Unifying model of carpal mechanics based on computationally derived isometric constraints and rules-based motion - the stable central column theory.

This study was part of a larger project to develop a (kinetic) theory of carpal motion based on computationally derived isometric constraints. Three-dimensional models were created from computed tomography scans of the wrists of ten normal subjects and carpal spatial relationships at physiological motion extremes were assessed. Specific points on the surface of the various carpal bones and the radius that remained isometric through range of movement were identified. Analysis of the isometric constraints and intercarpal motion suggests that the carpus functions as a stable central column (lunate-capitate-hamate-trapezoid-trapezium) with a supporting lateral column (scaphoid), which behaves as a 'two gear four bar linkage'. The triquetrum functions as an ulnar translation restraint, as well as controlling lunate flexion. The 'trapezoid'-shaped trapezoid places the trapezium anterior to the transverse plane of the radius and ulna, and thus rotates the principal axis of the central column to correspond to that used in the 'dart thrower's motion'. This study presents a forward kinematic analysis of the carpus that provides the basis for the development of a unifying kinetic theory of wrist motion based on isometric constraints and rules-based motion.

A simple tool for identifying unaffected women at a moderately increased or potentially high risk of breast cancer based on their family history.

Family history of breast cancer is a more important aspect of clinical management following the discovery of the genes BRCA1 and BRCA2. The authors developed a short questionnaire to categorize risk according to breast cancer history in close relatives. It was completed by 559 women attending for screening mammograms in Sydney, Australia. Twenty-three per cent reported a family history sufficient to be classified at a moderately increased or potentially high risk according to national guidelines (category II or III). Only 29 women (5%) made errors such that their risk category could not be determined. Validation of responses from 89 women, 44 from category II or III, found 100% agreement with classification after interview by a genetic counsellor. This questionnaire has the potential to accurately triage risk based on a woman's knowledge of her family history, and could be used in a variety of settings to identify women who may require further assessment, management and referral advice.

Response of developing rat fast muscles to partial denervation.

The changes of motor unit size following partial denervation of the extensor digitorum longus muscles in rat neonates (at five to six days) and later in development (at 18-20 days) were studied. Extensor digitorum longus muscle is innervated mainly by axons from L4 ventral ramus and to a lesser extent by axons from L5 ventral ramus. In neonates the motor units in extensor digitorum longus are large, and they become restricted to their adult size during the first two weeks of life. Six to 10 weeks after removing the major input to extensor digitorum longus, i.e. L4 ventral ramus at five to six days, the motor unit sizes of axons in the remaining L5 ventral ramus decrease from their expanded neonatal territory to their adult smaller size. In spite of partial denervation the motor units remain small throughout the animal's life and the denervated muscle fibres do not become "occupied" by sprouts from the remaining axons of L5 ventral ramus motor nerves. Partial denervation of extensor digitorum longus muscles at 18-20 days by section of the L4 ventral ramus leads to the expected two- to three-fold increase in the size of motor units of L5 ventral ramus. These results are taken to show that fast motor units of neonatal rats are unable to maintain their enlarged peripheral field, while later in development their axons can sprout and occupy an expanded peripheral field.

Partial denervation of the rat soleus muscle at two different developmental stages.

Rat soleus muscles were partially denervated at two developmental stages. The L5 ventral ramus was sectioned in rats which were 4-6 days old, when the motor unit size of soleus muscles was still large, and at 17-19 days, when motor unit territory reached its adult value. The response of axons in the L4 ventral ramus to this procedure was then investigated. The removal of the L5 ventral ramus at 4-6 days results in an initial brief increase of motor unit size, after which the motor units retain the territory they occupied at 4-6 days. After removal of the L5 ventral ramus at 17-19 days, the L4 ventral ramus is able to expand to occupy a territory comparable in size to that of animals operated at 4-6 days. In both cases the final percentage of mean motor unit tension is two- to three-fold greater than that in normal muscles. Although the final motor unit territory is similar for both groups, it is achieved by different mechanisms. In animals operated on at 4-6 days the normal elimination of terminals does not occur, and the large neonatal motor units are retained, whereas in animals operated on at 17-19 days the peripheral field of L4 axons expands by axonal sprouting.

The Effect of Inhibiting the Calcium Activated Neutral Protease, on Motor Unit Size after Partial Denervation of the Rat Soleus Muscle.

Rat soleus muscles were partially denervated by removal of the L5 ventral ramus at either 4 - 6 days or 17 - 19 days. Local application of leupeptin, a potent inhibitor of the calcium activated neutral protease to these operated muscles, resulted in a significantly greater maximal tetanic tension and motor unit size, when compared to untreated partially denervated muscles. This was achieved in the 4 - 6 day operated animals by an increased number of terminals and in the 17 - 19 day old animals by increased number of axonal sprouts that maintain contact with muscle fibres. In both groups of operated animals in the leupeptin treated muscles large numbers of motor units were able to maintain or achieve an expanded territory, whilst the size of the largest motor unit did not appear to be increased. It is proposed that leupeptin exerts its effect by inhibiting the degradative action of the neuronal calcium activated neutral protease on the axonal cytoskeleton. Such inhibition may act to prevent or decrease the degradation of cytoskeletal structures in the nerve terminal, and so provide protection for weak terminals at a synapse and growth cones of sprouting axons following partial denervation.

Relationship between cell age, glutathione and cation concentrations in sheep erythrocytes with a normal and a defective transport system for amino acids.

Percoll density gradients were used to separate sheep erythrocytes according to cell age. Erythrocytes with low intracellular levels of glutathione (GSH) caused by an inherited deficiency of the System C amino acid transporter exhibited large age-related decreases in GSH and K+ content. In contrast, there was no age-related loss of intracellular GSH in normal sheep erythrocytes or in sheep erythrocytes with low GSH resulting from a diminished activity of gamma-glutamylcysteine synthetase. Loss of GSH from amino acid transport-deficient erythrocytes was paralleled by the progressive appearance of Heinz bodies in the cells, indicating an increased susceptibility to oxidative damage.

Clinical and immunologic spectrum of the DiGeorge syndrome.

This report summarizes the spectrum of clinical and immunologic findings gathered prospectively in 13 patients with the DiGeorge syndrome. Our patients demonstrated marked variability in both the clinical manifestations and the degree of immunodeficiency, confirming the findings of earlier individual case reports and retrospective autopsy reviews. Ages at the time of presentation ranged from one day to 4 months. Congenital heart defects including truncus arteriosus, ventricular septal defect, interrupted aortic arch, and tetralogy of Fallot commonly brought these infants to medical attention within the first two weeks of life. Abnormal calcium homeostasis was found in all patients. Those patients presenting after the first month of life often had hypocalcemic seizures as the initial clinical manifestation. Parathyroid hormone levels and the number and location of parathyroid glands varied considerably. Immunologic evaluation revealed that total lymphocyte counts, percent T-cells, total T-cells, and T-lymphocyte function ranged from normal to severely depressed. The most consistent immunologic abnormality, found in 11 of the 13 patients, was a decrease in total T-cells. Sequential studies in five patients demonstrate that spontaneous resolution of immunodeficiency may occur in some, yet progressive loss of immune function may be observed in others. Complete immunologic evaluation and careful followup is mandatory in infants with persistent hypocalcemia and congenital heart disease who are suspected to have DiGeorge syndrome.