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Biomedical subjects

A Smith

Publications and source records attributed to A Smith.

At least 91 records · Page 5Linked to original sources

Knock-in of nuclear localised beta-galactosidase reveals that the tyrosine phosphatase Ptprv is specifically expressed in cells of the bone collar.

Ptprv is a member of the transmembrane tyrosine phosphatase gene family reported to be expressed in osteoblasts and gonads. To better define the developmental and tissue specificity of Ptprv expression, we generated knock-in mice expressing a nuclear localised beta-galactosidase reporter under the control of resident Ptprv regulatory elements. Histochemical staining of Ptprv-nLacZ mice revealed that Ptprv expression is readily detectable in the foetal gonadal ridge of both sexes and in adult gonads where it is localised to Sertoli cells of the testis and celomic epithelial cells of the ovaries. During early limb development, Ptprv expression is prominent in the apical ectodermal ridge of the limb bud. At latter stages of development, Ptprv is predominantly expressed in the perichondrial and periosteal region of long bones, known as the bone collar. In contrast to previous indications from in vitro studies, there is little if any expression in mature osteoblasts in vivo. Analysis of Ptprv mRNA localisation by in situ hybridization in parallel with molecular markers of chondrocytes and osteoblasts confirmed the specific expression of Ptprv in immature bone collar cells. The specificity of Ptprv expression in these cells may be a useful tool to elucidate their role in the transition of skeletal elements from cartilage template to bone.

Animals↗

3-Pyridyl ethers as SPECT radioligands for imaging nicotinic acetylcholine receptors.

To develop a suitable single photon emission computed tomography (SPECT) radioligand for neuronal nicotinic acetylcholine receptors (nAChRs) that displays faster in vivo kinetics than 5-[123I]iodo-A-85380, we synthesised the radioiodinated analogue of A-84543. 5-[123I]Iodo-A-84543 was prepared by electrophilic iododestannylation in a modest yield of 23%. In the baboon brain, 5-[123I]iodo-A-85380 displayed a profile consistent with the known distribution of nAChRs, however, 5-[123I]iodo-A-84543 displayed a homogenous uptake with no preferential localisation in regions known to contain nAChRs. To examine the effect of halogen substitution on the 3-pyridyl ether, A-84543, the 5-chloro, 5-bromo and 5-iodo analogues were synthesised and evaluated with respect to nAChR binding. In vitro binding data revealed that halogen substitution at the 5-position of A-84543 was not well tolerated with an increase in halogen size resulting in lower binding towards nAChRs. The 5-chloro analogue 4 displayed highest affinity, Ki =1.3 nM, compared to the 5-bromo and 5-iodo compounds, 5 Ki =3.3 nM and 3 Ki =40.8 nM, respectively. Taken together, these results clearly indicate that 5-[123I]iodo-A-84543 is not suitable for the study of nAChRs in vivo using SPECT.

Animals↗

The role of sport-fish consumption advisories in mercury risk communication: a 1998-1999 12-state survey of women age 18-45.

BACKGROUND: In 2002, in the United States, 48 states issued advisories for sport-fish consumers that included 39 chemical contaminants. The most commonly identified chemical was methyl mercury, which is linked to reproductive and developmental effects. Advisories to reduce consumption of contaminated fish have been issued by states since the early 1970s. Advisories are being integrated to include both sport and commercial fish. METHODS: As part of a comprehensive risk-communication project, from December 1998 through August 1999 the Wisconsin Division of Public Health and the State of Maine Bureau of Health conducted a 12-state random-digit-dial telephone survey of 3015 women of childbearing age (ages 18-45). The goal was to assess the prevalence of fish consumption, understanding of mercury toxicity, and awareness of state sport-fish consumption advisories for mercury. We gathered information concerning respondents' demographic characteristics, understanding of mercury toxicity, fish consumption during the preceding 12 months, and sport-fish consumption advisory awareness. RESULTS: The overall survey completion rate was 57% with a Council of American Survey Research Organizations (CASRO)-calculated response rate of 50%. Completion rates varied from 37% in New Jersey to 73% in Minnesota. Fish consumption during the previous 12 months was reported by 87% of respondents (range by state of 82-90%). Nearly 10% of women reported consuming two or more fish-meals per week over the prior 12 months. Twenty-nine percent reported sport-fish consumption during the same time period, with a greater state-to-state variability (14-43%). Most women (71%) were aware of mercury's toxicity to a developing child (87% among those aware of an advisory and 67% among those unaware of an advisory). However, awareness of state advisories was only 20%, ranging by state from 8% to 32%. Women who were older, had more than a high school education, and had a household member with a fishing license were the most informed about mercury and fish-consumption advisories. CONCLUSIONS: Most women of childbearing age consume commercial fish and a substantial number also consume sport-caught fish. Despite this potential exposure to dietary mercury, most are unfamiliar with their state's mercury fish-consumption advisory. Most women were aware of the most toxic effects of mercury but less informed about mercury and its relationship to types of fish and fish characteristics. Minorities, women over age 30, family incomes above 25,000 US dollars, and those with some collage education were more likely to be consuming two or more fish-meals per week. Until source control and environmental remediation efforts can reduce the environmental burden of mercury below levels of concern, combined sport and commercial fish consumption advisories will remain the primary means of reducing human exposure to methylmercury. Assuring and assessing the effectiveness of such advisories is paramount. Our survey documents that current efforts to inform vulnerable populations are far from optimal.

Adolescent↗

Volumetric evaluation of facial swelling utilizing a 3-D range camera.

Quantitative analysis of facial volume is important in the assessment of facial swelling. Previous research has demonstrated that the Fiore trade mark light-structured 3-D range camera is a rapid, non-invasive, and safe imaging technology for the quantitative analysis of facial morphology. The development of the Rugle-3D trade mark volumetric measurement software programme has allowed for the development of a powerful imaging and measurement system. This study aimed to determine the accuracy and reproducibility of Fiore trade mark by measuring simulated facial swelling. A model involving 20 human subjects was devised to simulate facial swelling for image acquisition and measurement in order to assess the accuracy and reproducibility of the device. A systematic error of 1.25% and reproducibility of 3.27% was determined for the imaging system. It is concluded that Fiore trade mark is an accurate and reproducible technology that is sensitive and would be applicable to clinical studies of facial swelling.

Edema↗

Testing men who have sex with men for Neisseria gonorrhoeae and Chlamydia trachomatis prior to the introduction of guidelines at an STD clinic in Melbourne.

BACKGROUND: Guidelines for testing men who have sex with men (MSM) were published in 2002. They did not recommend asymptomatic screening for urethral gonorrhoea or pharyngeal screening for chlamydia. To determine if these guidelines were appropriate, we audited gonorrhoea and chlamydia testing of MSM at our Centre. METHODS: We carried out two audits at our Centre between August 2001 and July 2002. The first was an audit of testing MSM for gonorrhoea and/or chlamydia over 12 days. The second was an audit of all positive tests over this 12-month period for gonorrhoea or chlamydia among MSM. RESULTS: During the 12 selected days 89 of 286 men tested (31%) were MSM. Among the MSM testing positive for gonorrhoea and/or chlamydia infection (15, 17%), symptomatic urethral infection was the most common (n = 8). No rectal and pharyngeal infections had site-specific symptoms. Based on the guidelines, 100 of the 334 tests ordered (30%) were not recommended according to the guidelines, and none of these 100 tests yielded a positive result. Over the 12-month audit period, 135 MSM were diagnosed with gonorrhoea and/or chlamydia. For gonorrhoea, site specific symptoms were present in 42 of 43 cases of urethral infection (98%), six of 23 cases of rectal infection (26%), and no cases of pharyngeal infection had symptoms. For chlamydia, site-specific symptoms were present in 29 of 48 cases of urethral infection (60%), six of 33 cases of rectal infection (18%), and in one of the two cases of pharyngeal chlamydia identified. A substantial proportion of cases occurred in clients with HIV infection (21, 16%). CONCLUSIONS: These findings strongly support screening among MSM and in particular not testing asymptomatic MSM for urethral gonorrhoea or any MSM for pharyngeal chlamydia.

Adult↗

Differential increase in taurine levels by low-dose ethanol in the dorsal and ventral striatum revealed by microdialysis with on-line capillary electrophoresis.

Ethanol increases taurine efflux in the nucleus accumbens or ventral striatum (VS), a dopaminergic terminal region involved in positive reinforcement. However, this has been found only at ethanol doses above 1 g/kg intraperitoneally, which is higher than what most rats will self-administer. We used a sensitive on-line assay of microdialysate content to test whether lower doses of ethanol selectively increase taurine efflux in VS as opposed to other dopaminergic regions not involved in reinforcement (e.g., dorsal striatum; DS). Adult male rats with microdialysis probes in VS or DS were injected with ethanol (0, 0.5, 1, and 2 g/kg intraperitoneally), and the amino acid content of the dialysate was measured every 11 sec using capillary electrophoresis and laser-induced fluorescence detection. In VS, 0.5 g/kg ethanol significantly increased taurine levels by 20% for 10 min. A similar increase was seen after 1 g/kg ethanol, which lasted for about 20 min after injection. A two-phased taurine efflux was observed with the 2.0 g/kg dose, where taurine was increased by 2-fold after 5 min but it remained elevated by 30% for at least 60 min. In contrast, DS exhibited much smaller dose-related increases in taurine. Glycine, glutamate, serine, and gamma-aminobutyric acid were not systematically affected by lower doses of ethanol; however, 2 g/kg slowly decreased these amino acids in both brain regions during the hour after injection. These data implicate a possible role of taurine in the mechanism of action of ethanol in the VS. The high sensitivity and time resolution afforded by capillary electrophoresis and laser-induced fluorescence detection will be useful for detecting subtle changes of neuronally active amino acids levels due to low doses of ethanol.

Animals↗

Risk of scrapie in British sheep of different prion protein genotype.

There is a well-established association between sheep prion protein (PrP) genotype and the risk of death from scrapie. Certain genotypes are clearly associated with susceptibility to the disease and others to resistance. However, there have been no attempts to quantify the disease risk for all 15 PrP genotypes. Here, datasets of the PrP genotypes of nearly 14 000 British sheep and of more than 1500 confirmed scrapie cases were combined to yield an estimate of scrapie risk (reported cases per annum per million sheep of the genotype, or RCAM) for British sheep. The greatest scrapie risk by far, ranging from 225 to 545 RCAM, was for the VRQ-encoding genotypes ARQ/VRQ, ARH/VRQ and VRQ/VRQ. The next greatest risk (37 RCAM) was for the ARQ/ARQ genotype. The ARR/ARR genotype was the only numerically significant genotype for which no scrapie cases have been reported. The AHQ allele conferred resistance and the risk of scrapie in AHQ/VRQ sheep was very low (0.7 RCAM), although there was a higher and moderate risk for the AHQ homozygote (5 RCAM). The ARH allele appeared to confer susceptibility when encoded with VRQ, but possible resistance when encoded with other alleles. Scrapie risk varied with age: for VRQ/VRQ and ARH/VRQ the risk peaked at 2 years of age; that for ARQ/VRQ peaked at 3 years. There was some evidence that, following the lower risk at 4 and 5 years, a second rise occurred from about 6 years. Comparison with other published data indicated that the scrapie risk of certain PrP genotypes may differ between Great Britain and other countries.

Age Factors↗

Maternal transmission studies of BSE in sheep.

If BSE (bovine spongiform encephalopathy) infected the UK sheep population concurrently with cattle, it would only now be maintained by transmission between sheep by routes which could include from mother to lamb either in utero or via perinatal close contact. In this study of experimental BSE, Cheviot ewes challenged orally with BSE cattle brain produced lambs of various PrP genotypes over the next 7 years. Of 72 surviving to >30 months of age, 29 are of the most susceptible PrP genotype (AQ/AQ) and born to mothers that were challenged with BSE. None of the progeny have shown any signs of disease. The results suggest that in these sheep, BSE could only transmit by the maternal route at a frequency of less than one in four (95 % confidence limit) from clinically affected ewes, a rate which if replicated in other breeds may not be sufficient to maintain BSE within the sheep population.

Animals↗

Women with intellectual disability who have offended: characteristics and outcome.

BACKGROUND: There have been a few reports describing the characteristics and outcomes of male offenders with intellectual disability (ID). Therefore, while we are building up a reasonable picture of this client group, there are almost no reports of female offenders with ID. This paper is a preliminary attempt to present information on a small cohort of female offenders. METHODS: Characteristics of female offenders are presented including information on age, IQ, mental illness, referring agents, crimes committed, problems identified, sexual and physical abuse and outcome. Some comparisons are made with corresponding descriptions of male cohorts in Lindsay et al. (2004). RESULTS: The main result is that females constitute 9% of referrals to the service. Other notable results are that: at 61% sexual abuse in the cohort of female offenders is higher than in male cohorts but at 38.5% physical abuse is no higher than in appropriate comparison groups; as with mainstream female offenders identification of mental illness is high at 67%; and total re-offending over 5 years was 22% but, excluding prostitution, was only 16.5%. CONCLUSIONS: In some respects, this cohort of female offenders shows similar characteristics to their male counterparts. However, there are higher levels of mental illness, higher levels of sexual abuse and lower levels of re-offending. It is hypothesized that as females constitute such a low percentage of referrals, it suggests that women with ID do not show the same levels of sexually abusive behaviour or aggressive behaviour--the two most frequent reasons for male referral. Therefore, an intervening variable such as mental illness may indeed be a significant factor. Lower re-offending rates may indicate the success of interventions directed at psychological problems and mental illness.

Adult↗

Acquired C1 esterase inhibitor deficiency or serendipity? The chance finding of a paraprotein after an apparently low C1 esterase inhibitor concentration.

Acquired C1 esterase inhibitor deficiency is a rare condition, usually presenting after the 2nd decade of life, and is often related to underlying conditions such as autoimmune and lymphoproliferative disorders. This case report describes a man whose initial clinical presentation with acute angioedema and whose initial estimation of a low C1 esterase inhibitor concentration indicated that he had an acquired angioedema, possibly secondary to a B cell neoplasm. A paraprotein was detected, and although its detection was serendipitous because it hinged on a spurious C1 esterase inhibitor result, this case confirms the role of C4 concentrations in the investigation of C1 esterase inhibitor deficiency. It also confirms the need to obtain repeat confirmatory samples before arriving at a diagnosis, however convincing the clinical signs may be.

Acute Disease↗

Osteogenic Cells Derived From Embryonic Stem Cells Produced Bone Nodules in Three-Dimensional Scaffolds.

An approach for 3D bone tissue generation from embryonic stem (ES) cells was investigated. The ES cells were induced to differentiate into osteogenic precursors, capable of proliferating and subsequently differentiating into bone-forming cells. The differentiated cells and the seeded scaffolds were characterized using von Kossa and Alizarin Red staining, electron microscopy, and RT-PCR analysis. The results demonstrated that ES-derived bone-forming cells attached to and colonized the biocompatible and biodegradable scaffolds. Furthermore, these cells produced bone nodules when grown for 3-4 weeks in mineralization medium containing ascorbic acid and beta-glycerophosphate both in tissue culture plates and in scaffolds. The differentiated cells also expressed osteospecific markers when grown both in the culture plates and in 3D scaffolds. Osteogenic cells expressed alkaline phosphatase, osteocalcin, and osteopontin, but not an ES cell-specific marker, oct-4. These findings suggest that ES cell can be used for in vitro tissue engineering and cultivation of graftable skeletal structures.

Journal Article↗

Routine unselected access to day case electrical cardioversion of persistent atrial fibrillation: anticoagulant preparation is the key factor.

OBJECTIVES: To determine the routine efficacy of a day case cardioversion system operating in a remote geographical area with an unselected case referral base and a proportion of direct GP access. DESIGN: Prospective analysis of all admitted cases in a 13 week period. PARTICIPANTS: 47 consecutive patients admitted for 49 planned episodes of electrical cardioversion. MEASUREMENTS: Pre procedural investigations and preparation, immediate and three-month outcome of rhythm following ECV. RESULTS: We found a predominant use by the cardiac unit despite working within a general medical service unit suggesting low case selection from non-cardiac sources. We suspected and confirmed a high rate of point of care treatment cancellation. Poor management of anticoagulation was the dominant reason for canceling planned treatment. Procedural preparation in terms of anti arrhythmic drug therapy and investigations seemed well preserved. CONCLUSION: New strategies for initiating and sustaining adequate outpatient warfarin therapy are needed to allow such systems to operate efficiently.

Aged↗

Unicompartmental knee arthroplasty. 2- to 12-year results in a community hospital.

We report the outcome of 135 knees with anteromedial osteoarthritis in which the Oxford meniscal-bearing unicompartmental arthroplasty was inserted in a district general hospital by a single surgeon. All the knees had an intact anterior cruciate ligament, a correctable varus deformity and the lateral compartment was uninvolved or had only minor osteoarthritis. The mean follow-up was 5.82 years (2 to 12). Using revision as the end-point, the outcome for every knee was established. Five knees have been revised giving a cumulative rate of survival of the prosthesis at ten years of 94.04% (95% confidence interval 84.0 to 97.8). Knee rating and patient function were assessed using the modified Knee Society scoring system. The mean knee score was 92.2 (51 to 100) and the mean functional score 76.2 (51 to 100). The survival of the implant is comparable to that reported by the designers of the prosthesis and not significantly different from that for total knee replacement. Unicompartmental knee replacement offers a viable alternative in patients with medial osteoarthritis. Appropriate selection of patients and good surgical technique are the key factors.

Aged↗

Antimicrobial use in paediatric wards of teaching hospitals in Bangladesh.

To ascertain the pattern of antimicrobial use and to assess its appropriateness a 4-month prospective study was conducted from January through April 1998 in paediatric wards of five selected medical college hospitals in Bangladesh. The hospitals were selected by simple random technique. Every patient in the paediatric wards of the selected hospitals who was being treated with antimicrobials during the data collection period was considered for the study. The treatment charts of 2171 admitted paediatric patients were reviewed. Pneumonia and diarrhoea were the two most common infectious diseases among them. The most commonly used antimicrobials were ampicillin, gentamicin, amoxicillin, cloxacillin and ceftriaxone. The majority of the admitted paediatric patients (56.1%) included in this study received two or more antimicrobials in combination for their treatment. The percentages of appropriate antimicrobial treatment of pneumonia, and diarrhoea were 57.1% and 67.8% respectively across the hospitals. The evident of high percentages of inappropriate antimicrobial treatment for the most common infectious diseases suggested the need for intervention to improve antimicrobial use in hospitals.

Adolescent↗