Regulation of the perilymphatic-endolymphatic water shunt in the cochlea by membrane translocation of aquaporin-5.

Volume homeostasis of the cochlear endolymph depends on radial and longitudinal endolymph movements (LEMs). LEMs measured in vivo have been exclusively recognized under physiologically challenging conditions, such as experimentally induced alterations of perilymph osmolarity or endolymph volume. The regulatory mechanisms that adjust LEMs to the physiological requirements of endolymph volume homeostasis remain unknown. Here, we describe the formation of an aquaporin (AQP)-based "water shunt" during the postnatal development of the mouse cochlea and its regulation by different triggers. The final complementary expression pattern of AQP5 (apical membrane) and AQP4 (basolateral membrane) in outer sulcus cells (OSCs) of the cochlear apex is acquired at the onset of hearing function (postnatal day (p)8-p12). In vitro, hyperosmolar perfusion of the perilymphatic fluid spaces or the administration of the muscarinic agonist pilocarpine in cochlear explants (p14) induced the translocation of AQP5 channel proteins into the apical membranes of OSCs. AQP5 membrane translocation was blocked by the muscarinic antagonist atropine. The muscarinic M3 acetylcholine (ACh) receptor (M3R) was identified in murine OSCs via mRNA expression, immunolabeling, and in vitro binding studies using an M3R-specific fluorescent ligand. Finally, the water shunt elements AQP4, AQP5, and M3R were also demonstrated in OSCs of the human cochlea. The regulation of the AQP4/AQP5 water shunt in OSCs of the cochlear apex provides a molecular basis for regulated endolymphatic volume homeostasis. Moreover, its dysregulation or disruption may have pathophysiologic implications for clinical conditions related to endolymphatic hydrops, such as Ménière's disease.

Inhibition of elastase enzyme release from human polymorphonuclear leukocytes by N-acetyl-galactosamine and N-acetyl-glucosamine.

We studied the effect of aminosugars on the elastase enzyme released from cytochalasin-B treated polymorphonuclear neutrophils (PMN) and stimulated by F-Met-Leu-Phe (FMLP). Both N-acetyl-galactosamine and N-acetyl-glucosamine can inhibit the release of leukocyte elastase enzyme. N-acetyl-galactosamine was a potent inhibitor of elastase enzyme release in a dose-related fashion. Inhibition ranged from 91.9% up to total inhibition. N-acetyl-glucosamine showed a mild inhibitory effect on elastase enzyme release; however, it too acted in a dose-related fashion. The range of inhibition was 17.17%-8.18%. Mannosamine showed an inhibitory effect in some donors, but this effect was not statistically significant. No effect on elastase enzyme release was shown with other sugars such as D-glucose and L-fucose. These results show that N-acetyl-galactosamine can inhibit the respiratory burst, which suggests that the aminosugars might do more than interfere with the carbohydrate lectin interaction.

Silent otitis media: clinical applications.

Silent (masked) otitis media refers to usually chronic pathological conditions behind an intact tympanic membrane which may be clinically "undetected" or "undetectable." Correlations are described for pathological changes in temporal bones and clinical considerations for silent otitis media associated with Hemophilus influenzae meningitis in infants, silent otitis media--the continuum, silent otitis media--sequelae, and chronic silent otitis media.

Sensitivity versus specificity of phonoarthrography as an indicator for cartilage degeneration.

In an attempt to update the idea of recording knee sounds, 400 osteoarthritic (OA) knees, 100 knees from a young age group (18-31 years) and 100 knees from an age-matching group (45-60 years) were recorded by a computerized device using a special program that enabled the conversion of sounds--recorded in a fixed lapse of time--to waves which were then analysed in terms of frequency/second and average amplitude. Radiological grading was done for all groups in order to compare both parameters. Reproducibility of the recordings for each knee was confirmed statistically. Phonoarthrography was found to be 100% sensitive for radiological changes and for clinically felt crepitus, simultaneously diagnosing early OA in 32.5% of subjects with no radiological changes and in 7.5% of subjects with no clinically felt crepitus. From the work it can be deduced that computerized phonoarthrography can diagnose early cases of OA and is excellent for assessing and following up cases. It may be regarded as an indicator for cartilage degeneration.

Direct extension of laryngeal carcinoma to the skin of the neck.

Invasion of the skin of the neck by laryngeal carcinoma is relatively uncommon. Twelve cases of cancer of the larynx fungating through the cervical skin are presented. They mostly followed initial treatment by deep X-ray therapy or partial laryngectomy. A high tracheostomy was also considered to be a contributing cause for the occurrence of such a mishap. The management and follow-up of these patients is described.

Volumetric staging (VS) is superior to TNM and AJCC staging in predicting outcome of head and neck cancer treated with IMRT.

The UICC classification (TNM) represents the validated standard tool to describe tumor extent and includes prognostic information on the probability of disease control. The American Joint Committee on Cancer (AJCC) stage grouping is based on the evaluation of treatment and outcome. Gross tumor volume (GTV) might be more relevant than pure description (TNM) or stage grouping as prognostic factor for local control in head and neck cancer (HNC). Based on the observation of GTV-correlated outcome in our initial HNC patient cohort treated with IMRT, we tested the hypothesis that the GTV is the most reliable predictive tool in HNC outcome. A GTV based volumetric staging system (VS) was introduced, using two volumetric cut-off values (15 and 70 cm3). VS, TNM, and AJCC stages were assessed and correlated with outcome following primary radiation in 172 HNC patients. Analyses were based on Kaplan-Meier survival curves. VS proved to be superior to the TNM/AJCC in predicting outcome. In addition, VS enabled to stratify high- and low-risk patients in advanced TN stages. GTV represented the most important prognostic indicator in HNC treated with IMRT and is recommended to be considered for therapeutic decisions and estimation of outcome.

Bilharzial arthropathy.

The joints of 124 young adult patients with bilharziasis were examined. Heels, sacroiliac joints, cervical spine, knee joint, dorsal spine, and tarsal joints were affected. Biopsy of the knee synovia showed synovitis, vasculitis, and the presence of bilharzial ova in three cases. Radiologically the heels and sacroiliac joints showed inflammatory changes. Schistosomiasis may cause an arthropathy.

Synovial fluid interleukin-8 and neutrophil function in rheumatoid arthritis and seronegative polyarthritis.

The relationships between synovial fluid (SF) interleukin-8 (IL-8) and neutrophil turnover as measured by cytidine deaminase (CD), and SF metabolites were studied in 28 patients, 16 with rheumatoid arthritis (RA; median age and disease duration 62 and 14 yr, respectively) and 12 with seronegative polyarthritis (SNP; median age and disease duration 32 and 5 yr, respectively). Knee SF samples were aspirated using indwelling cannulae following a period of rest for 1 h. SF IL-8 levels (measured by an ELISA) were significantly elevated in RA compared to SNP (median 2.35 vs 0.22 ng/ml, P < 0.001), as were median levels of CD (55.8 vs 8.11 U/ml, P < 0.01), lactic acid (29.6 vs 16.6 mg/dl, P < 0.001), glucose (57.9 vs 84.5 mg/dl, P < 0.05) and the lactate to glucose ratio (0.85 vs 0.19, P < 0.001). Measures of disease activity, C-reactive protein, plasma viscosity and articular index were also elevated in RA compared to SNP (P < 0.05). SF IL-8 levels correlated strongly with CD, lactate, glucose and the lactate to glucose ratio when both disease groups were considered together (P < 0.001). These parameters also showed some association with the measures of disease activity (P < 0.05). All these associations were less marked when the individual disease groups were analysed separately. These results suggest that factors responsible for neutrophil accumulation and priming (probably IL-8) are present in SF, and these coincide with products of their activation (CD). The degree of neutrophil turnover is linked to the anaerobic metabolism of the synovial cavity.

Outcome of bought living non-related donor kidneys followed up at a single centre.

Between October 1985 and November 1991, 16 dialysis patients travelled to Bombay and bought kidneys from living non-related Indian donors for U.S. $7,372. One patient died peri-operatively; one contracted HIV and another hepatitis B virus infections. Six patients are presently positive for hepatitis C virus antibody compared to two cadaver graft recipients (P = 0.03); two of the six patients have chronic active hepatitis. Five-year patient and graft survival rates (75% and 43%, respectively) were similar to those of recipients of 24 cadaver grafts obtained in the United States (67% and 55%, respectively), as was graft function during the first 5 years of follow-up. Graft survival may have improved following commercial kidney transplantation in Bombay, but this practise still poses a risk of dangerous infections and exploitation of donors and recipients. The establishment of a centralized programme of anonymous "rewarded gifting" in countries that cannot eradicate rampant organ commerce may help to expunge exploitation and to ensure uniform, acceptable clinical standards and the safety of patients.

Left subclavian-aortic bypass grafting in primary isolated adult coarctation.

In the adult patient, bypassing the coarcted segment with a tube graft has been described, among others, as a method of repair in re-do cases and in high-risk patients. Since 1992, and owing to its simplicity, it has become our elected approach in all adult cases. Twenty-two patients (mean age 22.8+/-7.18 years) with isolated aortic coarctation distal to the left subclavian artery were primarily treated with left subclavian-lower descending thoracic aorta bypass using a Hemashield woven double velour graft. There was no hospital mortality nor major postoperative complications. The patients were followed-up for a mean period of 2.36+/-1.29 years (range 1-5 years). Systolic blood pressure as well as the pressure gradient across the coarcted segment dropped significantly from 181.82+/-15.7/65.7+/-13.3 mm Hg to 124+/-13.63/7.41+/-6.49 mm Hg (P = 0.009 and 0.001). Sixteen patients (72.6%) were recorded to be symptom-free and normotensive and seven patients (31.8%) did not show any residual pressure gradient when last seen. The postoperative systolic pressure correlated positively with its preoperative value (P = 0.017) as well as with patient age (P = 0.015). Partial correlation, however, suggested that advanced age upon surgery was the determinant factor responsible for residual postoperative systemic hypertension (P = 0.007). Besides being simple, the procedure is low-risk, permits a significant drop in pressure gradient and improves systolic hypertension through an intermediate follow-up period.

Mitral valvotomy in pregnancy.

Our experience over an 8-year period with 42 pregnant women with mitral stenosis who underwent valvotomy formed the basis of this study. Striking clinical disability was the indication for operation. Closed transventricular valvotomy offered excellent low-risk palliation. Pregnancy per se did not increase the operative risk. The long-term results of mitral valvotomy in pregnant women were the same as those of operations carried out in nonpregnant women. Mitral valvotomy done during pregnancy has no untoward effect on the fetus.