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Biomedical subjects

S White

Publications and source records attributed to S White.

At least 73 records · Page 4Linked to original sources
PubMed2001

A longitudinal study of the biometric and refractive changes in full-term infants during the first year of life.

Changes in ocular axial dimensions and refraction were followed longitudinally, using ultrasonography and retinoscopy, during the first year of life (mean ages 4-53 weeks) of a group of 20 full-term infants (10 male, 10 female). Using a mixed-model regression analysis, axial length changes as a function of time were found to be best described by a quadratic expression (AL=17.190+0.128x-0.0013x(2), where AL is the axial length in mm and x is the age in weeks), while anterior chamber depth changed linearly (ACD=2.619+0.018x, where ACD is the anterior chamber depth in mm): lens thickness was essentially constant. Spherical equivalent refraction through most of the first year showed a steady reduction in hypermetropia (SER=2.982-0.032x, where SER is the spherical equivalent refraction in dioptres): astigmatism also tended to diminish. Mean hyperopic refractive errors through the year were negatively correlated with corresponding axial lengths (SER=12.583-0.541AL), but some individual subjects showed marked departures from this pattern. These results are discussed in relation to concepts of emmetropization.

Age Factors↗
PubMed2001

Levetiracetam, oxcarbazepine, remacemide and zonisamide for drug resistant localization-related epilepsy: a systematic review.

OBJECTIVE: To undertake a systematic review and meta-analysis of placebo controlled add-on trials of levetiracetam, oxcarbazepine, remacemide and zonisamide for patients with drug resistant localization related epilepsy. METHODS: We searched Medline, The Cochrane Library and contacted the relevant pharmaceutical companies. Outcomes were 50% or greater reduction in seizure frequency and treatment withdrawal for any reason. Data were synthesised in a meta-analysis. The effect of dose was explored in regression models for levetiracetam and remacemide. RESULTS: We found four trials (1023 patients) of levetiracetam, two (961) of oxcarbazepine, two (388) of remacemide and three (499) of zonisamide. Ignoring dose, the relative risks (95% CI) for a 50% response were 3.78 (2.62-5.44), 2.51 (1.88-3.33), 1.59 (0.91-2.97) and 2.46 (1.61-3.79), respectively. There was evidence for increasing effect with increasing dose for levetiracetam, oxcarbazepine and remacemide. The relative risks for treatment withdrawal were 1.21 (0.88-1.66), 1.72 (1.35-2.18), 1.90 (1.00-3.60) and 1.64 (1.02-2.62), respectively. CONCLUSIONS: These data suggest a useful effect for levetiracetam, oxcarbazepine and zonisamide. Levetiracetam has the more favourable 'responder-withdrawal ratio' followed by zonisamide and oxcarbazepine.

Acetamides↗
PubMed2001

Caelyx (stealth liposomal doxorubicin) in the treatment of advanced breast cancer.

Anthracyclines are amongst the most active drugs in the treatment of breast cancer. Stealth liposomal doxorubicin (Caelyx, Doxil, Alza Pharmaceuticals Inc.) is a promising new agent under investigation for the treatment of breast cancer and other solid tumours. The liposomal encapsulation alters drug pharmacokinetics and leads to a marked change in toxicity profile compared to non-liposomal doxorubicin. The results of recently completed and ongoing clinical trials in breast cancer are reviewed.

Antineoplastic Agents↗
PubMed2001

alpha(1B) adrenergic receptors in gonadotrophin-releasing hormone neurones: relation to Transport-P.

1. Peptidergic neurones accumulate amines via an unusual uptake process, designated Transport-P. [(3)H]-prazosin binds to alpha(1) adrenoceptors on these cells and is displaceable by unlabelled prazosin in concentrations up to 10(-7) M. However, at greater concentrations of prazosin, there is a paradoxical accumulation of [(3)H]-prazosin which we have attributed to Transport-P. Uptake of prazosin via Transport-P is detectable at 10(-10) M prazosin concentration, is linear up to 10(-7) M and at greater concentrations becomes non-linear. In contrast, in noradrenergic neurones, noradrenaline uptake is linear and saturates above 10(-7) M. In noradrenergic neurones and in non-neuronal cells, there is no uptake of prazosin in concentrations up to 10(-6) M, suggesting that Transport-P is a specialised function of peptidergic neurones. 2. Using a mouse peptidergic (gonadotrophin-releasing hormone, GnRH) neuronal cell line which possesses Transport-P, we have studied the interaction of alpha(1) adrenoceptors with Transport-P. Polymerase chain reactions and DNA sequencing of the products demonstrated that only the alpha(1B) sub-type of adrenoceptors is present in GnRH cells. 3. In COS cells transfected with alpha(1b) adrenoceptor cDNA and in DDT(1) MF-2 cells which express native alpha(1B) adrenoceptors, [(3)H]-prazosin was displaced by unlabelled prazosin in a normal equilibrium process, with no prazosin paradox in concentrations up to 10(-6) M. In DDT(1) MF-2 cells, [(3)H]-prazosin was displaced likewise by a series of alpha(1) adrenergic agonists, none of which increased the binding of [(3)H]-prazosin. Hence, the prazosin paradox is not due to some function of alpha(1) adrenoceptors, such as internalization of ligand-receptor complexes. 4. In neurones which possess Transport-P, transfection with alpha(1b) adrenoceptor cDNA resulted in over-expression of alpha(1B) adrenoceptors, but the prazosin paradox was unaltered. Thus, alpha(1) adrenoceptors and Transport-P mediate distinct functions in peptidergic neurones.

Adrenergic alpha-Antagonists↗
PubMed2001

A prospective study of the workload of a newly formed PEG advice team.

BACKGROUND: A multidisciplinary advice team may be the optimal way of providing the long-term nutritional and percutaneous endoscopic gastrostomy (PEG)-related care for patients dependent on PEG feeding but the workload involved is unknown. AIM: To study prospectively the workload of a proactive, multidisciplinary PEG advice team over a 2-year period. METHODS: Separate documentation from main case notes of each episode of the team's contact with PEG or potential PEG patients, including assessment, advice and therapy given, from the time of its establishment, for four consecutive 6-monthly periods. RESULTS: During the audit, 89 patients were referred to the team for consideration of PEG insertion and PEGs were placed in 74. Eighty-nine additional patients were referred for follow up having had a PEG placed elsewhere. During the four audit periods the rate of new PEG insertions increased by 53%, the rate of PEG replacements by 315%, and the number of patients under the team increased from 16 to 70, an increase of 337%. Numbers of inpatient and outpatient consultations, and visits to other institutions by members of the team increased commensurately. CONCLUSIONS: The rapidly increasing workload of the team suggests it is playing a valued role but there are significant resource implications.

Enteral Nutrition↗
PubMed2001

Lichen planus-like eruption following autologous bone marrow transplantation for chronic myeloid leukaemia.

A 47-year-old female treated with an autologous bone marrow transplant and cytotoxic chemotherapy developed a lichen planus-like eruption 12 months later. It involved the skin and oral mucosa, with the histological features of a lichenoid graft-versus-host reaction, including satellite cell necrosis. This eruption developed de novo. The eruption resolved with topical betamethasone valerate 0.1% cream despite the ongoing use of the immunomodulatory agent interferon-alpha2b. Such a reaction in an autologous setting has only been described once previously.

Administration, Cutaneous↗
PubMed2001

Executive summary: developing objectives, content, and competencies for the training of emergency medical technicians, emergency physicians, and emergency nurses to care for casualties resulting from nuclear, biological, or chemical incidents.

STUDY OBJECTIVE: The task force assessed the needs, demands, feasibility, and content of training for US civilian emergency medical responders (paramedics, nurses, and physicians) for nuclear/biological/chemical (NBC) terrorism. METHODS: A task force representing key professional organizations, stakeholders, and disciplines involved in emergency medical response conducted an iterated instructional-design analysis on the feasibility and content of such training with input from educational professionals. We then analyzed 6 previously developed training courses for their congruence with our recommendations. RESULTS: The task force produced descriptions of learning groups, content and learning objectives, and barriers and challenges to NBC education. Access to training and sustainment of learning (retention of knowledge) represent the significant barriers. The courses analyzed by the task force did not meet all objectives and challenges addressed. CONCLUSION: The task force recommends training programs and materials need to be developed to overcome the identified barriers and challenges to learning for these audiences. Furthermore, the task force recommends incorporating NBC training into standard training programs for emergency medical professionals.

Bioterrorism↗
PubMed2001

Variability of study cast assessment among orthodontists.

This study examined the accuracy and reliability with standardized definitions among 30 orthodontists in assessing different aspects of malocclusion from the study casts of 10 patients. Previous studies have indicated a lack of consistency among orthodontists in describing malocclusions. The diagnostic subcategories measured in this study included maxillary and mandibular crowding, overbite, overjet, and a modified molar, premolar, and canine Angle classification. Intraclass correlations indicated that the reliability of all parameters was good (intraclass correlation > 0.80), with overbite being the most reliable (0.98) and maxillary crowding and canine classification somewhat less reliable (0.89 and 0.87, respectively). Among Angle classifications, molar classification was the highest (0.95), followed by premolar (0.92) and canine (0.87). This study also measured the accuracy of the orthodontists' measurements compared with established true values (validity). T tests indicated that mandibular arch crowding and overbite were not statistically different from the true values. Overjet and molar classification were assessed very close to the true values. Although premolar and canine classifications were statistically different from the true values, they were within a one-eighth cusp of the true value (a clinically insignificant difference). The orthodontists consistently overestimated the amount of maxillary arch crowding or spacing. The results suggest that high reliability and reasonable accuracy can be expected for assessing study casts when using standardized definitions for the diagnostic subcategories.

Humans↗
PubMed2001

Computerised analysis of fetal heart rate recordings in maternal type I diabetes mellitus.

OBJECTIVE: 1. To study computerised cardiotocograph parameters from women with type I diabetes; 2. to examine the significance of observed differences from the expected normal values. DESIGN: Prospective observational study in the third trimester of pregnancy. SETTING: The medical antenatal clinic of a tertiary referral centre. POPULATION: Twenty-six women with type I diabetes mellitus with a singleton pregnancy. METHODS: Computerised cardiotocograph recordings were made weekly from 28 to 39 weeks. Derived parameters were compared with the published figures for uncomplicated singleton pregnancies. Details of maternal blood sugar, labour and delivery and neonatal outcome were recorded. Data were compared between groups according to the computerised analysis of the antenatal CTGs. RESULTS: One-hundred and thirty-one recordings were made with a median of five per patient (range 1-12). 1 1.3% showed absent episodes of high variation compared with the expected value of 0.8%, a difference of 9.5% (95% CI 4.5-15.3). Differences in short term variation, basal heart rate, frequency of fetal movements and heart rate accelerations were also found which changed with gestation. Overall these changes represented a more immature form of fetal heart rate than that which would be expected. No relationship between the changes and adverse fetal outcome could be identified. CONCLUSIONS: Significant differences exist in cardiotocographs in maternal type I diabetes compared with normal fetuses. The changes may represent a delay in fetal maturation. The analysis mode of the computer will register these as abnormal features, but there is no evidence that they are pathological. We would recommend that computerised analysis is not used to assess pregnancies complicated by maternal type I diabetes mellitus.

Cardiotocography↗
PubMed2001

Quantification of autolysis in Penicillium chrysogenum by semiautomated image analysis.

An image analysis method is described for the characterization of empty (autolyzed and inactive) regions within the mycelia of filamentous fungi. It extends a previous method that characterized only regions filled with cytoplasm or vacuoles (i.e., the active biomass). The method is semiautomatic, requiring some manual editing before automated measurements. When the method was used for samples from a batch fermentation of an industrial strain of Penicillium chrysogenum, the empty regions were observed to constitute up to 15% (by projected area) of the biomass during the growth phase. After nutrient exhaustion, however, the proportion of empty regions rose rapidly, eventually representing more than 50% of the biomass by the end of fermentation. The increase in the percentage of empty regions coincided with a decrease in biomass (as measured by dry cell weight) and a fall in penicillin titre. Further morphological analysis revealed that fragmentation of mycelia, particularly clumps, coincided with increases in the levels of empty regions. This new image analysis method gave additional information on hyphal differentiation and a measure of autolysis. It was also a useful indicator of the processes leading to autolysis.

Biomass↗
PubMed2001

Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer.

The phosphoinositide 3-kinase (PI3K) family of enzymes is recruited upon growth factor receptor activation and produces 3' phosphoinositide lipids. The lipid products of PI3K act as second messengers by binding to and activating diverse cellular target proteins. These events constitute the start of a complex signaling cascade, which ultimately results in the mediation of cellular activities such as proliferation, differentiation, chemotaxis, survival, trafficking, and glucose homeostasis. Therefore, PI3Ks play a central role in many cellular functions. The factors that determine which cellular function is mediated are complex and may be partly attributed to the diversity that exists at each level of the PI3K signaling cascade, such as the type of stimulus, the isoform of PI3K, or the nature of the second messenger lipids. Numerous studies have helped to elucidate some of the key factors that determine cell fate in the context of PI3K signaling. For example, the past two years has seen the publication of many transgenic and knockout mouse studies where either PI3K or its signaling components are deregulated. These models have helped to build a picture of the role of PI3K in physiology and indeed there have been a number of surprises. This review uses such models as a framework to build a profile of PI3K function within both the cell and the organism and focuses, in particular, on the role of PI3K in cell regulation, immunity, and development. The evidence for the role of deregulated PI3K signaling in diseases such as cancer and diabetes is reviewed.

Animals↗
PubMed2001

Transforming growth factor and neutralizing antibodies in subglottic stenosis.

Transforming growth factor beta 1 (TGF-beta1), which is implicated in the pathogenesis of fibrotic diseases such as interstitial fibrosis, may be associated with subglottic stenosis. To study this hypothesis, we measured TGF-beta1 expression sequentially in 28 rats after posterior cricoid injury, using both standard immunohistochemistry and reverse transcriptase-polymerase chain reaction. In addition, an osmotic pump infused TGF-beta1 in 18 rats, normal saline solution in 9 rats, and neutralizing antibodies in 9 rats. Specimens were stained for fibronectin and procollagen at 1, 7, and 21 days and underwent optical density analysis. In the injured airway, TGF-beta1 expression peaked at 1 day and returned to baseline by 21 days. The TGF-beta1 infusion led to an increase in the expression of extracellular matrix proteins relative to controls. In contrast, neutralizing antibodies led to a decrease in extracellular matrix protein expression. These findings suggest that TGF-beta1 may possibly play a role in the pathogenesis of subglottic stenosis.

Animals↗
PubMed2001

Developing mental health services in a primary care setting: Liverpool Primary Care Mental Health Project.

The Liverpool Primary Care Mental Health Project (PCMHP) was set up in 1996 to provide mental health services in a primary care setting. This study describes and evaluates an impact of a working model of a multi-disciplinary team in close association with five Liverpool practices. The data were collected on all patients who came in contact with the PCMHP team during a three-year period and compared with the data available for the five neighboring teams on waiting time between referral and assessment, clinical outcome, in-patient bed usage, GPs' and patients' satisfaction with services. The number of new referrals remained the same over three years. The usage of inpatient beds dropped by 38% in the same period. Waiting time between referral and assessment for new patients reduced from six weeks to one-two weeks. GP's were highly satisfied with access to CMH Nurses, overall communication with the team and overall delivery of the services. Over 80% of patients were satisfied with the services. Integrated mental health services with primary care proved to be effective and satisfactory to GPs as well as to patients. This approach did not increase the workload of the mental health team.

Community Mental Health Services↗
PubMed2001

A role for near infrared spectroscopy in the assessment of intermittent claudication.

BACKGROUND: Near infrared spectroscopy (NIRS) can be used to monitor muscle oxyhemoglobin (HbO2), deoxyhemoglobin (Hb) and cytochrome oxidase (CytOx) oxidation. We evaluated the changes in NIRS in patients with intermittent claudication (IC) pre- and postexercise. Microalbuminuria is an index of endothelial dysfunction. Therefore, we also assessed whether the urinary excretion of albumin increased postexercise in patients with IC. METHODS: Each participant (14 patients with IC and 10 controls) underwent a treadmill test; NIRS was continuously recorded. The urinary albumin:creatinine ratio (ACR) and ankle: brachial systolic pressure index (ABPI) were measured pre- and postexercise. RESULTS: The ABPI in the claudicants dropped significantly (p<0.001) postexercise. The pre-exercise ACR did not differ between claudicants and controls but postexercise, the ACR increased significantly (p<0.001) in the claudicants. There was a significant (p<0.001) difference in the degree of HbO2 deoxygenation between claudicants and controls; the rate of deoxygenation was significantly higher in claudicants than in controls (-8.4 vs. -3.4 mol/L.min, p=0.024). The period of recovery of HbO2 postexercise was also significantly slower in claudicants (192 vs 68 sec, p=0.003). There was a significant correlation between the increase in the ACR and time of recovery of HbO2 levels postexercise (r=0.86, p<0.001, n=24). A similar pattern was seen with CytOx. CONCLUSIONS: NIRS may provide a simple, non-invasive assessment of the severity of IC. Furthermore, because the ACR is a marker of endothelial damage, it is possible that NIRS changes also reflect endothelial integrity. These applications of NIRS technique should be assessed in a larger study.

Aged↗
PubMed2001

Dialysis and disaster: San Francisco's dialysis community remembers the Loma Prieta earthquake. Interview by Susan L. Robertson.

Unlike many regions of the United States that live with seasonal disasters such as hurricanes, snow storms, or flooding from torrential rains, the greatest threat of natural disaster in California still comes from earthquakes (TransPacific Renal Network, 1998). This was proven on October 17, 1989 when the Loma Prieta earthquake rolled through northern California. Measured as 7.1 on the Richter scale, the quake's epicenter was located about 10 miles northeast of Santa Cruz along a segment of the San Andreas Fault near the town of Loma Prieta in the Santa Cruz Mountains. The impact, however, was felt throughout most of the northern portion of the state.

Adaptation, Psychological↗
PubMed2000

p190-A, a human tumor suppressor gene, maps to the chromosomal region 19q13.3 that is reportedly deleted in some gliomas.

To date, two distinct genes coding for Ras GAP-binding phosphoproteins of 190kDa, p190-A and p190-B, have been cloned from mammalian cells. Rat p190-A of 1513 amino acids shares 50% sequence identity with human p190-B of 1499 amino acids. We have previously demonstrated, using rat p190-A cDNA, that full-length p190-A is a tumor suppressor, reversing v-Ha-Ras-induced malignancy of NIH 3T3 cells through both the N-terminal GTPase (residues 1-251) and the C-terminal Rho GAP (residues 1168-1441) domains. Here we report the cloning of the full-length human p190-A cDNA and its first exon covering more than 80% of this protein, as well as its chromosomal mapping. Human p190-A encodes a protein of 1514 amino acids, and shares overall 97% sequence identity with rat p190-A. Like the p190-B exon, the first exon of p190-A is extremely large (3.7 kb in length), encoding both the GTPase and middle domains (residues 1-1228), but not the remaining GAP domain, suggesting a high conservation of genomic structure between two p190 genes. Using a well characterized monochromosome somatic cell hybrid panel, fluorescent in situ hybridization (FISH) and other complementary approaches, we have mapped the p190-A gene between the markers D19S241E and STD (500 kb region) of human chromosome 19q13.3. Interestingly, this chromosomal region is known to be rearranged in a variety of human solid tumors including pancreatic carcinomas and gliomas. Moreover, at least 40% glioblastoma/astrocytoma cases with breakpoints in this region were previously reported to show loss of the chromosomal region encompassing p190-A, suggesting the possibility that loss or mutations of this gene might be in part responsible for the development of these tumors.

Amino Acid Sequence↗