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Biomedical subjects

J Kingston

Publications and source records attributed to J Kingston.

At least 19 recordsLinked to original sources

The comparative energetics and growth strategies of sympatric Antarctic and subantarctic fur seal pups at Iles Crozet.

The period of maternal dependence is a time during which mammalian infants must optimise both their growth and the development of behavioural skills in order to successfully meet the demands of independent living. The rate and duration of maternal provisioning, post-weaning food availability and climatic conditions are all factors likely to influence the growth strategies of infants. While numerous studies have documented differences in growth strategies at high taxonomic levels, few have investigated those of closely related species inhabiting similar environments. The present study examined the body composition, metabolism and indices of physiological development in pups of Antarctic fur seals (Arctocephalus gazella) and subantarctic fur seals (Arctocephalus tropicalis), congeneric species with different weaning ages (4 months and 10 months, respectively), during their overlap in lactation at a sympatric breeding site in the Iles Crozet. Body lipid reserves in pre-moult pups were significantly greater (t28=2.73, P<0.01) in subantarctic (26%) than Antarctic fur seals (22%). Antarctic fur seal pups, however, had significantly higher (t26=3.82, P<0.001) in-air resting metabolic rates (RMR; 17.1 +/- 0.6 ml O2 kg(-1) min(-1)) than subantarctic fur seal pups (14.1 +/- 0.5 ml O2 kg(-1) min(-1)). While in-water standard metabolic rate (SMR; 22.9 +/- 2.5 ml O2 kg(-1) min(-1)) was greater than in-air RMR for Antarctic fur seal pups (t9=2.59, P<0.03), there were no significant differences between in-air RMR and in-water SMR for subantarctic fur seal pups (t12=0.82, P>0.4), although this is unlikely to reflect a greater ability for pre-moult pups of the latter species to thermoregulate in water. Pup daily energy expenditure was also significantly greater (t27=2.36, P<0.03) in Antarctic fur seals (638 +/- 33 kJ kg(-1) day(-1)) than in subantarctic fur seals (533 +/- 33 kJ kg(-1) day(-1)), which corroborates observations that pups of the former species spend considerably more time actively learning to swim and dive. Consistent with this observation is the finding that blood oxygen storage capacity was significantly greater (t9=2.81, P<0.03) in Antarctic (11.5%) than subantarctic fur seal (8.9%) pups. These results suggest that, compared with subantarctic fur seals, Antarctic fur seal pups adopt a strategy of faster lean growth and physiological development, coupled with greater amounts of metabolically expensive behavioural activity, in order to acquire the necessary foraging skills in time for their younger weaning age.

Animals↗

Diffusional behaviour of metals in a passive sampling system for monitoring aquatic pollution.

Passive sampling systems are an emerging technology for detecting pollutants in the aquatic environment. A passive sampling system has been developed based on diffusion through a porous surface to a receiving phase, where the analyte is removed by chelation at a solid phase. The diffusion process can be described by Fickian diffusion through the sampler. The sampler has a well-defined surface area, which permits calibration in terms of concentration. Passive sampling systems can be used to determine pollutant concentrations if the diffusion process can be described and understood within environmental limits. In natural water systems, diffusion coefficients for metal transport across the porous membrane will be affected by external conditions, including biofouling and variation in turbulence and temperature. Uptake rates for the analytes Cu, Cd and Pb have been determined for the complete passive sampling system. Two different cases have been investigated, a batch case, where the bulk concentration decreases with time, and a flow-through case, where the bulk concentration remains constant. Diffusion coefficients were determined for the two conditions and compared with the calculated value obtained for the Stokes-Einstein equation in pure water. Diffusion coefficients for metals were found to be lower than for diffusion in pure water, a difference attributed to the effect of the porous membrane. The effect of the hydraulic conditions on the metal diffusion was studied for both a conventional magnetic stirrer creating turbulence in the system and for a rotated sampler, the latter providing a well-defined boundary layer system. The boundary layer was found to be negligible compared with the diffusion limiting membrane in the presence of sufficient turbulence or if the rotation of the sampler was high.

Calibration↗

Effect of frusemide and hypertonic saline on electrolytes during post exercise anaesthesia.

This study evaluated the effects of pre-exercise frusemide administration and hypertonic saline (H) infusion during anaesthesia on arterial pH, blood gases and electrolytes in 6 Thoroughbred horses anaesthetised immediately post exercise. Horses received either frusemide (F) (0.5 mg/kg, i.v.) or a saline placebo (P) injection 4 h prior to treadmill exercise. Exercise consisted of a 3 min warm-up at 40% VO2max followed by exercise to fatigue. Detomidine (40 micrograms/kg, i.v.) was given within 5 min of stopping and followed 5 min later by zolazepam-tiletamine (1.25 mg/kg, i.v.) to induce anaesthesia. During maintenance of anaesthesia using isoflurane in O2, either isotonic saline solution (I) or 7.5% H (4 ml/kg, i.v.) was administered. Arterial blood was sampled at the following times: prior to (Pre-F/P) and 4 h after (Pre-ex) F or P administration, 1 min after fatigue (Fatigue), 5 min after induction of anaesthesia (Post-ind), and just prior to and 15, 30 and 60 min after beginning isoflurane (ISFL) anaesthesia. Arterial pH and blood gas tensions, pulmonary arterial blood temperature, plasma [lactate], total protein and plasma [Na+], [K+], and [Cl-] were measured. Data were analyzed using 2-way ANOVA for repeated measures (P < 0.05). There were significant differences over time for all variables except total protein. Plasma [Na+] increased at Fatigue compared to Pre-F/P or Pre-ex in all treatment groups. Plasma [Na+] and [Cl-] increased during ISFL anaesthesia compared to Pre-F/P and Pre-ex in horses given H. During ISFL anaesthesia, plasma [Cl-] decreased compared to Pre-F/P in Group F+I horses. We conclude that acid-base, blood gas, and electrolyte changes associated with F are unlikely to influence management of horses anaesthetised immediately following supramaximal exercise to fatigue. Hypertonic saline infusion may help restore plasma [Cl-] faster in hypochloraemic horses requiring anaesthesia immediately after strenuous exercise.

Acid-Base Equilibrium↗

Integrality of nasalization and F1. II. Basic sensitivity and phonetic labeling measure distinct sensory and decision-rule interactions.

In vowel perception, nasalization and height (the inverse of the first formant, F1) interact. This paper asks whether the interaction results from a sensory process, decision mechanism, or both. Two experiments used vowels varying in height, degree of nasalization, and three other stimulus parameters: the frequency region of F1, the location of the nasal pole/zero complex relative to F1, and whether a consonant following the vowel was oral or nasal. A fixed-classification experiment, designed to estimate basic sensitivity between stimuli, measured accuracy for discriminating stimuli differing in F1, in nasalization, and on both dimensions. A configuration derived by a multidimensional scaling analysis revealed a perceptual interaction that was stronger for stimuli in which the nasal pole/zero complex was below rather than above the oral pole, and that was present before both nasal and oral consonants. Phonetic identification experiments, designed to measure trading relations between the two dimensions, required listeners to identify height and nasalization in vowels varying in both. Judgments of nasalization depended on F1 as well as on nasalization, whereas judgments of height depended primarily on F1, and on nasalization more when the nasal complex was below than above the oral pole. This pattern was interpreted as a decision-rule interaction that is distinct from the interaction in basic sensitivity. Final consonant nasality had little effect in the classification experiment; in the identification experiment, nasal judgments were more likely when the following consonant was nasal.

Humans↗

A hominoid genus from the early Miocene of Uganda.

Fossils from a large-bodied hominoid from early Miocene sediments of Uganda, along with material recovered in the 1960s, show features of the shoulder and vertebral column that are significantly similar to those of living apes and humans. The large-bodied hominoid from Uganda dates to at least 20.6 million years ago and thus represents the oldest known hominoid sharing these derived characters with living apes and humans.

Animals↗

Multidisciplinary management of refractory orbital rhabdomyosarcoma.

PURPOSE: Combined chemotherapy and radiation therapy have improved the survival of children with primary orbital rhabdomyosarcoma, but recurrence or persistence of the local orbital tumor still occurs. There are no established guidelines for dealing with these uncommon patients, and the authors present a review of the combined method treatment and outcome of children with refractory primary orbital rhabdomyosarcoma. METHODS: From clinical databases, 67 children with orbital rhabdomyosarcoma were identified. Seven (10%) of the 67 children had tumors refractory to combined chemotherapy and radiation therapy and underwent exenteration or eye-sparing tumor excision. Their clinical course and outcome were reviewed retrospectively. RESULTS: No patient was lost to follow-up, which ranged from 3.2 to 11 years. Five (71%) of the seven children with refractory tumor are still alive at more than 3 years after surgery (3.2-11 years; mean, 6.9). In one of the two children who died, tumor extended beyond the operative margins at exenteration, and the other child died with regional metastasis within a month of exenteration. CONCLUSIONS: Although more than 90% of children with orbital rhabdomyosarcoma respond to combined therapy by pediatric oncologists and radiotherapists, local orbital (salvage) surgery by ophthalmologists may be of value in the minority of children with refractory tumors. All of the five surviving children appear to be disease free.

Adolescent↗

Integrality in the perception of tongue root position and voice quality in vowels.

In English and a large number of African and Southeast Asian languages, voice quality along a tense-lax dimension covaries with advancement of the tongue root in vowels: a laxer voice quality co-occurs with a more advanced tongue root. As laxing the voice increases energy in the first harmonic relative to higher ones and advancing the tongue root lowers F1, the acoustic consequences of these two articulations may integrate perceptually into a higher-level perceptual property, here called spectral "flatness." Two Garner-paradigm experiments evaluated this interaction across nearly the entire range of tense-lax voice qualities and a narrow range of F1 values. The acoustic consequences of laxness and advanced tongue root integrated into spectral flatness for tenser and laxer but not for intermediate voice qualities. Detection-theoretic models developed in earlier work proved highly successful in representing the perceptual interaction between these dimensions.

Humans↗

Integrality of nasalization and F1 in vowels in isolation and before oral and nasal consonants: a detection-theoretic application of the Garner paradigm.

In vowel height contrasts, tongue height and soft palate height covary. A series of vowel classification experiments examined the perceptual interactions between F1 and nasalization, the principal acoustic correlates of these articulations. Listeners classified imperfectly discriminable stimuli in the set of tasks that compose the Garner paradigm. Detection-theoretic models applied to the data led to the conclusion that vowels, whether in isolation, before oral consonants, or before nasal consonants, display integrality of F1 and nasalization. The contrary conclusion reached by Krakow et al. [J. Acoust. Soc. Am. 83, 1146-1158 (1988)] on the basis of data from a trading relations experiment reflect a limitation of that design for studying perceptual interaction. A second experiment used an array "rotated" in the stimulus space to determine whether F1 and nasalization are privileged, perceptually primary dimensions. A new method for predicting classification performance for the rotated array without the assumption of primacy showed that they are not.

Humans↗

Investigation and management of Clostridium difficile colonisation in a paediatric oncology unit.

Little is known about Clostridium difficile infection in children with cancer but a presumed outbreak has previously been described. The carriage rate before admission to hospital and morbidity is reported to be high, especially in younger children. The prevalence of C difficile infection on a paediatric oncology ward was monitored from June 1991 to May 1992. Twenty eight (13%) of 214 children were found to be infected. Though the temporal distribution suggested an outbreak, polyacrylamide gel electrophoresis identified several different types. Unlike previous reports, infection appeared to be possibly endogenous or possibly environmental in origin rather than due to cross infection; the morbidity was low and age was not a determinant for infection. The duration of hospital stay and the primary diagnosis were found to be determinants for infections, those with lymphoid malignancies being at the highest risk. The diagnostic category at greatest risk were those most intensively treated, with protracted neutropenia and prolonged antibiotic exposure. Early identification of cases and prompt institution of simple control measures will prevent cross infection. It is therefore important that diarrhoea is not accepted as a normal symptom of cancer chemotherapy and stool specimens are sent for full bacteriological and viral investigation.

Adolescent↗

Pilot study of high-dose vincristine, etoposide, carboplatin and melphalan with autologous bone marrow rescue in advanced neuroblastoma.

The efficacy and toxicity of a high-dose multiagent consolidation regimen, OMEC (vincristine, melphalan, etoposide and carboplatin), with autologous bone marrow rescue was studied in patients with poor-prognosis neuroblastoma, 20 patients were treated with OMEC, 18 after induction chemotherapy and 2 following relapse. All patients received, per m2, vincristine 4 mg, etoposide 1 g, carboplatin 1.0-1.75 g and melphalan 180 mg followed by bone marrow rescue. 4 patients (20%) died of treatment-related complications. Severe gastrointestinal toxicity occurred in all of these patients, and in 75% of patients overall. 1 of 5 patients with evaluable disease achieved complete remission. 13 patients (65%) have relapsed a median of 10 months (range 3-26) after receiving OMEC. Thus, OMEC was not more effective, yet more toxic, than high-dose melphalan given alone, and the use of similar multiagent regimens with overlapping toxicities in advanced neuroblastoma appears inadvisable.

Antineoplastic Combined Chemotherapy Protocols↗

'VEEP' in children with Hodgkin's disease--a regimen to decrease late sequelae.

In an attempt to decrease the risk of second malignancies and future infertility in children with Hodgkin's disease (HD) while retaining acceptable remission rates, an anthracycline based regimen containing no alkylating agent has been devised. VEEP contains vincristine, epirubicin, etoposide and prednisolone given at 3 weekly intervals. Forty-four patients, aged 2-15 years, have been treated: ten relapsed patients and 34 previously untreated with chemotherapy (including three relapsed stage I treated initially with radiotherapy). The median follow up for all patients is 25 months (range 6-52 months). The response rate in previously treated patients was 80% (95% CI 44-97%) and five remain alive in remission. The response rate in untreated patients was 88% (95% CI 72-97%) with 62% CR + CR(u) (uncertain/unconfirmed) (95% CI 44-77%). Of four patients who had a final response of CR(u) three have relapsed at 9, 16 and 38 months. Two of the children in CR have relapsed at 6 and 16 months. The relapse free rate at 3 years is 67% (95% CI 17-82%). In this pilot study the event free survival appears somewhat poorer than conventional combinations and further follow up is required to confirm the salvagability of relapsed patients.

Adolescent↗

Renal size and function after cure of Wilms' tumour.

Now that most patients with Wilms' tumour are cured, it is practicable to study the long-term morbidity of their treatment and use this information to reduce treatment sequelae in the future. In this study we evaluate the size and function of the remaining kidney in 53 survivors of Wilms' tumour with a mean off treatment follow-up of 13 years. There was evidence of renal dysfunction in 17 (32%), including ten (19%) with a low GFR (< 80 ml/min/1.73 m2SA), six (11%) with hypertension and five (9%) with increased urinary albumin excretion. Measurements of renal size showed 'good' renal compensatory hypertrophy in only 55% of patients. 'Good' refers to renal size of more than 2 s.d. above the mean renal length for children with two kidneys. There were no correlations between GFR, renal size, blood pressure, microalbuminuria or type of treatment. However, children less than 24 months at diagnosis and children receiving chemotherapy with radiation doses to remaining kidney of more than 1200 cGy had a worse renal prognosis. Patients whose Wilms' tumour is diagnosed in infancy should have careful long-term follow-up of renal function and size. Older patients may safely be followed up less often, unless their remaining kidney was received > 1200 cGy.

Blood Pressure↗

Protein components specifically associated with prespliceosome and spliceosome complexes.

We have carried out a systematic analysis of the protein composition of highly purified mammalian spliceosomes. We show that > 30 distinct proteins, including 20 previously unidentified components [designated spliceosome-associated proteins (SAPs)], are specifically associated with the spliceosome in a salt-resistant complex. In contrast to these spliceosome-specific proteins, we show that hnRNP proteins are not tightly associated with purified prespliceosome and spliceosome complexes. The splicing factor U2AF65, U1 snRNP-specific proteins, and several SAPs are present in the earliest prespliceosome complex (E). A set of 10 proteins is then added to the first ATP-dependent prespliceosome complex (A), and concomitantly, a significant decrease in the level of U2AF65 is observed. The fully assembled spliceosome is formed by the addition of 12 proteins in a reaction that requires ATP and both the 5' and 3' splice sites.

Adenosine Triphosphate↗

Diagnosis of acute promyelocytic leukaemia by RT-PCR: detection of PML-RARA and RARA-PML fusion transcripts.

Acute promyelocytic leukaemia (APL; AML M3) is identified by a unique t(15;17) translocation which fuses the PML gene to the retinoic acid receptor alpha gene (RARA). Reverse transcription coupled with the polymerase chain reaction (RT-PCR) has been used to develop a diagnostic test for APL based on the PML-RARA fusion message. Separate PCR assays were designed to amplify either PML-RARA (15q+ derived) or RARA-PML (17q- derived) chimaeric transcripts. PML-RARA transcripts were detected in every case from a series of 18 APL patients with cytogenetically confirmed t(15;17) translocations, whereas RARA-PML messages were detected in only 67% (12/18) of these patients. This suggests that it is the 15q+ derivative which mediates leukaemogenesis. Furthermore the PCR approach (or Southern analysis) may be used to identify in which of the alternative PML introns the breakpoint occurs; 52% of cases (15/29 patients) utilize a 5' PML intron and 48% the 3' intron (14/29 cases). Neither the choice of PML intron nor the expression of the 17q- derivative could be correlated with the microgranular variant of APL (M3V), overall survival rate, age, sex or presence of coagulopathy. Finally, the fusion message is undetectable in five remission samples. This indicates a possible use for RT-PCR in monitoring remission patients for evidence of relapse.

Adolescent↗

Repeated ECS enhances dopamine D-1 but not D-2 agonist-induced behavioural responses in rats.

The present study examined the effect of acute and repeated administration of electroconvulsive shock (ECS) on behaviours induced by various dopamine agonists in rats. Components of behavioural arousal induced by the dopamine D-1 agonist SKF 38393, the dopamine D-2 agonist RU 24213 and the mixed D-1/D-2 agonist apomorphine were assessed using a behavioural check-list method. Also, the overall behavioural syndrome produced by these drugs was measured using rating scales. Rats receiving repeated (5 times over 10 days) but not a single ECS showed enhanced grooming and sniffing in response to SKF 38393 (7.5 mg/kg) when compared to controls. Repetitive sniffing induced by apomorphine (0.5 mg/kg) was also enhanced by repeated ECS. Neither repeated nor a single ECS significantly changed behaviours induced by RU 24213 (0.75 mg/kg), although a downward trend was evident. The behaviour rating scale measurements also demonstrated that repeated administration to ECS increased behavioural responsiveness to SKF 38393 and apomorphine but not RU 24213. These results suggest that the increase of dopamine-mediated behaviour in rats seen after chronic ECS relates to an increase in central dopamine D-1 receptor function.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Identification and characterization of IgA and Vicia villosa-binding T cell subsets in rheumatoid arthritis.

Autoimmunity may be due to augmentation of immune responses by human CD8 cells which bind the lectin Vicia villosa (VV). We have investigated T cells in rheumatoid arthritis (RA) by double immunofluorescence flow cytometry, in order to assess VV-binding CD8 and CD4 cells from the peripheral blood and synovial fluid. A significant increase in CD8+VV adherent (P less than 0.0001) and CD4+VV adherent cells (P less than 0.001) was found in synovial fluid, as compared with peripheral blood from patients with RA. A significant increase in VV-binding CD8+ or CD4+ cells was, however, not found in the blood of patients with RA, as compared with controls. We suggest that the lack of VV-binding T cells separated from blood, in contrast to those from synovial fluid, may be due to an inhibiting agent expressing N-acetyl D-galactosamine. Indeed, IgA1 is rich in N-acetyl D-galactosamine, it inhibits VV binding to T cells and is significantly bound to CD8 cells (P less than 0.001). The IgA1 was then characterized and in about half the patients J chains and secretory component was found, suggesting that the IgA1 is of the polymeric and secretory variety. IgA bound to the T cells engaged the Fc alpha receptors and a significant decrease in the Fc alpha receptors was found in CD8 cells (P less than 0.0001) and CD4 cells (P less than 0.01). Desorption studies were then carried out on CD8 and CD4 cells which showed that a loss of cell-bound IgA1 was associated with an increase in VV binding. Conversely, adsorption of IgA to T cells was associated with a loss in VV binding. The results suggest that the failure of VV binding to CD8+ and CD4+ cells from peripheral blood of patients with RA can be ascribed to cell-bound IgA1. Cytophilic IgA1 may inhibit the function of CD8+VV binding cells, thereby preventing augmentation of the systemic immune response, consistent with the lack of extra-articular disease in these patients with RA.

Adult↗

Reducing the incidence of infection after caesarean section: implications of prophylaxis with antibiotics for hospital resources.

OBJECTIVES: To estimate the cost effectiveness of giving prophylactic antibiotics routinely to reduce the incidence of wound infection after caesarean section. DESIGN: Estimation of cost effectiveness was based, firstly, on a retrospective overview of 58 controlled trials and, secondly, on evidence about costs derived from data and observations of practice. SETTING: Trials included in the overview were from obstetric units in several different countries, including the United Kingdom. The costing study was based on data referring to the John Radcliffe Maternity Hospital, Oxford. SUBJECTS: A total of 7777 women were included in the 58 controlled trials comparing the effects of giving routine prophylactic antibiotics at caesarean section with either treatment with a placebo or no treatment. Cost estimates were based on data on 486 women who had caesarean sections between January and September 1987. MAIN OUTCOME MEASURE: Cost effectiveness of prophylaxis with antibiotics. RESULTS: The odds of wound infection are likely to be reduced by between about 50 and 70% by giving antibiotics routinely at caesarean section. Forty one (8.4%) women who had caesarean section were coded by the Oxford obstetric data system as having developed wound infection. The additional average cost of hospital postnatal care for women with wound infection (compared with women who had had caesarean section and no wound infection) was estimated to be 716 pounds; introducing routine prophylaxis with antibiotics would reduce average costs of postnatal care by between 1300 pounds and 3900/100 pounds caesarean sections (at 1988 prices), depending on the cost of the antibiotic used and its effectiveness. CONCLUSIONS: The results suggest that giving antibiotics routinely at caesarean section will not only reduce rates of infection after caesarean section but also reduce costs.

Ampicillin↗