Biomedical subjects
Publications and source records attributed to M Freedman.
A 45-year-old woman was diagnosed as having the unclassified form of botulism. Her intestines may have been predisposed to colonization with Clostridium botulinum because of a jejunoileal bypass procedure that had been done several years earlier. One other similar case has been reported.
The relationship between semantic encoding deficits and memory dysfunction was evaluated for the following groups: amnesic patients with bilateral frontal lobe lesions; nonamnesic patients with bilateral frontal lesions; and alcoholic Korsakoff patients. Semantic encoding was assessed using the Wickens' release from proactive interference (PI) paradigm. Korsakoff patients and the poor memory frontal lobe patients failed to show automatic PI release, while good memory frontal patients did show a release. These results support the view that an encoding disability is a contributor to amnesics' memory disorder and they suggest a possible neuroanatomical correlate for impaired semantic encoding.
The terms "cortical" and "subcortical" dementia are controversial; however, the clinical distinction between them is real. For example, although Alzheimer's and Parkinson's disease (prototypical of cortical and subcortical dementia, respectively) share clinical features, they differ in the presence of aphasia, apraxia, and agnosia in Alzheimer's disease but not in Parkinson's dementia. We review our studies aimed at clarifying the mechanisms underlying the differences between these neurological disorders. Experimental paradigms adopted from animal models were used to study the functional anatomy and neuropsychological characteristics of Alzheimer's and Parkinson's disease. The tasks administered include delayed alternation (DA) and delayed response (DR), which are sensitive to frontal system damage, and tactile discrimination learning (TOL) and reversal (TRL) paradigms sensitive to parietal system damage. Alzheimer's patients were significantly impaired on all tasks whereas Parkinsonians with dementia were impaired only on DR and TRL. Consideration of neuroanatomical and neuropsychological mechanisms involved in DA, DR, TOL, and TRL appears to have sharpened the distinction between Alzheimer's and Parkinson's dementia. Dementia in Alzheimer's disease may involve dorsolateral frontal, orbitofrontal and parietal systems. In contrast, dementia in Parkinson's disease may involve prominent dorsolateral frontal system damage.
The performance of patients with frontal lobe disease was compared with that of amnesic patients (with etiology of alcoholic Korsakoff's disease or surgically treated ruptured anterior communicating artery aneurysm) on tasks known to be sensitive to frontal lobe damage in nonhuman primates: delayed alternation (DA) and delayed response (DR). Alcoholic patients with no clinical memory impairment served as controls. Results showed that bilateral frontal lobe damage in humans is associated with impairment on both tasks. In addition, there was no relation between performances on DA and DR and performance on standardized tests of memory, a result strengthening the suggestion that the former tasks are not sensitive to anterograde amnesia in humans.
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Despite 60 years of study, the brain mechanisms for stuttering are unknown. In an effort to shed light on these mechanisms, we studied two cases in which the fluency of speech changed after brain damage in adulthood. The first, an ambidextrous man, ceased to stutter after a head injury. The second, a converted left-handed man, experienced recurrence of childhood stuttering after a stroke.
Amnesic patients were able to retrieve an object hidden at an initial location after a brief delay, but subsequently failed to retrieve an object at a new location, and instead searched for it at the old place. This phenomenon, which we call mnemonic precedence, resembles the AB error that has been observed in 8-10-month-old infants. The parallel performance of amnesics and infants on object search tasks is consistent with the hypothesis that memory deficit, rather than defective object concept, plays a major role in the AB error. The influence of memory processes on tests of symbolic representation is discussed.
The symphysis pubis is a nonsynovial amphiarthrodial joint that is situated at the confluence of the two pubic bones. A thick intrapubic fibrocartilaginous disc is sandwiched between thin layers of hyaline cartilage. The inferior pubic ligament provides most of the joint's stability. Anatomic sections demonstrate a symphysis by the end of the second month of gestation. Thick cartilaginous end-plates are present at birth but become thin by the time of skeletal maturity. Congenital diseases resulting in failure of symphysis formation include exstrophy of the bladder and cleidocranial dysostosis. Both pyogenic and tuberculous infectious diseases involve the symphysis. Metabolic disease, such as renal osteodystrophy, produces widening, while ochronosis results in calcific deposits in the symphysis. Inflammatory disease, such as ankylosing spondylitis, results in bony fusion of the symphysis. Osteitis pubis, the most common inflammatory disease, is treated with anti-inflammatory medication and rest. Degenerative joint disease of the symphysis, which can cause groin pain, results from instability or from abnormal pelvic mechanics. As is the case with most joints, the symphysis serves as a barrier to tumor invasion. The patterns of trauma include diastasis, straddle fracture, intraarticular fracture and overlapping dislocation, and combinations of injuries.
A 50-year-old man underwent emergency aortic valve replacement. He had been treated with five antihypertensive agents before the procedure; this contributed to the development of profound hypotension after induction of anaesthesia. The hypotension did not respond to conventional treatment with an incremental intravenous infusion of phenylephrine HCl, probably due to the direct vasodilator action of the hydralazine group of drugs which renders the peripheral vascular smooth muscle unresponsive to sympathomimetic stimulation. The hypotension did, however, respond rapidly to low-dose infusion of a synthetic vasopressor, ornipressin (POR 8; Sandoz), a drug with a direct action on vascular smooth muscle, especially the capacitance vessels. Ornipressin thus restores vascular smooth-muscle tone even when the integrity of the adrenergic pathways is no longer intact.
Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured in the sixth, 13th, and 20th milliliters of CSF in patients with dementia of the Alzheimer's type (DAT) and Parkinson's disease (PD), and in an aliquot of CSF in controls. In patients with PD there was a positive correlation between 5-HT and 5-HIAA levels in the 20th milliliter of CSF, while in patients with DAT there was a negative correlation of these levels in this CSF fraction. In patients with the senile form of DAT the 5-HIAA levels in the 20th milliliter of CSF were higher than in patients with PD. These results indicate differential involvement of the serotoninergic system in DAT and PD, and may lead to the development of a chemical marker for DAT.
A Vermont health risk survey was performed to gain information on health knowledge and behaviors of the population. Telephone interviews with 1,594 individuals ascertained respondents' demographic characteristics, preventive health behaviors, and health knowledge. Risk prevalence was obtained on five health risks: alcohol (12%), smoking (33%), lack of exercise (70%), overweight (39%), and non-use of seatbelts (86%). Low income, less education, and blue collar occupation status were associated with increased risks of smoking, lack of exercise, and non-use of seatbelts. Increased prevalence of certain risks are associated with the 18-24 year old age group; 32% of those males reported an alcohol risk and 94% reported non-use of seatbelts. Combined risk scores were increased in groups with low income, less education, and blue collar occupations. These variations in health behaviors by social group were not explained by differences in health knowledge. Design of primary prevention activities needs to be community wide, utilize information on the epidemiology of health behaviors, influence diverse community groups and intervene before risk behaviors are established.
Cholinesterases, including pseudocholinesterase (BChE) of human plasma and acetylcholinesterase (AChE) of erythrocytes and cerebrospinal fluid (CSF), have been considered as possible markers in dementia of the Alzheimer type (DAT). Reported data, however, are widely varied, and no significant pattern emerges when total enzyme activity is assayed. In the present studies, we have reexamined the relationship of ChE activities in DAT and control patients. ChE activity was measured in plasma, erythrocytes, and CSF from DAT patients and compared with normal controls as well as with samples from patients with a diagnosis other than DAT. Early age onset (presenile) and late age onset (senile) DAT were also compared. No significant differences in total enzyme activity were found in any of the comparisons. Calculations of AChE/BChE ratios in CSF also provided no significant indication of any changes in ChE activities in DAT. It is suggested that measurements of total AChE or BChE activity in these biological materials do not provide a useful index of alterations in central cholinergic function in patients with DAT.
Three, 4-dihydroxyphenylacetic acid (DOPAC); 3-methoxy, 4-hydroxyphenylacetic acid (HVA); 3-methoxy; 4-hydroxyphenylglycol (MHPG); adenosine 3', 5'-cyclic monophosphate (cyclic AMP); and guanosine 3', 5'-cyclic monophosphate (cyclic GMP) were measured in cerebrospinal fluid (CSF) of patients with dementia of Alzheimer type (DAT) and controls. DOPAC levels were lower and HVA levels were higher in DAT patients than in controls. In the most rostral fractions of CSF from DAT patients there was a negative correlation between DOPAC and cyclic AMP levels. In addition, patients with onset of DAT symptoms before the age of 65 had lower DOPAC levels, a higher HVA/DOPAC ratio, and higher cyclic nucleotide levels than patients with late onset of DAT. By combining DOPAC and cyclic AMP levels, we could clearly distinguish these two groups.
The application of the indicator dilution technique for the estimation of blood loss during transurethral resection of the prostate gland is explained. The feasibility of using potassium ions as an intrinsic indicator was investigated. The most important factors affecting blood loss are considered. The advantages and inherent sources of error are discussed and some tentative conclusions drawn concerning the factors affecting blood loss.
Six serotonin antagonists (pizotifen, mianserin, cyproheptadine, ketanserin, trazodone and methysergide) were tested in mice in a behavioral despair procedure. The behavioral despair procedure detects most antidepressant compounds. Pizotifen, mianserin and cyproheptadine were found to be active and the others were inactive. The serotonin binding potency at serotonin1 or serotonin2 receptors, or the ratio of potency at these receptors did not correlate with activity in the behavioral despair procedure. However, the serotonin antagonists that were active in the behavioral despair procedure were all found to be potent antagonists at histamine1 receptors. It is suggested that the activity of some serotonin antagonists in the behavioral despair procedure is best explained by their antihistaminergic potency.
Retrograde amnesia was assessed in demented and non-demented Parkinson's patients using a test of remote memory spanning the years from 1920-1979. Results indicated that the demented patients 1) scored significantly below normal controls and 2) had equal impairment for all time periods. This pattern was like that seen in other dementing illnesses (i.e., Huntington's and Alzheimer's diseases), but different from that in amnesic disorders, such as Korsakoff's syndrome. The data, therefore, suggest qualitative differences in pattern of remote memory loss between the dementias and amnesic syndromes.
The principles of using indicator dilution techniques for the estimation of blood loss on swabs are explained. The feasibility of an intrinsic indicator such as intracellular and extracellular potassium ions was investigated. An empirical mathematical relationship between the total potassium content per litre of whole blood and the haemoglobin concentration of whole blood was established. The correlation between these two variables is statistically highly significant. The derived total potassium content per litre was then used with the indicator dilution technique to calculate the volume of blood lost. The accuracy, sources of error and advantages of the technique are discussed.
Analysis of language profiles and CT anatomy in transcortical motor aphasia (TCMA) suggests that the essential lesion is disruption of connections at sites between the supplementary motor area and the frontal perisylvian speech zone. If the lesion is extended, there may also be poor articulation (lesion deep to motor strip for face), impaired auditory comprehension (lesion in anterior head of caudate, anterior limb internal capsule, anterior putamen, and anterior portion of external capsule, claustrum, extreme capsule, and insula), or stuttering (lesion in pars opercularis and lower third of premotor region). This concept unifies disparate anatomic and psychophysiologic observations about three syndromes: classical TCMA, aphasia after left medial frontal infarction, and TCMA during recovery from Broca's aphasia.