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Biomedical subjects

H M Moore

Publications and source records attributed to H M Moore.

10 recordsLinked to original sources
PubMed2001

The sequence of the human genome.

A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

Algorithms↗
PubMed2001

In contrast to forskolin and 3-isobutyl-1-methylxanthine, amrinone stimulates the cardiac voltage-sensitive release mechanism without increasing calcium-induced calcium release.

The objective of this study was to determine whether the voltage-sensitive release mechanism (VSRM) can be stimulated independently from Ca(2+)-induced Ca(2+) release (CICR) by drugs that elevate intracellular cAMP. Contractions were measured in voltage-clamped guinea pig ventricular myocytes at 37 degrees C. Na(+) current was blocked. We compared effects of agents that elevate cAMP through activation of adenylyl cyclase (1 microM forskolin), nonspecific inhibition of phosphodiesterases (PDEs) [100 microM 3-isobutyl-1-methylxanthine (IBMX)], and selective inhibition of PDE III (100-500 microM amrinone) on contractions initiated by the VSRM and CICR. Forskolin and IBMX significantly increased peak Ca(2+) current and CICR. In addition, these agents also markedly increased contractions elicited by test steps from -65 to -40 mV, which activate the VSRM. However, because these steps also induced inward current in the presence of forskolin or IBMX, CICR could not be excluded. In contrast, amrinone caused a large, concentration-dependent increase in VSRM contractions but had no effect on CICR contractions or Ca(2+) current. Sarcoplasmic reticulum Ca(2+), assessed by rapid application of caffeine (10 mM), was increased only modestly by all three drugs. Normalization of contractions to caffeine contractures indicated that amrinone increased fractional release by the VSRM, but not CICR. Forskolin and IBMX increased fractional release elicited by steps to -40 mV. Increases in CICR induced by forskolin and IBMX were proportional to caffeine contractures. Thus, positive inotropic effects of cAMP on VSRM contractions may be compartmentalized separately from effects on Ca(2+) current and CICR.

1-Methyl-3-isobutylxanthine↗
PubMed2000

Therapeutic embolization for acute haemorrhage in the abdomen and pelvis.

Therapeutic embolization for acute haemorrhage is increasingly being utilized. An audit of 34 patients undergoing therapeutic embolization for acute abdominal or pelvic haemorrhage was undertaken, in an attempt to assess the importance of the following variables in determining a successful outcome: coagulation status, transfusion status, time to procedure after onset of circulatory instability, duration of procedure, and the effect of the embolization technique employed. Overall success was 79%, with definitive control of haemorrhage achieved by embolization; 21% required surgical management for rebleeding 4-24 h post embolization. The duration of the procedure and transfusion status of the patient were the most important factors associated with a successful outcome.

Abdomen↗
PubMed1998

Severe acute respiratory distress syndrome secondary to acute pancreatitis successfully treated with extracorporeal membrane oxygenation in three patients.

OBJECTIVE: To review three patients who underwent extracorporeal membrane oxygenation (ECMO) for acute respiratory failure secondary to pancreatitis. SUMMARY BACKGROUND DATA: Severe acute pancreatitis often causes the acute respiratory distress syndrome (ARDS), and if ventilation is required, the mortality rate is more than 50%. If the ratio of PaO2/FiO2 falls below 100 mm Hg or the Murray lung injury score exceeds 3.5, the mortality rate rises to more than 80%. Three patients who have severe ARDS secondary to pancreatitis, who were hypoxic despite ventilation with 100% oxygen and high airway pressures, and who were all successfully treated with ECMO are reported here. The consensus here is that all three patients would have died without ECMO. METHODS: Retrospective chart review and discussion of the literature. RESULTS: Pre-ECMO data: mean PaO2/FiO2 59.3 mm Hg, mean Murray lung injury score 3.7, one patient administered 20 ppm inhaled nitric oxide. ECMO data: mean extracorporeal flow at initiation of ECMO 56.3 mL/kg per minute, all patients administered veno-venous ECMO, mean duration of ECMO 104.7 hours. All patients were successfully weaned from ECMO and extubated. One patient had a protracted hospital stay because of a colo-cutaneous fistula. All patients are long-term survivors. CONCLUSIONS: Extracorporeal membrane oxygenation proved an effective therapy for severe ARDS complicating acute pancreatitis. Extracorporeal membrane oxygenation was conducted without bleeding complications in these three patients.

Acute Disease↗
PubMed1997

Extracorporeal membrane oxygenation for adult respiratory failure.

OBJECTIVES: To review the first 50 patients to receive extracorporeal membrane oxygenation (ECMO) for respiratory failure at Glenfield Hospital, and to compare them with published series of patients receiving positive pressure ventilation. DESIGN: Retrospective chart review. SETTING: Extracorporeal Life Support Organization/European Extracorporeal Life Support Organization recognized ECMO center. PATIENTS: Fifty consecutive patients referred for ECMO with respiratory failure refractory to conventional management between 1989 and 1995. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Primary end point was survival to hospital discharge, 66%. Other data (mean and SD): Murray Lung Injury Score, 3.4 (0.5); ratio of PaO2 to fraction of inspired oxygen, 65 (36.9) mm Hg; duration of ventilation pre-ECMO, 76.5 (83.7 h); peak airway pressure, 39.6 (7.4) cm H2O; end-expiratory pressure, 10 (3.3) cm H2O; minute ventilation, 12.6 (3.32) L/min; age, 30.1 (10.8) years; duration of ECMO, 207.4 (177.8) h; and units of blood transfused, 19 (17.3). Survival was significantly better than two previously reported series of patients receiving positive pressure ventilation (55.6% and 42% survival), p=0.036 and p=0.0006. Odds ratio for improved survival was 0.46 (95% confidence interval, 0.22 to 0.97, p=0.036). CONCLUSIONS: Survival with ECMO is 66% for adults with severe respiratory failure. ECMO should be considered in patients who remain hypoxic despite maximal positive pressure ventilation.

Adult↗
PubMed1996

Cannulation of neonates for venovenous extracorporeal life support.

Venovenous access via a double-lumen cannula in the right internal jugular vein is the extracorporeal life support mode of choice for neonates with respiratory failure. We report a simplified method of cannulation. The advantages of this "semi-Seldinger" method include the ability to cannulate without ligating the internal jugular vein, and to adjust the position of the cannula and decannulate without re-exploring the wound.

Cardiac Catheterization↗
PubMed1995

Extracorporeal membrane oxygenation for the treatment of massive pulmonary embolism.

After witnessing the death of a patient following pulmonary embolectomy, John H. Gibbon, Jr, developed the idea of a device for extracorporeal oxygenation and circulation. What followed has led to the present-day method of extracorporeal membrane oxygenation as an effective method of cardiorespiratory support. In this case of massive acute pulmonary embolism, its use in a conscious patient completes the circle from the first ideas of Gibbon.

Acute Disease↗