Salmonella Isolates from wild-caught Tokay Geckos (Gekko gecko) imported to the U.S. from Indonesia

Reptiles account for ～10% of live animal shipments imported to the United States (U.S.), the majority of which are sold in the pet trade. Characterizing Salmonella shedding by imported reptiles is of value to public health, the pet industry, and veterinary medicine. Here we report results of a pilot survey of Salmonella serotypes isolated from wild-caught Indonesian Tokay geckos (Gekko gecko) imported to the U.S. Upon arrival, the geckos were individually housed until a fecal sample was acquired for Salmonella culture. The geckos were divided into three groups with variable numbers to investigate density effects. A second group was imported after 3 months and combined with the previous groups. A total of 88 Salmonella isolates were obtained from 110 geckos surveyed, representing 14 serogroups and 17 unique serotypes. Group prevalence ranged from 31-73%. A significant increase in prevalence and a change in serotype richness were detected between the time of import and 6 months later at necropsy. Six isolates (6.8%) expressed resistance to more than one antibiotic. All S. enterica subsp. enterica Adelaide isolates were resistant to nalidixic acid and sulfisoxazole, one S. enterica subsp. arizonae 61:k:z35 isolate was resistant to ampicillin and sulfisoxazole, and another 61:k:z35 isolate was resistant to streptomycin and sulfisoxazole. Forty-three additional isolates expressed resistance only to sulfisoxazole. The mechanisms for increased prevalence and apparent change in serotype richness are unknown, but could be due to stress associated with trade, transport, and captivity, increased transmission from unnaturally high densities, or contact with other species shedding Salmonella along the trade route. Future studies to differentiate the physical, social, and physiological effects of trade-related conditions on Salmonella shedding and transmission among reptiles will benefit the industry by identifying ways to reduce mortality, and safeguard the individuals handling animals along the transport chain and other species encountered en route.     

Distortion product otoacoustic emissions measured as vibration on the eardrum of human subjects

It has previously not been possible to measure eardrum vibration of human subjects in the region of auditory threshold. It is proposed that such measurements should provide information about the status of the mechanical amplifier in the cochlea. It is this amplifier that is responsible for our extraordinary hearing sensitivity. Here, we present results from a laser Doppler vibrometer that we designed to noninvasively probe cochlear mechanics near auditory threshold. This device enables picometer-sized vibration measurements of the human eardrum in vivo. With this sensitivity, we found the eardrum frequency response to be linear down to at least a 20-dB sound pressure level (SPL). Nonlinear cochlear amplification was evaluated with the cubic distortion product of the otoacoustic emissions (DPOAEs) in response to sound stimulation with two tones. DPOAEs originate from mechanical nonlinearity in the cochlea. For stimulus frequencies, f1 and f2, with f2/f1 = 1.2 and f2 = 4-9.5 kHz, and intensities L1 and L2, with L1 = 0.4L(2) + 39 dB and L2 = 20-65 dB SPL, the DPOAE displacement amplitudes were no more than 8 pm across subjects (n = 20), with hearing loss up to 16 dB. DPOAE vibration was nonlinearly dependent on vibration at f2. The dependence allowed the hearing threshold to be estimated objectively with high accuracy; the standard deviation of the threshold estimate was only 8.6 dB SPL. This device promises to be a powerful tool for differentially characterizing the mechanical condition of the cochlea and middle ear with high accuracy.     

Comparison of the auditory systems of heterosexuals and homosexuals: Click-evoked otoacoustic emissions

Click-evoked otoacoustic emissions (CEOAEs) are echo-like waveforms emitted by normal-hearing cochleas in response to a brief transient. CEOAEs are known to be stronger in females than in males. In this experiment, the CEOAEs of homosexual and bisexual females were found to be intermediate to those of heterosexual females and heterosexual males. A parsimonious explanation is that the auditory systems of homosexual and bisexual females, and the brain structures responsible for their sexual orientation, have been partially masculinized by exposure to high levels of androgens prenatally. No difference in CEOAEs was observed between homosexual and heterosexual males.     

畸变产物耳声发射检测对早期梅尼埃病的诊断价值

目的探讨早期梅尼埃病的畸变产物耳声发射（DPOAE）特点。方法选取22例梅尼埃病患者和15例正常对照,分别于口服甘油前及30rain后测试DPOAE。结果患者组DPOAE幅值在783、1105、1560Hz出现下降,与对照组有明显差异（P＜0．05）,2kHz以上幅值较对照组偏低,但无明显差异;口服甘油30min后,DPOAE幅值在783、1105、1560Hz明显升高．与口服前比较有明显差异（P＜0．05）,较对照组偏低但差异不显著。结论DPOAE有助于早期梅尼埃病的诊断。     

Effects of spontaneous ventilation on the circulation

Spontaneous inspiration causes an increase in right ventricular stroke volume due to a transient increase in venous return. In contrast, spontaneous inspiration causes a fall in left ventricular stroke volume which is exaggerated in conditions of accentuated pleural pressure swings and pericardial disease. This is manifested by the clinical sign ofpulsus paradoxus. Recent evidence supports the idea thatpulsus paradoxus is the result of two mechanisms. First, negative pleural pressure surrounding the left ventricle is equivalent to an increase in aortic pressure and impedes emptying of the left ventricle much like an increase in afterload. Second, distention of the right ventricle due to the transient increase in venous return causes an elevation of left ventricular diastolic pressure due to ventricular interdependence and therefore impedes left ventricular filling. The mechanism of negative pleural pressure “afterload” is thought to be the major cause of pulsus paradoxus when pleural pressure swings are accentuated. Ventricular interdependence is thought to predominate when pericardial disease is present.     

Salient features of otoacoustic emissions are common across tetrapod groups and suggest shared properties of generation mechanisms

Otoacoustic emissions (OAEs) are faint sounds generated by healthy inner ears that provide a window into the study of auditory mechanics. All vertebrate classes exhibit OAEs to varying degrees, yet the biophysical origins are still not well understood. Here, we analyzed both spontaneous (SOAE) and stimulus-frequency (SFOAE) otoacoustic emissions from a bird (barn owl, Tyto alba) and a lizard (green anole, Anolis carolinensis). These species possess highly disparate macromorphologies of the inner ear relative to each other and to mammals, thereby allowing for novel insights into the biomechanical mechanisms underlying OAE generation. All ears exhibited robust OAE activity, and our chief observation was that SFOAE phase accumulation between adjacent SOAE peak frequencies clustered about an integral number of cycles. Being highly similar to published results from human ears, we argue that these data indicate a common underlying generator mechanism of OAEs across all vertebrates, despite the absence of morphological features thought essential to mammalian cochlear mechanics. We suggest that otoacoustic emissions originate from phase coherence in a system of coupled oscillators, which is consistent with the notion of “coherent reflection” but does not explicitly require a mammalian-type traveling wave. Furthermore, comparison between SFOAE delays and auditory nerve fiber responses for the barn owl strengthens the notion that most OAE delay can be attributed to tuning.Numerous fundamental biophysical questions regarding cochlear mechanics remain unanswered, such as the relative dominance between viscous and inertial fluid forces affecting the stimulation of hair cells and the longitudinal coupling between them (1, 2). These aspects, combined with relative experimental inaccessibility, have led to much uncertainty with regard to the micromechanics at work in the organ of Corti, and thereby precisely how auditory information is initially peripherally encoded (i.e., forward transduction). One area in which there is broad agreement, however, is the notion of an “active” ear: A nonlinear amplification mechanism(s) (i.e., reverse transduction) boosts detection of low-level sounds and compresses a wide range of sound intensities into a narrower range of vibration magnitude (3). One manifestation of this process is the existence of otoacoustic emissions (OAEs), sounds measurable noninvasively in the external ear canal using a sensitive microphone (4). Because only healthy ears tend to emit, OAEs have had a significant clinical impact (e.g., pediatric audiology). Emissions can arise spontaneously (SOAEs) or be evoked by an external stimulus. In fact, SOAEs are commonly pointed to as salient evidence for active amplification, especially given their connections to perception such as “rippling” in audiograms (threshold microstructure), indicative of localized changes in detection thresholds (5, 6). SOAEs are, however, idiosyncratic in nature: Not all mammalian species have them, whereas several nonmammalian classes such as lizards exhibit robust activity. Humans have a high incidence of SOAEs, although some (healthy) ears have them but others do not. So, although SOAEs are not required per se for sensitive hearing, they provide a powerful and noninvasive means to study the function of the inner ear.A common thread through vertebrate OAEs studies is that of an active oscillator, typically a stereovillar hair cell, acting as the essential transducer (3, 7–10). A comprehensive theory for SOAE generation across vertebrates is lacking, however, because knowledge of hair cell physiology has not yet been well connected to the collective behavior of the system as a whole. Vertebrate ears contain anywhere from 50 to 20,000 hair cells, all coupled together to varying degrees. Two different, and seemingly diametric, theoretical approaches explaining SOAEs have emerged. One model class considers the ear as a system of coupled nonlinear oscillators exhibiting a limit cycle (3, 11–13). Typically, these models are “local” in that a given oscillator is only directly coupled to its nearest neighbors. The other class focuses predominantly on the mammalian cochlea (14–19), where “global” coupling between elements arises from the hydromechanics that give rise to wave mechanics. One salient example is the standing wave model (16), where the peak of the traveling wave and stapes act as the two reflecting boundaries with a nonuniform gain medium in between, somewhat akin to a laser. That study predicted and verified interrelationships between spontaneous and evoked OAEs. Furthermore, acknowledging that nonmammalian ears exhibit different mechanics, Shera (16) proposed that the appearance of “standing waves” need not necessarily depend upon traveling waves along the basilar membrane (BM) but could arise via other mechanisms that create appropriate phase differences (e.g., delays due to tuning). Motivated by the uncertain role of BM traveling waves in nonmammals, our present goal was to exploit the large morphological differences that exist across vertebrate ears (20) to gain quantitative insight into SOAE generation mechanisms.Here we focus on two different nonmammalian species: a bird, the barn owl, and a lizard, the green anole. Both species exhibit robust OAE activity (21–25). The barn owl (Tyto alba), is known for its remarkable ability to hunt by auditory cues alone (26). The peripheral auditory morphology, neurophysiology, and psychophysics of this species have been well characterized (27–30). Owl auditory nerve fiber (ANF) responses show average frequency tuning but have remarkably high phase-locking capabilities extending out to 10 kHz (31). Furthermore, the tonotopic map along the basilar papilla (in contrast to the mammalian organ of Corti) is nonexponential, with representation of higher frequencies (5–10 kHz) greatly expanded. The role of BM waves is unknown in owls, although data from pigeons are suggestive of their existence in birds (32). The inner ear of lizards is profoundly different from that of both humans and barn owls. In anoles, the short auditory papilla (∼0.5 mm) contains ∼150 hair cells and has no overlying tectorial membrane over the SOAE-producing cells (33). Bundle orientations for hair cells in a given radial cross-section are arranged in a self-opposing fashion. Furthermore, there is ample evidence indicating a lack of a traveling wave on the BM (34, 35). In this study, we systematically explored interrelationships within individual ears between SOAEs and stimulus frequency emissions (SFOAEs), the simplest type of evoked emission via a single low-level stimulus tone (15). In short, we found that important OAE characteristics are shared between the two species and with published data from humans. This we interpret as revealing generic features of the underlying active processes.     

Pharmacokinetics of salicylates in elderly.

In order to study changes in the pharmacokinetics of salicylates in old people, we used two groups of inpatients without hepatic or renal impairment: the first comprised 15 patients more than 65 years old, mean age 77 years; the second, 7 patients of mean age 21 years. Each patient was given 1 g of acetylsalicylic acid orally in the morning while fasting. Blood samples were subsequently taken after 30, 60 and 90 min and 2, 3, 4, 6, 8, 10, and 24 h. Fluorimetric assay results were analyzed kinetically with a mathematical model corresponding to a single diffusion compartment model. The results showed only a slight increase in the absorption half-time in old subjects, and a marked increase in elimination half-time (3.71 and 2.38 h in old and young subjects, respectively; t = 2.33: p less than 0.05) and in the volume of distribution (5.51 and 3.83 liters respectively; t = 3.20: p less than 0.1). On the other hand, bioavailability varied little, as did metabolic clearance. This study confirms that intestinal absorption of this drug is not much impaired in old people, while hepatic and/or renal elimination functions are changed. This finding agrees with results found for aminopyrine, antipyrine, and digoxin.     

Effect of intravenous salicylates on the gastric mucosal barrier in man

A high incidence of gastric ulceration is reported in patients with rheumatoid arthritis and in addicts taking large doses of aspirin. In rheumatoid arthritis a serum salicylate level of 15 mg% is considered to be therapeutic. We studied gastric mucosal permeability to ions in 9 healthy subjects given 3 g aspirin intravenously over 2 hours (mean serum salicylate, 17 mg%). Atropine was injected intravenously to reduce acid secretion which masks H⁺ loss. H⁺ and Na⁺ fluxes during aspirin infusion were not significantly different from those during intravenous saline infusion. Thus, high blood levels of salicylates did not impair the gastric mucosal barrier. Intragastric salicylic acid following intravenous aspirin infusion increased gastric mucosal permeability to H⁺ and Na⁺ ions. Under the conditions of these studies the effect was more marked in males. Gastric absorption of salicylic acid was similar in males and females, and the amount absorbed was unaffected by the presence of high blood levels of salicylates. Absorption of salicylic acid was significantly greater in the first period of salicylic acid instillation (mean, 28%) than in the second (mean, 21%) and third (mean, 16%) periods. Percentage absorption of undissociated salicylic acid was at least three times greater than that of H⁺ ions.This study was supported by research grants from the N. S. W. State Cancer Council and the National Health and Medical Research Council.     

Effects of spontaneous hypertension and age on arterial connective tissue in the rat

Weights of aorta and heart and accumulation of collagen and elastin in aorta were determined in spontaneously hypertensive and control Wistar rats of 14 weeks, six months, one year and 18 months of age. It was found that in control rats weights of aorta and heart increased as a function of age but when expressed as percent of body weight there was no change with age. However, changes in SHR's were more marked, with the aortic and heart weights increasing progressively with age to a much greater extent than in control rats. Expressed as percent body weight, aortic weight increased progressively in SHR and heart weight increased by 18 months indicating hypertrophy of the cardiovascular system in the SHR with age.

Absolute quantities of connective tissues increased in aorta in both control and hypertensive rats with age. However, the accumulation was more marked in hypertensive. If connective tissue is expressed as percent of aortic weight, collagen plus elastin actually decreased as a function of age in control and to a much greater extent in SHR. The results indicate (1) increased accumulation of connective tissue in aortae of rats with age and even greater increase in aortae of hypertensive rats with age. (2) Increase in aortic smooth muscle mass with age in control and even greater increase in hypertensive aortae. It is concluded that long term spontaneous hypertension in the rat results in an increase over control rats in the major aortic wall components with smooth muscle increase greater than connective tissue increase. These changes occur in late stages of hypertension as well as early stages.     

Pharmacodynamics and dosing of aminoglycosides

Aminoglycosides are concentration-dependent killing agents whose pharmacodynamic predictors of efficacy are the area-under-the-curve to minimum inhibitory concentration ratio and the peak to minimum inhibitory concentration ratio. Prospective studies have shown that these agents can be given once-daily or less frequently in most clinical settings, with equal efficacy and possible reduced toxicity. Dosages for different clinical settings have been studied and methods are available to monitor once-daily dosing.