Biomedical subjects

M Gallagher

Publications and source records attributed to M Gallagher.

At least 127 records · Page 7Linked to original sources

PubMed1994

Correlation of microtrauma in the lumbar spine with intraosseous pressures.

This study was conducted to determine the relationship between intraosseous pressure and vertebral microtrauma in the lumbar spine. Functional spinal units were excised from human cadavers. Radio-opaque dye was injected into the nucleus. Miniature transducers were inserted into the vertebrae to record intraosseous pressures. Compressive loading was applied quasistatically (2 mm/sec) until injury occurred. Movement of the contrast medium was monitored under fluoroscopy. The subchondral endplate was the most vulnerable component for initiation of injury to the lumbar spine segment. In the initial stages of loading, the vertebral endplates gradually bulged outward, with the contrast medium staying within the nucleus. However, at higher physiologic load levels, before reaching the limiting load, the deformations increased, resulting in buckling of one of the endplates. This was followed by the contrast medium impregnating the spongiosa. Microlevel trauma was not observed radiographically after load removal, indicating that one cannot always equate a normal radiograph with normal spinal anatomy. Mean forces, deformations, stiffnesses, energies, and strains were 7.8 kN (+/- 1.4), 5.23 mm (+/- 0.78), 1940 N/mm (+/- 226), 18.7 J (+/- 4.4), and 35.5% (+/- 3.7), respectively. Pressure in the vertebral body containing the injured endplate before the onset of microtrauma was different (P < 0.05) from the pressure after injury; the pressures in the body containing the intact endplate, however, were not statistically different. Significant differences (P < 0.05) in the intraosseous pressures occurred between the two spinal levels at low-level physiologic loads before the onset of microtrauma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Expression of insulin-like growth factor binding protein-4 and -5 mRNAs in adult rat forebrain.

Accumulating evidence indicates that the insulin-like growth factors (IGFs) can act as neurotrophic factors. A family of at least six IGF binding proteins (IGFBPs) has been characterized. The IGFBPs prolong the half-life of IGFs in plasma and may modulate IGF action in a cell- or tissue-specific fashion. Two recently characterized IGFBPs, IGFBP-4 and -5, have been shown by northern blot hybridization to be expressed in rat brain, but their cellular sites of synthesis are poorly characterized. Because IGFBP-4 and IGFBP-5 could potentially modulate IGF actions in the brain, we used in situ hybridization histochemistry and 35S-labeled IGFBP-4 and IGFBP-5 riboprobes to localize sites of IGFBP-4 and -5 mRNA expression in adult rat brain. The two IGFBP mRNAs are abundantly expressed within discrete regions of brain. The expression patterns of the two genes are largely nonoverlapping. Notably, IGFBP-4 mRNA is highly expressed within hippocampal and cortical areas, whereas IGFBP-5 mRNA is not detected above background in these areas. Within the hippocampus, abundant IGFBP-4 mRNA expression is detected in pyramidal neurons of the subfields of Ammon's horn and the subiculum and in the granule cell layer of the anterior hippocampal continuation. In the cortex, IGFBP-4 mRNA is widely expressed in most areas and layers. In contrast, IGFBP-5, but not IGFBP-4, mRNA is detected within thalamic nuclei, leptomeninges, and perivascular sheaths. The distinct expression patterns of IGFBP-4 and -5 mRNAs within the brain suggest that these IGFBPs may modulate paracrine/autocrine actions of the IGFs in discrete brain regions or compartmentalization of the IGFs within the brain.

Animals↗

PubMed1994

Sotalol controlled-release systems for arrhythmias: in vitro characterization, in vivo drug disposition, and electrophysiologic effects.

An array of controlled-release formulations of sotalol were investigated for epicardial drug delivery in short-term and chronic long-term treatment models with dogs. A nondegradable matrix formulation of sotalol made with polyurethane was studied by use of short-term treatment model with dogs, and the electrophysiologic effects were compared with those resulting from an intravenous dose of 2 mg/kg of body weight. Epicardial sotalol-polyurethane matrices were also used in 7-day canine implant studies. A sotalol-silicone rubber matrix was used in 60-day epicardial canine implant studies. A biodegradable poly(dl-lactide-co-glycolide) (PLGA) microsphere formulation of sotalol was also studied as a pericardial injection in another series involving 30-day dog experiments. The short-term treatment electrophysiologic effects observed with the epicardial (left ventricular) implantation of a sotalol-polyurethane matrix formulation were comparable to those observed with intravenous sotalol. However, the total dose delivered by the matrix over a 2-h experimental period was 25 times smaller than the intravenous dose (0.077 versus 2 mg/kg). Furthermore, coronary venous sotalol levels after sotalol-polyurethane matrix implantation were in the therapeutic range (1812.4 +/- 415.1 ng/mL), whereas simultaneous peripheral venous levels were more than 1 order of magnitude lower (149.8 +/- 14.1 ng/mL). An intravenous bolus administration of sotalol (2 mg/kg) resulted in coronary venous levels (1537.1 +/- 44.6 ng/mL) that were very close to simultaneous peripheral venous levels (1428.6 +/- 63.9 ng/mL).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Effect of recovery method on yield of bovine oocytes per ovary and their developmental competence after maturation, fertilization and culture in vitro.

An important aim of an oocyte recovery method is to maximize the number of oocytes per ovary which can be employed for in vitro maturation (IVM), in vitro fertilization (IVF) and in vitro culture (IVC). In this study, primary bovine oocytes were collected by 2 methods: aspiration of visible follicles (2 to 6mm in diameter) or surface dissection in which the ovary surface is finely dissected. The oocytes were classified on the basis of cumulus cover and cytoplasmic appearance. The total number of oocytes and the yield of good-quality oocytes recovered per ovary by surface dissection and aspiration were 44.2 and 13.9 and 13.5 and 4.6 (P<0.05), respectively. When a sample group of selected oocytes recovered by each method was measured, no significant difference was found in the mean diameter (144.11m vs 142.54m). A representative sample of good-quality oocytes recovered by each method was put through the IVM/IVF/IVC procedure: no significant difference in cleavage rate, cleavage index or blastocyst yield was found. However, when the blastocyst yield was compared on a per ovary basis, a significant difference was observed in favor of surface dissection (3.30+/-0.46 vs 0.96+/-0.16;P<0.05). When unselected oocytes recovered by surface dissection of the ovaries were put through the standard embryo production system, an average of 15.4 blastocysts per dam was obtained.

Journal Article↗

PubMed1994

Epicardial administration of ibutilide from polyurethane matrices: effects on defibrillation threshold and electrophysiologic parameters.

Polymer-drug composites known as controlled-release systems have been used effectively to prevent and treat ventricular arrhythmias in experimental studies. We wished to determine if such systems could be useful in reducing ventricular defibrillation energy requirements in an acute canine model without producing undesirable electrophysiologic effects. Ibutilide-polyurethane monolithic controlled-release matrices were formulated with ibutilide fumarate and a polyether polyurethane. In vitro drug-release characteristics of the drug matrices were determined. Two formulations were investigated: (a) 20% ibutilide by weight in polyether polyurethane, and (b) 4% ibutilide/16% dimethyl tartrate in polyurethane. Based on in vitro release studies, 20% ibutilide matrices (25 mg) would provide a 25-kg dog with a dose of 25 micrograms/kg ibutilide in a 2-h acute experimental period, and 4% ibutilide matrices were estimated to provide 3.5 micrograms/kg. We used each of these types of matrices in acute open-chest dog studies to assess electrophysiologic effects and the influence of epicardial controlled-release ibutilide, as compared with intravenous (i.v.) administration, on defibrillation energy thresholds (DFTs), using epicardial defibrillation electrodes. In monophasic defibrillation waveform studies, 20% matrices significantly decreased DFT as compared with a predrug control period [2.54 +/- 0.59 (mean +/- SEM) vs. 7.23 +/- 1.73 J, respectively, p = 0.038]. Administration of the same dose i.v. did not cause significant reduction in energy requirement. With a biphasic defibrillation waveform, 4% ibutilide matrices significantly decreased DFT as compared with control (2.53 +/- 0.34 vs. 3.42 +/- 0.46 J, respectively, p = 0.003). Administration of an equivalent i.v. dose did not cause a significant reduction in biphasic energy requirement. Both types of controlled-release systems significantly prolonged refractoriness and conduction times of ventricular extrastimuli as compared with vehicle. No proarrhythmia events were observed. Epicardial polymeric controlled-release ibutilide significantly prolonged ventricular refractoriness and conduction and thus may enhance antiarrhythmia activity. In addition, controlled-release ibutilide formulations significantly decreased DFT requirements. Thus, ibutilide-polymeric controlled-release matrix systems may be useful in conjunction with implantable defibrillators in preventing ventricular arrhythmias and reducing defibrillation energy requirements.

Animals↗

PubMed1994

Chemiluminescent hybridization assay for hepatitis delta virus RNA in serum.

A nonradioactive hybridization assay for the detection of hepatitis delta virus RNA in serum is described. This assay utilizes a digoxigenin-labeled RNA hybridization probe and chemiluminescent immunodetection. The probe can detect as little as 0.4 pg of cDNA with a 60-min exposure. Results obtained are in agreement with serological indicators of hepatitis delta virus infection and are comparable to those obtained by hybridization assays employing radioactively labeled RNA.

Evaluation Studies as Topic↗

PubMed1994

Intravertebral pressure changes caused by spinal microtrauma.

Clinical studies indicate variations in intravertebral pressures in patients with and without low back pain. It is known that not all patients with back pain have abnormal lumbar radiographs and, furthermore, microfractures of the endplate may be one of the causes in the origin of low back pain. Consequently, this study was conducted to determine the interrelationship between microtrauma and intraosseous pressures in the lumbar spine. Miniature pressure transducers were inserted into the vertebral bodies and spinous processes of human cadaver spinal units. Radio-opaque medium was injected into the nucleus to fluoroscopically monitor the movement of the fluid from the disc as the preparation was loaded up to the initiation of microtrauma (before reaching the ultimate load-carrying capacity). The onset of injury was evidenced by the microfracture of one of the two endplates and impregnation of the contrast medium into the spongiosa. After relaxation, another cycle of loading was applied by limiting the deflections to the maximum compression sustained under the intact configuration. The load, stiffness, and energy-absorbing capacities were lower (P < 0.05) for the injured specimen compared with the intact configuration. The intraosseous pressures were higher (P < 0.05) in the vertebral body and the spinous process of the vertebra where the endplate exhibited microtrauma in the injured cycle compared with the intact cycle. In contrast, the intraosseous pressures in the vertebral body and the spinous process at the level where the endplate remained intact were not significantly different between the two cycles of loading.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Pain inhibition of shoulder strength in patients with impingement syndrome.

Fourteen patients with Stage II or III impingement syndrome (average age 58 years) were studied. Nine patients had full-thickness rotator cuff tears documented by arthrograms. Patients initially underwent a thorough shoulder examination followed by baseline isokinetic strength testing. Abduction/adduction testing was performed utilizing a Biodex dynamometer. Maximum concentric contractions were performed, and values for peak torque (PT), total work (W), and power (P) were obtained. All patients received a subacromial injection of 5 cc 1% lidocaine plus 5 cc 0.5% bupivacaine (Marcaine). After 5 minutes the testing sequence was repeated. Clinically, patients demonstrated marked improvement following injection. Eighty-six percent reported complete pain relief; the remaining two patients reported only mild discomfort at the extremes of motion. Improvement in functional activity of the affected shoulder was noted by all subjects. On manual muscle testing, 13 of 14 patients (93%) demonstrated increased abduction strength; 11 of 14 (79%) had improvement in external rotation. Mean increases in active forward elevation and external rotation were 36 degrees and 11 degrees, respectively (P < .01). Postinjection isokinetic changes in PT, W, and P for abduction/adduction were dramatic. For abduction, all patients showed significant increases in P (mean 82%), W (mean 90%), and PT (mean 48%) (all P < .05). No significant differences in range of motion testing or strength parameters were noted based on the presence or absence of a rotator cuff tear. For adduction, all patients showed significant increases in P (mean 208%), W (mean 183%), and PT (mean 41%) (all P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Animal models of normal aging: relationship between cognitive decline and markers in hippocampal circuitry.

Alzheimer's disease (AD) occurs against a background of cognitive and neurobiological aging. Animal models of normal aging may be used to study the neurobiological structures that are most involved in AD pathology, i.e. hippocampal/cortical systems. For example, spatial learning is dependent upon the integrity of the hippocampus, a structure that is much affected in humans with AD. Spatial learning tasks, such as the Morris water maze, have been used to screen aged rats for cognitive status prior to neurobiological assessment of hippocampal circuitry. Manifestations of the aging process, which are often minimal or entirely obscured in studies comparing young and aged brains, become apparent when the cognitive status of aged animals is taken into account. For example, studies examining the septohippocampal cholinergic system in behaviorally-characterized rodents have shown that there is a decline in many markers for these cholinergic neurons that coincides with severity of spatial learning impairment. Another advantage of cognitive assessment in animal models used to study aging is that it may help to distinguish between those neurobiological changes that are functionally detrimental and those that may represent compensatory adaptations to maintain cognitive function. Age-related changes in two neurobiological measures in the hippocampus are discussed in this report. Alterations in the opioid peptide dynorphin (increased peptide content and prodynorphin mRNA) in hippocampus may contribute to impairment in that the greatest changes occur in those aged rats with severe spatial learning deficits.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1993

The effects of aging on diurnal water intake and melatonin binding in the suprachiasmatic nucleus.

In vitro autoradiography was used to quantify [125I]melatonin binding in young rats and in aged rats that were screened for diurnal drinking prior to neurobiological study. Among the aged subjects studied, some rats exhibited a blunted diurnal rhythm in that a decreased percentage of water was consumed during the dark phase. Other aged animals maintained a strong nocturnal pattern of water intake similar to young rats. The density of [125I]melatonin binding in the suprachiasmatic nucleus (SCN) of the hypothalamus was significantly correlated with diurnal drinking, i.e. lower binding was associated with a more blunted rhythm. Thus, [125I]melatonin binding in the SCN may provide a marker for age-related decline in some aspects of biological functions.

Aging↗

PubMed1993

Peptide splicing in the vacuolar ATPase subunit A from Candida tropicalis.

Subunit A of the vacuolar proton pump appears to be responsible for the ATP hydrolysis which is coupled to the pumping of protons into a variety of intracellular acid compartments, including the fungal vacuole. We report here the cloning and sequence determination of the gene encoding subunit A from Candida tropicalis. Southern blot hybridization analysis indicates that there is a single gene which encodes this protein. The gene contains a single intron at the extreme 5'-end of the coding region. The gene is predicted to encode a polypeptide of 1088 residues with a calculated molecular mass of 119,019 daltons, yet the mature polypeptide appears to be approximately 67 kDa, indicating that this protein probably undergoes the same sort of processing that is evidenced in the homologous protein from Saccharomyces cerevisiae in which an approximately 50-kDa polypeptide (the spacer) is spliced out of the mature protein. The Candida gene, with and without this middle portion, has been expressed in S. cerevisiae and found to restore a Saccharomyces subunit A deletion mutant (tfp1-delta 8) to apparently wild-type growth at pH 7.6, and normal vacuolar acidification. The peptide sequence of the two predicted mature ends is very similar to the sequences of the analogous proteins from Daucus carota, S. cerevisiae, and Neurospora crassa (60.5, 87.4, and 72.9% identity, respectively), but the middle portion bears only very limited homology with the Saccharomyces protein sequence. Processing of the gene product occurs in S. cerevisiae, Escherichia coli, and in rabbit reticulocyte-mediated in vitro translation, indicating that the excision is probably autocatalytic. The limited sequence identity seen between the Saccharomyces and Candida spacer domains may considerably narrow the functionally important regions responsible for the excision event.

Adenosine Triphosphatases↗

PubMed1993

Alterations in [3H]-kainate receptor binding in the hippocampal formation of aged Long-Evans rats.

The present study used in vitro autoradiography to examine the density of [3H]-kainate (KA) binding in subregions of the hippocampal formation and certain cortical areas in young (7-8 months) and aged (27-29 months) Long-Evans rats. In addition, the topography of KA binding in the dentate molecular layer was examined for evidence of reactive reorganization in the aged brain. This investigation of age-related changes in [3H]-KA binding included correlations with the animals' spatial learning performance in a Morris water maze. The results showed an age-related decrease in the density of [3H]-KA binding in several regions of the hippocampal formation (CA3, CA1, hilus) and within related cortical areas (subicular complex, entorhinal cortex, perirhinal cortex). In addition, an expanded zone of KA binding in the molecular layer of the dentate gyrus was observed in the aged group. This expansion of KA binding may reflect sprouting due to a loss of perforant path input to the dentate. The results of additional correlational analyses, however, indicated that these changes in the density and topography of [3H]-KA binding were not strongly correlated with a decline in place learning ability.

Aging↗

PubMed1993

Effects of amygdala central nucleus lesions on blocking and unblocking.

The effects of lesions of the amygdala central nucleus (CN) on blocking and unblocking of appetitive Pavlovian conditioning were examined in 2 experiments with rats. In both lesioned and unlesioned rats, prior pairing of one conditioned stimulus (CS) with a food unconditioned stimulus (US) blocked the acquisition of conditioning to a second CS when a compound of both stimuli was paired with that same US. If the value of the US was increased or decreased when the second CS was added, unlesioned rats acquired substantial conditioning to the second cue (unblocking). Unblocking occurred in lesioned rats only when the US value was increased. In both lesioned and unlesioned rats, unblocking was prevented if the compound cue was paired with the original US prior to the change in US value. These data suggest that the CN is involved in increasing attention to signals for significant events but not in tuning out redundant cues.

Amygdala↗

PubMed1993

Amygdala central nucleus lesions disrupt increments, but not decrements, in conditioned stimulus processing.

The effects of neurotoxic lesions of the amygdala central nucleus (CN) on changes in the associability of a conditioned stimulus (CS) in appetitive Pavlovian conditioning were examined in 2 experiments with rats. In Experiment 1, CN lesions had no effect on the reduction in the associability of a CS produced by preexposure to that cue (latent inhibition). In Experiment 2, CN lesions prevented the enhancement of the associability of a CS that is normally observed when an inconsistent predictive relation is arranged between that CS and another cue. The results support previous claims that the amygdala CN is involved in broad-based incremental, but not decremental, changes in the processing of CSs in Pavlovian conditioning.

Amygdala↗

PubMed1993

Severity of spatial learning impairment in aging: development of a learning index for performance in the Morris water maze.

The Morris water maze task was originally designed to assess the rat's ability to learn to navigate to a specific location in a relatively large spatial environment. This article describes new measures that provide information about the spatial distribution of the rat's search during both training and probe trial performance. The basic new measure optimizes the use of computer tracking to identify the rat's position with respect to the target location. This proximity measure was found to be highly sensitive to age-related impairment in an assessment of young and aged male Long-Evans rats. Also described is the development of a learning index that provides a continuous, graded measure of the severity of age-related impairment in the task. An index of this type should be useful in correlational analyses with other neurobiological or behavioral measures for the study of individual differences in functional/biological decline in aging.

Aging↗

PubMed1993

The nominal group technique: a research tool for general practice?

Qualitative methods are increasingly recognized as valuable, yet practitioners face difficult decisions in their choice of method and the process of analysis. The nominal group technique combines quantitative and qualitative data collection in a group setting, and avoids problems of group dynamics associated with other group methods such as brainstorming, Delphi and focus groups. Idea generation and problem solving are combined in a structured group process, which encourages and enhances the participation of group members. The stages involved in conducting a nominal group are described, and practical problems of its use in a health care setting are discussed with reference to a study of the priorities of care of diabetic patients, carers and health professionals. Some potential applications of the technique in audit and exploratory research are also outlined.

Data Collection↗

PubMed1993

Delta hepatitis: molecular biology and clinical and epidemiological features.

Hepatitis delta virus, discovered in 1977, requires the help of hepatitis B virus to replicate in hepatocytes and is an important cause of acute, fulminant, and chronic liver disease in many regions of the world. Because of the helper function of hepatitis delta virus, infection with it occurs either as a coinfection with hepatitis B or as a superinfection of a carrier of hepatitis B surface antigen. Although the mechanisms of transmission are similar to those of hepatitis B virus, the patterns of transmission of delta virus vary widely around the world. In regions of the world in which hepatitis delta virus infection is not endemic, the disease is confined to groups at high risk of acquiring hepatitis B infection and high-risk hepatitis B carriers. Because of the propensity of this viral infection to cause fulminant as well as chronic liver disease, continued incursion of hepatitis delta virus into areas of the world where persistent hepatitis B infection is endemic will have serious implications. Prevention depends on the widespread use of hepatitis B vaccine. This review focuses on the molecular biology and the clinical and epidemiologic features of this important viral infection.

Animals↗

PubMed1993

Temperature-guided radiofrequency catheter ablation with very large distal electrodes.

BACKGROUND: Previous studies have shown that the size of lesions produced by radiofrequency catheter ablation correlates with the temperature and surface area of the electrode-tissue interface. The purpose of the present study was to compare the effects of ablation using very large distal electrodes (8F, 8 and 12 mm long) with those made by a conventional radiofrequency ablation catheter (distal electrode 8F, 4 mm long). METHODS AND RESULTS: Each catheter had a thermistor in the tip of the distal electrode. Radiofrequency energy (500 kHz) was supplied by a generator that continuously monitored temperature and produced up to 100 W. In 10 dogs, each of the three ablation catheters were introduced percutaneously and positioned under fluoroscopic guidance at disparate left ventricular endocardial sites. Radiofrequency power output was titrated to achieve a temperature of 80 degrees C for 60 seconds at each ablation site. The power required to produce a steady-state temperature of 80 degrees C was directly proportional to electrode size (15 +/- 7, 46 +/- 15, and 62 +/- 32 W using the 4-mm-, 8-mm-, and 12-mm-long electrodes, respectively). Lesions produced by the 8-mm electrode were nearly twice as deep (11 +/- 2.4 versus 6 +/- 1.2 mm, P < .001) and four times as large (905 +/- 410 versus 210 +/- 100 mm3, P < .001) as those made with a conventional 4-mm electrode. Lesions produced by the 12-mm electrode were intermediate in size (depth, 8 +/- 1.2 mm; volume, 465 +/- 225 mm3) and sometimes were associated with charring and crater formation. Ablation with the larger electrodes caused a drop in arterial pressure and more ventricular ectopy than ablation using a 4-mm distal electrode. CONCLUSIONS: Thermistor-equipped elongated ablation electrodes coupled to high-power outputs can reproducibly produce lesions approximately 1 cm in diameter. This system may prove useful for ablation of ventricular tachycardias in patients with coronary artery disease.

Animals↗