Lung ultrasonography for assessment of oxygenation response to prone position ventilation in ARDS

Purpose

Prone position (PP) improves oxygenation and outcome of acute respiratory distress syndrome (ARDS) patients with a PaO₂/FiO₂ ratio <150 mmHg. Regional changes in lung aeration can be assessed by lung ultrasound (LUS). Our aim was to predict the magnitude of oxygenation response after PP using bedside LUS.

Methods

We conducted a prospective multicenter study that included adult patients with severe and moderate ARDS. LUS data were collected at four time points: 1 h before (baseline) and 1 h after turning the patient to PP, 1 h before and 1 h after turning the patient back to the supine position. Regional lung aeration changes and ultrasound reaeration scores were assessed at each time. Overdistension was not assessed.

Results

Fifty-one patients were included. Oxygenation response after PP was not correlated with a specific LUS pattern. The patients with focal and non-focal ARDS showed no difference in global reaeration score. With regard to the entire PP session, the patients with non-focal ARDS had an improved aeration gain in the anterior areas. Oxygenation response was not associated with aeration changes. No difference in PaCO₂ change was found according to oxygenation response or lung morphology.

Conclusions

In ARDS patients with a PaO₂/FiO₂ ratio ≤150 mmHg, bedside LUS cannot predict oxygenation response after the first PP session. At the bedside, LUS enables monitoring of aeration changes during PP.

     

Women's angiographic vitamin and estrogen trial: design and methods

The Women's Angiographic Vitamin and Estrogen trial was a randomized, double-blind, placebo-controlled study designed to test the efficacy of estrogen replacement and antioxidant vitamins for preventing angiographic progression of coronary artery disease. Postmenopausal women with one or more angiographically documented coronary stenoses of 15-75% at baseline were assigned in a 2 x 2 factorial randomization to active hormone replacement therapy (conjugated estrogens for women who had had a hysterectomy or conjugated estrogens with medroxyprogesterone for women with intact uteri) or placebo and to active vitamins E and C or their placebos. Seven clinical centers, five in the United States and two in Canada, randomized 423 women between July 1997 and July 1999. Quantitative coronary angiography was performed at baseline and repeated after projected mean follow-up of 3 years.     

Circulating immune complexes in patients with gram negative septic shock

Summary In order to explain complement components abnormalities observed during septic shock, circulating immune complexes (C.I.C.) were searched for in sera from 34 patients with gram negative sepsis by two different methods: polyethylene glycol precipitation test based on physical properties of C.I.C. and C1q deviation test based on the property of radiolabelled C1q to react with C.I.C. Serum immunoglobulins (IgG, IgA, IgM) and complement components (C1q, C3, C4) levels were simultaneously determined. Seventeen patients with minimal haemodynamic abnormalities had normal or increased levels (except C4 at 62% of normal) and in eleven cases both tests for C.I.C. were simultaneously positive. Seventeen patients with severe septic shock had a decrease in IgG, IgM, C1q, C3 and C4 and none had both tests for C.I.C. simultaneously positive (P<10^–4). The disappearence of C.I.C. in patients with severe septic shock associated with evidence of complement activation suggests their involvement in the pathogenesis of septic shock in man.This work was supported by grants from Conseil Scientifique de l'Université Paris Val de Marne and Délégation Générale de la Recherche Scientifique et Technique, Contracts N° 7510954 and 7771396     

Biosynthesis of Kitasamycin(Leucomycin) by Leucine Analog-Resistant Mutants of Streptomyces kitasatoensis

The biosynthesis of kitasamycin in Streptomyces kitasatoensis B-896 was profoundly influenced by the addition of precursors to complex and defined media: l-valine and l-leucine directed biosynthesis towards the pairs A(4)/A(5) (R(2) = butyryl) and A(1)/A(3) (R(2) = isovaleryl), respectively, and total kitasamycin titers were doubled and quadrupled, respectively. S. kitasatoensis B-896 was very resistant (>20 mg/ml) to alpha-aminobutyric acid, an analog of l-valine, but very susceptible to l-leucine analogs 5', 5', 5'-trifluoroleucine and 4-azaleucine (5 to 10 mug/ml). The inhibition by 4-azaleucine could be reversed by l-leucine, but by none of the other amino acids of the pyruvate family or the amino acids of the aspartate pathway. 4-Azaleucine-resistant mutants were isolated which in the absence of any precursors overproduced l-leucine and a kitasamycin complex mainly consisting of the pair A(1)/A(3). These 4-azaleucine-resistant mutants are presumed to be regulatory mutants in which alpha-isopropylmalate synthase, the first enzyme of the l-leucine pathway, has become either derepressed or desensitized to leucine feedback inhibition. l-Leucine-regulatory mutants have economic value: in the absence of expensive precursors, they produce a kitasamycin complex in which the most potent pair A(1)/A(3) is dominant and the least active components are absent.     

Decrease in serum procalcitonin levels over time during treatment of acute bacterial meningitis

Introduction

The aim of this study was to describe the change in serum procalcitonin levels during treatment for community-acquired acute bacterial meningitis.

Methods

Out of 50 consecutive patients presenting with bacterial meningitis and infection at no other site, and who had received no prior antibiotic treatment, 48 had a serum procalcitonin level above 0.5 ng/ml on admission and were enrolled in the study.

Results

The mean age of the patients was 55 years, and mean Glasgow Coma Scale score on admission was 13. The time from symptom onset to admission was less than 24 hours in 40% of the patients, 24–48 hours in 20%, and more than 48 hours in 40%. The median (interquartile) interval between admission and initial antibiotic treatment was 160 min (60–280 min). Bacterial infection was documented in 45 patients. Causative agents included Streptococcus pneumoniae (n = 21), Neisseria meningitidis (n = 9), Listeria monocytogenes (n = 6), other streptococci (n = 5), Haemophilus influenzae (n = 2) and other bacteria (n = 2). The initial antibiotic treatment was effective in all patients. A lumbar puncture performed 48–72 hours after admission in 34 patients showed sterilization of cerebrospinal fluid. Median (interquartile) serum procalcitonin levels on admission and at day 2 were 4.5 (2.8–10.8) mg/ml and 2 (0.9–5.0) mg/ml, respectively (P < 0.0001). The corresponding values for C-reactive protein were 120 (21–241) mg/ml and 156 (121–240) mg/ml, respectively. Five patients (10%) died from noninfectious causes during their hospitalization.

Conclusions

Serum procalcitonin levels decrease rapidly with appropriate antibiotic treatment, diminishing the value of lumbar puncture performed 48–72 hours after admission to assess treatment efficacy.     

The case for an “abnormal” insulin in diabetes mellitus

Summary Understanding of diabetes in molecular terms has advanced very little. The possibility that a structural difference exists in the circulating and pancreatic insulin moiety of diabetics is supported by three lines of evidence obtained in the authors' laboratory. — Immunologically purified circulating insulin from diabetic subjects untreated with insulin was noted to be relatively resistant to degradation by a crude muscle insulinase preparation. The pancreatic insulin of five diabetic pancreases was found to have a decreased biological activity in its ability to enhance glycogen synthesisin vivo and in its capacity to stimulate RNA turnover in tissue culture. — The nature of this abnormal insulin and its hypothetical role in the physiopathology of diabetes are discussed in the light of the need for a specific definition of the precise molecular change.This work was supported by U.S. Public Health Service Grants nos. HD-2578-01 and FR-69.     

Serum hepatitis B virus DNA levels and liver histology in inactive HBsAg carriers

BACKGROUND/AIMS: A recent NIH research workshop on hepatitis B virus (HBV) revisited the definition of healthy HBsAg carriers. The new definition inactive surface antigen (HBsAg) carriers includes an estimated serum HBV DNA level below 105 copies/ml. However, this cut-off value needs to be confirmed. METHODS: Eighty-five consecutive patients, HBsAg-positive/HBeAg-negative with persistently normal alanine aminotransferase (ALT) and undetectable serum HBV DNA with standard assay (Versant HBV DNA Assay (bDNA), Bayer) were prospectively followed for 3.2+/-2.6 (range 0.5-11) years; 58 underwent a liver biopsy. Serum HBV DNA was quantified with a sensitive polymerase chain reaction assay (Cobas Amplicor HBV Monitor, Roche) (sensitivity 200 copies/ml), and liver histology was assessed using the Ishak scoring system. RESULTS: The median serum HBV DNA level was 1300 copies/ml (<200-179 x 10(3) copies/ml), 16% of the subjects had no detectable serum HBV DNA and 98% had levels below 10(5) copies/ml. Histologic lesions were mild (total score <7) in all cases. Loss of HBsAg was observed in three patients, three patients experienced a transient increase in ALT (<2 x upper limit of normal), and serum HBV DNA levels remained stable (1-6 years) in 97% of the 38 patients retested. CONCLUSIONS: In our study of inactive HBsAg carriers, the median serum HBV DNA level was 1300 copies/ml, the serum HBV DNA level was below 10(5) copies/ml in 98% of the patients, and remained stable; histological lesions were mild in all cases.     

Ultimate journey of the terminally ill: Ways and pathways of hope

ObjectiveTo better understand the role of hope among terminally ill cancer patients.DesignQualitative analysis.SettingA tertiary specialized cancer centre in Canada.ParticipantsCancer patients in palliative care with an estimated remaining life expectancy of 12 months or less (N = 12) and their loved ones (N = 12) and treating physicians (N = 12).MethodsEach patient underwent up to 3 interviews and identified a loved one who participated in 1 interview. Treating physicians were also interviewed. All interviews were fully transcribed and analyzed by at least 2 investigators. Interviews were collected until saturation occurred.ConclusionApproaches aimed at sustaining hope need to reflect that patients’ reactions might fluctuate between despair and a form of acceptance that leads to a certain serenity. Clinicians need to maintain some degree of hope while remaining as realistic as possible. The findings also raise questions about how hope influences patients’ perceptions and acceptance of their treatments.