Fibronectin, a dimeric cell-adhesive extracellular matrix glycoprotein, is secreted by mesenchymal cells and assembled into insoluble matrices which have important biological functions in embryologic development as well as in tissue response to injury. Fibronectin interacts with numerous cell types including mesenchymal cells and inflammatory cells which bear appropriate fibronectin receptors. In vitro, fibronectin serves as an adhesive substrate and promotes cell proliferation and cytodifferentiation. During development, fibronectin-rich matrices are deposited in specific location and regulate the directional migration of embryonic cells. In particular, fibronectin matrices appear to be of critical importance to normal cardiopulmonary development. Following embryologic development, the tissue expression of fibronectin is greatly reduced, but increases markedly following tissue injury, where newly expressed fibronectin matrices appear critical to tissue repair. Recent evidence has documented increased expression of fibronectin in numerous pulmonary conditions including the adult respiratory distress syndrome (ARDS), bronchiolitis obliterans organizing pneumonia (BOOP) and idiopathic pulmonary fibrosis (IPF). Additionally, fibronectin also interacts with a large number of microorganisms and therefore also is potentially important in microbial adherence to airway epithelium and subsequent infections of the respiratory system.

An American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference was held in Northbrook in August 1991 with the goal of agreeing on a set of definitions that could be applied to patients with sepsis and its sequelae. New definitions were offered for some terms, while others were discarded. Broad definitions of sepsis and the systemic inflammatory response syndrome were proposed, along with detailed physiologic parameters by which a patient may be categorized. Definitions for severe sepsis, septic shock, hypotension, and multiple organ dysfunction syndrome were also offered. The use of severity scoring methods when dealing with septic patients was recommended as an adjunctive tool to assess mortality. Appropriate methods and applications for the use and testing of new therapies were recommended. The use of these terms and techniques should assist clinicians and researchers who deal with sepsis and its sequelae.

There are four cases of Actinobacillus actinomycetemcomitans pulmonary infections reported in the English literature prior to 1990. We report a case of A actinomycetemcomitans pulmonary infection with invasion of overlying soft tissue, rib, and sternum. This manifestation has not been previously reported. The clinical manifestation is similar to that of Actinomyces israelii, which may be misinterpreted as malignancy initially. The portal of entry of A actinomycetemcomitans may be via hematogenous spread or aspiration. The diagnosis depends on culture after prolonged incubation of the involved tissue obtained by aspiration or biopsy. Elevated serum antibody is helpful for diagnosis of active infection. A actinomycetemcomitans is susceptible to most antibiotics, but is frequently resistant to penicillin, vancomycin, clindamycin, and erythromycin. Isolation of the organism and an in vitro drug sensitivity testing are important in managing the patient. Our patient recovered after a three-month regimen of penicillin.

We describe a pseudoepidemic due to nontuberculous mycobacteria contaminating the water tank of a machine used to clean and disinfect fiberoptic endoscopes. Forty-six bronchoscopies performed on 41 patients during a six-month period yielded 16 specimens positive for acid-fast bacilli (AFB). One specimen showed Mycobacterium avium complex from an AIDS patient and one, M tuberculosis from a patient with active cavitary tuberculosis. In four patients, only the smears showed AFB; subsequent cultures remained negative. Of the rest, seven contained M chelonae and three M gordonae, all in patients with no clinical signs of mycobacterial disease. Two of the three M gordonae isolates represented laboratory contamination from an antimicrobial solution in a culture medium. Four patients in the beginning of the pseudoepidemic were treated for presumed tuberculosis until negative culture results were available. Control of the "outbreak" was achieved by regular disinfection of the implicated water tank in the cleaning machine. Contamination of bronchoscopes with nontuberculous mycobacteria can lead to unnecessary diagnostic and therapeutic interventions.

Multiple compensatory mechanisms operate to preserve exercise tolerance in patients with left ventricular failure. Exercise capacity of most patients with chronic heart failure is limited by dyspnea or fatigue, or both. Maximal stress testing with direct assessment of peak O2 uptake is an essential measurement in planning exercise conditioning programs, which are now attracting patients with chronic heart failure. The biochemical and histologic patterns of skeletal muscle changes seen in chronic heart failure patients are consistent with the effects of long-term exercise deconditioning in normal subjects. Recent studies have suggested beneficial effects of training in subjects with moderate or even severe left ventricular dysfunction by showing increased exercise tolerance or peak O2 consumption, anaerobic threshold, peak leg blood flow, peak central arteriovenous oxygen difference and decreased lactate accumulation. However, a number of questions remain unanswered. Exercise training for the treatment of chronic heart failure should be determined on an individual basis and used with caution.

Although the pathophysiology of exercise intolerance in patients with chronic heart failure (CHF) is not fully understood, it appears that the cardiac output response plays an important role in limiting exercise in this disorder. Although previous studies have demonstrated that peak VO2 is not related to left ventricular (LV) ejection fraction, studies have consistently identified peak exercise cardiac output as an important predictor of peak VO2. It is likely that a reduced cardiac output to work rate relationship in CHF causes hypoperfusion of both working skeletal muscle and visceral organs, which leads to early anaerobic metabolism and fatigue. Several factors may influence the cardiac output response in patients with severe systolic LV dysfunction, including heart rate, diastolic LV function, and the mitral regurgitation fraction. Although stroke volume increases through use of the Frank-Starling mechanism in many patients with severe systolic LV dysfunction, some patients with this disorder may not increase stroke volume during exercise due to diastolic LV dysfunction or pericardial constraint. The finding that this latter group has more severe exercise intolerance suggests that diastolic dysfunction may further decrease peak VO2 in this disorder. Variations in the mitral regurgitation fraction also have been found to have an important effect on exercise stroke volume in some patients with CHF. Therefore, the finding that LV ejection fraction at rest or during exercise is not related to peak VO2 in patients with systolic LV dysfunction does not necessarily indicate that central hemodynamics do not play a role in exercise intolerance. Rather, it is likely that variability in the LV ejection fraction with exercise, which does not take variable increases in LV end-diastolic volume or mitral regurgitation into account, plays only a modest role in determining the stroke volume and cardiac output response to exercise in patients with severe systolic dysfunction.

Work by a number of laboratories over the last decade has revealed that skeletal muscle in patients with congestive heart failure (CHF) exhibits altered metabolism, biochemistry, and histology. These alterations appear to be at least in part independent of systemic hemodynamic abnormalities and they lead to abnormal muscle function. Furthermore, muscle dysfunction may play a role in limiting exercise capacity. While blood flow to exercising muscle may be impaired in CHF, both the functional and metabolic changes are, to some degree, independent of the changes in blood flow. Deconditioning and muscle atrophy may be responsible for some of these functional metabolic alterations in muscle, but other factors appear to be operating as well. Finally, the finding that many of the changes in skeletal muscle associated with CHF can be reversed by exercise training suggests that activity should be encouraged in patients with CHF.

The factors that contribute to the symptoms of breathlessness and fatigue, and that limit exercise capacity in patients with chronic heart failure are poorly understood. Recent evidence suggests that the major mechanism is not related to central hemodynamics but to a reduction of skeletal muscle mass and diminished blood flow to skeletal muscle on exercise.

Although several studies have shown that physical training lowers blood pressure values both in normotensives and in hypertensives, the mechanisms accounted for this effect are not clearly elucidated. It has been reported that the decrease in blood pressure and heart rate that accompanies physical training is associated not only with an increase in vagal tone but also with a reduction in plasma norepinephrine levels. Whether this reduction really means a decrease in sympathetic neural discharge is unknown, however. To clarify this issue, we have performed in 7 normotensives direct recording of postganglionic muscle sympathetic nerve activity from the peroneal nerve by microneurography before and after 10 weeks of an endurance training which increased oxygen consumption by 10%. It was shown that the blood pressure lowering effect of the training program was accompanied by a marked reduction in resting sympathetic nerve activity. These data provide the first direct evidence that in man, the blood pressure reduction induced by physical training is mediated by the neural sympathetic mechanisms.

The majority of US patients with clinical evidence of coronary heart disease are elderly. Appropriately prescribed and designed exercise training can improve physical and psychologic functional status and encourage maintenance of an independent life-style. Exercise testing, in addition to helping identify elderly coronary patients at high risk of recurrent events who warrant added therapies, can guide the recommendations for their exercise regimen.