The genome sequence of Schizosaccharomyces pombe.

We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.

The accuracy of the estimation of body weight and height in the intensive care unit.

A telephone survey of 20 English intensive care units (ICUs) confirmed that visual estimation of patient weight is often performed. Four experienced intensive care staff (three doctors and one nurse) estimated the weight and measured the height of 30 volunteers and the estimates were compared with accurate reference measurements. The estimates were shown to be significantly inaccurate for individual observers. We consider the degree of inaccuracy to be of clinical importance. However, pooling the individual estimates of weight as mean values improved accuracy. Recommendations are made concerning the performance of height and weight determination.

Convulsions and respiratory arrest in association with desmopressin administration for the treatment of a bleeding tonsil in a child with borderline haemophilia.

Desmopressin (DDAVP) may be used to augment the action of factor VIII in mild haemophilia. Its use has been associated with serious adverse effects. We report a case of a three-year-old child with a family history of haemophilia who suffered complications due to severe acute hyponatraemia following the administration of this drug for post-tonsillectomy bleeding.

Severe non-ketotic hyperosmolar coma--intensive care management.

We report a case of non-ketotic hyperosmolar coma, which presented with blood sugar levels far exceeding any previously recorded in the literature. The patient developed acute renal failure, probably because of rhabdomyolysis, which was successfully managed with continuous veno-venous haemofiltration. He developed blurring of vision resulting from biochemical changes, which was managed conservatively. We discuss the mechanisms of causation of the renal failure and visual blurring.

Large-scale sequence comparisons reveal unusually high levels of variation in the HLA-DQB1 locus in the class II region of the human MHC.

Comparison of genomic sequences flanking the HLA-DQB1 locus in the human MHC class II region reveals local sequence variation of up to 10%, which is the highest level of sequence variation found in the human genome so far. The variation is haplotype-specific and extends far beyond the transcriptional unit of the DQB1 gene, suggesting hitch-hiking along with functionally selected alleles as the most likely mechanism. All major insertions/deletions (indels) were found to be of retroviral origin and in the immediate upstream region of DQB1. Possible cis-acting effects of these indels on the transcriptional regulation of DQB1 are discussed.

The chromosome 6 sequencing project at the Sanger Centre.

Chromosome 6 is probably best known for encoding the major histocompatibility complex (MHC) which is essential to the human immune response. In addition, it has been shown to be associated with many diseases such Schizophrenia, Diabetes, Arthritis, Haemochromatosis, Narcolepsy, Epilepsy, Retinitis Pigmentosa, Deafness, Ovarian Cancer, and many more. Chromosome 6 is about 180 Mb in size and is estimated to encode around 3500 genes of which only about 10% are currently known. It is our aim to map, sequence and annotate the entire chromosome in close collaboration with the chromosome 6 community.

Can consultants resuscitate?

Twenty-four of 53 hospital consultants responded to an offer to attend a resuscitation training course. Fourteen of them had never had resuscitation training. Their performance of basic life-support was assessed before and after training according to the Resuscitation Council UK recommendations. Their initial performance of basic life-support on a manikin was extremely poor. One hour of training and practice resulted in statistically significant improvements.

Comparison of the effects of high frequency oscillation and controlled mechanical ventilation on hyaline membrane formation in a rabbit model of the neonatal respiratory distress syndrome.

Saline lavage of the lungs of eight anaesthetized New Zealand White rabbits was performed to produce a surfactant-depletion model of the neonatal respiratory distress syndrome. A characteristic change in the shape of the pressure-volume curve occurred, with the appearance of an inflection point on the inspiratory limb. The animals were treated with high frequency oscillation (HFO) at 15 Hz and the results compared with those of a previously studied group of eight similar rabbits treated with controlled mechanical ventilation (CMV) with end-expiratory pressure equal to the pressure at the inflection point, but with the same mean airway pressure of 15 mm Hg. The animals treated with HFO had significantly higher arterial oxygen tensions and end-expiratory lung volumes than those treated with CMV, but there was no significant difference between hyaline membrane scores. Although there was no significant difference in mean survival times, five of the HFO treated animals showed reversion of the shape of their pressure-volume curves towards the prelavage configuration, suggesting a recovery of surfactant function.

Effects of altered patterns of ventilation and of increased cardiac output on blood flow to a collapsed lung in anaesthetized, closed-chest dogs.

Right-to-left shunt (Qs/Qt) was measured by the SF6 and oxygen methods in 13 anaesthetized closed-chest dogs intubated with a double-lumen endobronchial tube. Collapse of the left lung increased Qs/Qt from 10% to 23%, suggesting that blood flow to the left lung had been reduced by about 60%. Increasing right lung mean airway pressure by the alteration of the inspiratory:expiratory time ratio or the application of PEEP produced a small but non-significant increase in Qs/Qt with significant increases in arterial and mixed venous carbon dioxide tensions, and arterial to right lung end-tidal carbon dioxide tension difference. Fluid loading during collapse increased cardiac output and pulmonary vascular pressures, but Qs/Qt did not differ significantly from the normovolaemic collapsed state. Increasing the right mean airway pressure in this condition had no effect on Qs/Qt or carbon dioxide tensions.

Effects of positive end-expiratory pressure on hyaline membrane formation in a rabbit model of the neonatal respiratory distress syndrome.

Sixteen rabbits were anaesthetized and subjected to saline lavage of the lungs to produce surfactant deficiency. This resulted in an arterial oxygen tension of less than 12 kPa on 100% inspired oxygen and an inflection point on the pressure-volume curve at a pressure of 8-12 mmHg. After lavage the animals were randomly assigned to receive either conventional mechanical ventilation (CMV) with a positive end-expiratory pressure (PEEP) of 1-2 mmHg (group I - low PEEP) or CMV with PEEP equal to the inflection point pressure (group II - high PEEP). Mean airway pressures were kept at 14-16 mmHg in both groups by increasing the inspiratory:expiratory time ratios in the low PEEP group. The 5-h protocol was completed by 4 animals in group I and 6 animals in group II, early death usually being associated with a metabolic acidosis. On 100% oxygen, the mean PaO2 at 2-h post-lavage was 15.2 +/- 8.3 kPa in group I and 39.6 +/- 21.8 kPa in group II. Group I had much lower end-expiratory lung volumes (3.0 +/- 1.5 ml above FRC) than group II (34.9 +/- 12.2 ml above FRC). Histological examination of the lungs revealed significantly less hyaline membrane formation in group II (p = 0.001). Thus, the prevention of alveolar collapse by the use of high PEEP levels appears to reduce lung damage in this preparation.

Studies on continuous positive airway pressure breathing systems.

A study was undertaken to compare CPAP/IMV systems shown to be in common use in the U.K. The most frequently used system (Servo 900B) has characteristics which are likely to increase the work of breathing. Recommendations are made regarding the theoretically most acceptable systems.