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Biomedical subjects

C Allison

Publications and source records attributed to C Allison.

At least 19 recordsLinked to original sources

Intragastric balloons: a temporary treatment for obesity.

(1) Intragastric balloons are a temporary non-surgical obesity treatment that induces short-term weight loss by partially filling the stomach to achieve satiety and reduce food intake. (2) Moderate weight loss may be achieved if patients adhere to a weight-reduction program. Weight gain often recurs when the balloon is removed after six months. (3) Abdominal pain, nausea, and vomiting are common, particularly in the first week after balloon implantation. (4) More data on benefits, harm, and cost effectiveness are required before the intragastric balloon can be compared with other short-term weight loss interventions, including low-calorie diets.

Bariatrics↗

BpTRU(tm) blood pressure monitor for use in a physician's office.

The BpTRU(tm) is an automated device that takes serial blood pressure (BP) measurements in a physician's office. (1) Preliminary data from non-randomized, uncontrolled trials suggest that the average of five BpTRU measurements, taken while the patient is alone, more reliably reflects "resting" BP compared to manual measurements taken with a stethoscope and sphygmomanometer. (2) BpTRU helps reduce the overestimation of BP due to improper measurement technique, or due to a patient's anxiety in a physician's presence ("white coat" effect). (3) The BpTRU device can improve hypertension management by replacing conventional manual BP measurements, which are often poorly performed and inaccurate. (4) BpTRU is more expensive than the manual manometers used in a physician's office. The serial measurement, taken in a private examining room, requires an average of six to 12 minutes, which could increase the duration of a patient's visit.

Automation↗

alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionate receptor autoradiography in mouse brain after single and repeated withdrawal from diazepam.

Withdrawal from chronic treatment with benzodiazepines is associated with increased neuronal excitability leading to anxiety, aversive effects and increased seizure sensitivity. After repeated withdrawal experiences, seizure sensitivity increases while withdrawal-induced anxiety and aversion decrease. We used autoradiographical methods employing [(3)H]Ro48 8587, a selective ligand for glutamatergic alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors, to study withdrawal-induced changes in AMPA receptor binding in areas of the mouse brain postulated to be involved in these responses. Mice were given 21 days treatment with diazepam (15 mg/kg, s.c. in sesame oil) followed by withdrawal (single withdrawal) or three blocks of 7 days treatment interspersed with 3-day periods to allow washout of drug (repeated withdrawal). In keeping with heightened excitability in withdrawal from chronic diazepam treatment, the single withdrawal group showed, 72 h after their final dose of diazepam, increased [(3)H]Ro48 8587 binding in several brain areas associated with emotional responses or seizure activity, including hippocampal subfields, amygdalar and thalamic nuclei and motor cortex. In contrast, the repeated withdrawal group showed no changes in [(3)H]Ro48 8587 binding in any brain area studied. These observations are consistent with up-regulation of AMPA receptor-mediated transmission being important in withdrawal-induced anxiety and aversion but not in increased seizure sensitivity associated with repeated withdrawal. As changes in AMPA receptor subunit expression alter the functionality of the receptor, future studies will address this possibility.

Animals↗

Minimally invasive hip resurfacing.

Metal-on-metal hip resurfacing is an emerging surgical alternative for younger patients who are expected to outlive a conventional total hip replacement implant. Minimally invasive hip resurfacing uses a smaller surgical incision and new techniques to expose the hip joint. Possible advantages include less damage to soft tissue, muscle and bone; smaller scars; less blood loss; and shorter hospital stays and rehabilitation. Possible disadvantages include damage to soft tissue, femur fracture, neurovascular damage, implant malposition and a longer operating time. The lack of published or unpublished trials or case reports makes it impossible to draw conclusions about the relative effectiveness of minimally invasive procedures for hip resurfacing. Developments in computer navigation systems and fluoroscopic imaging may permit more widespread use of minimally invasive hip resurfacing in the future.

Acetabulum↗

Abatacept as add-on therapy for rheumatoid arthritis.

Abatacept is a co-stimulation blocker that inhibits T-cell activation and interrupts the process leading to inflammation in rheumatoid arthritis. Patients with severe arthritis who took abatacept with at least one other disease-modifying antirheumatic drug in six and 12-month clinical trials demonstrated statistically significant improvement in tender, swollen joints and other clinical measures compared with placebo. Mild to moderate adverse events included headache, nasopharyngitis, hypertension and back pain. The adverse events were similar to those seen in placebo groups. Abatacept should not be used in combination with other biologic agents because of reported increased rates of serious adverse events, including serious infections. With its different mechanism of action, abatacept may be an alternative add-on therapy for patients with an inadequate response to other arthritis therapies.

Antirheumatic Agents↗

Neuroadaptive processes in GABAergic and glutamatergic systems in benzodiazepine dependence.

Knowledge of the neural mechanisms underlying the development of benzodiazepine (BZ) dependence remains incomplete. The gamma-aminobutyric acid (GABA(A)) receptor, being the main locus of BZ action, has been the main focus to date in studies performed to elucidate the neuroadaptive processes underlying BZ tolerance and withdrawal in preclinical studies. Despite this intensive effort, however, no clear consensus has been reached on the exact contribution of neuroadaptive processes at the level of the GABA(A) receptor to the development of BZ tolerance and withdrawal. It is likely that changes at the level of this receptor are inadequate in themselves as an explanation of these neuroadaptive processes and that neuroadaptations in other receptor systems are important in the development of BZ dependence. In particular, it has been hypothesised that as part of compensatory mechanisms to diazepam-induced chronic enhancement of GABAergic inhibition, excitatory mechanisms (including the glutamatergic system) become more sensitive [Behav. Pharmacol. 6 (1995) 425], conceivably contributing to BZ tolerance development and/or expression of withdrawal symptoms on cessation of treatment, including increased anxiety and seizure activity. Glutamate is a key candidate for changes in excitatory transmission mechanisms and BZ dependence, (1) since there are defined neuroanatomical relationships between glutamatergic and GABAergic neurons in the CNS and (2) because of the pivotal role of glutamatergic neurotransmission in mediating many forms of synaptic plasticity in the CNS, such as long-term potentiation and kindling events. Thus, it is highly possible that glutamatergic processes are also involved in the neuroadaptive processes in drug dependence, which can conceivably be considered as a form of synaptic plasticity. This review provides an overview of studies investigating changes in the GABAergic and glutamatergic systems in the brain associated with BZ dependence, with particular attention to the possible differential involvement of N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors in these processes.

Anti-Anxiety Agents↗

Diazepam withdrawal-induced anxiety and place aversion in the rat: differential effects of two chronic diazepam treatment regimes.

The ability of the benzodiazepine antagonist flumazenil to precipitate a withdrawal subjective state in rats receiving chronic diazepam was investigated in a biased conditioned place aversion (CPA) procedure. Conditioning with flumazenil (10 mg/kg i.p.) in rats receiving chronic diazepam subcutaneously (s.c. in oil, 15 mg/kg/day for 28 days) but not intraperitoneally (i.p., 5 mg/kg for 28 days) resulted in the formation of a conditioned place aversion. These results indicate that precipitated withdrawal from diazepam injected s.c. but not i.p. produces a negative subjective state and that the conditioned place aversion paradigm may be useful in detecting the negative subjective effects of diazepam withdrawal. In parallel studies, the same s.c. treatment protocol produced an anxiogenic effect in the elevated plus-maze on spontaneous diazepam withdrawal, whereas rats treated with the i.p. protocol displayed no signs of withdrawal anxiety. The results of the present study are consistent with the interpretation that rats withdrawn from chronic i.p. diazepam did not demonstrate a CPA due to the 'repeated withdrawal' experiences induced by the i.p. injection route attenuating the subsequent ability of flumazenil to precipitate a subjective withdrawal state. Pharmacokinetic evidence and previous evidence showing that repeated withdrawal from diazepam in mice attenuates the aversive effects of the withdrawal experience in a conditioned taste aversion (CTA) paradigm support this interpretation.

Animals↗

Oral topical doxepin rinse: analgesic effect in patients with oral mucosal pain due to cancer or cancer therapy.

Oral mucositis is a treatment limiting toxicity of cancer therapy. The purpose of this study was to assess the impact of doxepin oral rinse in the management of oral mucosal pain in cancer patients. Forty-one cancer patients with oral mucosal pain were provided a solution of doxepin (0.5%) for oral rinsing. Oral pain was assessed prior to rinsing, and following rinsing for 4 h using a visual analogue scale (VAS). Adverse effects were recorded. Doxepin rinse resulted in a reduction of pain intensity of more than 50%, with pain relief extending for more than 3 h with pain not returning to baseline 4 h after rinsing. The rinse was tolerated by patients with mucosal damage, and had acceptable taste, and infrequent mucosal stinging with use. Some patients reported sedation after use, likely due to systemic absorption. The results of this single dose trial suggest that topical doxepin rinse has significant ability to provide clinically significant pain relief in patients with mucosal damage with an extended duration of effect.

Adult↗

A continuous culture biofilm model of cariogenic responses.

AIMS: To validate an in vitro model for the analysis of physiological and ecological responses to sugar challenge in bacterial populations, and subsequent changes in enamel mineralization. METHODS AND RESULTS: A seven-organism bacterial consortium was grown in a biofilm mode on enamel and hydroxyapatite (HA) surfaces in a continuous culture system and exposed to repeated sucrose challenges. This produced 'pH-cycling' conditions within the system. Populations on HA surfaces were enumerated. Changes in relative proportions of the different populations, and in the total viable count, were observed, between different treatments. Microradiography of the enamel sections showed increasing demineralization with increasing sucrose concentration. The lesions formed were similar to 'white-spot' lesions found in vivo. Differences in the quality of biofilms formed were also observed using Confocal Laser Scanning Microscopy. CONCLUSION: An in vitro model has been validated for the analysis of both physiological and ecological responses to sucrose challenges in bacterial populations, and subsequent changes in enamel mineralization. SIGNIFICANCE AND IMPACT OF THE STUDY: This model should facilitate the study of changes in bacterial populations in response to application of putative anticaries agents and concomitant changes in enamel mineralization.

Bacteria↗

A fully automated microscope bacterial enumeration system for studies of oral microbial ecology.

A fast and fully automated image analysis technique for the enumeration of fluorescence-labeled bacteria in oral sampleswas developed. This paper describes the system configuration, application strategy, automated operation, and initial validation experiments using fluorescent microspheres, bacterial cultures, in vitro grown biofilms and human dental plaque. Following a series of brief operator-controlled calibration steps, the technique automatically performs all necessary microscope operations (stage translation, focus, sampling and analysis) on slides with up to 48 wells for as many different samples. It quantifies bacteria from differential interference contrast images, images showing cells that had been labeled by immunofluorescence with monoclonal antibodies, or images with cells labeled by a fluorescent DNA stain. With all evaluated samples, close agreement between the automated system and the assessor's visual counts was observed. This novel automated image grabbing and analysis procedure is applicable to the enumeration of specific taxa in clinical samples by both immunofluorescence and fluorescent in situ hybridization.

Automation↗

The predominant aciduric microflora of root-caries lesions.

The etiology of root caries is not fully understood, and although mutans streptococci, lactobacilli, and A. naeslundii have been implicated in its initiation and progression, this study was designed to determine the potential role of other microbial species and the nature of predominant aciduric microflora in the root caries process. We isolated the predominant aciduric microflora from root-caries lesions (n = 14) and sound root surfaces in subjects with (n = 13) or without (n = 10) root caries, using both a "most probable numbers" method and conventional plating methods. The predominant aciduric bacteria from root lesions were lactobacilli and A. israelii, while from sound root surfaces in subjects with root caries, A. gerencseriae comprised over 60% of aciduric isolates. Mutans streptococci were not among the aciduric isolates. Subjects without root caries harbored fewer bacteria, and S. anginosus (pH 4.8) and S. oralis (pH 5.2) were the predominant aciduric bacteria. The microbial etiology of root caries is more complex than was previously appreciated, and factors underlying the microbial succession occurring during the disease process are not known. Taxa with previously unrecognized aciduric characteristics have been isolated routinely, and the role of these organisms in the root caries process requires further investigation.

Actinomyces↗

Genotypic heterogeneity of Streptococcus oralis and distinct aciduric subpopulations in human dental plaque.

The genotypic heterogeneity of Streptococcus oralis isolated from the oral cavity was investigated using repetitive extragenic palindromic PCR. Unrelated subjects harbored unique genotypes, with numerous genotypes being isolated from an individual. S. oralis is the predominant aciduric bacterium isolated from noncarious tooth sites. Genotypic comparison of the aciduric populations isolated at pH 5.2 with those isolated from mitis-salivarius agar (MSA) (pH 7.0) indicated that the aciduric populations were genotypically distinct in the majority of subjects (chi(2) = 13.09; P = 0.0031). Neither the aciduric nor the MSA-isolated strains were stable, with no strains isolated at baseline being isolated 4 or 12 weeks later in the majority of subjects. The basis of this instability is unknown but is similar to that reported for Streptococcus mitis. Examination of S. oralis strains isolated from cohabiting couples demonstrated that in three of five couples, genotypically identical strains were isolated from both partners and this was confirmed by using Salmonella enteritidis repetitive element PCR and enterobacterial PCR typing. These data provide further evidence of the physiological and genotypic heterogeneity of non-mutans streptococci. The demonstration of distinct aciduric populations of S. oralis implies that the role of these and other non-mutans streptococci in the caries process requires reevaluation.

Dental Plaque↗

A role for AMPA/kainate receptors in conditioned place preference induced by diazepam in the rat.

There is increasing evidence for a role of glutamate receptors in the reinforcing properties of dependence producing drugs such as the psychostimulants and opiates. Activation of AMPA/kainate receptors are implicated in the acquisition of amphetamine-induced reinforcement but a role for this receptor in benzodiazepine-induced reinforcement has not been examined. In the present study the ability of the orally active AMPA/kainate antagonist GYKI 52466 was assessed for its ability to block the reinforcing properties of diazepam in a conditioned place preference paradigm. Diazepam (2.5 and 5.0 mg/kg, i.p.) produced a robust place preference and GYKI 52466 inhibited the acquisition of place preference conditioning-induced by diazepam. These results suggest that glutamatergic pathways are an important component of the circuitry involved in the acquisition of a benzodiazepine induced place preference.

Animals↗

Negative correlation between oral malodour and numbers and activities of sulphate-reducing bacteria in the human mouth.

The majority of cases of oral malodour are thought to be due to bacterial activities in the mouth, but many of the bacterial species responsible have not been identified. Volatile sulphide compounds have been proposed as constituents of oral malodour. Therefore, the relation between intensity of odour and numbers of bacteria in the mouth that are sulphide-producing from sulphate was investigated. Numbers of such dissimilatory sulphate-reducing bacteria (SRB) and sulphide reduction rates were evaluated in samples from different oral sites in relation to measures of oral malodour. Results showed that sulphate-reducing bacterial numbers and activities were negatively correlated with malodour, as determined by organoleptic assessment and measurement with a sulphide-monitoring instrument, the Halimeter. The data indicate that sulphide produced by oral SRB may not be an important contributor to oral malodour. A rather poor correlation was observed between Halimetric and organoleptic values, indicating that these methods may measure different aspects of oral malodour intensity.

Adult↗

Measurement of serum bone-specific alkaline phosphatase activity in cynomolgus macaques.

Serum levels of bone-specific alkaline phosphatase activity (B-ALP) in cynomolgus monkeys were evaluated as an index of elevated bone turnover following ovariectomy. The enzyme immunoassay 96-well microtiter plate B-ALP assay, developed by Metra Biosystems (Mountain View, CA) for human use, was employed and compared with a standard automated assay measuring total serum levels of alkaline phosphatase activity (T-ALP). The B-ALP assay was first validated for use in these monkeys. Ovariectomy led to increased bone turnover as indicated by approximately 2-fold higher activity in both assays and this elevation was inhibited by daily estradiol administration. Although both assays provided generally similar results, several monkeys were observed to have greatly elevated values of T-ALP but not B-ALP. This discrepancy is believed to result from high levels of the liver isoform of alkaline phosphatase in monkeys with hepatic dysfunction, which are not detected by the B-ALP assay.

Alkaline Phosphatase↗

Depth penetration and detection of pH gradients in biofilms by two-photon excitation microscopy.

Deep microbial biofilms are a major problem in many industrial, environmental, and medical settings. Novel approaches are needed to understand the structure and metabolism of these biofilms. Two-photon excitation microscopy (TPE) and conventional confocal laser scanning microscopy (CLSM) were compared quantitatively for the ability to visualize bacteria within deep in vitro biofilms. pH gradients within these biofilms were determined by fluorescence lifetime imaging, together with TPE. A constant-depth film fermentor (CDFF) was inoculated for 8 h at 50 ml. h(-1) with a defined mixed culture of 10 species of bacteria grown in continuous culture. Biofilms of fixed depths were developed in the CDFF for 10 or 11 days. The microbial compositions of the biofilms were determined by using viable counts on selective and nonselective agar media; diverse mixed-culture biofilms developed, including aerobic, facultative, and anaerobic species. TPE was able to record images four times deeper than CLSM. Importantly, in contrast to CLSM images, TPE images recorded deep within the biofilm showed no loss of contrast. The pH within the biofilms was measured directly by means of fluorescence lifetime imaging; the fluorescence decay of carboxyfluorescein was correlated with biofilm pH and was used to construct a calibration curve. pH gradients were detectable, in both the lateral and axial directions, in steady-state biofilms. When biofilms were overlaid with 14 mM sucrose for 1 h, distinct pH gradients developed. Microcolonies with pH values of below pH 3.0 were visible, in some cases adjacent to areas with a much higher pH (>5.0). TPE allowed resolution of images at significantly greater depths (as deep as 140 microm) than were possible with CLSM. Fluorescence lifetime imaging allowed the in situ, real-time imaging of pH and the detection of sharp gradients of pH within microbial biofilms.

Biofilms↗

The effects of histatin-derived basic antimicrobial peptides on oral biofilms.

Susceptibility of bacteria to antimicrobial agents is strongly reduced by the formation of complex biofilms. We investigated whether synthetic histatin analogs with broad-spectrum antibacterial activity in vitro were also active against these complex mixtures of bacteria, as present in saliva and plaque. In a simplified model system for dental plaque, hydroxyapatite discs were placed in a continuous culture system comprised of Streptococcus mutans, S. sanguis, S. salivarius, Actinomyces naeslundii, Veillonella parvula, Fusobacterium nucleatum, and Prevotella intermedia. Ex situ treatment of the biofilms formed on these discs with 100 microg/mL of peptide dhvar4 significantly reduced facultative anaerobic, total anaerobic, and obligate anaerobic Gram-negative counts with 0.8, 0.5, and 0.5 log units, respectively. Ex vivo treatment of salivary bacteria gave reductions of 0.4, 0.7, and 1.5 log units, respectively. For ex vivo treatment of plaque bacteria, reductions of 0.4, 0.4, and 1.4 log units, respectively, were found. In both saliva and plaque samples, obligate anaerobic Gram-negative bacteria were significantly more susceptible to dhvar4 than facultatively anaerobic or anaerobic bacteria as a whole (p=0.013 and p=0.018, for salivary bacteria, and p=0.021 and p=0.020 for plaque bacteria, respectively). Although the oral bacteria are protected by biofilm formation, the synthetic histatin analog caused a significant reduction of viable counts in a model for oral biofilm as well as in isolated oral biofilms.

Actinomyces↗

The diving physiology of bottlenose dolphins (Tursiops truncatus). III. Thermoregulation at depth.

During diving, marine mammals initiate a series of cardiovascular changes that include bradycardia and decreased peripheral circulation. Because heat transfer from thermal windows located in peripheral sites of these mammals depends on blood flow, such adjustments may limit their thermoregulatory capabilities during submergence. Here, we demonstrate how the thermoregulatory responses of bottlenose dolphins (Tursiops truncatus) are coordinated with the diving response. Heart rate, skin temperature and heat transfer from the dorsal fin and flank were measured while dolphins rested on the water surface, stationed 5-50 m under water and floated at the surface immediately following a dive. The results showed that heat flow ranged from 42.9+/-7.3 to 126.2+/-23.1 W m(-)(2) and varied with anatomical site and diving activity. Upon submergence, heat flow declined by 35 % from the dorsal fin and by 24 % from the flank. An immediate increase in heat flow to levels exceeding pre-dive values occurred at both sites upon resurfacing. Changes in heart rate during diving paralleled the thermoregulatory responses. Mean pre-dive heart rate (102.0+/-2.6 beats min(-)(1), N=26) decreased by 63.4 % during dives to 50 m and immediately returned to near resting levels upon resurfacing. These studies indicate that heat dissipation by dolphins is attenuated during diving. Rather than challenge the diving response, heat transfer is delayed until post-dive periods when the need for oxygen conservation is reduced.

Animals↗