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G Reid

Publications and source records attributed to G Reid.

At least 73 records · Page 4Linked to original sources

Human axons contain at least five types of voltage-dependent potassium channel.

1. We investigated voltage-gated potassium channels in human peripheral myelinated axons; apart from the I, S and F channels already described in amphibian and rat axons, we identified at least two other channel types. 2. The I channel activated between -70 and -40 mV, and inactivated very slowly (time constant 13.1 s at -40 mV). It had two gating modes: the dominant ('noisy') mode had a conductance of 30 pS (inward current, symmetrical 155 mM K+) and a deactivation time constant (tau) of 25 ms (-80 mV); it accounted for most ( approximately 50-75 %) of the macroscopic K+ current in large patches. The secondary ('flickery') gating mode had a conductance of 22 pS, and showed bi-exponential deactivation (tau = 16 and 102 ms -80 11 mV); it contributed part of the slow macroscopic K+ current. 3. The I channel current was blocked by 1 microM alpha-dendrotoxin (DTX); we also observed two other DTX-sensitive K+ channel types (40 pS and 25 pS). The S and F channels were not blocked by 1 microM DTX. 4. The conductance of the S channel was 7-10 pS, and it activated at slightly more negative potentials than the I channel; its deactivation was slow (tau = 41.7 ms at -100 mV). It contributed a second component of the slow macroscopic K+ current. 5. The F channel had a conductance of 50 pS; it activated at potentials between -40 and +40 V, deactivated very rapidly (tau = 1.4 ms at -100 mV), and inactivated rapidly (tau = 62 ms at +80 mV). It accounted for the fast-deactivating macroscopic K+ current and partly for fast K+ current inactivation. 6. We conclude that human and rat axonal K+ channels are closely similar, but that the correspondence between K+ channel types and the macroscopic currents usually attributed to them is only partial. At least five channel types exist, and their characteristics overlap to a considerable extent.

Adolescent↗

Analysis of the CAVEOLIN-1 gene at human chromosome 7q31.1 in primary tumours and tumour-derived cell lines.

We identified CAVEOLIN-1 as a candidate for a tumour suppressor gene mapping to human chromosome 7q31.1. A number of studies suggest that caveolin could function as a tumour suppressor. Expression of caveolin, and in turn the number of caveolae within a cell, are inversely correlated with the transforming ability of numerous oncoproteins, including H-ras, v-abl, and bcr-abl, and caveolin is a major transformation-dependent substrate of v-src. Heterologous expression of caveolin has been shown to abrogate anchorage-independent growth and induce apoptosis in transformed fibroblasts and also to suppress anchorage-independent growth in human mammary carcinoma cells. We have analysed the status and expression of the human CAVEOLIN-1 gene in primary tumours and tumour-derived cell lines. We found no evidence for mutation of CAVEOLIN-1 in human cancers. Additionally, we found that while the first two exons of CAVEOLIN-1 are associated with a CpG island, this is not methylated in either primary tumours or in tumour-derived cell lines in which Caveolin-1 expression is low or undetectable. The level of expression of Caveolin-1 does not correlate with loss of heterozygosity at the CAVEOLIN-1 locus in these same cell lines. Contrary to other published studies, we have shown that CAVEOLIN-1 is not expressed in normal breast ductal epithelial cells in vivo. CAVEOLIN-1 is however highly expressed in breast myoepithelial cells and its expression is retained in tumours derived from breast myoepithelium. Together our data refute a role for CAVEOLIN-1 as a breast tumour suppressor gene in vivo.

Breast Neoplasms↗

A functional role of the erg-like inward-rectifying K+ current in prolactin secretion from rat lactotrophs.

The functional role of the inward-rectifying erg-like K+ current in rat lactotrophs was studied by the use of a selective blocker, the class III antiarrhythmic agent E-4031. The erg-like current was measured as drug-sensitive current in physiological K+ gradient. In the range of the normal resting membrane potential of rat lactotrophs (around -45 mV) the erg-like current constituted a steady outward current. A selective block of this current by E-4031 resulted in a moderate (5 mV) depolarization of the membrane potential in 64% of the lactotroph cells. Measurements of basal prolactin secretion with the reverse hemolytic plaque assay showed that the number of prolactin secreting cells and the amount of prolactin secreted from single lactotrophs was significantly increased in the presence of E-4031. The data show that the contribution of the erg-like K+ current to the maintenance of the resting membrane potential is functionally important for the regulation of prolactin secretion.

Animals↗

Potential preventive strategies and therapies in urinary tract infection.

There are perhaps five strategies either presently advocated or under investigation for prevention of recurrent urinary tract infection (UTI): antibiotics, including natural peptides; functional foods; vaccines; probiotics; and miscellaneous, including avoidance of spermicides and maintenance of good hygiene. It is not possible to state the proportion of patients using antibiotics versus foods such as cranberry or using alternative approaches such as avoidance of spermicides. The majority of women who are referred to specialists will be prescribed long-term, low-dose antibiotics. However, given the magnitude of the problem, it is safe to state that large numbers of women are at least experimenting with alternative remedies such as drinking of cranberry juice or ingestion of herbal remedies with a view to enhancing their immune response. Vaccine development remains a long way from human use and has yet to be developed for organisms other than Escherichia coli. The use of probiotics of restore the normal vaginal flora and provide a competitive bacterial barrier to pathogens is close to becoming available as an alternative preventive approach. The next decade should see the introduction of new methods for reduction of the high incidence of UTI and better management of recurring urogenital infections.

Anti-Bacterial Agents↗

Asymptomatic bacteriuria in spinal cord patients and the elderly.

The prevalence and incidence of symptomatic and asymptomatic bacteriuria will remain high for many years to come. Antimicrobial agents are necessary to treat symptomatic UTI because no natural methods have been shown to be effective. Treatment of ABU is not appropriate. There is growing resistance to antibiotics, biocides, and antiseptics and, simultaneously, a decreasing rate of introduction of new antibacterial agents; thus the problem of resistance is magnified and potentially complicates the management of patients with SCI and elderly persons. New options of managing health and of preventing ABU and UTI and the complications arising from these diseases must be investigated vigorously and urgently. In particular, further study of the role of bacterial biofilms, the normal microflora, the influence of diet and hygiene, and the importance of the host immune response in the process of urinary tract colonization and infection is relevant and necessary.

Aged↗

Frequency filtering improves ultrasonic embolic signal detection.

Problems in detection of Doppler cerebral embolic signals primarily occur for embolic signals of low relative intensity. A characteristic feature of embolic signals is that the intensity increase is maximal over a narrow frequency band. Therefore, frequency filtering of the data might improve embolic signal relative intensity and detectability. We implemented an off-line finite impulse response filter in software running on a commercially available transcranial Doppler system, using the time-domain audio data as input. The range of the filter was chosen by placing a box around the embolic signal on the spectral display. One hundred consecutive embolic signals from patients with carotid stenosis were analyzed; all had been recorded by a bigate system and the signal was analyzed in both proximal and distal channels. There was a highly significant increase in embolic signal relative intensity following frequency filtering; mean (SD) proximal channel prefiltering 12.75 (4.83) dB, postfiltering 16.36 (4.93) dB; distal channel prefiltering 13.42 (4.98) dB, postfiltering 16.60 (5.11) dB, for both p < 0.001. Despite all embolic signals being audible and visible in at least one channel on the frequency spectral display, in 17 cases, the amplitude increase associated with the embolic signal could not be clearly seen in time-domain data of one or both channels prior to filtering. Following frequency filtering, this was reduced to 5. Incorporation of such a frequency-filtering approach to an online system is likely to improve the sensitivity of online detection for embolic signals of low relative intensity.

Carotid Stenosis↗

Biofilms in infectious disease and on medical devices.

Microbial biofilms constitute a major reason for infections to occur and persist at various sites in the human body, especially in association with medical devices. The organisms invariably form these biofilms on surfaces which have host proteins and other substances coating them. Once adherent, the bacteria multiply and anchor themselves in quite intricate structures which appear to allow for communication and information transfer between organisms. For the treating physician, many antibiotics are unable to eradicate dense biofilms, and therefore much work is required to devise ways to prevent their occurrence and clear them from the host.

Anti-Bacterial Agents↗

Biomaterials in Urology II: future usage and management.

It seems likely, and indeed inevitable, that medical device usage will continue its rapid increase over the next 10 to 20 years and beyond. For surgeons, these new inventions will come in many forms but should take into account biocompatibility and resistance to encrustations and to microorganisms. This review focuses on research under way at present in vitro and in vivo on materials and coatings, use of bioelectrics, use of artificial organs and tissues, application of indigenous bacteria, and other alternative device management techniques, which could well become part of clinical practice in the future. By necessity, some of these citations are speculative, but supporting documentation for their inclusion is presented.

Animals↗

Microlaparoscopic left upper quadrant entry in patients at high risk of periumbilical adhesions.

We performed a prospective study of microlaparoscopic direct entry in the left upper quadrant (LUQ) to determine the efficacy of this technique and the incidence and site of anterior abdominal wall adhesions in high-risk patients. Direct insertion of the MiniPort introducer was successful with 1 attempt in 16 patients and in 2 attempts with 1 patient. Overall, 12 patients (71%) had either bowel or omentum adherent to the anterior abdominal wall. Eight of the 12 patients (75%) with a previous midline abdominal wall incision were found to have subumbilical adhesions. Two patients were noted to have LUQ omental adhesions. Direct insertion of a 2 mm microlaparoscopic primary port in the LUQ appears to be simple, safe and quick to perform. It provides an excellent view of the peritoneal surface of the anterior abdominal wall and umbilical area. This procedure is likely to be the preferred method of peritoneal entry in high-risk patients in the future.

Abdominal Muscles↗

Early use of inhaled nedocromil sodium in children following an acute episode of asthma.

BACKGROUND: Current guidelines on the treatment of childhood asthma recommend the introduction of an anti-inflammatory drug in children who have persistent symptoms and require regular treatment with a bronchodilator. The efficacy and safety of inhaled nedocromil sodium (Tilade Mint aerosol) administered using a Fisonair spacer at a dose of 4 mg three times daily was compared with placebo in the treatment of asthmatic children aged 6-12 years who are symptomatic and recovering from an acute exacerbation of asthma. METHODS: A group comparative, double blind, placebo controlled trial was performed in children who were recovering from an acute episode of asthma following treatment in the emergency department of the hospital or in children referred from their general practitioner following a wheezing episode and documented evidence of at least two previous episodes of wheezing. A two week baseline period on existing bronchodilator treatment was followed by a 12 week treatment period on either nedocromil sodium (2 mg/puff) or placebo. Both treatments were administered using a Fisonair spacer at a dose of two puffs three times daily. Changes from baseline values in daytime asthma and night time asthma symptom scores, usage of rescue bronchodilators, mean peak expiratory flow (PEF) recorded twice daily on diary cards, patients' opinion of treatment, and withdrawals due to treatment failure were measured during the primary treatment period (last six weeks of treatment). RESULTS: One hundred and forty two children aged 6-12 years entered the baseline period. Sixty three were withdrawn due to failure to meet the entry criteria (18) or the criteria for asthma symptom severity (15) or reversibility (9), because they developed uncontrolled asthma (2), because they took disallowed treatment (2), or for other non-trial related reasons (17). Seventy nine patients (46 boys) of mean age 8. 8 years entered the treatment period. There were significant differences in the changes from baseline values during the last six weeks of treatment in favour of nedocromil sodium compared with placebo in the primary variables of daytime asthma and night time asthma, morning and evening PEF, and the usage of rescue inhaled bronchodilators; 53% of patients reported nedocromil sodium to be very or moderately effective compared with 44% placebo. Improvement in asthma symptoms, PEF, and reduction in use of rescue bronchodilators did not reach statistical significance until after six weeks of treatment. Twenty two patients were withdrawn or dropped out during the treatment phase, 12 due to uncontrolled asthma or persistence of asthma symptoms, four due to suspected adverse drug reactions (nedocromil sodium 3 (headaches 2, angio-oedema/urticaria 1), placebo 1(persistent cough)), and six due to non-treatment related reasons. Seventy one adverse events were reported by 27 patients in the nedocromil group and 75 by 30 patients in the placebo group. CONCLUSIONS: Asthma symptoms, use of bronchodilators, and lung function can be improved significantly in children recovering from an acute exacerbation of asthma or wheeze and currently receiving treatment with bronchodilators alone by the addition of inhaled nedocromil sodium at a dose of 4 mg three times daily administered using a Fisonair holding chamber.

Acute Disease↗

The effect of water, ascorbic acid, and cranberry derived supplementation on human urine and uropathogen adhesion to silicone rubber.

In this study, urine was collected from groups of volunteers following the consumption of water, ascorbic acid, or cranberry supplements. Only ascorbic acid intake consistently produced acidic urine. Photospectroscopy data indicated that increased water consumption produced urine with lower protein content. Surface tension measurements of the collected urine showed that both water and cranberry supplementation consistently produced urine with surface tensions higher than the control or urine collected following ascorbic acid intake. These urine samples were also employed to study uropathogen adhesion to silicone rubber in a parallel plate flow chamber. Urine obtained after ascorbic acid or cranberry supplementation reduced the initial deposition rates and numbers of adherent Escherichia coli and Enterococcus faecalis, but not Pseudomonas aeruginosa, Staphylococcus epidermidis, or Candida albicans. Conversely, urine obtained from subjects with increased water intake vastly increased the initial deposition rates and numbers of adherent E. coli and E. faecalis (P < 0.05).

Adult↗

Improved automated detection of embolic signals using a novel frequency filtering approach.

BACKGROUND AND PURPOSE: Asymptomatic embolic signal detection with the use of Doppler ultrasound has a number of potential clinical applications. However, its more widespread clinical use is severely limited by the lack of a reliable automated detection system. Design of such a system depends on accurate characterization of the unique features of embolic signals, which allow their differentiation from artifact and background Doppler speckle. We used a processing system with high temporal resolution to describe these features. We then used this information to design a new automated detection system. METHODS: We used a signal processing approach based on multiple overlapping band-pass filters to characterize 100 consecutive embolic signals from patients with carotid artery disease as well as both episodes of artifact resulting from probe tapping and facial movement and episodes of Doppler speckle. We then designed an automated detection system based both on these embolic signal characteristics and on the fact that embolic signals have maximum intensity over a narrow frequency range. This system was tested in real time on stored 5-second segments of data. RESULTS: The value of peak velocity at maximal intensity discriminated best between embolic signals and artifact and allowed differentiation with 100% sensitivity and specificity. Relative intensity increase, intensity volume, area under volume, average rise rate, and average fall rate appeared to discriminate best between embolic signals and Doppler speckle. For the majority of embolic signals, the intensity increase was spread over a narrow frequency or velocity range. The automated system we developed detected 296 of 325 carotid stenosis embolic signals from a new data set (sensitivity, 91.1%). All 200 episodes of artifact from a new data set were differentiated from embolic signals. Only 2 of 100 episodes of speckle were misidentified as embolic signals. CONCLUSIONS: Using a novel system for automated detection, which utilizes the fact that embolic signals have maximum intensity over a narrow frequency range, we have achieved detection with a high sensitivity and high specificity. These results are considerably better than those previously reported. We tested this initial system on short 5-second segments of data played in real time. This approach now needs to be developed for use in a true online system to determine whether it has sufficient sensitivity and specificity for clinical use.

Artifacts↗

Microbial biofilms: their development and significance for medical device-related infections.

Microbial adhesion and biofilm formation on medical devices represent a common occurrence that can lead to serious illness and death. The process by which bacteria and yeast colonize open and closed implants is fairly complicated and involves a series of steps commencing with deposition of host substances onto the material. Prevention and treatment of established biofilms with antimicrobial agents are difficult because the organisms are encased within a protected microenvironment. Efforts to reduce adhesion using specially developed materials, such as hydrophilic or heparin coated, have had modest success once applied to the patient. The reason, at least for the most part, is the diverse milieu into which devices are placed and the multitude of ways in which organisms can colonize surfaces. A better understanding of the process is required, and the knowledge gained must be used to devise new strategies as alternatives to the traditional employment of antibiotics. These new approaches may still use antibiotics but at different concentrations (low to prevent and high to treat infection) and in a different manner (perhaps spiked therapy in which there is a delay between doses to reduce the risk of drug resistance and impact on normal flora). The possibility of applying functional foods to patient management should also be pursued.

Anti-Bacterial Agents↗