Biomedical subjects

J Madsen

Publications and source records attributed to J Madsen.

At least 37 records · Page 2Linked to original sources

PubMed2000

The bicarbonate concentration in human saliva does not exceed the plasma level under normal physiological conditions.

Depending on the secretion rate and nature of the stimulus applied, the bicarbonate concentration ([HCO3-]) in human saliva has been shown to vary from 1 to 60 mM, with the highest values obtained in secretions from the parotid and submandibular glands. We conducted the present study on five healthy young males, in order to determine whether human saliva [HCO3-] can exceed the plasma level under normal physiological conditions, and applied a strategy in which we measured the secretory response to various stimulus intensities. Whole saliva stimulation was initiated by chewing paraffin (50-100 chewing cycles/min), parotid saliva stimulation by citric acid taste (0.2-4% citric acid solutions), and both secretions were also collected during systemic medication using pilocarpine (5 mg). Our results showed that the parotid and whole saliva flow rates were closely correlated to the intensity of the secretion-inducing stimulus applied (taste, chewing, and pilocarpine). This was also the case for saliva [HCO3-], all of which was present in the form of physically dissolved CO2, H2CO3, and HCO3-. The highest mean [HCO3-] (i.e. 37.75 mM) was found in parotid saliva after stimulation by pilocarpine in combination with 4% citric acid taste. Under normal physiological conditions (i.e. without pilocarpine) the saliva [HCO3-] was similar to or below the plasma level in both secretions.

Bicarbonates↗

PubMed1999

The genomic structure of the DMBT1 gene: evidence for a region with susceptibility to genomic instability.

Increasing evidence has accumulated for an involvement of the inactivation of tumour suppressor genes at chromosome 10q in the carcinogenesis of brain tumours, melanomas, and carcinomas of the lung, the prostate, the pancreas, and the endometrium. The gene DMBT1 (Deleted in Malignant Brain Tumours 1) is located at chromosome 10q25.3-q26.1, within one of the putative intervals for tumour suppressor genes. DMBT1 is a member of the scavenger-receptor cysteine-rich (SRCR) superfamily and displays homozygous deletions or lack of expression in glioblastoma multiforme, medulloblastoma, and in gastrointestinal and lung cancers. Based on these properties, DMBT1 has been proposed to be a candidate tumour suppressor gene. We have determined the genomic sequence of DMBT1 to allow analyses of mutations. The gene has at least 54 exons that span a genomic region of about 80 kb. We have identified a putative exon with coding potential for a transmembrane domain. Our data further suggest that alternative splicing gives rise to isoforms of DMBT1 with a differential utilization of SRCR domains and SRCR interspersed domains. The major part of the gene harbours locus specific repeats. These repeats may point to the DMBT1 locus as a region susceptible to chromosomal instability.

Agglutinins↗

PubMed1999

Cloning of gp-340, a putative opsonin receptor for lung surfactant protein D.

Surfactant protein D (SP-D) is an oligomeric C type lectin that promotes phagocytosis by binding to microbial surface carbohydrates. A 340-kDa glycoprotein (gp-340) has been shown to bind SP-D in the presence of calcium but does so independently of carbohydrate recognition. This protein exists both in a soluble form and in association with the membranes of alveolar macrophages. The primary structure of gp-340 has been established by molecular cloning, which yielded a 7,686-bp cDNA sequence encoding a polypeptide chain of 2, 413 amino acids. The domain organization features 13 scavenger receptor cysteine-rich (SRCR) domains, each separated by an SRCR-interspersed domain, except for SRCRs 4 and 5, which are contiguous. The 13 SRCR domains are followed by two C1r/C1s Uegf Bmp1 domains separated by a 14th SRCR domain and a zona pellucida domain. gp-340 seems to be an alternative spliced form of DMBT1. Reverse transcription-PCR analysis showed that the main sites of synthesis of gp-340 are lung, trachea, salivary gland, small intestine, and stomach. Immunohistochemistry revealed strong staining for gp-340 in alveolar and other tissue macrophages. Immunostaining of the macrophage membrane was either uniform or focal in a way that suggested capping, whereas other macrophages showed strong intracellular staining within the phagosome/phagolysosome compartments. In some macrophages, SP-D and gp-340 were located in the same cellular compartment. Immunoreactive gp-340 was also found in epithelial cells of the small intestine and in the ducts of salivary glands. The distribution of gp-340 in macrophages is compatible with a role as an opsonin receptor for SP-D.

Amino Acid Sequence↗

PubMed1999

Splanchnic haemodynamics after intravenous terlipressin in anaesthetised healthy pigs.

BACKGROUND/AIMS: Terlipressin is used for the treatment of bleeding oesophageal varices. We evaluated the effects of terlipressin on hepatic haemodynamics, with special focus on the interactions between portal venous flow and hepatic arterial flow over time. Secondly, we evaluated the estimated hepatic blood flow by the ICG clearance method against direct measurements of hepatic blood flow. METHODS: Eight healthy anaesthetised pigs received terlipressin 1 mg or placebo intravenously in a randomised, blind, cross-over design. Hepatic arterial flow, portal venous flow, systemic haemodynamics, and portal vein diameter were recorded simultaneously. Portal venous flow and hepatic arterial flow were measured by transit time ultrasound flowmetry. Estimated hepatic blood flows at baseline and after terlipressin were compared with the sum of the portal venous flow and hepatic arterial flow. RESULTS: Portal venous flow decreased significantly 5 min after administration of terlipressin (p<0.05). At 30 min it had decreased by 34% (p<0.01) and the hepatic arterial flow had increased by 81% (p<0.01). The estimated hepatic blood flow and the hepatic blood flow decreased by 23% (p<0.015). At baseline the estimated hepatic blood flow and the hepatic blood flow correlated significantly (r=0.85, p<0.01), but this correlation disappeared after administration of terlipressin (r=0.06, p=ns). The hepatic blood flow was 12% higher than the estimated hepatic blood flow before and after terlipressin. CONCLUSIONS: Terlipressin decreased the portal venous flow, hepatic blood flow, and estimated hepatic blood flow significantly and was accompanied by a substantial increase in hepatic arterial flow. The estimated hepatic blood flow and hepatic blood flow were strongly correlated at baseline, but after terlipressin the correlation disappeared.

Anesthesia↗

PubMed1999

Endoscopic ultrasound duplex scanning for measurement of portal venous flow. Validation against transit time ultrasound flowmetry in pigs.

BACKGROUND: Endoscopic ultrasound (EUS) is a new technique that makes it possible to measure portal venous flow when transabdominal ultrasound fails. As the technique has not been evaluated previously, we compared simultaneous measurements of portal venous flow using EUS Doppler with that of transit time ultrasound (TTU) in healthy pigs. The ability of EUS to detect changes in the portal venous flow after pharmacologic intervention was also investigated. METHODS: Six anaesthetized pigs were studied. Portal venous flow was measured simultaneously by EUS duplex scanning, using a Pentax FG-32UA echoendoscope connected to a Hitachi EUB 515-A ultrasound scanner, and by TTU with a Cardiomed CM 4000 flowmeter probe placed on the portal vein. Terlipressin, 1 mg, and placebo were administered in a blind, randomized, crossover design. Measurements were taken at base line and 30 min after each drug administration. RESULTS: Portal venous flow measured by EUS flowmetry and TTU flowmetry correlated significantly (R = 0.92, P < 0.001, n = 18). The limits of agreement in a Bland-Altman plot were from -0.262 l/min to +0.164 l/min. The change in portal venous flow after terlipressin measured by EUS and TTU correlated significantly (R = 0.88, P < 0.05, n = 6). All values used for analyses were the means of five repeated measurements. CONCLUSIONS: EUS measures portal venous flow with an acceptable correlation and agreement with TTU in anaesthetized pigs. The method is capable of monitoring the effects of pharmacologic intervention on the portal system.

Animals↗

PubMed1999

A mathematical model of aerosol holding chambers.

A mathematical model of aerosol delivery from holding chambers (spacers) was developed incorporating tidal volume (VT), chamber volume (Vch), apparatus dead space (VD), effect of valve insufficiency and other leaks, loss of aerosol by immediate impact on the chamber wall, and fallout of aerosol in the chamber with time. Four different spacers were connected via filters to a mechanical lung model, and aerosol delivery during "breathing" was determined from drug recovery from the filters. The formula correctly predicted the delivery of budesonide aerosol from the AeroChamber (Trudell Medical, London, Ontario, Canada), NebuChamber (Astra, Södirtälje, Sweden) and Nebuhaler (Astra) adapted for babies. The dose of fluticasone proportionate delivered by the Babyhaler (Glaxco Wellcome, Oxbridge, Middlesex, UK) was 80% of that predicted, probably because of incomplete priming of this spacer. Of the above-mentioned factors, initial loss of aerosol by impact on the chamber wall is most important for the efficiency of a spacer. With a VT of 195 mL, the AeroChamber and Babyhaler were emptied in two breaths, the NebuChamber in four breaths, and the Nebuhaler in six breaths. Insufficiencies of the expiratory valves were demonstrated by comparison of pressure flow curves during "inspiratory" flow with and without occluded expiratory openings. Insufficient inspiratory valves were demonstrated by comparison of "expiratory" pressure flow curves with and without occluded inspiratory openings. With children breathing through the spacers, mask pressure variations were generally on the same order as that seen with the mechanical respiratory, supporting the clinical relevance of the in vitro findings.

Aerosols↗

PubMed1999

Evaluation of the microdialysis technique in the dog fat pad.

In the present study the microdialysis technique was evaluated in an isolated autoperfused dog fat pad. Concentrations of glucose, lactate, and glycerol were measured in interstitial fluid by microdialysis and simultaneously in arterial and adipose venous plasma. Adipose tissue blood flow was measured by both 133Xe washout and timed weighing of venous blood. Metabolite concentrations in adipose venous plasma calculated from interstitial and arterial metabolite concentrations and 133Xe washout were positively correlated with measured venous concentrations (glucose: r = 0.95, lactate: r = 0.92, glycerol: r = 0.81). Calculated and measured venous plasma concentrations did not differ for either glucose or lactate, but for glycerol, calculated concentration was on average 76% of measured concentration. Metabolite exchanges (Fick's principle) calculated from interstitial metabolite concentrations were positively correlated with measured exchanges only for lactate (r = 0.69). In conclusion, metabolite concentrations in adipose venous plasma can be calculated from microdialysis measurements with greater accuracy for glucose and lactate than for glycerol. The precision, however, is too low to allow calculation of metabolite exchange when arteriovenous metabolite differences are low.

Adipose Tissue↗

PubMed1998

Fas ligand- mediated killing by intestinal intraepithelial lymphocytes. Participation in intestinal graft-versus-host disease.

In vitro studies have demonstrated that intestinal intraepithelial lymphocytes (IEL) are constitutively cytotoxic; however, the mechanism and target of their cytotoxicity are unknown. Apoptosis of intestinal epithelial cells (IEC) and an increase in IEL numbers are classical signs of intestinal graft-versus-host disease (GVHD), although whether IEL can mediate IEC apoptosis directly in GVHD is unclear. Recent evidence suggests that target epithelial organ injury observed in GVHD is predominantly Fas-mediated; therefore, we investigated the possibility that IEL induce apoptosis of IEC through a Fas-mediated mechanism. Here, we demonstrate that the IEL isolated from normal mice readily display potent Fas ligand (FasL)-mediated killing activity after CD3 stimulation, and that IEC express Fas, suggesting that IEC are potential targets for FasL-mediated killing by IEL. In vitro, IEL isolated from GVHD mice have markedly increased FasL-mediated killing potential and are spontaneously cytolytic toward host-derived tumor cells predominantly through a Fas-mediated pathway. In vivo transfer of IEL isolated from GVHD mice induced significantly more IEC apoptosis in F1 wild-type mice than in Fas-defective F1lpr mice. Thus, these results demonstrate that FasL-mediated death of IEC by IEL is a major mechanism of IEC apoptosis seen in GVHD.

Animals↗

PubMed1998

Molecular analysis of the adaptive response of intestinal bile acid transport after ileal resection in the rat.

BACKGROUND & AIMS: The apical sodium-dependent bile acid transporter is critical for intestinal reclamation of bile salts. Its expression and activity, along with the ileal lipid-binding protein, were studied before and after intestinal resection in the rat. METHODS: The effects of surgical resection and bile acid feeding on the expression of ileal bile acid transport were assessed by a combination of functional (taurocholate uptake into crude brush border membrane vesicles) and molecular assays (Northern and Western blotting). RESULTS: Transport, apical sodium-dependent bile acid transporter and ileal lipid-binding protein messenger RNA and protein expression were restricted to the distal 30 cm of ileum. After resection, transport and expression were limited to the remaining portions of this segment. Limited ileal resection increased protein mass and, therefore, transport in the terminal 5 cm of ileum without a specific increase in transporter gene expression. Increased bile acid presentation to the terminal ileum did not induce ileal hyperplasia. Eighty-five percent intestinal resection led to ileal hypertrophy and a specific repression in bile acid transport activity. CONCLUSIONS: Native and compensatory bile acid transporter gene expression occur predominantly in the terminal 30 cm of ileum. The specific ileal responses to intestinal resection are dependent on the extent of resection.

Adaptation, Physiological↗

PubMed1998

The effect of prolonged clamping and vascular stasis on the patency of arterial and venous microanastomoses.

During free tissue transfer, an artery and one or two veins must be sutured. Either the artery or the vein can be repaired first, but the optimal order of vascular repair has not been established. Maintaining a clamp on a vessel is associated with vessel injury, and releasing the clamp may cause bleeding and vascular stasis. The purpose of this study was to determine if the order of vessel repair and the length of vascular clamping affects surgical outcome. Free flaps were created on Sprague-Dawley rats (400-450 g) as follows: Bilateral abdominal skin flaps (3 x 3 cm) based on the superficial inferior epigastric vessels were elevated. The femoral artery and vein were tied and divided distal to the branching of the inferior epigastric vessels. Proximal to the branching, the artery and vein were divided. The animals were then randomized into four groups as follows: In group I (N=16), the artery was repaired and then the clamps were released to revascularize the flap. Venous stasis occurred as the vein was being repaired because of the venous clamp. In group II (N=15), the artery was repaired, but the clamp was maintained to prevent blood from coming in contact with the fresh arterial anastomosis and to prevent venous stasis. The vein was then repaired. In group III (N=15), the vein was repaired first but the venous clamp was not released until the artery was repaired. In group IV (N=15), the vein was repaired first and the clamps were released, allowing venous blood to contact the fresh anastomosis while the artery was being repaired. After final clamp removal, all anastomoses were assessed immediately for evidence of thrombosis. Five days postoperatively the skin flap was evaluated for evidence of necrosis and the anastomosis was inspected for evidence of late thrombosis. The anastomoses were resected for histopathological evaluation. Flap success was compared between groups using chi-squared analysis. Eleven of 16 flaps failed (69%) in group I, and 3 of 15 flaps failed (20%) in each of groups II, III, and IV. Statistical significance was reached in comparing group I with the other three groups (p < 0.01). All failures in group I were caused by immediate venous thrombosis. The other failures were secondary to arterial thrombosis. Histopathological analysis failed to demonstrate any differences between the groups. According to these results, arterial repair followed by clamp release prior to the completion of the venous repair results in a low success rate, probably secondary to venous stasis within the draining vein while the venous anastomosis is being completed. If the arterial repair is performed first, then it is recommended that the arterial clamp be maintained until the venous repair is completed. If the vein is repaired first, then it can be clamped or unclamped with similar results.

Anastomosis, Surgical↗

PubMed1998

Fat metabolism in formerly obese women.

An impaired fat oxidation has been implicated to play a role in the etiology of obesity, but it is unclear to what extent impaired fat mobilization from adipose tissue or oxidation of fat is responsible. The present study aimed to examine fat mobilization from adipose tissue and whole body fat oxidation stimulated by exercise in seven formerly obese women (FO) and eight matched controls (C). Lipolysis in the periumbilical subcutaneous adipose tissue, whole body energy expenditure (EE), and substrate oxidation rates were measured before, during, and after a 60-min bicycle exercise bout of moderate intensity. Lipolysis was assessed by glycerol release using microdialysis and blood flow measurement by 133Xe clearance technique. The FO women had lower resting EE than C (3.77 +/- 1.01 vs. 4.88 +/- 0.74 kJ/min, P < 0.05) but responded similarly to exercise. Adipose tissue glycerol release was twice as high in FO than in C at rest (0.455 +/- 0.299 vs. 0.206 +/- 0.102 mumol.100 g-1.min-1, P < 0.05) but increased similarly in FO and C in response to exercise. Despite higher plasma nonesterified fatty acids (NEFA) in FO (P < 0.001), fat oxidation rates during rest and recovery were lower in FO than in C (1.32 +/- 0.84 vs. 3.70 +/- 0.57 kJ/min, P < 0.02) and fat oxidation for a given plasma NEFA concentration was lower at rest (P < 0.001) and during exercise (P = 0.01) in the formerly obese group. In conclusion, fat mobilization both at rest and during exercise is intact in FO, whereas fat oxidation is subnormal despite higher circulation NEFA levels. The lower resting EE and the failure to use fat as fuel contribute to a positive fat balance and weight gain in FO subjects.

Adipose Tissue↗

PubMed1998

In vitro performance of three combinations of spacers and pressurized metered dose inhalers for treatment in children.

The performance of pressurized metered dose inhalers (pMDIs) and spacers in correct dose recommendations is important, but limited information on dose delivery and fine-particle dose from different combinations of spacers and pMDIs is available. In this study, three combinations of spacers and pMDIs were investigated: NebuChamber and AeroChamber with budesonide pMDI and Babyhaler with fluticasone propionate pMDI. Doses were withdrawn onto a filter either with a breathing simulator (dose to ventilator) or with constant flow (maximal dose). The fine-particle dose was assessed with a cascade impactor (Andersen Sampler). The effect of repeated use and cleaning of the spacers on the passive fallout of aerosol within the spacers was determined by evacuating the dose on a filter 2, 5, 10 and 30 s after actuating the spray. The drugs were quantified by liquid chromatography. The NebuChamber delivered the highest doses, both maximal dose and dose to ventilator. The recovered doses (means+/-SD) were 55+/-6% and 51+/-2%, respectively, of the delivered dose from the pMDI. The corresponding results for the Babyhaler were 41+/-7% and 24+/-4% and for the Aerochamber 27+/-3% and 17+/-3%. The passive fallout of aerosol, determined as half-life (t1/2) was around approximately 30 s for the NebuChamber, 9-15 s for the Babyhaler and approximately 10 s for the AeroChamber. The present study confirms that there are significant differences in dose output from different combinations of pressurized metered dose inhalers and spacers, with the NebuChamber giving the highest dose, both as delivered dose and in droplets <4.7 microm. Interactions with the spacer material, dead space in the inspiratory line and entrainment of air during inhalation due to inefficient valve control could account for these differences.

Aerosols↗

PubMed1997

Clinical characteristics of complex partial seizures: a temporal versus a frontal lobe onset.

The site of origin of complex partial seizures (CPS) is predominantly in the temporal lobe, but frontal, parietal, and occipital lobes may also be involved. In order to correlate clinical behaviours with either a temporal or frontal site of origin, we analysed 211 seizures occurring during invasive monitoring in 26 patients with temporal lobe epilepsy (TLE) and in eight patients with frontal lobe epilepsy (FLE). Although leg movements, defined as thrashing, pedalling and kicking, hand posturing, facial twitching, sitting up, and tonic-clonic movements occurred more frequently in FLE, and hand automatisms were more frequent in TLE, no statistically significant difference was found between the two groups. When analysing only electrographic seizures that did not spread or propagated only to homologous controlateral lobes, leg movements and hand posturing were seen only with FLE, and oral automatisms only in TLE. Seizures of temporal lobe origin were longer in duration and had a higher frequency of auras. We therefore conclude that the reliability of clinical behaviour alone to predict the site of origin of an epileptic discharge is limited when the surface EEG is equivocal or the neuroradiologic evidence of a focus is not clear.

Adolescent↗

PubMed1996