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Biomedical subjects

J M Miller

Publications and source records attributed to J M Miller.

At least 73 records · Page 4Linked to original sources

Intense noise induces formation of vasoactive lipid peroxidation products in the cochlea.

This study investigates the correlation between the formation of reactive oxygen species (ROS) and auditory damage in noise-induced hearing loss. The noise exposure (4-kHz octave band, 115 dB SPL, 5 h) created permanent threshold shifts at frequencies from 2 to 20 kHz. The lipid peroxidation product, 8-isoprostane, was determined biochemically and histochemically as an indicator of ROS. Noise exposure increased 8-isoprostane levels in the cochlea in a time-dependent manner. After 5 h of exposure, 8-isoprostane levels were more than 30-fold greater than baseline, and decreased rapidly after the termination of noise. The immunoreactivity to 8-isoprostane was increased in the stria vascularis, spiral ganglion cells and the organ of Corti. In the organ of Corti, immunostaining was restricted to the second turn in a region 10-12 mm from the apex. This region sustained most of the permanent hair cell damage as revealed in surface preparations. Outer hair cells were more heavily immunostained than inner hair cells while Hensen's cells showed still less immunostain. These data are consistent with the view that ROS are involved in noise-induced damage. However, the relationship between ROS formation and tissue damage appears complex. In the organ of Corti, the pattern of noise-induced lipid peroxidation correlates well with subsequent morphological damage. The stria vascularis, however, does not sustain permanent damage despite intense lipid peroxidation. Differences in endogenous antioxidant levels and commitment to different apoptotic or survival pathways may underlie such differential responses.

Animals↗

Cruise ships: high-risk passengers and the global spread of new influenza viruses.

In 1997, passengers on North American cruises developed acute respiratory illnesses (ARIs); influenza was suspected. We reviewed 1 ship's medical records for 3 cruises: cruise 1 (31 August to 10 September 1997), cruise 2 (11-20 September 1997), and cruise 3 (20-30 September 1997). Medically attended ARI was defined as any 2 of the following symptoms: fever (temperature, > or =37.8 degrees C) or feverishness, sore throat, cough, nasal congestion, chills, myalgia, and arthralgia. During cruise 2, we collected nasopharyngeal swabs for viral culture from people with ARI and surveyed passengers for self-reported ARI (defined as above except feverishness was substituted for fever). The outbreak probably began among Australian passengers on cruise 1 (relative risk, 3.3; 95% confidence interval, 1.89-5.77). Of 1284 passengers on cruise 2, 215 (17%) reported ARI, 994 (77%) were aged > or =65 years, and 336 (26%) had other risk factors for respiratory complications. An influenza strain not previously identified in North America was isolated. We concluded that an "off-season" influenza outbreak occurred among international travelers and crew on board this cruise ship.

Adolescent↗

Craniofacial variation in Homo habilis: an analysis of the evidence for multiple species.

The question of heterogeneity in the Homo habilis sample continues to be controversial. Various lines of evidence have been used to reject the null hypothesis of intraspecific variation. This evidence derives from analyses of endocranial volume variation, probability estimates of sexual dimorphism, facial variation, cranial angles, CV analysis of craniofacial variation, the multivariate pattern of sexual dimorphism, the pattern of variability (CV) profiles, distance data using exact randomization methods, and various kinds of quantitative ordinations of fossils. Although consensus is lacking as to how the H. habilis sample is to be split, there is a growing perception that the degree of variation among the fossils is too great and the pattern of variation is too different to be explained by intraspecific variation. This has resulted in the recognition of new species such as "Homo rudolfensis." The present study critically examines the evidence commonly cited as the basis for recognizing multiple species in the extended H. habilis hypodigm. Reanalysis and reinterpretation of these data indicates that: (1) the degree of variation in the H. habilis sample is typical of modern hominoids, and (2) the pattern of variation among specimens of the H. habilis sample is consistent with intraspecific variation. Thus, at present, there is no sound basis to reject the null hypothesis of intraspecific variation as an adequate explanation of the morphological variation seen among specimens of the extended H. habilis sample. If multiple species are indeed represented, then their presence has not yet been satisfactorily demonstrated.

Animals↗

Evaluation of the accuracy and reproducibility of a practical PCR panel assay for rapid detection and differentiation of Mycobacterium avium subspecies.

The Mycobacterium avium subspecies (MAs) include the closely related MAs avium and MAs paratuberculosis. This study was conducted to evaluate the performance of a PCR panel assay as a diagnostic tool to detect and differentiate MAs avium and MAs paratuberculosis infection. Specific oligonucleotides primers derived from the 16 S rRNA (MAs) sequence, insertion elements IS 901 (MAs avium), IS 1245 Mycobacterium avium complex (MAC), IS 900 (MAs paratuberculosis), and the hspX (MAs paratuberculosis) gene sequences were synthesized and used in preassembled PCR reaction mixtures. These five primer sets made up the PCR panel assay. To determine the accuracy of the PCR panel assay for MAs avium and MAs paratuberculosis strain detection and differentiation, lysates of mycobacterial DNA from 120 (n=120) strains were tested with the PCR panel assay by one laboratory (#1). The PCR panel assay specifically detected and differentiated 91/91 (100%) of MAs avium and MAs paratuberculosis strains tested in this study. The PCR panel assay also specifically differentiated all MAs avium and MAs paratuberculosis strains from all but one (M. intracellulare, serovar 23) of the other mycobacterial strains tested. To confirm the accuracy and evaluate the reproducibility of the PCR panel assay, samples were numbered and given to a different laboratory (#2) as 'unknowns' for identification by the PCR panel assay. In this study, the overall accuracy for strain identification using the PCR panel assay was 99.2% (119/120). The reproducibility of the PCR panel assay when comparing data from laboratory #1 with laboratory #2 was found to be 100% (120/120). These results indicate that this 'easy-to-use', rapid PCR method can accurately and reliably detect and differentiate closely related MAs avium and MAs paratuberculosis from each other and from other mycobacterial species. The PCR panel assay can also differentiate mixed cultures of MAs. The simplicity of this PCR method could be beneficial to laboratories that test for members of MA.

Animals↗

Differential effects of cough, valsalva, and continence status on vesical neck movement.

OBJECTIVE: We tested the null hypothesis that vesical neck descent is the same during a cough and during a Valsalva maneuver. We also tested the secondary null hypothesis that differences in vesical neck mobility would be independent of parity and continence status. METHODS: Three groups were included: 17 nulliparous continent (31.3 +/- 5.6; range 22-42 years), 18 primiparous continent (30.4 +/- 4.3; 24-43), and 23 primiparous stress-incontinent (31.9 +/- 3.9; 25-38) women. Measures of vesical neck position at rest and during displacement were obtained by ultrasound. Abdominal pressures were recorded simultaneously using an intravaginal microtransducer catheter. To control for differing abdominal pressures, the stiffness of the vesical neck support was calculated by dividing the pressure exerted during a particular effort by the urethral descent during that effort. RESULTS: The primiparous stress-incontinent women displayed similar vesical neck mobility during a cough effort and during a Valsalva maneuver (13.8 mm compared with 14.8 mm; P =.49). The nulliparous continent women (8.2 mm compared with 12.4 mm; P =. 001) and the primiparous continent women (9.9 mm compared with 14.5 mm; P =.002) displayed less mobility during a cough than during a Valsalva maneuver despite greater abdominal pressure during cough. The nulliparas displayed greater pelvic floor stiffness during a cough compared with the continent and incontinent primiparas (22.7, 15.5, 12.2 cm H(2)O/mm, respectively; P =.001). CONCLUSION: There are quantifiable differences in vesical neck mobility during a cough and Valsalva maneuver in continent women. This difference is lost in the primiparous stress-incontinent women.

Adult↗

Mental health professionals' experiences reporting suspected child abuse and maltreatment.

OBJECTIVE: The purpose of this study was to provide systematic data on the experiences of mental health professionals (e.g., psychiatrists, psychologists, and social workers) who reported cases of suspected child abuse and maltreatment concerning their clients. METHOD: Mail surveys were completed by 258 mental health professionals known to have reported a case of suspected child abuse and maltreatment to the New York State Central Register (NYSCR) in 1993. Subjects were asked to complete a survey describing their experience with making reports, referring to a specific case they reported. RESULTS: About 40% did not inform the client about the limits of confidentiality until reportable material came up. Most clinicians reported that informing clients about the limits of confidentiality did not deter them from entering treatment. Many clinicians learned about abuse/maltreatment after approximately 3 months into therapy. Even very experienced clinicians usually consulted with others before making the report. Clinicians most typically informed the client about the report directly and before it was made, but did not call the NYSCR in the presence of the client. Following the report, most clinicians performed additional activities such as calling clients and scheduling additional sessions. When clients evidenced resistance to continuing therapy, it usually dissipated after a brief period of time. In over 72% of the cases, making the report did not disrupt the relationship and in many instances it was helpful in the therapeutic process; about 27% were continuously resistant or terminated therapy shortly after the report was made. CONCLUSIONS: Implications for practice, training, program development, and research are discussed.

Adolescent↗

Glial cell line-derived neurotrophic factor has a dose dependent influence on noise-induced hearing loss in the guinea pig cochlea.

We examined the effectiveness of glial cell line-derived neurotrophic factor (GDNF) to attenuate cochlear damage from intense noise stress. Subjects were exposed to 115 dB SPL one octave band noise centered at 4 kHz for 5 h. They received artificial perilymph with or without GDNF into the left scala tympani at 0.5 microliter/h from 4 days before noise exposure through 8 days following noise exposure. Different concentrations of GDNF (1 ng/ml, 10 ng/ml, 100 ng/ml, and 1 microgram/ml) were applied chronically directly into the guinea pig cochlea via a microcannula and osmotic pump. Noise-induced hearing loss was assessed with pure tone auditory brainstem responses (at 2, 4, 8 and 20 kHz), measured prior to surgery, 1 day before noise exposure, and 7 days following noise exposure. Subjects were killed on day 8 following exposure for histological preparation and quantitative assessment of hair cell (HC) damage. A dose-dependent protective effect of GDNF on both sensory cell preservation and hearing function was found in the treated ears. At 1 ng/ml, GDNF showed no significant protection; at 10 ng/ml, GDNF showed significant HC protection; and at 100ng/ml, it was greater and bilateral. At 1 microgram/ml, GDNF appeared to have a toxic effect under noise stress in some cochleae. These findings indicate that GDNF at certain concentrations can effectively protect the inner ear from noise-induced hearing loss.

Animals↗

Cochleotopic fos immunoreactivity in cochlea and cochlear nuclei evoked by bipolar cochlear electrical stimulation.

Fos-like immunoreactivity evoked by basal, second or apical turn bipolar intracochlear electrical stimulation was evaluated in the spiral ganglion and cochlear nuclei. At stimulation levels of six times the electrically evoked auditory brain stem response thresholds, immunoreactive neurons were observed at appropriate discrete cochleotopic regions relative to stimulation site. The number of neurons increased with stimulus level and closely correlated to wave I amplitude. At 10 times thresholds, some spread in fos-like immunoreactivity to adjacent cochlear turns was found. However, fos-like immunoreactivity at this high level of stimulation still clearly showed a differential distribution in density of expression. These results indicated that the restricted topographic distribution of activity evoked by high levels of electrical stimulation is initiated at first order primary neurons of the system. For the profoundly deaf with cochlear implants, this indicates that place (channel) information can be maintained in the spiral ganglion and central nervous system even at very high levels of electrical stimulation. Together with our previous studies, these results indicate that fos provides a marker which can be used for evaluation of extent and pattern of cellular activation throughout the central auditory pathways, including activation of auditory nerve cells.

Animals↗

Glutathione limits noise-induced hearing loss.

The generation of reactive oxygen species (ROS) is thought to be part of the mechanism underlying noise-induced hearing loss (NIHL). Glutathione (GSH) is an important cellular antioxidant that limits cell damage by ROS. In this study, we investigated the effectiveness of a GSH supplement to protect GSH-deficient animals from NIHL. Pigmented guinea pigs were exposed to a 4 kHz octave band noise, 115 dB SPL, for 5 h. Group 1 had a normal diet, while groups 2, 3 and 4 were fed a 7% low protein diet (leading to lowered tissue levels of GSH) for 10 days prior to noise exposure. One hour before, immediately after and 5 h after noise exposure, subjects received either an intraperitoneal injection of 5 ml/kg body weight of 0.9% NaCl (groups 1 and 2), 0.4 M glutathione monoethyl ester (GSHE; group 3) or 0.8 M GSHE (group 4). Auditory thresholds were measured by evoked brain stem response at 2, 4, 8, 12, 16 and 20 kHz before and after noise exposure. Ten days post exposure, group 1 showed noise-induced threshold shifts of approximately 20 dB at 2, 16 and 20 kHz and 35 to 40 dB at other frequencies. Threshold shifts in group 2 were significantly greater than baseline at 2, 4, 16 and 20 kHz. GSHE supplementation in a dose-dependent fashion attenuated the threshold shifts in the low protein diet animals. Hair cell loss, as evaluated with cytocochleograms, was consistent with the auditory-evoked brainstem response results. Group 2 exhibited significantly more hair cell loss than any of the other groups; hair cell loss in group 3 was similar to that seen in group 1; group 4 showed less loss than group 1. These results indicate that GSH is a significant factor in limiting noise-induced cochlear damage. This is compatible with the notion that ROS generation plays a role in NIHL and that antioxidant treatment may be an effective prophylactic intervention.

Animals↗

Differential protective effects of neurotrophins in the attenuation of noise-induced hair cell loss.

The protective efficacy of neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) at 1 or 10 microg/ml was assessed in guinea pigs exposed to 4 kHz octave band noise at 115 dB SPL for 5 h. BDNF, NT-3 or artificial perilymph was delivered to the scala tympani via a mini-osmotic pump, beginning 4 days prior to noise exposure and continuing for 1 week post-exposure. Protection was assessed physiologically by the change in auditory brainstem response (ABR) threshold, and histologically by outer hair cell (OHC) survival. There was a statistically significant increase in OHC survival and a decrease in ABR threshold shift in animals receiving NT-3 at a concentration of 10 microg/ml. In animals receiving 1 microg/ml NT-3, there was a significant increase in OHC survival in the first row of OHC, but no significant change in ABR threshold, relative to control animals. In animals treated with BDNF, no significant functional or histological protection was observed. The protection afforded by NT-3 (10 microg/ml) treatment was similar in magnitude to that reported previously with glial cell line-derived neurotrophic factor and suggests that several factors may be involved in the protective response.

Animals↗

Changes in cochlear electrical stimulation induced Fos expression in the rat inferior colliculus following deafness.

Fos immunoreactive (IR) staining was used to examine changes in excitatory neuronal activity in the rat inferior colliculus (IC) between normal hearing and 21 day deaf rats evoked by basal or apical monopolar cochlear electrical stimulation. The location of evoked Fos IR neurons was consistent with expected tonotopic areas. The number of Fos IR cells increased as stimulation intensity increased in both normal and 21 day deaf animals. Stimulation at 1. 5x threshold evoked fewer Fos IR cells in 21 day deafened animals compared to normal hearing animals. At 5x and above, however, significantly increased numbers of Fos IR neurons (in a larger grouping) were evoked in 21 day deafened animals compared to normal hearing animals. Another group of animals had 7 days of deafness followed by 14 days of chronic basal cochlear electrical stimulation. In this group basal monopolar stimulation at 5x evoked not only a greater number of Fos IR neurons, compared to normal hearing animals, but the location of their grouping was slightly shifted to a more dorso-lateral region in the contralateral IC, compared to the normal hearing and 21 day deaf groups. These observations indicate that both deafness and chronic electrical stimulation may alter central auditory processing.

Animals↗

Technical report: chronic and acute intracochlear infusion in rodents.

As a follow-up to the Brown et al., 1993 technique, we have made several improvements to the micro-cannula, osmotic pump procedure, enabling chronic intracochlear infusions while maintaining hearing. In addition, acute bolus injection techniques are briefly described in guinea pig, rat and mouse.

Acoustic Stimulation↗

Management of postinfarct ventricular tachycardias.

The clinical profile of patients with postinfarct VT has changed in the past two decades. Along with these changes, existing treatments have improved, and entirely new therapeutic approaches have been developed. The expanded range of treatment options has made postinfarct VT a less imposing clinical problem than it once was. Emerging therapies promise to make an even greater beneficial impact. The challenge in treating patients with postinfarct VT has changed from merely keeping patients alive to keeping up with innovations in therapy that can provide them with a better quantity and quality of life.

Anti-Arrhythmia Agents↗

Violence in the schools: clinical issues and case analysis for high-risk children.

School violence in rural communities has gained considerable attention nationally. Examined are theoretical considerations involving escape theory, the risk and protective factors for school violence, case analyses of recent case studies, and discussion of recent school violence involving fatal injuries to others. Also discussed are diagnostic issues in understanding children who are at-risk for school violence and ways school violence maybe managed in the schools. Suggestions and recommendations including recommendations provided by the National School Safety Center for school personnel are offered, as are steps to be taken in creating a safe school environment. This information may be helpful to child psychiatry and clinical personnel who provide services to school aged children.

Adolescent↗

Focal modification of electrical conduction in the heart by viral gene transfer.

Modern treatment of cardiac arrhythmias is limited to pharmacotherapy, radiofrequency ablation, or implantable devices. Antiarrhythmic medications suppress arrhythmias, but their systemic effects are often poorly tolerated and their proarrhythmic tendencies increase mortality. Radiofrequency ablation can cure only a limited number of arrhythmias. Implantable devices can be curative for bradyarrhythmias and lifesaving for tachyarrhythmias, but require a lifetime commitment to repeated procedures, are a significant expense, and may lead to severe complications. One possibility is the use of gene therapy as an antiarrhythmic strategy. As an initial attempt to explore this option, we focused on genetic modification of the atrioventricular node. First, we developed an intracoronary perfusion model for gene delivery, building on our previous work in isolated cardiac myocytes and hearts perfused ex vivo. Using this method, we infected porcine hearts with Adbetagal (recombinant adenovirus expressing Escherichia coli beta-galactosidase) or with AdGi (adenovirus encoding the Galphai2 subunit). We hypothesized that excess Galphai2 would mimic the effects of beta-adreneric antagonists, in effect creating a localized beta-blockade. Galphai2 overexpression suppressed baseline atrioventricular conduction and slowed the heart rate during atrial fibrillation without producing complete heart block. In contrast, expression of the reporter gene beta-galactosidase had no electrophysiological effects. Our results demonstrate the feasibility of using myocardial gene transfer strategies to treat common arrhythmias.

Adenoviridae↗

Effect of transgenic GDNF expression on gentamicin-induced cochlear and vestibular toxicity.

Gentamicin administration often results in cochlear and/or vestibular hair cell loss and hearing and balance impairment. It has been demonstrated that adenovirus-mediated overexpression of glial cell line-derived neurotrophic factor (GDNF) can protect cochlear hair cells against ototoxic injury. In this study, we evaluated the protective effects of adenovirus-mediated overexpression of GDNF against gentamicin ototoxicity. An adenovirus vector expressing the human GDNF gene (Ad.GDNF) was administered into the scala vestibuli as a rescue agent at the same time as gentamicin, or as a protective agent, 7 days before gentamicin administration. Animals in the Rescue group displayed hearing thresholds that were significantly better than those measured in the Gentamicin or Ad.LacZ/Gentamicin groups. In the Protection group, Ad.GDNF afforded significant preservation of utricular hair cells. The data demonstrated protection of the inner ear structure, and rescue of the inner ear structure and function against ototoxic insults. These experiments suggest that inner ear gene therapy may be developed as a clinical tool for protecting the ear against environmentally induced insults.

Adenoviridae↗

Knowing and not knowing. Some thoughts about insight.

This paper examines the concept of insight from the point of view that insight is about knowing. As a process it is how one comes to know, and as a construct it is what becomes known. Utilizing detailed clinical material from the analysis of a young girl, the paper approaches this issue by asking. How did Amy go about knowing? The multifaceted analytic relationship, the dimensions of change, and the analyst's technique are highlighted.

Anxiety, Separation↗