Biomedical subjects

G Laurell

Publications and source records attributed to G Laurell.

At least 19 recordsLinked to original sources

PubMed2004

Percutaneous endoscopic gastrostomy (PEG) - a long-term follow-up study in head and neck cancer patients.

Many patients with head and neck cancer experience problems related to swallowing. A retrospective study of 156 consecutive patients who received a percutaneous endoscopic gastrostomy (PEG) at a teaching hospital is presented. The results showed that 42% had complications. Fatal complications were seen in connection with PEG tube placement, but severe and minor complications could occur much later. The method of PEG tube insertion did not affect the complication rates. The spectrum of observed complications is different to that reported earlier, suggesting that the learning curve of surgeons under training could have influenced the outcome. It may be concluded that for a very sick patient a theoretically easy surgical procedure could turn into a potentially dangerous operation. It is important to select suitable candidates for a PEG. Head and neck cancer patients with a PEG need special attention in connection with the PEG tube placement and also in a long perspective, e.g. by follow-up at a nurse-led outpatient clinic.

Aged↗

PubMed2003

Intracochlear administration of thiourea protects against cisplatin-induced outer hair cell loss in the guinea pig.

Amelioration of cisplatin-induced side-effects is of great clinical importance. Local administration of a cytoprotective agent to the inner ear offers a possibility to prevent cisplatin-induced ototoxicity without risk of interference with the antitumour effect. The ideal substance for local administration has yet to be identified. Thiourea (TU) has unique properties that make it an interesting candidate. This study was initiated to test the hypothesis that TU given by local administration protects against cisplatin ototoxicity in the guinea pig. After baseline auditory brainstem response (ABR) assessment, the left cochlea was implanted with a microtip catheter connected to an osmotic pump filled with either 27 mg/ml TU in artificial perilymph (AP), or AP administered for the full duration of the study. Three days post-implant, animals with normal ABRs received an intravenous injection of 8 mg/kg body-weight cisplatin. Five days after the cisplatin treatment ABRs were reassessed, animals decapitated and bilateral cytocochleograms prepared. TU-treated ears demonstrated significantly lower outer hair cell (OHC) loss as compared to contralateral untreated ears, and significantly lower OHC loss compared to AP-treated ears. ABR threshold shift did not differ significantly between the two groups. It can be postulated that TU demonstrates partial protection against cisplatin-induced ototoxicity.

Animals↗

PubMed2002

Local administration of antioxidants to the inner ear. Kinetics and distribution(1).

Round window (r.w.) administration of drugs involves the delivery of medication directly into the inner ear via the r.w. membrane, avoiding a systemic effect of the therapy. Earlier experimental studies suggest that a number of antioxidants and scavengers hold promise for ameliorating the tissue damaging capacity of reactive oxygen species in some acquired cochlear disorders. D-Methionine and thiourea are two small sulfur-containing molecules with an antioxidative and scavenging effect. The passage through the r.w. of radioactive D-methionine and thiourea administered by 1 h infusion to the r.w. was studied in a rat model. Levels of the tracers were measured in scala tympani perilymph (PLT) 17-254 min after r.w. administration. Both tracers pass the r.w. membrane readily. Peak levels were found in the earliest taken samples after the administration. The radioactivity in PLT of the basal turn reached a peak to about 1.5-1.9% of the irrigating medium radioactivity. Following the r.w. administration, the concentration of radioactive D-methionine and thiourea declined with a terminal half-life of 0.57 and 0.77 h, respectively. The distribution of the tracers at the cellular level was analyzed by autoradiography. The most intense expression was found in the lateral wall of the cochlea. It can be postulated that local delivery to the cochlea of D-methionine and thiourea via the r.w. gives high local concentrations of the substances in PLT in the basal turn.

Animals↗

PubMed2000

Cisplatin-induced hearing loss: influence of the mode of drug administration in the guinea pig.

Cisplatin (8 mg/kg) was given intravenously to guinea pigs either as a 15 s bolus injection (25 animals) or as a 1 h infusion (28 animals). To determine the influence of the mode of cisplatin administration and pharmacokinetics on the ototoxic side-effect, the concentrations of cisplatin and the biotransformation product monoaquated cisplatin were determined in blood ultrafiltrate using liquid chromatography with post-column derivatization. Ototoxic effect was evaluated as difference in pre- and 96 h post-exposure auditory brainstem response (ABR) threshold. The cisplatin peak concentration was considerably higher, 19.2+/-2.4 microg/ml, in the bolus injection group than in the infusion group, 6.7+/-0.5 microg/ml (mean+/-S.E.M.). The area under the blood ultrafiltrate concentration time curve (AUC) for cisplatin was slightly greater in the infusion group, 442+/-26 microg/ml/min, than in the bolus injection group, 340+/-5 microg/ml/min. For monoaqua cisplatin, the AUC was not different between the groups (bolus injection: 30.8+/-1. 5 microg/ml/min, infusion: 34.1+/-3.3 microg/ml/min). A significant ototoxic effect was observed in both groups at 20 and 12.5 kHz, but there was no difference between the groups in the extent of threshold shift. The interindividual variability in susceptibility to ABR threshold shift was far greater than the variability in pharmacokinetics, suggesting that other factors are more important in determining the degree of hearing loss.

Animals↗

PubMed2000

Blood-perilymph barrier and ototoxicity: an in vivo study in the rat.

Cisplatin and gentamicin are two ototoxicants that are supposed to be transported by the paracellar route, i.e. via cellular junctions, to the perilymphatic compartment. This study was initiated to test the hypothesis that susceptive variation of individuals to ototoxic drugs may be explained by variability in transport properties. The transport of radioactive mannitol through the blood-perilymph barrier was correlated in vivo with the acute effect of cisplatin and gentamicin on auditory function. Transport of radioactive mannitol across the blood-perilymph barrier was monitored by sampling of scala vestibuli perilymph at 60 and 120 min after an intravenous infusion of the tracer to nephrectomized Long Evans rats. Counting of hair cell loss was performed in the animals receiving 16 mg/kg body weight cisplatin. The transport of radioactive mannitol across the blood-perilymph barrier did not correlate with the ototoxic effect of cisplatin, evaluated as changes in the auditory-evoked brainstem response thresholds or loss of outer hair cells. The results provide evidence that the barrier function is not involved in the interindividual variability of the ototoxic effect of cisplatin. Furthermore, it can be postulated that neither cisplatin nor gentamicin induce a disruption of endothelial cell junction stability in the inner ear.

Animals↗

PubMed1999

Lead in plasma and whole blood from lead-exposed children.

In 31 children exposed to lead and 13 considerably less exposed children ("unexposed"), the plasma (Pb-P) concentrations ranged from 0.46 to 18.4 (median, 2.4) and from 0.14 to 0.38 (median, 0.21) microg/L, respectively. Corresponding whole-blood concentrations (Pb-B) were 99-920 (median, 370) and 39-120 (median, 66) microg/L, respectively. The relation between Pb-B and Pb-P was nonlinear; when Pb-P rose, the Pb-B increased relatively less. There was a close association between Pb-B and log Pb-P (r=0.95; P=0.0001). When these data were compared to previous data on adults, there was no major difference between children and adults in the Pb-B/Pb-P relation. Free erythrocyte protoporphyrins in blood were associated with Pb-P (r=0.75; P=0.0001) and Pb-B (r=0.90; P=0.0001). Also, there was an association between blood-hemoglobin concentration and Pb-P in both exposed (r=-0.67; P=0.0001) and unexposed (r=-0.67; P=0.01) children; the corresponding figures for Pb-B were r=-0.42; P=0.02, and r=-0.80; P=0.001, respectively. Thus, at least with regard to toxicity on hematopoiesis at high lead levels, Pb-P may be a more relevant indicator of exposure and risk than Pb-B. Because the curved Pb-B/Pb-P relation indicates a saturation of binding sites for lead in red cells, exposure and risk at high lead levels may easily be underestimated from Pb-B data.

Adolescent↗

PubMed1999

Distortion product oto-acoustic emissions in Andean children and adults with chronic lead intoxication.

Neuroauditory disorders and sensory-neural hearing loss have been suggested as possible etiologic factors in the neurodevelopmental learning disabilities attributed to lead (Pb) intoxication. However, studies relating hearing loss to Pb poisoning have presented disparate results, suggesting that auditory sensitivity may not be a reliable marker of Pb intoxication. Oto-acoustic emissions, sounds that can be recorded non-invasively from the ear canal and are preneural responses of the outer hair cells of the inner ear, have been found to be diminished in ears exposed to some toxic agents. In the current study, distortion product oto-acoustic emissions (DPOAEs) were obtained from 28 ears of 14 children and 10 ears of 5 adults living in a highly Pb-contaminated environment in remote villages in the Andes Mountains of Ecuador. Blood lead (PbB) levels for the children (ages: 5-14 years) ranged from 33.4 to 118.2 microg/dl (mean: 51.5; SD: 22.9 microg/dl), or 3-12 times higher than the U.S. Centers for Disease Control and Prevention's toxic level of 10 microg/dl. The PbB levels for the adults ranged from 19.2 to 55.7 microg/dl. Despite the high PbB levels, the children had normal hearing thresholds, and DPOAEs were present for the children at the following f2 frequencies: 1187, 1500, 1906, 2406, 3031, 3812, 4812 and 6031 Hz. Although there was a tendency for the children to have diminished DPOAEs, no consistent correlation of DPOAEs with PbB level was found. The adults had diminished DPOAEs that were consistent with their observed, probably noise-related hearing loss. Contrary to some reports in the literature, the current results show no unequivocal clinical or subclinical evidence that high PbB levels have a toxic effect on the cochlea.

Adolescent↗

PubMed1998

Blood mercury and auditory neuro-sensory responses in children and adults in the Nambija gold mining area of Ecuador.

This study investigated blood mercury (B-Hg) levels and the auditory neuro-sensory status of children and adults in the remote Andean settlement of Nambija, Ecuador where Hg is used in the extensive gold mining operations. The mean B-Hg level in 75 Nambija (Study Area) inhabitants (36 children and 39 adults) was 17.5 micrograms/L (SD = 11.0) vs 3.0 micrograms/L (SD = 1.6) in a second group of 34 subjects (15 children and 19 adults) in a non-gold mining area (Reference Area), the difference being statistically significant (p < 0.0001). Neuro-otological examinations revealed 34 subjects (45%) with complaints of headaches and/or memory loss, 3 cases of severe neurological impairment and 4 cases of middle ear pathology. Audiological tests on 40 persons in the Study Area (21 children and 19 adults) showed hearing thresholds ranging from normal to mildly abnormal at 2, 3, 4, 6 and 8 kHz for children, and normal to severely abnormal for adults. Correlation coefficients showed a significant relationship between B-Hg level and hearing level in children at 3 kHz in the right ear, and at no frequency for adults. Auditory brainstem evoked responses (ABR) on subjects in the Study Area showed a significant correlation between B-Hg and the I-III interpeak latency on the right side. The results indicated that the study population of the Nambija gold mining area had abnormally elevated B-Hg levels, and may be at neurological risk from exposure to methylmercury (MeHg) from the consumption of contaminated food and possibly from elemental Hg vapors inhaled during amalgam burning in the gold extraction process.

Adolescent↗

PubMed1998

Field screening of blood lead levels in remote Andean villages.

Blood lead (PbB) levels were investigated in chronically lead (Pb) exposed Andean children and adults living in a highly Pb contaminated area of Ecuador where Pb glazing of ceramics is prevalent. A comparative study was made of the PbB levels of Pb-glazing and non-Pb-glazing families living in close proximity, using three PbB analysis techniques. Fifty-one, 50-microl blood samples from children and adults were analyzed in the field by a finger-stick capillary screening technique using the portable ESA LeadCare Blood Lead Testing System (LCS). Venous blood samples of 2-4 ml were collected from the same 51 participants and analyzed in the laboratory by inductively coupled plasma mass spectrometry (ICP-MS) and by graphite furnace atomic absorption spectrometry (AAS). The median PbB levels for the Pb-glazing group as determined by the ICP-MS, AAS and LCS techniques were 37.2 microg/dl (range 11.6-101.0), 32.0 microg/dl (range 8.0-70.0 microg/dl) and 44.0 microg/dl (range 19.0-105.0), respectively. The median PbB levels for the non-Pb-glazing group were 9.2 microg/dl (range 5.0-21.7) with ICP-MS, 9.0 microg/dl (range 4.3-32.0) with AAS, and 11.3 microg/dl (range 7.3-21.1) with LCS. The differences in PbB levels between the Pb glazing and non-Pb glazing groups were statistically significant (p = < .0001) for each PbB analysis method. Correlations between paired samples were: LCS and ICP-MS: r = 0.913, LCS and AAS: r = 0.829, and ICP-MS and AAS: r = 0.905. The results suggest that neighboring Pb glazing and non-Pb glazing families have significantly different PbB levels, and that the portable LCS field technique may be useful for screening and periodic monitoring of relatively low and high PbB levels of persons in remote high altitude Andean areas.

Adolescent↗

PubMed1997

Normal auditory brainstem and cochlear function in extreme pediatric plumbism.

Lead (Pb) intoxication in children has been associated with encephalopathy, sensory and cognitive impairments. We investigated the prevalence and neuro-sensory effects of Pb exposure in children living in Andean villages of Ecuador with high Pb contamination from discarded automobile batteries used in the local ceramics glazing industry. Venous blood samples were collected from 107 children in the Pb glazing area and from 39 children living in a geographically distant area with no known Pb contamination and measured for blood lead (PbB) levels. Auditory brainstem responses (ABR) and audiological/otological tests were conducted on children in the Pb-Glazing Group. The median PbB level for children in the Pb-Glazing Group was 40.0 microg per dl (range: 6.2-128.2 microg per dl) and for the non Pb-Glazing Group 6.0 microg per dl (1.9-18.0 microg per dl). The differences in PbB levels for children in the study and control areas were statistically significant (t-test, P<0.0001). ABR tests on the Pb-Glazing Group indicated normal wave latencies and neural transmission times, and no statistical correlation between PbB level and interpeak latencies. Audiological tests showed normal cochlear function and no statistical relation between auditory thresholds and PbB level. Contrary to prevailing assumptions, elevated PbB levels in children do not invariably impair auditory brainstem neural transmission or sensory-neural cochlear function, both of which have been implicated as significant contributors to the neurodevelopmental disabilities associated with childhood plumbism.

Adolescent↗

PubMed1997

Extensive lead exposure in children living in an area with production of lead-glazed tiles in the Ecuadorian Andes.

We have determined the concentrations of lead (Pb), cadmium (Cd), and mercury (Hg) in the blood of children living in two Andean villages in Ecuador with many family-owned cottage-type industries using Pb from discarded car batteries and occasionally, utility batteries containing Cd and Hg for the production of glazed tiles. The battery metals are ground together with water to a suspension, which is applied manually onto the tiles and then fused at about 1,200 degrees C in sawdust-fired kilns. Children aged 4-15 years were recruited from the schools with the assistance of the school-teachers. Children from homes with and without tile-glazing activities were to be included. Blood metal concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS). The children had extremely high blood lead concentrations (B-Pb), which ranged between 100 and 1,100 micrograms/l (median 510 micrograms/l, n = 82). Children from families engaged in tile-glazing production had significantly higher B-Pb (median 600 micrograms/l) than those living in homes with no such activity (median 210 micrograms/l), although the B-Pb of the latter were nonetheless clearly elevated. B-Cd and B-Hg were low (medians 0.25 microgram Cd/l and 1.6 micrograms Hg/l, respectively), indicating that the exposure from utility batteries containing Cd and Hg was low. The blood hemoglobin concentrations decreased significantly with rising B-Pb, indicating an effect on the heme synthesis. This was supported by a marked increase in the blood concentration of protoporphyrins with increasing B-Pb. It can be concluded that children from families with cottage industries producing glazed tiles are at risk for severe health effects due to high lead exposure.

Adolescent↗

PubMed1997

Paracellular transport properties of inner ear barriers do not account for cisplatin toxicity in the rat.

The interindividual variability for the ototoxic effect of the antineoplastic drug cisplatin has still to be explained. To examine if the variability can be related to differences in drug kinetics, the effect of cisplatin on the paracellular transport properties of the inner ear barriers was studied in vivo in cisplatin treated Long-Evans rats. The concentration of [3H]mannitol was followed in plasma, scala vestibuli perilymph, and endolymph after an intravenous infusion of the tracer. Cisplatin had no effect on paracellular transport of the inner ear barriers 3 days after administration of 8 mg/kg cisplatin. However, an interindividual variability for the transport of [3H]mannitol across the blood-perilymph barrier was evident, indicating a variability for the passive transport of solutes to the inner ear.

Animals↗

PubMed1997

High lead exposure and auditory sensory-neural function in Andean children.

We investigated blood lead (B-Pb) and mercury (B-Hg) levels and auditory sensory-neural function in 62 Andean school children living in a Pb-contaminated area of Ecuador and 14 children in a neighboring gold mining area with no known Pb exposure. The median B-Pb level for 62 children in the Pb-exposed group was 52.6 micrograms/dl (range 9.9-110.0 micrograms/dl) compared with 6.4 micrograms/dl (range 3.9-12.0 micrograms/dl) for the children in the non-Pb exposed group; the differences were statistically significant (p < 0.001). Auditory thresholds for the Pb-exposed group were normal at the pure tone frequencies of 0.25-8 kHz over the entire range of B-Pb levels, Auditory brain stem response tests in seven children with high B-Pb levels showed normal absolute peak and interpeak latencies. The median B-Hg levels were 0.16 micrograms/dl (range 0.04-0.58 micrograms/dl) for children in the Pb-exposed group and 0.22 micrograms/dl (range 0.1-0.44 micrograms/dl) for children in the non-Pb exposed gold mining area, and showed no significant relationship to auditory function.

Adolescent↗

PubMed1997

Blood flow-independent accumulation of cisplatin in the guinea pig cochlea.

Considerable interindividual variability in the ototoxic effect of cisplatin has become the unpredictable dose-limiting factor in its use as curative as well as palliative therapy. The drug accumulates in highly vascular areas in the cochlea, causing dose-related hair cell loss. The purpose of this study was to assess blood flow-dependent aspects of cisplatin absorption in the cochlea in order to better understand factors that may influence cisplatin-induced ototoxicity. The effect of reduced cochlear blood flow on the ototoxic action of cisplatin was studied in guinea pigs. Before cisplatin administration the cochlear vasculature in each animal was unilaterally pre-constricted, by the application of 2% epinephrine to the round window. A 20-30% reduction in cochlear blood flow, assessed by laser Doppler flowmetry, was maintained before and after intravenous infusion of 0.1% cisplatin. Cisplatin infusion affected cochlear blood flow but not vessel conductivity. The cochlear blood flow decrease, maintained by local epinephrine application to the round window during cisplatin infusion, did not alter the cisplatin-induced hearing loss. In addition, the concentration of free cisplatin in scala tympani perilymph did not differ between epinephrine-treated and non-treated ears. Our results indicate that cisplatin transport into the cochlea is not an energy-dependent process in the lateral wall vasculature.

Animals↗

PubMed1997

Radiotherapy enhanced ototoxicity of cisplatin in children.

We reviewed and re-examined 31 children (6 months-14 years at the time of diagnosis), who had been treated for a neoplasm in Turku University Central Hospital between 1989 and 1994. The children were divided into 3 groups according to the site of the neoplasm and the type of therapy. Group I included 13 children, operated on for an intracranial tumor and received postoperative radio- and cisplatin-based chemotherapy. Group II included 14 children operated on for intracranial tumors and treated with radiotherapy, but not given chemotherapy. Group III included 4 children suffering from extracranial malignancies and they had received chemotherapy including cisplatin. The children in Group I had significantly worse hearing thresholds in the middle- and high-frequency range than children in Groups II and III. In a precise analysis of the different factors, no single dose of cisplatin, inner ear irradiation dose or totally to the central nervous system (CNS) received irradiation dose correlated to the detected hearing loss. However, multiple linear correlation analyses suggest a combined effect of radiotherapy plus cisplatin resulting in a high frequency hearing loss. This is in accordance with earlier random case reports, and supports the idea that radiotherapy should be considered cautiously in children treated with cisplatin for intracranial malignancies.

Adolescent↗

PubMed1996

Cisplatin administration to gynecologic cancer patients. Long-term effects on hearing.

BACKGROUND: Cisplatin is known to create an acute dose-related ototoxic effect. There are unanswered questions regarding the long term effect of cisplatin on hearing in gynecologic cancer patients. METHODS: A retrospective review of 59 to 115 months' duration was performed on 184 women with gynecologic cancer who were treated with cisplatin-based chemotherapy between 1982 and 1986. Twenty-six of 40 survivors were again tested audiometrically with the same audiologic equipment. RESULTS: Fourteen patients (54%) had significantly progressive hearing loss (> or = 15 decibels) at long term follow-up compared with the posttreatment control. These changes were generally small and restricted to three frequencies or fewer in one of the patient's ears. The changes corresponded to the expected age effect upon hearing. Only 2 patients (8%) showed more severe hearing threshold changes. The hearing loss in one of the two patients might represent degenerative changes induced by cisplatin treatment, whereas in the other patient the etiologic background to the hearing loss remains unknown. CONCLUSIONS: This study does not provide any strong evidence for a delayed ototoxic effect of cisplatin that should influence therapeutic strategy. Patients who receive moderate dose cisplatin therapy, 50 mg/m2 per body surface area every 4 weeks, have a negligible long term risk of a drug-induced social hearing handicap.

Adult↗

PubMed1995

Distribution of cisplatin in perilymph and cerebrospinal fluid after intravenous administration in the guinea pig.

The concentration of free cisplatin was followed in plasma, scala tympani perilymph and cerebrospinal fluid (CSF) after an intravenous injection (12.5 mg/kg) in guinea pigs. Liquid chromatography with postcolumn derivatization was used for quantitative determination of the drug. The distribution of cisplatin to CSF was fast; at 10 min after drug administration the concentration was 7 micrograms/ml and the CSF:plasma ratio was 0.37. Cisplatin seems to distribute more slowly to the perilymphatic compartment. The highest concentration measured was 4 micrograms/ml at 20 min after the injection, and the perilymph:plasma ratio was 0.40 at that time. The concentration-time curves generated for cisplatin in perilymph and CSF were similar. No accumulation in the perilymphatic compartment or CSF was observed.

Animals↗

PubMed1995

Effect of cisplatin administration on the electrochemical composition of endolymph in the rat cochlea.

The effect of cisplatin on the electrochemical composition of the cochlear endolymph was studied in Long-Evans rats three days after a single intraperitoneal injection (8 mg/kg b.w.). A dose 2/3 of LD50 induced a decrease of the endolymphatic concentration of potassium whereas the endocochlear potential was unaffected. The discrepancy between these two findings indicated that cisplatin did not alter the mechanisms involved in the genesis of the endocochlear potential but modified the passive K transport into endolymph.

Analysis of Variance↗