Biomedical subjects

M Harvey

Publications and source records attributed to M Harvey.

At least 91 records · Page 5Linked to original sources

PubMed1996

Expression of a bovine kappa-CN cDNA in the mammary gland of transgenic mice utilizing a genomic milk protein gene as an expression cassette.

Transgenic mice were produced by microinjection of a DNA construct composed of the bovine kappa-casein (kappa-CN) cDNA under the control of the goat beta-CN 5' promoter elements and 3' flanking regions into pronuclear-stage embryos. The gene construct targeted the expression of bovine kappa-CN RNA to the mammary gland and secretion of bovine kappa-CN in the milk. In the three lines studied (BC-7, BC-31 and BC-67) the transgene was stably integrated and propagated as a Mendelian locus. Expression of the bovine protein in lactating mice from the three transgenic lines was demonstrated by northern and western blots. In ten different tissues analysed by northern blotting, expression was confined to the mammary gland of lactating transgenic mice from line BC-7, with low-level expression also observed in the salivary gland of lines BC-31 and BC-67. Transgene expression in the mammary gland paralleled normal casein gene expression during lactation and was not observed in virgin females. The level of bovine kappa-CN mRNA expression on day 10 of lactation in hemizygous transgenic females in relation to endogenous mRNA of whey acid protein (WAP) gene expression was 14%, 69%, and 127% in lines BC-7, BC-31 and BC-67, respectively. No association between transgene copy number and expression was observed. The bovine kappa-CN concentration in milk on day 10 of lactation ranged from 0.94 to 3.85 mg of protein per ml of milk. The bovine kappa-CN expressed in mouse milk had the same molecular mass and immunoactivity with polyclonal antibodies as did kappa-CN from bovine milk. A high degree of variation in the production of bovine kappa-CN within each of the transgenic lines was observed.

Amino Acid Sequence↗

PubMed1996

Visuomotor sensitivity for shape and orientation in a patient with visual form agnosia.

We have previously demonstrated that a patient with visual form agnosia (DF), who is unable to report the orientation or size of visual targets, can nevertheless use these same visual attributes to control motor acts. In the first of three new experiments, we found that DF is able to grasp everyday tools and utensils proficiently (i.e. with a well-formed hand posture) but has difficulty in visually selecting the correct part of the object to grasp (e.g. the handle) for subsequent use of that object. A second experiment revealed that DF's visuomotor system is able to adjust concurrently to variations in both the size and orientation of target objects; when these visual attributes were both varied, she adjusted both her grip aperture and the orientation of her hand well in advance of target contact. These spared visuomotor abilities do not seem to extend to shape processing per se, however. In the final experiment we found that DF was insensitive to changes in the orientation of a cross-shaped object, where no single principal axis could be extracted to control orientation of the grasp. These observations extend our knowledge of DF's residual visuomotor abilities, and suggest limitations on the visual processing capacities of the human dorsal stream.

Adult↗

PubMed1996

Prospective randomized comparison of anodal monophasic shocks versus biphasic cathodal shocks on defibrillation energy requirements.

Biphasic shocks are believed to be superior to monophasic shocks. Monophasic anodal shocks, as opposed to cathodal shocks, are associated with improved defibrillation energy requirements (DERs). However, it is unclear how the DER of anodal monophasic shocks compare with conventional biphasic shocks. Therefore the purpose of this study was to prospectively compare the DER of an anodal monophasic shock with that of a cathodal biphasic shock. A transvenous defibrillation lead with distal and proximal shocking electrodes was used. The subjects of this study were 20 consecutive patients with a mean age of 64.2 +/- 10.5 years ( +/- SD) and a mean left ventricular ejection fraction of 0.36 +/- 0.18. Six had had cardiac arrest. The DER, defined as the lowest energy that converted ventricular fibrillation to sinus rhythm, was determined twice with a step-down protocol (25 J, 20 J, 15 J, 10 J, 5 J, 3 J, 1 J). If the DER was > or = 25 J, then a subcutaneous patch was deemed necessary for system implantation. In random order the DER was determined with a monophasic anodal shock (distal electrode positive) and then with a cathodal (first phase, distal electrode negative) biphasic shock. The mean DER with anodal monophasic shocks was 15.1 +/- 8.5 J compared with 13.6 +/- 8.1 J with cathodal biphasic shocks (p = 0.4). A DER > or = 25 J was present in three patients with the monophasic waveform and in three patients with the biphasic waveform (p = NS). In conclusion, the DER and frequency of subcutaneous patch use with an anodal monophasic waveform is comparable to that obtained with cathodal biphasic waveform.

Aged↗

PubMed1996

Atrioventricular node properties in patients with accessory pathways.

A study during the era of surgical ablation suggested that atrioventricular (AV) nodal conduction is faster in patients with accessory pathways than in controls. In the present study, AV nodal characteristics were studied in 30 patients who underwent radiofrequency ablation of an accessory pathway and compared to 23 control patients. Sinus cycle length, AH and HV intervals, AV block cycle length, ventriculoatrial (VA) block cycle length, AV nodal effective refractory period, and VA effective refractory periods were measured in control and postablation accessory pathway patients before and after autonomic blockade with 0.04 mg/kg of atropine and 0.2 mg/kg of propranolol. The mean sinus cycle length in the control and accessory pathway groups did not differ significantly at baseline (798 +/- 211 and 766 +/- 156 msec, respectively) or after autonomic blockade (654 +/- 98 and 649 +/- 108 msec, respectively). The mean AH interval in the accessory pathway group (77 +/- 15 msec) was significantly shorter than in the control group (91 +/- 22 msec; p < 0.05) at baseline; however, there was no difference after autonomic blockade. No other significant differences were observed between the accessory pathway and control groups. These results demonstrate that AV nodal properties of patients with accessory pathways are not significantly different from controls and suggest that previously reported differences may have been due to selection bias.

Adult↗

PubMed1996

Comparison of atrial-His intervals in patients with and without dual atrioventricular nodal physiology and atrioventricular nodal reentrant tachycardia.

The purpose of this study was to compare the atrial-His intervals generated during programmed atrial stimulation in patients with and without dual atrioventricular nodal physiology and with and without inducible atrioventricular nodal reentrant tachycardia. Programmed atrial stimulation at a basic-drive cycle length of 500 to 600 msec was performed in 180 patients. The minimum atrial-His interval was defined as the atrial-His interval of the basic-drive beats. The maximum atrial-His interval was defined as the longest A2H2 interval. The criterion for dual atrioventricular nodal physiology was an increment of 50 msec in the A2H2 interval in association with a 10 msec decrement in the A1A2 interval. The minimum atrial-His interval was significantly shorter (106 +/- 34 msec vs 116 +/- 29 msec; p < 0.05) and the maximum atrial-His interval significantly longer (304 +/- 101 msec vs 222 +/- 56 msec; p < 0.001) in the 87 patients who had atrioventricular nodal reentry than in the 93 patients who did not. Among the 87 patients who had atrioventricular nodal reentry, the maximum atrial-His interval was significantly longer in 53 patients who had dual atrioventricular nodal physiology than in 34 patients who did not (340 +/- 105 msec vs 249 +/- 62 msec; p < 0.001). Among the 66 patients who had dual atrioventricular nodal physiology, the maximum atrial-His interval was significantly longer in 53 patients who had atrioventricular nodal reentry than in 13 patients who did not (340 +/- 105 msec vs 268 +/- 61 msec; p < 0.01). The insensitivity of the conventional dual atrioventricular nodal physiology criterion for the detection of dual atrioventricular nodal pathways is in part attributable to a lesser degree of slowing of conduction in the slow pathway relative to the fast pathway in some patients who have atrioventricular nodal reentry. The inability to demonstrate atrioventricular nodal reentry despite the presence of dual atrioventricular nodal physiology in some persons may be attributable in part to an inadequate degree of conduction delay in the slow pathway.

Atrioventricular Node↗

PubMed1996

Comparison of the ages of tachycardia onset in patients with atrioventricular nodal reentrant tachycardia and accessory pathway-mediated tachycardia.

Atrioventricular nodal reentrant tachycardia and accessory pathway-mediated tachycardia may have different ages of tachycardia onset. Symptom onset data were obtained in 519 patients (atrioventricular nodal reentrant tachycardia, 231, accessory pathway-mediated tachycardia, 288). The mean age of the patients at the time of evaluation was 47 +/- 17 years (atrioventricular nodal reentrant tachycardia) and 37 +/- 15 years (accessory pathway-mediated tachycardia). The mean age of symptom onset was 32 +/- 18 years for atrioventricular nodal reentrant tachycardia and 23 +/- 14 years for accessory pathway-mediated tachycardia. A significantly greater proportion of patients with atrioventricular nodal reentrant tachycardia had the initial onset of symptoms after the age of 20 years (atrioventricular nodal reentrant tachycardia, 67% vs accessory pathway-mediated tachycardia, 41%, p < 0.001). In summary, there is a different mean age of symptom onset for patients with atrioventricular nodal reentrant tachycardia and accessory pathway-mediated tachycardia.

Adult↗

PubMed1996

Evaluation and extraction of the Accufix atrial J lead.

The Accufix (Telectronics Pacing Systems, Englewood, Colo.) atrial active fixation pacemaker lead has a preformed J stiff retention wire that can fracture and erode through the atrium. We screened 85 patients with digital fluoroscopy and detected 18 (21%) lead fractures. Fourteen (16%) leads were successfully extracted by percutaneous techniques. The mean time for extraction and placement of a new atrial lead was 109 +/- 53 min, and a lead > 1 year old but not in the presence of a fracture was associated with a significantly longer extraction time. There were two extraction complications. One patient had a fever following the extraction, and one patient had a focal sensory deficit 1 week after the extraction probably caused by a paradoxical embolus. Standard percutaneous extraction tools can be used for successful and safe removal of a fractured Accufix lead.

Aged↗

PubMed1996

Use of isoproterenol during programmed ventricular stimulation in patients with coronary artery disease and nonsustained ventricular tachycardia.

Twenty-three consecutive patients (20 men and 3 women) with coronary artery disease and nonsustained ventricular tachycardia (VT) in whom sustained VT was not inducible in a baseline electrophysiology test underwent repeated testing during isoproterenol infusion to determine the inducibility of sustained monomorphic VT. After the baseline study, each patient received a 2 to 4 microgram/min infusion of isoproterenol (mean 2.5 +/- 0.8 microgram/min). The sinus cycle length shortened by a mean of 29% +/- 9% and programmed stimulation was repeated. Nineteen patients had no inducible sustained, monomorphic VT, two patients had only inducible nonsustained VT, and two patients had ventricular fibrillation. Patients were followed up for 10 to 20 months (mean 14.4 +/- 2.9 months) and had no syncope, sustained monomorphic VT, or sudden death. Isoproterenol infusion during programmed stimulation in patients with coronary heart disease and nonsustained VT does not facilitate the induction of sustained monomorphic VT.

Aged↗

PubMed1996

Slow pathway ablation in patients with documented but noninducible paroxysmal supraventricular tachycardia.

OBJECTIVES: The purpose of this study was to assess the clinical efficacy of radiofrequency ablation of the slow pathway in patients with documented but noninducible paroxysmal supraventricular tachycardia (PSVT) who have evidence of dual atrioventricular (AV) node pathways. BACKGROUND: Patients with a documented history of PSVT at times do not have inducible PSVT in the electrophysiology laboratory. Because dual AV node pathways serve as the substrate for AV node reentrant tachycardia (AVNRT), ablation of the slow pathway potentially may be useful in these patients. METHODS: The subjects in this prospective study were seven consecutive patients who underwent an electrophysiologic procedure because of documented PSVT and were found to have dual AV node physiology or inducible single AV node echo beats, but no inducible PSVT despite the administration of isoproterenol and atropine. Their mean (+/- SD) age was 33 +/- 13 years, and they had been symptomatic for 12 +/- 12 years. The frequency of the episodes of PSVT ranged from > or = 1/day to 1/month. The rate of the documented episodes ranged from 170 to 260 beats/min, and discrete P waves were not apparent. Slow pathway ablation was performed with 9 +/- 4 applications of radiofrequency energy using a combined anatomic and electrogram mapping approach. RESULTS: All evidence of dual AV node pathways was eliminated in six patients, and dual AV node physiology remained present in one patient. During a mean follow-up period of 15 +/- 10 months (range 8 to 27), no patient had a recurrence of symptomatic tachycardia (success rate 95% confidence interval 65% to 100%). CONCLUSIONS: Slow pathway ablation may be clinically useful in patients with documented but noinducible PSVT who have evidence of dual AV node pathways.

Adult↗

PubMed1996

2:1 atrioventricular block during atrioventricular node reentrant tachycardia.

OBJECTIVES: The purpose of this study was to determine the incidence and to clarify the mechanism of 2:1 atrioventricular (AV) block during AV node reentrant tachycardia induced in the electrophysiology laboratory. BACKGROUND: In patients with 2:1 AV block during AV node reentrant tachycardia, the absence of a His bundle potential in the blocked beats has been considered evidence of intranodal, lower common pathway block. METHODS: In consecutive patients with AV node reentrant tachycardia, the incidence of 2:1 AV block and the response to atropine and a single ventricular extrastimulus was observed. RESULTS: Persistent 2:1 AV block occurred in 13 of 139 patients with AV node reentrant tachycardia. A His bundle deflection was present in the blocked beats in eight patients and absent in five. Patients with 2:1 AV block had a shorter tachycardia cycle length than did patients without such block (mean +/- SD 312 +/- 32 vs. 353 +/- 55 ms, p < 0.01). Atropine did not alter the 2:1 block in any patient. In every patient, a single ventricular extrastimulus introduced during the tachycardia converted the 2:1 block to 1:1 conduction. CONCLUSIONS: The incidence of induced 2:1 AV block during AV node reentrant tachycardia is approximately 10%. The lack of a response to atropine and the consistent conversion of 2:1 block to 1:1 conduction by a ventricular extrastimulus indicate that, regardless of the presence or absence of a His bundle potential in blocked beats, 2:1 block during AV node reentrant tachycardia is due to functional infranodal block.

Adult↗

PubMed1996

Impact of a 12-month exercise program on the physical and psychological health of osteopenic women.

OBJECTIVE: To describe the effect of a supervised physical activity program on the physical and psychological health of osteopenic women. DESIGN: A randomized controlled trial. SETTING: Sherbrooke, Quebec, Canada. PARTICIPANTS: A total of 124 community-living postmenopausal women, between 50 and 70 years of age, with low bone mass took part in the study. INTERVENTION: Subjects allocated to the experimental group performed weight-bearing exercises (walking, stepping up and down from benches), aerobic dancing, and flexibility exercises for 60 minutes, three times a week, over a period of 12 months. All subjects were invited to attend bi-monthly educational seminars covering topics related to osteoporosis. OUTCOME MEASURES: Spinal and femoral bone mineral density (BMD), functional fitness (flexibility, coordination, agility, strength/endurance, cardiorespiratory endurance), psychological well-being, back pain intensity, and self-perceived health. RESULTS: Spinal BMD stabilized in the exercisers while decreasing significantly in the controls (P = .031). No change in femoral BMD was observed in either group (P = .597). Four of the five parameters chosen to evaluate functional fitness, namely flexibility, agility, strength, and endurance, were affected positively by the exercise program (all P < .01). Adjusting for prescores by means of an analysis of covariance revealed a significant difference between the groups in psychological well-being, which favored the exercisers (P = .012). After 12 months, back pain reported by exercisers was lower than that reported by controls (P = .008). Finally, self-perceived health increased in the exercise group, whereas no difference was observed in the control group (P = .790). CONCLUSION: These results suggest that after 12 months, exercising can produce a significant increase above initial levels in the functional fitness, well-being, and self-perceived health of osteopenic women. Intensity of back pain can also be lowered by exercise. The exercise program succeeded in stabilizing spinal BMD but had no effect on femoral BMD.

Aged↗

PubMed1996

Incidence of lead system malfunction detected during implantable defibrillator generator replacement.

Implantable cardioverter-defibrillator (ICD) generator replacement due to a depleted battery is a frequently performed procedure. The frequency with which sensing and defibrillation system failures are identified during device replacement procedures has not been previously described. Therefore, the purpose of this study was to prospectively determine the frequency of lead system malfunction detected at the time of device replacement in 55 consecutive patients undergoing ICD generator replacement. The mean age of the patients was 63 +/- 10 years and 40 of them were men. Forty-nine patients had an epicardial lead system, and six patients had a nonthoracotomy lead system. Four [7%] of these 55 patients were noted to have previously undetected lead system failure, either sensing (n = 3) or defibrillation (n = 1), necessitating system revision. The lead systems that failed were 40 +/- 6 months old (33-49 months). In summary, during ICD generator replacement, previously undetected problems with sensing or defibrillation may be identified in approximately 10% of patients. Therefore, a comprehensive evaluation of the sensing and the defibrillation functions should be an essential component of the ICD generator replacement procedure.

Defibrillators, Implantable↗

PubMed1996

Temperature and impedance monitoring during slow pathway ablation in patients with AV nodal reentrant tachycardia.

INTRODUCTION: Successful radiofrequency ablation of an accessory pathway has been demonstrated to be associated with an electrode-tissue interface temperature of approximately 60 degrees C or an impedance change of -5 to -10 omega. However, the temperature and impedance changes associated with ablation of AV nodal reentrant tachycardia (AVNRT) using the slow pathway approach have not been reported. Therefore, the purpose of this study was to define the temperature and impedance changes achieved during ablation of AVNRT: METHODS AND RESULTS: The study included 35 consecutive patients with AVNRT undergoing radiofrequency ablation of the slow pathway with a fixed power output of 32 W, and using a catheter with a thermistor bead embedded in the distal 4-mm electrode. The procedure was successful in each patient. The steady-state electrode-tissue interface temperature during successful applications of energy was 48.5 +/- 3.3 degrees C (range 42 degrees to 56 degrees C), and the steady-state temperature during ineffective applications was 46.8 degrees +/- 5.5 degrees C (P = 0.03). The mean impedance change during all applications of energy was -1.4 +/- 2.8 omega, and did not differ significantly during effective and ineffective applications. Coagulum formation resulted during five applications (2.7%) in two patients (5.7%). There were no recurrences during 114 +/- 21 days of follow-up. CONCLUSIONS: Successful ablation of AVNRT using fixed power output is achieved at an electrode-tissue interface temperature of approximately 48 degrees C and is associated with a drop in impedance of 1 to 2 omega. These findings suggest that slow pathway ablation requires less heating at the electrode-tissue interface than does accessory pathway or AV junction ablation.

Adult↗

PubMed1996

Randomized comparison of two techniques for titrating power during radiofrequency ablation of accessory pathways.

INTRODUCTION: The purpose of this study was to prospectively compare the value of impedance and temperature monitoring during accessory pathway ablation. Temperature and impedance monitoring can be used during radiofrequency ablation of accessory pathways to titrate power to achieve adequate but not excessive tissue heating. METHODS AND RESULTS: One hundred thirty-two patients with a single accessory pathway were randomly assigned to undergo ablation using either impedance monitoring or temperature monitoring. During impedance monitoring, the endpoint for titration of power was a 5- to 10-omega decrease in the measured impedance while for temperature monitoring the endpoint was to achieve a temperature of 58 degrees to 62 degrees C. Two protocols were used. In protocol 1 (90 patients), impedance monitoring was performed with a nonthermistor catheter and temperature monitoring was performed with a thermistor catheter. In protocol 2 (42 patients), a thermistor catheter was used in all patients. In protocol 1, the success rate (93% vs 93%; P = 1.0), ablation procedure duration (57 +/- 56 vs 41 +/- 41 min), fluoroscopy time (48 +/- 29 vs 41 +/- 23 min; P = 0.3), number of applications (6.2 +/- 4.7 vs 5.7 +/- 4.6; P = 0.8), and the number of applications associated with coagulum formation (0.1 +/- 0.3 vs 0.3 +/- 0.6; P = 0.1) were similar in the two groups. In protocol 2, as in protocol 1, there were no differences in the success rate (91% vs 95%; P = 1.0), ablation procedure duration (49 +/- 37 vs 62 +/- 55 min; P = 0.4), fluoroscopy time (46 +/- 24 vs 49 +/- 36 min; P = 0.8), number of applications (6.8 +/- 7.0 vs 7.8 +/- 12.1; P = 0.7), or number of applications associated with coagulum formation (0.3 +/- 0.6 vs 0.2 +/- 0.7; P = 0.6), between the impedance and temperature monitoring groups. CONCLUSION: Temperature and impedance monitoring are equally effective in optimizing the results of accessory pathway ablation.

Adult↗

PubMed1996

Mutations affecting the development of the embryonic zebrafish brain.

In a large scale mutagenesis screen for embryonic mutants in zebrafish, we have identified 63 mutations in 24 loci affecting the morphogenesis of the zebrafish brain. The expression of marker genes and the integrity of the axonal scaffold have been studied to investigate abnormalities in regionalization, neurogenesis and axonogenesis in the brain. Mutants can be broadly classified into two groups, one affecting regionalization along the anterior-posterior or dorsal-ventral axis, and the other affecting general features of brain morphology. The first group includes one locus that is required to generate the anlage of the midbrain-hindbrain boundary region at the beginning of somitogenesis. Four loci were identified that affect dorsal-ventral patterning of the brain, including the previously described cyclops locus. Mutant embryos of this class show a reduction of ventral neuroectodermal structures and variable fusion of the eyes. The second group includes a large class of mutations affecting the formation of brain ventricles. Analysis of this class reveals the requirement of a functional cardiovascular system for ventricle enlargement during embryogenesis. Mutations in one locus lead to the formation of supernumerary primary neurons, a phenotype reminiscent of neurogenic mutants in Drosophila. Other mutant phenotypes described here range from abnormalities in the fasciculation and outgrowth of axons to defects in the diameter of the neural tube. The identified loci establish the genetic foundation for a further analysis of the development of the zebrafish embryonic brain.

Animals↗

PubMed1996

Mutations affecting neural survival in the zebrafish Danio rerio.

Programmed cell death is a prominent feature of normal animal development. During neurogenesis, naturally occurring cell death is a mechanism to eliminate neurons that fail to make appropriate connections. To prevent accidental cell death, mechanisms that trigger programmed cell death, as well as the genetic components of the cell death program, are tightly controlled. In a large-scale mutagenesis screen for embryonic lethal mutations in zebrafish Danio rerio we have found 481 mutations with a neural degeneration phenotype. Here, we present 50 mutations that fall into two classes (termed spacehead and fala-like) that are characterized by two main features: first, they appear to affect cell survival primarily within the neuroectodermal lineages during somitogenesis, and second, they show an altered brain morphology at or before 28 hours of development. Evidence for the specificity of cell death within the central nervous system comes from visual inspection of dying cells and analysis of DNA fragmentation, a process associated with apoptotic cell death. In mutants, the level of dying cells is significantly increased in brain and spinal cord. Furthermore, at the end of somitogenesis, the cell count of radial glia and trigeminal neurons is reduced in some mutants of the spacehead class. A variety of neurodegenerative disorders in mouse and humans have been associated with abnormal levels of programmed cell death within the central nervous system. The mutations presented here might provide a genetic framework to aid in the understanding of the etiology of degenerative and physiological disorders within the CNS and the activation of inappropriate programmed cell death.

Animals↗

PubMed1996

Conditioned whisking in the rat.

The rat's mystacial vibrissae are active during exploratory and discriminative behaviors, with individual vibrissae serving as elements in a receptive array scanned across object surfaces. To facilitate neurobehavioral analysis of this sensorimotor system, we have developed an experimental paradigm that confines vibrissa movements to a defined physical location, makes possible on-line monitoring of "whisking" activity, and brings such activity under associative control using operant conditioning procedures. Rats were secured, and movements of an identified bilaterally homologous pair of vibrissae (right and left gamma straddlers) were detected by laser-based photodetectors. Subjects were maintained on a water deprivation schedule, and whisker movements were monitored during adaptation to the test situation and after the clipping of other vibrissae on both sides of the snout. Rats were reinforced with water delivery for emitting vibrissa movements in the presence of a conditioned stimulus (tone) whose presentation was made contingent upon a prior period of nonwhisking. The rate and temporal distribution of vibrissa movements were brought under experimental control by means of interval and ratio reinforcement schedules. Although the procedures provide minimal information about the kinematics or topography of conditioned vibrissa movements, they permit the investigator to manipulate response parameters normally under the voluntary control of the animal in a preparation amenable to neurophysiological analysis.

Animals↗

PubMed1996

Development of cancer prevention and control initiatives in a state health agency: the New York experience.

The public health response to cancer in the New York State Department of Health has evolved over many years. A number of organizational units contribute to surveillance and monitoring, quality assurance, policy analysis and advocacy, education, service delivery, and evaluation components. Extensive cooperation with health professionals and consumers outside of state government is also essential.

Adolescent↗