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[Skeletal muscle pathology of chronic graft versus host disease accompanied with myositis, affecting predominantly respiratory and distal muscles, and hemosiderosis].

We report the muscle pathology in a 43-year-old woman who died of chronic graft versus host disease (GVHD) complicated by myositis and systemic transfusional hemosiderosis, after an allogeneic bone marrow transplantation and a donor leukocyte transfusion for acute myelogenous leukemia. Despite cyclosporin A treatment, fatal ventilatory failure progressed while she was still ambulant. Autopsy revealed the presence of chronic GVHD mildly involving the liver, skin, pericardium, pancreas, and salivary glands, in addition to skeletal muscles. Myopathic changes with mild inflammation and prominent iron deposition were found in the tibialis anterior muscle and, to a lesser degree, in the diaphragm and the intercostal muscle. There were iron deposits in both macrophages and sarcoplasm in the tibialis anterior. The iliopsoas and pectoralis major muscles showed prominent type 2 fiber atrophy; inflammation and iron deposition were minimal in the iliopsoas, but none in the pectoralis. Although we ascribed respiratory failure largely to GVHD myositis, weakness of the lower leg appeared to be aggravated by iron deposition superimposing the underlying GVHD myositis.

Adult↗

Cell culture as a tool for the study of poultry skeletal muscle development.

Postnatal development of skeletal muscle is the responsibility of the myogenic satellite cells. Satellite cells, isolated from the pectoralis major muscle of young growing tom turkeys, have been cultured in vitro to provide a system for studying cellular and hormonal aspects of poultry skeletal muscle development. Satellite cell clones derived from primary cultures have been developed so that in vitro observations would not be confounded by the presence of nonmyogenic cells. Likewise, a serum-free medium that promotes proliferation of the turkey satellite cell has been developed to provide a hormonally controlled environment for in vitro developmental studies. These two techniques have enabled us to examine the following: 1) factors that influence satellite cell proliferation and differentiation, 2) the interaction of hormones with cellular receptors, 3) secretion of biologically important proteins from cells and 4) the expression of genes important to muscle development.

Animals↗

Regulation of inspiratory neuromuscular output during synchronized intermittent mechanical ventilation.

BACKGROUND: In synchronized intermittent mandatory ventilation, it is generally accepted that the work of the inspiratory muscles is decreased by the ventilator so that their activity can be modulated by the frequency of assisted breaths. We examined the validity of this concept, which recently has been questioned. METHODS: We studied five patients receiving synchronized intermittent mandatory ventilation because of an acute exacerbation of chronic obstructive pulmonary disease. The level of machine assistance, defined as the percentage of total ventilation delivered by the ventilator, was varied from a high (> 60%) to a medium (20-50%) and to the lowest tolerated value (0% in four patients). Esophageal pressure, air flow, and the electromyograms of the diaphragm and sternocleidomastoid muscles were recorded. At each level of machine assistance, distinguishing assisted from spontaneous breaths, the duration of electrical activation, the integrated electromyograms, and the work of breathing were computed. RESULTS: The durations of electrical activation and the integrated electromyograms of the diaphragm and sternocleidomastoid were similar in successive spontaneous and assisted breaths. At > 60% of machine assistance, the cumulative values per minute of the integrated electromyograms of the diaphragm and sternocleidomastoid and the work of breathing were reduced only by 38, 32, and 44%, respectively, compared with the lowest tolerated level of machine assistance. The durations of electrical activation did not change with increasing level of machine assistance. CONCLUSIONS: The degree of inspiratory muscle rest achieved by synchronized intermittent mandatory ventilation is not proportional to the level of machine assistance; furthermore, the inspiratory motor output is not regulated breath by breath but rather is constant for a given level of machine assistance.

Aged↗

Insulin-stimulated entry of glucose into muscle in vivo as a major factor in the regulation of blood glucose.

1. The entry of glucose into the pectoralis major muscle of living rats was measured over a wide range of plasma glucose concentrations. A technique was used by which steady concentrations of substances are maintained in the circulation throughout the experiments. 2. Raising the concentration of glucose in the plasma caused saturation of the mechanism by which it is transported into muscle. Estimates of the values of the kinetic constants for this transport system were: Kt, 34 mumole ml-1 and V, 1-2 mumole min-1-g-1 muscle. 3. When the plasma glucose concentration was raised up to at least twelve times normal, there was no sign of saturation of the transport system in insulin-treated animals. This finding could be explained if insulin increased greatly both V and Kt for glucose transport. 4. Insulin increased the rate of entry of glucose into muscle over the entire range of plasma glucose concentrations studied (4-8 mumole ml.-1). There was evidence that endogenous insulin produced a similar increase in entry rate some 10 min after the injection of glucose. Fasting, which is associated with a decrease in insulin level, depressed the rate of entry. In hyperglycaemia insulin caused a rise in the concentration of glucose within the muscle cells. 5. The insulin-induced increase in the rate of glucose entry into muscle ensured that approximately 25% of an I.V. dose of glucose entered the muscle cells of insulin-treated animals within one minute. This illustrates the quantitatively important regulatory role that skeletal muscle plays in these circumstances in limiting the extent of a rise in circulating glucose.

Animals↗

Myonuclear addition to uninjured laryngeal myofibers in adult rabbits.

OBJECTIVES: In normal mature limb skeletal muscle, satellite cells are quiescent and myonuclei do not divide after formation of their associated myofibers in the absence of injury. The possibility of myonuclear addition in uninjured laryngeal myofibers of adult rabbits was investigated in an immunohistochemical pilot study. METHODS: Bromodeoxyuridine (brdU), a marker for cell division, was administered by intraperitoneal injection over a 12-hour period in rabbits. The number of brdU-positive myonuclei per myofiber was determined on cross sections through the thyroarytenoid (TA) and posterior cricoarytenoid (PCA) muscles. RESULTS: In the TA muscle, 0.13% +/- 0.03% (mean +/- SEM) of the myofibers counted had a brdU-positive nucleus. In the PCA muscle, 0.13% +/- 0.01% of the myofibers counted had a brdU-positive nucleus. Approximately 0.2% and 0.3% of the myofibers of the TA and PCA muscles, respectively, had brdU-positive satellite cells associated with them. Tibialis anterior and pectoralis major muscle controls were negative for brdU-positive myonuclei. CONCLUSIONS: These data support the possibility of continuous remodeling in uninjured adult laryngeal myofibers and accentuate the distinct nature of laryngeal muscle relative to limb skeletal muscle in the rabbit model.

Animals↗

Axillary dissection for breast carcinoma. The myth of skip metastasis.

The question of what constitutes an adequate axillary dissection for breast cancer remains open for debate. Central to this controversy is whether axillary nodal metastasis occurs in a stepwise fashion or spreads sporadically, creating skip metastases. The therapeutic aim of axillary dissection also must be considered. To resolve this controversy, a prospective study involving 129 patients who underwent complete axillary dissection for breast carcinoma was performed. The tissue from the axillary dissections was divided intraoperatively and sent to the pathologist as two specimens. The first specimen contained all nodes lateral to the pectoralis minor muscle (Level I), whereas the second contained all nodes beneath and medial to the pectoralis minor (Levels II and III). The tissue was analyzed to determine the frequency of skip metastasis. Only two patients, 1.6 per cent of the total group or 3.2 per cent of the positive node group, were found to have a positive node in Level II-III with no metastasis in Level I. A thorough dissection of Level I alone is sufficient to detect more than 98 per cent of all axillary lymph node metastases from breast cancer. Thus, proper staging of the disease can be obtained. When Level I contained positive nodes, the probability of metastatic disease to higher levels was significant (45%), indicating further treatment is necessary in incomplete axillary dissections.

Breast Neoplasms↗

The effect of vitamin A deficiency on some postmortem parameters of avian muscle.

The effect of the dietary status of vitamin A on carbohydrate metabolism, postmortem isometric tension development, and shear resistance of Pectoralis major muscle was studied. Depletion studies conducted over a 5-week period indicated a definite influence of vitamin A deficiency on muscle carbohydrate metabolism. Mild hypovitaminosis A induced an increase in glycogen deposition, whereas severe deficiency led to a reduction of these elevated stores. Vitamin A deficiency did not affect the ability of P. major strips to develop isometric tension postmortem. The P. major strips sampled from deficient cockerels generally required longer to reach maximum tension than those of controls. The extended times to maximum tension reflected an increased muscle glycogen content. A significant increase in shear value similarly corresponded to the increased myofibrillar contraction noted in the later deficiency stages. Cockerels which had previously received for five weeks a ration completely deficient in vitamin A were utilized for a two-week repletion study. Although there was a distinct delay in response to the feeding of a vitamin A adequate ration, the muscle glycogen content, isometric tension parameters, and shear values of repleted birds were similar to those of controls within the two-week period.

Adenosine Triphosphate↗

Identification of optimal strategies for increasing whole arm strength using Karush-Kuhn-Tucker multipliers.

OBJECTIVE: The purpose of this study was to develop a computer model for identifying muscles critical to improving functional upper extremity strength. DESIGN: A three-dimensional biomechanical model of the upper extremity was developed, and the predictions were compared to maximal arm strength data collected from healthy volunteers. BACKGROUND: Although several optimization-based mathematical models of the shoulder have been developed, none have utilized the mathematical properties of the Karush-Kuhn-Tucker multipliers to efficiently estimate the effect of strengthening individual muscles on functional strength of the whole arm. METHODS: A static three-dimensional biomechanical model of the glenohumeral, radio-humeral, ulno-humeral and wrist joints was developed for predicting maximal hand exertion forces. The model was formulated as a linear program. Constraints consisted of moment equilibrium conditions and limits on maximum and minimum allowable muscle forces. Predicted arm strengths were compared to maximal pull strength measurements made on 10 subjects (5 male; 5 female). The task involved pulling toward the mid-sagittal plane of the body with the arm flexed 45 degrees. The Karush-Kuhn-Tucker variables associated with the maximal limits on muscle force were computed to estimate the effect of altering the strength of individual muscles on functional arm strength. RESULTS: Maximum pull strengths were predicted well by the model. Karush-Kuhn-Tucker values ranged from 0 (for muscles not at their upper force limits) to 0.11 for the flexor carpi radialis and pectoralis major muscles. Karush-Kuhn-Tucker multipliers were found to be insensitive to the assumed specific tension of muscle. CONCLUSIONS: Upper extremity strength can be predicted from musculoskeletal geometry and physiology using linear programming. RELEVANCE: Karush-Kuhn-Tucker multipliers associated with the muscle force upper limits give insight into the effect of strengthening individual muscles on whole arm exertion strength. Such an analysis may provide insight into the development of optimal rehabilitation protocols.

Adult↗

Use of muscle flaps in the treatment of infected sternotomy.

Deep wound infection after open-heart surgery remains a major problem. In this paper potential indications and techniques for use of muscle flaps in the treatment of chronic sternal infections are discussed and the authors' early experience with such treatment is presented. A well vascularized muscle flap fills out the defect, may help to control infection, and accelerates healing. After adequate excision of infected tissue, bone and cartilage, the resulting defect is covered with a muscle flap immediately or after a period of open treatment. Coverage with a flap of pectoralis major muscle was used in five patients 3 weeks to 6 months after cardiac surgery. Primary healing occurred in two patients, secondary healing in one and healing with residual fistula in one patient. In the fifth case there was uneventful recovery with primary healing until death occurred from cerebral haemorrhage after 3 weeks. Use of muscle flaps seems to be a valuable complement in the management of severe sternotomy infections.

Aged↗