International classification of osteochondrodysplasias. International Working Group on Constitutional Diseases of Bone.
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Biomedical subjects
Publications and source records attributed to J Hall.
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BACKGROUND: Low-molecular-weight heparin has a high bioavailability and a prolonged half-life in comparison with conventional unfractionated heparin. Limited data are available for low-molecular-weight heparin as compared with unfractionated heparin for the treatment of deep-vein thrombosis. METHODS: In a multicenter, double-blind clinical trial, we compared fixed-dose subcutaneous low-molecular-weight heparin given once daily with adjusted-dose intravenous heparin given by continuous infusion for the initial treatment of patients with proximal-vein thrombosis, using objective documentation of clinical outcomes. RESULTS: Six of 213 patients who received low-molecular-weight heparin (2.8 percent) and 15 of 219 patients who received intravenous heparin (6.9 percent) had new episodes of venous thromboembolism (P = 0.07; 95 percent confidence interval for the difference, 0.02 percent to 8.1 percent). Major bleeding associated with initial therapy occurred in 1 patient receiving low-molecular-weight heparin (0.5 percent) and in 11 patients receiving intravenous heparin (5.0 percent), a reduction in risk of 91 percent (P = 0.006). This apparent protection against major bleeding was lost during long-term therapy. Minor hemorrhagic complications were infrequent. Ten patients receiving low-molecular-weight heparin (4.7 percent) died, as compared with 21 patients receiving intravenous heparin (9.6 percent), a risk reduction of 51 percent (P = 0.049). CONCLUSIONS: Low-molecular-weight heparin is at least as effective and as safe as classic intravenous heparin therapy under the conditions of this study and more convenient to administer. The simplified therapy provided by low-molecular-weight heparin may allow patients with uncomplicated proximal deep-vein thrombosis to be cared for in an outpatient setting.
The synthesis and secretion of a truncated Clostridium thermocellum endoglucanase (EGE') encoded by the celE' gene was investigated in Chinese hamster ovary (CHO) cells. Fusion genes consisting of the human growth hormone (hGH) gene and celE', transcribed from the SV40 early enhancer/promoter, were constructed and stably transfected into CHO cells. A gene consisting of celE' inserted into the first exon of the hGH gene resulted in the synthesis of truncated proteins (less than or equal to 22 kDa) lacking endoglucanase activity. Cloning celE' into the second exon of the hGH gene, resulted in the synthesis and secretion of a 50 kDa protein with endoglucanase activity. A 50 kDa protein was also synthesised by cells transfected with celE' cloned into the fifth exon of the hGH gene. However, despite a 5-fold increase in enzyme activity compared to the exon 2 transfected cell line less than 40% of the protein was secreted. Constructs devoid of introns, in which celE' was fused to the SV40 early promoter and to the rabbit beta-globin polyadenylation sequence resulted in a 2-18-fold increase in endoglucanase activity compared to the constructs containing introns. In addition more than 75% of the synthesised protein was secreted. Analyses of EGE' encoded mRNA from the transfected cell lines suggests that the presence of introns results in the aberrant splicing of message by the use of cryptic splice sites in the celE' gene. These results demonstrate that introns are not required for the efficient expression of a bacterial endoglucanase in mammalian cells, rather introns appear to reduce expression of the encoded protein.
Our recent observations (1) that there is a difference in circadian patterns of plasma cortisol levels between male and female macaques and (2) that after gonadectomy these differences in the patterns and in the levels of cortisol were reduced prompted us to investigate how 17 beta-estradiol (E2) and progesterone affect cortisol secretion in orchidectomized male rhesus macaques. Five male macaques, castrated as adults, were implanted subcutaneously with segments of silastic tubing filled with E2 and with progesterone in a manner such that the levels and the sequence of these hormones mimicked those that occur during the menstrual cycle of intact female macaques. Since previous studies had shown that the difference in cortisol patterns was due to higher levels in females during the day, these studies were conducted from 0800 to 2000 hours. Blood samples were collected in an adjacent room at 15-minute intervals. Separate trials were conducted 2 weeks after E2 was implanted and levels were 110 +/- 14 pg/ml and again 2 weeks later after progesterone was implanted and E2 levels were 59 +/- 15 pg/ml; progesterone levels averaged 4.0 +/- 0.65 ng/ml. Mean plasma concentrations of cortisol (microgram/100 ml) for the 12-hour period were three-fold higher in orchidectomized males treated with E2 (17.2) and with E2 + progesterone (18.0) than in intact males (4.9). Levels in males treated with ovarian steroids were double that (8.5 micrograms/100 ml) observed for intact females.(ABSTRACT TRUNCATED AT 250 WORDS)
Cost utility analysis is the preferred method of analysis when quality of life instead is an important outcome of the project being appraised. However, there are several methodological issues to be resolved in implementing cost utility analysis, including whether to use generalised measures or direct disease specific outcome assessment, the choice of measurement technique, and the combination of different health states. Screening for breast cancer meets this criterion as mammographic screening has been shown to reduce mortality; and it is said that earlier treatment frequently results in less radical surgery so that women are offered the additional benefit of improved quality of life. Australia, like many other countries, has been debating whether to introduce a national mammographic screening programme. This paper presents the results of a cost utility analysis of breast cancer screening using an approach to measuring outcome, Healthy Year Equivalents, developed within this study to resolve these problems. Descriptions of breast cancer quality of life were developed from surveys of women with breast cancer, health professionals and the published literature. The time trade off technique was then used to derive values for breast cancer treatment outcomes in a survey of women in Sydney, Australia. Respondents included women with breast cancer and women who had not had breast cancer. Testing of (i) the effect of prognosis on the value attached to a health scenario; and (ii) whether the value attached to a health scenario remains constant over time has been reported. The estimate of the net costs of screening are reported. The costs of breast cancer screening include the screening programme itself, the further investigations and the subsequent treatment of breast cancer cases. Breast cancer is treated in the absence of screening, many commentators claim earlier treatment is costly but there is little evidence. Therefore we have investigated current patterns of breast cancer treatment, current use of investigations for women presenting with symptoms and current use of covert mammography screening. The results are extrapolated to obtain estimates of the costs and outcomes presented as cost per healthy year equivalent. This analysis produces important information for the Australian policy debate over mammography. It also contributes to the development of cost utility analysis and the approach developed here can be applied more generally.
The effects of dietary selenium deficiency and excess on N-nitrosomethylbenzylamine-(NMBA) induced esophageal neoplasia in rats and forestomach tumors in mice and the effects of dietary selenium on DNA adduct formation and on the activities of DNA adduct-repairing enzyme and oncogene expression in rat esophagus were investigated. The esophageal and forestomach tumors were induced by administration of NMBA by gavage with a total dose of 39 mg/kg body wt in rats and 12 mg/kg body wt in mice. Neither selenium dietary deficiency (Se < 0.02 ppm) nor selenium excess (2.0 ppm) showed any significant effect on the incidence of tumors or number of tumors per tumor-bearing animal. For the DNA adduct formation studies, rats were given a dose of NMBA intraperitoneally after six weeks on the different selenium-containing diets. No significant difference in the amount of the DNA adduct O6-methyldeoxyguanosine was found among the different selenium-treated groups. In a parallel group of rats that did not receive NMBA, the levels of esophageal O6-methyldeoxyguanosine DNA methyltransferase were not significantly altered by dietary selenium levels. The c-myc oncogene expression in rat esophagus was induced by the administration of NMBA (3 mg/kg body wt) by gavage once a week for eight weeks. Dietary selenium did not show any effects on its expression. On the basis of the results of these studies, dietary selenium has no effects in the NMBA-induced tumor model.
From a study of 526 patients having automatic ECG analysis, criteria were established which diagnosed acute evolving Q wave myocardial infarction with 71% sensitivity and 98% specificity. Specificity was 100% when patients with known previous Q wave infarction were excluded. In pre-hospital practice the high sensitivity and specificity were maintained. This method appears appropriate, when other criteria are met, for paramedic-initiated pre-hospital thrombolysis with remote supervision of a cardiologist by telephone.
The Oregon Plan is an ambitious attempt to address the widespread problem in the United States of a growing number of individuals who are without private health insurance and are not eligible for federal assistance programs. Its aim is to provide universal access for all Oregonians, without increasing total health care expenditure, by restricting the cover of some treatments. It has aroused interest in Australia and elsewhere. The appeal of the Oregon Plan lies in its explicit approach to rationing, in community participation in setting priorities, and the use of a cost-effectiveness framework. This paper describes the beginnings and the development of the Oregon Plan, and compares the actual development of the Plan with the rhetoric. There is a gap between the rhetoric of the Plan and its reality. The Oregon plan should be considered in the context of the United States health care system. We compare the American problems with those facing the Australian health care system and conclude that the answer to the question of whether Oregon should be transported to Australia is no. Nevertheless there are elements of the rhetoric of the Plan which could be applied in rationing health care in Australia.
The constitutive (or default) pathway for protein secretion was investigated in two epithelial cells, Madin-Darby canine kidney (MDCK) and human colonic adenocarcinoma (Caco-2), using a bacterial enzyme. The choice of a bacterial protein was based on the requirement to identify a protein devoid of sorting signals. The sorting of a bacterial endoglucanase derived from Clostridium thermocellum, endoglucanase E, from stably transfected MDCK and Caco-2 cells was examined. The choice of a bacterial endoglucanase for these studies has advantages of simple, sensitive and quantitative detection, while higher eukaryotic cells do not express endoglucanase activity. Both cell lines secreted a 50 kDa form of the bacterial protein, while smaller intracellular forms were also observed. In polarized layers of MDCK cells the endoglucanase was secreted into both membrane domains in the ratio 62% apical and 38% basolateral. In Caco-2 cells secretion was predominantly, 70%, through the basolateral membrane. These results define the constitutive pathway for protein secretion in these two model epithelial cells.
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Angioedema of the face and neck is a rare but potentially fatal complication of angiotensin-converting enzyme inhibitor (ACEI) use. We retrospectively reviewed five cases of ACEI angioedema seen at our institution over the past 2 1/2 years. Four of the cases occurred with enalapril and one with lisinopril. Onset of symptoms varied from two days to ten months. Importantly, three of the five patients had been receiving medication three months or longer, suggesting clinicians must consider this complication during long-term administration of these agents. Three of the five patients were markedly obese, had a history of previous face and neck surgery, or had been intubated in the past. Thus, we propose that previous manipulation or trauma of the upper airway, perhaps resulting in airway narrowing, may represent a risk factor for upper airway obstruction secondary to ACEI-induced angioedema.
Seventy free-ranging koalas (Phascolarctos cinereus) from Magnetic Island (Queensland, Australia) underwent an ocular examination, blood collection and serological examination for Chlamydia psittaci antibodies, and an examination of their teeth and genitalia. In 12 koalas long-standing unilateral keratitis was noted and in another 10 animals long-standing bilateral keratitis was observed. All animals were seronegative for Chlamydia psittaci and apart from some nasal discharge and a variety of assorted medical findings there was no sign of chlamydial infection. These ocular findings probably represent a new disease of unknown etiology.
Pre-admission hospital visiting gives people an ideal opportunity to discuss with nursing staff what their hospital stay will entail. Such preparation has been shown to improve patients' recovery and enhance the overall quality of care.
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The past ten years the market for dentists in Denmark has been shrinking. This is having an effect on the financial position of dental practices. It is more difficult for dentists to maintain a certain income level. Several problems are analysed and possible solutions are being discussed.
This study examined practice patterns of medical laboratory personnel and investigated relationships of job-related variables and job satisfaction for single- and multiskilled practitioners. Data were collected from a random sample of American Society of Clinical Pathologist-registered practitioners in a five-state region. Twenty-five percent of the sample was categorized as multiskilled. Regression analysis revealed that work performed had a significant positive contribution to overall job satisfaction for medical laboratory technicians (MLTs) and medical technologists. The strength of the relationship was weakest for multiskilled MLTs. Results support the contention that when jobs are redesigned, enriching them by adding tasks of increased complexity and challenge is possibly more effective than simply enlarging the jobs with lower- or parallel-level tasks.
Mature endoglucanase E (EGE) from Clostridium thermocellum consists of 780 amino acid residues and has an Mr of 84,016. The N-terminal 334 amino acids comprise a functional catalytic domain. Full-length EGE bound to crystalline cellulose (Avicel) but not to xylan. Bound enzyme could be eluted with distilled water. The capacity of truncated derivatives of the enzyme to bind cellulose was investigated. EGE lacking 109 C-terminal residues (EGEd) or a derivative in which residues 367-432 of the mature form of the enzyme had been deleted (EGEb), bound to Avicel, whereas EGEa and EGEc, which lack 416 and 246 C-terminal residues respectively, did not. The specific activity of EGEa, consisting of the N-terminal 364 amino acids, was 4-fold higher than that of the full-length enzyme. The truncated derivative also exhibited lower affinity for the substrate beta-glucan than the full-length enzyme. It is concluded that EGE contains a cellulose-binding domain, located between residues 432 and 671, that is distinct from the active site. The role of this substrate-binding domain is discussed.
The solution structure of endothelin-1, a newly discovered potent bicyclic peptide vaso-constrictor agent, has been investigated using 1H NMR conformational constraints and distance geometry calculations. The conformation is constrained by two disulphide bridges between Cys1-Cys15 and Cys3-Cys11 but the NMR data and computed conformers show additional helical structure between residues Leu6 and Cys11. Our results are compared with previous conflicting reports on the solution conformation of this peptide.