Development of the tubotympanum in the rat

Objective: To investigate the relationship between the anatomical maturation of the middle ear and that of the eustachian tube and paratubal muscles in the rat. Design: Wistar rats ranging from gestational day 12 to postnatal day 40 were used. Methods: Tissue specimens were examined with routine light microscopy and electron microscopy. Epithelial differentiation was studied immunohistochemically with antibodies to different cytokeratins. Results: The epithelial lining of the tubotympanum showed differentiation-related cytokeratin expression throughout the whole developmental period. The mucociliary epithelium reached mature features around birth. A dorsal extension and its framing cartilage started forming around 5 days after birth. This extension became lined by stratified nonciliated epithelium and attained maturity around 10 days after birth concurrently with the attachment of the dilatory muscles. This process was immediately followed by aeration of the middle ear cavity. Conclusions: The continuous expression of cytokeratins demonstrates that the epithelial lining of the tubotympanum is only derived from the embryonal endoderm. Furthermore, this study demonstrates that the eustachian tube shows a two-stage postnatal development. First, the mucociliary system matures, providing protection/clearance when the animal starts respiration and swallowing. Subsequently, the dorsal part attains maturity. The features of the epithelial lining of the dorsal part of the eustachian tube and the coincidence of the maturation of this part with the attachment of the dilating muscle fibers and the aeration of the middle ear indicates that this part provides ventilation. These findings support the authors' hypothesis that different parts of the eustachian tube serve different purposes: clearance, protection and ventilation.     

A home education program for older adults with hearing impairment and their significant others: a randomized trial evaluating short- and long-term effects

This paper addresses the development and effectiveness of a home education program. The program, designed for hearing-impaired elders and their significant others (SO), deals with communication strategies and speech reading. Participants were randomly assigned to a training group (hearing aid fitting+home education program) or a control group (hearing aid fitting). The training group included 24 hearing-impaired subjects and 24 SO's. Controls were 24 affected individuals and 22 SO's. Questionnaires addressing emotional response, communication strategies and the IOI-HA, IOI-AI and IOI-SO were used. A repeated measures analysis of variance was applied to test group differences between pre, post, and 6-months follow-up measures. Increased awareness of benefits of speech reading and improved interaction with the SO were observed in the training group only (p < 0.05). No group difference on 'emotional response' was found. IOI-AI and IOI-SO demonstrated favorable attitudes towards the program. Follow-up measures showed improved quality of life and satisfaction in the training group, while a decrease was observed among the controls (p < 0.05). Some effects differed between first-time and experienced hearing aid users. Addition of services to amplification and involvement of the SO are relevant in aural rehabilitation.     

International validation of a preoperative nomogram for prostate cancer recurrence after radical prostatectomy.

PURPOSE: We evaluated the predictive accuracy of a recently published preoperative nomogram for prostate cancer that predicts 5-year freedom from recurrence. We applied this nomogram to patients from seven different institutions spanning three continents. METHODS: Clinical data of 6,754 patients were supplied for validation, and 6,232 complete records were used. Nomogram-predicted probabilities of 60-month freedom from recurrence were compared with actual follow-up in two ways. First, areas under the receiver operating characteristic curves (AUCs) were determined for the entire data set according to several variables, including the institution where treatment was delivered. Second, nomogram classification-based risk quadrants were compared with actual Kaplan-Meier plots. RESULTS: The AUC for all institutions combined was 0.75, with individual institution AUCs ranging from 0.67 to 0.83. Nomogram predictions for each risk quadrant were similar to actual freedom from recurrence rates: predicted probabilities of 87% (low-risk group), 64% (intermediate-low-risk group), 39% (intermediate-high-risk group), and 14% (high-risk group) corresponded to actual rates of 86%, 64%, 42%, and 17%, respectively. The use of neoadjuvant therapy, variation in the prostate-specific antigen recurrence definitions between institutions, and minor differences in the way the Gleason grade was reported did not substantially affect the predictive accuracy of the nomogram. CONCLUSION: The nomogram is accurate when applied at international treatment institutions with similar patient selection and management strategies. Despite the potential for heterogeneity in patient selection and management, most predictions demonstrated high concordance with actual observations. Our results demonstrate that accurate predictions may be expected across different patient populations.     

A modeling approach to the analysis of nerve regenerative experiments

Many experiments aiming at the investigation of nerve repair involve elaborate testing over a certain time period. Data arising from such experiments are often analyzed by time-point. Such a cross-sectional approach is often very inefficient. In this paper, we consider a case study in which repeated measurements of two response variables assumed to be Poisson distributed are obtained. We show how a repeated measures modeling approach, based on generalized linear models, can handle both responses in one model and improve the inference in the nerve repair experiments. The benefits of the model as well as problems that can occur are illustrated and discussed.     

Pharmacological correlation between the formalin test and the neuropathic pain behavior in different species with chronic constriction injury

Research on mechanisms of drug action, and preclinical screening of molecules with a potential activity on neuropathic pain requires extensive animal work. The chronic constriction injury model is one of the best-characterized models of neuropathic pain behavior in rats, but requires extensive time consuming operations and animal handling. The formalin test is easier to perform, and a well validated model. The latter may serve as an effective prescreening test of molecules and may facilitate drug targeting. In the present study the activity of different pharmacological reference compounds was tested in rats and gerbils on the cold plate for animals that had undergone chronic constriction injury and in the second phase of the formalin test. In rats, a comparable outcome in both test conditions was observed for morphine, fentanyl, MK-801 and flunarizine. Clonidine had more activity in the second phase of the formalin test, whereas baclofen, tramadol, amitryptiline, ketamine and topiramate showed more activity in the cold plate. In gerbils, both test conditions yielded comparable results for fentanyl and ketoprofen. Tramadol and CP-96345 tended to have more activity in the second phase of the formalin test, whereas morphine, SR-48968, SR-142801 and R116301 demonstrated more activity in the cold plate test. This study demonstrates a good correlation between the second phase of the formalin test and the cold allodynia in the CCI model for, both for rats and gerbils. Drugs with a proven activity in humans, used as reference compounds, also showed good pharmacological activity in this animal study.     

Molecular and cellular mechanisms of protective immunity to coccidioidomycosis

Coccidioides immitis is endemic in the soil of the desert Southwest. It causes a respiratory infection that is usually mild, but can last months and may disseminate beyond the lung. Disseminated infections can be fatal or require life-long therapy. Development of an effective vaccine may be a successful method of preventing serious disease. In this paper, we show that immunostimulatory-oligodeoxynucleotides (ISS-ODN) are an effective adjuvant for a recombinant coccidioidal protein known as antigen 2/proline rich antigen. Protective immunity induced by this ISS-ODN-based vaccine requires IL-12, interferon-gamma and MHC Class II-restricted T-cells. Cytotoxic CD8 T-cells are not required. This study elucidates the mechanisms needed to elicit successful immunity against coccidioidomycosis, and holds promise for development of an effective coccidioidal vaccine against coccidioidomycosis.