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Biomedical subjects

W Smith

Publications and source records attributed to W Smith.

At least 37 records · Page 2Linked to original sources

Current multimodality management of infectious intracranial aneurysms.

OBJECTIVE: To implement an algorithm for and assess multimodality (medical, endovascular, and microsurgical) treatment of patients with infectious intracranial aneurysms. METHODS: Twenty patients with 27 infectious aneurysms were treated during a 10-year period. Bacterial endocarditis was the most common cause (65%). Most aneurysms presented with rupture (75%), and the middle cerebral artery was the most common location (70%). RESULTS: Five patients were treated endovascularly, with direct coiling for three patients and parent artery occlusion for two patients. Ten patients (15 aneurysms) were treated surgically, with 6 aneurysms being trapped/resected, 2 trapped/bypassed, 4 clipped, and 3 wrapped. Five patients were treated medically. Treatment-associated neurological morbidity was observed for two patients (10%), and two patients died (10%). Good outcomes were observed for 16 patients (80%). CONCLUSION: Factors that guide management decisions for these patients include aneurysm rupture, hematomas with increased intracranial pressure, and the eloquence of brain tissue supplied by the parent artery. Patients with unruptured infectious aneurysms are initially treated medically, with antibiotics and serial angiography. Patients with ruptured aneurysms that are not associated with hematomas and that do not involve eloquent vascular territory are treated endovascularly. Patients with ruptured aneurysms are treated surgically when there is a hematoma or the risk of ischemic complications in eloquent territory. Therefore, endovascular therapy is the first option for patients in stable condition with ruptured aneurysms; surgical therapy is the first option for patients in unstable condition with ruptured aneurysms and the second option for patients in stable condition who experience failure of endovascular therapy. Medically treated patients with enlarging or dynamic unruptured aneurysms also require direct surgical or endovascular intervention. Favorable patient outcomes can be achieved with this multimodality management.

Adolescent↗

Exploring extra-binomial variation in teratology data using continuous mixtures.

Discrete data from animal teratology experiments are known to exhibit extra-binomial variation. For example, we discuss a dominant lethal assay experiment in which male mice are exposed to various levels of radiation and are then mated to females. The response of interest is the number of resorptions out of the number of implantations. Most statistical work on analyzing such data has focused on modeling response rates as a function of dose of a suspected teratogen (radiation in this case) while accounting for the extra-binomial variability when calculating standard errors of the regression coefficients. Sometimes, however, when an unobserved genetic or exposure variable is suspected, the shape of the mixing distribution is of interest. We propose a mixture of beta-binomials (MBB) family of distributions that includes the non-parametric mixture of binomials model of Laird (1978) as a special case. The MBB family can accommodate a mixing distribution with one or more modes, and we develop a bootstrap test for multimodality. We apply the method to data from a dominant lethal teratology experiment.

Animals↗

Recording and analyzing high-density event-related potentials with infants. Using the Geodesic sensor net.

This article provides an overview of the use of the Geodesic sensor net system for high-density event-related potential (ERP) recording in infants. Some advantages and disadvantages of the system, as applied to infants, are discussed. First, we illustrate that high-density data can be recorded from infants at comparable quality to that observed with conventional (low density) ERP methods. Second, we discuss ways to utilize the greater spatial information available by applying source separation and localization procedures. In particular, we focus on the application of one recent source separation method, Independent Component Analysis (ICA). Finally, we show that source localization can be applied to infant high-density data, although this entails adopting a number of assumptions that remain to be verified. In the future, with improved source separation algorithms, we suggest that single-trial or single-subject analyses may become feasible.

Adult↗

The role of meaning and familiarity in mental transformations.

Eighty-four participants mentally rotated meaningful and meaningless objects. Within each type of object, half were simple and half were complex; the complexity was the same across the meaningful and meaningless objects. The patterns of errors were examined as a function of the type of stimuli (meaningful vs. meaningless), complexity, and angle of rotation. The data for the meaningful objects showed steeper slopes of rotation for complex objects than that for simple objects. In contrast, the simple and complex meaningless objects showed comparable increases in error rates as a function of angle of rotation. Furthermore, the slopes remained comparable after pretraining that increased familiarity with the objects. The results are discussed in terms of underlying representations of meaningful and meaningless objects and their implications to mental transformations. The data are consistent with a piecemeal rotation of the meaningful stimuli and a holistic rotation of the meaningless stimuli.

Adolescent↗

The distribution of plantar pressures in American Indians with diabetes mellitus.

The primary purpose of this study was to determine the magnitude and duration of plantar pressures acting on the feet of American Indians with diabetes mellitus. A secondary purpose was to determine whether differences in the range of motion of the ankle and first metatarsophalangeal joints existed between American Indians with and without diabetes. Three groups of American Indian subjects were tested: a control group (n = 20); a group with diabetes but no peripheral neuropathy (n = 24); and a group with diabetes and peripheral neuropathy (n = 21). A floor-mounted pressure sensor platform was used to collect plantar pressure data while subjects walked barefoot. The results indicated that American Indians with diabetes have 1) a pattern of peak plantar pressure similar to patterns previously reported for non-American Indians with diabetes and 2) a reduction in ankle and first metatarsophalangeal joint range of motion in comparison with nondiabetic American Indians.

Adult↗

Topoisomerase I inhibitors in the treatment of head and neck cancer.

Traditionally, the role of chemotherapy in the treatment of squamous carcinoma of the head and neck has been confined to patients with recurrent or metastatic disease who are deemed incurable with surgery or radiation therapy. Over the past decade, however, the role of chemotherapy has changed dramatically. The use of primary combined chemoradiation to preserve function or to enhance survival in patients with unresectable disease has become a standard approach. As the use of chemotherapy in squamous carcinoma of the head and neck has expanded, investigators have been interested in identifying new active agents. Topoisomerase I inhibitors, a new class of drugs, have been found to be active in a number of solid and hematologic malignancies. Three topoisomerase I inhibitors have been investigated in the treatment of metastatic or recurrent squamous carcinoma of the head and neck: 9-aminocamptothecin (9-AC), topotecan (Hycamtin), and irinotecan (CPT-11, Camptosar). Neither 9-AC nor topotecan has demonstrated clinically significant activity in the treatment of metastatic or recurrent squamous carcinoma of the head and neck. In contrast, irinotecan has demonstrated a modest overall response rate of 21.2% (95% confidence interval [CI] = 9%-38.9%), with a median survival of 214 days and a 1-year survival rate of 30.2%. The response and toxicity appear to be dose dependent. Further investigation of irinotecan in combination with other active agents and radiotherapy is warranted.

Antineoplastic Agents↗

Characterisation of a gene cluster involved in bacterial degradation of the cyanobacterial toxin microcystin LR.

A novel pathway for degradation of the cyanobacterial heptapeptide hepatotoxin microcystin LR was identified in a newly isolated Sphingomonas sp. (Bourne et al. 1996 Appl. Environ. Microbiol. 62: 4086-4094). We now report the cloning and molecular characterisation of four genes from this Sphingomonas sp. that exist on a 5.8-kb genomic fragment and encode the three hydrolytic enzymes involved in this pathway together with a putative oligopeptide transporter. The heterologously expressed degradation pathway proteins are enzymatically active. Microcystinase (MlrA), the first enzyme in the degradative pathway, is a 336-residue endopeptidase, which displays only low sequence identity with a hypothetical protein from Methanobacterium thermoautotrophicum. Inhibition of microcystinase by EDTA and 1,10-phenanthroline suggests that it is a metalloenzyme. The most likely residues that could potentially chelate an active-site transition metal ion are in the sequence HXXHXE, which would be unique for a metalloproteinase. Situated immediately downstream of mlrA with the same direction of transcription is a gene mlrD, whose conceptual translation (MlrD, 442 residues) shows significant sequence identity and similar potential transmembrane spanning regions to the PTR2 family of oligopeptide transporters. A gene mlrB is situated downstream of the mlrA and mlrD genes, but transcribed in the opposite direction. The gene encodes the enzyme MlrB (402 residues) which cleaves linear microcystin LR to a tetrapeptide degradation product. This enzyme belongs to the "penicillin-binding enzyme" family of active site serine hydrolases. The final gene in the cluster mlrC, is located upstream of the mlrA gene and is transcribed in the opposite direction. It codes for MlrC (507 residues) which mediates further peptidolytic degradation of the tetrapeptide. This protein shows significant sequence identity to a hypothetical protein from Streptomyces coelicolor. It is suspected to be a metallopeptidase based on inhibition by metal chelators. It is postulated on the basis of comparison with other microorganisms that the genes in this cluster may all be involved in cell wall peptidoglycan cycling and subsequently act fortuitously in hydrolysis of microcystin LR.

Amino Acid Sequence↗

Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure. Study Investigators.

BACKGROUND: We determined the short-term hemodynamic and clinical effects of levosimendan, a novel calcium-sensitizing agent, in patients with decompensated heart failure. METHODS AND RESULTS: One hundred forty-six patients with New York Heart Association functional class III or IV heart failure (mean left ventricular ejection fraction 21+/-1%) who had a pulmonary capillary wedge pressure >/=15 mm Hg and a cardiac index </=2.5 L x min(-1) x m(-2) were enrolled in a multicenter, double-blind, placebo-controlled study and randomized 2:1 to intravenous infusion of levosimendan or placebo. Drug infusions were uptitrated over 4 hours from an initial infusion rate of 0.1 microg x kg(-1) x min(-1) to a maximum rate of 0.4 microg x kg(-1) x min(-1) and maintained at the maximal tolerated infusion rate for an additional 2 hours. Levosimendan caused dose-dependent increases in stroke volume and cardiac index beginning with the lowest infusion rate and achieving maximal increases in stroke volume and cardiac index of 28% and 39%, respectively. Heart rate increased modestly (8%) at the maximal infusion rate and was not increased at the 2 lowest infusion rates. Levosimendan caused dose-dependent decreases in pulmonary capillary wedge, right atrial, pulmonary arterial, and mean arterial pressures. Levosimendan appeared to improve dyspnea and fatigue, as assessed by the patient and physician, and was not associated with a significant increase in adverse events. CONCLUSIONS: Levosimendan caused rapid dose-dependent improvement in hemodynamic function in patients with decompensated heart failure. These hemodynamic effects appeared to be accompanied by symptom improvement and were not associated with a significant increase in the number of adverse events. Levosimendan may be of value in the short-term management of patients with decompensated heart failure.

Cardiotonic Agents↗

Dietary sodium intake and cataract: the Blue Mountains Eye Study.

A population-based cross-sectional study (n = 2,873) was conducted near Sydney, Australia, from January 1992 to January 1994 to assess the relation between dietary sodium intake and risk of cataract. Photographs of subjects' lenses were graded for cortical, nuclear, and posterior subcapsular cataracts. Dietary sodium intake was assessed with a food frequency questionnaire. The study found that higher sodium intakes were associated with greater risk of posterior subcapsular cataract (p for trend = 0.006). The adjusted relative risk was 2.0 (95% confidence interval: 1.2, 3.4) for subjects in the highest versus the lowest quintile of sodium intake. These findings suggest that a high-salt diet may increase the risk of posterior subcapsular cataract.

Aged↗

Dietary fat and fish intake and age-related maculopathy.

OBJECTIVE: To assess whether dietary intake of fat or fish is associated with age-related maculopathy (ARM) prevalence. DESIGN: Cross-sectional, urban population-based study. PARTICIPANTS: People (N = 3654) aged 49 years or older. MAIN OUTCOME MEASURES: Subjects with ARM were identified from masked grading of retinal photographs. A 145-itemself-administered, semiquantitative food frequency questionnaire was completed adequately by 88.8% of participants and was used to assess intakes of dietary fat and fish. RESULTS: A higher frequency of fish consumption was associated with decreased odds of late ARM (odds ratio for frequency of consumption more than once per week compared with less than once per month, 0.5). Subjects with higher energy-adjusted intakes of cholesterol were significantly more likely to have late ARM, with an increased risk for late ARM for the highest compared with the lowest quintile of intake (odds ratio, 2.7). CONCLUSION: The amount and type of dietary fat intake may be associated with ARM.

Aged↗

Diet and cataract: the Blue Mountains Eye Study.

PURPOSE: To investigate relationships between a wide range of macro- and micronutrients, including antioxidant vitamins, and the three main types of cataract in older people. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Two thousand nine hundred people aged 49 to 97 years living in an urban community near Sydney, Australia. TESTING: Food frequency questionnaires and lens photography. MAIN OUTCOME MEASURE: Lens photographs were graded for presence and severity of cortical, nuclear, and posterior subcapsular cataracts. RESULTS: Higher intakes of protein, vitamin A, niacin, thiamin, and riboflavin were associated with reduced prevalence of nuclear cataract. After adjusting for multiple known cataract risk factors, the odds ratios for those in the highest intake quintile groups compared to those in the lowest intake quintiles were 0.5 (95% confidence interval [CI], 0.3-0.8) for protein, 0.5 (95% CI, 0.3-0.9) for vitamin A, 0.6 (95% CI, 0.4-0.9) for niacin, 0.6 (95% CI, 0.4-0.9) for thiamin, and 0.5 (95% CI, 0.3-0.9) for riboflavin. Intake of polyunsaturated fats was associated with reduced prevalence of cortical cataract. No nutrients were associated with posterior subcapsular cataract. CONCLUSIONS: The nucleus of the lens is particularly sensitive to nutrient deficiencies. Protein, vitamin A, niacin, thiamin, and riboflavin protected against nuclear cataract in this study.

Aged↗

Risk factors and significance of finding asymptomatic retinal emboli.

PURPOSE: To assess the prevalence rates for asymptomatic retinal emboli among both younger and older individuals, with single and multiple potential risk factors, in order to alert clinicians to the probability of finding retinal emboli in patients with varying characteristics. METHODS: In all, 3654 people aged 49-97 attending the Blue Mountains Eye Study had a detailed eye examination which included retinal photographs of the central and peripheral retinal fields. Retinal emboli were identified during masked photographic grading and definite cases were adjudicated. RESULTS: Retinal emboli were found in 51 subjects (1.4% of the population); these included 1.1% of people aged 49-69 years (middle-aged subjects) and 2.0% of people aged more than 70 years (older subjects). Risk factors identified were male sex, increasing age, hypertension, current smoking, history of any vascular event (angina, myocardial infarct, stroke) or history of vascular surgery. Among middle-aged subjects, current smoking and history of hypertension or a vascular event were significantly associated with emboli (odds ratios (OR) 2.3-3.1), while in older subjects, history of vascular surgery was related (OR 4.7). The highest prevalence of emboli (5.5%) was found in people who reported a history of hypertension and also smoked (OR 6.0). Among hypertensive men who smoked, emboli were present in 7.6%. CONCLUSIONS: This study indicates that although asymptomatic retinal emboli are relatively infrequent in the general older population, these lesions are surprisingly common in people (particularly men) with multiple risk factors. Ophthalmologists could routinely screen for emboli and consider alerting the patients' general practitioners to review vascular risk factors.

Aged↗

Peripheral arterial embolization: Doppler ultrasound scan diagnosis.

Use of intraoperative monitoring with transcranial Doppler scanning during carotid endarterectomy has enabled identification of embolus signals in the ultrasound spectrum. Extension of this technique to preoperative screening has enabled identification of actively embolizing lesions and correlation with neurologic deficits. We report embolus signals in the peripheral circulation before operation, which aided diagnosis and decision to operate. The patient had been transferred from another institution after multiple revascularization procedures, including posterior tibial artery thrombectomy. Angiography performed on arrival at our institution confirmed an open bypass graft, although a small indentation was noted at the site of the previous posterior tibial artery thrombectomy. Runoff was intact to the plantar arch where there was attenuation of that vessel and occlusion of most digital branches. Duplex monitoring revealed no embolic signals in the graft or in the posterior tibial artery proximal to the previous arteriotomy. Distal to this site, embolic signals were detected. At the time of operation, a large platelet thrombus was identified at the site of the previous arteriotomy, and platelet thrombus was obtained from the plantar artery. It is concluded that doppler ultrasound scanning enables detection of peripheral embolization and the identification and location of lesions with such embolic activity. Diagnostic accuracy may be improved when there is clinical suspicion of embolization, enabling better patient selection for surgical procedures. This report provides the first clinicopathologic characterization of the emboli detected.

Amputation, Surgical↗

A case study of co-ordinative decision-making in disaster management.

A persistent problem in the management of response to disasters is the lack of co-ordination between the various agencies involved. This paper reports a case study of inter-agency co-ordination during the response to a railway accident in the UK. The case study examined two potential sources of difficulty for co-ordination: first, poorly shared mental models; and, second, a possible conflict between the requirements of distributed decision-making and the nature of individual decision-making. Interviews were conducted with six individuals from three response agencies. Analysis of reported events suggested that inter-agency co-ordination suffered through a widespread difficulty in constructing a reflexive shared mental model; that is, a shared mental representation of the distributed decision-making process itself, and its participants. This difficulty may be an inherent problem in the flexible development of temporary multi-agency organizations. The analysis focused on a distributed decision over how to transport casualties from an isolated location to hospital. This decision invoked a technique identified here as the progression of multiple options, which contrasts with both recognition-primed and analytical models of individual decision-making. The progression of multiple options appeared to be an effective technique for dealing with uncertainty, but was a further source of difficulty for inter-agency co-ordination.

Communication↗

Effect of infection control measures on the frequency of upper respiratory infection in child care: a randomized, controlled trial.

BACKGROUND: Acute upper respiratory infections are common in children who attend child care, and preventing transmission of disease in this setting depends on actions by child care staff. We set out to discover whether transmission of respiratory infections in child care could be reduced by improved infection control procedures. METHODS: We performed a cluster, randomized, controlled trial of an infection control intervention conducted in child care centers in 1 city in Australia. The intervention was training of child care staff about transmission of infection, handwashing, and aseptic nosewiping technique. Implementation of the intervention was recorded by an observer. Illness was measured by parent report in telephone interviews every 2 weeks. RESULTS: There were 311 child-years of surveillance for respiratory symptoms. By multivariable analysis, there was no significant reduction in colds in intervention center children across the full age range. However, a significant reduction in respiratory illness was present in children 24 months of age and younger. When compliance with infection control practices was high, colds in these children were reduced by 17%. CONCLUSIONS: This trial supports the role of direct transmission of colds in young children in child care. The ability of infection control techniques to reduce episodes of colds in children in child care was limited to children 24 months of age and under.

Australian Capital Territory↗