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Biomedical subjects

R Keil

Publications and source records attributed to R Keil.

At least 37 records · Page 2Linked to original sources

[Rupture of the pancreas in children--present trends in diagnosis and therapy].

Evaluation of pancreatic injuries is presented in the professional literature in retrospective studies and views on treatment vary. The authors evaluated also in a retrospective study a group of eight child patients with a serious injury of the pancreas. The patients were 3-13 years old and were hospitalized at the Clinic of Paediatric Surgery at the Faculty Hospital Motol in 1985-1999. The group is formed by patients with pancreatic injuries (according to the Japanese classification type II and III). The authors evaluate not only diagnostic but also therapeutic procedures. In the diagnosis they evaluate the ultrasonographic examination (USG) as the examination of first choice which however need not record the extent and severity of the pancreatic injury. Computing tomography (CT) and magnetic resonance (MRI) can make the original suspicion of injury more accurate, ERCP is an examination which reveals in particular type III injuries--i.e. those with affection of the pancreatic duct. Injured children where a serious pancreatic lesion was not diagnosed primarily, had to be subjected to repeated surgical revisions. All children in the presented group recovered, none of the patients died.

Adolescent↗

[A new method of administering analgesic sedation before gastroscopy--a comparative study of 100 patients].

The authors administered to two groups (56 and 44) patients before gastroscopy analgosedation-5 mg diazepam and local anaesthesia of the throat. To the first group diazepam was administered by the i.v., to the second group by the sublingual route. The objective was to find out whether analgosedation is desirable from the patients aspect and whether the sublingual form of premedication is accepted by the patients. The authors found that 90% of the patients wish to have analgosedation and anaesthesia before the procedure. The sublingual form of administration was accepted by 89% of the patients.

Administration, Sublingual↗

Central application of a nitric oxide donor activates heat defense in the rabbit.

In chronically instrumented, conscious rabbits at moderately warm ambient thermal conditions, infusion of the NO-donor SIN-1 into the anterio-ventral 3rd cerebral ventricle (1-2 microg/min per kg BW, 2-4 microl/min, 30 min) initiated a co-ordinated activation of autonomic heat loss mechanisms, as indicated by the rise in ear skin temperature and by increases in panting frequency and respiratory evaporative water loss, while oxygen consumption decreased slightly. The heat loss responses were similar to those attributed to NO in studies employing systemic application of NO-donors. Different from NO acting peripherally, which causes arterial hypotension and tachycardia, centrally acting NO induced arterial hypertension and bradycardia. The observation of the same heat loss responses despite opposing circulatory actions suggests that NO is specifically involved in thermoregulation as a central activator of heat defense mechanisms.

Animals↗

[Vasculitis course of neuroborreliosis with thalamic infarct].

A-20-year-old man without vascular risk factors presented with paraesthesia of the left side of the body with acute onset. Cerebral magnetic resonance imaging showed an infarction in the right thalamus. Intra-arterial digital subtraction angiography revealed stenosis of the right thalamic vessels. Recent infection by Borrelia burgdorferi was demonstrated by typical findings in the cerebrospinal fluid: lymphocytic pleocytosis and intrathecal synthesis of borrelial-specific antibodies. The diagnosis of a borrelial-induced vasculitis with secondary thalamic infarction was made from these findings. After antibiotic treatment with cefrtriaxone, the patient was discharged without residual complaints.

Adult↗

Nitric oxide increases cutaneous and respiratory heat dissipation in conscious rabbits.

The influence of systemic nitric oxide (NO) donor infusion and NO synthase inhibition on major thermoregulatory mechanisms was investigated under thermoneutral conditions (24 degrees C) in the conscious rabbit. Both low (25 nmol.min-1.kg-1) and high-dose (75 nmol.min-1.kg-1) infusion of the NO donors 3-morpholinosydnonimine-hydrochloride and S-nitroso-N-acetylpenicillamine augmented respiratory heat dissipation due to raised respiratory frequency (RF) and evaporative water loss (REWL). At the higher dose of NO donor, RF and REWL increased (from 107 +/- 16 to 156 +/- 19 breaths/min and from 7.12 +/- 0.97 to 11.29 +/- 1.29 mg.min-1.kg-1; P < 0.05), and, combined with a moderate rise in cutaneous heat dissipation (ear skin temperature increased from 29.03 +/- 1.76 to 33.29 +/- 2.71 degrees C; P < 0.05), deep body temperature was slightly reduced (-0.1 degrees C, P > 0.05) without a change in metabolic heat production. In contrast, blockade of endogenous NO synthesis induced a sustained rise in body temperature (0.2 degrees C, P < 0.05), concomitant with a reduction in both RF and REWL (from 131 +/- 11 to 94 +/- 12 breaths/min and from 10.86 +/- 1.14 to 8.70 +/- 0.88 mg.min-1.kg-1, P < 0.05), whereas metabolic heat production decreased slightly and cutaneous heat dissipation was minimally altered. The data indicate that, under thermoneutral conditions, systemically applied NO primarily influences body temperature in the conscious rabbit by modulating the rate of respiratory heat dissipation, whereas the roles of cutaneous heat dissipation and metabolic heat production are relatively minor.

Animals↗

Vasodilation and glomerular binding of adrenomedullin in rabbit kidney are not CGRP receptor mediated.

The polypeptide adrenomedullin (ADM) was infused systemically to conscious rabbits to elucidate its actions on overall circulation and especially the renovascular bed and the formation and/or release of hormones important for body fluid homeostasis, including adrenocortical steroids. ADM lowered mean arterial pressure from 71.5 +/- 3.2 to 64.7 +/- 3.2 mmHg only at the highest dose of 25 pmol.min-1.kg-1 infused intravenously for 20 min and concomitantly induced tachycardia, possibly due to both baroreflex activation and direct cardiostimulatory effects. Renal blood flow (RBF) determined in rabbits chronically equipped with a perivascular ultrasonic flow probe increased from 55.4 +/- 2.1 to 67.4 +/- 2.7 and from 58.2 +/- 3.5 to 75.2 +/- 6.0 ml/min at ADM infusions of 5 and 25 pmol.min-1.kg-1, respectively. The elevation in RBF persisted even in the presence of the calcitonin gene-related peptide (CGRP1 receptor antagonist CGRP-(8-37). Of all osmoregulatory hormones tested, only corticosterone (Cort) plasma concentration increased in response to the highest ADM dose from 17.6 +/- 3.1 to 38.9 +/- 6.2 ng/ml, probably due to haroreflex activation. Subdepressor doses of ADM, however, caused a mild reduction in circulating Cort. Expression of functional high-affinity binding sites specific for ADM in vitro could be demonstrated for the renal artery and outer cortical glomeruli using 125I-labeled rat ADM as radioligand and determination of cellular adenosine 3',5'-cyclic monophosphate (cAMP) formation within the glomeruli. The ineffectiveness of CGRP-(8-37) to displace radiolabeled ADM from its binding sites, to inhibit ADM-induced glomerular cAMP formation, and to prevent ADM-induced renal vasodilation supports the hypothesis of ADM altering renal hemodynamics by interacting with ADM- and not CGRP-specific membrane receptors.

Adrenomedullin↗

Fluorine-18-FPCT: a PET radiotracer for imaging dopamine transporters.

UNLABELLED: Fluorine-18-labeled 2 beta-carbomethoxy-3 beta-(4-chlorophenyl)-8-[-3-fluoropropyl) nortropane (FPCT) has been synthesized as a new dopamine transporter imaging agent. METHODS: Fluorine-18 was introduced into 2 beta-carbomethoxy-3 beta-(4-chlorophenyl)-8-[-3-fluoropropyl) nortropane by preparation of 1-[18F]fluoro-3-iodopropane followed by alkylation of 2 beta-carbomethoxy-3 beta-(4-chlorophenyl)nortropane. RESULTS: Tissue distribution studies in rats with [18F]FPCT showed high striatal uptake (0.70% dose/g at 60 min; 0.38% dose/g at 120 min) and good striatal-to-cerebellum ratios (5.5 at 60 min; 6.2 at 120 min). Imaging studies in rhesus monkeys (n = 2) with [18F]FPCT showed high uptake and retention in the putamen (P) (P = 0.03%-0.12% dose/g; at 115 min) and good putamen-to-cerebellum ratios of 3.40-3.43 at 115 min. Plasma metabolites were analyzed in rhesus monkeys (n = 2) by ether extraction and HPLC. The radioactivity in the ether-extractable fraction displayed a single peak that corresponded on HPLC to unmetabolized authentic FPCT. CONCLUSION: These results suggest that [18F]FPCT is an excellent candidate for PET imaging of dopamine transporters.

Animals↗

Hormonal secretion patterns but not autonomic effector responses elicited by hypothalamic heating and cooling are altered in febrile rabbits.

The effects of hypothalamic heating and cooling on thermoregulatory effector activities, lipid and carbohydrate metabolism, insulin, glucagon, thyroxine, arginine vasopressin (AVP) and cortisol were investigated in conscious rabbits and compared with those obtained in the febrile state. The study shows that under control conditions hypothalamic heating lowers, and cooling raises core temperature. Core temperature always rose to similar degrees in response to bacterial lipopolysaccharide (LPS) during an observation time of 150 min, but it started to rise from lower and higher levels, respectively, during hypothalamic heating and cooling. The effects of hypothalamic thermal stimulation on specific thermoregulatory effector activities support the conclusion that, within 60 min after LPS, the hypothalamic warm signal input is reduced relative to the cold signal input. The increase of thyroxine levels following LPS suggests that the elevation of the thermoregulatory setpoint was caused by an increased input of hypothalamic TRH neurons, known to induce the full autonomic pattern of cold defense also in response to non-thermal stimuli. With the exception of an increase of glucagon during hypothalamic cooling at control conditions, hypothalamic thermal stimulation alone did not alter lipid and carbohydrate metabolism, insulin, thyroid hormone, AVP and cortisol secretion. A spontaneous heat loss effector response separated the first from the second fever phase 60 min after LPS. Subsequently AVP and cortisol plasma levels rose in febrile animals, irrespective of hypothalamic heating and cooling, presumably as a consequence of pyrogenic activation of corticotropin releasing factor (CRF) producing neurons and their reciprocal interaction with TRH neurons on the one hand, and by a reciprocal interaction of the latter with AVP neurons on the other.

Animals↗

Molecular analysis of the genomic structure of the human Y chromosome in the euchromatic part of its long arm (Yq11).

Conventional methods of long range restriction mapping for analysis of the genomic DNA structure failed in Yq11, because single-copy DNA probes for blot hybridization analyses are rare and the rate of DNA methylation is high in this Y region. Numerous repetitive sequence blocks of unknown extensions are scattered throughout Yq11 and a patchwork of X-Y homologous DNA blocks were found by different investigators. Therefore, our approach towards a molecular analysis of this Y region reduced this complexity by performing first its molecular analysis in YAC clones mapping to Yq11. YACs contain only a part of the whole Yq11 DNA structure. In this paper, we present our first results of this approach based on quantitative blot analysis of 51 DNA loci in 67 YAC clones. The YACs were isolated from the three CEPH libraries and mapped to a contig of 13 Mb from proximal to distal Yq11 with aid of a detailed interval map. In distal Yq11, our analysis revealed the presence of local amplification events of different DNA domains. A model of their possible arrangement is presented.

Chromatin↗

Hypothalamic thermal stimulation modulates vasopressin release in hyperosmotically stimulated rabbits.

Under thermoneutral conditions conscious rabbits received systemic infusions of NaCl as hypertonic solution (90 mueq.min-1.kg body wt-1), which raised their plasma osmolality from 283 to 312 mosmol/kgH2O. Rabbits receiving isotonic saline served as controls. Hypertonic stimulation induced a 60% reduction of both respiratory frequency and evaporative water loss. Rectal temperature rose by 0.4 degrees C despite enhanced peripheral vasodilation as indicated by increased ear skin temperature. Plasma vasopressin (AVP), aldosterone (ALDO), and corticosterone (COR) were significantly elevated from 6 to 16 pg/ml, 90 to 180 pg/ml, and 17 to 40 ng/ml, respectively. To elucidate the importance of central temperature for AVP and adrenal corticosteroid release, hypothalamic thermal stimulations (20 min) were superimposed during established iso- and hyperosmotic steady-state conditions. Different from isosmotic controls, hyperosmotic animals responded to hypothalamic cooling (37 degrees C) with a significant decrease in plasma AVP from 16 to 13 pg/ml and to hypothalamic warming (41 degrees C) with a significant rise from 16 to 19 pg/ml. A weak temperature effect on COR release was also disclosed, especially of hypothalamic cooling, which significantly lowered plasma COR from 42 to 34 ng/ml. These results provide evidence for positive local temperature coefficients of hypothalamic control of AVP release and suggest a similar property also for the control of COR release by the hypothalamo-adenohypophysial axis.

Aldosterone↗

[Mechanical lithotripsy of a gastric bezoar].

At the First Medical Clinic of the Faculty Hospital Prague Motol the authors detected during a routine gastroscopic examination of a 71-year-old female patient the presence of a gastric bezoar. The examination was indicated on account of dyspeptic complaints. With regard to the size of the bezoar (50 x 20 mm) the authors decided for mechanical lithotripsy. It proved possible to reduce the concrement during the first session and during subsequent sessions it was broken down to small size and the fragments were eliminated per vias naturales. Several fragments were extracted. Chemical analysis provided evidence of the origin of the concrement in the biliary pathways--the concrement was pure cholesterol. ERCP did not reveal an artificial communication between the biliary system and the stomach or duodenum. It did not prove possible to visualize the gallbladder by ultrasonography. The selected therapeutic procedure was successful.

Aged↗

Affinity of central adenosine A1 receptors is decreased in spontaneously hypertensive rats.

Functional defects in purinergic neurotransmission have been related to the development of arterial hypertension in spontaneously hypertensive rats. In order to elucidate the molecular basis of this perturbation, we have directly characterized adenosine A1 receptors using radioligand binding to rat brain membranes of Wistar Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Saturation studies with [3H]1,3-dipropylcyclopentylxanthine ([3H]DPCPX) showed a lower affinity in both 5- and 48-week-old SHRSP in comparison with age-matched WKY. Similarly, competition experiments with [3H]DPCPX showed lower affinity of R-N6-phenylisopropyladenosine for the low-affinity binding site in 5- and 48-week-old SHRSP in comparison with WKY. In both studies, the difference in KD values was abolished by guanosine-5'-triphosphate in 5-week-old rats and mitigated in 48-week-old animals. No differences in Bmax values were observed in 5-week-old rats, whereas in 48-week-old SHRSP the number of receptors was significantly higher in comparison with age-matched WKY. Saturation experiments with the A1-selective agonist [3H]2-chloro-N6-cyclopentyladenosine ([3H]CCPA) demonstrated a higher affinity in 5-week-old SHRSP, whereas in 48-week-old hypertensive animals it was lower than in control WKY rats. No difference in receptor number was detected in comparison with age-matched WKY. In conclusion, our data demonstrated a diminished affinity of central adenosine A1 receptors for antagonists and for the low affinity state of the agonist binding site in genetically hypertensive rats. This might be due to structural changes of the receptor protein, to an altered G protein or defective receptor-G protein coupling in arterial hypertension.

Adenosine↗

Microdeletions in interval 6 of the Y chromosome of males with idiopathic sterility point to disruption of AZF, a human spermatogenesis gene.

For males with idiopathic sterility, a molecular screen specific for small lesions (microdeletions) in interval 6 of the Y chromosome was set up using 29 Y-DNA probes. A "de novo" microdeletion in Y interval 6 was detected in 2 out of 19 "chromosomally normal" sterile males. The first microdeletion includes the Y-DNA probes pY6HP35 and 12f3; the second microdeletion includes the Y-DNA probes pY6HP52, 49f, FR15-II and the subinterval "C" of probe 50f2. A probe of the pY6H sequence family is present in both deletions. Sequences of this family cross-hybridize to dhMiF1, a DNA sequence of a fertility gene structure on the Y chromosome of Drosophila hydei. It was possible to map the position of the Y-deletion of one patient to the distal part of Yq11.22 or the proximal part of Yq11.23, and the deletion of the second patient to the distal part of Yq11.23. These microdeletions probably do not overlap. Since AZF, a human spermatogenesis gene, has been mapped to Y interval 6, we postulate that the microdeletions detected in this chromosome region affect the functional DNA structure of the AZF gene. If this holds true, it is possible that the AZF locus, cytogenetically mapped to distal Yq11, contains two spermatogenesis genes (AZFa and AZFb) or a large gene structure comparable to the Y fertility genes of Drosophila.

Chromosome Deletion↗

Towards the molecular localisation of the AZF locus: mapping of microdeletions in azoospermic men within 14 subintervals of interval 6 of the human Y chromosome.

We have used a series of 30 DNA probes previously mapped to the long arm of the human Y chromosome, to screen a panel of 21 patients with structural abnormalities in Yq, by genomic blot hybridisation. The results have allowed us to construct a detailed map of interval 6 of the Y chromosome, in which 28 of the probes could be assigned to 14 sub-intervals within interval 6. Some probes detect two or more loci within this region, each of which has been localised. The same set of probes has been used to screen a panel of 19 chromosomally normal azoospermic men, two of whom have been found to carry microdeletions within this region. With the completion of this map we have been able accurately to localise these microdeletions within interval 6 and show that they do not overlap. We believe these microdeletions may disrupt the azoospermia factor (AZF) involved in spermatogenesis, and which is known to lie in this region. These results are an important step towards the localisation of the AZF locus.

Blotting, Southern↗

D20S19, linked to low voltage EEG, benign neonatal convulsions, and Fanconi anaemia, maps to a region of enhanced recombination and is localized between CpG islands.

Recent linkage studies located genes responsible for the low voltage EEG, benign neonatal convulsions and for the Fanconi anaemia to the vicinity of the VNTR marker CMM6 (D20S19). Physical mapping experiments using pulsefield electrophoresis in the distal part of chromosome 20q were chosen as a first step towards cloning of these genes. The observed pattern of shared fragments lead to the locus order 'tel-IP20K09-RMR6-CMM6-MS214-cen', which differs from previously reported genetic linkage maps. The physical intervals between these probes are markedly shorter compared with the genetic distances. Clusters of rare cutter sites around CMM6 point to at least four closely related CpG islands.

Base Sequence↗

Inhibition of vasopressin and aldosterone release by atrial natriuretic peptide in conscious rabbits.

To elucidate the regulatory role of atrial natriuretic factor (ANF) on vasopressin (AVP) and aldosterone release in conscious rabbits, ANF was administered systematically at a rate of 15 pmol min-1 (kg body wt)-1 for 15 min in two series of experimental animals in which AVP and/or aldosterone production was stimulated. In euhydrated rabbits (series I), systemic administration of angiotensin II (Ang II) (10 pmol min-1 (kg body wt)-1, 15 min) stimulated aldosterone release threefold from basal plasma concentrations (140 pg ml-1). The co-application of ANF inhibited the Ang II-induced release of aldosterone without influencing the non-stimulated AVP system. In dehydrated rabbits (series II) with elevated plasma osmolality and AVP concentration, exogenously applied ANF increased plasma ANF fourfold at marginally reduced arterial pressure. Plasma AVP concentrations were reduced by 3.4 pg ml-1 (25%) on average, and plasma aldosterone concentrations were lowered by 34 pg ml-1 (23%) at unchanged levels of plasma corticosterone. Receptor binding studies using [125I]ANF as radioligand revealed Ang II-independent high-affinity receptors for ANF in the zona glomerulosa of the adrenal gland. With regard to the hypothalamo-neurohypophyseal AVP system, ANF binding sites were localized to the median eminence and neurohypophysis, but not to the magnocellular nuclei. ANF receptors were also labelled in structures lacking a blood-brain barrier such as the subfornical organ and the choroid plexus.

Adrenal Glands↗

[The organ topography of nonpoisonous snakes of the Boidae (boas and pythons) and Colubridae (adders) families].

In order to assist veterinarians with the diagnosis of diseases in snakes, the organ topography of 142 dissected snakes of 35 different species was analysed and examined in relation to body size and normal biotope. Apart from characteristic species specific differences, it was shown that there is a clear difference between arboreal and terrestrial snakes. It was recorded that nearly in all species the organs shifted along the body in relation to increase in growth.

Animals↗

Selection of DNA sequences from interval 6 of the human Y chromosome with homology to a Y chromosomal fertility gene sequence of Drosophila hydei.

An experimental approach towards the molecular analysis of the male fertility function, located in interval 6 of the human Y chromosome, is presented. This approach is not based on the knowledge of any gene product but on the assumption that the functional DNA structure of male fertility genes, evolutionary conserved with their position on the Y chromosome, may contain an evolutionary conserved frame structure or at least conserved sequence elements. We tested this hypothesis by using dhMiF1, a fertility gene sequence of the Y chromosome of Drosophila hydei, as a screening probe on a pool of cloned human Y-DNA sequences. We were able to select 10 human Y-DNA sequences of which 7 could be mapped to Y interval 6 (the pY6H sequence family). Since the only fertility gene of the human Y chromosome is mapped to the same Y interval, our working hypothesis seems to be strongly supported. Most interesting in this respect is the isolation of the Y-specific repetitive pY6H65 sequence. The pY6H65 locus extends to a length of at least 300 kb in Y interval 6 and has a locus-specific repetitive sequence organization, reminiscent of the functional DNA structure of Y chromosomal fertility genes of Drosophila. We identified the simple sequence family (CA)n as one sequence element conserved between the Drosophila dhMiFi fertility gene sequence and the homologous human Y-DNA sequences.

Animals↗