The contribution of a non-invasive test to clinical care. The impact of echocardiography on diagnosis, management and patient anxiety

We prospectively studied the impact of echocardiography on a cardiologist's diagnosis and management plan and on patient anxiety for 300 consecutive referrals. There was an impact on diagnosis in 90% of patients. Most common was confirmation of diagnosis usually with the addition of information pertinent to management (81%); change of disease category or resolution of diagnostic doubt was uncommon (9%). The consultant cardiologist believed the heart to be normal in 48 patients who did not have any associated disease; none had any echocardiographic abnormality. The cardiologist reported increased diagnostic confidence in 74% of all patients but management changed in only 9%. One-third of all patients reported reduced anxiety when this was an important clinical issue but in less than half of them did the cardiologist consider that echocardiographic information was essential for reassurance. Anxiety was increased in 6%, and in 12% the anxiety response was inconsistent with the test result. The clinical contribution of the test report was most obvious for those patients (30%) in whom this data was required for (a) a decision concerning specific diagnostic or technical intervention (b) a change of management plan which implied obvious or likely health benefit (c) reassurance which was a clinically important issue. The magnitude of this contribution was related to the study indication. The value of echocardiography is obvious when assessing patients for invasive intervention or when proper treatment or adequate reassurance are impeded by diagnostic doubt. However, for many current indications, we need better definition of factors which predict a clinically useful result. In particular, when the aim is to rule-out disease, our results suggest that an expert cardiological opinion would often be more appropriate than an echocardiogram.     

Sensorineural hearing loss in patients with typical retinitis pigmentosa

We performed detailed audiologic testing in 45 patients with retinitis pigmentosa and 45 age- and sex-matched controls. Ten (22%) of the retinitis pigmentosa patients had a sensorineural hearing loss that varied from mild to severe. None of the control subjects had a hearing loss. Audiograms measured over a ten- to 30-year period were available for four patients with retinitis pigmentosa and each showed progressive hearing loss. The results indicate the important role of audiologic evaluation in treating patients with retinitis pigmentosa.     

Organic brain damage and occupational solvent exposure.

Three hundred and nine men with organic dementia, cerebral atrophy, or psycho-organic syndrome admitted for five nights or more to one of 18 Quebec hospitals were individually matched with patients admitted (1) with some other psychiatric diagnosis and (2) to a general hospital. Lifetime occupational histories were obtained by telephone. Occupational exposure to solvents was assessed blind to type of case by (1) individual ratings and (2) a job exposure matrix; men who worked in moderate or high solvent concentrations for at least 10 years were considered exposed. With the psychiatric referent series, an odds ratio of 1.4 (90% CI 1.0-2.0) was calculated by individual exposure ratings and 1.4 (90% CI 0.9-2.2) by job matrix. Increased risk was mainly in those with organic dementia or cerebral atrophy and an alcohol related diagnosis. The same pattern of risk was found against the general hospital referents. Adjustment for possible confounders did not alter the risk estimates appreciably. Also, lifetime job histories, compared in selected case-referent pairs, gave similar evidence of increased risk (odds ratio 2.3; 90% CI 1.0-5.5). It is concluded that the combined effect of occupational solvent exposure and alcohol intake is probably an important cause of organic brain damage.     

Comparison of the use of nalbuphine and fentanyl during third molar surgery

In a double-blind, randomized plan of drug administration, nalbuphine, fentanyl, and a placebo were compared for efficacy in sedation and analgesia during third molar removal. Fifty-eight patients participated in this study. Using accepted intravenous sedation and surgical techniques, fentanyl and nalbuphine were found to be better than placebo for anxiety and pain control in third molar surgery. Fentanyl had a longer duration of pain relief postoperatively than did nalbuphine. The study confirmed the need for a narcotic supplement to sedation techniques for third molar surgery.     

Chronic application of NMDA decreases the NMDA sensitivity of the evoked tectal potential in the frog.

The activity-dependent mechanism that refines the topography of the retinotectal projection in frogs is mediated by the NMDA receptor. Earlier studies found that chronic treatment of the optic tectum with the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (DL-AP5) desegregated eye-specific stripes in three-eyed frogs, while chronic treatment with NMDA sharpened stripe borders (Cline et al., 1987; Cline and Constantine-Paton, 1990). We now report that this same chronic treatment with NMDA decreases the electro-physiologically measured sensitivity of the optic tectum to applied NMDA: acute application of a given concentration of NMDA decreased the evoked tectal potential to a lesser extent in animals chronically treated with NMDA than it did in normal and sham-treated animals. This is observed as a shift to the right in the NMDA dose-response curves for both the positive and negative postsynaptic components of the evoked tectal response. We believe that this decreased NMDA receptor effectiveness further restricts the intermingling of axon branches from the two eyes by limiting synapse stabilization to areas where afferent activity is most correlated. This would account for the anatomical sharpening of stripe borders (i.e., increased afferent segregation). Quantitative autoradiographic analysis of 3H-glutamate binding to NMDA receptors indicated that binding densities within the tectum did not differ between control groups and NMDA chronically treated groups. We suggest that in the experimental animals the response to NMDA may be decreased by a change in the effectiveness of individual NMDA receptors rather than by decreases in receptor number. This experimentally induced change may be analogous to naturally occurring decreases in receptor function that correlate with the end of some periods of visual plasticity in mammals.     

Organization of amygdaloid projections to the mediodorsal thalamus and prefrontal cortex: a fluorescence retrograde transport study in the rat

Previous studies have shown that the amygdala projects to both the mediodorsal thalamic nucleus (MD) and its cortical projection area, the prefrontal cortex (PFC). In this investigation rats received injections of different fluorescent retrograde tracers (true blue and diamidino yellow) into MD and either the lateral, polar, or medial PFC in order to examine the relationship of amygdaloid neurons with cortical and/or thalamic projections. PFC injections labeled neurons in the basolateral (BL), basomedial (BM), ventral endopiriform (EnV), and rostral lateral nuclei as well as the periamygdaloid cortex (PAC) and the medial part of the amygdalohippocampal area (AHA). In BL, which contained the great majority of neurons projecting to PFC, most labeled cells were concentrated in particular parts of the nucleus and were topographically organized. The overwhelming majority of labeled neurons in BL were large pyramidal or piriform cells that correspond to class I neurons described in Golgi studies. Occasional small neurons with thin dendrites were also observed; these cells may be class II neurons. MD injections labeled numerous cells in the anterior division of the cortical nucleus, medial nucleus, and caudomedial part of the central nucleus. Moderate numbers of labeled cells were found in caudal portions of BM and PAC, whereas scattered cells were observed throughout the rest of the amygdala with the exception of the lateral nucleus. In BL and AHA many MD-projecting neurons were observed along nuclear boundaries and in the adjacent white matter. Neurons in BL, BM, and AHA usually had large elongated or irregular somata and two to four primary dendrites that branched sparingly. Other cells had smaller ovoid somata. The morphology and distribution of MD-projection cells in the basolateral amygdala indicate that they are primarily large class II neurons. Double-labeled amygdaloid neurons, labeled by both cortical and thalamic injections, were observed only in a small number of animals. Control experiments suggest that most of the double-labeled cells in these cases were artifacts caused by spread of the thalamic injectate into the third ventricle with subsequent uptake by fibers in the anterior commissure. Thus the findings of this study suggest that different neuronal populations in the amygdala project to the two poles of the MD-PFC system. In the basolateral amygdala class I neurons are the predominant cell type involved in PFC projections, whereas a subpopulation of class II neurons, hitherto thought to be primarily local-circuit neurons, project to MD.     

Neurotransmitters and neuropeptides in Alzheimer's disease.

The neurotransmitter and neuropeptide changes in Alzheimer's disease are outlined in Table 1. Many of the changes, such as decreases in CSF ACh and SRIF, are well documented and correlate with the severity of the dementia; however, they are relatively nonspecific. The changes in neurotransmitter availability have offered new insight into both the pathophysiology and possible treatment strategies in Alzheimer's disease. It is evident that the disease is characterized by pathologic involvement of multiple neurotransmitter systems, including those that utilize ACh, SRIF, CRF, and, most probably, monoamines and excitatory amino acids. The role each system has in the signs and symptoms of Alzheimer's disease remains obscure.