Dr Kevorkian's challenge: time for us to face the truth.
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Biomedical subjects
Publications and source records attributed to P Murphy.
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OBJECTIVE: To identify factors influencing pregnancy management decisions following identification of a perinatal lethal condition. METHODS: One hundred thirty pregnancies with perinatal lethal conditions diagnosed before 24 weeks' gestation were examined. Information collected included demographic data, estimated gestational age at presentation, referral indication, nature of the defect, and performance of autopsy. RESULTS: Eighty-seven families elected to abort affected pregnancies and 43 elected to continue. Demographic factors did not influence decision making, nor did gestational age at diagnosis or referral indication. When comparing the diagnosis of one lethal condition with diagnoses of all other lethal conditions, pregnancies with a central nervous system defect or severe urinary tract defect were more often aborted; those with unexplained severe oligohydramnios and twin pregnancies in which at least one twin was affected were more often continued. Autopsy was obtained much more often in pregnancies that were aborted than in those that were continued. CONCLUSION: The type of defect correlates well with the pregnancy management decision. It is important to consider the type of malformation, certainty of the diagnosis, and level of medical understanding when counseling patients after the diagnosis of a lethal fetal defect. Because many patients will continue pregnancies diagnosed with a perinatal lethal condition, the physician should convey understanding and acceptance of a decision not to abort such a pregnancy. The importance of follow-up testing, including autopsy when appropriate, should be stated clearly.
The human hepatoma HuH-7 cell line was shown to constitutively express both a plasminogen activator (PA) and a plasminogen activator inhibitor (PAI). Four sublines of the HuH-7 cell line were analyzed and found to express differing amounts of both PA and PAI. The plasminogen activator produced by these cells was identified as urokinase based upon molecular weight, inhibition of activity with anti-UK but not anti-t-PA antibodies, adherence to an anti-UK affinity column and by Northern blotting demonstrating positive hybridization with the cDNA for UK, but not with the t-PA cDNA. The inhibitor produced by HuH-7 cells was identified as PAI-1 by molecular weight, immunoblotting techniques, adherence to an anti-PAI-1 affinity column, and by Northern blotting demonstrating positive hybridization with the cDNA for PAI-1, but not with the PAI-2 cDNA. The expression of both UK and PAI-1 by HuH-7 cells could be modulated by cytokines known to influence the acute phase response. The addition of interleukin-1 (IL-1) induced the expression of both UK and PAI-1. The increase of PAI-1 was due to an increase in amount of the PAI-1 mRNA. The presence of both interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF) also increased UK and PAI-1 levels, although not as dramatically as IL-1. The addition of IL-1 together with IL-6 produced a slight synergistic response with respect to PAI-1 expression. This suggests that PAI-1 is able to respond to mediators which aid in the induction of the acute phase response. These studies demonstrate that cells of liver origin are able to produce components of the fibrinolytic system. The synthesis of these components can be altered by inflammatory mediators and thus may be involved in hepatic regulation of fibrinolysis in both normal and diseased states.
Non-invasive assessment of lower limb vasculature may avoid unnecessary angiography in claudicants. Colour duplex ultrasonography of the femoral and popliteal arteries was performed to assess patency and the presence of any stenoses, and pulse-generated run-off (PGR) was used to assess the distal vasculature. In 65 legs colour duplex scanning was successful, compared with angiography, in identifying the site and type of disease in the femoropopliteal segment and 23 lesions were correctly identified as suitable for angioplasty. More patent distal vessels were demonstrated by PGR than by angiography; no vessels patent on angiography were missed by PGR. The estimated cost of diagnostic angiography was 330 pounds per test compared with 52 pounds for non-invasive assessment. By using duplex examination as a screening test, a potential saving of 8062 pounds could have been made in this series. Duplex ultrasonography offers a non-invasive and cost-effective alternative to diagnostic angiography for clinically suspected infrainguinal arterial disease presenting as claudication. PGR was not of clinical value in assessing suitability for angioplasty.
This study measured the concentrations of ondansetron in plasma and cerebrospinal fluid (CSF) in six volunteers after oral dosing to steady state. Ondansetron concentrations ranged from 39.5-147 ng ml-1 in plasma and from 2.6-15.4 ng ml-1 in CSF. There was good correlation between plasma and CSF concentrations (r = 0.89, p = 0.017). CSF concentrations were less than 15% of plasma concentrations in all cases, indicating that the rate of penetration of the blood brain barrier by ondansetron is low.
This is the second part of a study on a mail order picking task. In the first part of the study, recognition time was addressed by varying colour, position and highlighting cues in a computer-simulated version of the picking task. This study addresses the product acquisition time. Shelf coding and continuous presentation of the address information were varied in a factorial experiment in which 14 subjects (seven experts and seven novices) had participated. Experts were slower but more accurate than the novices. Continuous display of address information appears to be a good training aid for implementing new shelf coding systems, and for new operators. Shelf coding effect appears to disappear with practice. A summary of the recommendations is given.
The human U373 glioblastoma/astrocytoma cell line was found to constitutively produce and secrete a plasminogen activator and a plasminogen activator inhibitor. The plasminogen activator was identified as urokinase based on apparent molecular weight, immunoblotting with anti-urokinase antibodies, and Northern blotting with a human urokinase cDNA probe. The inhibitor secreted by U373 cells was found to be related to the PAI-1 molecule based on reactivity with anti-human PAI-1 antibodies, apparent molecular weight, and Northern blot analysis with a human PAI-1 cDNA probe. The expression of both urokinase and the PAI-1-like molecule by U373 cells could be modulated by phorbol myristate acetate or by inflammatory mediators such as interferon-gamma and interleukin-1. In the case of interleukin-1, the alpha form exhibited no detectable effect while the beta form not only elevated inhibitor levels, it also appeared to induce the production of tissue plasminogen activator. Thus, in these cells interleukin-1 beta induces alterations in PA and PAI expression and interleukin-1 alpha does not, even though the two forms are reported to utilize the same cellular receptor.
We evaluated the antigenic characteristics of chimeric picornaviruses created by inserting peptide sequences from hepatitis A virus (HAV) capsid proteins into the B-C loop of VP1 of Sabin strain type 1 poliovirus (PV-1). Fifteen viable chimeras were generated. Each retained the ability to be neutralized by polyclonal PV-1 antisera. Two chimeras (H15 and H2) stimulated production of low levels of HAV neutralizing antibodies in immunized rabbits or mice, although in both cases only a small fraction of immunized animals produced this response. The H15 chimera, which contains residues 13-24 of HAV VP1, elicited HAV neutralizing antibodies in three of nine rabbits and at least one of seven immunized mice. These results indicate that a neutralization domain exists in this region of VP1. However, human sera with high titers of antibodies to HAV failed to neutralize or immunoprecipitate this chimera, suggesting the absence of a significant antibody response to this neutralization domain following natural infection. Sera from rabbits immunized with H15 that did not develop HAV neutralizing antibodies contained antibodies reactive with the HAV peptide segment expressed by the H15 virus, indicating substantial differences in the specificities of antibodies elicited by this peptide segment among individual immunized rabbits. The H15 peptide insert was an effective antigen, as indicated by a high level of sensitivity of the H15 chimera to neutralization by a related anti-peptide antibody which was itself devoid of HAV neutralizing activity. One of 16 rabbits immunized with the H2 chimera (residues 101-108 of HAV VP1) developed HAV neutralizing antibodies, confirming both the presence and the highly conformational nature of a neutralization antigenic site involving these residues of HAV.
Nine children with burns caused by contact with electric fire-guards are presented. A method of preventing such injuries is recommended.
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Twelve patients requiring temporary pacing following acute myocardial infarction (AMI) (10 heart block, 2 junctional bradycardia) had hemodynamic measurements taken with ventricular demand pacing at 80 ppm (VVI80), ventricular demand pacing at the atrial rate (VVIa), physiological pacing (DDD), and spontaneous (intrinsic) rhythm. VVI80 mode did not improve any hemodynamic parameter compared with spontaneous rhythm. VVIa mode improved diastolic and mean arterial pressures only. DDD mode improved most hemodynamic parameters compared with spontaneous rhythm (cardiac output by 29% [P less than 0.0001]; blood pressure: diastolic by 24% [P less than 0.01], systolic by 19% [P less than 0.01], mean by 21% [P less than 0.005]; pulmonary wedge pressure by 10% [P = 0.057] and right atrial pressure by 24% [P less than 0.005]) and also significantly improved some parameters compared with VVIa (cardiac output by 20% [P less than 0.001], systolic blood pressure by 11% [P less than 0.01] and right atrial pressure by 15% [P less than 0.01]). Physiological pacing is hemodynamically superior both to ventricular pacing and spontaneous rhythm for patients requiring temporary pacing following AMI. Ventricular pacing at 80 ppm has little hemodynamic advantage over spontaneous rhythm.
Passage of human hepatitis A virus (HAV) in cell culture results in attenuation of the virus as well as progressive increases in the efficiency of virus replication in cell culture. Because the presence of identical mutations within the 5' nontranslated regions (5'NTRs) of several independently isolated cell culture-adapted HAV variants suggests that the 5'NTR may play a role in determining this change in virus host range, we constructed chimeric infectious cDNA clones in which portions of the 5'NTR of cell culture-adapted HM175/p35 virus were replaced with cDNA from either wild-type virus (HM175/wt) or a second independently isolated, but closely related cell culture-adapted virus (HM175/p16). Substitution of the complete 5'NTR of HM175/p35 with the 5'NTR of HM175/wt resulted in virus with very small replication foci in continuous African green monkey kidney (BS-C-1) cells, indicating that 5'NTR mutations in HM175/p35 virus are required for optimal growth in these cells. A chimera with the 5'NTR sequence of HM175/p16 retained the large foci of HM175/p35 virus, while the growth properties of other viruses having chimeric 5'NTR sequences indicated that mutations at bases 152 and/or 203 to 207 enhance replication in BS-C-1 cells. These findings were confirmed in one-step growth experiments, which also indicated that radioimmunofocus size is a valid measure of virus replication competence in cell culture. An additional mutation at base 687 of HM175/p16 had only a minor role in enhancing growth. In contrast to their effect in BS-C-1 cells, these 5'NTR mutations did not enhance replication in continuous fetal rhesus monkey kidney (FRhK-4) cells. Thus, mutations at bases 152 and/or 203 to 207 enhance the replication of HAV in a highly host cell-specific fashion.
The hemodynamic effects of a new orally active vasodilator, flosequinan, were compared with placebo (single blind) over 24 h in eight patients with pulmonary hypertension secondary to severe chronic obstructive pulmonary disease. Mean pulmonary artery pressure was reduced by 5.1 (3.4, 6.7) mm Hg (mean 95 percent CI) (p < 0.003) and pulmonary vascular resistance was reduced by 70 (23, 189) dynes.s.cm-5 (p < 0.013) by active drug compared with placebo. Cardiac output increased significantly with flosequinan by 0.47 (0.03, 0.91) L/min (p < 0.04) and systemic oxygen delivery increased by 90 (50, 120) ml/min/m2) (p < 0.05). A significant reduction in systemic vascular resistance was observed, 132 (35,230) dynes.s.cm-5 (p < 0.02) but no significant changes were seen in systemic arterial blood pressure or arterial blood gas tensions. Flosequinan favorably altered pulmonary hemodynamics relative to systemic and resulted in a significant improvement in oxygen delivery. The hemodynamic and blood gas effects of this compound suggest that it is a promising vasodilator for the treatment of pulmonary hypertension.
The relationship of parental nurturance to self-esteem for seven distinct adolescent and early-adulthood age groups (N = 784) was investigated. Analysis showed that even though mothers' and fathers' nurturance together were more strongly related to self-esteem during the junior high school years (R2 values greater than 50% were obtained in each of the junior high samples) than during the high school and college years (R2 values less than 40% were obtained in each of these samples), parental nurturance still remained a robust predictor of self-esteem during these latter years. These results were discussed within the context of (a) the stability at different ages of the bases upon which one's judgments of self-esteem are made, and (b) parental nurturance as a stabilizing influence during the transitional years of adolescence and early adulthood.
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Between 1986 and 1988, 38 patients (29 men and nine women), median age 65 years (range 38-85 years), underwent local intra-arterial streptokinase therapy for acute lower limb ischaemia. Three patient groups were identified: 15 with acute on chronic ischaemia (group 1), 12 postangioplasty (group 2) and 11 postfemorodistal bypass (group 3). Distal arteriographic run-off was a significant discriminant between success and failure in group 1 (n = 15, chi 2 = 11.5, P = 0.001) and in the overall group (n = 38, chi 2 = 17.2, P less than 0.001). In group 2, four patients with good run-off had an unsuccessful outcome; this was due in all cases to technical problems (haemorrhage in two and intimal dissection in two). In group 3, two patients with good run-off had unsuccessful streptokinase infusions. In both cases the graft failed in the early postoperative period (less than 30 days). By contrast, the four patients whose grafts occluded after 30 days had successful streptokinase infusions and long-term graft patency was achieved by further surgery and balloon dilatation. In all groups, no patient with a poor run-off had a successful outcome following streptokinase administration. The role of local intra-arterial streptokinase therapy in the critically ischaemic limb remains controversial, but these results suggest that an adequate run-off is an important factor in the selection of patients for treatment.