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Biomedical subjects

J L Moran

Publications and source records attributed to J L Moran.

At least 37 records · Page 2Linked to original sources
PubMed2002

Phosphate metabolism in intensive care patients with acute respiratory failure.

OBJECTIVE: To determine the variables predicting the change of plasma phosphate over the first 24 hr period in intensive care in patients with acute respiratory failure. METHODS: Fifty-seven patients were studied prospectively in a university teaching hospital intensive care unit (ICU). Thirty two patients were classified as having acute respiratory failure and a primary respiratory system diagnosis (group I), 10 were classified as having acute cardiogenic pulmonary oedema (group II) and 15 were general ICU patients (group III). Arterial blood specimens at intensive care unit admission (T0) and at 24 hr post-admission (T24) were assayed for multiple plasma biochemical parameters including phosphate (PO4) and red blood cell 2,3-diphosphoglycerate (2,3-DPG). Timed urine collections were used to determine 24 hr urine phosphate loss and renal phosphate threshold concentration (RTP). During the measurement period glucose-free fluids only were infused. RESULTS: Fifty seven patients had a mean (+/- SD) age of 67 +/- 12 years and Apache II score of 22 +/- 6. The plasma PO4 at T0 was 1.55 +/- 0.71 mmol/L and showed a significant 24 hr decrease of 0.55 mmol/L (p < 0.0001) at T24. Hypophosphataemia at T0 was observed in 26% of patients. Red blood cell 2,3-DPG was not elevated at T0 (13.5 +/- 3.3 umol/gHb) and showed a non-significant increment over 24 hr. Urine phosphate loss over the 24 hr period was 21.8 +/- 14.0 mmol with RTP being reduced below the lower reference range limit in groups I (0.65 +/- 0.29 mmol/L) and II (0.57 +/- 0.29 mmol/L). The naive form of phosphate change (PO4T24-PO4T0) was significantly related to initial plasma PO4 and was subject to regression to the mean, which was estimated to have inflated the relationship by 25%. The appropriate form of phosphate change was found to be log ratio T24/T0 phosphate. Independent predictors of log ratio T24/T0 phosphate were 24 hr change (T24-T0) in both 2,3-DPG and arterial pH, RTP, prescription of aminophylline (categorical factor) and the interaction of aminophylline and RTP (R2 = 0.65, ordinary least squares regression). CONCLUSIONS: Twenty-four hour plasma phosphate decrement in intensive care unit patients was multi-factorial and was attended by a lowered renal threshold phosphate concentration.

Journal Article↗
PubMed2000

A high incidence of Shigella-induced arthritis in a primate species: major histocompatibility complex class I molecules associated with resistance and susceptibility, and their relationship to HLA-B27.

The human major histocompatibility complex (MHC) class I gene, HLA-B27, is a strong risk factor for susceptibility to a group of disorders termed spondyloarthropathies. Rodents that express HLA-B27 develop spondyloarthropathies, implicating HLA-B27 in the etiology of these disorders. To determine whether an HLA-B27-like molecule was associated with spondyloarthropathies in nonhuman primates, we analyzed the MHC class I cDNAs expressed in a cohort of rhesus macaques that developed reactive arthritis after an outbreak of shigellosis. We identified several cDNAs with only limited sequence similarity to HLA-B27. Interestingly, one of these MHC molecules had a B pocket identical to that of HLA-B39. Pool sequencing of radiolabeled peptides bound by this molecule demonstrated that, like HLA-B27 and HLA-B39, it could bind peptides with arginine at the second position. However, extensive analysis of the MHC class I molecules in this cohort revealed no statistically significant association between any particular MHC class I allele and susceptibility to reactive arthritis. Furthermore, none of the rhesus MHC class I molecules bore a strong resemblance to HLA-B27, indicating that reactive arthritis can develop in this animal model in the absence of an HLA-B27-like molecule. Surprisingly, there was a statistically significant association between the rhesus macaque MHC A locus allele, Mamu-A*12, and the absence of reactive arthritis following Shigella infection.

Alleles↗
PubMed1999

A potential mechanism underlying the increased susceptibility of individuals with a polymorphism in NAD(P)H:quinone oxidoreductase 1 (NQO1) to benzene toxicity.

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a two-electron reductase that detoxifies quinones derived from the oxidation of phenolic metabolites of benzene. A polymorphism in NQO1, a C609T substitution, has been identified, and individuals homozygous for this change (T/T) have no detectable NQO1. Exposed workers with a T/T genotype have an increased risk of benzene hematotoxicity. This finding suggests NQO1 is protective against benzene toxicity, which is difficult to reconcile with the lack of detectable NQO1 in human bone marrow. The human promyeloblastic cell line, KG-1a, was used to investigate the ability of the benzene metabolite hydroquinone (HQ) to induce NQO1. A concentration-dependent induction of NQO1 protein and activity was observed in KG-1a cells cultured with HQ. Multiple detoxification systems, including NQO1 and glutathione protect against benzene metabolite-induced toxicity. Indeed, exposure to a noncytotoxic concentration of HQ induced both NQO1 and soluble thiols and protected against HQ-induced apoptosis. NQO1 protein and activity increased in wild-type human bone marrow cells (C/C) exposed to HQ, whereas no NQO1 was induced by HQ in bone marrow cells with the T/T genotype. Intermediate induction of NQO1 by HQ was observed in heterozygous bone marrow cells (C/T). NQO1 also was induced by HQ in wild-type (C/C) human bone marrow CD34(+) progenitor cells. Our data suggest that failure to induce functional NQO1 may contribute to the increased risk of benzene poisoning in individuals homozygous for the NQO1 C609T substitution (T/T).

Adult↗
PubMed1999

Genomic structure, mapping, and expression analysis of the mammalian Lunatic, Manic, and Radical fringe genes.

The three members of the mammalian fringe gene family, Manic fringe (Mfng), Radical fringe (Rfng), and Lunatic fringe (Lfng), were identified on the basis of their similarity to Drosophila fringe (fng) and their participation in the evolutionarily conserved Notch receptor signaling pathway. Fringe genes encode pioneer secretory proteins with weak similarity to glycosyltransferases. Both expression patterns and functional studies support an important role for Fringe genes in patterning during embryonic development and an association with cellular transformation. We have now further characterized the expression and determined the chromosomal localization and genomic structure of the mouse Mfng, Rfng, and Lfng genes; the genomic structure and conceptual open reading frame of the human RFNG gene; and the refined chromosomal localization of the three human fringe genes. The mouse Fringe genes are expressed in the embryo and in adult tissues. The mouse and human Fringe family members map to three different chromosomes in regions of conserved synteny: Mfng maps to mouse Chr 15, and MFNG maps to human Chr 22q13.1 in the region of two cancer-associated loci; Lfng maps to mouse Chr 5, and LFNG maps to human Chr 7p22; Rfng maps to mouse Chr 11, and RFNG maps to human Chr 17q25 in the minimal region for a familial psoriasis susceptibility locus. Characterization of the genomic loci of the Fringe gene family members reveals a conserved genomic organization of 8 exons. Comparative analysis of mammalian Fringe genomic organization suggests that the first exon is evolutionarily labile and that the Fringe genes have a genomic structure distinct from those of previously characterized glycosyltransferases.

Animals↗
PubMed1998

Nitrate therapy is an alternative to furosemide/morphine therapy in the management of acute cardiogenic pulmonary edema.

BACKGROUND: Nitrates are superior to furosemide in the management of acute pulmonary edema associated with myocardial infarction; however, their role in the absence of infarction is unclear. METHODS AND RESULTS: A randomized comparison was undertaken of the relative effectiveness of primary therapy with either intravenous morphine/furosemide (men/women; n = 32) or nitroglycerin/N-acetylcysteine (NTG/NAC; n = 37) in consecutive patients with acute pulmonary edema. The primary end point was change in PaO2/FIO2 over the first 60 minutes of therapy. Secondary end points were needed for mechanical respiratory assistance (ie, continuous positive airway pressure via mask or intubation and ventilation) and changes in other gas exchange parameters. Both treatment groups showed improvement in oxygenation after 60 minutes of therapy; however, this reached statistical significance only with NTG/NAC therapy. There was no significant difference between groups in the assessed parameters (95% CI for differences in Pao2/FIO2: furosemide/morphine -12 to 23 and NTG/NAC 4 to 44), a finding also confirmed in 32 patients presenting with respiratory failure. Only 11% of the study group required mechanical ventilatory assistance (continuous positive airway pressure in 4 patients and intubation and ventilation in 3 patients). CONCLUSIONS: NTG/NAC therapy is as effective as furosemide/morphine in the initial management of acute pulmonary edema, regardless of the presence or absence of respiratory failure. The necessity for mechanical ventilatory assistance is infrequent in these patients, regardless of the initial medical treatment regimen.

Acetylcysteine↗
PubMed1998

Acute exacerbations of chronic obstructive pulmonary disease and mechanical ventilation: a reevaluation.

OBJECTIVE: To review the intensive care unit (ICU) experience of patients admitted with acute exacerbations of chronic obstructive pulmonary disease. DESIGN: Retrospective case series. SETTING: University teaching hospital. PATIENTS: We reviewed the records of 100 consecutive ICU admissions of patients with acute exacerbations of chronic obstructive pulmonary disease over a period of 4.25 yrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were characterized using a computerized prospective database and case note review. Multivariate analysis identified variables predicting ICU and hospital length of stay. The Cox proportional hazards model was used to analyze survival after hospital discharge. Seventy-five patients (24 female and 51 male, mean age 68.5 +/- 7 [SD] yrs) with 100 ICU admissions were identified. Premorbid airway obstruction was severe, with forced expiratory volume in 1 sec (FEV1)/forced vital capacity (FVC) of 0.7 +/- 0.34 L and FEV1/FVC of 39 +/- 16%. Thirty-two percent received home-administered oxygen and 42% were housebound. The pre-ICU admission PaCO2 was 86 +/- 28 torr (11.5 +/- 3.7 kPa), with a pH of 7.24 +/- 0.11 and a PaO2/FIO2 of 190 +/- 66. ICU admission Acute Physiology and Chronic Health Evaluation II score was 18 +/- 5. Forty-three patients were mechanically ventilated for a median of 4 days (range 0.08 to 30). Tracheostomy, in seven patients, was maintained for 21 +/- 7 days. Ventilation time and tracheostomy frequency predicted length of ICU stay (median 3 days; range 1 to 40) and hospital stay (17 days; 4 to 97), respectively. ICU and hospital case-fatality rates were 1% and 11%. Out-of-hospital (24-month) probability of survival was predicted by plasma albumin concentration at the time of ICU admission; this probability of survival was .64 at an albumin concentration of 38 g/L. CONCLUSIONS: ICU admission of severely ill chronic obstructive pulmonary disease patients results in acceptable outcomes. Survival of < or =2 yrs is not affected by mechanical ventilation or tracheostomy requirement.

APACHE↗
PubMed1996

Drugs and brain death.

IN THE EARLY HOURS of the morning, a fit young man leaves a party, where drugs are reported to have been consumed, to walk home. A short time later he is found unconscious by the roadside, with severe head injuries. En route to hospital by ambulance, he suffers a cardiac arrest and is successfully resuscitated. On arrival at the Emergency Department he has obvious head injuries and is deeply unconscious, but shows spontaneous ventilatory movements. Available history is that he is a 20-year-old student with well-controlled epilepsy for which he takes phenytoin. It is not known how he sustained his injuries. Pupils are equal, small and react sluggishly to light. There is generalised flaccidity and an extensor-plantar response to painful stimuli. Skull x-rays show no fractures and computed tomography shows early cerebral oedema and scattered cerebral contusions with evidence of subarachnoid haemorrhage. He is transferred to the intensive care unit and measures to inhibit cerebral oedema, including mannitol, are commenced. An N-methyl-D-aspartate (NMDA) inhibitor is administered for neuroprotection and ventilatory support is commenced. Over the next 24 hours haemodynamic support is needed with fluid loading and vasopressors. A urine drug screen by Toxilab (Toxilab Incorporated, Irvine, Calif.) shortly after arrival shows the presence of phenytoin and morphine. The report states that the presence of benzodiazepines is suspected. Plasma phenytoin concentration at the time of arrival was 78 mumol/L (optimal range, 40-80 mumol/L). Forty hours after admission his condition has deteriorated. His pupils are at midposition, no longer reactive to light and his lower limbs exhibit only spinal reflexes. His relatives begin to prepare themselves for the fact he may not survive and raise the issue that he would have been keen to donate organs under such circumstances. What is the opinion regarding withdrawal of life support at this time?

Adult↗
PubMed1996

Weaning and extubation in the intensive care unit. Clinical or index-driven approach?

OBJECTIVE: To assess the outcome of a clinical judgement-based approach to weaning and extubation and to adduce the predictive accuracy of various mechanical respiratory indices measured in parallel. DESIGN: Prospective study. SETTING: Multidisciplinary intensive care unit at a university teaching hospital. PATIENTS: 163 consecutive mechanically ventilated patients, excluding tracheotomy, for weaning trial and extubation. INTERVENTIONS: Using bedside clinical assessment, aided by arterial gas analysis, patients were weaned from mechanical ventilation to spontaneous ventilation via to continuous positive airway pressure (CPAP) circuit (with pressure support) of a microprocessor-controlled ventilator. Extubation occurred from the CPAP circuit at 7 cmH2O pressure support, fractional inspired oxygen (FIO2) < or = 0.5 and CPAP level of < or = 5 cmH2O, such that the partial pressure of oxygen in arterial blood (PaO2) was > or = 65 mmHg. Before extubation, observation for a 1-h (T0 and T60) trial period allowed measurement of vital capacity (VC), expired minute volume (VE), respiratory rate/tidal volume (f/VT) and maximal inspiratory pressure (MIP) using a one-way valve technique over 25 s. MEASUREMENTS AND MAIN RESULTS: Over 7 months, 163 patients (62 females and 101 males; mean (SD) age 64(15) years) were considered. There were 91 surgical (18 with chronic obstructive pulmonary disease; COPD) and 72 medical (28 with COPD) patients. Ventilation was for > or = 1 day (median 5 days, range 1-31) in 115 [group I; APACHE II score 23(8)] and < or = 1 day in 48 [Group II; APACHE II score 17(6)]. Three patients (all Group I: 2 surgical, 1 medical) were reintubated within 24 h, an overall extubation failure rate of 1.8%. In group I, at T0, PaO2/FIO2 was 238(65), f/VT 50(26), MIP 44(21) cmH2O, VE 10.6(3.7) l/min, VC 13(5) ml/kg. Cardiorespiratory variables did not change significantly in either group, T0 to T60. For prediction of reintubation (n = 163), only VE (threshold > 10 l/min) and f/VT (threshold > 100) demonstrated moderate sensitivity and specificity at T60: 67 and 52% and 33 and 94%, respectively. CONCLUSIONS: Bedside clinical judgement of weaning and extubation produces satisfactory outcomes. As a routine, mechanical predictive indices have limited utility.

APACHE↗
PubMed1996

ERG measurements of the spectral sensitivity of common chimpanzee (Pan troglodytes).

The spectral sensitivity of the common chimpanzee (Pan troglodytes) was measured with electroretinogram (ERG) flicker photometry. Chromatic adaptation conditions were used to establish the presence of S-, M- and L-cone pigments. Each of 26 chimpanzees showed substantial and approximately equivalent adaptational changes over the middle and long wavelengths implying an absence of any significant polymorphic variations in the M- and L-cone pigments. As inferred from ERG measurements, the S-cone pigment of the chimpanzee has a spectral peak of about 430 nm. Chimpanzee spectral sensitivity measurements were compared to those obtained from equivalently tested normal human trichromats. The spectral sensitivity of the two species is very similar, chimpanzees being slightly more sensitive to short wavelength lights and slightly less sensitive to long wavelength lights than human subjects. Curve-fitting analyses suggest that spectral filtering may be lower in the chimpanzee lens than it is in the human lens, and that the L/M cone ratio is lower in the chimpanzee.

Adaptation, Ocular↗
PubMed1996

N-acetyl-L-cysteine depresses cardiac performance in patients with septic shock.

OBJECTIVE: To investigate the effects of adjunctive therapy with parenteral N-acetyl-L-cysteine in patients with newly diagnosed septic shock. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Multidisciplinary intensive care unit at a university teaching hospital. PATIENTS: Twenty patients (N-acetyl-L-cysteine group [n = 10], placebo group [n = 10]), 15 male and five female, of mean age 64 +/- 15 (SD) yrs and Acute Physiology and Chronic health Evaluation (APACHE) II score 33 +/- 6, with septic shock within 24 hrs of diagnosis. INTERVENTIONS: After a 2-hr stabilization period (time-zero minus 2 hrs to time-zero), patients received either N-acetyl-L-cysteine in 5% dextrose (150 mg/kg in 100 mL over 15 mins, followed by 50 mg/kg in 250 mL over 4 hrs, and then 100 mg/kg/24 hrs in 500 mL for 44 hrs; N-acetyl-L-cysteine group) or the equivalent volume of 5% dextrose (placebo group). MEASUREMENTS AND MAIN RESULTS: Hemodynamic and oxygen transport indices were measured at time-zero minus 2 hrs and time-zero, and at multiple time points thereafter until completion of the trial infusion (time-zero plus 48 hrs). A daily Organ Failure Score was recorded for 14 days. Treatment group demographics and hemodynamic variables did not differ significantly between the two groups at time-zero. Mean (SD), pooled mean arterial pressure (MAP), and cardiac index were 75 +/- 15 mm Hg and 3.9 +/- 1.2 L/min/m2, respectively. Over the next 48 hrs, in the N-acetyl-L-cysteine group, there was a progressive decrease, relative to both time-zero and the placebo group, in MAP, cardiac index, and left ventricular stroke work index (p < .01, repeated-measures analysis of variance). Percentage reductions in these values relative to the placebo group at 48 hrs were 23%, 18%, and 43%, respectively Oxygen transport indices, arterial blood gas analyses, Pao2/Fio2 ratio, and shunt did not differ over time between the groups. There was no difference in either daily Organ Failure Score over time (p > .01, repeated-measures analysis of variance) or hospital mortality rate (90% N-acetyl-L-cysteine group, 50% placebo group) (p > .1, logistic regression) between the two groups. CONCLUSION: Adjunctive therapy with N-acetyl-L-cysteine in newly diagnosed septic shock was associated with a depression in cardiovascular performance, as indicated by progressive reductions in cardiac index, left ventricular stroke work index, and MAP.

APACHE↗