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Biomedical subjects

M A Howard

Publications and source records attributed to M A Howard.

At least 19 recordsLinked to original sources
PubMed2002

Gene transfer of inducible nitric oxide synthase impairs relaxation in human and rabbit cerebral arteries.

BACKGROUND AND PURPOSE: These studies evaluated whether gene transfer of inducible nitric oxide synthase (iNOS) is a sufficient stimulus to produce vascular dysfunction in cerebral arteries. METHODS: Intracranial (pial) arteries were dissected from human brain tissue obtained during elective surgery. Isolated human arteries were incubated in vitro with adenovirus containing iNOS (AdiNOS) or a nonexpressive transgene (control, AdBglII) (500 micro L, 3x10(9) plaque-forming units per milliliter), and vascular function was examined 24 hours later. In anesthetized rabbits, AdiNOS or AdBglII (300 microL 1x10(10)) was injected into the cisterna magna. Three days later, the basilar artery was removed, and reactivity was examined ex vivo. RESULTS: In submaximally precontracted vessels, we observed impairment of NO-dependent relaxation in human cerebral arteries after gene transfer of iNOS. Maximum relaxation to bradykinin (1 micromol/L, an endothelium-dependent agonist) was 77+/-11% (mean+/-SE) after AdBglII and 31+/-22% (P<0.05) after AdiNOS. After AdiNOS, responses to nitroprusside (an endothelium-independent NO donor) also were impaired. Responses to both nitroprusside and bradykinin were improved by aminoguanidine (300 micromol/L), an inhibitor of iNOS. AdiNOS produced no change in vasoconstrictor responses to U46619. In basilar arteries from rabbits examined in vitro after gene transfer in vivo, responses to histamine, serotonin, and nitroprusside all were similar after AdiNOS or AdBglII. In contrast, relaxation to acetylcholine was significantly depressed after AdiNOS. Maximum relaxation to acetylcholine (10 micromol/L) was 90+/-3% after AdBglII and 68+/-5% (P<0.05) after AdiNOS. Relaxation of arteries after AdiNOS was improved by aminoguanidine. CONCLUSIONS: These studies suggest that expression of iNOS may impair NO-dependent relaxation in both human and rabbit cerebral arteries.

Animals↗
PubMed2001

Postmastectomy reconstruction of the previously augmented breast: diagnosis, staging, methodology, and outcome.

Although many of the health and safety issues associated with breast augmentation have been thoroughly discussed over the past decade, the literature is remarkably silent regarding postmastectomy reconstruction of the previously augmented breast. A retrospective review of the senior author's reconstructive practice was performed for the years 1983 through March of 1999, revealing 21 women who underwent postmastectomy breast reconstruction after previous breast augmentation. For purposes of measuring aesthetic results, these 21 patients were matched to a carefully selected control group of 15 patients. They were also compared with other, larger populations, including 777 of the senior author's other breast reconstructions, the breast cancer registry at the Lombardi Cancer Center in Washington, D.C., and several large, published epidemiologic studies. The interval between the previous augmentation and the diagnosis of breast cancer ranged from 9 months to 18 years, with a mean of 9.3 years. None of the previous augmentation implants was ruptured at the time of mastectomy. Of the nine patients with previous subpectoral augmentation, cancer was detected mammographically in five (56 percent), whereas of the 12 patients with previous subglandular augmentation, cancer was first detected mammographically in only three (25 percent). This difference was not statistically significant (p = 0.2). Overall, eight of the study patients' tumors (38 percent) were first detected mammographically, which is similar to other published reports of breast cancer patients in the general population. Seventy-one percent of the 21 study patients were node-negative, which also compares favorably with other published series. Sixteen of the women with previous augmentation (76 percent) had purely prosthetic reconstructions. Flaps were used in the other five reconstructions (23 percent): three latissimus dorsi flaps (14 percent) and two transverse rectus abdominis musculocutaneous flaps (9 percent). All five flaps were used in patients who had undergone radiation therapy. Throughout the senior author's entire reconstructive practice history, transverse rectus abdominis musculocutaneous flaps were more frequently used [282 of 777 nonaugmented reconstructions (36 percent)], whereas latissimus dorsi flaps were less frequently used [17 of 777 nonaugmented reconstructions (2.2 percent)] (p < 0.001). The cosmetic results of the breast reconstructions in the previously augmented study group were generally good-to-excellent, with a mean score by blinded observers of 3.35 of a possible 4.0. These results were comparable to or better than those in the matched controls, who scored a mean of 3.0.

Adult↗
PubMed2001

Single-neuron responses to emotional visual stimuli recorded in human ventral prefrontal cortex.

Both lesion and functional imaging studies in humans, as well as neurophysiological studies in nonhuman primates, demonstrate the importance of the prefrontal cortex in representing the emotional value of sensory stimuli. Here we investigated single-neuron responses to emotional stimuli in an awake person with normal intellect. Recording from neurons within healthy tissue in ventral sites of the right prefrontal cortex, we found short-latency (120-160 ms) responses selective for aversive visual stimuli.

Adult↗
PubMed2001

Consonance and dissonance of musical chords: neural correlates in auditory cortex of monkeys and humans.

Some musical chords sound pleasant, or consonant, while others sound unpleasant, or dissonant. Helmholtz's psychoacoustic theory of consonance and dissonance attributes the perception of dissonance to the sensation of "beats" and "roughness" caused by interactions in the auditory periphery between adjacent partials of complex tones comprising a musical chord. Conversely, consonance is characterized by the relative absence of beats and roughness. Physiological studies in monkeys suggest that roughness may be represented in primary auditory cortex (A1) by oscillatory neuronal ensemble responses phase-locked to the amplitude-modulated temporal envelope of complex sounds. However, it remains unknown whether phase-locked responses also underlie the representation of dissonance in auditory cortex. In the present study, responses evoked by musical chords with varying degrees of consonance and dissonance were recorded in A1 of awake macaques and evaluated using auditory-evoked potential (AEP), multiunit activity (MUA), and current-source density (CSD) techniques. In parallel studies, intracranial AEPs evoked by the same musical chords were recorded directly from the auditory cortex of two human subjects undergoing surgical evaluation for medically intractable epilepsy. Chords were composed of two simultaneous harmonic complex tones. The magnitude of oscillatory phase-locked activity in A1 of the monkey correlates with the perceived dissonance of the musical chords. Responses evoked by dissonant chords, such as minor and major seconds, display oscillations phase-locked to the predicted difference frequencies, whereas responses evoked by consonant chords, such as octaves and perfect fifths, display little or no phase-locked activity. AEPs recorded in Heschl's gyrus display strikingly similar oscillatory patterns to those observed in monkey A1, with dissonant chords eliciting greater phase-locked activity than consonant chords. In contrast to recordings in Heschl's gyrus, AEPs recorded in the planum temporale do not display significant phase-locked activity, suggesting functional differentiation of auditory cortical regions in humans. These findings support the relevance of synchronous phase-locked neural ensemble activity in A1 for the physiological representation of sensory dissonance in humans and highlight the merits of complementary monkey/human studies in the investigation of neural substrates underlying auditory perception.

Acoustic Stimulation↗
PubMed2000

Convergent neuroanatomical and behavioural evidence of an amygdala hypothesis of autism.

In this study we report a convergence of behavioural and neuroanatomical evidence in support of an amygdala hypothesis of autism. We find that people with high-functioning autism (HFA) show neuropsychological profiles characteristic of the effects of amygdala damage, in particular selective impairment in the recognition of facial expressions of fear, perception of eye-gaze direction, and recognition memory for faces. Using quantitative magnetic resonance (MR) image analysis techniques, we find that the same individuals also show abnormalities of medial temporal lobe (MTL) brain structure, notably bilaterally enlarged amygdala volumes. These results combine to suggest that developmental malformation of the amygdala may underlie the social-cognitive impairments characteristic of HFA. This malformation may reflect incomplete neuronal pruning in early development.

Adolescent↗
PubMed2000

Auditory cortex on the human posterior superior temporal gyrus.

The human superior temporal cortex plays a critical role in hearing, speech, and language, yet its functional organization is poorly understood. Evoked potentials (EPs) to auditory click-train stimulation presented binaurally were recorded chronically from penetrating electrodes implanted in Heschl's gyrus (HG), from pial-surface electrodes placed on the lateral superior temporal gyrus (STG), or from both simultaneously, in awake humans undergoing surgery for medically intractable epilepsy. The distribution of averaged EPs was restricted to a relatively small area on the lateral surface of the posterior STG. In several cases, there were multiple foci of high amplitude EPs lying along this acoustically active portion of STG. EPs recorded simultaneously from HG and STG differed in their sensitivities to general anesthesia and to changes in rate of stimulus presentation. Results indicate that the acoustically active region on the STG is a separate auditory area, functionally distinct from the HG auditory field(s). We refer to this acoustically sensitive area of the STG as the posterior lateral superior temporal area (PLST). Electrical stimulation of HG resulted in short-latency EPs in an area that overlaps PLST, indicating that PLST receives a corticocortical input, either directly or indirectly, from HG. These physiological findings are in accord with anatomic evidence in humans and in nonhuman primates that the superior temporal cortex contains multiple interconnected auditory areas.

Acoustic Stimulation↗
PubMed2000

Ethanol-conditioned place preference is reduced in dopamine D2 receptor-deficient mice.

Pharmacological blockade studies have supported a role of the dopamine system in ethanol reward for many years, but receptor subtype specificity has been difficult to establish. Recently, genetically engineered mice lacking functional dopamine D2 receptors have been shown to drink less ethanol in a two-bottle choice task. To determine whether reduced ethanol intake reflects a reduction in ethanol reward, D2 receptor-deficient [knockout (KO)] mice were compared to heterozygous (HET) and wild-type (WT; C57BL/6xDBA/2 F2 hybrid) mice in a place conditioning task. Under conditions that produced reliable place preference in both WT and HET mice, KO mice showed no evidence of place conditioning, suggesting that D2 receptor gene inactivation reduced ethanol reward or the ability to learn about ethanol reward. Consistent with previous findings, this mutation also produced a gene dose-related reduction in basal activity levels. Moreover, KO and HET mice showed enhancement of ethanol-stimulated activity relative to WT mice. However, differences in basal and ethanol-stimulated activity did not explain the differences in place conditioning. Overall, this study strongly supports the conclusion that dopamine D2 receptors normally influence ethanol reward in mice.

Animals↗
PubMed2000

Digital X-ray stereophotogrammetry for cochlear implantation.

Multielectrode, intracochlear implant systems are effective treatment for profound sensorineural hearing loss. In some cases, these systems do not perform well, which may be partially due to variations in implant location within the cochlea. Determination of each electrode's position in a patient's inner ear provides an in vivo basis for both the cochlear modeling of electrical fields and the future design of electrode arrays that deliver electrical stimulation to surviving auditory neurons, and may improve speech processor programming for better speech recognition. We developed an X-ray stereophotogrammetric approach to localize implanted electrodes in three dimensions. Stereophotogrammetry of implanted electrodes is formulated in weak perspective geometry, with knowledge of a three-dimensional (3-D) reference structure and electrode positions in each of two digital stereo-images. The localization error is theoretically, numerically, and experimentally quantified. Both numerical and experimental results demonstrate the feasibility of the technique.

Biomedical Engineering↗
PubMed2000

Experimental study of the magnetic stereotaxis system for catheter manipulation within the brain.

OBJECT: The magnetic stereotaxis system (MSS) is a device designed to direct catheter tips through magnetic forces. In this study the authors tested the safety and performance of the MSS in directing catheters through a nonlinear path to obtain biopsy specimens in pig brains. METHODS: Sixteen pigs underwent biopsy of the frontal brain region with the aid of an MSS (11 pigs) or a standard stereotactic biopsy tool (five pigs). Surgical preparation consisted of placement of six fiducial markers in the skull and the creation of a burr hole for attachment of a cranial bolt and passage of the biopsy catheter. The pigs underwent magnetic resonance (MR) imaging of the head to define a biopsy target and to plan a nonlinear path. Guided by the MSS, which used nearly real-time fluoroscopic imaging fused to the preoperative MR image, the authors advanced a catheter to the biopsy target. A biopsy tool was passed through the catheter and a tissue sample was obtained. The animals were observed for 3 to 5 days postoperatively, when they were assessed for neurological abnormalities or other signs of morbidity. Actual catheter placement was within 1.5 mm of the planned path to the biopsy site, using a minimum path radius of 30 mm. The registration error associated with the use of the MSS x-ray fluoroscopy and MR imaging averaged 1.7 mm. Tissue disruption caused by the MSS was similar to that of standard stereotactic procedures. CONCLUSIONS: The MSS affords accurate and safe guidance of brain catheters in animals. The application tested here, brain biopsy, is one of a number of potential catheter-guided procedures.

Animals↗
PubMed2000

Paraparesis induced by inflammatory contents of a pneumonectomy cavity. Case report.

The authors report on a patient who developed acute-onset paraparesis after underoing a thoracotomy 40 years earlier for a carcinoid adenoma. No infectious or neoplastic origin could be found to explain the patient's current clinical course and radiographic findings. The postoperative events in this case are discussed, as well as the literature regarding postthoracotomy complications.

Carcinoid Tumor↗
PubMed1999

The effect of the aqueous solubility of xanthine derivatives on the release mechanism from ethylcellulose matrix tablets.

Release data from ethylcellulose (EC) matrix tablets was analyzed to determine which release equation provides the best fit to the data and to observe the effect of drug solubility on the release mechanism(s). Tablets were prepared by direct compression of drug, EC, and lubricant in an appropriate mass ratio to achieve a high and a low drug loading. Theophylline, caffeine, and dyphylline were selected as non-electrolyte xanthine derivatives with solubilities from 8.3 to 330 mg/ml at 25 degrees C. Drug release studies were conducted in 37 degrees C water with UV detection at 272 nm. Several equations to characterize release mechanisms were tested with respect to the release data. Drug diffusion, polymer relaxation, and tablet erosion were the mechanisms considered. Parameters were generated and ANOVA data presented by WinNonlin Pro(R) software. The Akaike Information Criterion was also considered to ascertain the best fit equation. At high drug loading, drug was released by a diffusion mechanism with a rate constant that increased with an increase in aqueous solubility. At low drug loading, polymer relaxation also became a component of the release mechanism. However, its contribution to drug release was less pronounced as solubility decreases, becoming negligible in the case of theophylline.

Algorithms↗
PubMed1999

Measurement of the force required to move a neurosurgical probe through in vivo human brain tissue.

The advent of high-precision magnetic and robotic computer-controlled neurosurgery systems makes it necessary to determine the range of forces that will be encountered by the probes of such devices as they are guided through the brain tissues to intraparenchymal targets. We have measured the penetration forces on 2.5-mm spheres and the drag forces on 3.0-mm ventricular shunt catheters advanced 2.0-3.5 cm deep into in vivo human brain tissues (in patients about to have those tissues resected during epilepsy surgery) at rates of approximately 0.33 mm s-1. Penetration forces of (8 +/- 2) grams were found for the spherical probe once it passed 0.5 cm below the cortical surface, and frictional drags of (2.8 +/- 0.3) grams cm-1 were exerted on the catheters. The variable nature of these forces is discussed and the results are compared with earlier studies on experimental animal tissues and brain phantom gelatins. The implications of these results for magnetic and robotic surgery systems are considered.

Biomechanical Phenomena↗
PubMed1999

Temporal encoding of the voice onset time phonetic parameter by field potentials recorded directly from human auditory cortex.

Voice onset time (VOT) is an important parameter of speech that denotes the time interval between consonant onset and the onset of low-frequency periodicity generated by rhythmic vocal cord vibration. Voiced stop consonants (/b/, /g/, and /d/) in syllable initial position are characterized by short VOTs, whereas unvoiced stop consonants (/p/, /k/, and t/) contain prolonged VOTs. As the VOT is increased in incremental steps, perception rapidly changes from a voiced stop consonant to an unvoiced consonant at an interval of 20-40 ms. This abrupt change in consonant identification is an example of categorical speech perception and is a central feature of phonetic discrimination. This study tested the hypothesis that VOT is represented within auditory cortex by transient responses time-locked to consonant and voicing onset. Auditory evoked potentials (AEPs) elicited by stop consonant-vowel (CV) syllables were recorded directly from Heschl's gyrus, the planum temporale, and the superior temporal gyrus in three patients undergoing evaluation for surgical remediation of medically intractable epilepsy. Voiced CV syllables elicited a triphasic sequence of field potentials within Heschl's gyrus. AEPs evoked by unvoiced CV syllables contained additional response components time-locked to voicing onset. Syllables with a VOT of 40, 60, or 80 ms evoked components time-locked to consonant release and voicing onset. In contrast, the syllable with a VOT of 20 ms evoked a markedly diminished response to voicing onset and elicited an AEP very similar in morphology to that evoked by the syllable with a 0-ms VOT. Similar response features were observed in the AEPs evoked by click trains. In this case, there was a marked decrease in amplitude of the transient response to the second click in trains with interpulse intervals of 20-25 ms. Speech-evoked AEPs recorded from the posterior superior temporal gyrus lateral to Heschl's gyrus displayed comparable response features, whereas field potentials recorded from three locations in the planum temporale did not contain components time-locked to voicing onset. This study demonstrates that VOT at least partially is represented in primary and specific secondary auditory cortical fields by synchronized activity time-locked to consonant release and voicing onset. Furthermore, AEPs exhibit features that may facilitate categorical perception of stop consonants, and these response patterns appear to be based on temporal processing limitations within auditory cortex. Demonstrations of similar speech-evoked response patterns in animals support a role for these experimental models in clarifying selected features of speech encoding.

Auditory Cortex↗
PubMed1998

Identification of Australian arboviruses in inoculated cell cultures using monoclonal antibodies in ELISA.

An ELISA using a panel of specific monoclonal antibodies was developed to identify all alpha and flaviviruses isolated from mosquitoes caught throughout Australia. This technique is sensitive and rapid and is more specific than the traditional methods used to identify flaviviruses. The ability to identify unknown virus isolates from field-caught mosquitoes quickly and accurately improves the efficiency of arbovirus surveillance programs and allows health authorities to give an early warning of an increased health risk from a mosquito-borne virus in a particular region.

Aedes↗
PubMed1998

An integrated multipurpose lesion-making electrode.

PURPOSE: Although excellent results are reported from centers using microelectrode mapping during stereotactic pallidotomy, the recording methods used are time-consuming and technically cumbersome. We sought to develop a new electrode concept that may, when eventually applied in clinical practice, improve the efficiency and safety of microelectrode-guided functional neurosurgical procedures. CONCEPT: The scout electrode uses a recently developed research technique for simultaneously obtaining multiple microelectrode recordings along the shaft of a macroelectrode. RATIONALE: By positioning recording sites on either side of a lesion-making contact, it is possible to functionally "scout" the brain tissue surrounding the proposed lesion site, thus eliminating the need for serial movements and electrode interchanges. DISCUSSION: The feasibility of the scout electrode concept was tested using prototypes placed into cat medial geniculate nucleus. High-quality unit recordings were simultaneously obtained from different regions within the medial geniculate nucleus. This ability to physiologically map sites above and below the lesion-making contact facilitated precise placement of radiofrequency lesions in the center of the medial geniculate nucleus. These results suggest that it may be possible to develop clinically useful devices based on this novel concept.

Action Potentials↗
PubMed1998

A combined surgical-endovascular device concept for giant aneurysm neck occlusion.

PURPOSE: In this report, we describe a new multimodality device concept for occluding giant aneurysms. The device is designed to exploit the advantages, and avoid the disadvantages, of conventional microneurosurgery and interventional neuroradiology methods. CONCEPT: Our device concept involves surgically placing small permanent magnets, incorporated into a partially occluded magnetic clip, about the extraluminal neck without mechanically compromising the perforating vessels. These magnets serve as optimally positioned anchor points for ferromagnetic materials subsequently introduced via the endovascular route. RATIONALE: Currently, neurosurgical extraluminal obliteration of giant aneurysms is achieved by mechanically closing the aneurysm neck with metal clip blades, which is a technique that risks inadvertent occlusion of critical perforating vessels. Perforating vessel strokes can largely be avoided using endovascular aneurysm occlusion methods. However, in the setting of the giant aneurysm, these endovascular techniques are associated with high rates of incomplete occlusion. DISCUSSION: Preliminary feasibility tests of this concept were conducted using a simple prototype constructed in our laboratories.

Aneurysm↗
PubMed1998

An illuminating retractor for intracranial microneurosurgery.

During certain microneurosurgical procedures, the illumination provided by current coaxial microscope light sources is suboptimal. One potential solution is the surgical light blade (SLB), a malleable retractor incorporating a flat fiberoptic bundle along its surface. The SLB provides intense illumination within the surgical field without decreasing the amount of limited operating space. A prototype of the SLB was tested in six patients. Results suggest that with further development the SLB could become useful for intracranial microneurosurgery.

Brain Diseases↗