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Endothelial damage is a hallmark of acute lung injury. Endothelial mediators may increase pulmonary vascular tone and induce pulmonary arterial muscularization, thereby contributing to the pulmonary hypertension seen with acute lung injury. We measured plasma levels and net pulmonary clearance of endothelin-1, a potent endothelium-derived vasoconstrictor peptide and smooth muscle mitogen, in 26 patients with early acute lung injury, the adult respiratory distress syndrome, and pulmonary hypertension. Nineteen had another data collection at clinical improvement or worsening. Control subjects (n = 25) had no pulmonary hypertension or lung injury. Initial mixed venous and systemic arterial plasma endothelin-1 levels were elevated (4.6 +/- 0.6 SEM and 4.9 +/- 0.6 pg/ml, respectively) as compared with control subjects (0.9 +/- 0.1 and 0.6 +/- 0.1 pg/ml). The systemic arterial/venous endothelin-1 ratio was 1.1 +/- 0.1 (0.7 +/- 0.1 in control subjects), indicating a reduction in normal net pulmonary endothelin-1 clearance. With clinical improvement, as compared with clinical worsening, mean plasma endothelin-1 levels, arterial/venous ratio, and pulmonary arterial pressure fell significantly towards normal. Thus, patients with acute lung injury have marked early increases in circulating plasma endothelin-1 levels, associated with abnormal pulmonary endothelin-1 metabolism. These abnormalities reverse in patients who recover. Through its actions, endothelin-1 could contribute to the pulmonary hypertension seen in acute lung injury.

The creation of a partnership, the hallmark of true collaborative practice, is an ongoing, dynamic process. It demands commitment, energy, and creativity. It is learned and therefore must be role modeled. One must remember that it takes time to develop collaborative relationships. One must begin slowly, walk not run, and have realistic expectations. It is a joy to work in an environment that has developed and is in the process of continually developing true collaborative practice. Hope for the future of health care lies in our ability to deliver coordinated and collaborative care. Nursing, medicine, and administration together can and must provide the solutions to our health care delivery problems before those solutions are legislated. We must set policies and priorities to appropriately allocate scarce resources. We must address personnel needs, credentialing, and compensation to ensure adequate numbers of qualified staff to meet the growing needs of our patients. We must evaluate technology and our physical environments to determine the types of services that we will offer. We must continue to broaden our collaborative efforts to extend from the patient care arena into the realms of education, research, and administration. It is up to each of us and each of our colleagues to work every day toward a more collaborative practice environment. By empowering each other, we can put into place a collaboration which "works jointly with others in intellectual endeavors" rather than one which merely "cooperates with an enemy force."

Intestinal bypass surgery, performed for weight reduction in the morbidly obese patient, is frequently complicated by the development and hepatic complications. In 44 morbidly obese individuals, 55 inches of proximal jejunum were anastomosed, end to side, to 5 inches of distal ileum. All the patients were followed with body composition measurements, performed by multiple isotope dilution, prior to and at regular time intervals following bypass surgery. In 33 patients a decrease in body fat accounted for the entire postbypass weight loss, while the lean body mass remained normal in both size and composition. In these patients, at 1 year, body weights had decreased by 24.4 +/- 2.1%, while the body cell masses had decreased by 2.1 +/- 7.1%. In the remaining 11 patients, the postbypass weight loss resulted from a loss of both body fat and body cell mass. Their body weights at 1 year had decreased by 27.0 +/- 3.0%, while the body fat and body cell mass. Their body weights at 1 year had decreased by 27.0 +/- 3.0%, while the body cell masses decreased by 22.0 +/- 6.1%. Furthermore, their body compositions were characteristic of protein malnutrition with a contracted body cell mass and an expanded extracellular mass. Six of these 11 patients have required admission to hospital on 10 occasions because of malaise, anorexia, debilitating weakness, hypokalemia, and abnormal liver function. They were treated for 14.5 +/- 1.9 days with an intravenous infusion of amino acids without additional nonprotein calories. The body composition, initially characteristic of malnutrition, became normal. Their symptoms disappeared and hepatic function returned to normal. Subsequently a high-protein diet was required to prevent a recurrence of symptoms and to maintain a normal body composition. The data indicate that protein malnutrition developed in 11 of 44 patients undergoing jejunoileal bypass for weight reduction.

The efficacy of intravenous hyperalimentation in the critically ill patient was evaluated by body composition measurements performed with a multiple isotope dilution technic. The size of the body cell mass was evaluated by measuring the total exchangeable potassium and the intracellular water volume. The total exchangeable sodium and the extracellular water volume were both measured to evaluate the extracellular supporting component of body composition. These measurements were performed in two groups of severely ill patients who were in a chronic catabolic state. The first group of sixteen patients received intravenous hyperalimentation and the second group of eighteen patients served as controls in that they were not hyperalimented. Similar measurements were performed in sixteen normal volunteers to define the normal range for the various body composition parameters. In the nonalimented patients, there was a significant decrease in the body cell mass accompanied by an expansion of the extracellular supporting component of body composition. Similar changes occurred in the patients receiving intravenous hyperalimentation. However, the magnitude of these changes was not great. Thus, intravenous hyperalimentation tended to preserve the body cell mass and prevent expansion of the extracellular component of body composition.

A technique is described for the indirect measurement of total exchangeable potassium (Ke) that involves neither the rapidly decaying radioisotopes of potassium nor a total body counter. Total exchangeable sodium (Nae) and total body water (TBW) are measured by isotope dilution. Ke is calculated from Ke = R (TBW) - Nae, where R is the ratio of the sodium plus potassium content divided by the water content, in a sample of whole blood. In 19 normal rats and four rats with uremia there was an insignificant difference between the indirect determination of Ke and its direct measurement by carcass analysis. A similar insignificant difference was recorded between the indirect determination of Ke and its direct measurement by potassium-42 dilution in 15 normal dogs, five dogs with uremia, 14 dogs in an hyposmolar state, and in 20 patients. In 25 normal volunteers, Ke was determined indirectly. The regression of Ke on TBW and the 95% confidence intervals of this population was similar to published data in which Ke was determined by potassium-42 dilution. The indirect measurement of Ke was, therefore, validated experimentally.

The caloric requirements of the critically ill patient was defined by body composition measurements performed in thirty-five patients before and after a course of total parenteral nutrition (TPN). A positive and statistically significant (p less than 0.001) correlation was observed between the number of kcal/kg/day infused and the mean daily change in Ke, which is a measure of the body cell mass. The intercept of the regression line was 46 kcal/kg/day indicating that balance is achieved when calories are infused at this rate. Fifteen of the thirty-five patients studied received less than 46 kcal/kg/day. In this group an average of 38.1 +/- 1.5 kcal/kg/day of TPN was infused for 13.3 +/- 1.2 days. The body composition of these patients was unchanged after TPN and was characteristic of malnutrition both before and after TPN. TPN was administered at a mean rate of 57.2 +/- 2.0 kcal/kg/day for 16.7 +/- 1.8 days in the twenty patients who all received more than 46 kcal/kg/day. The body composition of these patients before TPN was also characteristic of malnutrition. However, a marked improvement of body composition was observed after the course of TPN. In all the patients in both groups the amino acids were infused at a rate that exceeded the minimal amount required to achieve nitrogen balance. The data indicate that the average patient receiving TPN requires at least 46 kcal/kg/day for balance. In the depleted patient infusion of calories in excess of this amount results in a rebuilding of the body cell mass.

The efficacy of the jejunolieal bypass operation, performed as a weight-reducing procedure in the morbidly obese patient, was assessed by measurements of body composition. In 20 patients measurements were performed by multiple isotope dilution, before and following jejunoileal bypass. Prior to bypass the excess body weight was due primarily to an increase in body fat (BF), which accounted for 52 percent of body weight. The nonfatty component of body composition, the lean body mass, although slightly increased in size, was essentially normal. Two distinct patterns were observed following bypass. In 12 patients followed for 8.4 +/- 1.5 months, there was a 21 percent decrease in body weight, resulting entirely from a loss of BF. The total exchangeable potassium and intracellular water volume, both measures of the body cell mass (BCM), were unchanged. In the second group of eight patients followed for 13.9 +/- 2.1 months, the mean body weight decreased by 27 percent or 38.8 Kg., due to a 26.6 Kg. reduction in BF and a 13.0 Kg. decrease in the BDM. This was accompanied by a relative expansion of the extracellular mass. As a result, the mean Nae/Ke ratio increased significantly (p less than 0.05) from a normal prebypass value of 0.95 +/- 0.7 to 1.46 +/- 0.11 following bypass. Thus in eight of the 20 patients following jejunoileal bypass, there was an undesirable loss of BCM with a relative expansion of extracellular supporting component of body composition, a pattern characteristic of malnutrition.

To assess the efficacy of cimetidine versus Mylanta II in the prevention of stress erosions, 44 patients at risk were randomized to receive cimetidine 300 mg/6 h intravenously to a maximum of 400 mg/4 h; or Mylanta II 30 ml/h through a nasogastric tube to a maximum of 90 ml/h. The minimum dose of medication was used to maintain hourly gastric pH greater than or equal to 4. All patients were to be endoscoped after 72 h and erosions graded by an endoscopist who had no knowledge of their treatment regime. Grade 3 or 4 erosions occurred in five of 21 cimetidine-treated patients and eight of 16 antacid-treated patients (p greater than 0.05). A gastric pH greater than or equal to 4 was maintained 79.5% of the time by cimetidine and 97.9% of the time by Mylanta II (p less than 0.001). Cimetidine and antacids are equal in the prevention of stress erosions although Mylanta II is superior in hourly pH control. Hourly pH control does not entirely explain the beneficial effect of cimetidine in the prevention of stress ulcers. There was no significant bleeding in this study. Fatalities in patients at risk of developing stress ulcers result from the underlying disease, not from hemorrhage from stress-induced mucosal lesions. In critically ill patients, endoscopic examination should be restricted to the rare case with manifest hemorrhage.

The postoperative protein-sparing effect of intravenously administered amino acids was assessed quantitatively by measuring body composition by multiple isotope dilution. Body composition was determined in two groups of 19 patients each, before and on the fifth day following a major abdominal operation. One group of patients received all of their required fluids and electrolytes as a 5% glucose solution. The second group received an isocaloric infusion of protein as a 5% casein hydrolysate solution. The preoperative body composition of both groups was normal. On the fifth day after operation, the mean body weight had decreased by 2.6 plus or minus 0.6 kg in the glucose group and by 2.0 plus or minus 0.5 kg in the protein group. In the patients receiving glucose, this postoperative weight loss was due to a decrease in both body fat and the lean body mass. The mean body cell mass, which represents the total mass of living, functioning cells, decreased from 23.1 plus or minus 1.5 to 19.9 plus or minus 1.4 kg (P less than 0.001), while the extracellular mass increased from 24.9 plus or minus 0.9 to 27.3 plus or minus 0.9 kg (P less than 0.001). In contrast, in the patients receiving protein, the loss of body weight resulted entirely from a loss of body fat, while the body cell mass and the extracellular mass both remained normal. Therefore protein sparing was achieved by the postoperative infusion of protein.