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Biomedical subjects

J Wersäll

Publications and source records attributed to J Wersäll.

At least 19 recordsLinked to original sources

Ototoxic antibiotics: a review.

Fifty years of experience with aminoglycoside antibiotics has confirmed their usefulness in many infections with Gram-negative bacteria. The ototoxic action has been investigated clinically in patients and in numerous animal studies. The increased knowledge about molecular structure, pharmacology and pharmacokinetics as well as information of the site of action in the labyrinth has resulted in reduced risks for severe toxic damage in kidneys and in the ear. Nevertheless, a number of cases of severe hearing loss and a few cases of deafness still occur every year. Further studies on modified molecular structure as well as site of action at the molecular level and ways of avoiding toxicity will make this group of antibiotics still more useful.

Animals↗

Auditory impairment in guinea pigs treated with isepamicin.

Groups of adult guinea pigs were treated intramuscularly with isepamicin at doses of 100, 150 and 225 mg/kg/day for 21 days. For comparison, two other groups were administered either saline or amikacin 225 mg/kg/day. Auditory function, as measured by the Preyer pinna reflex and the brain stem evoked response, was impaired in both the isepamicin and amikacin groups treated with 225 mg/kg/day, and to a lesser extent in the group receiving isepamicin 150 mg/kg/day. Morphological evaluation of the organ in Corti, performed either by scanning electron microscopy or by light microscopy, showed the typical pattern of damage associated with the aminoglycosides. The greatest damage was observed at 225 mg/kg/day, with no difference between isepamicin and amikacin. Isepamicin 100 mg/kg/day produced no impairment in auditory function and very little change in the morphology of the organ of Corti.

Amikacin↗

Haemorrhagic pituitary tumours.

In a group of 69 patients with pituitary tumours, 12 were found to have evidence of intratumoral haemorrhage on MRI, characterized by high signal intensity on short TR/TE sequences. This was verified in all but 1 patient. The majority of the bleedings occurred in macroadenomas. Five (42%) were prolactinomas and 4 (33%) were non-functioning adenomas. There were 2 GH- and 1 ACTH-secreting tumours. All 5 patients with prolactinomas were on bromocriptine medication. Two of the patients had a clinical picture of pituitary apoplexy. The haemorrhage was not large enough to prompt surgery in any of the patients. However, surgical verification of the diagnosis was obtained in 5 cases, while 6 patients were examined with follow-up MRI.

Adenoma↗

Hair cell damage after continuous and interrupted pure tone overstimulation: a scanning electron microscopic study in the guinea pig.

In our earlier investigations [Fredelius et al., Hear. Res. 30, 157-167 (1987)] acoustic trauma was studied after continuous 3.85-kHz pure tone exposures of different intensities and durations. In the present investigation, the importance of the introduction of a break during longer 3.85-kHz pure tone exposures was studied. Female pigmented guinea pigs were exposed to 108, 114, or 120 dB SPL for 6 h with or without a 1-h break after the first 3 h. Four weeks after exposure the cochleas were prepared for scanning electron microscopy and the resulting hair cell damage was evaluated according to a 4-grade damage scale. Significant differences could be demonstrated in the hair cell damage in the animals exposed to continuous acoustic overstimulation and those exposed to intermittent overstimulation. The importance of rest periods to decrease hair cell damage during long periods of acoustic overstimulation was clearly demonstrated.

Acoustic Stimulation↗

The presence of laminin in the fetal human inner ear.

The expression of laminin was analyzed in the human fetal inner ear using immunohistochemical methods. In the 11-week-old human fetus, the presence of laminin was found in the basement membrane of the immature cochlea, endolymphatic sac and vestibular end organs. The reaction of the basement membrane of the endolymphatic sac was strong in the 15-week-old human fetus. A laminin reaction was seen in the cochlea, Reissner's membrane, epithelial cells of the limbus spiralis, the basilar membrane and the stria vascularis. In particular, the capillaries and basement membrane of the stria vascularis were strongly positive. These results suggest that laminin may be an essential component in the development of the inner ear and may possibly be related to filtration of the endolymph.

Basement Membrane↗

Glycoconjugates in the human fetal endolymphatic sac as detected by lectins.

The distribution of glycoconjugates in the 11 to 16 weeks old human fetal endolymphatic sac (ES) was analyzed using six biotinylated lectins; Wheat germ agglutinin (WGA), Abrus precatorius agglutinin (APA), Ulex europaeus agglutinin I (UEA-I), Ricinus communis agglutinin 120 (RCA120), Helix pomatia agglutinin (HPA), Concanavalin A (ConA). In the 11 week old human fetus, fluorescent reactions with WGA, APA, RCA120 and ConA were detected in the ES. There was almost no reaction with HPA and UEA-I. In the 14 week old human fetus, however fluorescent reactions with HPA and UEA-I appeared. This result suggests that the presence of glycoconjugates changes during the maturation process of the ES. Glycoconjugates detected with HPA were related to the epithelial cell elements of the ES epithelium. The reaction with UEA-I suggests that the stainable substance present in the ES lumen may be secreted locally by the ES itself.

Concanavalin A↗

Long-term effects of radiotherapy and bromocriptine treatment in patients with previous surgery for macroprolactinomas.

The long-term effect of radiotherapy and bromocriptine treatment was retrospectively evaluated in 25 patients who had previously undergone transsphenoidal surgery for treatment of macroprolactinomas. Surgery had reduced the median serum prolactin (PRL) value from 613 micrograms/l, a reduction of 53%. Postoperative bromocriptine was administered to 21 of the 25 patients. In 14 of these patients, serum PRL values became normal or almost normal with medication. There were no radiological or ophthalmological signs of progressive tumor growth during bromocriptine treatment. Fourteen patients received postoperative radiotherapy. After withdrawal of bromocriptine in 13 of these patients an average of 7 years after radiotherapy, the median serum PRL value had further decreased by 95%. The PRL reduction was similar for all doses applied, 38 to 52 Gy. After withdrawal of bromocriptine in 8 patients not receiving radiotherapy an average of 7 years after operation, the median serum PRL level had further decreased by 75%. At follow-up, 18 additional instances of pituitary insufficiency had developed in the group receiving radiotherapy, compared with 8 cases of insufficiency in the group not receiving radiotherapy. Thus, because bromocriptine has a long-standing effect on prolactin secretion, and radiotherapy is associated with a notably high incidence of pituitary insufficiency, we propose that photon irradiation should be considered mainly for patients who are not candidates for surgical or medical treatment.

Adult↗

Electron microscopic demonstration of sialic acid residues in the organ of Corti with lectin from Limax flavus.

The localization of sialic acid (N-acetyl- and N-glyconylneuraminic acid) in the organ of Corti of the mongolian gerbil was examined with electron microscopy by postembedding labeling using Limax flavus agglutinin and feutin-gold. Gold labeling was observed on the fibrous structure of the tectorial membrane, the basilar membrane and the spiral limbus. The labeling was also observed on the cuticular plate of the hair cells, the head and cone of the pillar cells and the head plate of Deiters' cells and other supporting cells. Collagen or cytoskeletal glycoproteins are suggested to be the source of the sialic acid in these structures.

Animals↗

Time-related changes in the guinea pig cochlea after acoustic overstimulation.

Forty-eight female pigmented guinea pigs were used to study the development of the morphologic and electrophysiologic changes occurring during a 4-week period after exposure to a 3.85-kHz pure tone at an intensity of 120 dB sound pressure level for 22.5 minutes. The morphologic results suggest an alteration in the permeability of ions between the inner ear fluids through gradual development of holes in the reticular lamina.

Animals↗

Initial changes in the sensory hair-cell membrane following aminoglycoside administration in a guinea pig model.

This study demonstrates the initial changes affecting the sensory hair-cell plasma membranes in the vestibular end organs of gentamicin-treated guinea pigs by using a ruthenium red staining technique. First, 0.1 ml of a solution containing 5 mg gentamicin sulfate was injected into the middle ear. After 7 days, the sensory hair cell cilia were observed to be degenerating. The various stages of this degeneration process were classified into two types: the decrease in glycocalyx was designated type I fusion, while type II fusion was characterized by a bleb formation of the plasma membrane of the sensory hair cells, followed by a decrease in glycocalyx. The latter mechanism allowed plasma membrane contact, with subsequent fusion of the plasma membrane of neighboring sensory hair-cell cilia. The material also illustrates the degeneration of ciliary actin filaments. These findings suggest that the aminoglycoside affects both the glycocalyx and the plasma membrane, and that the decrease in glycocalyx may be the first sign of sensory hair-cell fusion.

Animals↗

Ultrastructural localization of carbonic anhydrase in the vestibular end organs of the guinea pig.

Carbonic anhydrase activity was demonstrated cytochemically on an ultrastructural level in the vestibular end organs of the guinea pig. Reaction product was found in the dark cells, transitional cells, cells of the planum semilunatum and supporting cells. In the dark cells, reaction product was observed in the cytoplasm as well as in the basal infoldings. Reaction product was also observed in the basal infoldings of the transitional cells and the cells of the planum semilunatum. The globular structures inside the supporting cells, transitional cells and the cells of the planum semilunatum were also surrounded by the reaction product. These findings suggest that carbonic anhydrase may have different functions, such as water and ion transport, respiration, nutrition and calcium carbonate deposition in the vestibular end organs.

Animals↗

The effect of gentamicin on the glycocalyx and the ciliary interconnections in vestibular sensory cells: a high resolution scanning electron microscopic investigation.

Changes in glycocalyx structure and ciliary interconnections of the vestibular sensory cells are demonstrated after gentamicin administration. A special high resolution scanning electron microscope and a tannic acid-osmium staining technique giving an almost three dimensional view were used to achieve this purpose. Guinea pigs were injected with a single dose of 5 mg of gentamicin directly into the middle ear. Seven days after the injection, it was possible to observe the degenerative process of the glycocalyx and the ciliary interconnections. The first detectable change was a disarrangement of the cilia with a loosening of the interconnections. The ciliary membrane presented with an irregular appearance. The tip links connecting the tips of the stereocilia to their neighbours were also affected showing elongation or even disappearance. In the later stages of the degeneration process, the sensory hairs presented with different degrees of fusion whereafter they finally disappeared totally. These findings suggest that the glycocalyx acts to maintain a normal stability and shape of the ciliary membrane and to keep the regular distance between cilia in order to maintain the arrangement of the whole ciliary bundle. Gentamicin probably affects the glycocalyx and the ciliary interconnections resulting in a disarrangement, detachment and fusion of cilia. The tip links, which are suggested to be involved in sensory cell transduction, seem to be also affected by gentamicin.

Animals↗

Distribution and metabolism of leukotriene C4 after cisternal injection in guinea pigs.

Following cisternal injection of [3H8]LTC4 into guinea pigs, leukotriene metabolites were identified in the brain, cerebellum, perilymph, blood, liver and kidneys. LTC4 was metabolized into LTD4 and LTE4 in the cerebrospinal fluid and LTE4 was transported into the blood for general circulation and uptake into the liver and kidneys. The excretion of LTE4 from CNS to blood seemed to be the rate-limiting step in the elimination of leukotrienes from the body. Leukotrienes were also transported into the perilymph. The conversion of LTC4 into LTD4 and LTE4 was lower in perilymph as compared to the cerebrospinal fluid, suggesting a rate limiting function of the cochlear aqueduct that can be defined as a cerebrospinal fluid-labyrinth barrier.

Animals↗