PubMed Health⌕ Search

Biomedical subjects

P Purcell

Publications and source records attributed to P Purcell.

18 recordsLinked to original sources
PubMed2001

Dach1 mutant mice bear no gross abnormalities in eye, limb, and brain development and exhibit postnatal lethality.

Drosophila dachshund is necessary and sufficient for compound eye development and is required for normal leg and brain development. A mouse homologue of dachshund, Dach1, is expressed in the developing retina and limbs, suggesting functional conservation of this gene. We have generated a loss-of-function mutation in Dach1 that results in the abrogation of the wild-type RNA and protein expression pattern in embryos. Homozygous mutants survive to birth but exhibit postnatal lethality associated with a failure to suckle, cyanosis, and respiratory distress. The heart, lungs, kidneys, liver, and skeleton were examined to identify factors involved in postnatal lethality, but these organs appeared to be normal. In addition, blood chemistry tests failed to reveal differences that might explain the lethal phenotype. Gross examination and histological analyses of newborn eyes, limbs, and brains revealed no detectable abnormalities. Since Dach1 mutants die shortly after birth, it remains possible that Dach1 is required for postnatal development of these structures. Alternatively, an additional Dach homologue may functionally compensate for Dach1 loss of function.

Alleles↗
PubMed2000

Toxicity of Passiflora incarnata L.

BACKGROUND: Herbal medicines may have significant adverse effects which are not suspected or recognized. CASE REPORT: A 34-year-old female developed severe nausea, vomiting, drowsiness, prolonged QTc, and episodes of nonsustained ventricular tachycardia following self-administration of a herbal remedy, Passiflora incarnata L., at therapeutic doses. The possible association of symptoms with passiflora was not recognized for several days. She required hospital admission for cardiac monitoring and intravenous fluid therapy. CONCLUSIONS: Passiflora incarnata was associated with significant adverse effects in this patient. It is important to ask specifically about the use of herbal medicines in patients with undiagnosed illnesses.

Adult↗
PubMed1999

BMP7 acts in murine lens placode development.

Targeted inactivation of the Bmp7 gene in mouse leads to eye defects with late onset and variable penetrance (A. T. Dudley et al., 1995, Genes Dev. 9, 2795-2807; G. Luo et al., 1995, Genes Dev. 9, 2808-2820). Here we report that the expressivity of the Bmp7 mutant phenotype markedly increases in a C3H/He genetic background and that the phenotype implicates Bmp7 in the early stages of lens development. Immunolocalization experiments show that BMP7 protein is present in the head ectoderm at the time of lens placode induction. Using an in vitro culture system, we demonstrate that addition of BMP7 antagonists during the period of lens placode induction inhibits lens formation, indicating a role for BMP7 in lens placode development. Next, to integrate Bmp7 into a developmental pathway controlling formation of the lens placode, we examined the expression of several early lens placode-specific markers in Bmp7 mutant embryos. In these embryos, Pax6 head ectoderm expression is lost just prior to the time when the lens placode should appear, while in Pax6-deficient (Sey/Sey) embryos, Bmp7 expression is maintained. These results could suggest a simple linear pathway in placode induction in which Bmp7 functions upstream of Pax6 and regulates lens placode induction. At odds with this interpretation, however, is the finding that expression of secreted Frizzled Related Protein-2 (sFRP-2), a component of the Wnt signaling pathway which is expressed in prospective lens placode, is absent in Sey/Sey embryos but initially present in Bmp7 mutants. This suggests a different model in which Bmp7 function is required to maintain Pax6 expression after induction, during a preplacodal stage of lens development. We conclude that Bmp7 is a critical component of the genetic mechanism(s) controlling lens placode formation.

Animals↗
PubMed1996

Coagulation changes during thoracoabdominal aneurysm repair.

PURPOSE: The cause of coagulopathic hemorrhage during thoracoabdominal aneurysm (TAA) repair has not been well defined in human studies. We investigated changes in the coagulation system associated with supraceliac versus infrarenal cross-clamping to address this critical issue. METHODS: Blood levels of fibrinogen, the prothrombin fragment F1.2, D-dimer, and factors II, V, VII, VIII, IX, X, XI, and XII were analyzed in 19 patients with TAAs and four patients with abdominal aortic aneurysms (AAAs) at: (A) induction; (B) 30 minutes into supraceliac (TAA) or infrarenal (AAA) clamping; (C) 30 minutes after release of supraceliac or infrarenal clamps; and (D) immediately after surgery. Preoperative and intraoperative variables, including but not limited to aneurysm type, pathologic findings, comorbid conditions, clamp times, volume and timing of blood products, and clinical outcome, were prospectively recorded. Significance was determined by analysis of variance, Student's t test, and univariate linear regression. RESULTS: Levels of fibrinogen and factors II, V, VIII, VIII, IX, X, XI, and XII decreased (p < 0.05) at time B versus time A and returned to near baseline by time D. D-dimer and F1.2 increased starting at time B and reached significance (p < 0.05) by time D. Data points were compared for the TAA and AAA groups. Although AAA groups demonstrated a trend to factor activity reduction and increased fibrinolysis, the effect was much less pronounced than in TAA and did not approach significance. No correlation of coagulation change with clamping time was present; however, visceral clamping times were all less than 65 minutes (mean, 44 minutes). Blood and factor replacement was initiated after time B. Univariate regression analysis of factor level versus total blood replacement demonstrated a significant (p < 0.04) correlation between the reduction in the levels of factors II, V, VII, VIII, X, and XII, and the increase in the level of D-dimer at time B and subsequent total blood replacement. CONCLUSIONS: Thoracoabdominal aneurysm repair is associated with a reduction in clotting factor activity and an increase in fibrinolytic function, which occurs after placement of the supraceliac clamp. Explanations include visceral ischemia or a greater and longer ischemic tissue burden as the likely cause of coagulation alterations. Total blood replacement during TAA procedures was correlated to the degree of factor reduction and fibrinolysis at the time of visceral cross-clamping. An aggressive approach to early blood component replacement and to coagulation monitoring could lessen blood loss during TAA repair and avoid potentially disastrous bleeding complications.

Aortic Aneurysm, Abdominal↗
PubMed1995

Flucloxacillin associated cholestatic hepatitis. An Australian and Swedish epidemic?

The clinico-pathological entity of flucloxacillin-associated cholestatic hepatitis is described and the recognition and documentation of cholestasis associated with flucloxacillin and with related isoxazolyl-penicillins (cloxacillin, dicloxacillin) is examined on an international basis, with particular reference to Australia. Data were obtained from the literature, from the Australian adverse drug reaction monitoring agency and from the Collaborative Centre for International Drug Monitoring (World Health Organisation) in Sweden. Approximately 600 cases of flucloxacillin-associated cholestatic hepatitis were collected, as well as 164 cases associated with other isoxazolyl penicillins. Jaundice and pruritus may first appear several weeks after administration of the drug has ceased and typically are severe and protracted. Liver tests may be abnormal for months after symptomatic recovery. Death is uncommon. Liver pathology shows centrizonal bile stasis with portal tract inflammation and variable loss of bile ducts. Approximately 1 in 15,000 users of flucloxacillin will develop the reaction. Increasing age (> 55 years) and prolonged intake (> 14 days) are particular risk factors. Cholestasis associated with cloxacillin/dicloxacillin appears to be similar in nature but is less well defined. Recognition and reporting of the reaction have been uncommon in the United Kingdom inter alia and high in Sweden and Australia, although estimates of risk have been similar. In Australia, the remarkably high rate of reports appears to be the result of sustained publicity for the reaction. There is only a trickle of reports of cholestatic hepatitis in association with the use of cloxacillin and dicloxacillin from the USA and Canada. The high level of awareness of the reaction and consequential regulatory action so far have not resulted in a diminution of its occurrence in Australia.

Australia↗
PubMed1993

Risk factors for development of flucloxacillin associated jaundice.

OBJECTIVES: To identify risk factors predisposing to the development of flucloxacillin associated jaundice. DESIGN: Case-control study. Medical records of cases and controls were reviewed and information recorded on standard data collection forms. SETTING: Alfred Hospital recruiting subjects from Melbourne, Sydney, and Brisbane. SUBJECTS: Cases were defined as patients who had developed jaundice within eight weeks of stopping flucloxacillin, biochemical test results suggesting cholestasis, normal calibre bile ducts, and not been taking recognised hepatotoxic drugs. 51 of the 53 patients referred were included in the study. Four controls for each case were randomly selected from the patient register of the prescribing doctor. These were defined as patients who had been prescribed flucloxacillin without developing jaundice. MAIN OUTCOME MEASURES: Demographic characteristics, medical history, indication for flucloxacillin, dose, route and duration of treatment, other drugs, smoking, and previous drug allergies or use of flucloxacillin. RESULTS: Increasing age and a prolonged duration of flucloxacillin treatment were found to be risk factors for the development of jaundice. Patients aged over 55 years had an odds ratio of 18.61 (95% confidence interval 5.16-67.17) compared with patients under 30. The odds ratio for patients prescribed flucloxacillin for over 14 days was 7.13 (2.90 to 17.58) compared with patients treated for 14 days or less. Dose and route of administration were not related to the risk of jaundice. CONCLUSIONS: Older patients and those receiving flucloxacillin for longer than two weeks are at a substantially greater risk of jaundice. Careful consideration of the risk-benefit ratio is required when flucloxacillin is used in these settings.

Adult↗
PubMed1991

Diclofenac hepatitis.

The characteristics of liver damage associated with the use of diclofenac, a popular nonsteroidal anti-inflammatory drug, were investigated by reviewing adverse drug reaction reports for Australia. Twenty six patients were reported for whom diclofenac was the sole suspected drug cause of their liver damage. The average age of the patients was 64 years (range 37-84 years); 19 (70%) were women. The most common clinical features were jaundice, hepatomegaly, anorexia, and nausea. Features of drug hypersensitivity were not reported. Duration of treatment with diclofenac before the onset of the illness ranged from 6-417 days (median 76 days). The most prominent biochemical abnormalities were raised serum aspartate transaminase and alanine transaminase activity of up to 30 to 40 times the upper limit of the normal range. Recovery generally started soon after withdrawal of diclofenac and the decrease in aspartate transaminase and alanine transaminase for the group was exponential, with half lives of around 13 days. The average total dose taken by 18 patients for whom accurate data were available was 8.7 g (range 1.4-63.5 g) and, unexpectedly, there was a significant relation between the logarithm of the dose of diclofenac and the logarithms of the peak and mean transaminase levels. Hepatocellular damage during treatment with diclofenac seems to be a rare event. From this analysis of Australian reports it seems that in a small subgroup of patients liver injury may be a direct toxic effect of diclofenac or a metabolite.

Aged↗
PubMed1990

Molecular cloning and sequence determination of four different cDNA species coding for alpha-subunits of G proteins from Xenopus laevis oocytes.

A cDNA library prepared from Xenopus laevis oocytes in lambda gt10 was screened with a mixture of three oligonucleotide probes designed to detect sequences found in different mammalian genes coding for alpha-subunits of G-proteins. In addition to a clone coding for a G alpha o-type subunit previously reported [(1989) FEBS Lett. 244, 188-192] four additional clones have been found coding for different G alpha protein subunits. By comparison with mammalian alpha-subunits, these oocyte cDNAs correspond to two closely related G alpha s-1a, to a G alpha i-1 and to a G alpha i-3 species. The derived amino acid sequences showed that both G alpha s species contain 379 residues, corresponding to the short species without the serine residue and with a calculated Mr of 42720. The G alpha i-1 gene encodes a 354 amino acid protein with an Mr of 39,000 and the G alpha i-3 encodes an incomplete open reading frame of 345 residues, lacking the first 9 amino acid residues at the NH2 terminus. All these G alpha-subunits showed high identity with their respective mammalian counterparts (75-80%), indicating a great degree of conservation through the evolution and the important cellular regulatory function that they play.

Amino Acid Sequence↗
PubMed1990

Characteristics of children and adolescents in a psychiatric hospital and a corrections facility.

Popular opinion holds that youngsters in corrections programs are delinquents in need of reform, whereas youngsters in psychiatric settings have mental health problems and need therapy. Yet some literature suggests that youth in the two settings may not differ greatly in their mental health status. The authors compared demographic, emotional, and behavioral characteristics of youngsters placed in public psychiatric hospital and corrections settings, and they found few differences. Child Behavior Checklist scores for social competence and total problems were high and quite similar for youngsters in the two settings. White children scored significantly worse than black children on Child Behavior Checklist Internalizing, Externalizing, and total problems in corrections settings but not in the psychiatric hospital. Moreover, race was the only variable that predicted the site in which youth were placed. The findings suggest a need to study (1) the mental health needs of youngsters in nonmental health settings and (2) the procedures by which youth are assigned to service settings.

Adolescent↗
PubMed1989

Molecular cloning and sequence determination of a cDNA coding for the alpha-subunit of a Go-type protein of Xenopus laevis oocytes.

Xenopus laevis oocytes are cells ideally suited to the study of signal transduction and of the G-proteins that are involved in this process. A X. laevis cDNA library in lambda gt10 has been screened with a mixture of three oligonucleotide probes designed to detect sequences found in various mammalian alpha-subunits of G-proteins. One of these clones has been purified through tertiary screening and the DNA insert has been sequenced. This clone was found to include the total sequence coding for a 354 amino acid protein that is 89% identical to the sequence of alpha-subunit of rat Go. The differences with the mammalian protein were clustered in amino acids 290-315, which have been postulated to define the region interacting with the receptor and effector molecule. The homology with the alpha-subunits of other mammalian G-proteins is lower (65-70% to Gi and 42% to Gs). On this basis, this clone can be classified as Go-like.

Amino Acid Sequence↗
PubMedDate not supplied

The case for national health data standards.

The Health Insurance Portability and Accountability Act of 1996 (HIPAA) contains groundbreaking provisions to encourage the development of a national health information system through the establishment of standards. This paper compares statewide inpatient data systems to one standard--the Uniform Bill (UB)--to understand how standards have been used and how they can be improved. We recommend changes to the UB, note the need for better compliance, and suggest new standards for common, derived elements.

Computer Communication Networks↗