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Biomedical subjects

C White

Publications and source records attributed to C White.

At least 19 recordsLinked to original sources

Renal transplantation in children 15 Kg or less: the British Columbia Children's Hospital experience.

PURPOSE: Small infants are the most challenging group of patients to undergo renal transplantation. PURPOSE: We reviewed the transplantation experience at our institution with children less than 15 kg at transplantation. MATERIALS AND METHODS: We retrospectively reviewed the records of 24 recipients in a 20-year period. Technical and allograft outcomes were compared to those in the North American Pediatric Renal Transplant Cooperative Study database. RESULTS: Since the inception of our program 24 recipients weighing 15 kg or less who were 6 years or younger have undergone transplantation. Seven grafts (29%) were from living donors. At transplantation mean age was 3.1 years (range 1.8 to 5.7) and mean weight was 13.4 kg (range 9.0 to 15.7). Average cold and warm ischemic times were 14.1 hours (range 3.4 to 37.2) and 23.1 minutes (range 21 to 41), respectively. Early complications were ureteral stricture requiring pyeloureterostomy in 1 case, reversible acute tubular necrosis in 2 and early arterial thrombosis salvaged by immediate thrombectomy in 1. Delayed complications were arterial stenosis requiring angioplasty in 2 cases, and 3 delayed deaths related to malignant hypertension in 2 and sepsis in 1. No grafts were lost due to thrombosis. Mean serum creatinine at years 1 to 3 and 5 were 48.5, 67.5, 79.1 and 84.4 mumol/l, respectively. Graft survival was 92% (22 patients after censoring 1 who died with a functioning graft) at 2 and 5 years. Overall results compare favorably to those in the North American Pediatric Renal Transplant Cooperative Study. CONCLUSIONS: With a multidisciplinary team effort successful results can be achieved in this challenging group of patients.

Body Weight↗

Disruption of TCBA1 associated with a de novo t(1;6)(q32.2;q22.3) presenting in a child with developmental delay and recurrent infections.

A boy with developmental delay, particularly of speech, a distinct face, antineutrophil cytoplasmic antibodies, and recurrent infections was found to have an apparently balanced de novo t(1;6)(q32.3;q22.3) translocation. Fluorescent in situ hybridisation with BAC/PAC clones and long range polymerase chain reaction products assessed in the human genome sequence localised the chromosome 1 breakpoint to a 9.8 kb segment within a hypothetical gene, LOC388735, and the chromosome 6 breakpoint to a 12.8 kb segment in intron 4 of the T-cell lymphoma breakpoint-associated target 1 (TCBA1) gene. Disruption and/or formation of TCBA1 fusion genes in T cell lymphoma and leukaemia cell lines suggests a role for this gene in tumorigenesis. The isolated mouse Tcba1 gene shows 91% amino acid sequence similarity with human TCBA1. It is expressed in fetal and adult brain and with lower levels in liver and testis. The human gene has been reported to be expressed exclusively in brain and thymus. Reduced TCBA1 expression in brain and thymus may explain at least some of the symptoms in this patient. It is concluded that germline alterations of the TCBA1 gene are associated with developmental delay and typical physical features.

Amino Acid Sequence↗

The financial cost of treating polytrauma: implications for tertiary referral centres in the United Kingdom.

This observational study was designed to evaluate the financial cost and resources needed to treat a polytrauma patient at a tertiary care centre in the United Kingdom. Sixty-nine patients, from outside the normal hospital catchment area, were referred to a University Hospital and treated for polytrauma (injury severity score>15). Fifty-one patients had head injuries in addition to other injuries. Fourteen patients died in hospital. Forty-seven patients spent 316 ITU days with a total of 832 hospital days. One hundred and ninety-six operating hours were used for their surgical treatment and only 13 patients required neurosurgical intervention. There were 580 radiological and 2967 blood investigations. The total cost of treating these patients was 974,874 pounds. The money received by the hospital from the respective primary care trusts was an average of 1500 pounds per patient for the full treatment including follow up. Thus, the fiscal deficit was 871,375 pounds. This study indicates that the financial accounting for complex cases is antiquated and inaccurate within the NHS. Tertiary referral centres receive only 10% of the appropriate money for treatment of polytrauma patients. The number of patients is relatively small, but their impact on the local services is very high.

Accounting↗

Early behavioral symptoms and course of Alzheimer's disease.

OBJECTIVE: To determine if behavioral symptoms detected at initial evaluation relate to cognitive or functional status or survival time in Alzheimer's disease (AD) patients. method: Review, in 100 cases of autopsy-proven AD, of the relationship of behavioral symptoms detected at initial evaluation to cognitive and global function measures and survival time. RESULTS: Behavioral symptoms had occurred in 74% of patients, including apathy (51%), hallucinations (25%), delusions (20%) and depressed mood (6.6%). Verbal aggression was common (36.8%); physical aggression less so (17%). The symptomatic group was more functionally (but not cognitively) impaired and had shorter median survival time (8 years: 95% CI: 7-9 years vs. 10 years: 95% CI: 8-12 years; P = 0.002) than the asymptomatic group. The presence of any one symptom at initial evaluation accounted for 6.1% of the variance in duration of illness. CONCLUSION: Presence of behavioral symptoms at initial evaluation of AD patients is associated with greater functional impairment and shorter survival time.

Aged↗

Person, place or time? The effect of individual circumstances, area and changes over time on mortality in men, 1995-2001.

This article uses the ONS Longitudinal Study to explore, for a cohort of adult males who were aged 26 or over in 1971, the relative influence on mortality in 1995-2001 of their place of residence and individual socioeconomic circumstances, at three censuses over a 20-year period. Factors examined in this analysis include social class, neighbourhoo deprivation (at ward level), unemployment, residence in the South East region in 1971 or 1981 housing tenure, and change in social class and housing tenure between 1971 and 1991. The variation in mortality attributable to the local authority district of residence in 1991 was also investigated.

Adult↗

Characterizing the "gold standard" image for laparoscopic surgery.

BACKGROUND: The term "gold standard" is often used to describe preferred display devices, frequently without substantiating evidence. A meaningful and objective measure of display quality for endoscopic surgery is required. METHODS: Typical colors from five tissue types were arranged in a striped pattern and displayed on four devices: a medical-grade cathode ray tube monitor, a liquid crystal display, a digital light projection display, and an obsolete cathode ray tube (CRT) monitor. The breadth and color contrast of the stripes were adjusted until the patterns became indiscernible to 12 subjects. The data provide a discernibility threshold. RESULTS: The liquid crystal display (LCD) monitor provided the best image. The medical grade and obsolete CRTs were second and third, respectively, and the projection display provided the most inferior image. CONCLUSIONS: A meaningful and relevant measurement of image display quality for laparoscopic surgery based on the discernibility threshold is provided. Of the devices tested, the LCD is the best in terms of image, although the CRT may be preferred at off-axis viewing angles. The projection system, however, offers compensatory ergonomic advantages.

Benchmarking↗

Electrophysiological and pharmacological characterization of K+-currents in muscle fibres isolated from the ventral sucker of Fasciola hepatica.

Fibres isolated from the ventral sucker of Fasciola hepatica were identified as muscle on the basis of their contractility, and their actin and myosin staining. They were voltage-clamped at a holding potential of -40 mV and depolarization-activated outward currents were characterized both electrophysiologically and pharmacologically. Activation was well fitted by a Boltzmann equation with a half-maximal potential of + 9 mV and a slope factor of -14.3 mV, and the kinetics of activation and deactivation were voltage-sensitive. Tail current analysis showed that the reversal potential was shifted by +46+/-3 mV when E(K) was increased by 52 mV, confirming that this was a K+-current with electrophysiological characteristics similar to delayed rectifier and Ca2+-activated K+-currents in other tissues. The peak current at + 60 mV was inhibited by 76+/-6% by tetrapentylammonium chloride (1 mM) and by 84+/-7% by Ba2+ (3 mM), but was completely resistant to block by tetraethylammonium (30 mM), 3,4-diaminopyridine (100 microM) and 4-aminopyridine (10 mM). Penitrem A, a blocker of high-conductance Ca2+-activated K+-channels reduced the current at +60 mV by 23+/-5%. When the effects of Ca2+-channel blocking agents were tested, the peak outward current at + 60 mV was reduced by 71+/-7% by verapamil (30 microM) and by 59+/-4% by nimodipine (30 microM). Superfusion with BAPTA-AM (50 microM), which is hydrolysed intracellularly to release the Ca2+-buffer BAPTA, also decreased the current by 44+/-16%. We conclude that voltage-and Ca2+-sensitive K+-channels are expressed in this tissue, but that their pharmacology differs considerably from equivalent channels in other phyla.

Actins↗

Image-guided robotic radiosurgery in a rat glioma model.

Despite the proven efficacy of radiosurgery for the treatment of brain tumors, limited histological information is available after treatment that might allow a better understanding of the relationship between radiation dose, the volume treated, and the response of the surrounding brain to the delivered radiation. The use of an animal model could provide the opportunity to clarify these relationships and answer several other key questions arising in clinical practice. We show here that treatment of small animals with radiosurgery is feasible using a robotically controlled linear accelerator, which offers the advantages of radiosurgery and preserves the potential for fractionated regimens without rigid immobilization. Specifically, we demonstrate the use of a robotically driven linear accelerator to provide radiosurgical treatment to a rat brain tumor model.

Animals↗

New pregnancies and loss of allergy.

BACKGROUND: Inverse associations between allergic disease and sibship have been consistently described and are frequently explained by purported lower rates of early infection among children from small families. Alternative explanations include the possibility that pregnancy itself determines maternal atopic status. OBJECTIVE: To test the hypothesis that atopy defined by skin prick test (SPT) declines with increasing numbers of pregnancies. METHODS: At enrollment to a birth cohort, mothers were skin prick tested to three common allergens. Seven years later these women underwent a second SPT and provided information on their reproductive histories. At both visits, information on allergic disease was also sought. RESULTS: Twenty five (15%) women who were initially atopic were no longer so at the second visit; loss of hayfever symptoms was reported by 33 (29%) women. Women with higher numbers of intervening pregnancies were more likely to 'lose' their atopy (P=0.05) and symptoms of hayfever (P=0.02); this was not true for asthma. The findings could not be accounted for by maternal age. CONCLUSION: Successive pregnancies may in part determine a mother's atopic state. Since maternal atopy is a risk factor for childhood atopic disease, this process may affect the atopic state of successive children. These findings suggest an alternative explanation for the sibship effect in allergic disease.

Adult↗

The introduction of solids in relation to asthma and eczema.

BACKGROUND: Despite scarce scientific evidence, current feeding guidelines recommend delayed introduction of solids for the prevention of asthma and allergy. AIMS: To explore whether late introduction of solids is protective against the development of asthma, eczema, and atopy. METHODS: A total of 642 children were recruited before birth and followed to the age of 5(1/2) years. Main outcome measures were: doctor's diagnosis of eczema ever, atopy according to skin prick test results against inhalant allergens, preschool wheezing, transient wheezing, all defined at age 5-5(1/2) years. Introduction of solids as main exposure measure was assessed retrospectively at age 1 year. RESULTS: There was no evidence for a protective effect of late introduction of solids for the development of preschool wheezing, transient wheezing, atopy, or eczema. On the contrary, there was a statistically significant increased risk of eczema in relation to late introduction of egg (aOR 1.6, 95% CI 1.1 to 2.4) and milk (aOR 1.7, 95% CI 1.1 to 2.5). Late introduction of egg was furthermore associated with a non-significant increased risk of preschool wheezing (aOR 1.5, 95% CI 0.92 to 2.4). There was no statistical evidence of feeding practices playing a different role in the development of asthma and eczema after stratification for parental asthma and atopy status. CONCLUSIONS: Results do not support the recommendations given by present feeding guidelines stating that a delayed introduction of solids is protective against the development of asthma and allergy.

Age Factors↗

Early allergen exposure, skin prick responses, and atopic wheeze at age 5 in English children: a cohort study.

BACKGROUND: For many years it has been assumed that the risk of childhood respiratory allergies is related to allergen exposures in early life. There are, however, few prospective data in support. We aimed to examine this relationship in a representative cohort of children born in Ashford, Kent (UK). METHODS: 625 children (94% of those eligible) were followed from birth to the age of 5.5 years at which time 552 underwent skin prick testing to extracts of house dust mite and cat fur allergens. Maternal reports of wheeze in the last year were collected by interview. These outcomes were related to individual domestic concentrations of Der p 1 and Fel d I allergens estimated from dust collection at the age of 8 weeks. RESULTS: 10% of children were sensitised to house dust mite or cat at age 5.5 years; 7% had atopic wheeze. No significant relationships between allergen exposure and either sensitisation or wheeze were found but, on examination, the exposure-response relationships for both allergens and for each outcome rose steeply at low levels of exposure and were attenuated at high levels of exposure. These patterns were modified by paternal atopy and by birth order. CONCLUSIONS: There are no linear relationships between early allergen exposure and the induction of childhood respiratory allergy; rather, the risks of IgE sensitisation and asthma rise at very low levels of exposure and are attenuated thereafter. These patterns are influenced by parental atopy and birth order. These findings suggest important gene-environment interactions in the development of atopy and asthma and imply that reductions in domestic allergen exposure alone are unlikely to have a major impact in decreasing the incidence of these diseases in childhood.

Allergens↗

Genitourinary medicine: an opportunity to reduce unwanted pregnancy.

We sought to investigate contraceptive use in women attending a genitourinary medicine (GUM) clinic, and to assess the need for a contraceptive service in this setting. Female attendees at Nottingham GUM clinic were invited to complete an anonymous questionnaire regarding past and present contraceptive use and whether a contraceptive service within GUM would be utilized. Four hundred and eighty-nine questionnaires were analysed. The majority had previously used condoms (89.8%) or the combined oral contraceptive pill (COCP) (74.6%), and 46.6% and 37.4%, respectively were currently using these methods. Contraception was frequently used for the dual aims of avoiding both pregnancy and infection (48.5%). General practitioners (GPs) and family planning clinics were most frequently cited as sources of regular contraceptive advice, 58.1% and 47.2% respectively, and emergency contraception 50.8% and 37.3%, respectively. If a contraceptive service was available within GUM 56.9% of respondents indicated they would use it.

Adolescent↗

Early prescriptions of antibiotics and the risk of allergic disease in adults: a cohort study.

BACKGROUND: It is frequently asserted that antibiotic prescriptions in childhood are associated with the development of allergic disease, especially asthma. A study was undertaken to establish the direction of this relationship. METHODS: A retrospective cohort study of 746 adults was performed in three general practices. Antibiotic prescriptions in the first 5 years of life, collected from contemporary medical records, were related to self-reports of asthma and hay fever and the results of skin prick testing with common aeroallergens. RESULTS: There was no relationship between early antibiotic prescription and atopy, either for all antibiotic use (OR 1.01) or for antibiotics prescribed at different ages. The significant associations between prescriptions at ages 4 and 5 and hay fever (OR 1.23 and 1.16, respectively) were explained by coexisting asthma. Relationships between antibiotic use and asthma (allergic or otherwise) were statistically significant and strengthened with increasing age of prescription, but were largely confined to antibiotics prescribed for lower respiratory symptoms. CONCLUSIONS: The reported associations between childhood antibiotic use and asthma are most plausibly explained by "reverse causation"--the tendency for prescriptions to be written for the early manifestations of pre-existing asthma.

Adult↗

Time profile of putrescine, cadaverine, indole and skatole in human saliva.

The concentrations of putrescine, cadaverine, indole and skatole were determined in the saliva of healthy human volunteers upon waking and at time points during the day. Putrescine was found to be the most abundant of the amines studied, followed by cadaverine then indole. Skatole could not be detected in the saliva samples at any time point. The amines were found in the highest concentrations immediately upon waking (mean concentrations (microg/ml): putrescine 33.0+/-19.0, cadaverine 17.6+/-16.7 and indole 0.4+/-0.4) with a rapid decrease following consumption of breakfast and brushing their teeth (mean concentrations (microg/ml): putrescine 7.0+/-6.4, cadaverine 3.1+/-4.7 and indole 0.04+/-0.09). Putrescine and cadaverine then increased in concentration during the day apart from a decrease post-lunch caused by increased salivary flow and mechanical cleaning due to mastication. An analytical method based on high performance liquid chromatography and fluorescence detection has been developed to quantify amines in human saliva. Sodium fluoride has been shown to be an effective inhibitor of amine formation in saliva at room temperature allowing samples to be collected and kept without requiring cold storage.

Adolescent↗

Non-invasive intravenous coronary angiography using electron beam tomography and multislice computed tomography.

BACKGROUND: Electron beam computed tomography (EBCT) and multislice computed tomography (MSCT) are both suitable for non-invasive identification of coronary stenoses. OBJECTIVE: To compare intravenous coronary EBCT angiography (EBCTA) and MSCT angiography (MSCTA) with regard to image quality and diagnostic accuracy. METHODS: EBCTA was done using an Imatron C-150 XP scanner in 101 patients following a standard protocol (slice thickness 3 mm, overlap 1 mm, acquisition time 100 ms, prospective ECG trigger). For MSCTA in a different set of 91 patients (using a Siemens Somatom Plus4VZ scanner), the whole volume of the heart was covered in a spiral technique by four simultaneous detector rows. Using retrospective ECG gating, the raw data were reconstructed in (mean (SD)) 215 (12) axial slices acquired in diastole (slice thickness 1.25 mm, overlap 0.5 mm, acquisition time 250 ms/slice). RESULTS: With EBCTA, 76% of predetermined coronary segments in a nine segment model could be assessed with diagnostic image quality, and with MSCTA, 82%. A low contrast to noise ratio with EBCTA, and the presence of motion artefacts with MSCTA were the main reasons for inadequate image quality. Using conventional angiography as the gold standard, 77% of stenoses of > 50% could be identified correctly with EBCTA and 82% with MSCTA. Significant stenoses were correctly ruled out in 93% of segments with EBCTA, and in 96% of segments with MSCTA. The average contrast to noise ratio was higher with MSCTA than with EBCTA (9.4 v 6.5; p < 0.001). CONCLUSIONS: EBCTA and MSCTA show similarly high levels of accuracy for determining and ruling out significant coronary artery stenoses. MSCTA is capable of providing good image quality in more coronary segments than EBCTA because of its better contrast to noise ratio and higher spatial resolution. Motion artefacts seen at heart rates of > 75 beats/min and a higher radiation exposure are the main limitations of MSCTA.

Coronary Angiography↗

Observation of the decay K- --> pi(-)mu(+)mu(-) and measurements of the branching ratios for K+/- --> pi(+/-)mu(+)mu(-).

Using data collected with the HyperCP (E871) spectrometer during the 1997 fixed-target run at Fermilab, we report the first observation of the decay K--->pi(-)mu(+)mu(-) and new measurements of the branching ratios for K+/--->pi(+/-)mu(+)mu(-). By combining the branching ratios for the decays K+-->pi(+)mu(+)mu(-) and K--->pi(-)mu(+)mu(-), we measure Gamma(K+/--->pi(+/-)mu(+)mu(-))/Gamma(K+/--->all) = (9.8+/-1.0+/-0.5)x10(-8). The CP asymmetry between the rates of the two decay modes is [Gamma(K+-->pi(+)mu(+)mu(-))-Gamma(K--->pi(-)mu(+)mu(-))]/[Gamma(K+-->pi(+)mu(+)mu(-))+Gamma(K--->pi(-)mu(+)mu(-))] = -0.02+/-0.11+/-0.04.

Journal Article↗

The quality of obstetrical clinical practice guidelines promulgated by a specialty society.

OBJECTIVE: To review the methodologic quality of all obstetrical clinical practice guidelines developed by the Society of Obstetricians and Gynaecologists of Canada (SOGC) from 1992 to August 2001. METHODS: Three reviewers independently assessed each of 37 guidelines according to a validated and reliable 37-item appraisal tool. A mean "global" score as well as three "dimension" scores were calculated for each guideline. The appraisal tool assessed each document according to three dimensions, which related to the rigour of its development (Dimension 1), its context and content (Dimension 2), and its application (Dimension 3). A repeated-measures analysis of variance was used to derive the interclass correlation coefficient. RESULTS: Mean global quality scores ranged from 8.1% to 54.0%. Only two guidelines were given a mean global score above 50% and 21 of the guidelines (56.8%) had mean global scores of less than 30%. Mean dimension scores were 19.9% for Dimension 1, relating to rigour of development, 47.3% for Dimension 2, relating to context and content, and 27.2% for Dimension 3, relating to application. The interclass correlation coefficient using a fixed-effects model was 0.72, reflecting reasonable agreement between the reviewers. CONCLUSION: Both the mean global scores and mean dimension-specific scores for the obstetrical clinical practice guidelines were lower than optimal. We were unable to reveal statistically significant improvements in guideline quality over time given the limited number of documents, but the scores for more recently drafted guidelines appear generally higher than earlier guidelines. This finding is consistent with new editorial policy adopted by the SOGC regarding guideline development. A broader review should be conducted by the SOGC on guidelines in development and under revision.

Canada↗

Imaging of changes in sarcoplasmic reticulum [Ca(2+)] using Oregon Green BAPTA 5N and confocal laser scanning microscopy.

We describe experiments in which the low affinity indicator Oregon Green BAPTA 5N was used to record the spatially resolved changes in [Ca(2+)] from intracellular stores in rat gastric myocytes. Cells were loaded with the membrane permeant form of the indicator and imaged using a confocal scanning laser microscope. In doubly stained cells the Oregon Green signal colocalized with BIODIPY 558/568 Brefeldin A, a label for the endo/sarcoplasmic reticulum (SR) and Golgi apparatus. Oregon Green BAPTA 5N was calibrated in gastric myocytes, giving an in situ K(d) of 90 microM. The resting free [Ca(2+)] within the SR averaged 65 microM. A reversible decrease in Oregon Green fluorescence was observed on bath application of Inositol triphosphate (IP(3)) (10 microM) to permeabilized cells. Similar changes were also observed when cyclopiazonic acid (5 microM) was applied to intact myocytes, again with recovery of store [Ca(2+)] following drug washout. Identical patterns of Ca(2+) depletion were seen when caffeine (1 microM) and carbachol (10 microM) were applied sequentially to the same cells, suggesting that activation of ryanodine and IP(3)-sensitive channels can result in the release of Ca(2+) from the same regions of the SR.

Animals↗