Studies in rats and guinea pigs indicate that local changes in inhibitory transmitters may underlie deafness-induced plastic changes in electrophysiological responsiveness of cells of the mature central auditory system. Following 21 days of bilateral deafness there is an increase in evoked Fos-immunoreactive neurones in the central nucleus of the inferior colliculus (CIC) to contralateral cochlear electrical stimulation, compared with normal or 1-day deafened animals. Deafness is also associated with a dramatic reduction in the population of CIC neurones that respond with suppression of activity to electrical stimulation. Moreover, in vivo microdialysis reveals a marked decrease in gamma-aminobutyric acid (GABA) release from the CIC cells in deafened animals. The results may have general implications for the mediation of central nervous system plasticity induced by deafferentation of sensory input.

Animals↗

PubMed1995

Effect of subendocardial resection on sinus rhythm endocardial electrogram abnormalities.

BACKGROUND: Patients with sustained ventricular tachycardia after acute myocardial infarction frequently have characteristic abnormalities of left ventricular endocardial electrical activity, including fractionated (prolonged, multicomponent, low-amplitude), split (having discrete widely separated deflections), and late (extending after the end of the QRS complex) electrograms. The exact cause and source of these electrograms are not clear. METHODS AND RESULTS: In this study, endocardial electrograms from 18 patients were recorded with a 20-electrode array from the same area immediately before and immediately after resection of subendocardial tissue at the time of surgery for ventricular tachycardia. Electrograms could be compared before and after resection from 298 of 360 (83%) of the electrodes. Before resection, split electrograms were present in 130 (44%) and late components in 81 (27%) of the recordings. Recordings made after resection showed fewer abnormalities, including complete absence of split electrograms as well as all previously recorded late components (P < .02). Mean electrogram amplitude increased from 0.5 +/- 0.8 to 1.0 +/- 1.6 mV (P < .0001) because of removal of the attenuating effect of endocardial scar; mean duration decreased from 112 +/- 38 to 65 +/- 27 ms (P < .0001) mainly because of loss of late and split components. Overall electrogram contour was very similar aside from these changes. CONCLUSIONS: These data show that (1) some of the signal recorded on the endocardial surface is derived from deeper tissue layers and (2) split and late electrogram components appear to be generated by cells in the superficial endocardial layers, since they are eradicated by removal of this tissue. These findings correspond well with previous histological studies of resection specimens that show bundles of surviving muscle cells separated by layers of dense scar that act as an insulator.

Adult↗

PubMed1995

Rebound increase in thrombin generation and activity after cessation of intravenous heparin in patients with acute coronary syndromes.

BACKGROUND: The abrupt cessation of heparin and other thrombin inhibitors when used to treat acute coronary syndromes has been accompanied by a clustering of thrombotic events. It is unknown whether these events are the result of inadequate antithrombin therapy or whether they represent a rebound increase in thrombin activity. This study was designed to determine whether there is a true rebound, as defined by an increase followed by a subsequent decrease, in thrombin activity after discontinuation of intravenous heparin therapy. METHODS AND RESULTS: Thirty-five patients with recent acute myocardial infarction or unstable angina who had received at least 48 hours of intravenous heparin were studied. Patients underwent ST-segment monitoring, and blood samples for determination of thrombin generation and activity were drawn at 0, 3, 6, 10, and 24 hours after heparin discontinuation. Median aPTT was 65 seconds before heparin discontinuation. Median fibrinopeptide A increased from 9.5 to 16.9 ng/mL at 3 hours (P < .0004) and returned to 10.5 by 24 hours. Prothrombin fragment 1.2 likewise transiently increased, from 0.34 to 0.51 nmol/L at 6 hours (P < .0002). Modified antithrombin III decreased over time (P < .002), and activated protein C increased from 2.3 to 4.5 ng/mL at 3 hours (P < .001). Although there were no clinical thrombotic events in the first 24 hours, 4 patients had evidence of ischemia by ST-segment monitoring at a median of 12 hours after heparin discontinuation. The degree of increase in fibrinopeptide A and prothrombin fragment 1.2 was not found to be associated with baseline diagnosis, duration of heparin therapy, baseline level of antithrombin III, or activated protein C. CONCLUSIONS: This study demonstrates a transient rebound increase in thrombin activity as well as in activated protein C upon abrupt discontinuation of intravenous heparin. Clinicians should be vigilant for associated thrombotic events. Further investigation of the significance, mechanism, and possible prevention of this rebound phenomenon is needed.

Aged↗

PubMed1995

Suicide, cancer, and other causes of death among California veterinarians, 1960-1992.

Previous studies reporting on mortality patterns in veterinarians have been restricted to deaths among white male veterinarians. In an effort to examine the mortality of male and female veterinarians of all races, we conducted a standardized proportionate mortality ratio (SPMR) analysis of 450 California veterinarians who died between January 1960 and December 1992. In comparison to State of California general population statistics, white male veterinarians had significantly elevated mortality from malignant melanoma of the skin (SPMR 3.47, 95% CI 1.74, 6.94), cancer of the large intestine (SPMR 1.74, 95% CI 1.04, 2.09), rheumatic heart disease (SPMR 3.50, 95% CI 1.90, 6.43), and suicide (SPMR 2.50, 95% CI 1.84, 3.38). White female veterinarians had significantly elevated mortality from suicide (SPMR 5.89, 95% CI 3.02, 11.48). We also examined veterinary mortality for different lengths of time in the profession. Significantly elevated SPMRs were noted for suicide in veterinarians in the profession for less than 30 years; deaths due to malignant melanoma of the skin and rheumatic heart disease in veterinarians in the profession 20 years or more; and cancer of the large intestine in veterinarians in the profession 30 years or more. Because of significant findings in mortality from suicide among veterinarians of both sexes, it was recommended that future studies and efforts toward suicide prevention include both male and female veterinarians.

Adult↗

PubMed1995

Relative blood velocity measurement in individual microvessels using the self-mixing effect in a fiber-coupled helium-neon laser.

A system has been developed for the measurement of relative blood velocity in micro-vessels by using the self-mixing effect of a laser. A helium-neon laser was coupled to a single-mode optical fiber and the pulled fiber tip (approximately 30 microns diameter) was positioned on a single microvessel. The backscattered Doppler-shifted laser light from moving red blood cells enters the laser cavity and modulates the laser output by influencing internal laser parameters. The signal of the laser output intensity change was produced using a fiber-coupled photodiode and processed by a signal processor. This processor yields an output signal proportional to the first moment of the power spectral density, i.e., the mean frequency of the Doppler shift, corresponding to the blood flow velocity on an arbitrary instrument scale. Results of the in vitro experiment demonstrated that the current method can detect moving particles in fluid and moving red blood cells in a small plastic tube. Data from the in vivo study showed that this system is capable of measuring relative blood velocity in arterioles and venules and can easily follow the cardiac cycle up to 360 beats/min. Primary data suggest that, in addition to high sensitivity, good spatial and temporal resolution, and convenience of use, the self-mixing technique may have an even greater capacity for analysis of blood flow in microvessels than explored in this study, since information on the absolute velocity and velocity distribution of red blood cells is available in self-mixing signal. Further study on its hematocrit dependence and particle bias effect is needed.

Animals↗

PubMed1995

Autoregulation of cochlear blood flow in young and aged mice.

Autoregulation is the capacity of an organ system to maintain organ blood flow constant in response to changes in arterial blood pressure (BP). The current study was carried out to investigate the effect of age on autoregulation of cochlear blood flow (CBF) in mice. CBF was measured using a laser-Doppler flowmeter while BP was increased by angiotensin II injections and decreased by exsanguination in 2-month-old, 10-month-old and 18-month-old CBA mice. Autoregulation of CBF was significantly weaker in the 2-month-old mice when compared to the older mice. Although CBF autoregulation was weaker in the 18-month-old mice compared to the 10-month-old mice, this difference was not statistically significant. These results suggest that autoregulation changes with maturation and age. Findings are discussed in relationship to the possible development of presbycusis.

Age Factors↗

PubMed1995

A case-control study of cocaine use in pregnancy.

OBJECTIVE: This study analyzed the relationships between cocaine use, various other parameters, and perinatal outcomes. STUDY DESIGN: A case-control study of cocaine use was conducted among pregnant women delivered at a large urban hospital in New Orleans, Louisiana. Two control patients for each case, matched for age, race, parity, and month of delivery, were selected. RESULTS: Between April and September 1990, there were 2332 admissions to the obstetric service; urine toxicology screens were obtained on 2225 patients. Cocaine metabolites were identified in 166 patients; 138 of these women had data that could be evaluated. These data were compared with those of 276 control patients, and the findings were analyzed. Complications that occurred significantly more often in study patients included vaginal bleeding, abruptio placentae, premature rupture of the membranes, meconium staining of the amniotic fluid, and low birth weight. Study patients were found to use prenatal care less often (45.0% vs 86.4%) and to smoke cigarettes more often (67.4% vs 35.1%). Regression analysis identified lack of prenatal care and smoking as important variables in birth weight. When these two variables were excluded, identifiable differences in bith weight between cocaine and control mothers were no longer present. CONCLUSION: The reduction in birth weight experienced by patients who used cocaine may be explained by lack of prenatal care and by smoking. Other identified differences observed between study and control patients were not significantly altered by smoking or prenatal care.

Adult↗

PubMed1995

Clotting by heparin of hemoaccess for hemodialysis in an end-stage renal disease patient.

Clotting of vascular access in hemodialysis patients remains a significant problem. The routine use of heparin to anticoagulate the blood during hemodialysis has been helpful in increasing the life span of vascular access in these patients. However, the use of heparin is not without complications. Heparin-induced thrombocytopenia is one of the well-recognized drug-induced thrombocytopenic disorders that by itself usually does not cause serious morbidity. A small proportion of these patients concomitantly develop "paradoxic" acute thrombotic complications. Myocardial infarction, ischemic damage to lower extremities leading to amputation, and cerebrovascular accident with permanent neurologic deficits or leading to death are just some of the disastrous complications. We report a case of paradoxic clotting of the hemoaccess in a patient receiving hemodialysis treatment associated with the use of heparin that has not been previously described. The patient had heparin-dependent platelet antibody resulting in a decrease in platelet count and clotting of the hemoaccess.

Adult↗

PubMed1995

The effect of noise trauma following training exposures in the mouse.

The effect of moderate level acoustic stimulation, or 'training', on a subsequent high intensity noise exposure was studied in CBA/Ca mice. Eight groups of mice were exposed to a variety of training paradigms as well as different intensity traumatic exposures. We sought a combination which would result in the maximum protective effect from acoustic trauma as measured by the auditory brainstem responses. Using a narrow band noise centered at 4.5 kHz, we investigated the effects of a 10-day 'interval' training regimen, allowing a rest period between successive training exposures, as well as several continuous training exposures. These training paradigms were followed by a 24 h traumatic noise exposure (also centered at 4.5 kHz) at one of three intensities, 107, 110, or 117 dB SPL which induce a temporary, a moderate, or a severe permanent threshold shift, respectively. In none of these trained groups was a protective effect demonstrated at any time up to one month following a subsequent traumatic noise exposure. Several groups demonstrated higher compound threshold shifts after the traumatic noise exposure compared to controls. After a recovery period of 4 weeks nearly all trained groups demonstrated a tendency toward higher permanent threshold shifts than the control, untrained, animals. While no protective effect was demonstrated, examination of the threshold shifts following the training periods and after the traumatic noise exposures raised interesting questions for future investigation regarding the inherent resistance to noise induced threshold shifts in the mouse.

Acoustic Stimulation↗

PubMed1995

Age-related changes in cochlear vascular conductance in mice.

Vascular changes contribute to age-related hearing loss but the mechanisms involved in microvascular reactivity, particularly in the aged ear, are still incompletely understood. In this study, possible age-related changes in cochlear blood flow (CBF) and vascular reactivity were studied in presbycusic mice (C57BL/6) and young, age-matched, and old controls (CBA/J) without presbycusis. Reactivity was monitored by laser Doppler flowmetry and assessed by change in cochlear vascular conductance (VC) (defined as the ratio of CBF to blood pressure) in response to round window-applied sodium nitroprusside, a vasodilating agent. Mean VC response of C57BL/6 mice differed from controls both in maximum response and in post-drug recovery time. In C57BL/6 mice, mean VC increased about 28%, in contrast to an increase of over 40% in young and age-matched CBA/J controls. A less elevated VC response, similar to that of the presbycusic mice, was shown by aged (20-21 month) controls. Also, VC response in C57BL/6 mice was sustained throughout the 60 min observation period, while response of most CBA/J controls recovered in 50 min or less. These changes suggest age-dependent, pathologically-related altered responsiveness in cochlear vascular reactivity.

Aging↗

PubMed1995

Capsaicin-induced release of substance P increases cochlear blood flow in the guinea pig.

Physiological evidence from several studies suggests that endogenous vasoactive peptides, such as substance P (SP), and their respective receptor populations may participate in the mechanisms that govern the autoregulatory capacity of the cochlear vascular system. However, these studies do not provide evidence regarding the origin or mechanism of action of SP. Capsaicin sensitivity has been used as a marker for sensory neurons, and the release of SP following capsaicin treatment suggests a sensory transmitter role for SP. The present investigation examines the relationship between the capsaicin-sensitive sensory neurons and SP in the regulation of cochlear blood flow (CBF). In 75 pigmented guinea pigs, the cochlea was surgically exposed and a laser Doppler flowmeter probe placed on the bony surface of the first turn to monitor CBF. Capsaicin solutions (2 microliters, 0.01%, 0.001% and 0.0001%) applied to the round-window membrane (RWM) resulted in a dose-related CBF increase, without change in the systemic blood pressure. This effect could be inhibited by application of a specific SP receptor antagonist, [D-Pro2,D-Trp7,9]-SP, after which none of the capsaicin concentrations used induced a change in CBF. Moreover, after RWM application of 50 nmol/2 microliters of SP there was a significant increase in CBF. No CBF change was observed with the lower concentrations of 10 nmol SP or 100 pmol SP. These results indicate a role of SP in CBF regulation and give indirect evidence that SP is released from capsaicin-sensitive primary sensory neurons.

Animals↗

PubMed1995

Autoregulation of cochlear blood flow in the hydropic guinea pig.

Previous data suggest that regulation of cochlear blood flow (CBF) may be abnormal in the hydropic guinea pig. The purpose of this study was to employ the technique of anterior inferior cerebellar artery (AICA) occlusion to measure CBF autoregulation in experimental endolymphatic hydrops. This study also addresses the role of the cochlear sympathetic neural innervation and nitric oxide in CBF regulation with hydrops. In anesthetized guinea pigs, CBF was measured with a laser Doppler flowmeter probe while the AICA was intermittently occluded with a microvascular occluder. The CBF response was measured in normal, 6-week, and 12-week chronically hydropic animals. The gain factors (0 = no autoregulation, 1 = complete autoregulation) for 1-min occlusion were 0.95 +/- 0.16 (control), 0.77 +/- 0.28 (6 week, P = 0.164), and 0.67 +/- 0.25 (12 week, P = 0.037). NG-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of nitric oxide synthase, was infused intravenously to assess basal nitric oxide (an endogenous vasodilator) production in the hydropic ear. With infusion of L-NAME, CBF was reduced by 9.16 +/- 11%, 10.7 +/- 10% (P = 0.87), and 16.6 +/- 18% (P = 0.95), in the control, 6-week, and 12-week animals, respectively. In a separate group of 12-week hydropic animals, the left superior cervical ganglion (SCG) was anesthetized with lidocaine, and AICA occlusions were performed pre- and post-blockade. Prior to blocking the SCG, the gain was 0.712 +/- 0.02 and afterwards 0.708 +/- 0.051 (P = 0.93). The above results show that there was a statistically significant reduction in CBF autoregulation in the 12-week hydropic animals. There was no difference in basal nitric oxide production in normal versus hydropic animals nor was there a change in autoregulation following blockade of the SCG. These data provide clear evidence for reduced CBF autoregulation in experimental endolymphatic hydrops.

Animals↗