Candidates for governor discuss health care issues.
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Delivery of Health Care↗
Biomedical subjects
G Allen
Publications and source records attributed to G Allen.
Revision arthroplasty using allograft bone.
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Acetabulum↗
Preventing transmission of bloodborne infections.
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Blood↗
Analysis of exon 7 of the human phenylalanine hydroxylase gene: a mutation hot spot?
Complete sequence analysis of 194 human phenylalanine hydroxylase genes from PKU patients originating from West Germany and Bulgaria revealed 13 different mutations within exon 7 of the gene. Four of these mutations (T238P: ACT-->CCT; L242F:CTC-->TTC; R252G:CGG-->GGG; and 1043 delta 11: nt 1043-nt 1053 deleted) have so far not been described in the literature. Including these new mutations at least 21 different gene lesions and one sequence polymorphism exist for exon 7. Despite this large number unbiased calculation of the mutation frequency/exon size ratio does not provide conclusive evidence that exon 7 is a hot spot for disease causing mutations. Extensive screening during our experiments also failed to demonstrate the existence of excessive polymorphism in this part of the gene. It might therefore be speculated that the functional importance of the highly conserved exon 7 sequence accounts for the clustering of observed mutations which result in clinically manifest PKU. In addition we report our experience in regard to the resolution capacity of denaturing gradient gel electrophoresis (DGGE), a nonradioactive technique for the rapid screening of unknown mutations in exon 7.
Alleles↗
Twinning and the r/K reproductive strategy: a critique of Rushton's theory.
The theory of r selection, favoring population growth, as opposed to K selection, favoring more efficient utilization of resources, has in recent years been applied by Rushton to contrast human ethnic groups in terms of their r/K reproductive strategies, suggesting the existence of a continuum from r groups, producing many offspring but providing little parental care, to K groups, producing few offspring but providing much parental care. Rushton's theory, which is largely based on ethnic differences in twinning rates, is here critically examined. It is pointed out that twinning rate differences are not necessarily genetic in origin since various environmental factors clearly play a role, and also that twinning, as a mode of reproduction, is not necessarily an r strategy, considering the high prenatal and perinatal selection to which it has been, and still is, associated. Moreover, Rushton misinterprets a number of relevant aspects related to the biology of twinning. The claim that ethnic differences in twinning rates provide evidence for an r/K typology in human populations with respect to reproductive strategies does not appear to be warranted.
Animals↗
Digoxin and digoxin derivative induced arrhythmias: in vitro binding and in vivo abolition of arrhythmias by digoxin immune Fab (DIGIBAND).
OBJECTIVE: The aim was to compare the binding characteristics of a highly purified digoxin specific antigen binding fragment (digoxin immune Fab: DIGIBIND) with digoxin and with two commonly used derivatives of digoxin, beta methyl digoxin and beta acetyl digoxin, and to assess its ability to abolish the arrhythmogenic effects of these digitalis glycosides. METHODS: The binding characteristics of DIGIBIND with digoxin, beta methyl digoxin, and beta acetyl digoxin were assessed in vitro by measuring their ability to inhibit the binding of DIGIBIND to 3H-digoxin. From these studies the affinities of the interactions between DIGIBIND and these glycosides, and the binding capacity of DIGIBIND for each of these glycosides, could be measured. The ability of DIGIBIND to abolish the arrhythmogenic effects of digoxin, beta methyl digoxin, and beta acetyl digoxin was assessed using an in vivo anaesthetised guinea pig model (n = 36, weight 300-400 g), in which these glycosides were infused intravenously (50 micrograms.kg-1 x min-1) until the onset of ventricular arrhythmias, at which point the total amount of glycoside given was calculated. A single bolus dose of either vehicle or DIGIBIND was then given intravenously, and the time to restoration of normal cardiac rhythm noted. After the administration of DIGIBIND, a second infusion of the same glycoside was given to reinitiate the ventricular arrhythmias. The time to onset of the arrhythmias was noted, and the additional amount of glycoside given calculated. RESULTS: In vitro studies showed the binding of DIGIBIND to 3H-digoxin to be inhibited by digoxin and by the two derivatives. The affinities of these interactions with DIGIBIND were significantly different, that for digoxin being some twofold greater than that for beta methyl digoxin and beta acetyl digoxin. The ED50 concentrations were 14.1 (95% CI 12.2, 15.2), 29.2(26.1, 32.7), and 36.2(33.0, 39.8) nM, respectively. However, there were no significant differences between these glycosides in their binding capacities. The in vivo studies showed that intravenous infusion of digoxin, beta methyl digoxin, or beta acetyl digoxin induced similar ventricular arrhythmias. The onset of the arrhythmias was clearly discernible, and required a significantly lower dose of digoxin compared with that of beta methyl digoxin and beta acetyl digoxin. These doses were 667(SEM 55), 868(33), and 854(40) nmol.kg-1, respectively. Termination of the infusion had no effect on the arrhythmias, and in those animals which received a bolus intravenous injection of saline there was no return to normal cardiac rhythm. By contrast, in animals which received a bolus intravenous injection of DIGIBIND, there was complete abolition of the arrhythmias within 4-6 min. Although the dose of DIGIBIND given to abolish digoxin induced arrhythmias was approximately 25% less than that given to abolish beta methyl digoxin and beta acetyl digoxin induced arrhythmias (p < 0.05), the time to restoration of normal cardiac rhythm after DIGIBIND was not significantly different for digoxin compared with beta methyl digoxin and beta acetyl digoxin, at 4.6(0.9), 4.9(0.8), and 5.7(0.8) min, respectively. To reinitiate the arrhythmias in those animals which had received DIGIBIND, a dose of glycoside was required which was not significantly different from that given prior to the DIGIBIND. This observation therefore confirmed the stoichiometric relationship between DIGIBIND and each of the glycosides in respect of the neutralising action of DIGIBIND in abolishing the arrhythmogenic effects of these agents. CONCLUSIONS: Although there is some small difference in the affinities of the binding interactions, there is no difference in the binding capacities of DIGIBIND for digoxin, beta methyl digoxin, or beta acetyl digoxin in vitro. These binding interactions are manifest as the ability of DIGIBIND to abolish the arrhythmogenic effects of digoxin and the two derivatives in vivo.
Acetyldigoxins↗
A bronchogenic cyst causing respiratory distress.
A case is reported of acute respiratory distress in an adult that was caused by a bronchogenic cyst. Bronchogenic cyst in an adult may be seen on chest X-ray and confirmed by computerized tomography (CT) scanning. Surgical excision can provide dramatic relief.
Adult↗
Experimental comparison of the effects of three treatment programs for homeless mentally ill people.
A longitudinal experimental design was used to compare the effectiveness of three community-based treatment programs serving homeless mentally ill people: traditional outpatient treatment offered by a mental health clinic, a daytime drop-in center, and a continuous treatment team program that included assertive outreach, a high staff-to-client ratio, and intensive case management. At 12-month follow-up, clients in all three treatment programs spent fewer days per month homeless, showed fewer psychiatric symptoms, and had increased income, interpersonal adjustment, and self-esteem. Clients in the continuous treatment program had more contact with their treatment program, were more satisfied with their program, spent fewer days homeless, and used more community services and resources than clients in the other two programs.
Activities of Daily Living↗
Possible association between toxic epidermal necrolysis and ciprofloxacin.
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Aged↗
Vacuum tumescence devices: the role of papaverine in the selection of patients.
We conducted a prospective study to determine the positive predictive value of papaverine testing to select patients in whom a vacuum constriction device would be a successful alternative to operative management of impotence. A total of 30 men presenting to an impotence clinic was evaluated with a series of papaverine dosages up to 60 mg. These patients then received a physician-administered trial of a vacuum constriction device, followed by 3 months of home use and a repeat objective evaluation. Initial responses to the device were poor, with 46% of the patients (14) achieving a rigid erection. However, after 3 months of home use 83% of the patients (25) achieved a rigid erection. The positive predictive value of a good response to the papaverine trial was 94%.
Equipment Design↗
A comparison of the caffeine halothane muscle contracture test with the molecular genetic diagnosis of malignant hyperthermia.
Malignant hyperthermia (MH) is currently diagnosed by the caffeine-halothane contracture (CHC) test. In a previous study, this test was used to establish linkage between the human gene for MH susceptibility and the ryanodine receptor (RYR) gene. The current study extends the genetic linkage analysis to a large French-Canadian kindred. In this family, genetic linkage between RYR and MH genes was not demonstrable using the currently recommended limits of normal for the CHC test in the identification of MH-susceptible individuals. With CHC test threshold limits below those currently recommended, however, complete linkage between the RYR and MH genes was seen. Comparisons of CHC test results with genetic linkage studies will increase the diagnostic accuracy of both tests as well as generate new insights into the biology of MH.
Alleles↗
A blinded comparison of noninvasive, in vivo phosphorus nuclear magnetic resonance spectroscopy and the in vitro halothane/caffeine contracture test in the evaluation of malignant hyperthermia susceptibility.
Malignant hyperthermia (MH) is a potentially fatal, anesthetic-induced syndrome. Currently, the only accurate means of diagnosing susceptibility to this syndrome is the testing of biopsied skeletal muscle for its contracture response to halothane and caffeine. A less invasive means of diagnosis is needed. The authors previously reported that MH-susceptible patients studied by in vivo phosphorus nuclear magnetic resonance (31P NMR) spectroscopy demonstrated a higher resting inorganic phosphate (Pi) to phosphocreatine (PCr) ratio in their skeletal muscle, as well as a slower postexercise recovery of PCr/Pi, when compared to normal controls. In the present blinded study, the authors compared in vivo 31P NMR determination of resting Pi/PCr and recovery rate of PCr/Pi in forearm muscles to in vitro halothane/caffeine contracture test results in 42 patients. Forty-three control subjects were studied to establish normal NMR values of resting Pi/PCr and recovery rate of PCr/Pi. Their findings were compared with those of 27 patients shown to be MH-susceptible and 15 patients MH-negative by contracture testing. The MH-susceptible group had a significantly (P less than 0.005) higher resting Pi/PCr value (0.202 +/- 0.044) than either the MH-negative (0.152 +/- 0.043) or the control (0.141 +/- 0.026) group. The MH-susceptible group also had a significantly (P less than 0.02) slower postexercise recovery rate of PCr/Pi (1.50 +/- 0.872 PCr.Pi-1.min-1) than either the MH-negative (2.11 +/- 1.07 PCr.Pi-1.min-1) or control (2.25 +/- 0.828 PCr.Pi-1.min-1) group. Twenty-six of the 27 MH-susceptible patients demonstrated abnormal NMR test results (a resting Pi/PCr greater than or equal to 0.18 or recovery rate less than 1.0 PCr.Pi-1.min-1), and 13 of the 15 MH-negative patients had normal NMR results. Although neither NMR parameter alone was diagnostically reliable, an NMR test utilizing both parameters was quite accurate. The NMR test and contracture test demonstrated an overall agreement of 93% with a copositivity of 96% and conegativity of 87%. The sensitivity and specificity of the NMR test is estimated to be 98.8% +/- 11.8% and 95.3% +/- 20.3%, respectively. The role of 31P NMR in the diagnosis of MH susceptibility and possible mechanisms underlying the observations are discussed.
Adolescent↗
Propofol and malignant hyperthermia.
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Anesthesia, Intravenous↗
Absence of structural alterations of the multidrug resistance genes in transitional cell carcinoma.
Tumor DNA from 27 patients with treated or untreated transitional cell carcinomas of the urinary tract was screened for genomic alterations of the multidrug resistance genes in order to determine whether structural changes of these genes are important in primary urothelial tumors. None of the tumors showed evidence of amplification or rearrangements of either mdr1 or mdr2. The lack of amplification or rearrangements observed in these tumors suggests that structural alterations of the mdr1 and mdr2 genes are not important mediators of drug resistance in TCC.
Blotting, Southern↗
Trends in monozygotic and dizygotic twinning rates by maternal age and parity. Further analysis of Italian data, 1949-1985, and rediscussion of US data, 1964-1985.
The dizygotic twinning rate in Italy, adjusted for maternal age and parity, declined from 8.9/1000 in 1949-1953 to 6.0/1000 in 1978-81, but may have stabilized or recovered slightly in the early 1980s. The long decline was greatest in the oldest mothers, and the recent increase, if any, has been principally in first births and in women under 30. The monozygotic rate rose from 3.8/1000 in 1969-73 to 4.3/1000 in 1982-85, having been relatively stable prior to that period. No good explanation for these trends is apparent.
Adult↗
Equine herpesvirus type 1 unique short fragment encodes glycoproteins with homology to herpes simplex virus type 1 gD, gI and gE.
The nucleotide sequence of a 6.4 kbp portion of the 10.6 kbp BamHI fragment D contained in the unique short region of the equine herpesvirus type 1 (EHV-1) genome has been determined. Analysis of this sequence revealed five open reading frames (ORFs), four complete and one incomplete, which were encoded by the same sense strand. Comparison of the EHV-1 DNA sequence with that encoding glycoproteins of other alphaherpesviruses has revealed no significant homologies. Comparison at the amino acid level, however, has demonstrated regions of significant sequence similarity between the three complete EHV-1 ORFs 2, 3 and 4, and the herpes simplex virus type 1 (HSV-1) glycoprotein gD encoded by the US6 gene, the HSV-1 glycoprotein gI encoded by the US7 gene and the HSV-1 glycoprotein gE encoded by the US8 gene, respectively. The interrupted ORF 5 was found to display partial homology with the HSV-1 US9-encoded protein, but no homology was found between the protein encoded by ORF 1 and other proteins. The three collinear EHV-1 ORFs encoding putative glycoproteins with homology to the HSV-1 glycoproteins were therefore designated EHV-1 gD, gI and gE, respectively. Moreover, further similarities were found between EHV-1 gD and pseudorabies virus (PRV) gp50, between EHV-1 gI and PRV gp63 and varicellazoster virus (VZV) gpIV, and between EHV-1 gE and PRV gI and VZV gpI. It is concluded that EHV-1, PRV, HSV-1 and VZV encode homologous glycoprotein genes in the small unique components of their genomes and that the genetic organization of these regions is conserved.
Amino Acid Sequence↗
Improving the quality of community health surveys and community health promotion campaigns by feedback from the community: experience from the Wallsend community and health project.
A lifestyle and health risk survey was conducted in two socially disadvantaged Collector's Districts, as the basis for a health promotion intervention in one of the Districts. After community input into the planning, and local advance publicity, 395 people responded to the survey (a response rate of 39%). Three sources of community feedback were used: (i) reasons for refusal to participate; (ii) written comments solicited at a two-month follow-up; (iii) later, in-depth interviews with a subset of respondents. The data from this feedback related both to the process and outcomes of the survey; the latter included increased personal and community awareness of health, as well as lifestyle changes. The data are discussed in terms of their representativeness and the factors influencing participation, the implications of the low response rate, the stages of health behaviour change, and the potential conflict between scientific and human value-systems in community research.
Australia↗
Coexpression by vaccinia virus recombinants of equine herpesvirus 1 glycoproteins gp13 and gp14 results in potentiated immunity.
The equine herpesvirus 1 glycoprotein 14 (EHV-1 gp14) gene was cloned, sequenced, and expressed by vaccinia virus recombinants. Recombinant virus vP613 elicited the production of EHV-1-neutralizing antibodies in guinea pigs and was effective in protecting hamsters from subsequent lethal EHV-1 challenge. Coexpression of EHV-1 gp14 in vaccinia virus recombinant vP634 along with EHV-1 gp13 (P. Guo, S. Goebel, S. Davis, M. E. Perkus, B. Languet, P. Desmettre, G. Allen, and E. Paoletti, J. Virol. 63:4189-4198, 1989) greatly enhanced the protective efficacy in the hamster challenge model over that obtained with single recombinants. The inoculum doses (log10) required for protection of 50% of hamsters were 6.1 (EHV-1 gp13), 5.2 (EHV-1 gp14), and less than 3.6 (vaccinia virus recombinant expressing both EHV-1 glycoproteins [gp13 and gp14]).
Amino Acid Sequence↗