Novel explant model to study mechanotransduction and cell-cell communication.

To understand in situ behavior of osteocytes, we characterized a model of osteocytes in their native bone matrix and demonstrated real-time biologic activity of osteocytes while bending the bone matrix. Using 43 male Sprague-Dawley rats, dumbbell-shaped explants were harvested from stainless steel femoral implants after 6-12 weeks and incubated in culture medium or fixed. Sixteen specimens were used to determine bone volume density (BV/TV), volumetric bone mineral density (BMD) and histology for different implantation periods. Osteocyte viability was evaluated by L-lactate dehydrogenase (LDH) activity in 12 cultured explants. Confocal microscopy was used to assess tracer diffusion in three explants and changes in osteocyte pH of a mechanically loaded explant. From 6 to 12 weeks, explant BV/TV and volumetric BMD trended up 92.5% and 101%, respectively. They were significantly and highly correlated. Tissues were uniformly intramembranous and all bone cell types were present. Explants maintained LDH activity through culture day 8. Diffusion at 200 microM was limited to 1,209 Da. Explants appeared capable of reproducing complex bone biology. This model may be useful in understanding osteocyte mechanotransduction in the context of a physiologically relevant bone matrix.     

Growth of children from 0-5 years: with special reference to mother's smoking in pregnancy

A cohort of 1163 pregnant women in two small towns in South Wales, UK, was identified and followed until the children born to them were five years of age. Growth in these children is described and a number of determinants identified. Social-class differences were very small at birth but differences in height became clear by the age of two years and in head circumference before this. In height the differences were largely accounted for by greater growth in social class I, but there was a gradient in head circumference throughout all the social classes. The social class effects gradually increased as the children became older. Parity of the mothers had a small effect on size at birth but age of the mother had no effect once parity was allowed for. Data on illnesses in the children were collected but no effect on growth could be detected. By far the most important determinant of growth which could be controlled is maternal smoking. About 40% of the women smoked, about 17% heavily (15 or more cigarettes per day) and the prevalence of smoking altered little during pregnancy. There was a graded effect of smoking on growth up to a 9% deficit in birth-weight, a 2% deficit in length at birth and a 1.5% deficit in head circumference in the babies born to the mothers who smoked most heavily (25 or more cigarettes per day) compared with non-smokers. There effects decreased with age but there were still residual effects at age five years.     

Intrathecal morphine for post-thoracotomy pain

We wished to investigate possible differences in the duration of postoperative analgesia and the incidence of respiratory depression after the intrathecal injection in the lumbar area of 10 micrograms/kg morphine in hypobaric and hyperbaric solution for relief of post-thoracotomy pain. Twenty-nine patients received morphine plus dextrose (hyperbaric) and 21 received morphine in preservative-free normal saline. The duration of analgesia was longer with the morphine in the normal saline group than in the hyperbaric group (P less than 0.04). One patient developed delayed respiratory depression. Our data support the use of morphine in normal saline mixtures for greater duration of analgesia after thoracic operations.     

Arthrodesis for chronic static scapholunate dissociation: a prospective study in 12 patients.

Twelve patients had limited arthrodesis between the scaphoid and the lunate for chronic static scapholunate dissociation using internal plate osteosynthesis. The median time between the injury and surgery was 50 months (range 9-180). They were followed up for a year postoperatively. Preoperative symptoms were pain, functional impairment, and restricted movement. During operation the scapholunate interosseous ligament was completely torn and the scaphoid malrotated in all patients. The range of motion was measured preoperatively and postoperatively, and the unaffected side used for control. For all patients except one postoperative extension, flexion, and radial deviation had considerably decreased. However, supination increased in seven of 12 patients postoperatively and so did pronation in seven of 12 patients. One patient (case 12) had an improved range of motion postoperatively in all directions. The mean grip strength was 76% of the unaffected side preoperatively, and has increased to 85% postoperatively. We found that bone healing was rare and most arthrodeses healed by a fibrous union. We found no correlation with preoperative arthrosis and clinical outcome. One patient had retired from work before operation because of back pain and one because of age. Two patients had taken early retirement because of wrist pain, and one patient was still on sick-leave at the follow-up a year postoperatively. Five patients returned to full-time work and two patients to part-time work. Four patients were on long-term sick-leave preoperatively and three of them returned to their previous occupations. Analysis of the patients' subjective outcome (including pain and functional scores) showed overall satisfaction, and objective data show that scapholunate arthrodesis for chronic static scapholunate dissociation provides substantial improvement over the preoperative condition.     

Hypoplasia of the cerebellar vermis in neurogenetic syndromes

There are conflicting reports on the relationship between cerebellar vermal lobule hypoplasia and autism. Using quantitative magnetic resonance image analysis, we measured the cerebellar vermis in 125 normal individuals with a broad age range and 102 patients with a variety of neurogenetic abnormalities. We conclude that hypoplasia of cerebellar vermal lobules VI and VII is a nonspecific finding that even occurs in several conditions without autistic behavior. This suggests that it is not a specific neuroanatomical marker for autism, nor is cerebellar dys- genesis likely to be solely responsible for clinical autistic behaviors.     

Patient-Physician Pairing: Does Racial and Ethnic Congruity Influence Selection of a Regular Physician?

Many public and private sector efforts are devoted toward increasing the training of physicians from under-represented minority groups, yet little has been documented regarding the association between physicians' racial backgrounds and the patient populations they serve. To address this question, we use 1987 National Medical Expenditure Survey to examine the impact of race/ethnicity on the matching between physician and patients. Our results show that minority patients are significantly more likely to report having a minority physician as their regular doctor. We estimate that minority patients are five times as likely as non-minorities to report that their regular physician is a member of a racial/ethnic minority. This effect is especially pronounced among Hispanics who identify a Hispanic physician as their regular provider 19 times more often than non-minorities. After controlling for other socio-economic factors, both these figures remain significant, but drop by approximately one-half. These results support the notion that minority patients tend to see minority physicians at a disproportional rate independent of other socio-economic factors.     

Neurochemical mechanisms mediating the behavioral and cognitive effects of nicotine

Data are reviewed, largely from experiments in the authors'laboratory, that suggest three modes of action of systemic nicotine in producing three different types of effect upon behavior and cognitive function. (1) Preexposure of a stimulus without consequence makes it harder subsequently to form associations to that stimulus, a form of selective attention known as latent inhibition. Latent inhibition is blocked by nicotine, an effect that is apparently mediated by a nicotine-induced increase in dopamine release in the nucleus accumbens. (2) A single dose of nicotine proactively increases the partial reinforcement extinction effect measured several weeks later: that is, resistance to extinction is decreased by nicotine in animals that have been trained on a continuous reinforcement schedule, and increased in animals trained on a partial reinforcement schedule. This effect appears to be due to increased synthesis of tyrosine hydroxylase in the cell bodies of noradrenergic neurons in the locus coeruleus, followed by axonal transport to the hippocampus and increased synthesis and release of noradrenaline in that structure. (3) Nicotine improves vigilance in animals with cognitive deficits due to destruction of the forebrain cholinergic projection system, either as a consequence of excitotoxic lesions of the nuclei of origin of this system or after prolonged alcohol consumption; and also in human subjects with Alzheimer's disease (in which this system undergoes degeneration). This effect is most likely due to an action at denervated cholinergic synapses in the hippocampus and neocortex. © 1994 Wiley-Liss, Inc.