Search PubMed⌕ Search

Biomedical subjects

A Stevens

Publications and source records attributed to A Stevens.

At least 145 records · Page 8Linked to original sources

Controlled heroin availability in Australia? How and to what end?

The general public, police, service providers, and users/ex-users were asked their views about options for trial design and trial outcomes with regard to a proposal for experimental controlled heroin availability. There was substantial agreement between the samples on issues concerning trial design. In general, the samples from the community, service providers and users/ex-users were more likely to report that a trial would result in positive outcomes, whereas the police sample was more likely to report that a trial would result in negative outcomes. This study illustrates the value of systematic consultation of key groups in exploring the options for change, raising potential difficulties, and highlighting different interests.

Acquired Immunodeficiency Syndrome↗

'Quick and clean': authoritative health technology assessment for local health care contracting.

Commissioners of health care require rapid, accurate and usable information on health technology effectiveness to help them to decide on the content of contracts. Despite major strides in the national initiatives in health technology assessment, such information is still in short supply at the local level. In 1991 the former Wessex region (now in the new South and West Region) established a mechanism which continues to provide carefully established recommendations on new technologies. Its features include: identification of locally important topics for evaluation by the purchasers and the providers; an evaluation team, working to a well-defined format in a service-led academic institute; an arbitration committee to deliver recommendations to purchasers on the basis of both the cost-utility of proposals and the quality of the evidence; and implicit obligations for purchasers to respond to strong recommendations.

Cost-Benefit Analysis↗

[Diagnosis and management of neurotic occupational disorders (before pension application)].

This paper summarizes how neurotic disorders affect working capability, with an emphasis on neurotic working disorders. According to official statistics neurotic disorders account for 5.5% of all disability pensions, but they figure less often as diagnoses in medical certificates issued prior to invalidation. The true impact of neurotic disorders may only be guessed, since the diagnosis is easy to miss and only reluctantly proffered when suspected. In contrast to other neurotic disorder afflicting working behaviour, the neurotic working disorder is thematically centered within the sphere of work and profession itself. The disorder is often treated inadequately and belatedly. Typical somatic complaints clusters, characteristic neurotic conflicts and personality traits often encountered with neurotic working disorder are outlined. Diagnosis requires the taking of a psychobiographic history and some knowledge of psycho- and soziotherapy. There are many options for therapy, and there are a few studies evaluating their efficacy. In order to install treatment early, a routine checkup by a psychotherapist is suggested for all patients exceeding a certain number of days off work per year.

Combined Modality Therapy↗

The effectiveness of putative anti-cataract agents in the prevention of protein glycation.

BACKGROUND: Recent data have favored non-enzymatic glycation as a likely mechanism in diabetic cataract formation. The advanced glycation end products (AGEs) that are formed lead to opacification of the lens by disrupting the short-range order between the proteins. Attempts to decrease AGE formation has led to the use of various anti-glycating agents. Their efficacy, however, has been questionable. METHODS: The extent of AGE formation was monitored in fetal bovine eyes using non-tryptophan fluorescence. The amount of carbohydrate bound to the proteins was measured after reduction with radio-labelled sodium borohydride. RESULTS: While the addition of glucose, glucose-6-phosphate or fructose increased the levels of glycation by only 25 percent and the levels of AGEs by 40 percent, glyceraldehyde resulted in a 70 percent increase in glycation and showed extensive AGE formation (an increase of over 6600 percent when compared to the unglycated protein). The anti-glycating agents aspirin and ibuprofen were unable to significantly decrease the extent of bound metabolite or reduce the amount of AGE formed. In contrast, penicillamine and aminoguanidine were more effective in reducing the levels of AGEs, even though the levels of bound metabolite appeared unchanged. CONCLUSIONS: Triose phosphates are likely to be the major metabolic intermediates that result in AGE formation. The anti-glycating agents, whereas penicillamine and aminoguanidine-which react with the Amadori-derived fragmentation products-significantly decreased levels of AGEs.

Animals↗

Comparison of features of the RNase activity of 5'-exonuclease-1 and 5'-exonuclease-2 of Saccharomyces cerevisiae.

Features of the catalytic specificities of 5'-exonuclease-1 (Xrn1) and 5'-exonuclease-2 of Saccharomyces cerevisiae have been compared. For analysis of in vitro properties, 5'-exonuclease-2 has been highly purified, and data show that it is present in yeast cells at about 5-10% of the level of Xrn1. The basic features of the exonuclease activity of the two enzymes, i.e., their activities with RNA and ssDNA and their mode of action, are similar. We have initiated an analysis of structural elements (artificial and natural) that stall the exonucleolytic hydrolysis by the enzymes. A (G)18 artificial sequence in MFA2 mRNA stalls the hydrolysis by both enzymes, yielding a 3' stall fragment. The specific structural element(s) involved is being investigated. To access a similar in vivo specificity of the two enzymes, the effect of overexpression of the essential HKE1 gene encoding exonuclease-2 on several of the phenotypes of xrn1 cells has been examined. The results show that the slow growth rate is partially overcome and that the level of accumulation of specific cytoplasmic RNAs (fragments of the internal transcribed spacer 1 of pre-rRNA and poly (A)-deficient mRNAs) is reduced to 30-40% of the value found in the xrn1 cells.

Exoribonucleases↗

[Endo-urological drainage in urinary outflow obstruction caused by cancer].

OBJECTIVE: To determine indications and results of endourological upper urinary tract drainage in patients with obstruction due to malignancy. DESIGN: Retrospective. SETTING: University Hospital Groningen. METHOD: In the period 1987-1992, 57 patients with upper urinary tract obstruction due to cancer were treated primarily with a double-J stent (n = 21) or a percutaneous nephrostomy (n = 36, later replaced by a double-J stent in 13). RESULTS: Indications were: severe renal failure following bilateral ureteral obstruction due to malignancy (n = 17), or unknown cause (n = 19), to optimise a compromised kidney function before chemotherapy (n = 7), to resolve pain caused by unilateral obstruction (n = 10), or other (n = 4). The tumours originated most often in the cervix uteri, followed by the urinary bladder, the prostate and the corpus uteri. Minor complications occurred in 34 of the 57 patients (60%): transient haematuria (22 x), urgency caused by the distal tip of the double-J catheter (8 x), dislocation (17 x) or obstruction (6 x) of the nephrostomy catheter. Major complications were observed in 5 patients with a double-J stent: sepsis (1 x), catheter break (1 x), ureteral perforation (2 x) and fistulization between the ureter and iliac artery (1 x). Survival after drainage varied from several days to 8 years (mean 23 months). In 5 patients treated with drainage only to prolong survival, survival was 0.5-16 months (mean 7.3). CONCLUSION: Endourological drainage may be applied to patients with localised disease, in whom further therapy holds the promise of prolonged survival. However, in view of the low complication rate, selected patients who are on a palliative course and still have rapidly progressive disease can also benefit from extended life-time after endourological drainage.

Adolescent↗

Indirect estimates of 'hidden' populations: capture-recapture methods to estimate the numbers of heroin users in the Australian Capital Territory.

This paper describes a method of estimating the size of a population based on matching the individuals from the population appearing in two or more nonrandom samples. The method has been developed by population biologists and demographers who have shown that the simple estimates based on only two samples are very sensitive to the assumption that the two samples are independent. This assumption is rarely met with human populations. However, estimates based on three or more samples can be derived by fitting a log-linear model to a 2k contingency table. The method is applied to a data set of heroin users seeking treatment or counselling or arrested on drug charges in 1988 or 1989 in a small Australian city. The method produced a stable estimate of 1250 heroin users. This includes only users who are vulnerable to arrest and/or interested in seeking treatment. Although estimates produced by this method should be validated with other techniques it provides a simple, quick method to estimate the numbers of people in other hidden populations which are difficult to access.

Australia↗

Design criteria for prompt radiation limits on the relativistic heavy ion collider site.

The Relativistic Heavy Ion Collider (RHIC) is a superconducting colliding beam accelerator facility that is currently under construction. Relatively small amounts of energy depositing in the coils of superconducting magnets can result in a "quench," the irreversible transition to the normal resistive state. The quench limit of superconducting magnets, therefore, constrains local beam loss throughout the injection, acceleration, and storage cycles to extremely low levels. From a practical standpoint, it follows that there is essentially no prompt radiation in most regions due to normal operations. The design of shielding is, therefore, principally driven by the consequences of a single pulse fault at full energy in one of the two storage rings. Since there are no regulatory requirements or guidance documents that prescribe radiological performance goals for this situation, the RHIC Project has proposed a scheme to classify the various areas of the RHIC complex based on Design Basis Accident faults. The criteria is then compared to existing regulatory requirements and guidance recommendations.

Equipment Design↗

Health technology assessment and gastroenterology.

Too much clinical practice is based on unproved opinion. Health technology assessment (HTA) encourages critical review of the literature in a particular area, from which an objective assessment can be made so that clinical practice may be more scientifically based. Only a small number of centers undertake this type of work, usually at a national level. We have been able to set up a more local HTA system (the Wessex Development and Evaluation Committee) with links to clinicians and both providers and purchasers of health care within a region of 3 million people. All aspects of medicine may be reviewed and discussed by the committee; 3 examples from within the field of gastroenterology are summarized herein. Active participation of a university-based institute to provide the reviews is essential. A local HTA facility confers a number of advantages.

Cholelithiasis↗

Assessment of protein rotational diffusion by 13C off-resonance rotating frame spin-lattice relaxation: effect of backbone and side-chain internal motion.

The 13C off-resonance rotating frame spin-lattice relaxation technique is applicable to the study of protein rotational diffusion behavior in a variety of experimental situations. The original formalism of James and co-workers (1978) (J. Am. Chem. Soc. Vol. 100, pp. 3590-3594) incorporated random isotropic reorientational motion of a rigid spherical rotor with no provision for backbone or side-chain carbonyl group internal motion. Here we demonstrate that the failure to include such internal motion may lead to erroneous rotational correlation time determinations for overall reorientational motion. The effect becomes severe for protein molecular masses in excess of 100 kD. Inclusion of both backbone and side-chain carbonyl carbon internal motion, using reasonable parameters derived from the literature [R. Levy and M. Karplus (1979), Chemical Physics Letters, Vol. 65, pp. 4-11; G. Careri, P. Fasella, and E. Gratton (1975), Critical Reviews in Biochemistry, Vol. 3, pp. 141-164; G. Lipari, A. Szabo, and R. LEvy (1982), Nature, Vol. 300, pp. 197-198], plus corrections for anisotropic tumbling [C. F. Morgan, T. Schleich, G. H. Caines, and D. Michael (1990), Biopolymers, Vol. 29, pp. 469-480] and microscopic viscosity [S. H. Koenig (1980), ACS Symposium Series, Vol. 127, pp. 157-176], leads to reliable values for the correlation time describing overall protein reorientation up to molecular masses of approximately 1000 kD.

Carbon Isotopes↗

13C NMR studies of protein motional dynamics in bovine, human, rat, and chicken ocular lenses.

The motional dynamics of lens proteins were studied by two 13C nuclear magnetic resonance (NMR) techniques sensitive to molecular motion to define the effect of lens water content on the presence of solid-like protein domains in ocular lenses from bovine (juvenile and adult), human, rat, and chicken eyes. The solid state 13C NMR technique of proton dipolar decoupling was used to study slow (solid-like) motions (correlation time, tau o > or = 10 microseconds), whereas for intermediate (mobile) protein, rotational reorientational motion (tau o range of 1-500 nsec) the 13C off-resonance rotating frame spin-lattice relaxation technique was employed. 13C NMR studies of calf lens cortical and nuclear homogenates indicated a reversible loss of lens protein motional freedom with decreasing water content. Values of 6% and 63% solid-like protein contents were obtained for native cortical and nuclear calf lens homogenates, respectively. At equivalent total protein concentrations cortical and nuclear calf lens homogenates exhibited essentially the same solid-like (motionally restricted) protein content. Lens protein rotational correlation times determined by off-resonance rotating frame spin-lattice relaxation measurements were consistent with lens protein aggregation. The solid-like protein content of the bovine nuclear lens region was observed to increase with age, whereas no significant change was detected for the cortex. Across lens species an inverse correlation between the percentage of solid-like protein content and water content was observed. Very broad 13C NMR resonances, even in the presence of proton dipolar decoupling, were observed for the lens proteins present in the cataractous human lens, indicating the presence of highly aggregated protein species. The occurrence of solid-like protein domains in lens tissue has implications for the interpretation of proton nuclear magnetic resonance dispersion (NMRD) measurements of lens homogenates and for proton magnetization transfer contrast enhanced magnetic resonance imaging of lens. Solid-like protein domains may play a protective role in the maintenance of lens transparency by minimizing enhanced refractive index fluctuations created by protein packing defects resulting from post-translational modification.

Adult↗

Intrathecal IgM response in disseminated cerebrospinal metastasis from malignant melanoma.

Neurological complications are a major cause of morbidity and mortality in patients with disseminated malignant melanoma. We have studied and correlated clinical and cerebrospinal fluid (CSF) findings in 20 patients with central nervous system metastases from malignant melanoma including 8 patients with metastatic meningeal melanomatosis (MMM) and 12 patients with solid cerebral metastases (SCM). The putative CSF tumor markers, fibronectin and beta 2-microglobulin, were elevated significantly in MMM but not in SCM patients. A prominent increase in the IgM index, which reflects intrathecal B-cell stimulation, and a rise of IgG index, interleukin-6, and tumor necrosis factor-alpha in MMM patients provide preliminary evidence for a local intrathecal immune response triggered by melanoma cell invasion of the subarachnoid space.

Humans↗

Origin of macrophages in central nervous tissue. A study using intraperitoneal transplants contained in Millipore diffusion chambers.

In order to determine the origin of brain phagocytes brain slices and optic nerve segments from adult Lewis rats were transplanted into the peritoneal cavity of syngenic recipients. The specimens were contained in Millipore diffusion chambers fitted with membranes of either 0.22 or 5.0 microns pore size. The either blocked or allowed the access of non-resident cells. Each recipient rat received both a 0.22 and 5.0 microns pore chamber. Later (3-16 days), the specimens were recovered and analyzed by monoclonal antibody techniques and electron-microscopy. Endothelia, GFAP+ astrocytes, ED1-/ED2+/RCA-1+/OX-6-perivascular cells and ED1-/ED2-/RCA-1+/lysozyme--microglia were found to have survived the procedure. Cells of the macrophage phenotype (ED1+/ED2+/RCA-1+/lysozyme+/vimentin+ with phagocytic vacuoles), however, were only found in large numbers in specimens kept within 5.0 microns pore size chambers, giving access to non-resident cells, and were exceedingly rare in specimens from 0.22-micron pore chambers. It has been concluded that the majority of brain phagocytes found after lesions do not originate from microglia or perivascular monocytic cells, but rather from invading cells.

Animals↗