distributed into tissues, especially the kidney. Following i.v. bolus injections at doses of 1.5 and 15 mg/kg, elimination of the parent compound by urinary excretion accounted for 12%–18% of the delivered dose. A phase-I starting dose (based on that equivalent to 1/10 of the LD₁₀ in the mouse) of 5 mg/m² CI-941 is recommended for single administration schedules. In addition, a pharmacokinetically guided dose-escalation strategy, based on achieving a target AUC of 110 M x min, is proposed.     

Exploring and embracing complexity in a distance-learning curriculum for physicians.

The recent pressures on clinical medicine such as the attention to medical error and the challenges of interdisciplinary care have also exerted pressure on health professions education. Educators must now gauge how to redesign education systems to adapt quickly to these disruptions. Sometimes disruptions can be self-inflicted, such as the VA National Quality Scholars Fellowship's decision to use interactive video (IV) as its primary medium for delivering the curriculum to its six sites around the nation. The authors describe how this disruption to their education system helped to fashion a learning environment that is adaptable. Along the journey from a classroom-based curriculum to an IV-based curriculum, the authors and others involved in the program learned the basic tenets of IV sessions, redefined the roles of the teachers and learners, and discovered an IV environment that functions as a complex adaptive learning system. This distance-learning curriculum can be a model for other health professions education, since it starts with simple rules, changes from within, has a tolerance for unpredictability, and continually moves forward and transforms itself despite tension.