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Biomedical subjects

H Bode

Publications and source records attributed to H Bode.

At least 37 records · Page 2Linked to original sources
PubMed1998

IL-1beta and TNF-alpha, but not IFN-alpha, IFN-gamma, IL-6 or IL-8, are secretory mediators in human distal colon.

Inflammatory bowel disease (IBD) and HIV infection can cause diarrhoea which is accompanied by elevated cytokine levels. To elucidate a pathogenic role of cytokines, their effect on ion secretion was studied in human distal colon using the Ussing technique. Interluekin 1beta (IL-1beta) dose dependently increased short-circuit current (ISC). An ISC maximum of 2.5+/-0.3 micromol. h-1.cm-2 was reached at 20 ng/ml within 43+/-4 min. 22Na+ and 36Cl- fluxes were not altered and residual flux increased by 2.4+/-1.0 micromol.h-1.cm-2 indicating that the IL-1beta-induced ISC is based on electrogenic bicarbonate secretion. IL-1beta had no effect on HT-29/B6 epithlial monolayers suggesting that IL-1beta does not act directly on the epithelium. Furthermore, in human colon the effect was not attenuated by removal of the submucosa (total stripping) pointing to a mediation step via subepithlial cells in the lamina propria. While tetrodotoxin and the 5-lipoxygenase inhibitor ICI-230487 had no effect, indomethacin completely blocked IL-1beta action. Prostaglandin determination by RIA revealed an increased production of PGE2. At half maximum effective concentrations an additive action of tumour necrosis factor alpha (TNF-alpha) could be demonstrated on IL-1beta-induced secretion. Interferon alpha (IFN-alpha), IFN-gamma, IL-6, and IL-8 had no seretory effect in human distal colon. None of the investigated cytokines altered the intestinal barrier function. By their secretory effects IL-1beta and TNF-alpha, but not IFN-alpha, IFN-gamma, IL-6, and IL-8, may contribute to diarrhoea in IBD and AIDS.

Chlorides↗
PubMed1998

The Australian Multicenter Trial of Growth Hormone (GH) Treatment in GH-Deficient Adults.

GH treatment in adults with GH deficiency has numerous beneficial effects, but most studies have been small. We report the results of an Australian multicenter, randomized, double-blind, placebo-controlled trial of the effects of recombinant human GH treatment in adults with GH deficiency. GH deficiency was defined as a peak serum GH of < 5 mU/liter in response to insulin-induced hypoglycemia. Patients were randomly assigned to receive either GH (0.125 U/kg per week for 1 month and 0.25 U/kg per week for 5 months) or placebo. After 6 months, all patients received GH. The primary end points were biochemical responses, body composition, quality of life, and safety. One hundred sixty-six patients (72 females and 91 males) with a mean age of 40 +/- 1 yr (+/- SEM; range 17-67 yr) were recruited. Serum insulin-like growth factor-I (IGF-I) increased from a standard deviation score of -2.64 +/- 0.27 (range -8.8 +3.82; n = 78) to +1.08 +/- 2.87 (range -7.21 to +6.42) at 6 months in the GH/GH group; 38% of the whole group were above the age-specific reference range following treatment [17.6% and 68.9% with subnormal (< 2 SD) or normal (+/- 2 SD) pretreatment levels, respectively]. Fasting total cholesterol (P = 0.042) and low-density lipoprotein cholesterol (P = 0.006) decreased over the first 6 months. Fat-free mass increased in the first 6 months whether measured by bioelectrical impedance (P < 0.001) or dual energy x-ray absorptiometry (DEXA; P < 0.001). Total-body water increased in the first 6 months whether measured by bioelectrical impedance (P < 0.001) or deuterium dilution (P = 0.002). Fat mass measured by DEXA (P < 0.001), skinfold thicknesses (P < 0.001), and waist/hip ratio (P = 0.001) decreased in the first 6 months. Most changes in body composition were complete by 3 months of treatment and maintained to 12 months. Whole-body bone mineral density (BMD) (by DEXA) was unaffected by GH treatment. Self-reported quality of life was considered good before treatment, and beneficial treatment effects were observed for energy, pain, and emotional reaction as assessed by the Nottingham Health Profile. In the initial 6 months, adverse effects were reported by 84% of patients in the GH and 75% in the placebo group, with more symptoms relating to fluid retention in the GH group (48% vs. 30%; P = 0.016). Such symptoms were mild and resolved in 70% of patients despite continued treatment. Resting blood pressure did not change over the initial 6 months. In summary, GH treatment in adults with GH deficiency resulted in 1) prominent increases in serum IGF-I at the doses employed, in some cases to supraphysiological levels; 2) modest decreases in total- and low-density lipoprotein cholesterol, together with substantial reductions in total-body and truncal fat mass consistent with an improved cardiovascular risk profile; 3) substantial increases in lean tissue mass; and 4) modest improvements in perceived quality of life. The excessive IGF-I response and side-effect profile suggests that lower doses of GH may be a required for prolonged GH treatment in adults with severe GH deficiency.

Adult↗
PubMed1997

The second case of a t(17;22) in a family with neurofibromatosis type 1: sequence analysis of the breakpoint regions.

A reciprocal t(17;22)(q11.2;q11.2) was found in a female patient with neurofibromatosis type 1 (NF1) and in her affected daughter. Sequence analysis of cloned junction fragments traversing the breakpoints allowed the identification of the structures involved in the rearrangement. Aberrant bands in Southern hybridizations of restriction enzyme-digested DNA of the patient pointed to the disruption of the NF1 gene in intron 31. Semispecific polymerase chain reaction analysis of the genomic DNA of the patient with the specific primer anchored at NF1 exon 31 was used to obtain the breakpoint-spanning fragment of the derivative chromosome 17. The intron 31 sequence turned out to be interrupted within a large irregular (AT) repeat. The chromosome 22-derived sequence of the der(17) junction fragment allowed us to identify cosmids of the corresponding region from a chromosome 22 specific cosmid library. With the support of the breakpoint-spanning cosmids, the chromosome 22 region upstream of the fragment carried by the der(17) was characterized. Primers deduced from the sequence of this upstream region were used in combination with a primer in NF1 intron 31 distal to the breakpoint on chromosome 17 to amplify the der(22) junction fragment. The structure of the junction sequences suggested that the translocation had arisen by unequal homologous recombination between (AT)-rich repeats on chromosome 22 and on chromosome 17 in intron 31 of the NF1 gene. However, our data support the assumption of additional rearrangements prior to, or in the course of, the recombination event, leading to a loss of the sequences between the involved (AT) repeats on chromosome 22. In the direct vicinity of these (AT) repeats, two members of a previously undescribed low-copy repetitive sequence have been found, copies of which are also present on human chromosome 13.

Adult↗
PubMed1996

Investigation of nifedipine absorption in different regions of the human gastrointestinal (GI) tract after simultaneous administration of 13C- and 12C-nifedipine.

OBJECTIVE: To evaluate the absorption of nifedipine in man from four different sites of the gastrointestinal tract. METHODS: On separate occasions, nifedipine solution was administered locally to the stomach, the small intestine and two sites in the colon in 4 healthy male volunteers (age 29-34 y weight 73-82 kg, non-smokers) using a remote controlled drug delivery device (HF-capsule). In order to assess absolute and relative bioavailabilities, an intravenous infusion was given on a separate occasion and all treatments were accompanied by a simultaneous oral dose of a stable-isotope labelled nifedipine solution. This allowed to minimise the influence of intra-individual variability. Plasma samples were collected up to 24 h post dose and faeces for 72 h. A new method of analysis of nifedipine in plasma and faeces using gas chromatography with mass-selective detection (GCMS) was employed. RESULTS: Dissolved nifedipine was found to enter the systemic circulation completely along the intestine, being absorbed from jejunum to colon. Absorption was less rapid from the colon than from the upper part of the gut, but this was not associated with a decrease in absorption and/or bioavailability: Absolute bioavailability, calculated from the normalised AUC values, ranged from 42 to 56%, and bioavailability relative to oral solution was 100 to 126% (medians of the application sites). CONCLUSION: The absence of an absorption window in the intestinal tract suggests that nifedipine is well suited for use in controlled-release formulations.

Adult↗
PubMed1996

Evidence for vacuolar-type proton pumps in nonmitochondrial and inositol 1,4,5-trisphosphate-sensitive calcium stores of insulin-secreting cells.

This study examines whether acidic, vacuolar-type, proton-pump-carrying organelles of insulin-secreting cells (clonal endocrine pancreatic cell line INS-1) function as rapidly exchanging, inositol 1,4,5-trisphosphate-sensitive calcium stores. Calcium uptake into calcium stores will be modulated by the proton concentration within the stores, since calcium pumps in general appear to mediate a countertransport of calcium with protons. We therefore tested for sensitivity of calcium sequestration by nonmitochondrial stores (inhibition of mitochondrial calcium uptake by 2 microM ruthenium red) in saponin-permeabilized cells to proton-conducting ionophores and proton pump inhibition, using this as a marker for involvement of acidic organelles. Calcium sequestration was partially inhibited by the protonophores nigericin (10-50 microM) and carbonylcyanide m-chlorophenylhydrazone (CCCP; 20-50 microM), as well as by inclusion of 30 mM NH4Cl. Bafilomycin A1, a potent and selective inhibitor of vacuolar-type proton pumps, alone (1 - 500 nM) had no effect on calcium sequestration. however, it induced an inhibitory effect in the presence of nigericin or CCCP, even at low concentrations (5 microM) of these ionophores, lacking itself an inhibitory action on calcium sequestration. Bafilomycin A1 then was already maximally active at a concentration as low as 10 nM. Corres ponding to inhibition of total nonmitochondrial calcium sequestration, filling of inositol 1,4,5-trisphosphate-sensitive stores was decreased or even abolished by the protonophores alone or the protonophores combined with bafilomycin A1. We conclude that vacuolar-type proton pumps are present in at least a part of nonmitochondrial and inositol 1,4,5-trisphosphate-sensitive calcium stores in INS-1 cells. This assigns these stores to organelles such as secretory granules, the trans Golgi network, or endosomes. Luminal acidity of these stores will stimulate calcium sequestration by providing more protons for countertransport of calcium by calcium pumps. High concentrations of protonophores may be required for inhibitory effects because otherwise the proton pumps may be able to compensate sufficiently for ionophore-mediated proton loss. The lack of effect of bafilomycin A1 without protonophores may be due to a sufficient luminal buffering capacity or to preceding inhibition of the pump by an inside-positive transmembrane potential.

Ammonium Chloride↗
PubMed1996

Mean input times of three oral chlorprothixene formulations assessed by an enhanced least-squares deconvolution method.

The efficacy and quality of drug formulations are determined mainly by their bioavailability, which is defined by the rate and extent of drug absorption. The zero and first moments of the serum concentration time profile provide relevant information on the bioavailability. On the basis of the body residence time distributions, mean input times may be used as drug absorption rate parameters, but due to computational errors the statistical moments procedure is in some instances of limited value. To circumvent these problems we have developed a procedure to calculate mean input times from input profiles obtained by least-squares deconvolution. We enhanced the performance of the deconvolution method by directly generating initial estimates of one input rate for each sampling interval and compared the statistical properties of various input rate characteristics using data from a bioavailability study on four chlorprothixene preparations. The analysis of variance revealed that estimates of mean input times depended on the calculation procedure. Mean input times estimated by the least-squares deconvolution method were more reliable and less variable than those computed as differences of mean body residence times.

Administration, Oral↗
PubMed1996

Tumor necrosis factor-alpha induces Cl- and K+ secretion in human distal colon driven by prostaglandin E2.

Increased levels of tumor necrosis factor-alpha (TNF-alpha) have been found in, for example, inflammatory bowel disease (IBD) and human immunodeficiency virus (HIV) infection. To investigate a possible contribution of TNF-alpha to the pathogenesis of diarrhea in these diseases, ion transport of human distal colon was studied in the Ussing chamber in vitro. Serosal addition of TNF-alpha increased short-circuit current (Isc) of partially stripped tissues in a dose-dependent manner. Maximum Isc increase of 1.8 +/- 0.2 mumol.h-1.cm-2 was reached after 60 +/- 9 min at 200 ng/ml TNF-alpha. Bidirectional tracer flux measurements revealed that TNF-alpha induced an increase in 36 Cl serosal-to-mucosal flux, a decrease in 36Cl- mucosal-to-serosal flux, and a slight increase in K+ secretion indicated by an increased secretory 86Rb net flux. In the highly differentiated colonic epithelial cell line HT-29/B6, TNF-alpha had no effect on Isc, suggesting a mediation step located in the subepithelium. This supposition was supported by measurements on totally stripped human tissues, since removal of subepithelial layers by total stripping reduced the TNF-alpha effect by 40%. Experiments with tetrodotoxin (10(-6)M) indicated that the TNF-alpha effect was not mediated by the enteric nervous system. The specific 5-lipoxygenase blocker ICI-230487 (5 x 10(-8)M) also had no effect on TNF-alpha action. In contrast, inhibition of cyclooxygenase by indomethacin (10(-6)M inhibited the effect of TNF-alpha. Radioimmunoassay of prostaglandin E2 (PGE2) in the serosal bathing solution revealed an increase in PGE2 production/release after addition of TNF-alpha, which paralleled the Isc response. We conclude that TNF-alpha changed Cl- and K+ transport toward secretion in human colon. This effect was mediated by PGE2 produced by subepithelial cells. Thus TNF-alpha could be a mediator of diarrhea during intestinal inflammation, e.g., in IBD and HIV infection.

Biological Transport↗
PubMed1995

Calcifying arteriopathy in the basal ganglia in human immunodeficiency virus infection.

Echogenic stripes in the basal ganglia were identified sonographically in a 4-month-old infant with human immunodeficiency virus (HIV) infection. This lenticulostriate arteriopathy correlated well with histologically identified early alterations of HIV encephalopathy in children. At 3 years and 5 months, CT examination performed after three seizures showed calcification in the area of the sonographically affected arteries but no signs of progressive encephalopathy. The child's mental and motor development have remained normal until now. Cerebral sonography performed in early infancy may allow identification of HIV encephalopathy even before its clinical manifestation.

AIDS Dementia Complex↗
PubMed1994

Congenital tetraplegia, respiratory insufficiency, and hypoplasia of medulla oblongata.

A term infant with normal delivery presented with congenital tetraplegia and respiratory insufficiency just after birth. Magnetic resonance tomography on days 8 and 72 of life revealed an extreme thinning of the lower medulla oblongata. Endoscopy confirmed this and demonstrated the presence of vascular anomalies around the lesion which were not detectable by angiography. It is presumed that this is a malformation of the lower medulla oblongata.

Arteries↗
PubMed1994

[Effect of halothane anesthesia on cerebral blood flow velocity in children].

The effects of halothane on the cerebral circulation were studied in 23 children during general anaesthesia. Blood flow velocity in one middle cerebral artery was recorded continuously by transcranial Doppler sonography. Furthermore arterial blood pressure, pulse rate, endtidal CO2partial pressure and endtidal halothane concentration were recorded. Mean flow velocities/mean arterial blood pressures were 79 cm x s-1/65 mmHg; 86 cm x s-1/61 mmHg; 78 cm x s-1/54 mmHg and 67 cm x s-1/48 mmHg with 1; 1.5; 2 and 2.5 per cent endtidal halothane concentrations, respectively. Endtidal CO2-partial pressure and pulse rate remained constant throughout the study. The higher cerebral blood flow velocities seen with 1.5 per cent halothane compared with 1 per cent can be explained by an increase in cerebral blood flow. The lower cerebral blood flow velocities and arterial blood pressure with 2.5 per cent halothane compared with 1.5 per cent indicate impaired cerebral autoregulation. However, cerebral blood flow appeared to be sufficient even with low arterial blood pressures.

Anesthesia, General↗
PubMed1994

Follow-up of optic pathway gliomas in children with neurofibromatosis type 1.

Optic pathway gliomas (OPG) are found in about 15% of patients with neurofibromatosis Type 1 (NF-1). The natural history of OPG is not yet well documented. Treatment in cases with growing tumors is still controversial. Twenty-one patients with NF-1 and OPG, diagnosed over a 20-year period, and followed neuroradiologically and ophthalmologically for at least two years, were reevaluated. The diagnosis of OPG was made at a mean age of 7.1 years (range 0-14.5 years); six children were asymptomatic, 15 were symptomatic. The mean follow-up was 9.0 years (2.0-18.5 (years). In eight initially operated or biopsied patients (three optic nerve and five chiasmal gliomas) tumor regrowth was found in one patient without progression on subsequent follow-up. Improvement of visual acuity occurred in one child after operation of a large suprasellar tumor and deterioration in one patient after biopsy of a chiasmal glioma. The neuroradiological follow-up of the 13 not-operated and not-radiated patients (four optic nerve and nine chiasmal gliomas) was stable in 10, progressive in three, resulting in visual loss in one patient. In 11 children (52%) a second tumor outside the optic pathway was found at a mean age of 4.0 years after the diagnosis of an OPG. Until now they are mostly asymptomatic. Second site tumors were operated in two children because of rapid tumor growth, one child died of a brainstem tumor. OPG are a frequent complication in children with NF-1, appearing within the first decade.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Effects of laryngoscopy and tracheal intubation on cerebral and systemic haemodynamics in children under different protocols of anaesthesia.

The effects of laryngoscopy and tracheal intubation on cerebral and systemic haemodynamics were studied in 30 children. The objective was to identify conditions in which the alterations of cerebral and systemic haemodynamics were minimal. The children were intubated after muscular relaxation and following 10 min of mechanical ventilation with end-tidal halothane concentrations of 1.5%, 2.0% and 2.5%, respectively. With 1.5%, 2.0% and 2.5% end-tidal halothane, the mean flow velocity increased by 26%, 19% and 5%, the mean blood pressure by 14%, 10% and 1%, and the heart rate by 26%, 8% and 5% respectively after intubation. Adverse effects of laryngoscopy and tracheal intubation on cerebral haemodynamics in children can be avoided by adequate anaesthetic protocols.

Anesthesia, Inhalation↗
PubMed1992

[Lissencephalia syndromes].

Lissencephaly is in most cases a genetic anomaly of the brain development with agyria and/or pachygyria. It causes severe psychomotor retardation and epilepsy, which is often resistant to therapy. Some patients with type-I lissencephaly show cranial and facial dysmorphism and a deletion of chromosome 17p13.3 (Miller-Dieker syndrome). The isolated lissencephaly sequence occurs without these features. Patients with type-II lissencephaly present additional malformations of the posterior fossa and of the eyes (Walker-Warburg syndrome) and in some cases muscular dystrophy (cerebro-oculomuscular syndrome). Lissencephaly can be suspected with a high probability by its typical EEG. It is proved by imaging techniques. Therapeutic success is limited, the life expectancy is strongly reduced.

Abnormalities, Multiple↗
PubMed1992

Conservation of the prohormone convertase gene family in metazoa: analysis of cDNAs encoding a PC3-like protein from hydra.

A subclass of proteolytic enzymes that correctly cleave precursor proteins at paired basic residues and are structurally related to the bacterial subtilisins has recently been identified. In yeast, a single membrane-bound proteolytic processing enzyme encoded by the kex2 gene has been found, whereas in higher vertebrates cDNAs encoding four distinct enzymes (PC2, PC3, furin, and PACE 4) have been identified. Like kex2, furin (also known as PACE) contains a hydrophobic transmembrane domain, but PC2, PC3, and PACE 4 lack this feature. All five enzymes exhibit striking similarities in their catalytic domains, and this suggests that they have arisen from a common ancestral subtilisin-like gene. We report here the identification of cDNAs encoding a protein that is similar in structure to PC3 from a simple metazoan, Hydra vulgaris (formerly Hydra attenuata). cDNAs encoding two isoforms of this PC3-like enzyme were obtained that differ only in their carboxyl-terminal sequences, probably due to alternative splicing of a common pre-mRNA. Neither form contains a transmembrane domain. Predicted amino acid sequence comparisons revealed that the hydra PC3-like enzyme is 55.4% and 56.7% identical in the catalytic domain to mouse PC3 and human furin, respectively. RNA blot analyses revealed that the PC3-like RNA is expressed predominantly in the hydra body column and not in the head region, although the hydra head contains a high density of nerve cells, which synthesize a variety of neuropeptides. For this reason, we suspect that another proprotein cleavage enzyme isoform may be expressed in head nerve cells. The isolation of a PC3-like cDNA from hydra is consistent with the presence of neuroendocrine cells and indicates that the PC/furin gene family has been well conserved in all metazoa. A simplified nomenclature for the group of mammalian processing proteases is proposed.

Amino Acid Sequence↗
PubMed1992

[Successful multiple resuscitation in flecainide poisoning].

After a family quarrel a 37-year-old woman swallowed, with suicidal intent, a large number of flecainide tablets (exact amount unknown) together with alcohol. On admission to hospital some hours later her pupils were fully dilated, fixed and of irregular outline; she was unconscious and in cardiorespiratory failure. Nine hours after admission several episodes of ventricular fibrillation and asystole occurred, two of them lasting for 2 and 3 hours, respectively, before successful resuscitation (after defibrillation). The highest plasma flecainide level, between 3 and 10 hours after swallowing the drug, was 6160 ng/ml, i.e. six times the maximal therapeutic level. Under the influence of flecainide the ECG of the previously healthy woman had shown idioventricular rhythm with marked QRS widening and Q-T prolongation. The tachyarrhythmias, at times torsades de pointes, were successfully treated with high doses of lidocaine (4 g daily) after repeated defibrillations. As a late complication the patient went into acute left ventricular failure with pulmonary edema and pneumonia. There were no recognizable permanent sequelae on discharge 37 days after admission.

Adult↗
PubMed1992

Abnormal cerebral hemodynamics during attacks of alternating hemiplegia.

Frequent episodes of bilateral weakness and apathy, followed later by hemiplegia of alternating sides were observed in a now 32-month-old girl. Transcranial Doppler ultrasonography showed reduced flow velocities in the middle cerebral artery of the affected side during a hemiplegic attack and increased flow velocities at different sites of the basilar artery during a bilateral episode. These abnormal cerebral hemodynamics appear to indicate that alternating hemiplegia and some forms of migraine have a similar pathophysiology.

Basilar Artery↗
PubMed1992

Intracranial blood flow velocities during seizures and generalized epileptic discharges.

In 51 children with different types of epilepsy, blood flow velocities in the middle cerebral artery were recorded continuously by transcranial Doppler sonography during a standard electroencephalogram of 30 min duration. In 16 children 33 epileptic seizures were recorded. During tonic seizures, the mean flow velocity increased to a maximum of 133%-191% (median 160%) of the baseline values. Tonic-clonic seizures were also accompanied by a velocity increase. During absence seizures the mean flow velocity decreased to a minimum of 46%-82% (median 71%) of the baseline values. Changes in cerebral metabolism and arterial blood pressure in the presence of disturbed autoregulation are thought to be factors causing these alterations. No alteration of the flow velocities occurred in cases of petit-mal status, electrical status epilepticus and in 35 children with generalized epileptic discharges of up to 5 s duration without clinical manifestations.

Adolescent↗