Evolution of the IgA heavy chain gene in the genus Mus.

To examine questions of immunoglobulin gene evolution, the IgA alpha heavy chain gene from Mus pahari, an evolutionarily distant relative to Mus musculus domesticus, was cloned and sequenced. The sequence, when compared to the IgA gene of BALB/c or human, demonstrated that the IgA gene is evolving in a mosaic fashion with the hinge region accumulating mutations most rapidly and the third domain at a considerably lower frequency. In spite of this pronounced accumulation of mutations, the hinge region appears to maintain the conformation of a random coil. A marked propensity to accumulate replacement over silent site changes in the coding regions was noted, as was a definite codon bias. The possibility that these two phenomena are interrelated is discussed.

Ipsilesional intentional neglect and the effect of cueing.

BACKGROUND: Contralesional hemispatial neglect may be induced by an attentional deficit where patients are inattentive to or unaware of stimuli in contralesional hemispace, an intentional deficit where patients are unable to act in or towards contralesional hemispace, or both. The deficits associated with ipsilesional neglect have not been as well characterized. Because cueing may be used as a rehabilitative assistive device, we wanted to learn whether the efficacy of an attentional or intentional cue was related to the type of bias. METHODS: We studied a patient with a right frontotemporal stroke who had ipsilesional neglect by using a video apparatus that dissociates sensory-attentional and motor-intentional systems. We also performed a cueing experiment with primarily sensory-attentional cues (i.e., read the letter at the end of the line) and primarily motor-intentional cues (i.e., touch the end of the line). RESULTS AND CONCLUSIONS: Ipsilesional neglect was primarily a motor-intentional deficit with a motor-action bias to the left and a secondary sensory-attentional bias for stimuli to the right. With cueing we found a double dissociation: the rightwards motor-intentional cue improved the primary left-sided intentional bias and the leftwards sensory-attentional cue improved the secondary right-sided attentional bias. Effective rehabilitation strategies need to address both sensory-attentional and motor-intentional deficits in patients with neglect.

Spatial bias: attentional and intentional influence in normal subjects.

Normal subjects often demonstrate a spatial bias on line bisection (LB) and cancellation (CA) tasks. We wanted to learn if horizontal spatial bias found in normal subjects may be dissociable into sensory-attentional (ATT) and motor-intentional (INT) subgroups similar to those described in brain-injured patients with spatial neglect. We studied the influence of ATT and INT factors on the spatial bias observed in normal subjects using a new technique that uncouples the direction of action from the direction of attention. This technique also allowed us to test both LB and CA tasks on the same individuals. Our results show that ATT bias significantly influenced performance on an LB task, whereas performance on a CA task was influenced by biases in both the ATT and INT systems. In addition, the overall bias on these two tasks reflects an interaction between the biases induced by the ATT and INT systems that may be in the same or different directions.

Testing memory for self-generated items in dementia: method makes a difference.

OBJECTIVE: To learn how pAD (probable Alzheimer's disease), PD+ ("Parkinson's Plus" syndrome), and control subjects remember internally generated material under different conditions. BACKGROUND: "Self-discovered," or internally generated knowledge, prized by educators and therapists, can bring about considerable behavioral change. Both parietal-temporal-limbic (pAD) and frontal-subcortical dementia (e.g. PD+) cause dysmemory, but may cause different internal-external memory bias. pAD subjects, confusing internal and external information (confabulation) and reporting internal information during memory testing (intrusions), may be biased to remember internal material. PD+ subjects, impaired at generative tests, may be externally biased. METHODS: Ten pAD, 5 PD+, and 10 control subjects generated words in a category without instruction to remember (INR), and took a list-learning test of incidental memory for internally and externally generated words. To test how INR influences memory, subjects then generated and attempted to recall four more words. RESULTS: All three subject groups remembered more internally generated than externally provided words without INR. Recall versus recognition of internally generated words differed by group, with PD+ subjects showing greatest improvement with recognition. The pAD subjects performed worse with INR than without INR, had the most intrusion errors, and, rather than demonstrating a release from proactive inhibition, recalled fewer words outside the category. Groups differed in overall recall/recognition improvement (p = 0.015). CONCLUSIONS: Aged subjects preferentially retained internally generated material. However, among demented subjects, memory for internally generated words was influenced by the testing method used. PD+ subjects have poor internal recall, but excellent internal recognition. In pAD, memory for internally generated words may exceed external memory, but only when subjects are not explicitly trying to remember.

Cerebellar degeneration associated with human immunodeficiency virus infection.

Cerebellar disorders associated with HIV infection are typically the result of discrete cerebellar lesions resulting from opportunistic infections such as toxoplasmosis and progressive multifocal leukoencephalopathy or primary CNS lymphoma. Clinical symptoms and pathologic abnormalities related to the cerebellum may also be observed with HIV dementia. A primary cerebellar degeneration with HIV has not previously been reported. Ten patients were identified over an 8-year period at five medical centers. All patients had clinical, laboratory, and radiologic evaluations, and three had neuropathologic examinations. Patients presented with progressively unsteady gait, slurred speech, and limb clumsiness. Examination revealed gait ataxia, impaired limb coordination, dysarthria, and abnormal eye movements. Cognition, strength, and sensory function remained normal. CD4 lymphocyte counts varied between 10 and 437 cells/mm3. Neuroimaging studies showed prominent cerebellar atrophy. Neuropathology showed focal degeneration of the cerebellar granular cell layer and unusual focal axonal swellings in the brainstem and spinal cord. Cultures, histopathology, and immunochemical studies showed no conclusive evidence of infection. We report a syndrome of unexplained degeneration of the cerebellum occurring in association with HIV infection.

Ventral tegmental area injury and frontal lobe disorder.

A patient developed acute behavioral changes implicating frontal-executive dysfunction. His clinical signs suggested mesencephalic injury, and a cranial MRI scan showed an abnormality restricted to a small region of the ventral midbrain. We suggest that the patient's behavioral disorder originated from disruption of the ventral tegmental area or it projections, structures that influence frontal brain processes via the mesocortical dopamine tract.

Anosognosia for hemiplegia: test of the personal neglect hypothesis.

OBJECTIVE: To test the personal neglect hypothesis of anosognosia for hemiplegia (AHP) using selective anesthesia of the right hemisphere. BACKGROUND: Although AHP most commonly follows right-hemisphere injury, the mechanism responsible for this hemispheric asymmetry has not been entirely elucidated. Because denial of ownership of parts on the contralesional side of one's body (personal neglect) also more commonly follows right-hemisphere damage, personal neglect might account for AHP. DESIGN/METHODS: AHP and personal neglect were assessed in 20 patients during right intracarotid barbiturate infusion. With vision restricted to the central field, patients were randomly presented with either their own hands or those of examiners matched for size, gender, and race. Patients were asked to read numbers placed on the hands to establish that hemianopia did not confound hand recognition. RESULTS: All subjects correctly read the numbers on all trials. Only 4 of 20 subjects misidentified their hands and denied awareness of left hemiplegia. All errors occurred for the left hand, indicating personal neglect. However, the 16 subjects without personal neglect also demonstrated AHP. CONCLUSION: Because AHP and personal neglect are dissociable, personal neglect cannot completely account for AHP.

Anosognosia and confabulation during the Wada test.

Feinberg et al. proposed that right-hemisphere-damaged stroke patients with anosognosia for hemiplegia (AHP) confabulate seeing stimuli on the left side but those without AHP admit to having inadequate visual information. This study examines the relationship between AHP and confabulation using selective anesthesia of the cerebral hemispheres. Seventeen patients with intractable epilepsy were tested during intracarotid methohexital infusion. For half of the trials, subjects were stimulated on their paretic hand with a material (sandpaper, metal, or cloth), and for the remaining trials they were not stimulated. The subjects were trained to use a pointing response to indicate if they been stimulated and the type of material they had felt. Admission of uncertainty was defined as pointing to a question mark. Confabulation was defined as any material response to a no-touch trial. During anesthesia of either hemisphere, subjects with and without AHP confabulated responses. The AHP and non-AHP groups did not differ in admission of uncertainty. Our results support the postulate that confabulation and AHP are independent disorders, and therefore confabulation cannot fully account for AHP.

Emotional conversations in Parkinson's disease.

OBJECTIVE: To learn how PD influences verbal description of emotional events. BACKGROUND: Individuals with PD exhibit emotional processing deficits. Emotional experience likely involves several dimensions (e.g., valence, arousal, motor activation) subserved by a distributed modular network involving cortical, limbic, basal ganglia, diencephalic, and mesencephalic regions. Although the neurodegeneration in PD likely affects components in this network, little is known about how PD influences emotional processing. Because PD is associated with activation deficits, one could predict that the discourse of emotional experiences involving high activation would be reduced in patients with PD compared to control subjects. Alternatively, because patients with PD exhibit paradoxical sensitivity to externally evoked motor activation (kinesia paradoxica), it is possible that emotional stimuli may facilitate verbal emotional expression more so in patients with PD than in control subjects. METHODS: The authors measured verbal descriptions of personal emotional experiences in subjects with PD and normal controls. RESULTS: Compared with control subjects, individuals with PD showed a relative increase in the number of words spoken and in discourse duration when talking about emotional experiences that are usually associated with high levels of arousal and motor activation. Although the authors did not measure arousal or activation, prior research has shown that, when asked to recall an emotional experience, people will often re-experience the emotion previously experienced during that episode. CONCLUSIONS: Recalling emotional episodes induces verbal kinesia paradoxica in patients with PD. Although recall of these emotional episodes may have been associated with increased arousal and activation, the mechanism underlying emotional verbal kinesia paradoxica is unclear.

Attentional grasp in far extrapersonal space after thalamic infarction.

Studies of animals and humans with focal brain damage suggest that attention in near and far extrapersonal space may be mediated by anatomically separate systems. Thalamic lesions have been associated with spatial neglect, but whether asymmetric attention specific to near or far space occur after thalamic damage has not been explored. It is also unclear if thalamic injury can induce contralesional defective response inhibition. We tested a woman with a left thalamic infarction who reported that, when driving, she had a tendency to veer towards people or objects on the right side of the road. Our patient and four controls performed a line bisection task with a laser pointer in near and far extrapersonal space. The experimenter marked each bisection either from the right of the presented line (right-distractor, RD) or the left (left-distractor, LD). RD and LD trials were pseudo-randomized. Our patient performed similarly to controls (mean -0.7 mm, controls -0.6 mm) on the line bisection task in near space. In far space she erred significantly rightward compared to her performance in near space (p<0.001). Controls performed similarly in near and far space. The experimenter position did not affect our patient's performance on near line bisections, nor did controls demonstrate a distractor effect for the near condition. In the far condition, however, our patient showed a significant distractor effect (LD -3.3 mm, RD 35.3 mm, p<0.001). Controls also demonstrated a distractor effect in the far condition (LD -6.4 mm, RD 0.7 mm, p<0.01), though of much smaller magnitude. Our results suggest that frontal-thalamic systems regulating visual attention may be disrupted by thalamic infarction. Such damage may produce an attentional grasp specific to far extrapersonal space.

Cognitive and vestibulo-proprioceptive components of spatial ability in Parkinson's disease.

Visual-spatial deficits are often associated with Parkinson's Disease (PD). Recent theories suggest that frontal-basal ganglionic dysfunction affects cognition in PD. Although this hypothesis does not entirely explain spatial deficits in PD, the inappropriate utilization of cues associated with executive dysfunction may induce spatial deficits. Alternatively, the vestibular system is also involved in spatial cognition, and vestibular dysfunction may affect visual-spatial ability in PD. To test these hypotheses, we administered the Water Jar Test, while perturbing vestibulo-proprioceptive input. Non-demented PD patients were significantly less accurate than controls in judging horizontal, and appeared to inappropriately utilize cues. No group effect was found for head tilt. These findings suggest the visual-spatial difficulties seen in PD are related to executive dysfunction that is associated with a disruption of the frontal-basal ganglionic and frontal-parietal systems.

Popliteal arterial aneurysms. Their natural history and management.

Eighty-seven popliteal aneurysms in 62 patients, of which 50 were treated surgically, were reviewed and their clinical characteristics summarized. The need for alertness in the clinical detection of these lesions was stressed. Because complications, namely thrombosis and embolization, were frequent (23% in the total group, 36% in the surgical group), we recommend surgical treatment not only in all symptomatic but also in asymptomatic aneurysms larger than 2 cm in diameter; nonsurgically treated cases must be followed up carefully. With this aggressive approach, no lives and only two limbs were lost (one in a case of irreversible gangrene of the foot). Of the two surgical techniques described, the bypass procedure with autogenous vein graft is, because of its simplicity, given preference over resection with graft.

Ipsilateral neglect: reversal of bias or exaggerated cross-over phenomenon?

When right brain injury produces contralesional neglect (CN), patients typically misbisect lines to the right. However, others demonstrate so-called "ipsilateral neglect" (IN) with misbisection to the left of midpoint. Paradoxically, most patients with CN also demonstrate a 'cross-over' phenomenon whereby they misbisect short lines to the left. It is not known whether patients with IN actually have a contralesional bias opposite the ipsilesional bias observed with CN, or if their performance reflects an exaggerated cross-over. These alternatives can be distinguished by power function analysis which evaluates the relationship between magnitude of perception and stimulus magnitude. Using line bisection tasks to derive a power function, an IN patient showed a reduced exponent (beta = 0.841), falling outside 95% confidence intervals (CI) for controls but within the CI for CN patients. The IN patient showed a greatly increased constant (K = 7.82), extending outside the CI for both controls and CN patients. The results suggest that the anomalous leftward misbisection with IN is associated with an exaggerated cross-over point and not simply reversal of spatial bias.

Crossed apraxia: implications for handedness.

Liepmann posited that right hand preference relates to left hemisphere dominance for learned skilled movements. Limb apraxia, impairment of skilled movement, typically occurs in individuals with left hemisphere (LH) lesions. The occurrence of apraxia in right-handed individuals following right-hemisphere lesions appears to refute Liepmann's hypothesis. We studied the apraxia of a right-handed man, RF, following a right frontal lesion to determine whether his apraxia paralleled the apraxia seen following LH lesions. Results of behavioral testing indicated that, like individuals with apraxia following left frontal lesions, RF was better at gesture recognition than gesture production which was significantly impaired across tasks. Kinematic motion analyses of movement linearity, planarity, and the coupling of temporospatial aspects of movements substantiated the parallel impairments in RF and patients with LH apraxia. The impairment seen in our patient with crossed apraxia provides evidence for the fractionation of systems underlying hand preference and skilled movement.

Rapidly progressive dementia: a clinicopathologic correlation.

We evaluated a 66-year-old man with a rapidly progressive, akinetic-rigid dementia syndrome. Despite extensive testing, which included magnetic resonance imaging (MRI), we were unable to make the correct antemortem diagnosis. Autopsy demonstrated spontaneous progressive multifocal leukoencephalopathy. This report illustrates that even in the absence of characteristic MRI findings, this uncommon cause of dementia should be considered in the differential diagnosis of rapidly progressive, akinetic-rigid syndromes with dementia.

Surgery of large angle exotropia.

In summary, 22 patients have been presented who have undergone lateral rectus recessions ranging from 8 to 14 millimeters. The overall cosmetic success rate (plus or minus 15 diopters of orthophoria) was 77%. Eight of these patients had unilateral recession-resection procedures. Surgically created incomitance ranged from 3 millimeters to 6 millimeters and correlated only poorly with the amount of surgery performed. None of the patients complained of cosmetic or symptomatic effects of the lateral incomitancy induced. We have restricted surgery of the large angle exotrope to a single, two-muscle procedure, thereby decreasing patient morbidity. It is therefore our recommendation that surgery for large angle exotropia be restricted to two horizontal muscles.

Physicians and lawyers: science, art, and conflict.

The relations between physicians and lawyers have deteriorated rapidly over the past several decades, most particulary since the early 70s when the perception that a medical malpractice crisis existed in America became widespread. Some believe that the factors dividing the two professions are linked (1) to professional jealousy, (2) to sometimes conflicting economic interests, or (3) to difficulties in communication, since both professions use many of the same words, or terms of art, but with different intended meanings. While the authors agree that these factors may have aggravated the problem, they believe that the conflict's real roots are in the very different ways in which physicians and lawyers are trained and in the different epistemologies that each profession has accepted, as a result of which each reasons and solves problems in a manner that not only diverges from but sometimes contradicts the other's. The authors conclude that only as the varying epistemologies begin to converge can physicians and lawyers begin to approach problems in more similar ways, and to discover the underlying compatibility of many of their interests and goals.