Health-related quality of life and patient-defined benefit of clobetasol 0.05% in women with chronic lichen sclerosus of the vulva.

BACKGROUND: This study investigates the health-related quality of life in patients with vulvar lichen sclerosus (LS) and the patient-defined therapeutic benefit of clobetasol. METHODS: A survey analysis of 96 women with LS after treatment with clobetasol was performed. Quality of life was assessed with the Skindex-29. The Patient Benefit Index (PBI) was used to determine the therapeutic benefit. RESULTS: The overall response rate was 59.2%. Quality of life was most impaired by somatic symptoms (scale 'Symptoms' score 3.2) and emotional stress (scale 'Emotions' score 3.1), while social interactions (scale 'Functioning' score 1.9) played an inferior role (p < 0.001). Primary therapeutic goals 'to have confidence in the therapy' and 'to be free of itching' were achieved in 73.2 and 69.0% of patients who indicated the goal applied to them. The global PBI score was 3.06. In 93.2% of patients it was >1, indicating a potential benefit from clobetasol. CONCLUSION: Topical clobetasol is of potential therapeutic benefit for patients with vulvar LS and might therefore improve quality of life.

Expression of fibroblast growth factors 1 and 2 in a human retinal pigment epithelium cell line (K1034).

The primary source of fibroblast growth factors (FGFs) is the retinal pigment epithelium (RPE). Investigations on FGF secretion in RPE primary cultures are hampered by the rapid run-down of cell vitality after a few passages. Therefore, long-term experiments require an alternative to primary cultures. We detected FGF-1 and FGF-2 in the established human K1034 cell line by immunohistochemistry. In addition, mRNA for both FGFs was found by RT-PCR. By immunohistochemistry, the signal was more pronounced with FGF-2 than with FGF-1. K1034 is capable of expressing both FGF-1 and FGF-2. With respect to these features, this cell line can be used as an alternative to primary cultured human RPE cells.

Sensorineural hearing loss in children after liver transplantation.

OBJECTIVE: To investigate risk factors for sensorineural hearing loss (SNHL) in children after liver transplantation. DESIGN: Retrospective medical record review. SETTING: Pediatric tertiary care hospital. PATIENTS: One hundred twenty-five consecutive children who received liver transplants between March 1, 1987, and June 30, 1996. MAIN OUTCOME MEASURES: The presence of SNHL (bone conduction threshold of >35 dB of hearing loss in at least 1 frequency) and the cause of the liver abnormality in all 125 patients. In addition, among the subset of children who had biliary atresia and underwent transplantation before 2 years of age, the total dose (milligrams per kilogram of body weight) of aminoglycoside antibiotic medications (tobramycin sulfate, gentamicin sulfate, and amikacin sulfate) and of intravenous loop diuretic agents (furosemide) was compared between children with and without SNHL. RESULTS: Audiologic evaluations were available for 66 of 125 patients, 15 (12%) of whom have SNHL. Of 5 survivors with the short-bowel syndrome, 4 have severe to profound SNHL. Of 46 children who have biliary atresia and who underwent transplantation before 2 years of age, 8 (17%) have SNHL. Among the 26 evaluable children with biliary atresia undergoing liver transplantation before 2 years of age, logistic regression analysis revealed that the most important risk factor for SNHL was the cumulative dose of amikacin (P = .05). CONCLUSIONS: Children receiving liver transplants are at an increased risk for SNHL. Those with the short-bowel syndrome have the greatest prevalence of SNHL. Among the subset of children with biliary atresia receiving liver transplants before 2 years of age, statistical analysis demonstrates a dose-response relationship between the receipt of amikacin and the occurrence of SNHL.

Basic, not acidic fibroblast growth factor stimulates proliferation of cultured human retinal pigment epithelial cells.

PURPOSE: In this study, we evaluated a possible effect of acidic and basic fibroblast growth factor (aFGF, bFGF) on the proliferation of human retinal pigment epithelial (RPE) cells in culture. As the RPE is the primary source for bFGF in the retina, such an effect would suggest autocrinic actions of FGFs. METHODS: Primary cultures of human and porcine RPE and an established human RPE cell line (D407) were subjected to aFGF and bFGF at different culture conditions. Cell proliferation was determined using the BrdU non-radioactive nucleotide analogue assay, and total protein was measured colorimetrically. The cells were subjected to aFGF and bFGF from 0.1 to 100 ng/ml for 1 to 14 days. RESULTS: In the presence of 100 ng/ml bFGF, cell proliferation doubled from day 2 (143+/-12 units) to day 6 (227+/-17). This effect was neither seen without bFGF nor with aFGF at the same concentration. The stimulating effect of bFGF on cell proliferation was dose-dependent, the ED50 being around 1-10 ng/ml. The bFGF effect was markedly greater at high fetal calf serum concentration (10% vs. 1%). No bFGF effect was seen on cells of the established human RPE cell line D407 nor on primary cultures from porcine RPE. CONCLUSIONS: bFGF, in contrast to its analogue aFGF, stimulates cell proliferation in cultured human RPE cells. It may act as an autocrinic agent (secretion by and action on the same cell) and thus be a specific regulator for cell proliferation in repair and replacement of the RPE cell monolayer.

Properties and regulation of pH-dependent cation channels in the apical membrane of cultured proximal tubule cells.

The established opossum kidney (OK) cell line serves as a model system for ion and substrate transport in the renal proximal tubule. Previous experiments on OK cells revealed a channel-mediated Na+ conductance which is regulated by intracellular pH (pHi). In this study we report on patch clamp experiments determining the properties and pHi dependence of a cation channel located in the apical membrane. This channel is selective for sodium over chloride but discriminates poorly between the monovalent cations Na+,K+,Li+ and Cs+. Its open probability (P(o)) rises at depolarising membrane potentials. Under normal conditions the channel is inactive in the cell-attached patch mode and is activated upon excision. However, after excision the channel usually runs down within 30-90 s which cannot be overcome by either altering the Ca(2+)-concentration (10(-3) mol/l, 10(-6) mol/l, Ca(2+)-free) or adding 1 mmol/l Mg-ATP to the bath solution. In the cell-attached patch mode the channel could be activated by decreasing pHi from pH 7.4 to pH 6.5, by either the ammonium prepulse technique or the nigericin K+ method, in more than 50% of the experiments performed. In the renal proximal tubule such a non-selective cation channel would constitute a functional Na+ channel and might therefore support Na+ reabsorption especially during the intracellular acidification due to hormonal inhibition of the Na+/H+ exchanger.

Mercapturic acid formation in cultured opossum kidney cells.

We investigated the last step of mercapturic acid formation, the N-acetylation of cysteine S-conjugates, in the established opossum kidney (OK) cell line which exhibits characteristics of the proximal tubule. S-Benzyl-L-cysteine was used as a model substance for such a cysteine S-conjugate. We succeeded in showing that OK cells absorb S-benzyl-L-cysteine via an active transport system which is inhibitable by phenylalanine. This transport follows Michaelis-Menten kinetics and the two characterizing parameters were determined: the Michaelis-Menten constant Km = 1.8 mmol/l, and the maximum of the difference between the intracellular and the extracellular concentration of S-benzyl-L-cysteine delta Cmax = 19.4 mmol/l. S-Benzyl-L-cysteine is converted to N-acetyl-S-benzyl-L-cysteine at a constant rate, which is independent of the extracellular S-benzyl-L-cysteine concentration. Under the tested experimental conditions this is probably due to saturation of the microsomal N-acetyltransferase catalyzing this reaction. In conclusion, we have shown that OK cells are a suitable model for studying mercapturate formation. They take up S-benzyl-L-cysteine mainly via the same carrier as phenylalanine, which is known to be transported in the rat by the high-capacity, low-affinity neutral amino acid carrier, and convert it to N-acetyl-L-benzyl-S-cysteine.

The origin of the human auditory brain-stem response wave II.

Auditory brain-stem responses (ABRs) were recorded from human subjects undergoing neurosurgical procedures which exposed the auditory nerve. Scalp recordings indicated that the latency of the negativity between waves I and II (In) and the latency of positive peak II (IIp) were shorter when the nerve was suspended in air than when the nerve was submerged in cerebrospinal fluid or saline, while earlier and later waves remained unaffected. These results could not be attributed to changes in stimulus or recording parameters or conduction velocity. Computational and somatosensory experimental evidence of stationary potentials generated by physical properties of the volume conductor, including changes in conductivity or geometry, are presented to develop a model of wave IIp generation. The results of this study suggest that wave IIp (and probably In) are manifestations of current flux asymmetries across conductivity boundaries created by the temporal bone-cerebrospinal fluid intradural space-brain-stem interfaces. The current flux asymmetries are generated as the propagating auditory nerve action potential crosses the conductivity boundaries. These results also indicate that the physical characteristics of the volume conductor and neural pathways must be considered when interpreting surface recorded evoked potentials.

New techniques of hearing assessment.

This article reviews current literature in the areas of otoacoustic emissions and auditory brain stem responses (ABRs) and their application to the evaluation of peripheral auditory function in infants and children. The different types of otoacoustic emissions are described along with their incidence, development, clinical applications, and interpretation in the pediatric group. The development of the auditory system, reflected by ABRs, is presented in detail with previously unpublished results from three-channel Lissajous' trajectory studies performed in infants. Clinical application of frequency-specific ABRs, both air and bone conducted, are presented. Finally, a discussion of the need to develop objective estimators of signal quality and threshold detection for otoacoustic emissions and ABRs in infants and children is presented, which includes previously unpublished results evaluating a new technique.

3CLT ABR analyses in a human subject with unilateral extirpation of the inferior colliculus.

Reported are the results of analyses of three-channel Lissajous trajectories (3CLTs) of the auditory brain stem responses (ABRs) in a human subject in whom a focal lesion of the brain stem was caused by stereotactic radiosurgery, the 'gamma knife'. The surgery caused total destruction of the right inferior colliculus. The results, using multiple measures for defining ABR components, confirm findings from more conventional 2-channel recordings which, in turn, suggested the presence of an intact wave IV but a negligible, if not totally absent, wave V with stimulation of the left (contralateral) ear. The results thus support theories that wave V is generated by crossed pathways and that wave IV is an independent wave generated by the lateral lemniscus. Since magnetic resonance imaging suggested no destruction of tissue below the inferior colliculus, the findings also support theories of wave V generation at or rostral to the inferior colliculus. In practical terms, the results demonstrate the value of multichannel recordings of the ABR in component identification and in interpreting ABR abnormalities.

Bipolar cochlear nerve recording technique: a preliminary report.

To preserve hearing during vestibular neurectomy and acoustic neuroma removal, the cochlear nerve must be identified. Present techniques, including monitoring eighth nerve action potentials, help the surgeon identify those maneuvers that increase the risk of nerve injury but do not help in the anatomic identification of the cochlear nerve or the cochlear-vestibular cleavage plane. The purpose of this study was to demonstrate an electrophysiologic method of identifying the cochlear portion of the eighth cranial nerve. A flush-tipped, bipolar electrode recording probe was used to directly record responses to monaural click stimuli from the cochlear nerve but not from surrounding tissue. It was also used to delineate the cochlear-vestibular cleavage plane. Stimulus intensity levels over 25 dB sensation level tended to reduce the accuracy of nerve identification, and lower levels prolonged recording time. This technique and its application to posterior fossa surgery is discussed.