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Biomedical subjects

C A Reid

Publications and source records attributed to C A Reid.

At least 19 recordsLinked to original sources

Oro-nasal fistula development and velopharyngeal insufficiency following primary cleft palate surgery--an audit of 148 children born between 1985 and 1997.

We present an audit of primary cleft palate surgery in our unit including rates of two important post-operative complications. Multidisciplinary audit clinics ran from March 1998 to April 2002 to follow up all local patients with a cleft lip or palate who had undergone primary palatal surgery in our unit. One hundred and forty eight patients were studied. Patient ages at follow-up ranged from 3 years and 10 months to 17 years and 4 months. Two surgeons performed the primary surgery. One hundred and twenty eight Wardill-Kilner and 20 Von Langenbeck repairs were performed. We found a 4.7% rate of oro-nasal fistula development requiring surgical closure, and a 26.4% rate of velopharyngeal insufficiency (VPI) requiring subsequent pharyngoplasty. We noted that the type of cleft involved affected the rate of VPI, 16% of patients with unilateral cleft lip and palate versus 29.2% of patients with a solitary cleft palate requiring secondary surgery. Outcome of surgery was determined by a 'Cleft Audit Protocol for Speech' (CAPS) speech therapy assessment at follow-up clinics. Only 14.9% of all patients assessed demonstrated any degree of hypernasality. Our results compare favourably with other recent studies including the Clinical Standards Advisory Group (CSAG) report into treatment of children with cleft lip and palate.

Adolescent↗

Development of low-affinity, membrane-targeted Ca2+ sensors suitable for measuring presynaptic Ca2+.

1. Our aim is to measure near-membrane Ca(2+) flux within the presynaptic terminals of central neurons by modifying new genetically encoded Ca(2+) sensors to develop tools capable of measuring localized Ca(2+) signals. 2. We used standard recombinant DNA technologies to generate the DNA coding for a fusion construct of a modified fluorescent 'pericam' Ca(2+) biosensor with a presynaptic P2X7 receptor (P2X7R). The Ca(2+) sensitivity of the biosensor was modified by rational site-directed mutagenesis of the calmodulin portion of the pericam. 3. Biosensor-receptor fusions were transfected into expression systems for evaluation. Expression studies in HEK-293 cells showed that biosensor-receptor fusion construct-delivered protein was localized exclusively to the plasma membrane, confirming that fusion did not affect the ability of the receptor to undergo normal protein synthesis and trafficking. 4. The Ca(2+)-dependent fluorescence of the pericam portion of the fusion protein was also retained. Site-direct mutagenesis within the calmodulin moiety of the pericam significantly reduced the Ca(2+) affinity of the complex. The dynamic range of the sensor following this modification is better matched to the higher Ca(2+) levels expected within presynaptic Ca(2+) microdomains.

Animals↗

Antiretroviral therapy in sub-Saharan Africa: adherence lessons from tuberculosis and leprosy.

Declining drug costs and increases in international donor interest are leading to greater availability of antiretroviral treatment programmes for persons living with the human immunodeficiency virus in parts of sub-Saharan Africa. Ensuring adequate adherence to antiretroviral drug therapy is one of the principal challenges facing successful implementation in Africa, where 70% of the world's infected persons live. Tuberculosis and leprosy are two diseases of global importance whose control programmes can provide important lessons for developing antiretroviral drug adherence strategies. This paper examines various approaches used in tuberculosis and leprosy control which could help enhance adherence to antiretroviral therapy in resource-limited settings.

Africa South of the Sahara↗

Conditions in lairages at abattoirs for ruminants in southwest England and in vitro survival of Escherichia coli O157, Salmonella Kedougou, and Campylobacter jejuni on lairage-related substrates.

Information on lairages (regarding design, construction materials, and use of bedding and cleaning regimes) was collected for 21 commercial cattle and/or sheep abattoirs in southwest England. Overall, roughened or grooved concrete was the most common lairage flooring material. Straw bedding was used in the majority of lairages and was changed between animal batches, daily, weekly, and monthly in roughly 5, 60, 15, and 10%, respectively, of the surveyed lairages. Lairages were commonly washed with cold water with no detergents and/or disinfectants, and only about half the lairages were washed daily. Also, a three-pathogen cocktail inoculum comprising Escherichia coli O157 (NCTC 12900), Salmonella Kedougou (VLA S488/01), and Campylobacter jejuni (VLA C4) (at 8, 8, and 7 log CFU/ml or 8, 8, and 7 log CFU/g, respectively) was suspended in either broth (for nonfecal contamination) or bovine feces (for fecal contamination). Samples of the four most common substrates present in lairages (concrete, straw, metal, and hide) were contaminated in vitro with either fecal or nonfecal inocula and subsequently held in the laboratory at 10 or 25 degrees C for 1 week. Bacterial counts for these samples were monitored daily and used to assess the number of days required for a 90% reduction of each pathogen population. In most cases, pathogens survived for >1 week, with survival rates being higher for straw or hide than for concrete or metal and higher for fecal contamination than for nonfecal contamination. Overall, if survival rates for the three pathogens under practical lairage conditions were similar to the in vitro survival rates found in this study, contamination of lairages with pathogens could be carried over from one batch of animals to another and/or from one day to the next.

Abattoirs↗

Potential for the spread of Escherichia coli O157, Salmonella, and Campylobacter in the lairage environment at abattoirs.

Prevalences of Escherichia coli O157, Salmonella spp., and Campylobacter spp. were examined in 270 swabs taken from selected sites along the unloading-to-slaughter routes of animal movement in lairages of six commercial abattoirs, three for cattle and three for sheep. The overall prevalences of the pathogens in the respective lairage environments were compared with those for 270 swabs from the pelts of 90 lambs examined in the present study and 270 swabs from the hides of 90 cattle examined in a previous study that were slaughtered at the same abattoirs on the same days. Also, the results obtained were analyzed with the aim of identifying critical points at which animal-environment-animal transfer of the pathogens in lairages occurs. The results showed that (i) the overall prevalences of E. coli O157, Salmonella spp., and Campylobacter spp. were 27.2, 6.1, and 1.1%, respectively, in cattle lairages and 2.2, 1.1, and 5.6%, respectively, in sheep lairages; (ii) the overall prevalences of the three pathogens on cow hides (28.8, 17.7, and 0%, respectively) and sheep pelts (5.5, 7.8, and 0%, respectively) were higher than the overall prevalences in the respective lairage environments; (iii) the most frequently contaminated sites in cattle lairages were holding pen floors (50% of swabs positive for one or more pathogens), entrance gates of stun boxes (27.8% of swabs positive for one or more pathogens), and stun box floors (22.2% of swabs positive for one or more pathogens); (iv) the most frequently contaminated sites in sheep lairages were unloading ramp floors, holding pen floors, and water troughs (33.3, 22.2, and 22.2%, respectively); and (v) overall, cattle lairages and cow hides were more frequently contaminated with the pathogens than were lamb lairages and lamb pelts. Further research is needed to develop strategies for the incorporation of pathogen control in lairages into integrated microbial meat safety systems.

Abattoirs↗

Pulsed-field gel electrophoresis characterization of Shiga toxin-producing Escherichia coli O157 from hides of cattle at slaughter.

Contamination of the brisket areas of the hides of healthy adult cattle with Shiga toxin-producing Escherichia coli O157 at slaughter in England was studied. In total, 73 cattle consignments comprising 584 animals delivered to one abattoir over 3 days during 1 week in July 2001 were studied: 26 cattle consignments arriving on Monday, 32 consignments arriving on Wednesday, and 15 consignments arriving on Friday. Consignment sizes ranged from 1 to 23 animals, with a mean consignment size of 8. The hide of the first animal to be slaughtered in each consignment was sampled by using a sponge swab moistened with 0.85% saline to rub an unmeasured brisket (ventral) area (ca. 30 by 30 cm). The process of isolating E. coli O157 from the swabs consisted of enrichment, screening with immunoprecipitation assay kits, and immunomagnetic separation. E. coli O157 was found on 24 of 73 (32.9%) cattle hides examined, and 21 of these 24 isolates produced Shiga toxins. The 24 E. coli O157 isolates produced six different pulsed-field gel electrophoresis profiles, and 18 (75%) of the isolates were of one prevalent clone. The high prevalence of one E. coli O157 clone on the hides of cattle at slaughter could be due to a high prevalence of that clone on the 18 farms involved (not investigated in the current study), in the postfarm transport or lairage environments, or both. Since the lairage environment, but not the farm of origin or the postfarm transport vehicle, was a factor common to all 18 cattle consignments, it could have played an important role in spreading the prevalent E. coli O157 clone to the cattle hides. Lairage pen floors and the stunning box floor were identified as the most probable sites along the unloading-to-slaughter route at which the brisket areas of cattle hides could become contaminated.

Abattoirs↗

Postsynaptic calcium transients evoked by activation of individual hippocampal mossy fiber synapses.

Control of Ca(2+) within dendritic spines is critical for excitatory synaptic function and plasticity, but little is known about Ca(2+) dynamics at thorny excrescences, the complex spines on hippocampal CA3 pyramidal cells contacted by mossy fiber terminals of dentate granule cell axons. We have monitored subthreshold stimulus-dependent postsynaptic Ca(2+) transients in optically and ultrastructurally characterized complex spines and find that such spines can act as discrete units of Ca(2+) response. In contrast to the more common "simple" spines, synaptically evoked Ca(2+) transients at complex spines have only a small NMDA receptor-dependent component and do not involve release of calcium from internal stores. Instead, they result mainly from AMPA receptor-gated Ca(2+) influx through voltage-activated calcium channels on the spine; these channels provide graded amplification of the response of thorny excrescences to individual mossy fiber synaptic events.

Action Potentials↗

Calcium stores in hippocampal synaptic boutons mediate short-term plasticity, store-operated Ca2+ entry, and spontaneous transmitter release.

Evoked transmitter release depends upon calcium influx into synaptic boutons, but mechanisms regulating bouton calcium levels and spontaneous transmitter release are obscure. To understand these processes better, we monitored calcium transients in axons and presynaptic terminals of pyramidal neurons in hippocampal slice cultures. Action potentials reliably evoke calcium transients in axons and boutons. Calcium-induced calcium release (CICR) from internal stores contributes to the transients in boutons and to paired-pulse facilitation of EPSPs. Store depletion activates store-operated calcium channels, influencing the frequency of spontaneous transmitter release. Boutons display spontaneous Ca2+ transients; blocking CICR reduces the frequency of these transients and of spontaneous miniature synaptic events. Thus, spontaneous transmitter release is largely calcium mediated, driven by Ca2+ release from internal stores. Bouton store release is important for short-term synaptic plasticity and may also contribute to long-term plasticity.

Action Potentials↗

The effects of yoghurt containing a novel fat emulsion on energy and macronutrient intakes in non-overweight, overweight and obese subjects.

OBJECTIVE: To investigate the effects of a yoghurt containing a novel fat emulsion on energy and macronutrient intakes up to 8 h post-consumption in non-overweight, overweight and obese subjects, and to assess energy compensation over the following 24 h. DESIGN: A double-blind, placebo-controlled, within-subject crossover design was used. Twenty (10 female, 10 male) non-overweight (body mass index (BMI) 20-24.9 kg/m(2)), 20 (10 female, 10 male) overweight (BMI 25-29.9 kg/m(2)) and 20 (13 female, 7 male) obese (BMI>30 kg/m(2)) subjects participated in the study. Subjects were given in random order, 7 days apart, either a 200 g portion of a test (5 g of a novel fat emulsion+1 g milk fat) or control (6 g milk fat) yoghurt at 09:00 h. At 4 and 8 h post-consumption subjects were given ad libitum access to a range of foods. Amounts of food consumed were determined by pre and post-covert weighing of individual serving dishes. Over the following 24 h subjects weighed and recorded all food intakes. RESULTS: Mean energy intakes were significantly lower after the test yoghurt compared with the control yoghurt in non-overweight (3.79 vs 5.43 MJ; P<0.01) and overweight (4.43 vs 6.12 MJ; P<0.001) subjects 4 h post-consumption and in non-overweight (3.82 vs 5.38 MJ; P<0.001), overweight (3.94 vs 5.80 MJ; P<0.001) and obese (4.91 vs 6.26 MJ; P<0.01) subjects 8 h post-consumption. The corresponding macronutrient intakes were also significantly reduced in non-overweight and overweight subjects (P<0.01) at 4 h post-consumption and in all subjects 8 h post-consumption (P<0.01). In the total group, energy intakes over the following 24 h were also significantly reduced (6.35 vs 7.70 MJ; P<0.01) after the test yoghurt relative to the control yoghurt. CONCLUSIONS: These results suggest that the effects of this novel fat emulsion are maintained at least up to 8 h and are evident in non-overweight, overweight and obese subjects.

Adult↗

Short-term effects of yoghurt containing a novel fat emulsion on energy and macronutrient intakes in non-obese subjects.

BACKGROUND: The satiating properties of fat remain poorly understood, particularly with reference to its physicochemical characteristics. OBJECTIVE: To investigate the short-term effects of consumption of yoghurt containing either a novel fat emulsion or normal milk fat, on the energy and macronutrient intakes of non-obese subjects. DESIGN: Two double-blind, placebo-controlled, within-subject crossover studies were conducted three months apart. Twenty-nine (15 F, 14 M) and thirty (16 F, 14 M) subjects participated in Study 1 and Study 2 respectively. In each study, subjects were given in random order, 7 days apart, either a 200g portion of a test (5g of a novel fat emulsion + 1 g milk fat) or control (6g milk fat) yoghurt at 1300 h. At 4h post-consumption subjects were given ad libitum access to a range of foods. Amounts of food consumed by individuals were determined by pre- and post-covert weighing of individual serving dishes. RESULTS: Mean energy intakes were significantly lower after the test yoghurt compared with the control yoghurt in Study 1 (6.4 vs 7.6 MJ; P< 0.001), Study 2 (6.9 vs 7.9 MJ; P<0.001), and for both studies combined (6.7 vs 7.7 MJ; P<0.001). The corresponding fat intakes in Study 1, Study 2 and in the combined studies were all significantly reduced (P< 0.001). Protein and carbohydrate intakes were also significantly reduced in Study 1 (P< 0.05), Study 2 (P< 0.01), and for the combined studies (P< 0.001). CONCLUSIONS: These results suggest that the physicochemical characteristics of small amounts of dietary fat affect short-term satiety.

Adult↗

Altering the temporal distribution of energy intake with isoenergetically dense foods given as snacks does not affect total daily energy intake in normal-weight men.

The objectives of the present study were to examine the effects of (1) ingesting mandatory snacks v. no snacks and (2) the composition of isoenergetically-dense snacks high in protein, fat or carbohydrate, on food intake and energy intake (EI) in eight men with ad libitum access to a diet of fixed composition. Subjects were each studied four times in a 9 d protocol per treatment. On days 1-2, subjects were given a medium-fat maintenance diet estimated at 1.6 x resting metabolic rate (RMR). On days 3-9, subjects consumed three mandatory isoenergetic, isoenergetically dense (380 kJ/100 g) snacks at fixed time intervals (11.30, 15.30 and 19.30 hours). Total snack intake comprised 30% of the subjects' estimated daily energy requirements. The treatments were high protein (HP), high carbohydrate (HC), high fat (HF) and no snack (NS). The order was randomized across subjects in a counterbalanced, Latin-square design. During the remainder of the day, subjects had ad libitum (meal size and frequency) access to a covertly manipulated medium-fat diet of fixed composition (fat:carbohydrate:protein, 40:47:13 by energy), energy density 550 kJ/100 g. All foods eaten were investigator-weighed before ingestion and left-overs were weighed after ingestion. Subjective hunger and satiety feelings were tracked hourly during waking hours using visual analogue scales. Ad libitum EI amounted to 13.9 MJ/d on the NS treatment compared with 11.7, 11.7 and 12.2 MJ/d on the HP, HC and HF diets respectively (F(3,21) 5.35; P = 0.007, SED 0.66). Total EI values were not significantly different at 14.6, 14.5, 15.0 and 14.2 MJ/d respectively. Snack composition did not differentially affect total daily food intake or EI. Average daily hunger was unaffected by the composition of the snacks. Only at 12.00 hours did subjects feel significantly more hungry during the NS condition, relative to the other dietary treatments (F(3,18) 4.42; P = 0.017). Body weight was unaffected by dietary treatment. In conclusion, snacking per se led to compensatory adjustments in feeding behaviour in lean men. Snack composition (with energy density controlled) did not affect the amount eaten of a diet of fixed composition. Results may differ in real life where subjects can alter both composition and amount of food they eat and energy density is not controlled.

Adult↗

Postsynaptic expression of long-term potentiation in the rat dentate gyrus demonstrated by variance-mean analysis.

1. Long-term potentiation (LTP) of synaptic transmission is the putative mechanism underlying learning and memory. Despite intensive study, it remains controversial whether LTP is expressed at a pre- or postsynaptic locus. A new approach was used to investigate this question at excitatory synapses from the medial perforant path (MPP) onto granule cells in the hippocampal dentate gyrus. The variance of the evoked synaptic amplitude was plotted against mean synaptic amplitude at several different Cd2+ concentrations. The slope of the variance-mean plot estimates the average amplitude of the response following the release of a single vesicle of transmitter (Qav). A presynaptic modulation should not affect Qav, but a postsynaptic modulation should alter it. 2. The variance-mean technique was tested by applying the analysis before and after three different synaptic modulations: (i) a reduction in Qav by the addition of the competitive antagonist CNQX; (ii) a reduction in the average probability of transmitter release (Pav) by the addition of baclofen; and (iii) an increase in the number of active synaptic terminals (N) by increasing the stimulus strength. CNQX reduced the average synaptic amplitude and Qav to the same extent, consistent with a postsynaptic action. In contrast, neither a change in N nor Pav altered Qav. This confirms that the variance-mean technique can distinguish between a pre- and a postsynaptic site of modulation. 3. Induction of LTP increased EPSC amplitude by 50 +/- 0.4 % (n = 5) and, in the same cells, increased Qav by 47 +/- 0.6 %. There was no significant difference between the increase in EPSC amplitude and the increase in Qav. Thus, LTP of the MPP input to dentate granule cells can be explained by an increase in the postsynaptic response to transmitter.

Algorithms↗

Prostheses for persons with lower-limb amputations: an extra joint increases range of motion.

This report describes two cases in which the addition of an extra joint enhanced range of motion and improved function in persons with unilateral lower-limb amputation. Both individuals had significant disability in the workplace and at home before this modification. In the first case, an individual with a hemipelvectomy had inadequate hip-joint flexion for maneuvering during photo shoots. In the second case, the individual's transfemoral prosthesis provided insufficient knee flexion for kneeling and working in tight spaces. In each case, a manual-locking, single-axis knee joint was added adjacent to the joint with the limited range of motion. In both cases, the addition of the second joint provided the increased flexibility needed. The first person's hip-flexion range improved from 125 degrees to 190 degrees, and the second person's knee-flexion range improved from 140 degrees to 170 degrees. In repeated follow-up, both patients remained highly satisfied with the intervention. The addition of an extra joint is an option that should be considered when inadequate range interferes with function.

Activities of Daily Living↗

Cross infection on a combined paediatric plastic surgery and burns unit: a clinical and microbiological audit.

To try and determine any presence of cross-infection between patients, prospective screening of 226 consecutive admissions on our burns unit was performed by taking nose, throat and wound swabs. Infected wounds were also swabbed and a correlation was sought between the organisms cultured on screening swabs and those responsible for infection. We did not find any evidence of cross- infection occurring between the burns patients and the other categories of patients on the ward. Screening swabs were useful in detecting carriers, who were found to be more of a risk to themselves than to other patients on the unit.

Bacterial Infections↗

Description and evaluation of an experimental model to examine changes in selection between high-protein, high-carbohydrate and high-fat foods in humans.

OBJECTIVE: To develop and test an experimental model designed to detect changes in selection between foods individually enriched in protein, carbohydrate and fat in human subjects. DESIGN: Randomised counterbalanced (Latin square) design. SETTING: The metabolic suite at the Rowett Research Institute's Human Nutrition Unit. SUBJECTS: 16 normal-weight men (mean BMI = 23.5). INTERVENTIONS: Subjects were each studied 4 times in a 2-day protocol. On day 1 subjects received a fixed maintenance diet; on day 2 they received a mandatory intake as breakfast (08.30) plus a drink at 10.30. This comprised 80% of resting energy requirements as high-protein (HP), high-carbohydrate (HC) or high-fat (HF) foods (60% of energy in each case) or an equal mixture (M) of macronutrients, 33% by energy. All mandatory treatments contained the same energy content and density. From 12.30 onwards, subjects had ad libitum access to a counter-balanced selection of three groups of familiar foods (10 HP, 10 HC and 10 HF; 30 foods in total). Most energy in each food was derived from one macronutrient (approximately 60%), the remainder being equally split between the other two macronutrients. RESULTS: Subjects were significantly less hungry before lunch on the HP and M (33% protein) treatments (F3.44 = 7.35; P < 0.001). At lunch, they ate more energy after the HF treatment than after any of the other treatment (F1,38 = 9.00; P = 0.005). This was largely in the form of fat and protein, and to a lesser extent carbohydrate. Subsequent energy intake (EI) were lower on the HF treatment, largely through selection of less fat in the afternoon (F1.42 = 6.90; P=0.012). Daily EIs were similar across treatments. CONCLUSION: This design appears sensitive meal-to-meal to changes in both nutrient and EIs.

Adult↗

N- and P/Q-type Ca2+ channels mediate transmitter release with a similar cooperativity at rat hippocampal autapses.

The relationship between extracellular Ca2+ concentration and EPSC amplitude was investigated at excitatory autapses on cultured hippocampal neurons. This relationship was steeply nonlinear, implicating the cooperative involvement of several Ca2+ ions in the release of each vesicle of transmitter. The cooperativity was estimated to be 3.1 using a power function fit and 3.3 using a Hill equation fit. However, simulations suggest that these values underestimate the true cooperativity. The role of different Ca2+ channel subtypes in shaping the Ca2+ dose-response relationship was studied using the selective Ca2+ channel blockers omega-agatoxin GIVA (omega-Aga), which blocks P/Q-type channels, and omega-conotoxin GVIA (omega-CTx), which blocks N-type channels. Both blockers broadened the dose-response relationship, and the Hill coefficient was reduced to 2.5 by omega-Aga and to 2.6 by omega-CTx. This broadening is consistent with a nonuniform distribution of Ca2+ channel subtypes across presynaptic terminals. The similar Hill coefficients in omega-Aga or omega-CTx suggest that there was no difference in the degree of cooperativity for transmitter release mediated via N- or P/Q-type Ca2+ channels. A model of the role of calcium in transmitter release is developed. It is based on a modified Dodge-Rahamimoff equation that includes a nonlinear relationship between extracellular and intracellular Ca2+ concentration, has a cooperativity of 4, and incorporates a nonuniform distribution of Ca2+ channel subtypes across presynaptic terminals. The model predictions are consistent with all of the results reported in this study.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Purpura fulminans localising to a recent burn injury.

The development of progressive, severe skin changes (purpura fulminans) is a serious complication of septicaemia, particularly meningococcal septicaemia. Purpura fulminans almost invariably leads to some full thickness skin loss and may lead to limb amputation. The pathophysiology may involve microemboli, endotoxins and direct bacterial damage to the vessels. We describe a case of purpura fulminans, probably as a result of meningococcal septicaemia, localising to a recent, healed burn with complete resolution. We can find no other record of the skin manifestations of meningococcal septicaemia localising to a previous injury.

Anti-Bacterial Agents↗