A controlled trial of digoxin in congestive heart failure.

Because of conflicting results from studies examining the usefulness of digoxin in congestive heart failure (CHF) patients in sinus rhythm, a cross-over trial was conducted in which 20 patients received 7 weeks of digoxin titrated to a level of 1.54 to 2.56 nmol/liter and 7 weeks of matched placebo.

Long-term outcome after respiratory rehabilitation.

To determine the long-term effect of respiratory rehabilitation, we followed up for 6 months after discharge 31 consecutive patients enrolled in a multidisciplinary inpatient rehabilitation program lasting 4 to 6 weeks. Of the 31, 24 showed improvement in quality of life (as measured with a previously validated questionnaire) and in functional exercise capacity (as measured with the 6-minute walk test) 2 weeks after discharge. The improvement was sustained for 6 months in 11 of the 24.

Treatment of cryptosporidiosis with spiramycin in AIDS. An "N of 1" trial.

We describe a randomized, double-blind, placebo-controlled, crossover trial with spiramycin in a single patient with acquired immune deficiency syndrome (AIDS) and a severe secretory diarrhea caused by cryptosporidium. Spiramycin, a potentially harmful antibiotic, had no clinical or microbiological effect in this patient. The application of the single patient (N of 1) trial to common clinical problems is a simple way to analyze the value of different therapeutic approaches.

A measure of quality of life for clinical trials in chronic lung disease.

Since the relationships between pulmonary function, exercise capacity, and functional state or quality of life are generally weak, a self report questionnaire has been developed to determine the effect of treatment on quality of life in clinical trials. One hundred patients with chronic airflow limitation were asked how their quality of life was affected by their illness, and how important their symptoms and limitations were. The most frequent and important items were used to construct a questionnaire evaluating four dimensions: dyspnoea, fatigue, emotional function, and the patient's feeling of control over the disease (mastery).

A controlled trial of ambroxol in chronic bronchitis.

Ambroxol is a mucolytic agent which is widely used in chronic bronchitis in Europe. We conducted a double-blind randomized controlled trial of ambroxol vs matched placebo in 90 patients with chronic bronchitis and difficulty clearing secretions. It was concluded that there was no advantage to taking ambroxol.

Flow redistribution in a hyperdynamic small animal burn: comparison to patterns in sepsis.

Visceral hypoperfusion with local accumulation of lactate in the ischemic tissues has been reported in a septic rat model despite a hyperdynamic systemic circulation. This visceral ischemia is felt to contribute to the multiple system organ failure (MSOF) syndrome associated with sepsis. The purpose of this study was to determine whether a similar redistribution of blood flow existed in rats after a severe thermal injury as it too is associated with MSOF.

Hepatic microsomal adenosine triphosphatase and mitochondrial function. Response to cold and warm ischemia.

We investigated the response of mitochondrial function and microsomal adenosine triphosphatase (ATPase) activity in rat liver tissue subjected to in vitro ischemia at either 0 degree C to 4 degrees C or 37 degrees C for 30 to 60 minutes. Mitochondrial coupling, expressed as respiratory control index, was preserved at up to 60 minutes' cold ischemia. However, respiratory control index was decreased significantly from control by 30 minutes of warm ischemia.

Bronchodilators in chronic air-flow limitation. Effects on airway function, exercise capacity, and quality of life.

We conducted a trial of inhaled salbutamol and orally administered theophylline in patients whose acute response to inhaled salbutamol was less than 25% of their baseline FEV1. Patients underwent 4 treatment periods, each of 2 wk duration, during which they received the following combinations: placebo-placebo, placebo-salbutamol, placebo-theophylline, and salbutamol-theophylline. The 19 patient who completed the study were all males with a mean age of 65 +/- 7.

Galactose elimination kinetics in sepsis. Correlations of hepatic blood blow with function.

To study hepatic blood flow with clearance techniques during sepsis, it is essential to work within the limitations of the test being applied. Based on galactose elimination kinetics, this study validates galactose clearance at low concentrations as an estimate of effective hepatic blood flow in a rat peritonitis model of cecal ligation and puncture. Hepatic function as determined by galactose elimination capacity fell 25% at ten hours after induction of peritonitis, which correlated closely with the 20% reduction in effective hepatic blood flow at the same time point despite a normal cardiac output.

Alterations in renal perfusion and renal energy charge in murine peritonitis.

Whether acute renal failure following overwhelming bacterial septicemia is a initially a consequence primarily of a cytotoxic insult or a perfusion insufficiency remains unclear. To assess the effects of intra-abdominal sepsis on the distribution of renal blood flow and renal cell bioenergy status, the glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and energy-charge ratios were measured in rats following cecal ligation/puncture (CLP) or sham laparotomies. The CLP animals demonstrated a decrease in ERPF of 42% and 58% from sham groups at ten and 20 hours, respectively.

Low-dose dopamine improves effective hepatic blood flow in murine peritonitis.

Diminished effective hepatic blood flow (EHBF) has been postulated as contributory to hepatocellular dysfunction in sepsis. In addition, dopamine has been demonstrated to increase perfusion to selective viscera. In order to examine the effects of peritonitis upon hepatic perfusion and its response to dopamine infusion, peritonitis was induced in rats via cecal ligation and perforation (CLP).

Effective hepatic blood flow and hepatic bioenergy status in murine peritonitis.

To assess the effects of sepsis on effective hepatic blood flow (EHBF) and hepatic tissue bioenergy status 250-350 g rats underwent either sham laparotomy or cecal ligation and perforation (CLP). At 5-, 10-, and 20-hr intervals cardiac output (CO), EHBF, and tissue adenine nucleotide levels were measured. CLP rats showed a hyperdynamic response to sepsis at 20 hr, with CO increased by 25% over sham rats.

A comparison of Likert and visual analogue scales for measuring change in function.

Many controlled trials rely on subjective measures of symptoms or quality of life as primary outcomes. The relative merits of different response options for these measures is an important, but largely unexplored, issue. Therefore, we compared the responsiveness of seven-point Likert vs visual analogue scales (VAS) in a questionnaire measuring quality of life in chronic lung disease.

Quality of life in patients with chronic airflow limitation.

One hundred patients with chronic airflow limitation (CAL) randomly selected from over 600 such patients seen in the previous 2 years at a respiratory referral centre were asked about the ways in which their lives were adversely effected by their lung problems. Major problem areas included dyspnoea on day-to-day activities, fatigue and certain areas of emotional function including embarrassment, depression, anxiety and frustration. Severity of airflow limitation was only weakly related to patients' problems.

Imidazole and indomethacin improve hepatic perfusion in sepsis.

Visceral microcirculatory insufficiency has been demonstrated in sepsis despite a hyperdynamic systemic circulation. This study examines the effect of the cyclo-oxygenase inhibitor indomethacin and the thromboxane synthetase inhibitor imidazole on septic hemodynamics and visceral perfusion in a septic rat model of cecal ligation and puncture. Animals received either indomethacin (INDO), imidazole (IMID), or saline intramuscularly at t = 0, 6, and 12 hr of peritonitis.

Effective renal blood flow and renal energy charge in murine peritonitis.

The temporal sequence of physiological derangements preceding acute renal failure (ARF) observed in overwhelming bacterial septicemia remains controversial. In order to examine the relationship of renal circulatory alterations and cellular dysfunction in murine sepsis, effective renal plasma flow (ERPF), renal tissue metabolites, and energy charge ratios were determined in Sprague-Dawley rats at 10 and 20 hours following induction of peritonitis by cecal ligation and perforation (CLP) or cecal manipulation alone (sham). Tissue levels of adenine nucleotides, lactate, and pyruvate were assayed after freeze-clamping kidneys unilaterally followed by enzymatic determinations.

Corticotropin-releasing activity in the rat gastric antrum.

Rat gastric antrum, duodenum, pancreas, and spleen were extracted in acetic acid, treated with acetone, and purified on a C-18 cartridge. These extracts, in a dose equivalent to one respective organ, were examined for CRF bioactivity in vitro using rat half pituitaries, with gastric antrum extract showing a significant CRF activity. The antrum extract showed a dose-related CRF activity in vitro using rat pituitary cell culture, and the dose-response curve appeared to be parallel with that of synthetic rat hypothalamic CRF.

Quality control aspects of pulmonary function testing in the Multiple Risk Factor Intervention Trial.

Pulmonary function testing was used in MRFIT to monitor the presence of airways disease and to assess changes in pulmonary function over time. The pulmonary function indices that were measured were FEV1, FVC, and MMEF, (FEF25-75). Quality control of technician training, equipment maintenance, data collection, and data measurement were essential to ensure that results, over time and from various clinics, could be compared.

Quality control aspects of expired air carbon monoxide measurement in the Multiple Risk Factor Intervention Trial.

The determination of carbon monoxide levels in the expired air of MRFIT participants was used to monitor the level of cigarette smoking in all participants and to assess the adherence of the SI participants to the MRFIT protocol, which required that they quit or reduce their cigarette smoking. Two problems affected the quality of the data. First, as with the measurements of pulmonary function (Chapter 12), the initial lack of training in adequate maintenance was responsible for inoperative instruments.

Effective organ blood flow and bioenergy status in murine peritonitis.

Whether organ dysfunction frequently encountered in overwhelming bacterial sepsis is a result of a direct cellular "toxic" effect or diminished cellular perfusion remains controversial. To assess the effects of peritonitis on cellular energy status and visceral blood flow, peritonitis was induced in rats by means of cecal ligation and perforation. Five, 10, or 20 hours after cecal ligation and perforation, cardiac outputs were determined by thermodilution, effective hepatic blood flow was determined by low-dose galactose clearance, and effective renal plasma flow was determined by paraminohippuric acid clearance.

Validation of hospital discharge diagnosis data for chronic obstructive pulmonary disease and other allied conditions.

The assumption that discharge diagnoses of chronic obstructive pulmonary disease and other allied conditions accurately reflect patient medical records was tested using a sample of 553 hospital discharges from the Pittsburgh, Pennsylvania area. Three validation criteria were used in reviewing patient hospital records: 1) the presence of abnormal spirometry test results; 2) reference made to a previous diagnosis of one of the conditions; and 3) reports of respiratory symptoms consistent with these conditions. The findings were that 1 per cent of the 432 cases with a primary diagnosis in this disease category and 10 per cent of the 121 cases with a primary diagnosis of heart disease and a secondary diagnosis in this disease category were not supported by any of the selected criteria.

Alterations of hepatic mitochondrial function in a model of peritonitis in immature rats.

Severe intra-abdominal infection results in significant metabolic dysfunction, multiple systems failure, and mortality. Although the course of peritonitis is particularly rapid and severe in neonates and small children, its physiologic consequences have been poorly studied in these age groups. In order to assess hepatic mitochondrial integrity in a model of fulminant peritonitis in immature animals, the following study was undertaken.