Safety and efficacy of molgramostim as an adjunctive therapy in critically ill patients with severe sepsis

The aim of this uncontrolled, prospective, clinical study was to investigate the efficacy and safety of molgramostim administration in patients with severe sepsis. The subjects were 20 critically ill, mechanically ventilated patients with severe sepsis in a university intensive care unit (ICU). Molgramostim 300 microg s.c. was given every 12 h for 3 d. Treatment for severe sepsis was also administered as medically indicated. No adverse events (clinical or serum chemistry) were considered as drug related. Temperature (p = 0.334) and PaO2/FiO2 index (arterial oxygen tension/inspiratory oxygen fraction) (p = 0.178) were not significantly changed. Total leukocyte and neutrophil count increased significantly (p < 0.001) during drug administration. Simplified Acute Physiology Score II (SAPS II) was not significantly increased (p = 0.955), but there was a statistically significant decrease (p = 0.006) in Sepsis-related Organ Failure Assessment (SOFA) score. Death probability was not statistically different compared with mortality rate on day 28 and overall mortality (p = 0.238 and 0.700, respectively). There were statistically significant decreases (p < 0.01) in serum tumor necrosis factor-alpha (TNF-alpha), TNF-RII and interleukin-2 (IL-2), and an increase in TNF-RI levels between study entry and day 3. Mean ICU stay was 40.2 +/- 7.7 d. In conclusion, molgramostim administration may not affect serum chemistry and PaO2/FiO2 index, may decrease SOFA score but does not produce significant clinical benefit in terms of patients' outcome compared with death probability. It may also influence TNF-alpha, TNF-RI and TNF-RII serum complex levels. These changes may be attributed to the natural clinical course of sepsis or therapy applied.     

Evaluation of attempted prevention of unexpected infant death in very high-risk infants by planned health care

Three hundred and ninety-six babies born in Sheffield between 1982 and 1990 identified as being at "very high risk" of unexpected infant death by means of a scoring system, received an intensive programme of health care including a case discussion between a paediatrician, the GP and the health visitor held in the family doctor's surgery, weekly visits from the health visitor and informal hospital admission. Significantly fewer sudden unexpected infant deaths occurred in this group than were expected by logistic regression anlysis or occurred in the best available control group with comparable scores ( p = 0.024). Problems in evaluation include identification of an adequate control population, ethical difficulties in introducing a controlled study when the programme is already perceived as effective, and the calculation of "expected death rates". The results of this study indicate that very energetic programmes of intervention may prevent some deaths in vulnerable infants.     

Outcome of congenital lung abnormalities detected antenatally

To determine the outcome of congenital lung abnormalities, data were collected retrospectively between January 1991 and December 1996 on any foetus found to have a lung lesion on antenatal ultrasound. A total of 23 foetuses had lung lesions on antenatal ultrasound. In two foetuses the antenatal ultrasound showed bilateral enlarged "bright" echogenic lungs with evidence of hydrops. Both pregnancies were terminated and tracheal atresia was confirmed. In 15 foetuses the antenatal ultrasound appearance was of a unilateral "bright" echogenic lung. There was one case of bronchial atresia and two cases of congenital lobar emphysema, which all had surgery. In nine cases there was a reduction in the size of the lesion on serial antenatal ultrasounds and no lesion was detected after birth. In three cases a small lesion was present after birth on chest radiography. In six foetuses the antenatal ultrasound appearance was of unilateral cystic or mixed cystic and echogenic lung lesions. Two pregnancies were terminated; both had congenital cystic adenomatoid malformation. Four pregnancies were continued and three infants had surgery soon after birth and were confirmed to have had congenital cystic adenomatoid malformation. One infant has been managed conservatively. In conclusion, a definitive diagnosis cannot usually be made antenatally. A large lesion on initial scan does not necessarily predict a poor outcome. The natural history of small asymptomatic postnatal lesions is unknown and a long-term prospective study is needed to determine the outcome of these lesions.     

Serotypes of Pseudomonas aeruginosa in clinical specimens in relation to antibiotic susceptibility.

Ninety-eight hospital strains of Pseudomonas aeruginosa isolated from six different hospitals in Athens were serotyped by a slide agglutination test with unabsorbed commercial antisera. Serotypes O6, O11, O12, and "pool E" strains (strains that agglutinated only in pool E, which contained antisera against O2, O5, O15, and O16 antigens, but did not agglutinate in the individual antisera) predominated, accounting for more than 62% of all isolates tested. In respect to serotypes, (i) there was no apparent correlation with hospital of origin, (ii) most strains of serotypes O6 and O11 were sensitive to gentamicin and carbenicillin (iii) most strains of pool E were from urine and were resistant to these drugs, (iv) all 9 strains of serotype O12 tested were resistant to carbenicillin and all 5 strains tested hydrolyzed this drug, and (v) 24 of 25 strains of pool E were resistant to carbenicillin but only 2 of 17 strains hydrolyzed it.     

Airway intervention in adult supraglottitis

Background The timing of aggressive airway intervention in adult epiglottitis is controversial. Aims To correlate Friedman’s staging of epiglottitis on admission with the airway interventions undertaken. Methods A retrospective study of 23 adult patients, mean age 51 years (range 29–81 years), who had been admitted with acute supraglottitis between March 1988 and December 2000 was undertaken. Results Three patients (13%) had airway interventions; two with tracheostomy and one with tracheal intubation. All were Friedman stage III and had rapid symptom progression during the 24 hours prior to admission. Three other stage III patients with symptom progression longer than 24 hours and all the remaining patients (stage II or less) were managed with observation and intravenous therapy. Conclusions Friedman originally advocated airway intervention in any patient stage II or worse, but this intubation threshold should probably be lowered to those patients with rapid-onset stage III (moderate respiratory distress, stridor, respiratory rate >30 per minute, pCO₂ >45mmHg) disease.     

Gradual increase in the minimum inhibitory concentration of penicillin among both susceptible and resistant Streptococcus pneumoniae isolates from Greek children during 1995-1997

A total of 140 non-replicate Streptococcus pneumoniae community isolates from Greek children collected during the period 1995-1997 were studied. Combined intermediate and high penicillin resistance rates were 23% in 1995, 29% in 1996, and 27% in 1997. The proportion of highly resistant isolates steadily increased from 2% in 1995 to 12% in 1997. There was no significant difference in penicillin resistance rates among colonizing and infecting isolates (23 and 27%, respectively). Over the study period, a clear shift towards higher penicillin MIC was observed among both the susceptible and resistant groups. Thus, penicillin resistance rates were equally high among colonizing and infecting isolates and resistance levels appeared to be gradually increasing throughout the entire S. pneumoniae population.     

Detection of carbamyl phosphate synthetase 1 deficiency using duodenal biopsy samples

The activity of urea cycle enzymes was assayed in duodenal biopsy specimens obtained from a female infant who presented with neonatal hyperammonaemia. All enzyme levels were normal except N-acetyl glutamate-dependent carbamyl phosphate synthetase 1 (CPS1) which was half the mean activity in normal control specimens. A similar deficiency of CPS1 was also shown in duodenal specimens from the patient's mother who became slightly symptomatic after relatively high protein meals and during pregnancy, and had spontaneously modified her diet to one with protein restriction. The patient is growing normally on a dietary regimen similar to that spontaneously adopted by her mother. Urea cycle enzyme activity in the duodenal biopsy material from the controls was similar to that found in the normal human liver and appears to have distinct advantages as a means of assaying for urea cycle defects in patients with hyperammonaemia and their relatives.