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Biomedical subjects

J Simpson

Publications and source records attributed to J Simpson.

At least 55 records · Page 3Linked to original sources
PubMed2001

Local factor production by MG63 osteoblast-like cells in response to surface roughness and 1,25-(OH)2D3 is mediated via protein kinase C- and protein kinase A-dependent pathways.

Titanium (Ti) surface roughness affects bone formation in vivo and osteoblast attachment, proliferation and differentiation in vitro. MG63 cells exhibit decreased proliferation and increased differentiation when cultured on rough Ti surfaces (Ra > 2 microm) and response to 1,25-(OH)2D3 is enhanced, resulting in synergistic increases in TGF-beta1 and PGE2. To examine the hypothesis that surface roughness and 1,25-(OH)2D3 exert their effects on local factor production through independent, but convergent, signaling pathways, MG63 cells were cultured on tissue culture plastic or on smooth (PT, Ra = 0.60 microm) and rough (SLA, Ra = 3.97 microm; TPS, Ra = 5.21 microm) Ti disks. At confluence (5 days), cultures were treated for 24h with 10(-8) M 1alpha,25-(OH)2D3 and active and latent TGF-beta1 in the conditioned media measured by ELISA. Cell layers were digested with plasmin and released TGF-beta1 was also measured. 1,25-(OH)2D3 regulated the distribution of TGF-beta1 between the media and the matrix in a surface-dependent manner; the effect was greatest in the matrix of cells cultured on SLA and TPS. Inhibition of PKA with H8 for the last 24 h of culture increased PGE2 on SLA and TPS, but when present throughout the entire culture period H8 caused an increase in PGE2 on all surfaces. 1,25-(OH)2D3 reduced the effect of H8 on PGE2 production in cultures treated for 24 h. H8 had no effect on TGF-beta1 in the media by itself but caused a complete inhibition of the 1,25-(OH)2D3 dependent increase. Inhibition of PKC with chelerythrine increased PGE2 in a surface-dependent manner and 1,25-(OH)2D3 reduced the effect of the PKC inhibitor. Chelerythrine also increased TGF-beta1 but the effect was not surface dependent; however, 1,25-(OH)2D3 reduced the effects of chelerythrine with the greatest effects on the smooth surface. Thus, the distribution of TGF-beta1 between the media and the matrix is regulated by 1,25-(OH)2D3 in a surface-dependent manner. Surface roughness exerts its effects on TGF-beta1 production via PKC but not PKA. The effect of 1,25-(OH)2D3 on TGF-beta1 production is not via PKC. PKA is involved in the surface-dependent regulation of PGE2 but not in the regulation of PGE2 by 1,25-(OH)2D3 on rough surfaces. Regulation of PKC affects PGE2 production but it is not involved in the surface roughness-dependent response to 1,25-(OH)2D3. These results suggest two independent but interconnected pathways are involved.

Animals↗
PubMed2001

Paediatric transfusion.

Paediatric transfusion encompasses a wide range of clinical circumstances including the consideration of maternal antibodies, the changing nature of the transfusion recipient with respect to growth and development, and the management of inherited conditions which if optimally treated in early life may have problems which are delayed or less severe in adult life. Whilst the transfusion of adults and children has much in common, a child cannot be considered as a scaled down adult; there are many important differences. Developmental changes are most marked in the neonate and, together with the fact that their antibodies are maternally derived, this population provide some of the most striking challenges. The increased use of intra uterine transfusion adds an extra dimension here. A particular paediatric concern is the long-term consequences of transfusion. It is to be hoped that paediatric transfusion recipients will live long enough that any potential problems will manifest themselves, thus the aim must be to minimize transfusion risks.

Blood Cells↗
PubMed2001

Problems with solutions: drowning in the brine of an inadequate knowledge base.

BACKGROUND & AIMS: We undertook a telephone questionnaire to determine current fluid prescribing practices and relevant knowledge among surgical preregistration house officers (PRHOs) and senior house officers (SHOs) working in 25 British hospitals. METHODS: One hundred PRHOs were surveyed within 10 days of starting their first job (Group A). Fifty other PRHOs were surveyed 6-8 weeks after starting their first job(Group B) along with 50 surgical SHOs (Group C). Outcome measures included responsibility for prescribing, knowledge of the composition of common intravenous fluids and the principles governing their use. RESULTS: PRHOs were responsible for prescribing in 89% of instances. Only 56% of respondents stated that fluid balance charts were checked on morning ward rounds. Less than half were aware of the sodium content of 0.9% saline or the daily sodium requirement. Although potassium supplements were usually correct, 25% of respondents prescribed two or more litres of 0.9% saline per day, which is far in excess of normal requirements. Although SHOs were more confident (P<0.0001), there was no significant difference between the three groups for most responses. CONCLUSIONS: Inadequate knowledge and suboptimal prescribing of fluid and electrolytes is common. Undergraduate and postgraduate training in this basic patient management skill needs improvement, with particular emphasis on the practical aspects.

Clinical Competence↗
PubMed2001

Large tables.

The traditional exploration of large contingency tables leads to multiple comparisons with the inherent generation of chance associations. To allow for this, a simple empirical Bayesian approach is used here to derive estimates of association 'shrunk' towards a global mean. Estimates are displayed on ordered normal plots, to allow visual detection of outliers, with the addition of 'guide rails', derived from simulation, to facilitate their detection. The methods, and the interpretation of results, are illustrated using a large table of occupations for cancer registrations in England and Wales for 1971-90.

Journal Article↗
PubMed2001

Delayed regional metastases, distant metastases, and second primary malignancies in squamous cell carcinomas of the larynx and hypopharynx.

OBJECTIVE: To determine the impact of delayed regional metastases, distant metastases, and second primary tumors on the therapeutic outcomes in squamous cell carcinomas of the larynx and hypopharynx. STUDY DESIGN: Chart review and statistical analysis. METHODS: A retrospective tumor registry analysis was made of patients with squamous cell carcinomas of the larynx and hypopharynx who were treated with curative intent in the Department of Otolaryngology-Head and Neck Surgery and the Radiation Oncology Center of the Washington University School of Medicine (St. Louis, MO) between January 1971 and December 1991 and developed delayed regional metastases (2 y after treatment), distant metastases, and second primary malignancies. RESULTS: In 2550 patients, the mean age (59.8 y), sex (8.5 male patients and 1 female patient), and tumor differentiation did not affect the incidence of delayed distant, regional, or second primary malignancies. The overall incidence of delayed regional metastases was 12.4% (317/2550 patients); distant metastases, 8.5% (217/2550); and second primary tumors, 8.9% (228/2550), with a 5-year disease-specific survival of 41%, 6.4%, and 35%, respectively. Second primary malignancies were not statistically related to the origin of the primary tumor, tumor staging, or delayed regional and distant metastases (P =.98). Delayed regional metastases and distant metastases were related to advanced primary disease (T4 stage), lymph node metastases (node positive [N+]), tumor location (hypopharynx), and locoregional tumor recurrence (P < or =.028). Advanced regional metastases at initial diagnosis (N2 and N3 disease) increased the incidence of delayed and distant metastases threefold (P =.017). These two metastatic parameters were significantly greater in hypopharyngeal tumors than in laryngeal tumors (P =.037). The incidences of delayed regional metastases by anatomical location of the primary tumor were as follows: glottic, 4.4%; supraglottic, 16%; subglottic, 11.5%; aryepiglottic fold, 21.9%; pyriform sinus, 31.1%; and posterior hypopharyngeal wall, 18.5%. The incidences of distant metastases were as follows: glottic, 4%; supraglottic, 3.7%; subglottic, 14%; aryepiglottic fold, 16%; pyriform fossa, 17.2%; and posterior hypopharyngeal wall, 17.6%. Seventeen hypopharyngeal tumors (2%) presented with M1 disease. Delayed regional metastases to the ipsilateral treated neck had a significantly worse survival prognosis than delayed metastases to the contralateral nontreated neck (P =.001). CONCLUSIONS: Conclusions are as follows: 1) The incidence of second primary tumors is independent from the primary tumor staging and distant and delayed regional metastases. The highest incidence occurred in patient groups with the highest disease-free survival rates (P =.0378). 2) Highest incidence of delayed and distant metastases occurred in hypopharyngeal tumors and was three times greater than in laryngeal cancers (P =.028). 3) Salvage therapeutic rates were poor for delayed metastases to the ipsilateral treated nodes and distant metastases as compared with contralateral neck metastases and second primary tumors (P =.001). 4) Delayed and distant lymph node metastases were significantly higher in advanced primary disease (T4 stage), locoregional recurrences, and regional disease (N2 and N3) (P =.028) in both the larynx and hypopharynx. 5) The higher incidence of delayed and distant metastatic disease was related to more advanced initial tumor presentation in hypopharyngeal cancer as compared with laryngeal cancer (P =.039). 6) Incidence of distant metastases was greatest between 1.5 and 6 years after initial treatment with a mean incidence being less than or equal to 3.2 years.

Adult↗
PubMed2001

Evidence base of incubation periods, periods of infectiousness and exclusion policies for the control of communicable diseases in schools and preschools.

BACKGROUND: The optimal control of communicable diseases requires accurate information on incubation periods, periods of infectiousness and the effectiveness of exclusion. We collected the available evidence for a wide range of infections and infestations and produced evidence-based guidelines for their control in schools and preschools. METHODS: A thorough MEDLINE literature search was conducted on the incubation period, period of infectiousness and effectiveness of exclusion for 41 infections. The quality of the information obtained was indicated by levels of evidence. The information was used to produce guidelines on exclusion, and the recommendations were graded according to the levels of evidence available. Grades A, B and C represented strongly, reasonably and poorly evidence-based recommendations, respectively. RESULTS: The quality of data obtained was highly variable. Information on incubation periods was obtained for all 41 infections and was generally of good quality. Information on periods of infectiousness and effectiveness of exclusion was of a lesser quality and was found for only 11 and 4 conditions, respectively. There were 3 Grade A, 17 Grade B and 21 Grade C recommendations on exclusion. Examples of exclusion periods include: 5 days for chickenpox, measles, mumps, rubella, pertussis and scarlet fever; and 24 h from the cessation of diarrhea for most gastrointestinal diseases In contrast to existing guidelines exclusion was not recommended for school age children with hepatitis A. CONCLUSIONS: We have been able to present the best available data on the incubation periods and periods of infectiousness of 41 childhood infections. It was possible to produce strongly or reasonably evidence-based guidelines on exclusion periods for approximately one-half of the infections.

Child↗
PubMed2001

Analysis for a limited number of gene codons can predict drug resistance of Mycobacterium tuberculosis in a high-incidence community.

Correct and rapid diagnosis is essential in the management of multidrug-resistant tuberculosis (MDR-TB). In this population-based study of 61 patients with drug-resistant tuberculosis, we evaluated the frequency of mutations and compared the performance of genotypic (mutation analysis by dot blot hybridization) and phenotypic (indirect proportion method) drug resistance tests. Three selected codons (rpoB531, rpoB526, and katG315) allowed identification of 90% of MDR-TB cases. Ninety percent of rifampin, streptomycin, and ethambutol resistance and 75% of isoniazid resistance were detected by screening for six codons: rpoB531, rpoB526, rrs-513, rpsL43, embB306, and katG315. The performance (reproducibility, sensitivity, and specificity) of the genotypic method was superior to that of the routine phenotypic method, with the exception of sensitivity for isoniazid resistance. A commercialized molecular genetic test for a limited number of target loci might be a good alternative for a drug resistance screening test in the context of an MDR "DOTS-plus" strategy.

Bacterial Proteins↗
PubMed2001

Outcome of staged reconstructive surgery for hypoplastic left heart syndrome following antenatal diagnosis.

BACKGROUND AND AIMS: Staged reconstructive surgery has radically altered the prognosis of hypoplastic left heart syndrome (HLHS). Antenatal diagnosis allows for appropriate counselling, and time to consider treatment options. We report outcome from a centre where most cases are antenatally diagnosed and delivered on site. METHODS: Information was collated on 188 consecutive cases of HLHS between 1995 and 2000, including timing of diagnosis, outcome of pregnancy, and age and outcome at each stage of surgery. At Guy's Hospital, 174 cases were diagnosed antenatally, of whom 50 underwent surgery. Fourteen others (five diagnosed antenatally at other centres, and nine diagnosed postnatally) also underwent surgery. RESULTS: Survival after stage I (the Norwood operation) was 52% (33/64). Postoperative survival after stage II (the hemi-Fontan operation, performed in 29), and stage III (the Fontan operation, performed in 10), was 100%. Two late deaths occurred 3 and 10 months after stage II, giving overall survival of 48% (31/64). At follow up, three children have neurological impairment, and one had poor right ventricular function necessitating cardiac transplantation. CONCLUSIONS: Antenatal diagnosis allows informed decisions about treatment options, and facilitates preoperative care. Mortality following stage I is high, irrespective of timing of diagnosis, but medium term outcome for survivors is good.

Cardiac Surgical Procedures↗
PubMed2001

Paradoxical embolism causing fatal myocardial infarction in a newborn infant.

A neonate who presented with circulatory collapse was found to have myocardial infarction caused by thrombotic occlusion of the left main coronary artery. At autopsy, a thrombus was found in the ductus venosus making paradoxical embolism through the foramen ovale the most likely mechanism of coronary occlusion.

Coronary Disease↗
PubMed2001

Evaluation of a routine telepsychiatry service.

An assessment was undertaken of a routine telepsychiatry service in rural areas of a Canadian province as a follow-up to a pilot telepsychiatry project. Over two years, there were 546 consultations at the five participating general hospitals, although the level of use varied considerably between them. Health professionals expressed high satisfaction with the service. While there were equipment problems in 17% of all consultations in the second year, they did not seem to affect acceptance of the technique. A cost analysis comparing consultations provided by a visiting psychiatrist and telepsychiatry found a break-even point of 348 consultations a year. However, when use of the videoconferencing network for administrative meetings was considered, the break-even point was 224 consultations a year, substantially below the actual utilization of telepsychiatry. Telepsychiatry appeared to result in increased access to community mental health services, suggesting future increased demand for these. From the perspective of health authorities and health professionals, telepsychiatry proved to be a useful and sustainable addition to existing mental health services.

Adult↗
PubMed2001

Telepsychiatry as a routine service--the perspective of the patient.

Patient perspectives were examined as part of an assessment of a routine telepsychiatry service in rural Alberta. Information was gathered through self-report questionnaires and telephone interviews. Of 379 questionnaires distributed to patients, 230 (61%) were returned. Of the patients who completed questionnaires, 89% reported being satisfied with the service and 96-99% were satisfied with the equipment and the room. Twenty-nine of 31 patients who were interviewed by telephone preferred telepsychiatry to waiting for a consultation, were willing to use the service again and would recommend telepsychiatry to a friend. While 25 of these 31 patients preferred telepsychiatry to travelling to a consultation, 15 indicated that they would prefer a face-to-face interview to telepsychiatry and a further seven were unsure. Twenty-three of the 31 patients interviewed would have had to miss time from work or pay for child care in order to travel to a conventional psychiatric consultation. The availability of telepsychiatry led to an estimated cost saving of $210 per consultation for patients who would otherwise have had to travel. From the patient's perspective, telepsychiatry was an acceptable technique in the management of mental health difficulties that both increased access to services and produced cost savings.

Adolescent↗
PubMed2000

Expression of the beta-chemokine receptors CCR2, CCR3 and CCR5 in multiple sclerosis central nervous system tissue.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) characterised by perivascular inflammatory cell infiltrates and plaques of demyelination. Chemokines have been shown to play an important role in the activation and directional migration of cells to sites of CNS inflammation. The action of chemokines requires the expression of their complementary chemokine receptors by their target cells. We have examined the expression of the beta-chemokine receptors CCR2, CCR3 and CCR5 in post-mortem MS CNS tissue using single- and double-labelling immunocytochemistry techniques. Low levels of CCR2, CCR3 and CCR5 were expressed by microglial cells throughout control CNS tissue. In chronic active MS lesions CCR2, CCR3 and CCR5 were associated with foamy macrophages and activated microglia. CCR2 and CCR5 were also present on large numbers of infiltrating lymphocytes. A smaller number of CCR3-positive lymphocytes were present, but we also noted CCR3 and CCR5 on astrocytes in five of the 14 cases of MS investigated, particularly associated with processes around vessels and at the glia limitans. Ligands for CCR2 and CCR3 include MCP-1 and MCP-3 which were co-localised around vessels with the infiltrating leukocytes, but were also present in unaffected areas of cortex. The elevated expression of CCR2, CCR3 and CCR5 in the CNS in MS suggests these beta-chemokine receptors and their ligands play a role in the pathogenesis of MS.

Adult↗