Factor V Leiden gene mutation in three South African families.
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Biomedical subjects
Publications and source records attributed to D Bowers.
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OBJECTIVE: To study the relationship between peripheral autonomic arousal and emotional experience. BACKGROUND: Several theories of emotional experience suggest that this experience is, at least in part, related to feedback from the viscera and the autonomic nervous system. METHOD: To partially test this hypothesis and to learn if there are hemispheric asymmetries of emotional experience, we studied skin conductance responses (SCR) and verbal report in patients with right hemisphere damage (RHD), patients with left hemisphere damage (LHD), and normal control subjects during the anticipation of electric shocks. RESULTS: During the shock condition, RHD and LHD subjects had smaller SCRs than did normal control subjects. Verbal report measures, however, revealed that subjects reported feeling less pleasant, more aroused, and less in control during the shock condition compared to the no-shock condition. Unlike the SCR results, the verbal report of emotional experience did not differ between the patients with RHD, patients with LHD, and normal control subjects. CONCLUSIONS: Emotional experience is not dependent upon activation of and feedback from the autonomic nervous system.
The potential for postoperative complications in irradiated intestinal anastomoses is well known. There has been limited evaluation of factors that may improve wound healing in radiation-injured bowel. Growth hormone (GH) has been shown to improve wound healing. In animal models GH has been demonstrated to increase strength of large bowel anastomoses in nonirradiated bowel. The purpose of this study was to evaluate, in a rat model, the effect of GH on the bursting pressure of radiation-injured terminal ileal anastomoses in a rat model. Fifty-four rats were treated with 1700 cGy of pelvic irradiation in a single dose. Seventeen weeks later resection of a segment of terminal ileum and an ileo-ileostomy was performed. Half the rats received GH (2.0 mg/kg/day) and the rest received normal saline subcutaneously for 7 days starting on the day of surgery. On the seventh postoperative day the anastomosis site was identified at reoperation and bursting pressure was measured in vivo. A significantly greater bursting pressure was observed in the GH-treated rats compared to the control group (208.9 +/- 27 cm H2O vs 177 +/- 53 cm H2O, P < 0.025). GH treatment resulted in an 18% greater strength of radiation-injured terminal ileal anastomotic segments, as measured by bursting pressure. These findings suggest a possible role for GH in decreasing the morbidity in patients who undergo intestinal surgery after radiation treatment.
Water samples from several ponds in Minnesota were evaluated for their capacity to induce malformations in embryos of Xenopus laevis. The FETAX assay was used to assess the occurrence of malformations following a 96-hr period of exposure to water samples. These studies were conducted following reports of high incidences of malformation in natural populations of frogs in Minnesota wetlands. The purpose of these studies was to determine if a biologically active agent(s) was present in the waters and could be detected using the FETAX assay. Water samples from ponds with high incidences of frog malformations (affected sites), along with water samples from ponds with unaffected frog populations (reference sites), were studied. Initial experiments clearly showed that water from affected sites induced mortality and malformation in Xenopus embryos, while water from reference sites had little or no effect. Induction of malformation was dose dependent and highly reproducible, both with stored samples and with samples taken at different times throughout the summer. The biological activity of the samples was reduced or eliminated when samples were passed through activated carbon. Limited evidence from these samples indicates that the causal factor(s) is not an infectious organism nor are ion concentrations or metals responsible for the effects observed. Results do indicate that the water matrix has a significant effect on the severity of toxicity. Based on the FETAX results and the occurrence of frog malformations observed in the field, these studies suggest that water in the affected sites contains one or more unknown agents that induce developmental abnormalities in Xenopus. These same factors may contribute to the increased incidence of malformation in native species.
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We studied imagery for learned, skilled movements (praxis imagery) in a patient with severe ideomotor apraxia and intact language abilities. This patient, who made predominantly spatial and movement errors when performing transitive movements demonstrating the use of tools (transitive gestures), was also impaired in her ability to answer imagery questions about joint movement or the spatial position of the hands during action. However, visual object imagery was spared. The finding of parallel praxis production and praxis imagery deficits in this patient suggests that the same representations used for gesture production are also activated during imagery of motor acts. Our findings also suggest that certain aspects of motor imagery may be dissociable from general object imagery.
We compared the duration of the EMG cortical stimulation silent period (CSSP) elicited in abductor pollicis brevis using transcranial magnetic stimulation (TMS) before and after stereotactic unilateral globus pallidus internus pallidotomy (PAL) in 12 patients with Parkinson's disease. We used TMS stimulus intensities of 200, 150, 120, and 100% of motor evoked potential (MEP) threshold before and after (86 +/- 25 days) PAL. PAL increased CSSP duration at stimulus intensities of 200% of MEP threshold in the hand contralateral to the stereotactic lesion. In a subset of five patients able to remain at rest during pre-PAL testing sessions, PAL decreased the resting MEP/M-wave area ratio in the hand contralateral to the lesion at a stimulus intensity of 120% of MEP threshold. PAL did not significantly modify the effects of TMS in the hand ipsilateral to the globus pallidus lesion. The results suggest that PAL improves the function of cortical motor inhibitory circuits in Parkinson's disease.
Neurobehavioral studies of gesturing have been largely limited to left hemisphere damaged (LHD) patients. We compared spontaneous gesturing in seven right hemisphere damaged (RHD) patients, seven LHD patients, and seven normal controls (NHD) during videotaped interviews. Two judges coded symbolic, expressive, grooming, and fidgeting gestures in 120 10-sec intervals of videotape per patient. We found that RHD patients made significantly more total gestures and grooming gestures with the hand ipsilateral to their lesion than did LHD patients. Furthermore, RHD patients made more total and grooming gestures with their right hand than NHD subjects did with either hand. There were no differences in gesture production between the right and left hands of NHD patients. These results suggest that RHD produces enhanced gesturing, particularly involving grooming behavior.
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Patients with Parkinson's disease (PD) may be impaired at expressing emotional faces and perceiving emotional facial affect. We tested the hypothesis that patients with PD may be impaired at imaging emotional faces. We first compared 12 patients with PD and 30 control subjects on perceptual and imagery tasks. Patients were significantly impaired on a task of emotional facial imagery but not on a control task of object imagery. Patients were also impaired on a task of perceiving emotional faces. Subsequently, we found that PD patients were impaired relative to controls on making emotional faces. Performance on both the perceptual and motor tasks of facial expression significantly correlated with performance on the emotional facial imagery task. We suggest that the basal ganglia, together with the right hemisphere, are part of a neural network subserving emotional facial tasks.
A man with an infarction of his inferior temporal and occipital association cortex bilaterally, which spared primary visual cortex, had impaired visual recognition of objects, faces, colors, words, and gestures. Analysis of visual function indicated that the recognition failures resulted from an agnosia, rather than elemental visual impairment. Whereas his impairment of gesture recognition appeared to be related to an associative agnosia, his inability to recognize objects was related to an apperceptive agnosia. There may be four subtypes of apperceptive agnosia: one where the internal object representations or structural descriptions are impaired, another where an adequate percept cannot be derived, a third where the internal referent and percept are dissociated, and a fourth where both levels are impaired. Our patient demonstrated a failure to relate individual elements to the whole, a failure to integrate multiple elements, and a reliance on global perception. He had normal object imagery. These results suggest that, whereas internal representations were intact, he was unable to form adequate perceptual representations.
Most studies of facial expressivity in patients with focal brain lesions have examined the ability to produce emotional expression in laboratory settings using various experimental paradigms. In this study, we compared facial expressivity in right hemisphere damaged patients (RHD), left hemisphere damaged patients (LHD), and normal controls (NHD) during videotaped semistructured interviews with the patient and spouse in their home. Three research assistants rated 120 10-sec segments of videotape per patient on a 7-point expressivity scale. We found that RHD patients showed reduced facial expressivity in comparison to both LHD and NHD subjects during spontaneous conversation. In particular, RHD patients demonstrated significantly less smiling and laughter than LHD patients and normal controls. These findings were not a general feature of communicative competence in RHD patients as discourse production equaled that of normal controls. These results support the hypothesis that the right hemisphere mediates facial expressivity during spontaneous social interaction.
Cholinergic deficient states, such as in Alzheimer's disease, are associated with amnesia. Therapeutic trials with cholinergic augmentation in Alzheimer's disease have had only equivocal results, but mechanisms other than cholinergic deficiency may contribute to the memory deficit. Normally the diagonal band of Broca provides much of the hippocampal cholinergic input. To learn if amnesia secondary to cholinergic deficiency can be ameliorated by cholinergic augmentation, we treated an amnestic man who had a lesion located primarily in the right diagonal band of Broca with physostigmine and lecithin. During the initial best-dose-finding phase, he demonstrated an inverted U-shaped curve for immediate recall of word lists, with peak performances at 3.0 and 3.5 mg of physostigmine. Single photon emission tomography showed decreased blood flow in the medial temporal region ipsilateral to the lesion at baseline, with a reversal of the asymmetry on 3.5 mg of physostigmine. A follow-up double-blind, placebo-controlled study on 3.5 mg of physostigmine, however, failed to demonstrate that cholinergic treatment improved memory.
Patients with a diagnosis of Alzheimer's disease and their families need the assistance of a case manager to deal with the issues of long-term care. The case manager assists with education, planning, linking to formal and informal resources, and addressing emotional needs in the family unit. This article discusses specific suggestions to address problems in the three stages of Alzheimer's disease from the time of medical diagnosis to the end of life.
Several well-defined coxsackievirus B3 (CVB3)-murine models of inflammatory heart disease are providing information about mechanisms which contribute to myocyte necrosis. Severity of disease induced and mechanisms responsible depend upon unresolved molecular activities of the viral genome, nonspecific defenses of the mouse at time of infection and immune responses of the mouse at the time of infection. Most important are the capabilities and directed responses of each mouse to infection which are determined by age and genetic background of the host. In addition to virus-induced contributions to tissue pathology during primary infection, persistence of viral genomes for week to months in some strains of mice forecast whether the acute disease will resolve or continue as chronic disease with sustained inflammatory reactions in the myocardium. Persistent infections can contribute to nascent cardiopathologic alterations by chronic induction of inflammatory events through expression of viral genes and altered expression of host genes during nonlytic infections. Products of these expressions include viral proteins and nonhomeostatic levels of cytokines and arachidonic acid cascade intermediates and final metabolites. Molecular mimicry via shared epitopes between virion capsid proteins and normal cell molecules/structures located on or within heart tissue cells may be the mechanism by which immune systems in certain strains of mice are persistently stimulated. The products of these immune responses, i.e. antibodies and cytotoxic T lymphocytes, may provide initial protection via termination of infection and virus clearance during acute disease but subsequently these autoreactive processes could contribute to chronic disease. The immune effector products (antibodies and T lymphocytes) have potential pro-inflammatory reactivities, capacity for exacerbating ongoing CVB3-induced disease and/or can induce disease in normal animals. In further support of the hypothesis that autoimmune reactions contribute to sustained inflammation of the heart, non-viral models of myocarditis have been developed. Cell constituents such as myosin and adenosine nucleotide translocator protein can induce cardiopathologic alterations in normal mice of strains known to develop CVB3-induced chronic disease. Thus host genetic background determines whether a mouse survives the initial infection, resolves the acute disease or inadvertently contributes to sustained inflammatory heart disease. Finally, shared epitopes among the enteroviruses may play a role in repeated episodes of disease during sequential infections by different serotypes.
The aetiology of non-iatrogenic causes of peripheral ischaemia and gangrene presenting either at birth or within a few hours of delivery is unknown in the majority of 56 confirmed cases. In this review of 47 cases occurring since 1941 the aetiology was clear in only 6, four due to compression by the encircling umbilical cord. There was no clear association with gestational age, birth weight, maternal age or type of delivery. Seven were infants of poorly controlled diabetic mothers and these may constitute a subgroup due to altered haemostatic mechanisms. Pregnancy hypertension was an association in 7 cases, oligohydramnios in 6. There is only limited support for birth trauma, sepsis, and thrombo-emboli from the ductus arteriosus as causes. There is indirect evidence that thrombo-emboli can migrate from the placental bed to the fetus. In recent years death from this condition has been rare with surgical thrombectomy increasingly successful in late presenting cases. When gangrene is established at birth surgical amputation, autoamputation, or some loss of function is usual. Peripheral ischaemic insults presenting at birth may be part of a wider spectrum of disorders, both prenatal and perinatal, attributable to occlusive vascular disruption.
Destructive lesions of the basal forebrain are associated with memory impairment in both humans and experimental animals. The basal forebrain is thought to contribute to memory function by providing cholinergic innervation to critical memory structures such as the hippocampus and amygdala. In previously reported clinical cases of basal forebrain amnesia, multiple neuroanatomical regions have been damaged, preventing identification of the minimal critical lesion necessary to produce an amnestic syndrome. We describe a patient who developed persistent, global anterograde and retrograde amnesia following resection of a low-grade glioma. Post-surgical magnetic resonance imaging studies revealed a small discrete lesion, centred in the right diagonal band of Broca, that included the preoptic area, the anterior hypothalamus, the lamina terminalis and the paraterminal gyrus. The septal nuclei and the cell bodies of the nucleus basalis of Meynert appeared to have been spared, as were other structures in the medial temporal lobe and diencephalon. Our case provides critical support for the independent contribution of the basal forebrain, in particular the diagonal band nuclei, in memory function. We propose that our patient's amnesia resulted from disconnection of pathways between the diagonal band nuclei and the hippocampal region, depriving the hippocampus of cholinergic innervation.