An epigenome-wide association study meta-analysis of educational attainment.

The epigenome is associated with biological factors, such as disease status, and environmental factors, such as smoking, alcohol consumption and body mass index. Although there is a widespread perception that environmental influences on the epigenome are pervasive and profound, there has been little evidence to date in humans with respect to environmental factors that are biologically distal. Here we provide evidence on the associations between epigenetic modifications-in our case, CpG methylation-and educational attainment (EA), a biologically distal environmental factor that is arguably among the most important life-shaping experiences for individuals. Specifically, we report the results of an epigenome-wide association study meta-analysis of EA based on data from 27 cohort studies with a total of 10 767 individuals. We find nine CpG probes significantly associated with EA. However, robustness analyses show that all nine probes have previously been found to be associated with smoking. Only two associations remain when we perform a sensitivity analysis in the subset of never-smokers, and these two probes are known to be strongly associated with maternal smoking during pregnancy, and thus their association with EA could be due to correlation between EA and maternal smoking. Moreover, the effect sizes of the associations with EA are far smaller than the known associations with the biologically proximal environmental factors alcohol consumption, body mass index, smoking and maternal smoking during pregnancy. Follow-up analyses that combine the effects of many probes also point to small methylation associations with EA that are highly correlated with the combined effects of smoking. If our findings regarding EA can be generalized to other biologically distal environmental factors, then they cast doubt on the hypothesis that such factors have large effects on the epigenome.

Hearing results of ossiculoplasty in Austin-Kartush group A patients.

OBJECTIVE: To compare hearing results in patients who underwent ossiculoplasty for Austin-Kartush group A impairments (incus erosion, malleus handle present, stapes superstructure present) with the results in patients with an intact ossicular chain who required only myringoplasty. The literature on hearing results of ossiculoplasty with different types of prostheses and different techniques is reviewed. PATIENTS AND STUDY DESIGN: This study retrospectively reviews a series of 181 consecutive ossiculoplasties and 204 consecutive myringoplasties. SETTING: The study was carried out partly at a private practice and partly in an academic tertiary referral center. MAIN OUTCOME MEASURES: This study complies with levels 1 and 2 of the guidelines recommended by the American Academy of Otolaryngology--Head and Neck Surgery (1995). RESULTS: When success was defined as a postoperative air-bone gap within 10 dB, the success rate was higher for myringoplasty (81%) than for ossiculoplasty (55%). When success was defined as a postoperative air-bone gap within 20 dB, the success rate was 97% in myringoplasties and 85% in ossiculoplasties. There was no significant deterioration over time of the mean postoperative air-bone gap for any frequency. CONCLUSION: Cumulative data from several authors show that -50% of patients undergoing partial ossiculoplasty have a postoperative air-bone gap of 0 to 10 dB, and 80% have a postoperative air-bone gap of 0 to 20 dB. Equally good results may be achieved with autograft (no difference was found between interposition of the incus or the head of the malleus), homograft, or alloplastic partial prostheses. With alloplastic total prostheses, 36% of patients have a postoperative air-bone gap of 0 to 10 dB, and 74% have a postoperative air-bone gap of 0 to 20 dB.

Malleus-handle fracture: historical review and three new cases.

OBJECTIVE: Isolated malleus-handle fracture is a clinical entity seldom reported in the medical literature but well known in the last century. The purpose of this paper was to review the literature over the last 150 years and describe three new cases. STUDY DESIGN: Extensive review of the literature and chart review of three patients with isolated malleus-handle fracture. SETTING: The study was performed partly at a private practice and partly in an academic tertiary referral center. PATIENTS: At least 43 malleus-handle fractures have been reported in the literature. Three new occurrences were studied. RESULTS: The review of the literature showed that head trauma with skull base fracture was the most frequent cause of malleus-handle fracture, followed by blows on the tympanic membrane and barotrauma, penetration of pen-holders or hair pins, penetration of twigs, and attempts to remove a foreign body pushed inside the ear. In the first patient reported here, the malleus-handle fracture was caused by a whirlpool bath, in the second, the cause was unknown, and, in the third, it was caused by a brisk decompression inside the ear canal. CONCLUSIONS: This lesion is not rare, and the diagnosis frequently is missed because the tympanic membrane appears intact. A careful otoscopic examination with pneumomassage, an abnormally high compliance at tympanometry, and a carefully recorded medical history may lead to the diagnosis of isolated malleus-handle fracture in a patient with a mild conductive hearing loss.

Comparison of long-term hearing results after vestibular neurectomy, endolymphatic mastoid shunt, and medical therapy.

OBJECTIVE: This study aimed to compare the hearing changes in the long term after vestibular neurectomy, endolymphatic mastoid shunt, and medical treatment in classic Meniere's disease. STUDY DESIGN: A retrospective case review was conducted based on audiologic follow-up between 5 and 21 years. SETTING: The study was performed at two centers in Bari University Hospital, one performing vestibular neurectomy as the first surgical procedure for Meinere's disease and the other, endolymphatic mastoid shunt. PATIENTS AND INTERVENTIONS: Of 68 patients with intractable idiopathic Meniere's disease, 29 underwent middle fossa vestibular neurectomy, and 17 had endolymphatic mastoid shunt; 22 were offered surgery but declined. MAIN OUTCOME MEASURES: Outcome measures were puretone average (PTA), speech reception threshold, and speech discrimination score before and after treatment. RESULTS: PTA declined by an average of 9.3 dB in neurectomy patients, 13.3 dB in patients undergoing endolymphatic mastoid shunt, and 18.1 dB in patients who were offered surgery but declined. Patients were subdivided into two cohorts based on their preoperative or initial PTA. In the patients who had PTA scores worse than 50 dB initially, the PTA declined an average of 4.3 dB in the vestibular neurectomy group, 11.5 dB in the endolymphatic sac group, and 4 dB in the nonsurgical group. In the patients with PTA > or = 50 dB initially, the PTA declined an average of of 25.3 dB in the vestibular neurectomy group, 16.1 in the endolymphatic sac group, and 26.2 dB in the nonsurgical group. Although shunt patients with good hearing initially deteriorated less than neurectomy patients and less than patients who declined surgery, the difference was not significant. CONCLUSIONS: These results indicate that patients with poor hearing stabilized, while patients with good hearing continued to deteriorate. The same conditions were observed in the patients who had surgery and those who were offered surgery but declined.

Cholesteatoma in children: histopathologic findings in middle ear ossicles.

Middle ear ossicles removed during ear surgery in 40 patients were examined in order to compare the histopathologic changes in children with those observed in adults. Bone resorption, mainly localized at the level of the periosteum and haversian canals in adults, was much more extensive in children. Replacement of bone by fibrous granulation tissue was observed in 60% of children's ossicles and in 27% of those belonging to adults. In children, extensive active resorptive osteitis of the ossicles was frequently associated with intensive round cell infiltration, which seems to play an important role in bone absorption and in the aggressiveness of cholesteatoma.

Long-term follow-up after middle fossa vestibular neurectomy for Ménière's disease.

Thirty-seven patients operated on by total vestibular neurectomy for Ménière's disease underwent follow-up examination for at least 5 years. Vertigo has been controlled in all the patients excepting one who developed Ménière's disease in the opposite ear. Three patients had a total hearing loss. Overall results in this study are comparable to those of other series in the literature. Vestibular neurectomy has been confirmed to be an effective procedure for relieving vertigo in intractable Ménière's disease with a success rate of 90-100% while preserving hearing in most of the patients. The results of vestibular neurectomy are far better than those obtainable with endolymphatic sac surgery.

The junctions of the spindle-shaped cells of the stria vascularis: a link that completes the barrier between perilymph and endolymph.

It is current opinion that the intercellular spaces of the stria vascularis represent a closed compartment isolated from the endolymph by the tight junctions of the marginal cells and from the perilymph by the junctional complexes of the basel cells. However, it has not yet been investigated whether these two barriers meet at the stria margins toward Reissner's membrane and the spiral prominence. Possible candidates for this sealing could be junctions between the spindle-shaped cells. In the present study freeze-fracture replicas of guinea pig specimens fixed in the presence of filipin were used in order to investigate the junctions of the spindle-shaped cells and to localize the cholesterol in their plasma membrane. Replicas reveal that, below the belt-like apical zonula occludens, the basolateral plasma membranes of the spindle-shaped cells adjacent to each other and to the basal cells are joined over their entire extension by a large number of junctional strands intermingled with numerous filipin-cholesterol-complexes. Gap junctions are present in the meshes formed by these junctional strands. Thus, the plasma membrane of the spindle-shaped cells shows morphological and cytochemical characteristics which indicate that they are the anatomical components completing the barrier isolating the intrastrial compartment from the surrounding fluids.

Very far-advanced otosclerosis.

The term very far-advanced otosclerosis is proposed to indicate otosclerotic patients with both bone and air conduction thresholds nonmeasurable on a standard clinical audiometer (blank audiogram). Three of these patients have undergone stapedotomy with satisfactory results. This confirms that cochlear implantation is not the best treatment for all profoundly deaf patients at least with implants available today. Some of the patients with a blank audiogram are better off with exploratory tympanotomy and stapedotomy.

Histopathology of spontaneous brain herniations into the middle ear.

Two patients with spontaneous brain herniation into the middle ear have been operated on with a combined otoneurological approach. In case No. 1, two 2 x 3 mm arachnoid tissue herniations were found in the tegmen antri of the left ear. Six years later, a 8 x 9 mm mass consisting of prolapsed brain was removed from the right ear. The histological examination showed normal but disorganized nervous tissue. The surface consisted of middle ear mucosa or modified glial cells. More deeply numerous well preserved neurons and synapses were observed. In case No. 2, a 2 x 1 cm herniation was found in contact with the ossicles and the bony walls of the middle ear. The herniation consisted of partly degenerated nervous tissue which could explain the episode of temporal lobe seizure the patient experienced 8 years before surgery. In the world literature during the last 40 years, 29 cases of spontaneous or idiopathic brain herniation into the middle ear and mastoid have been reported. In 10, the herniations were multiple, as in our case No. 1. Case No. 1 is interesting also because the spontaneous brain herniation was bilateral.

[Clinical study of the efficacy and tolerability of nimesulide in suppositories compared to flurbiprofen in gynecology]. / Studio clinico sull'efficacia e la tollerabilità della nimesulide in formulazione supposte in confronto al flurbiprofen in ginecologia.

The efficacy and tolerability of nimesulide in a new pharmaceutical suppository form were assessed in a double blind study versus flurbiprofen in pain-inflammatory pathologies of obstetrico-gynecological nature. One hundred patients with pelvic inflammatory disease were randomly assigned to treatment with nimesulide or flurbiprofen. Both drugs, administered in a dose of 2 suppositories a day for 7 days, evidenced speedy, effective analgesic and anti-inflammatory activity combined with good tolerability. Specifically, as regards the pain component, nimesulide demonstrated a significantly more marked analgesic effect than flurbiprofen in the first two hours of treatment.

Brain herniation into the middle ear: two idiopathic cases treated by a combined intracranial-mastoid approach.

One hundred thirty-nine cases of brain herniation into the middle ear and mastoid have been reported in the world literature during the last 40 years. In 29 cases the herniation was idiopathic. In idiopathic cases, intermittent CSF otorhinorrhea, a history of intermittent "serous otitis media," and a conductive hearing loss were the main clinical findings. Polytomography or CT-scan revealed a tegmen antri or tympani defect in some patients. There are three surgical approaches for treatment of brain herniation into the middle ear: neurosurgical, otological, and combined.

Cochlear morphology from Würzburg (1951) to Turin (1987): old and new aspects.

A review is given of the methods employed in human temporal bone pathology, from the camera lucida drawings of the last century to the sophisticated techniques of today.

EEC hearing impairment programme: collaboration in Europe, 1974-1988.

The Commission of the European Communities funds a 'concerted action' programme in the area of hearing impairment. The programme does not fund research directly, but is intended to provide funds for coordination of research in different countries. Previous projects funded by the programme include a comprehensive study of the prevalence of childhood deafness in the European Community, and meetings on cochlear implants, human temporal bone histopathology, diagnostic techniques and hearing impairment in children. The programme is currently concerned with new technologies for communication in the hearing impaired and activities in 1988 will include workshops on signal processing hearing aids and early diagnosis in children.

Hair cell distributions in the normal human cochlea. A report of a European working group.

Cochlear hair cell counts from individuals who had clinically normal hearing prior to their death have been plotted for various age bands as a function of the number of hair cells per millimetre against their position in the cochlea. Position has been expressed as the distance of that observation of hair cell density from the base of the cochlea, divided by the total length of the cochlea, thereby giving a proportional representation of the cochlea in the range of 0.0 to 1.0 with 20 subdivisions of 0.05. There is an age-related decrease in the number of hair cells in the normal population, and this is more marked for the outer hair cells.

Degeneration patterns in the organ of Corti and spiral lamina.

The relation between organ of Corti degeneration and radial nerve fibre degeneration in the osseous spiral lamina was studied in two human cochleas.