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.     

Low birthweight in African Americans: does intergenerational well-being improve outcome?

The primary antecedent of infant mortality is low birthweight. Vital statistics data have shown that women of low socioeconomic status, regardless of race, are at greater risk for delivering low birthweight infants; however, prevailing data show that black women of the same socioeconomic status as white women have a twofold higher risk of giving birth to an infant weighing < 2500 g and a threefold risk of delivering a very low birthweight infant weighing < 1500 g. There is also evidence that intergenerational effects on birth outcome exist. However, virtually all studies of the effect of socioeconomic status on perinatal outcome have been cross-sectional; the effect of sustained intergenerational well-being has not been measured. To address this gap, this study was designed to demonstrate that in an African-American population with sustained high socioeconomic status and equal risk factors, the birthweight distribution and other reproductive outcomes are the same as those for comparable US white populations. Preliminary findings are reported here.     

Interaction between rod and cone systems in dichoptic visual masking

The brightness of a brief flash of light is reduced by the suitable presentation of a second flash in an adjacent region of the visual field. This making effect (metacontrast) can be induced dichoptically, that is with the test flash presented to one eye and the masking flash to the other. By a suitable choice of wavelengths and conditioning field, the test flash may be arranged to effectively stimulate only rod receptors and the masking flash only cone receptor. A dichoptic masking effect is still obtained.     

Effects of cholinergic and adrenergic blocking agents on the activity of the eccrine sweat glands

1. The effects of blocking agents on the responsiveness of the cast' pad and human forearm sweat glands have been studied.2. Of the anti-adrenergic substances examined (dibenamine, phenoxybenzamine, bretylium, guanethidine and phentolamine) only high doses of guanethidine and phentolamine produced any consistent and significant measure of blockade, and small doses of atropine were as effective as these large doses of guanethidine or phentolamine.3. It is concluded from the blockade of chemical stimulation as well as transmission by these substances that (1) there are only cholinergic fibres innervating eccrine sweat glands, and (2) any inhibitory action by anti-adrenergic substances is due to interaction with cholinergic receptors in the glands.     

Impaired proliferative responses of peripheral blood B cells from splenectomized subjects to phorbol ester and ionophore.

The responses of peripheral blood B cells to mitogenic stimulation were examined in 12 splenectomized subjects without residual splenic function, as determined by pitted erythrocyte counts. These were compared to a group of healthy controls matched for age and sex. Polyclonal anti-immunoglobulin evoked a normal transient elevation in intracellular free Ca2+ in splenectomized subjects, thereby suggesting that the early events of the signal transduction pathway are not impaired. However, mitogenic stimulation by pre-treatment with phorbol ester and culture in presence of a calcium ionophore (Ionomycin) resulted in reduced uptake of 3H-thymidine and subsequent proliferation. Nevertheless, entry into the mitotic cycle, as assessed by expression of Ki67, was slightly, but not significantly impaired. Unlike in normal controls, where up to 7% of freshly-isolated B cells were Ki67+, almost no Ki67+ peripheral B cells were observed in splenectomized subjects. The data are consistent with the hypothesis that peripheral B cells in splenectomized subjects are in a reduced state of activation compared with normal controls and require additional growth factor stimulation before they can undergo mitosis.     

Retinoic acid receptor beta variant‐related colonic hypoganglionosis

Retinoic acid receptor beta (RARB) variants are heavily linked to pathologies of neural crest cell migration. The purpose of this report is to present a 23‐month‐old male with the previously described R387C RARB gain‐of‐function variant whose gastrointestinal issues and long‐term constipation lead to the discovery of colonic hypoganglionosis. This case further delineates the pattern of malformation associated with RARB variants. The findings are also consistent with the known etiology of aganglionic colon due to failed neural crest cell migration.     

Defective potassium currents in ataxia telangiectasia fibroblasts

Similarities exist between the progressive cerebellar ataxia in ataxia telangiectasia (AT) patients and a number of neurodegenerative diseases in both mouse and man involving specific mutations in ion channels and/or ion channel activity. These relationships led us to investigate the possibility of defective ion channel activity in AT cells. We examined changes in the membrane potential of AT fibroblasts in response to extracellular cation addition and found that the ability of AT fibroblasts to depolarize in response to increasing concentrations of extracellular K⁺ is significantly reduced when compared with control fibroblasts. Electrophysiological measurements performed with a number of AT cell lines, as well as two matched sets of primary AT fibroblast cultures, reveal that outward rectifier K⁺ currents are largely absent in AT fibroblasts in comparison with control cells. These K⁺ current defects can be corrected in AT fibroblasts transfected with the full-length ATM cDNA. These data implicate, for the first time, a role for ATM in the regulation of K⁺ channel activity and membrane potential.