Evaluation of a Supervised Exercise Program in a Geriatric Population

Most studies that assess the effects of exercise in the elderly involve subjects who are in good health. The objective of this prospective longitudinal study was to examine the impact of exercise on cardiovascular fitness, flexibility, and strength in an elderly population that included chronically ill individuals. Patients were recruited initially from a population of veterans over 64 years of age who use a VA outpatient clinic as their regular source of care. The exercise intervention consisted of 90 minutes of exercise 3 days per week at 70% of the patient's maximal capacity. Activities included stationary cycling, stretching, weight training, and walking. Of 69 patients who began the program, 49 (71%) reached 4-month follow-up. Most patients completing follow-up (76%) had at least one chronic disease, such as arthritis, hypertension, or heart disease. Patients who dropped out were more likely to have multiple chronic illnesses than those who remained in the program. Average weekly attendance was 65% and was stable over time. Improvements in cardiovascular fitness at 4-month follow-up were significant: Metabolic equivalents increased from 7.1 ± 2.3 to 8.3 ± 1.6 (P < .001), treadmill time increased from 8.5 ± 3.8 to 11.2 ± 4.1 minutes (P < .001), submaximal heart rate decreased from 123.7 ± 18.8 to 118.8 ± 19.4 beats per minute (P < .001) and resting heart rate decreased from 68.1 ± 10.6 to 63.3 ± 11.6 beats per minute (P = .005). Hip flexibility also increased significantly from 58.5 ± 13.8 to 67.7 ± 9.9 degrees (P < .001), and abdominal strength increased significantly from 88.8 ± 32.4 to 104 ± 28.4 foot-pounds (P < .001). No major complications resulted from exercise. This study demonstrates that elderly individuals, including those with chronic diseases, will participate in an exercise program and experience improvements in cardiovascular fitness, strength, and flexibility. Whether these improvements will enable elderly individuals to live independently for a longer period of time and avoid or postpone the need for long-term care requires additional study and follow-up.     

Mechanisms of tumor necrosis factor-granulocyte-macrophage colony- stimulating factor-induced dendritic cell development

In a previous report, we described that tumor necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) synergistically enhanced the development of dendritic cell (DC) progeny from early stem cells and that there is a common monocyte-DC progenitor cell. Low levels of DC were obtained with GM-CSF alone, and TNF by itself failed to induce stem cell development. Here, we investigate mechanisms by which TNF and GM-CSF institute increases in DC, and how these same molecules support later stages of DC differentiation. We show that TNF is required as the first signal, that there is upregulation of GM-CSF receptors (GM-CSFRs), and that TNF inhibits the differentiation of colony-forming units-granulocyte. High levels of GM- CSFR were always associated with conditions yielding a large number of DC, and a kinetic analysis showed a close ontogenic relationship between DC and GM-CSFR levels. The addition of anti-GM-CSF or anti-TNF antibodies blocked synergistic responses related to DC development, including high levels of GM-CSFRs. Anti-GM-CSF was the most potent inhibitor of proliferation (80%) and macrophage, DC, and polymorphonuclear (PMN) cell development. With polyclonal anti-TNF, inhibition was less (35%), and there was a shift from myelomonocytic and DC to PMN progeny. Our results support the concept that receptor upregulation is an important mechanism for growth factor synergy. Our data also indicate that the opposing effects of TNF on hematopoiesis contribute to the selection of the DC pathway and emphasize the importance of GM-CSFRs not only in initiated DC development, but also in controlling DC viability and function.     

PAROXYSMAL TACHYCARDIA IN INFANCY AND CHILDHOOD II. Paroxysmal Ventricular Tachycardia and Fibrillation

A retrospective 3–20-years follow-up study of 1 infant and 10 children with paroxysmal ventricular tachycardia (8 cases) or fibrillation (3 cases) is presented. Additional heart disease has been observed in 60% (myocarditis 3 cases, cardiomyopathy 3 cases, congenital heart disease 1 case). Symptoms of tachycardia were: palpitation, tiredness, weakness, dyspnoea, precordial and abdominal pain. Syncopes were observed in 3 cases; 1 child had no symptoms. Tachycardia of hours to days' duration have been noted in 8 patients, 7 had tachycardia of repetitive type with a-v dissociation, one continuous tachycardia without any intervening sinus beats after the onset of tachycardia and with retrograde atrial activation. The remaining 3 children had brief malignant tachycardia, i.e. stress-provoked bursts of ventricular activity occasionally converting to ventricular fibrillation causing syncope. The diagnosis of brief malignant tachycardia had to be based on exercise ECG (2 cases) or long-term ECG-monitoring by telemetry (one case). One child with cardiomyopathy had died at the time of follow-up and the 3 patients with brief malignant tachycardia had experienced repeated life-threatening attacks—one of which had to be stopped by emergency d.c. countershock. The period of attacks ceased in 5 cases within 2 years after onset, in 1 patient, 9 years elapsed between first and second attack. Preventive treatment with betablocking agents proved beneficial in the 3 children with brief malignant tachycardia.     

Value of chest radiography in excluding traumatic aortic rupture

A retrospective review of chest radiographs from 205 patients with blunt chest trauma who also underwent aortography was performed. Forty-one of the 205 had aortographically proved aortic rupture. Discriminant analysis of 16 radiographic signs indicated that the most discriminating signs were loss of the aorticopulmonary window, abnormality of the aortic arch, rightward tracheal shift, and widening of the left paraspinal line without associated fracture. No single or combination of radiographic signs demonstrated sufficient sensitivity to indicate all cases of traumatic aortic rupture on plain chest radiographs without the performance of a large number of aortographically negative studies. The bedside anteroposterior "erect" view of the chest proved far more valuable than the supine view in detecting true-negative studies. Despite significant reader variability in the interpretation of the various radiographic signs, in general the analysis confirmed the role of chest radiography in this clinical situation, but suggests that its most beneficial use is in excluding the diagnosis and eliminating unwarranted aortography rather than in predicting aortic rupture.     

4Modulation of maturation and function of dendritic cells by female sex steroid hormones

Problem:  Pregnancy represents an exclusive situation in which the immune and the endocrine system cooperate to prevent rejection of the embryo by the maternal immune system. While immature dendritic cells (iDC) in the early pregnancy decidua presumably contribute to the establishment of peripheral tolerance, hormones like estradiol (E2), progesterone (Prog) and bHCG are candidates that could direct the differentiation of DCs into a tolerance-inducing phenotype.
Methods and Results:  To test this hypothesis we generated iDCs from peripheral-blood-monocytes and exposed them to E2, Prog, bHCG and Dexamethasone (Dex) as control. Surprisingly, E2, Prog and bHCG upregulated the expression of HLA-DR, CD 40, CD 83 and CD 86. Visualization of the F-actin cytoskeleton confirmed these observations. In contrast, the T-cell stimulatory capacity of DCs was reduced after E2, Prog and bHCG exposure.
Conclusion:  These findings suggest that E2, Prog and bHCG interfere with selected aspects of DC maturation and may thereby help preventing activation of allogenic T-cells by the embryo.     

Preimplantation diagnosis of non-deletion Duchenne muscular dystrophy (DMD) by linkage polymerase chain reaction analysis

The use of preimplantation diagnosis for sex determination and detection of exon deletion means that unaffected babies can be born to parents suffering from Duchenne muscular dystrophy (DMD). However, those who do not have exon deletion should also be considered for further investigation. A new method, known as linkage analysis, has been developed to diagnose the presence of non-deletion DMD in preimplantation embryos. Linkage analysis uses informative intragenic and flanking markers to track the chromosome bearing the mutated gene. The present study reports the analysis of two polymorphic sites, in blastomeres biopsied from embryos from a female carrier of DMD. A single male embryo was obtained who had inherited alternate maternal alleles to the woman's affected surviving son, and this embryo was transferred.