Activation of 5-HT3 receptor by 1-phenylbiguanide increases dopamine release in the rat nucleus accumbens

The serotonin-3 (5-HT₃) agonist 1-phenylbuguanide (0.1–1.0 mM in perfusate) caused a robust, dose-dependent enhancement of extracellular dopamine content in nucleus accumbens as measured by in vivo microdialysis. This action was antagonized by co-perfusion of the 5-HT₃ antagonists zacopride and GR38032F (1 mM in perfusate). Similar effects were observed in 5-HT-denervated rats. These findings suggest that there is a potent modulation of dopamine (DA) release in the nucleus accumbens mediated via 5-HT₃ receptors, which appear to be located presynaptically on DA terminals of the mesolimbic DA pathway.     

Cardioprotective effects of diltiazem when given before, during or delayed after infusion of norepinephrine in anesthetized dogs

Catecholamine excess has been shown to produce 2 distinct forms of irreversible myocardial necrosis termed contraction band lesions. Calcium channel blocking agents provided a variable protective effect from these contraction band lesions. The purpose of this study was to determine the temporal responses of the most effective of these blocking agents, diltiazem, when given before, simultaneous with or after an initial exposure to a necrogenic infusion of norepinephrine (NE). Forty-one adult mongrel dogs were anesthetized with sodium pentobarbital (32 mg/kg) and infused with saline solution or NE (4 micrograms/kg/min) for 60 minutes or diltiazem at a rate of 20 micrograms/kg/min for the first 5 minutes and 10 micrograms/kg/min for the remaining 70 minutes. Diltiazem was infused as pretreatment 15 minutes before continued infusion with NE for 60 minutes, simultaneously infused with NE for 60 minutes or delayed 30 minutes after the start of NE infusion. Diltiazem alone exhibited no significant effect on hemodynamics, but pretreatment with diltiazem was able to moderate the rapid NE-induced increases in heart rate. NE infusion produced significant numbers of the 2 forms of contraction band lesions: (1) paradiscal contraction band lesions involving a small portion of the cell adjacent to the disc, and (2) holocytic contraction band lesions involving the entire cell. Diltiazem reduced the number of contraction band lesions, particularly the holocytic contraction band lesions, provided diltiazem was available before the insult and massive influx of calcium with a pharmacologic dose of NE. Although the exact mechanism of diltiazem's cardioprotective properties is not known, the timing of drug administration does appear to affect the degree of protection.     

Variability in consultation rates and practitioner level of diagnostic certainty.

BACKGROUND. This study was designed to determine the variability in the consultation practices of family physicians and family nurse practitioners in an urban group practice, and to examine the relation between the referring practitioner's diagnostic certainty at the time of the consultation request, the specificity of the request to the consultant, and the frequency with which the practitioner ordered consultations in that specialty. METHODS. This study examined consultations requested by six family physicians and two family nurse practitioners that were directed to nine medical and surgical specialties in connection with 35,218 family practice visits made over a 19-month period in an urban family practice. Requests for consultation were scored based on the level of certainty of the referring practitioner's diagnosis at the time of consultation and the specificity of the consultation request. RESULTS. There was nearly a fivefold variation in the overall specialty consultation rates among providers, with even greater variation in each individual specialty area studied. Referral rate correlated positively with certainty of diagnosis (r = .40). There was no consistent relation between request specificity and referral rate. CONCLUSIONS. Consultation rates vary widely, even among family physicians and nurse practitioners within the same practice. The rate at which a practitioner orders consultations in a specialty area increases in relation to the practitioner's certainty of the diagnosis at the time the consultation was requested. Diagnostic certainty is discussed as a possible indicator of a referring practitioner's knowledge in a specialty area, implying that the greater a practitioner's knowledge in a specialty area, the more he or she consults with specialists in the field. Financial incentives that attempt to decrease specialty consultation should be reexamined in light of these findings.     

Does cardiac SPECT using attenuation and scatter correction accurately predict coronary artery disease in a minority women population?

BACKGROUND: Myocardial perfusion imaging (MPI) is a well-established diagnostic method for evaluation and risk stratification of coronary artery disease (CAD).We undertook this study to validate both the positive predictive value (when compared to cardiac catheterization) and the prognosis afforded by MPI in a group of minority women patients. MATERIAL/METHODS: The database of our Nuclear Imaging and Catheterization Laboratory was retrospectively queried for consecutive minority (African-American, Hispanic and Asian) women patients who underwent MPI and cardiac catheterization within 90 days of each other. Patients with recent revascularization were excluded. Attenuation/scatter correction was utilized in the final interpretation of the study. RESULTS: Of the 54 women patients who underwent MPI, 7 underwent exercise stress testing, 26 had stress testing with adenosine, 18 with dipyridamole and 3 with dobutamine. Eighteen patients (53%) had same number of vessels predicted by MPI and coronary angiography (7 patients with triple vessel disease, 7 with 2-vessel disease and 4 with single vessel disease). Five (3 with intermediate and 2 with high risk scans) out of the 54 patients (9.3%) were dead at 2 years. The sensitivity, specificity and positive predictive value of MPI as compared to angiography were 87.2%, 26.7%, 75.6% and 44.4% respectively. CONCLUSIONS: The sensitivity of MPI in this group of patients is comparable to the general population though the specificity is lower in spite of using attenuation and scatter correction. Low risk perfusion scan signifies favorable prognosis at 2 years with regards to mortality.     

In vivo measurement of the shear modulus of the human vocal fold: interim results from eight patients

The shear modulus of the vocal fold is an essential parameter required to enhance our understanding of how the vocal fold operates, to develop mathematical models of phonatation, and to provide benchmarks to quantify the effectiveness of surgical procedures. The authors announced the successful deployment of an instrument to measure vocal fold elasticity in vivo last year, and now present the data taken from eight patients in vivo. The shear modulus was measured at the mid-membranous point, in a transverse direction with respect to the axis drawn between the anterior commissure and vocal process. The range of mean shear modulus results is 701–2,225 Pa, with a mean value of 1,371 Pa.     

Computerized follow-up of discrepancies in image interpretation between emergency and radiology departments

Radiographs are ordered and interpreted for immediate clinical decisions 24 hours a day by emergency physicians (EP’s). The Joint Commission for Accreditation of Health Care Organizations requires that all these images be reviewed by radiologists and that there be some mechanism for quality improvement (QI) for discrepant readings. There must be a log of discrepancies and documentation of follow up activities, but this alone does not guarantee effective Q.I. Radiologists reviewing images from the previous day and night often must guess at the preliminary interpretation of the EP and whether follow up action is necessary. EP’s may remain ignorant of the final reading and falsely assume the initial diagnosis and treatment were correct. Some hospitals use a paper system in which the EP writes a preliminary interpretation on the requisition slip, which will be available when the radiologist dictates the final reading. Some hospitals use a classification of discrepancies based on clinical import and urgency, and communicated to the EP on duty at the time of the official reading, but may not communicate discrepancies to the EP’s who initial read the images. Our computerized radiology department and picture archiving and communications system have increased technologist and radiologist productivity, and decreased retakes and lost films. There are fewer face-to-face consultations of radiologists and clinicians, but more communication by telephone and electronic annotation of PACS images. We have integrated the QI process for emergency department (ED) images into the PACS, and gained advantages over the traditional discrepancy log. Requisitions including clinical indications are entered into the Hospital information System and then appear on the PACS along with images and readings. The initial impression, time of review, and the initials of the EP are available to the radiologist dictating the official report. The radiologist decides if there is a discrepancy, and whether it is category I (potentially serious, needs immediate follow-up), category II (moderate risk, follow-up in one day), or category III (low risk, follow-up in several days). During the working day, the radiologist calls immediately for category I discrepancies. Those noted from the evening, night, or weekend before are called to the EP the next morning. All discrepancies with the preliminary interpretation are communicated to the EP and are kept in a computerized log for review by a radiologist at a weekly ED teaching conference. This system has reduced the need for the radiologist to ask or guess what the impression was in the ED the night before. It has reduced the variability in recording of impressions by EP’s, in communication back from radiologists, in the clinical follow-up made, and in the documentation of the whole QI process. This system ensures that EP’s receive notification of their discrepant readings, and provides continuing education to all the EP’s on interpreting images on their patients.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Characterization of a 34-kDa soybean binding protein for the syringolide elicitors

Syringolides are water-soluble, low-molecular-weight elicitors that trigger defense responses in soybean cultivars carrying the Rpg4 disease-resistance gene but not in rpg4 cultivars. ¹²⁵I-syringolide 1 previously was shown to bind to a soluble protein(s) in extracts from soybean leaves. A 34-kDa protein that accounted for ¹²⁵I-syringolide 1 binding activity was isolated with a syringolide affinity-gel column. Partial sequences of internal peptides of the 34-kDa protein were identical to P34, a previously described soybean seed allergen. In soybean seeds, P34 is processed from a 46-kDa precursor protein and was shown to have homology with thiol proteases. P34 is a moderately abundant protein in soybean seeds and cotyledons but its level in leaves is low. cDNAs encoding 46-, 34-, and 32-kDa forms of the soybean protein were cloned into the baculovirus vector, pVL1392, and expressed in insect cells. The resulting 32- and 34-kDa proteins, but not the 46-kDa protein, exhibited ligand-specific ¹²⁵I-syringolide binding activity. These results suggest that P34 may be the receptor that mediates syringolide signaling.     

Reduced high-energy phosphate levels in rat hearts. I. Effects of alloxan diabetes.

Significant alterations in heart carbohydrate and lipid metabolism are present 48 h after intravenous injection of alloxan (60 mg/kg) in rats. It has been suggested that uncoupling of oxidative phosphorylation occurs in the alloxanized rat heart in vivo, whereas normal oxidative metabolism has been demonstrated in alloxan-diabetic rat hearts perfused in vitro under conditions of adequate oxygen delivery. We examined the hypothesis that high-energy phosphate metabolism might be adversely affected in the alloxan-diabetic rat heart in vivo. Phosphocreatine and ATP were reduced by 58 and 45%, respectively (P is less than 0.001). Also, oxygen-dissociation curves were shifted to the left by 4 mmHg, and the rate of oxygen release from blood was reduced by 21% (P is less than 0.01). Insulin administration normalized heart high-energy phosphate compounds. ATP production was accelerated in diabetic hearts perfused in vitro with a well-oxygenated buffer. These studies support the hypothesis that oxidative ATP production in the alloxan-diabetic rat heart is reduced and suggest that decreased oxygen delivery may have a regulatory role in the oxidative metabolism of the diabetic rat heart.