The precarious situation of the medical student.
Explore the source record for details and available documents.
Cost Control↗
Biomedical subjects
J M Miller
Publications and source records attributed to J M Miller.
Vignette of medical history: George Washington and smallpox.
Explore the source record for details and available documents.
Famous Persons↗
Whose eponym? The case for Edward Selleck Hare.
Explore the source record for details and available documents.
Eponyms↗
Influence of calcitonin-gene related peptide on cochlear blood flow and electrophysiology.
Intra-arterially infused calcitonin gene-related peptide (CGRP) induced dose-dependent decreases in both systemic blood pressure and cochlear blood flow (CBF). However, when subjects were pretreated systemically or locally with the specific receptor antagonist CGRP(8-37), CBF increased, despite decreases in systemic blood pressure in response to CGRP infusions. Micro-infusions of CGRP directly into the supplying arterial network of the cochlea induced dose-dependent increases in CBF that were blocked by CGRP(8-37) pretreatment. Cochlear electrophysiology, as assessed by cochlear action potential and cochlear microphonics, remained unchanged following each condition tested. These results indicate that CGRP is involved in systemic regulation of blood pressure and contributes to the regulation of CBF.
Animals↗
A prospective evaluation of surgically treated groin complications following percutaneous cardiac procedures.
During an 18-month study period, 100 noncardiac surgical complications of a percutaneous cardiac interventional procedure were treated at Emory University Hospital. These were predominantly pseudoaneurysms (61.2%), groin hematomas (11.2%) arteriovenous fistulae (10.2%), and external bleeding (6.1%). Less common complications included retroperitoneal hematomas (5.1%), arterial thromboses (3.1%), groin abscess (2.0%), and a mycotic pseudoaneurysm (1.0%). The complication rate following diagnostic catheterization was 0.6 per cent, after percutaneous transluminal angioplasty, 1.5 per cent, atherectomy 2.2 per cent, and after stent placement 16 per cent (P < 0.0001). The arterial puncture site was other than the common femoral artery in 34 per cent of cases. Risk factors for the development of complications were postprocedure anticoagulation (P < 0.0001), female gender (P < 0.005), increased age (P < 0.0001), and small stature (P < 0.0001). Duplex scanning had 98 per cent accuracy in diagnosis of suspected groin complications, and clinical diagnostic accuracy was 77 per cent. We describe our technique for repair of pseudoaneurysms and arteriovenous fistula and discuss the possible future role of ultrasound guided compression. Mean hospital stay after the procedure was 3.2 days. Morbidity of surgical repair was 21 per cent and mortality was 2.1 per cent. Groin complications following percutaneous cardiac procedures are related to the type of procedure performed, female gender, and periprocedure anticoagulation.
Abscess↗
Epinephrine-induced changes in human cochlear blood flow.
Cochlear blood flow (CBF) was monitored over the basal turn stria vascularis using laser Doppler flowmetry in five human subjects during middle ear surgery. The effects of systemically administered epinephrine (0.3 microgram/kg) and topically applied epinephrine (1:10,000) on the round window membrane (RWM) were examined. Topical epinephrine caused a mean reduction of 60 percent in CBF (maximum peak reduction 65-85% across subjects), which slowly recovered ( > 10 min) toward baseline following epinephrine removal from the RWM. The changes in CBF are similar to those found in animal studies, but are much larger, indicating a relatively more pronounced role of adrenergic agents in CBF control in humans. Systemic epinephrine caused a 40 percent decrease in skin blood flow, a 90 percent increase in blood pressure (BP), above a resting hypotensive mean level of 65 mmHg, and a 50 percent increase in CBF. The CBF change followed the change in BP, but recovered toward baseline more slowly. The dramatic and somewhat prolonged decreases in CBF with RWM application of epinephrine may compromise sensory function and could account for the occasional unexplained sensorineural hearing loss or tinnitus associated with middle ear procedures that use topical epinephrine. The semipermeability of the RWM may, on the other hand, offer a route for therapeutic increases in CBF with vasodilative agents and provide an appropriate treatment for some cases of sensorineural hearing loss.
Administration, Topical↗
The DNA strand in DNA.RNA hybrid duplexes is neither B-form nor A-form in solution.
The structure of the DNA.RNA hybrid (GTCACATG).(caugugac), where lowercase letters designate RNA residues, has been determined on the basis of J-coupling analysis and 2D-NOE studies. The central hexamer in this sequence has been previously studied [Reid, D. G., Salisbury, S. A., Brown, T., Williams, D. H., Vasseur, J.-J., Rayner, B., & Imabach, J.-L. (1983) Eur. J. Biochem. 135, 307-314] via one-dimensional NOE methods and circular dichroism studies. Contrary to their results, we find that this duplex does not assume a B-form conformation in solution. Instead, the RNA residues retain their C3'-endo (A-form) conformation, as indicated by the absence of H1'-H2' couplings and by strong H6/H8 to (n-1) H2'NOEs. The sugars of the DNA residues, on the other hand, do not assume an A-form (or a B-form) conformation but an intermediate conformation in the O4'-endo range (P approximately 72-110 degrees), as indicated by the presence of strong H1'-H4' NOEs, medium-strength H2"-H3' COSY cross peaks, strong H3'-H4' DQF-COSY cross peaks, and H1'-H2' coupling constants that are of approximately the same magnitude as the H1'-H2" coupling constants. These results suggest that the RNA strand not only retains its N-type structure but also exerts an influence on the conformation of the DNA strand. Our results provide strong evidence that DNA.RNA hybrid duplexes do not assume an all-C2'-endo B-type conformation; neither do they assume an all-C3'-endo A-type conformation in solution. Furthermore, although not the main focus of this study, a comparison of the longitudinal relaxation times of the DNA and RNA residues indicates the need for extended relaxation delays in two-dimensional NMR spectra of hybrid duplexes, as has been previously observed for DNA.RNA chimeric duplexes (Wang, A. C., Kim, S.-G., Chou, S.-H., Orban, J., Flynn, P., & Reid, B. R. (1992) Biochemistry 31, 3940-3946).
Base Sequence↗
Increased levels of truncated nerve growth factor receptor in urine of mildly demented patients with Alzheimer's disease.
OBJECTIVE: In Alzheimer's disease, cholinergic basal forebrain neurons, which have receptors for nerve growth factor (NGF), degenerate, while NGF receptors increase in some areas of the neocortex. Levels of the truncated, extracellular portion of the NGF receptor (NGF-Rt) are elevated in urine of patients with peripheral neuropathies and in animals with peripheral-nerve injury, but it has not been determined whether urine levels of NGF-Rt are altered by the presence and/or progression of dementia-related neuropathologic changes in patients with Alzheimer's disease. In this study, we developed an enzyme-linked immunosorbent assay to determine whether urine levels of NGF-Rt are altered in patients with Alzheimer's disease. DESIGN: Survey of urine NGF-Rt levels in neurologically normal (n = 19), mildly demented (n = 31), and moderately to severely demented (n = 31) patients. SETTING: Subjects were participants in the Rochester Alzheimer's Disease Project and mildly demented patients about to begin a clinical drug study. PATIENTS: All patients met established criteria for a clinical diagnosis of probable Alzheimer's disease. Aged, nondemented, neurologically normal controls were selected from the families of the demented subjects. RESULTS: Urine NGF-Rt levels were substantially elevated in mildly demented patients relative to those of nondemented controls. CONCLUSIONS: These results suggest that an enzyme-linked immunosorbent assay on urine samples may provide an antemortem measure of dementia-related neuropathologic changes, but further study is needed to determine the source and potential clinical utility of increased NGF-Rt levels in urine of mildly demented patients.
Aged↗
Metabolic activity of the central auditory structures following prolonged deafferentation.
The goal of this work was to evaluate, using autoradiographic techniques, the effects of variable periods of deafness on resting and evoked metabolic activity in central auditory structures elicited by direct electrical cochlear nucleus (CN) stimulation. Thirty-five pigmented guinea pigs, divided into five groups, underwent acute implantation of bipolar electrodes in the CN. One group was not deafened and served as hearing controls. The other four groups were deafened using an established protocol of sequential kanamycin/ethacrynic acid treatment and were tested at 4 weeks, 9 weeks, 16 weeks, and 15 months after deafening. Threshold currents for eliciting evoked middle latency responses (EMLRs) with direct CN stimulation were not significantly different between hearing and deafened groups. Autoradiographic data showed progressive reduction of the evoked metabolic response with incremental periods of deafferentation. Nevertheless, central auditory structures remained responsive to direct electrical stimulation of the CN. These data indicate that direct CN stimulation remains capable of activating the auditory tract despite prolonged periods of deafness.
Animals↗
A cluster of coagulase-negative staphylococcal bacteremias associated with peripheral vascular catheter colonization in a neonatal intensive care unit.
BACKGROUND: A cluster of six neonatal cases of coagulase-negative staphylococcal bacteremias occurred in a Los Angeles County neonatal intensive care unit in March 1989. METHODS: A retrospective cohort study assessed the impact of host-and delivery-related variables, length of hospitalization, duration of antibiotic treatment, performance or duration of invasive procedures, and staffing variables on risk of coagulase-negative staphylococcal bacteremia. RESULTS: Unstratified analyses yielded eight risk factors with risk ratios greater than 2. After stratification by gestational age (less than 29 weeks) and low birth weight (less than 1500 gm), frequency of blood transfusions, duration of respiratory therapy, heparin lock and central vascular line placement, and hyperalimentation remained associated with elevated risk. Two species were identified, arguing against a common source of infection. Of four cohort months with more than 15 very low birth weight infants in the neonatal intensive care unit, an elevation of coagulase-negative staphylococcus-positive blood cultures and diagnosed bacteremias occurred in only two. CONCLUSIONS: This cluster of coagulase-negative staphylococcal bacteremia was probably caused by frequent manipulation of catheters in neonates who were at heightened risk because of low birth weight and prematurity.
Bacteremia↗
Variability occurs in the inverted repeat region of genomic DNA from bovine herpesvirus 1 respiratory, genital and bovine herpesvirus 5 encephalitic isolates.
Restriction fragment length polymorphisms (RFLPs) were detected within BHV1.1, BHV1.2, and BHV5 genomes using the restriction enzyme PstI. The genomic areas of these changes has not been previously reported. Using Southern blot hybridization with DNA probes representing the entire genome of BHV1.1, areas of genomic variation were located for a respiratory isolate (BHV1.1), four vaccine isolates (BHV1.1), a genital isolate (BHV1.2), and two encephalitic isolates (BHV5). The most frequently observed RFLPs of BHV1.1 and BHV1.2 occurred within the internal repeat region and the left terminus of the unique long region. When two separate isolates of the encephalitic BHV5 were compared, RFLPs were detected in the internal and right terminal repeat regions. These are the regions of each genome from which immediate early genes are transcribed. No genomic variation was observed throughout the unique long and unique short regions for all BHV1 and 5 isolates examined.
Animals↗
Stellate ganglion drives sympathetic regulation of cochlear blood flow.
The functional properties of the sympathetic fibers innervating the cochlea are not well understood. Adrenergic fibers supplying lateral wall structures of the cochlea have been observed terminating on radiating arterioles and collecting venules. Adrenergic fibers also terminate as 'free' endings in the spiral osseous lamina. Stimulation or transection of sympathetic fibers originating from superior cervical chain and supplying the cochlea have yielded mixed results concerning many aspects of cochlea physiology. In order to clarify the origin of sympathetic fibers and their role in control of cochlear blood flow (CBF), we examined the effect of electrical stimulation of the stellate ganglion (ESS) and transection of postganglionic fibers from the stellate on CBF measured by laser Doppler flowmetry and on systemic blood pressure (BP) in the guinea pig. ESS produced a 20-35% increase in BP and 10-15% decrease in CBF. The decrease in CBF presumably reflects the net result of increased perfusion pressure, local autoregulatory mechanisms, and a direct sympathetic-induced vasoconstriction. Section of the immediate postganglionic sympathetic trunk had little or no effect on the ESS-related change in BP; however, it eliminated the CBF reduction. Intravenously infused beta 1-blocker diminished the BP increase due to ESS, while the electrically-evoked reduction in CBF remained. Local application of an alpha-blocker on the round window blocked ESS evoked CBF reductions without altering the BP increase. These data confirm the functional role of sympathetic projections from the stellate ganglion in CBF regulation in guinea pig.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic Fibers↗
Contribution of the anterior inferior cerebellar artery to cochlear blood flow in guinea pig: a model-based analysis.
This study was performed to determine the contribution of the anterior inferior cerebellar artery (AICA) to cochlear blood flow (CBF) in guinea pig. The AICA and the basilar-vertebral arterial complex in twelve animals was exposed through the basal portion of the skull. The cochlea was ventrally approached and the CBF of the apical area monitored with laser Doppler flowmetry. A specially designed microclamp was held in a micromanipulator and used to obstruct the AICA. When the AICA was clamped, CBF decreased to approximately 60% of baseline (BL) (not to 'biological zero'), followed by a gradual increase. When the clamp was released, CBF quickly increased to more than 160% BL and then slowly declined to baseline. To quantify the contribution of AICA to CBF, we formulated an electrical analog model of the cochlear vessel system. With this model, AICA contribution to CBF and the relationship among blood pressure, blood flow, and vascular resistance or vascular conductance in the cochlea can be explored. Results in the present study indicate that the AICA contributes only about 45% of CBF to the cochlea; 55% of CBF must come from other supplying vessels. Contrary to previous reports, CBF response to AICA clamping did not exhibit a stable or constant decrease but showed time-dependent dynamic changes. In addition, the cochlear vascular system showed a marked autoregulatory response, instead of a passive response, to the perfusion pressure change. AICA clamping is, therefore, not a suitable model for investigation of ischemia effects in the guinea pig cochlea, but it is a useful approach to study autoregulation and the myogenic mechanism of the cochlear vascular system.
Animals↗
Substance P increases cochlear blood flow without changing cochlear electrophysiology in rats.
Carotid artery infusions of substance P yielded reductions in systemic blood pressure and elevations in cochlear blood flow (CoBF), measured via laser Doppler flowmeter, with no alterations in cochlear action potentials or cochlear microphonics in Wistar-Kyoto rats. Additionally, direct micro-infusions of substance P into the anterior inferior cerebellar artery, which contributes to the local vascular perfusion of the cochlea, yielded elevations in CoBF with no changes in systemic blood pressure. Pretreatment with a specific substance P receptor antagonist, ([D-Pro2,D-Trp7,9]SP) via the carotid artery or the anterior inferior cerebellar artery, diminished subsequent substance P-induced vascular responses. These results suggest that endogenous substance P, like other vasoactive peptides, may interact with a substance P-specific receptor population in the cochlea and may therefore participate in the ongoing regulation of CoBF. These findings also support the premise that vasodilatory hormones, along with vasoconstrictive agents, may be involved in the autoregulation of CoBF.
Action Potentials↗
Detection of HSP 72 synthesis after acoustic overstimulation in rat cochlea.
The purpose of this study was to determine if high intensity acoustic stimulation would induce HSP 72 in rat cochlea. The animals were exposed to 110 dB SPL broad band noise for 1.5 h and sacrificed 4, 6 and 8 h after stimulation. Immunocytochemistry and western blotting were used to detect the expression of HSP 72 in the cochlear tissues. Western blots showed an intense 72 kD band in the noise exposed animals compared to a very light band in non-stimulated control animals. Immunocytochemical results in the cochlea revealed noise induced HSP 72 immunoreactive staining of outer hair cells. Only a few immunoreactive stained inner hair cells were seen and spiral ganglion cells were not stained. These results indicate that acoustic overstimulation can induce the expression of HSP 72 in outer hair cells of the rat cochlea. HSP 72 may serve as a marker for cellular stress and potential damage and may be involved in protection from insult.
Acoustic Stimulation↗
The vascular component of sodium salicylate ototoxicity in the guinea pig.
Drugs of the salicylate family (aspirin-like drugs) are reversibly ototoxic. Electrophysiologic and ultrastructural evidence suggests an impairment of the sensory hair cells of the cochlea following salicylate treatment. In addition, since these drugs can cause vasoconstriction, the ototoxicity of salicylates may also involve an impairment of the blood circulation in inner ear. However, a vascular hypothesis of salicylate toxicity has not received much attention. In the current study, we simultaneously measured cochlear blood flow (by laser Doppler flowmetry) and the sound-evoked potentials from the round window. Sodium salicylate caused a decrease in cochlear blood flow that appeared within 30 min following an intramuscular injection of a low dose of sodium salicylate (100 mg/kg). This sodium salicylate dose did not cause a change in auditory sensitivity. For higher doses (200 mg/kg and 300 mg/kg), both cochlear blood flow and auditory sensitivity were affected. The 300 mg/kg dose decreased blood flow by about 25% and elevated compound action potential thresholds by 10 to 25 dB for high frequencies (> or = 8 kHz). Further experiments showed that salicylate-induced threshold shifts were significantly reduced for the mid-frequencies when cochlear blood flow is increased by the vasodilating drug hydralazine (negating the flow reduction caused by salicylate). These data indicate that in addition to the direct effect of systemically administered salicylate on neurosecretory function a decreased blood flow contributes to the ototoxicity of salicylates.
Action Potentials↗
Osmotic pump implant for chronic infusion of drugs into the inner ear.
Continuous long-term delivery of experimental drugs to the cochlea of a small animal, such as a young guinea pig, presents several technical problems. A method of placing and securing a cannula-osmotic pump system is described in this paper. Guinea pigs (225-410 g) were unilaterally implanted with an Alzet micro-pump and cannula for delivery of 20 mM tetrodotoxin (TTX) (six animals) or saline (three animals) for three days (1 microliter/h). Auditory brainstem responses (ABRs) were recorded under light anesthesia on post-implant day 1 and day 3 and compared with pre-implant baseline values. In all six cochleas infused with TTX, most frequencies showed a 30-60dB decrease in sensitivity within 24 h. Saline control animals showed little or no change from baseline sensitivity for most frequencies. In three TTX-infused animals, the cannula-pump unit was removed on day 3, and ABRs were followed during recovery. Most frequencies returned to, or near, pre-implant levels after pump removal but recovery times varied. By day 6, all animals had recovered post-surgical weight loss and showed a gain of 10-40 g. Brains and cochleas were removed and processed for sectioning. Assessment of the cochlear nucleus of non-recovery TTX-treated animals showed a deafness-related flattening of auditory nerve active zones on the treated side.
Animals↗
Chronic electrical stimulation reverses deafness-related depression of electrically evoked 2-deoxyglucose activity in the guinea pig inferior colliculus.
The [14C]-2-deoxyglucose (2-DG) autoradiographic technique was used to study how auditory-related metabolic activity changes with deafness, and how chronic electrical stimulation of the deafened system may modify these changes. Guinea pigs were deafened by administration of kanamycin and ethacrynic acid. After nine weeks of deafness, the basal unstimulated uptake of 2-DG in the inferior colliculus (IC) was lower than in normal hearing control animals. 100 microA of acute cochlear electrical stimulation significantly increased 2-DG uptake in normal hearing animals but did not evoke a significant increase in four or nine week deafened animals. Electrically elicited 2-DG uptake in the IC is therefore depressed by prolonged deafness. In a second series of experiments, after four weeks of deafness, animals were chronically electrically stimulated via a cochlear implant 2.5-3.5 h a day, five days a week for five weeks at 100 microA. Acute cochlear electrical stimulation following this chronic stimulation significantly increased 2-DG uptake in the contralateral IC over unstimulated levels. This suggests that some depressive effects of profound deafness on the auditory brain stem may be reduced or reversed with chronic electrical stimulation by a cochlear implant.
Animals↗