Search PubMed⌕ Search

Biomedical subjects

M Smith

Publications and source records attributed to M Smith.

At least 37 records · Page 2Linked to original sources

Bovine kidney tissue/biological fluid correlation for penicillin.

Penicillin is one of the most commonly misused drugs in steers and dairy cows. In the US, at slaughter the tolerance is 50 ng/g in kidney and other edible tissues. If the tolerance is exceeded, the carcass may not be used for human food. A preslaughter test for penicillin in an easily accessible biological fluid is needed to predict if the concentration of penicillin is below tolerance in the kidney before the bovine is slaughtered. In this study, 12 steers were injected three times with the approved dose (7000 IU) of penicillin at 12-h intervals. Blood and urine samples were collected at intervals after the final dose of penicillin. At each sampling point, one kidney biopsy sample was collected by laparoscopic surgery in the live animal. Another kidney sample was collected at slaughter. Correlations between plasma and kidney concentrations and between urine and kidney concentrations were determined. These correlations predict with 95% confidence that 99% of the animals will have kidney tissue below penicillin tolerance when the plasma concentration of penicillin is below 0.4 ng/mL and/or the urine penicillin concentration is below 140 ng/mL.

Abattoirs↗

Perspectives of staff on student outreach placements.

OBJECTIVE: To explore the perspectives of placement staff on outreach training. INTERVENTION: Block clinical placements in primary care settings for dental undergraduates and hygiene and therapy students. METHOD: After completion of the placements, 32 participating staff across nine primary care locations took part in qualitative interviews and focus groups. The staff provided data on placement organisation, the students' development and their supervision, and any effects on themselves as hosts. RESULTS: The major themes included the learning environment, supervision and communication. The staff saw benefits to students in working in a smaller primary care clinic with nursing support and immediately available supervision by a dental generalist. Other benefits included increased confidence, broader clinical experience and applying theoretical learning to new communities. Effective communication and adequate resourcing were critical success factors. There was some disruption of clinics' normal working, but many unanticipated benefits. Staff supported the outreach placements in primary care settings to enhance students' dental education. CONCLUSIONS: These findings provide a planning and evaluation framework for dental educators involved in outreach.

Attitude of Health Personnel↗

Student perspectives on their recent dental outreach placement experiences.

BACKGROUND: Dental schools are developing new curricula, with outreach placements enhancing the hospital-based training. OBJECTIVES: To assess the students' experience of outreach as one component of determining the value and feasibility of outreach placements. INTERVENTION: Six-week block placements for 10 undergraduates and 3 weeks for 11 hygiene and hygiene and therapy students in existing primary care clinics, in areas of need, to work supervised by local dentists. METHODS: Semi-structured interviews with 20 students by staff independent of the course team. Interviews were audio-recorded, transcribed and content analysed before being verified by a second observer. Findings were triangulated against a peer-run focus group and students' clinical records. RESULTS: Students were very positive about their experience and the potential role of outreach training in dental education. They described: gaining greater experience of new types of patients and their communities; learning from broader clinical experience, alternative approaches and practicing or observing dentistry in different settings; the benefits of team working; and, acquiring a more holistic and pragmatic view of health care. Many students reported gaining greater confidence, wider awareness of potential careers in dentistry and a greater sense of realism in their experience. Some reflected on their own training needs. Students also discussed the importance of preparation for the placements and the merits of different styles of supervision. CONCLUSION: Dental outreach training can provide students with valuable learning experience in a range of areas. It requires careful management to ensure those experiences match individuals' needs and the programme's purposes.

Attitude of Health Personnel↗

Altruistic living donors: evaluation for nondirected kidney or liver donation.

A program was established within our regional procurement organization to permit evaluation of altruistic living donors (LD) interested in nondirected kidney or liver segment donation prior to transplant center referral. During the initial 30 months of program operations, 731 donor inquiries were received of which 131 individuals called back after review of mailed information materials. Forty-seven candidates initiated and 19 completed the evaluation process. Seven underwent donation to include six kidneys and one liver segment, five are actively pending donation, five were excluded from donation following transplant center evaluation and two took no further action after their intended liver recipients received deceased donor (DD) transplants. Psychological evaluation of these 19 candidates found them to be free of psychopathology, highly cooperative and self-directed. They did not exhibit attention-seeking or religious motivations for their actions. All seven donors and recipients continue to do well postoperatively. This evaluation program has made possible large-scale screening and education of prospective altruistic LD within the general population and also provides a unique opportunity to further our understanding of those individuals interested in living-nondirected donation.

Adult↗

Work system design for patient safety: the SEIPS model.

Models and methods of work system design need to be developed and implemented to advance research in and design for patient safety. In this paper we describe how the Systems Engineering Initiative for Patient Safety (SEIPS) model of work system and patient safety, which provides a framework for understanding the structures, processes and outcomes in health care and their relationships, can be used toward these ends. An application of the SEIPS model in one particular care setting (outpatient surgery) is presented and other practical and research applications of the model are described.

Ergonomics↗

Reference data for cerebrospinal fluid and the utility of amino acid measurement for the diagnosis of inborn errors of metabolism.

BACKGROUND: Cerebrospinal fluid (CSF) amino acid analysis is fundamental to the investigation of several inherited metabolic diseases, particularly those presenting with unexplained seizures. CSF glycine measurement is often crucial to the diagnosis of glycine encephalopathy (GE), low CSF serine concentrations are characteristic of 3-phosphoglycerate dehydrogenase deficiency (3-PGDD) and the presence of sulphocysteine is pathognomonic of sulphite oxidase deficiency (SOD), and a vital clue to molybdenum cofactor deficiency (MCD). Limited information is available in the literature on reference values of amino acids in CSF during infancy and CSF samples from healthy individuals are not easily obtained. METHODS: In order to establish paediatric CSF amino acid reference ranges, we performed a retrospective analysis of all quantitative CSF amino acid data collected in our laboratory over a five-year period. Amino acid analysis was performed using ion-exchange chromatography on a Biochrom-20 amino acid analyser with ninhydrin detection. CSF samples were collected from infants undergoing investigation for unexplained seizures. RESULTS: About 18 of the 95 samples received were excluded from the reference data-set; one was from a patient in whom a diagnosis of GE was confirmed by enzyme analysis, one was from a patient with CSF sulphocysteine of 19 micromol/L in whom a diagnosis of SOD was confirmed by enzyme analysis; the remaining 16 were clearly bloodstained (n = 4) or xanthochromic (n = 12). Frequency of distribution analysis revealed that concentration values for each amino acid demonstrated a right-skewed distribution which was not normalized by log transformation. Data were therefore analysed using non-parametric descriptive statistics and reference ranges were defined by the 2.5th and 97.5th centile limits. CONCLUSIONS: Our reference data were derived from 77 CSF samples taken from 77 infants. Median CSF glycine concentration was 9 micromol/L with a reference range of 3-19 micromol/L. For serine, the median CSF concentration was 52 micromol/L with a reference range of 25-105 micromol/L. Sulphocysteine was not normally present in detectable quantities (<1 micromol/L).

Amino Acid Metabolism, Inborn Errors↗

Sequence variants of the DRD4 gene in autism: further evidence that rare DRD4 7R haplotypes are ADHD specific.

A high prevalence of rare dopamine receptor D4 (DRD4) alleles in children diagnosed with attention-deficit hyperactivity disorder (ADHD) has been reported [Grady et al., 2003]. In this prior study, extensive resequencing/haplotype data of the DRD4 locus was used to suggest that population stratification was not the explanation for the high prevalence of rare alleles. In the current study, DNA resequencing/haplotyping was conducted on 136 DRD4 alleles obtained from autism probands, collected from the same geographic population as the prior ADHD probands (Orange County, CA). A number of studies have suggested that the susceptibility genes underlying these two disorders might partially overlap. Rare DRD4 variants were not uncovered in this autism sample beyond that expected by chance. These results suggest strongly that the high prevalence of rare DRD4 alleles in ADHD probands is due to ascertainment of the sample by diagnosis of ADHD.

Alleles↗

Extracellular fluid S100B in the injured brain: a future surrogate marker of acute brain injury?

The authors describe the measurement of S100B protein in brain extracellular fluid (ECF) of patients with acute brain injury (traumatic brain injury and subarachnoid haemorrhage) using the technique of microdialysis. To our knowledge, this is the first report of S100B measurement in the human brain. Acute Brain Injury (ABI) is a leading cause of death and disability and the need for a practical and sensitive biochemical marker for monitoring these patients is urgent. The calcium binding astrocyte protein, S100B, may be a candidate for this role. Previous serum studies have shown S100B to be a sensitive predictor of mortality and rise in intracranial pressure in ABI, but it has never before been measured directly within the brain. The ECF reflects the local biochemistry of the brain parenchyma, and the use of intracerebral microdialysis opens up the possibility of studying many novel surrogate markers of injury in the laboratory, in addition to the conventional markers it measures at the bedside (lactate, pyruvate, glucose, and glycerol). In this preliminary report of two cases, the authors demonstrate the quantification of S100B in ECF microdialysate, and investigate whether changes in hourly S100B profile can be related to secondary brain injury. It is shown that extracellular concentrations of S100B change markedly in response to secondary brain injury. Further investigation is required to determine whether extracellular S100B measurement in ABI could assist in patient management.

Adult↗

[Treatment of penetrating injuries of neck, chest and extremities].

Penetrating injuries such as gunshot wounds have traditionally been rare in Europe, with the result that European surgeons have only limited experience in their management. Socio-economic changes in the last decade have led to an increase in the frequency of injuries of this type, partly due to the expansion of organized crime and partly because of involvement of the European military in peace-keeping missions in Europe and elsewhere in the world. The purpose of this article is to offer some guidelines in the management of extremely serious or rarely encountered injuries to the neck, chest and peripheral arteries and discuss controversies and possible future changes in their management as a result of the extensive experience of treating penetrating trauma in our hospital.

Amputation, Surgical↗

Phase I study of concomitant chemoradiation with raltitrexed in locally advanced head and neck cancer.

In patients with non-resectable head and neck cancer concomitant chemoradiotherapy is increasingly used, especially in cases of oropharyngeal and hypopharyngeal tumours. Most chemoradiotherapy regimes contain cisplatin as a single agent or in combination with fluorouracil. However, not all patients are fit enough for a cisplatin-containing regime or they refuse hospital admission. Raltitrexed is a specific thymidylate synthase inhibitor that has been studied as a radiosensitiser in rectal cancer. Raltitrexed can be administered easily in an outpatient setting and has few short-term effects. We studied raltitrexed at escalating doses combined with standard radiotherapy in advanced head and neck cancer patients. Seventeen patients with locally advanced head and neck cancers were enrolled in the study. Raltitrexed was administered at dose levels of 1.5, 2.0, 2.5 and 3.0 mg/m(2) intravenously (i.v), once every 3 weeks, for two doses. Radiotherapy consisted of 70 Gy given over 7 weeks in five fractions of 2 Gy per week. In general, treatment toxicity (DLT), complicated febrile neutropenia, was observed at 3.0 mg/m(2) in two of four patients. The dose of 2.5 mg/m(2) was extended thereafter with additional patients without major toxicity. Radiotherapy had to be interrupted in one patient. Five patients had a clinical complete response(CR) and eleven a partial response (PR) six weeks after the last fraction of radiotherapy. Twelve out of 17 patients remained free of locoregional recurrence after a median follow-up of 24(+) months (range 3-60+ months). Raltitrexed, at a dose of 2.5 mg/m(2) given twice 3 weeks apart, can be administered in combination with 70 Gy of radiotherapy in locally advanced head and neck cancer patients with a manageable tolerability profile. The clinical results and convenience of the schedule make raltitrexed an attractive drug to explore further in patients considered unfit for cisplatin-containing chemoradiation regimens.

Aged↗

Visual outcomes following ICG assisted ILM peel for Macular Hole.

PURPOSE: To evaluate the anatomical and visual outcome of indocyanine green (ICG)-assisted internal limiting membrane (ILM) peeling for macular hole surgery. A literature search identified potential factors that may affect the functional success of the procedure. METHODS: Retrospective case note review of 14 consecutive patients undergoing phaco-vitrectomy, gas and ICG-assisted ILM peeling for macular hole from July 2001 to July 2002. A 0.5% ICG solution (osmolarity 270 mOsm) was left in contact with the retina for 1-3 min. The outcome measures were hole closure, change in visual acuity, and macular pigmentary changes. RESULTS: Anatomical hole closure was achieved in 13 of 14 eyes (92.8%). The mean logMAR Snellen acuities were 0.80 (range 0.60-1.30) preoperatively and 0.77 (0.48-1.30) postoperatively. Seven eyes (50%) developed retinal pigmentary changes in the macular area. CONCLUSIONS: ICG-assisted ILM peeling for macular hole surgery achieves high rates of anatomical hole closure, but functional results are less encouraging. Previous studies suggest toxicity of the ICG to the retina, at the level of the RPE or inner retina. The results may be optimized by using a lower concentration, iso-osmolar, viscous solution, and by minimizing contact time of the solution and intensity, and duration of illumination.

Aged↗

Autism and the serotonin transporter: the long and short of it.

Autism is a neurodevelopmental disorder manifesting early in childhood. Some symptoms of autism are alleviated by treatment with selective serotonin reuptake inhibitors, which are known to interact with the serotonin transporter. Moreover, variation in the gene that encodes the transporter (SLC6A4), especially the HTTLPR locus, is known to modulate its expression. It is natural, therefore, to evaluate whether this variation plays a role in liability to autism. We investigated the impact of alleles at HTTLPR and three other loci in SLC6A4 by using a large, independent family-based sample (390 families, 1528 individuals) from the NIH Collaborative Programs of Excellence in Autism (CPEA) network. Allele transmissions to individuals diagnosed with autism were biased only for HTTLPR, both for the narrow diagnosis of autism (P=0.035) and for the broader diagnosis of autism spectrum (P=0.007). The short allele of HTTLPR was significantly overtransmitted. Investigation of haplotype transmissions suggested that, in our data, biased transmission was only due to HTTLPR. With respect to this locus, there are now seven of 12 studies reporting significant transmission bias of HTTLPR alleles, a noteworthy result in itself. However, the studies with significant findings are almost equally divided between overtransmission of short and overtransmission of long alleles. We place our results within this extremely heterogeneous field of studies. Determining the factors influencing the relationship between autism phenotypes and HTTLPR variation, as well as other loci in SLC6A4, could be an important advance in our understanding of this complex disorder.

Adult↗

Axonal pathology in subarachnoid and intracerebral hemorrhage.

Electrically active axons degenerate in the presence of nitric oxide (NO) in vitro. High CSF NO concentrations have been observed in patients with hemorrhagic brain injury such as subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH). This study investigated the evidence for axonal injury in SAH and ICH and related this to CSF NO levels. In this study, neurofilament phosphoforms (NfH(SMI34), NfH(SMI35), NfH(SMI38), NfH(SMI310)), surrogate markers for axonal injury, and NO metabolites (nitrate, nitrite = NOx) were measured by ELISA in cerebrospinal fluid (CSF) from patients with SAH and ICH and from a group of controls. Injury severity was classified using the Glasgow Coma Scale, and survival was used as the outcome measure. Compared to the control group, a higher proportion of patients with SAH and ICH had elevated NfH(SMI34) levels from day 0 to day 6 (p < 0.001), elevated NfH(SMI35) levels from day 1 to 6 (p < 0.001), and elevated NfH(SMI310) levels at day 0, 1, 4, and 6 (p < 0.001). The NOx levels were higher in the SAH and ICH patients than in the controls (p < 0.05) and distinguished the non-survivors from the survivors (p < 0.05). No direct correlation was found for NOx with any of the NfH phosphoforms. This study provides evidence for primary and secondary axonal injury in patients with SAH and ICH, with non-survivors also having higher NOx levels. CSF NfH phosphoforms might emerge as a putative surrogate marker for monitoring the development for secondary axonal degeneration in neurocritical care and guiding targeted neuroprotective strategies.

Adult↗

Failure to detect capsule gene bexA in Haemophilus influenzae types e and f by real-time PCR due to sequence variation within probe binding sites.

Detection of the conserved capsule gene bexA is used to distinguish capsulate from non-capsulate Haemophilus influenzae. While developing a real-time PCR assay to detect bexA, it was found that bexA probes produced a detectable signal for H. influenzae types a to d, but failed to do so for H. influenzae types e and f. Sequencing revealed differences compared with H. influenzae types a to d within probe binding sites. To prevent misclassification of strains as non-capsulate, assays must detect all capsular types.

ATP-Binding Cassette Transporters↗

Constructing a 7-day ahead forecast model for grass pollen at north London, United Kingdom.

BACKGROUND: A number of media outlets now issue medium-range ( approximately 7 day) weather forecasts on a regular basis. It is therefore logical that aerobiologists should attempt to produce medium-range forecasts for allergenic pollen that cover the same time period as the weather forecasts. OBJECTIVE: The objective of this study is to construct a medium-range (</=7 day) forecast model for grass pollen at north London. METHOD: The forecast models were produced using regression analysis based on grass pollen and meteorological data from 1990 to 1999 and tested on data from 2000 and 2002. The modelling process was improved by dividing the grass pollen season into three periods; the pre-peak, peak and post-peak periods of grass pollen release. The forecast consisted of five regression models: two simple linear regression models predicting the start and end date of the peak period, and three multiple regression models forecasting daily average grass pollen counts in the pre-peak, peak and post-peak periods. RESULTS: Overall, the forecast models achieved 62% accuracy in 2000 and 47% in 2002, reflecting the fact that the 2002 grass pollen season was of a higher magnitude than any of the other seasons included in the analysis. CONCLUSION: This study has the potential to make a notable contribution to the field of aerobiology. Winter averages of the North Atlantic Oscillation were used to predict certain characteristics of the grass pollen season, which presents an important advance in aerobiological work. The ability to predict allergenic pollen counts for a period between five and seven days will benefit allergy sufferers. Furthermore, medium-range forecasts for allergenic pollen will be of assistance to the medical profession, including allergists planning treatment and physicians scheduling clinical trials.

Air Pollutants↗