PubMed Health⌕ Search

Biomedical subjects

D Berggren

Publications and source records attributed to D Berggren.

16 recordsLinked to original sources

Round window membrane delivery of L-methionine provides protection from cisplatin ototoxicity without compromising chemotherapeutic efficacy.

Cisplatin (cis-diamminedichloroplatinum(II) (CDDP)) is a widely used, highly effective, oncolytic agent that has serious ototoxic side-effects. To test the effectiveness of local delivery, of L-methionine (L-Met) as an otoprotective agent against CDDP ototoxicity, we used a rat model of a highly metastatic breast cancer tumor, i.e. Fisher 344 rats implanted with MTLn3 breast cancer cells. Four experimental groups were evaluated--I: untreated; II: CDDP-treated (three dosages); III: systemically-delivered L-Met + CDDP-treated; IV: locally delivered L-Met + CDDP-treated. The integrity of the outer hair cells (OHCs) was determined using scanning electron microscopy (SEM); hearing was assessed by recording auditory brainstem responses (ABRs) at multiple frequencies. The chemotherapeutic effectiveness of CDDP was quantified by measuring changes in tumor mass and the presence of tumor metastasis. L-Met provided otoprotection of the OHCs against CDDP toxicity in the cochleae of rats following either systemic (III) or local (IV) administration. The ABRs were unchanged in each of the L-Met protection Groups (III and IV) and in the untreated animals of Group I. Treatment with CDDP only (II) induced significant hearing losses at both 16 and 18 kHz when compared to ABRs of untreated rats(I). CDDP was effective in controlling the MTLn3 initiated breast cancer tumors in the CDDP-treated (II) and the local L-Met protection, CDDP-treated (IV) Groups. In contrast, the tumors in the systemic L-Met protection, CDDP-treated Group (III) were not controlled by the CDDP treatment regime. This study demonstrates that local delivery of L-Met to the scala tympani of the cochlea via the round window membrane (IV) provides effective protection against CDDP ototoxicity without compromising its ability to control a highly metastatic form of cancer.

Adenocarcinoma↗

Swallowing dysfunction related to snoring: a videoradiographic study.

Biopsy studies of the soft palatal and oropharyngeal tissues in habitual snorers and patients suffering from obstructive sleep apnoea have shown signs of neurogenic lesions. These lesions might affect the pharyngeal swallowing function, which is dependent on adequate sensitivity. The objective of the present study was to test the hypothesis that snoring is associated with aberrant pharyngeal swallowing function. Forty-one consecutive patients without dysphagia, seeking medical attention because of heavy snoring and various degrees of daytime sleepiness, were prospectively selected. Fifteen non-snoring volunteers without dysphagia served as controls. Patients and volunteers were videoradiographically examined in lateral and posteroanterior views during the oral and pharyngeal phases of swallowing. The hypothesis was verified. Snoring patients demonstrated deviant pharyngeal swallowing function seven times more frequently than did the non-snoring volunteers. Deviant pharyngeal swallowing function was observed in 22 (54%) of the snorers compared with 1 (7%) of the non-snoring volunteers. Impaired bolus control with premature leakage of bolus into the pharynx and a delayed evocation of the swallowing reflex was the most common finding, followed by bolus residual in the pharynx and laryngeal penetration. The conclusion was that snoring is associated with subclinical pharyngeal swallowing dysfunction.

Adult↗

Fine structure of extracellular matrix and basal laminae in two types of abnormal collagen production: L-proline analog-treated otocyst cultures and disproportionate micromelia (Dmm/Dmm) mutants.

L-Azetidine-2-carboxylic acid (LACA), a naturally occurring vegetable imino acid, can be incorporated into mammalian proteins in place of proline, thereby eliciting an inhibitory effect on collagen secretion. Exposure of explants of the embryonic mouse inner ear to LACA reduces the number of collagen fibrils in the otic capsule, gives rise to a dose-dependent derangement of the basal lamina, and ultimately results in dysmorphogenesis and retarded differentiation of the inner ear. Disproportionate micromelia (Dmm) is an incomplete dominant form of dwarfism characterized by a reduced quantity of type II collagen in the cartilaginous extracellular matrix (ECM). Abnormal morphogenesis in homozygotic Dmm mice resembles the abnormal morphogenesis observed in LACA-exposed otic explants, resulting in malformed inner ears with a bulky cartilaginous capsule and a lack or reduction of defined perilymphatic spaces (Van De Water and Galinovic-Schwartz, 1987). In this study, we examined by ultrastructural analysis LACA-exposed otic explants and inner ears of Dmm/Dmm mouse embryos for abnormalities in the collagenous constituents of the basal laminae and capsular ECM. We demonstrate, in comparison to normal embryonic mouse inner ears, a reduction in collagen fibrils and irregular cytodifferentiation of chondrocytes in the ECM of LACA-exposed and Dmm/Dmm inner ears as well as in the basal laminae of LACA-exposed specimens. In addition, we provide evidence of dysmorphogenesis of the otic capsule and perilymphatic spaces in LACA-exposed explants. Moreover, while previous studies demonstrated the anomalous development of sensory structures in otocyst explants following LACA exposure, in this study we provide evidence of the normal morphogenesis of otic epithelial-derived sensory structures in homozygotic Dmm/Dmm mouse embryos.

Animals↗

Falls leading to femoral neck fractures in lucid older people.

OBJECTIVE: To analyze the mechanisms of falls that result in femoral neck fractures among lucid older people. DESIGN: A cross-sectional study. SETTING: An orthopedic university hospital department. PARTICIPANTS: A consecutive series of 123 lucid patients, 65 years of age or more, who were admitted for femoral neck fractures. MEASUREMENTS: On admission, the subjects were interviewed about fracture accident characteristics, and falling mechanisms were classified. An arterial blood gas sample was taken from each patient soon after admission. Based on data regarding drug consumption and social and medical characteristics, a fall-risk index was calculated for each subject. RESULTS: It was ascertained that 95% of the fractures were caused by falls and < 2% were spontaneous. Most accidents (68%) took place indoors, 47% of the falls were classified as extrinsic, 24% as intrinsic, 7% as nonbipedal, and 22% remained unclassified. Almost all outdoor falls were extrinsic; however, intrinsic falls were as common as extrinsic falls indoors (P < .001). Extrinsic fallers presented a significantly lower fall-risk index score than subjects with fractures caused by intrinsic, nonbipedal, and unclassifiable falls. A large proportion of subjects (24%) wre hypoxemic (pO2 < 8 kPa) on admission, and patients who sustained fractures at night had lower oxygen tension than that of daytime fallers (P = .006). CONCLUSIONS: Accidental falls are the primary cause of femoral neck fractures. Preventive actions should be directed toward intrinsic, as well as extrinsic, risk factors for falls. Hypoxemia might be a risk factor for falls, especially those falls that occur at night.

Accidental Falls↗

Age-dependent disruption of basal lamina and extracellular matrix formation in L-proline analog treated otic explants.

L-azetidine-2-carboxylic acid, LACA, a naturally occurring vegetable imino acid, can be incorporated into mammal proteins instead of proline. This incorporation has an especially inhibitive effect on collagen secretion. Exposure of embryonic mouse inner ear explants to LACA causes dysmorphogenesis and retarded differentiation, reduces the number of collagen fibrils in the perilymphatic spaces and capsules, and gives rise to a dose-dependent derangement of the basal lamina. In control specimens, both in vivo and in vitro, the inner ear epithelia had a dense contiguous basal lamina overlying a well-developed network of collagen fibrils. When the inner ears were exposed to LACA at a concentration of 150 micrograms per ml of medium, there was a loss of the collagen network and gaps appeared in the basal lamina. At exposure to 300 micrograms LACA/ml, scarcely any collagen fibrils were present and the basal lamina was disrupted in many areas, especially beneath the sensory epithelia.

Animals↗

Characteristic ionic composition of endolymph is maintained in cultured inner ear.

Inner ear anlagen from mouse were explanted on the 16th gestational day (gd) and cultured for 5 days, i.e. corresponding to the time of birth. By using energy dispersive X-ray technique an elemental composition characteristic for endolymph was found within the membranous labyrinth of the explants. The sodium to potassium ratio in the endolymphatic space of the cultured inner ears corresponded to endolymph of the 16th gd fetus in vivo. There was no difference in the endolymph compartment between the cochlear and vestibular halves of the in vitro specimens. Differences in Na to K ratio between endolymph of the inner ears and the surrounding medium were statistically significant. Thus, endolymph-regulating mechanisms are active also under organ culture conditions, although not fully optimal.

Animals↗

A geriatric-anesthesiologic program to reduce acute confusional states in elderly patients treated for femoral neck fractures.

The aim of this study was to evaluate the effect of a geriatric-anesthesiologic intervention program for the prevention and treatment of acute confusional states (ACS) in elderly patients treated for femoral neck fractures. The intervention program was based on the results of previous prospective studies in similar patient populations. The outcome of the intervention, comprising 103 patients, was compared with that of an earlier study comprising 111 patients. The intervention program consisted of pre- and post-operative geriatric assessments, oxygen therapy, early surgery, prevention and treatment of peri-operative blood pressure falls and treatment of post-operative complications. The incidence of ACS was lower, 47.6%, in the intervention study compared with 61.3% (P less than 0.05) in the control study. Furthermore, the ACS that occurred in the intervention study was less severe and of shorter duration than that in the control study. The incidence of post-operative decubital ulcers, severe falls, and urinary retention was also lower. The mean duration of orthopedic ward stay was 17.4 days in the control study and 11.6 days in the intervention study (P less than 0.001). It can be concluded that the intervention program reduced the incidence, severity, and duration of ACS which resulted in a shortened orthopedic ward stay.

Aged↗

Lack of differentiation of the isolated murine statoacoustic ganglion during organ culture.

The isolated 12th gestational day statoacoustic ganglion (SAG) of the CBA/CBA mouse was cultured in vitro for 4-8 days. After 4 days, 25% of the SAG had survived, having nerve fibers growing in a circular pattern around the SAG. A further separation into a vestibular and a cochlear part, which occurs in vivo, was not observed. It is concluded that a trophic interaction between the SAG and target tissues is needed for further differentiation of the SAG.

Animals↗

Acute confusional states in elderly patients treated for femoral neck fracture.

The aims of this study were to estimate the incidence of acute confusional state (ACS), its predisposing factors and consequences in 111 consecutive patients operated for fractured neck of the femur. The incidence of ACS was 61 percent and the predicting factors were old age and dementia. Drugs with anticholinergic effect, depression, and previous stroke were factors that seemed to be associated with the development of ACS. Ninety-two percent of the patients who had severe perioperative blood pressure drops developed ACS. The consequences of ACS were prolonged ward-stay at the orthopedic department, a greater need for long-term care after discharge, and poor walking ability at discharge and six months after surgery. The confused patients also had more complications, such as urinary problems, feeding problems and decubital ulcers, as compared with the nonconfused patients.

Aged↗

Postoperative confusion after anesthesia in elderly patients with femoral neck fractures.

Fifty-seven patients, all over the age of 64, with femoral neck fracture were randomized to receive epidural or halothane anesthesia to see if the anesthetic technique influenced the incidence of postoperative confusion. All patients were lucid on admission. Using the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-III) as criteria for confusion, we found that 44% of the patients developed confusion that correlated closely to a history of mental depression (P less than 0.01) and to the use of drugs with anticholinergic effect (P less than 0.005). There was no difference in the incidence of confusion between the two anesthetic groups. In patients given halothane, however, early postoperative hypoxemia was associated with confusion (P less than 0.05). Patients with confusion had significantly more postoperative complications and almost four times longer hospitalization times. It is concluded that anticholinergic medication and a history of mental depression are predominant risk factors for development of postoperative confusion and in this respect are more important than the anesthetic technique.

Aged↗

Borreliosis as a cause of peripheral facial palsy: a multi-center study.

Borreliosis is known to be a common cause of peripheral facial palsy in Stockholm and its vicinity. The aim of the present study was to investigate the frequency and characteristics of borreliosis among patients with peripheral facial palsy in different parts of Sweden. All serological tests were performed in one laboratory. Ten Swedish Ear Nose and Throat clinics participated in a prospective 1-year study of patients seeking medical attention for acute peripheral facial palsy. Twenty-eight (6%) out of totally 446 patients fulfilled the criteria for the diagnosis of borreliosis. The frequency varied between 1 and 16% and was highest along the southeast coast of Sweden whereas no case was reported from the northern part of the country. Borreliosis was more common among children with facial palsy than among adults. The infection occurred during all seasons although it appears to be less frequent during the spring months. Only a minority of the borrelial patients had a history of a preceding tick bite or erythema migrans. The fairly low overall frequency of this secondary stage of borreliosis in the study may be a result of better knowledge of the disease and earlier treatment of its early manifestations. In Sweden's endemic areas borreliosis is a common cause of peripheral facial palsy, and therefore all patients with facial palsy in these regions should be examined for borrelial infection.

Adolescent↗

Formation of junctional complexes in otocysts developed in vitro. A freeze-fracture study.

The thirteenth gestational day inner ear anlage (otocyst) was explanted to an in vitro system and cultured for 8 days, i.e. to a time corresponding to birth. The freeze fracturing technique was used to evaluate morphological differentiation, particularly as regards cell membrane specializations. The epithelial cells were found fully differentiated, e.g. there were regularly arranged stereocilia on the hair cells. The development of tight junctions and gap junctions followed the same pattern as in vivo, but tight junctions did not reach the same degree of regularity and maturation as they did in vivo. There were very few gap junctions in our in vitro specimens. Several tight junctions had an odd appearance, with loss of the normally punctate structure of the strands and areas with considerable thickening. It is possible that this specific morphology can be explained by differentiation in the in vitro system.

Animals↗

Tissue binding kinetics of tobramycin. An experimental study in the mouse inner ear in vitro.

The tissue-binding capacity of tritiated tobramycin (TM) was analysed in an organ culture system in the embryonic inner ear of the mouse. A rapid and probably irreversible binding of TM occurs within 10 min, showing about 100 micrograms TM per gram protein in the vestibular half and about 75 micrograms TM per gram protein in the cochlear half of the labyrinth. A steady state is reached within 60 min. The TM uptake was then 390 micrograms TM per gram protein in the vestibular part and 270 micrograms in the cochlear part of the inner ear. A minor fraction of TM, of the same magnitude as initially bound, becomes irreversibly bound, whereas the slow accumulation which reaches the steady state level seems reversible.

Animals↗

Intermediate filament proteins in the embryonic inner ear of mice under normal conditions and after exposure to ototoxic drugs.

The expression of the intermediate filament subclasses cytokeratins (CKs), vimentin, and neurofilament triplet proteins (NFs) was analysed in the embryonic inner ear of the CBA/CBA mouse, in vivo and in vitro, using well-defined monoclonal antibodies. Some of the cultured inner ears were exposed to 1-10 micrograms/ml of the ototoxic drugs gentamicin, ethacrynic acid or cisplatin. There was no difference in the expression of IF pattern in the cultured inner ears as compared with the in vivo developed labyrinths. Exposure to the ototoxic drugs did not affect the expression of CKs, vimentin, or NFs. CKs 8 and 18 were identified in all inner ear epithelia. In the mature hair cells, only the apical surfaces showed immunoreactivity to CKs. In addition, CKs 7 and 19 were visualized in the epithelia involved in maintaining endolymph homeostasis. The ganglion cells showed co-expression of CKs, vimentin and NFs, each having a characteristic localization in the cells.

Animals↗

Antitumour effect of L-2,4 diaminobutyric acid on a hepatoma cell line.

Pharmacological treatment of malignant disease is often insufficient highlighting the need for more efficient treatment based on new principles. We have observed that the amino acid analogue diaminobutyric acid (DAB), accumulates in malignant cells apparently without saturation kinetics, leading to hyperosmosis and subsequently to cell lysis. In the first in vitro part of the present study hepatoma cells were incubated with DAB in miniwells in the presence or absence of physiological amino acids. In the in vivo part malignant cells were inoculated into rat liver after laparotomy. The tumour was treated by continuous infusion of DAB via a catheter, the tip of which was placed in the center of the tumour. DAB had a significant antitumour effect both in vitro and in vivo. The principle of action of DAB as an antitumour agent is unique and therefore would be the ideal partner to practically any other cytostatic drug for a combined treatment to achieve a synergistic effect.

Aminobutyrates↗