The use of self-interaction chromatography in stable formulation and crystallization of proteins.

This paper reviews the basic principles of the recently developed self-interaction chromatography (SIC) technique with regard to protein solution stability and protein crystallization. It gives experimental protocols for both normal-scale and micro-scale SIC experiments and reviews recent developments and current applications of this novel technique in the biopharmaceutical area. This paper aims to be a benchmark in the further proliferation of this highly effective and fast technology for the rational design of stable aqueous formulations of therapeutic proteins and the determination of solution conditions favoring protein crystallization.

Surviving severe acute respiratory distress syndrome: utility of open-lung biopsy and large doses of dexamethasone.

The etiology of acute respiratory distress syndrome is wide and mortality is extremely high. We describe a patient dying from severe acute respiratory distress syndrome who had a tremendous recovery after receiving dexamethasone (1 g daily). This patient required positive end-expiratory pressure (up to 18 mm/Hg) and fractional inspiratory oxygen (up to 100%). Thirty-six hours after the large dose of corticosteroids, the respiratory mechanics and oxygenation were acceptable for extubation. Acute respiratory distress syndrome was proven and other etiologies of respiratory failure were ruled out by a bedside open-lung biopsy. The biopsy proven acute respiratory distress syndrome dramatically resolved with this salvage therapy. High-dose usage of corticosteroids for acute respiratory distress syndrome has tremendous potential.

The incidence of infectious complications of central venous catheters at the subclavian, internal jugular, and femoral sites in an intensive care unit population.

OBJECTIVE: The objective was to assess the risk of central venous catheter infection with respect to the site of insertion in an intensive care unit population. The subclavian, internal jugular, and femoral sites were studied. DESIGN: An epidemiologic, prospective, observational study. SETTING: The setting is a well-functioning intensive care unit under a unified critical care medicine division in a university teaching hospital. Critical care medicine attendings and fellows covered on site 17 and 24 hrs per day, respectively. PATIENTS: Patients were critically ill. All patients were triaged into the intensive care unit by on-site critical care medicine fellows. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In an intensive care unit population, we prospectively studied the incidence of central venous catheter infection and colonization at the subclavian, internal jugular, and femoral sites. The optimal insertion site for each individual patient was selected by experienced intensive care physicians (critical care medicine attendings and fellows). All of the operators were proficient in inserting catheters at all three sites. Confounding factors were eliminated; there were a limited number of experienced operators inserting the catheters, a uniform protocol stressing strict sterile insertion was enforced, and standardized continuous catheter care was provided by dedicated intensive care nurses proficient in all aspects of central venous catheter care. Two groups of patients were analyzed. Group 1 was patients with one catheter at one site, and group 2 was patients with catheters at multiple sites. Group 1 was the primary analysis, whereas group 2 was supporting.A total of 831 central venous catheters and 4,735 catheter days in 657 patients were studied. The incidence of catheter infection (4.01/1,000 catheter days, 2.29% catheters) and colonization (5.07/1,000 catheter days, 2.89% catheters) was low overall. In group 1, the incidence of infection was subclavian: 0.881 infections/1,000 catheter days (0.45%), internal jugular: 0/1,000 (0%), and femoral: 2.98/1,000 (1.44%; p = .2635). The incidence of colonization was subclavian: 0.881 colonization/1,000 catheter days (0.45%), internal jugular: 2.00/1,000 (1.05%), and femoral: 5.96/1,000 (2.88%, p = .1338). There was no statistically significant difference in the incidence of infection and colonization or duration of catheters (p = .8907) among the insertion sites. In group 2, there was also no statistically significant difference in the incidence of infection and colonization among the three insertion sites. CONCLUSION: In an intensive care unit population, the incidence of central venous catheter infection and colonization is low overall and, clinically and statistically, is not different at all three sites when optimal insertion sites are selected, experienced operators insert the catheters, strict sterile technique is present, and trained intensive care unit nursing staff perform catheter care.

Length-normalized pulse photoplethysmography: a noninvasive method to measure blood hemoglobin.

To determine whether blood hemoglobin concentration ([Hb]) could be measured noninvasively as the ratio of pulsatile changes in attenuation (absorbance plus scatter) of light (D) across a body part to changes in light path length (l), we measured transmission of near-infrared light (905 +/- 10 nm) through a finger, using a modified pulse oximeter, and simultaneously monitored fingertip diameter, using a sonomicrometer. In 25 subjects with [Hb] ranging from 3.1 to 18.2 gm/dl, and with normal oxygenation, average D/l ratio over 30-60 s correlated strongly with [Hb] measured by Coulter counter (r = 0.84, p << 0.001), though with considerable scatter, with absolute value of differences averaging 17% of the mean. Using 12 gm/dl and 0.75 mm(-1) as the lower limits of normal for [Hb] and D/l, respectively, two of nine normals had low (D/l) (78% specificity), and only one of 16 anemic subjects had borderline normal (D/l) (94%-100% sensitivity). The positive predictive value of a low (D/l) was 88% and the negative predictive value was 87.5%. With further development, this technique may reduce the need for phlebotomy, thereby reducing risks and costs and improving the experience of being a patient.