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Biomedical subjects

D A Robinson

Publications and source records attributed to D A Robinson.

At least 19 recordsLinked to original sources

Measurement of vestibular ocular reflex (VOR) time constants with a caloric step stimulus.

A protocol is described for measuring responses to a broad-band (1-2 Hz) caloric step stimulus from which the vestibular ocular reflex (VOR) and adaptation time constants can be estimated. This novel stimulation is the caloric equivalent to a rotatory step of head acceleration. In this protocol, the ear is irrigated continuously for 5 min with water at a constant temperature. During the initial 2-min period of irrigation the subject is seated and leaning forward in a nonstimulable position (horizontal canals in a horizontal plane). This irrigation phase establishes a steady-state thermal gradient across the horizontal canal, effectively eliminating thermal dynamic properties of the caloric transmission as a confounding factor. At the end of this phase, the subject is rapidly reclined to a stimulable position (horizontal canals in vertical plane) that elicits the VOR nystagmus response to an on-step of force on the cupula. Consistent with adaptation processes, the VOR response first increases and then declines gradually over the 2-min period that the step of force is maintained. Four minutes after the onset of irrigation, the subject is rapidly returned to the nonstimulable position (off-step), which is then maintained for a final 1 min. The response after the off-step, which releases the force on the cupula, reveals reversed after-nystagmus due to adaptation. Five subjects provided caloric step responses for 26 caloric temperature conditions spanning the range from 28.4 to 43.0 degrees C. The resulting responses were fitted with an adaptation model similar to models applied to rotatory acceleration step responses. Estimates of the model parameters for robust caloric stimulation, including time constants for the VOR (18.3 sec) and for vestibular adaptation (153.2 sec), are considered in relation to corresponding values reported in the literature for rotatory and caloric vestibular stimulation. The results suggest that caloric step stimulation can be used successfully to probe VOR dynamics.

Adult↗

Nystagmus induced by pharmacological inactivation of the brainstem ocular motor integrator in monkey.

A common cause of pathological nystagmus is malfunction of the mechanism by which the brain integrates eye velocity signals to produce eye position commands. For horizontal gaze, neurons in the nucleus prepositus hypoglossi-medial vestibular nucleus region (NPH-MVN) play a vital role in this neural integrator function. We studied the effects on gaze stability of pharmacological intervention in the NPH-MVN of monkeys by microinjections of eight drugs. Agents with agonist or antagonist actions at gamma-aminobutyric acid (GABA), glutamate, and kainate receptors all caused gaze-evoked nystagmus with centripetal eye drifts; glycine and strychnine had no effect. When the GABAA-agonist muscimol was injected near the center of MVN, the eyes drifted away from the central position with increasing-velocity waveforms, implying an unstable neural integrator. The observed effects of these drugs on gaze stability may be related to inactivation either of neurons within NPH-MVN or the cerebellar projections to them that control the fidelity of neural integration. Drugs that influence GABA or glutamine transmission may have a role in the treatment of nystagmus due to an abnormal neural integrator.

Animals↗

Graft dilatation following abdominal aortic aneurysm resection and grafting.

BACKGROUND: It has been suggested that graft dilatation following repair of abdominal aortic aneurysm (AAA) is associated with complications such as anastomotic aneurysm and graft rupture. The purpose of the present study was to document the degree of dilatation observed in grafts after aneurysm repair and to correlate this with any graft-related complications. METHODS: Between January 1987 and December 1992, 219 patients had elective repair of their AAA at St George Hospital. A follow-up ultrasound scan was available for 154 of these patients. The following factors were examined: age, sex, size of aneurysm, type and size of graft, time of follow-up scan, size of graft at follow-up and any graft-related complications. RESULTS: The mean graft dilatation observed in knitted grafts (42.6%; 95% CI: 39.1-46.1%) was significantly greater than that observed for woven grafts (25.5%; 95% CI: 19.0-32.1%; P < 0.0001). There were no graft-related complications. CONCLUSIONS: Graft dilatation is a predictable phenomenon following AAA repair. It is more pronounced in knitted than in woven grafts, but does not necessarily lead to graft-related complications or failure.

Aged↗

Molecular characterization of a globally distributed lineage of serotype 12F Streptococcus pneumoniae causing invasive disease.

These studies have identified a major genetic lineage of capsule serotype 12F Streptococcus pneumoniae, which has maintained two different types of the pneumococcal surface protein A (PspA) virulence factor and caused invasive disease in geographically disjoint locations. Twenty outbreak strains from a Texas jail and Maryland day care center and 16 reference strains from Texas, Maryland, Washington, Michigan, Oklahoma, Missouri, Alaska, and Australia were examined. Although the Texas and Maryland outbreak strains were indistinguishable by IS1167 and boxA genotyping procedures, all strains examined were members of a genetically similar lineage. The microevolutionary history of pspA differed from that of the overall genetic background of the strains. Taken together, these findings suggested that the Texas and Maryland outbreaks were caused by different clones of a major genetic lineage of serotype 12F pneumococci, within which at least one PspA has been acquired via localized genetic recombination.

Amino Acid Sequence↗

The IS1167 insertion sequence is a phylogenetically informative marker among isolates of serotype 6B Streptococcus pneumoniae.

The phylogenetic utility of the IS1167 insertion sequence was examined with restriction fragment length polymorphism (RFLP) analyses of a sample of 50, predominantly invasive, capsular serotype 6B Streptococcus pneumoniae isolates previously characterized by multilocus enzyme electrophoresis (MLEE). The strains represented a genetically diverse assemblage of 34 distinct clonotypes composed of 26 restriction fragment types and 23 multilocus enzyme types. All isolates carried the IS1167 insertion sequence, with an average of 9.5 copies. The cross-classification of isolates based on RFLP and MLEE typing schemes was 81% concordant. Phylogenetic analyses demonstrated a significant (P < 0.0001) association between strains of a given RFLP lineage with those of a given MLEE lineage. A significant correlation (P < 0.00004) was also found between the proportion of restriction fragments shared by any given pair of isolates and their genetic distances estimated from the MLEE data. Parity between the two genetic markers implied that the sampled isolates were in linkage disequilibrium. The existence of nonrandom associations among genetic loci was confirmed by Monte Carlo analyses of the MLEE data. These studies, thus, demonstrated that invasive pneumococcal isolates of a single capsule type recovered on a regional scale can retain a largely clonal population structure over a period of 8 years. The ability to detect linkage disequilibrium and generate relatively congruent dendrograms based on distance and parsimony methods suggested that the restriction fragment data were robust to phylogenetic analysis.

Arctic Regions↗

Administration of ATP-MgCl2 after trauma-hemorrhage and resuscitation restores the depressed cardiac performance.

Although adenosine triphosphate (ATP)-MgCl2 has been shown to improve cardiac performance under normal and postischemic conditions, it is not known whether this agent has any salutary effects on cardiac performance following trauma-hemorrhage and crystalloid resuscitation. To determine this, rats underwent laparotomy (i.e., trauma induction) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximum shed blood volume was returned in the form of Ringer's lactate. The animals were then resuscitated with four times the volume of shed blood using Ringer's lactate over 60 min and received either ATP-MgCl2 (50 mumole/kg body wt) in 1 ml volume or an equivalent volume of normal saline intravenously over 95 min. Maximum dP/dt during contraction as well as relaxation (+/-dP/dtmax) and ventricular peak systolic pressure (VPSP) were determined 15 min prior to the end of resuscitation and every 30 min thereafter for 4 hr after the completion of resuscitation. The results indicate that both -dP/dtmax and +dP/dtmax decreased significantly beginning at 0 and 2 hr after the completion of resuscitation, respectively, and remained depressed throughout the duration of the study in saline-treated animals. In addition, VPSP was significantly depressed at 2-4 hr after resuscitation. Treatment with ATP-MgCl2, however, restored these parameters. Moreover, the depressed heart rate was also restored following ATP-MgCl2 administration. Since ATP-MgCl2 restores various left ventricular performance parameters, this agent appears to be a promising adjunct for improving cardiac function after trauma and hemorrhage, even in the absence of blood resuscitation.

Adenosine Triphosphate↗

The oculomotor integrator: testing of a neural network model.

An important part of the vestibulo-ocular reflex is a group of cells in the caudal pons, known as the neural integrator, that converts eye-velocity commands, from the semicircular canals for example, to eye-position commands for the motoneurons of the extraocular muscles. Previously, a recurrently connected neural network model was developed by us that learns to simulate the signal processing done by the neural integrator, but it uses an unphysiological learning algorithm. We describe here a new network model that can learn the same task by using a local, Hebbian-like learning algorithm that is physiologically plausible. Through the minimization of a retinal slip error signal the model learns, given randomly selected initial synaptic weights, to both integrate simulated push-pull semicircular canal afferent signals and compensate for orbital mechanics as well. Approximately half of the model's 14 neurons are inhibitory, half excitatory. After learning, inhibitory cells tend to project contralaterally, thus forming an inhibitory commissure. The network can, of course, recover from lesions. The mature network is also able to change its gain by simulating abnormal visual-vestibular interactions. When trained with a sine wave at a single frequency, the network changed its gain at and near the training frequency but not at significantly higher or lower frequencies, in agreement with previous experimental observations. Commissural connections are essential to the functioning of this model, as was the case with our previous model. In order to determine whether a commissure plays a similar role in the real neural integrator, a series of electrical perturbations were performed on the midlines of awake, behaving juvenile rhesus monkeys and the effects on the monkeys' eye movements were examined. Eye movements were recorded using the coil system before, during, and after electrical stimulation in the midline of the pons just caudal to the abducens nuclei, which reversibly made the integrator leaky. Eye movements were also recorded from two of the monkeys before and after a midline electrolytic lesion was made at the location where stimulation produced a leaky integrator. This lesion disabled the integrator irreversibly. The eye movements that were produced by the monkeys as a result of these perturbations were then compared with eye movements produced by the model after analogous perturbations. The results are compatible with the hypothesis that integration comes about by positive feedback through lateral inhibition effected by an inhibitory commissure.

Algorithms↗

Pentoxifylline restores the depressed cardiac performance after trauma-hemorrhage and resuscitation.

Although studies have shown that pentoxifylline (PTX) improves tissue perfusion and hepatocellular function after trauma-hemorrhage and resuscitation, it is not known whether this agent has any beneficial effects on left ventricular performance under such conditions. To study this, rats underwent laparotomy (i.e., trauma induced) and were bled to and maintained at a blood pressure of 40 mm Hg until 40% of the maximum shed blood volume was returned in the form of Ringer's lactate. The animals were then resuscitated with four times the volume of shed blood with Ringer's lactate over 60 min, following which PTX (50 mg/kg body wt) or an equivalent volume of normal saline was infused intravenously over 100 min. Maximum dP/dt during contraction (+dP/dtmax) and relaxation (-dP/dtmax), maximum rate of a "pressure-normalized" change in ventricular pressure during ventricular contraction (dP/dtmax/P), and ventricular peak systemic pressure (VPSP) were determined at 15 min before the completion of resuscitation and every 30 min up to 4 hr after resuscitation. The results indicated that both +dP/dtmax and -dP/dtmax decreased significantly beginning at 0.5 h after resuscitation and remained depressed throughout the study period in saline-treated animals. In addition, VPSP was significantly depressed at 2.5 to 4 hr after resuscitation. Treatment with PTX, however, significantly improved the above parameters as well as dP/dtmax/P and heart rate. Since PTX restores various left ventricular performance parameters, this agent appears to be a useful adjunct for improving cardiac function after trauma and hemorrhagic shock, even in the absence of blood resuscitation.

Animals↗

Evidence for the simultaneous expression of two PspAs by a clone of capsular serotype 6B Streptococcus pneumoniae.

Pneumococcal surface protein A (PspA) has been shown to be a serologically variable virulence factor of Streptococcus pneumoniae. In mice, PspA can elicit antibodies capable of protecting them against otherwise fatal infections with encapsulated pneumococci. In previous studies it has been reported that almost all isolates have two apparently unlinked genomic sequences that are highly homologous to the 5' and 3' halves of Rx1 pspA, although out MAbs to PspA have not detected more than one PspA in any given isolate of S. Pneumoniae. Recently, we have identified four isolates from a clone of capsular serotype 6B pneumococci (MC25-28) that simultaneously express two distinct PspAs. Each of the isolates (MC25-28) exhibited the same two Kpn I fragments (each containing a Hind III site) that hybridized with Rx1 pspA. MAbs specific for PspA detected two PspAs characterized by different molecular weights and different serologic patterns of reactivity (PspA type 6 detected by MAbs XiR278 and 2A4, and PspA type 34 detected only by MAb 7D2) in each of the four isolates. In previous studies XiR278 and 2A4 frequently have been observed to react with PspA epitopes of the same strain. Based on molecular weight data both epitopes were always present on the same molecule. Our present findings raise the possibility that pneumococci make a second serologically variable PspA which is generally not detected by currently available MAbs to PspA.

Antigens, Bacterial↗

Synchronous, bilateral mastectomy.

Sixty-four patients (mean age, 51 years) had mastectomies which were synchronous and bilateral. Sixty-one premastectomy biopsies (bilateral, 34 and unilateral, 27) demonstrated the following: invasive carcinoma, 17; noninvasive carcinoma, 24; combination of above, 10; and benign disease, 10. Twenty-two patients had bilateral mastectomy because of bilateral positive biopsy. Twenty-nine patients with unilateral carcinoma on biopsy had bilateral mastectomy. Thirteen patients had bilateral mastectomy despite benign disease only on biopsy (10) or no biopsy (3). Ten unexpected carcinomas (34%) were found in the contralateral breast in the 29 patients with carcinoma diagnosed on unilateral biopsy. The biopsy pathology of these 10 specimens was invasive ductal carcinoma in 1 and multifocal, noninvasive carcinoma (ductal, 3 and lobular, 6) in 9. An unexpected carcinoma may be found in the contralateral breast in a significant number of patients who are selected for bilateral mastectomy, particularly if the selection is on the basis of a noninvasive, lobular histology. Bilateral mastectomy may be appropriate for such patients, particularly when complicated by a strong family history and breasts which are difficult to assess by physical or mammographic examination.

Adult↗

Gain changes of the cat's vestibulo-ocular reflex after flocculus deactivation.

Motor learning can be demonstrated in the vestibulo-ocular reflex (VOR) by changing its gain (eye velocity/head velocity) with goggles and optokinetic (OK) drums. It is known that the flocculus is essential for this plasticity but there is controversy about whether the modifiable synapses mainly responsible are in the flocculus. To investigate this further we utilized the known reciprocal relationship between complex spikes and simple spikes in Purkinje cell discharges. By stimulating climbing fibers from the olive to the flocculus at 7 Hz, the simple spike rate of almost all recorded floccular cells could be driven to zero. This was termed floccular shutdown and it felt to effect a functional, reversible flocculectomy. Sixty single units in the flocculi of four cats were recorded. Stimulation of the climbing fibers at 7 Hz caused the discharge rate to decrease to zero in 95% of these cells. The gain of the horizontal VOR in three cats was driven repeatedly to twice or half its normal value by rotation within a moving OK drum and also by wearing magnifying or fixed-field goggles; this process required 3 days. If, on the 4th day, the cat was exposed to an OK drum rotating in the opposite direction, the gain was driven back to normal in 30 min. If, however, the climbing fibers were stimulated at 7 Hz during these 30 min, the gain did not return--learning was blocked. This verified that loss of floccular activity by this method abolishes VOR gain plasticity. Moreover, when 7 Hz stimulation first began, after 3 days of adaptation, the adapted gain remained at its adapted value, either half or twice normal, even in the face of floccular shutdown. This result appears incompatible with the hypothesis that the modifiable synapses are in the flocculus.

Adaptation, Physiological↗

The natural history of asymptomatic carotid artery disease.

PURPOSE: The purpose of this article is to determine the natural history of carotid artery disease among asymptomatic patients with cervical bruits or other risk factors for stroke and to study the value of duplex ultrasonography in predicting future neurologic events. METHODS: Two hundred forty-two asymptomatic, unoperated patients, referred for evaluation of asymptomatic carotid artery disease, were followed prospectively with duplex ultrasonography. RESULTS: Fifteen ischemic strokes (6.2%) and 20 transient ischemic attacks (TIA) (8.3%) occurred in 34 patients during a mean follow-up of 27.4 months. Annual stroke, TIA, and combined event rates were 2.7%, 3.6%, and 6.2%, respectively. Although patients with 80% to 99% lesions had a 20.6% annual event rate, most events occurred contralateral to these lesions; the vessel-specific annual event rate for 80% to 99% disease was 5.1%. Only one of 15 strokes occurred ipsilateral to an 80% to 99% stenosis. Echolucent plaques were associated with TIA and stroke (5.7% annual vessel event rate vs 2.4% for echogenic plaques, p = 0.03). Disease progression was highly correlated with TIA and stroke (p < 0.0001), but it usually occurred in association with rather than before ischemic events, thus proving more useful in explaining pathogenesis than in predicting future events. There was no association between aspirin use and TIA, but patients taking aspirin had a threefold higher annual stroke rate (1.6% vs 4.8%, p = 0.027). CONCLUSIONS: This study, while confirming significant risk for asymptomatic patients with critical stenosis or echolucent plaque, demonstrates the importance of contralateral disease and the absence of orderly progression from minimal disease through high-grade stenosis to symptomatic cerebral ischemia. TIA and stroke commonly occur in association with abrupt, unpredictable, quantum changes in carotid artery disease.

Adult↗

Visually induced cross-axis postsaccadic eye drift.

1. It has been previously shown that, if a visual pattern is transiently moved just after every saccade, it is possible to induce horizontal, postsaccadic, ocular drift after horizontal saccades that persists in the dark. In this study we show that horizontal ocular drift can also be created after vertical saccades. Five human subjects viewed binocularly the interior of a full-field hemisphere filled with a random-dot pattern. They were encouraged to make frequent vertical saccades. During training, eye movements were recorded by the electrooculogram. A computer detected the end of every saccade and immediately moved the pattern to the left after up saccades and right after down saccades. The motion was exponential, its amplitude was 25% of the vertical component of the antecedent saccade, its time constant was 50 ms. Before and after 2-3 h of training, movements of both eyes were measured by the eye-coil/magnetic-field method while subjects were instructed to make vertical saccades in the dark, in the presence of the movable adapting pattern, and between stationary targets for calibration. 2. After training (approximately 20,000 saccades) all subjects developed a zero-latency, exponential ocular drift to the left after up saccades and to the right after down saccades. The amplitude of the horizontal drift, expressed as a percentage of the vertical component of the preceding saccade, was 2.7% in the dark. This rose to 10.2% in the presence of the movable adapting stimulus. The latter rise is not due to visual following systems but to a zero-latency increase in initial drift velocity. 3. The horizontal drifts were usually unequal between the two eyes, indicating the presence of disconjugate movements. We measured intrasaccadic disconjugate horizontal movements of all subjects. In agreement with studies by others of saccades in the light, we measured a divergence during up saccades (1.3 degrees) and a convergence for down (0.4 degrees), but in this case for spontaneous saccades in the dark. After training, these values increased for saccades in the dark but decreased in the light in the presence of the adapting stimulus. These changes were largely idiosyncratic and statistically significant in only a few subjects. 4. The cross-axis postsaccadic drifts were separated into their conjugate and disconjugate components. The disconjugate components were small and idiosyncratic, and the means were small for saccades in the dark. The only consistent trend was in the presence of the adapting stimulus where up saccades were often followed by convergence.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗

A neural network model of the vestibulo-ocular reflex using a local synaptic learning rule.

Vertebrates use the vestibulo-ocular reflex to maintain clear vision during head movements. This reflex requires eye-velocity commands from the semicircular canals to be integrated (mathematically) to produce eye-position commands for the extraocular muscles. This is accomplished by a neural network in the caudal pons. A model of this network is proposed using positive feedback via lateral inhibition. The model has been adapted to a learning network. We have developed a synaptic learning rule using only local information to make the model more physiological.

Algorithms↗