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Biomedical subjects

P Arnold

Publications and source records attributed to P Arnold.

At least 37 records · Page 2Linked to original sources
PubMed2001

Dual phase helical CT versus portal venous phase CT for the detection of colorectal liver metastases: correlation with intra-operative sonography, surgical and pathological findings.

AIM: To assess whether dual phase helical computed tomography (DPCT) of the liver improves the detection of colorectal liver metastases compared with portal venous phase (PVP) imaging alone. MATERIALS AND METHODS: DPCT was performed in 33 consecutive patients before laparotomy for resection of colorectal liver metastases. CT comprised 8-mm slice collimation with a pitch of 1 to 1.25; imaging was commenced 20-25 and 65-70 s after the start of injection of 150 ml of contrast medium at 5 ml/s to coincide with hepatic arterial phase (HAP) and PVP contrast enhancement, respectively. Four blinded observers independently reviewed the HAP, PVP and DPCT images recording the site and size of all lesions. Alternative-free response receiver operating characteristic (AFROC) methodology was used to analyse the results, which were correlated with surgery, intra-operative ultrasound and histology. RESULTS: The mean observer sensitivities for malignant lesion detection were 75.3% for DPCT, 69.7% for PVP imaging and 66.7% for HAP imaging alone. There was a statistically significant improvement in malignant lesion detection using DPCT when compared with PVP imaging alone (P < 0.05). The mean areas under the AFROC curves were 0.84 for DPCT and 0.82 for PVP (P < 0.03) imaging alone. CONCLUSION: The detection of colorectal liver metastases was marginally better with DPCT than with PVP imaging alone, but the discovery of additional lesions did not affect the management of any of the patients in this study.

Aged↗
PubMed2001

Bioavailability investigation of two different oral formulations of doxepin.

Two different oral doxepin (CAS 1668-195) formulations (Doxepin-ratiopharm 25 mg film-coated tablets as test preparation and 25 mg dragées of the reference preparation) were investigated in 30 healthy male and female volunteers in order to prove bioequivalence between these preparations. A single 75 mg oral dose (3 units of test or reference preparation) was given according to a randomised two-way cross-over design in the fasted state. Blood samples for determination of plasma concentration of doxepin and its metabolite N-desmethyldoxepin were collected at pre-defined time points up to 168 h following drug administration. A wash-out period of three weeks separated both treatment periods. Doxepin and N-desmethyldoxepin plasma concentrations were determined by means of a validated LC-MS/MS method. Values of 193,463 pgh/ml (test preparation) and 197,988 pg h/ml (reference preparation) for doxepin as well as values of 313,298 pg h/ml (test preparation) and 306,663 pgh/ml (reference preparation) for N-desmethyldoxepin for the parameter AUC0-infinity demonstrate a nearly identical extent of drug absorption. Maximum concentrations (Cmax) for doxepin/N-desmethyldoxepin of 15,960.06/6,883.69 pg/ml and 18,614.73/6,846.62 pg/ml were achieved for test and reference preparation. Time to reach doxepin maximum plasma concentration (tmax) was 1.98 h for both preparations and for N-desmethyldoxepin tmax was 4.52 h (test preparation) and 4.15 h (reference preparation). Cmax and AUC0-infinity values were tested for statistically significant differences by means of the Two One-Sided T-Tests procedure following ln-transformation of data. Bioequivalence was assumed if the 90% confidence intervals of the T/R-ratios were in the range of 80%-125% for ln-transformed AUC0-infinity and 70%-143% for ln-transformed Cmax. Based on the results obtained in this study, bioequivalence between the test and the reference preparation was demonstrated.

Administration, Oral↗
PubMed2001

Bisensory augmentation of complex spoken passages.

The role of the complexity of spoken passages on the magnitude of bisensory augmentation was investigated. The comprehension of 30 undergraduates was measured when listening to clearly audible but conceptually difficult auditory-visual (AV) spoken passages, which showed an advantage over similar spoken passages heard alone (A), at three levels of complexity. Comprehension was superior in the AV relative to the A condition and the bisensory augmentation effect increased with linguistic complexity.

Adult↗
PubMed2001

Leeching as initial treatment in a cat with polycythaemia vera.

Polycythaemia vera was diagnosed in a three-year-old domestic shorthaired cat referred because of seizures and a high packed cell volume (PCV). Laboratory examination revealed severe erythrocytosis (PCV 79 per cent). Diagnosis was reached by excluding causes for relative and secondary absolute polycythaemia. As phlebotomy proved impossible for initial treatment due to hyperviscosity, four leeches were used to suck blood and the PCV was consequently reduced to 64 per cent. A further 24 hours later, when bleeding at the sites of sucking had stopped, the PCV was 56 per cent. Long-term management of the condition was achieved with hydroxyurea (100 mg/cat once daily) and intermittent phlebotomy. Initial treatment using leeches in cases of polycythaemia vera is a simple, non-invasive, well tolerated and effective method where phlebotomy is not possible.

Animals↗
PubMed2001

A mutation in the cofactor-binding domain of 11beta-hydroxysteroid dehydrogenase type 2 associated with mineralocorticoid hypertension.

Renal 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) is an enzyme responsible for the peripheral inactivation of cortisol to cortisone in mineralocorticoid target tissues. Mutations in the gene encoding 11betaHSD2 cause the syndrome of apparent mineralocorticoid excess (AME), an autosomal recessive form of inherited hypertension, in which cortisol acts as a potent mineralocorticoid. The mutations reported to date have been confined to exons 3-5. Here, we describe two siblings, 1 and 2 yr old, who were diagnosed with hypokalemic hypertension and low plasma aldosterone and renin levels, indicating mineralocorticoid hypertension. Analysis of urinary steroid metabolites showed a markedly impaired metabolism of cortisol, with (tetrahydrocortisol + 5alpha-tetrahydrocortisol)/tetrahydrocortisone ratios of 40-60, and nearly absent urinary free cortisone. Although phenotypically normal, the heterozygous parents showed a disturbed cortisol metabolism. Genetic analysis of the HSD11B2 gene from the AME patients revealed the homozygous deletion of six nucleotides in exon 2 with the resultant loss of amino acids Leu(114) and Glu(115), representing the first alteration found in the cofactor-binding domain. The deletion mutant, expressed in HEK-293 cells, showed an approximately 20-fold lower maximum velocity but increased apparent affinity for cortisol and corticosterone. In contrast, two additionally constructed substitutions, Glu(115) to Gln or Lys, showed increased maximal velocity and apparent affinity for 11beta-hydroxyglucocorticoids. Functional analysis of wild-type and mutant proteins indicated that a disturbed conformation of the cofactor-binding domain, but not the missing negative charge of Glu(115), led to the observed decreased activity of the deletion mutant. Considered together, these findings provide evidence for a role of Glu(115) in determining cofactor-binding specificity of 11betaHSD2 and emphasize the importance of structure-function analysis to elucidate the molecular mechanism of AME.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2001

Bisensory augmentation: a speechreading advantage when speech is clearly audible and intact.

Reisberg, McLean, and Goldfield (1987) have shown that vision plays a part in the perception of speech even when the auditory signal is clearly audible and intact. Using an alternative method the present study replicated their finding. Clearly audible spoken messages were presented in audio-only and audio-visual conditions, and the adult participants' resulting comprehension was measured. Stories were presented in French (Expt 1), in a Glaswegian accent (Expt 2), and by presenting spoken information that was semantically and syntactically complex (Experiment 3). Three separate groups of 16 adult female participants aged 19-21 participated in the three experiments. In all three experiments, comprehension improved significantly when the speaker's face was visible.

Acoustic Stimulation↗
PubMed2000

Gene sam1 encoding adenosylmethionine synthetase: effects of its expression in the fission yeast Schizosaccharomyces pombe.

By screening gene libraries of Schizosaccharomyces pombe with a DNA fragment encoding part of the Saccharomyces cerevisiae S-adenosylmethionine synthetase (SAMS), we isolated the fission yeast sam1 gene. Its sequence exhibits good homology to SAMSs of other organisms and reveals the motifs characteristic for SAMSs. SAMS activity and sam1 mRNA levels decrease when cells enter stationary phase. In haploid strains, gene sam1 is essential for growth; if weakly expressed, cells mate and sporulate at a reduced rate. Strains overexpressing sam1 exhibit methionine-sensitive growth. This methionine-induced growth inhibition is partially relieved by adenine. We assume that methionine reduces the level of one or several adenine nucleotides by a SAMS-mediated mechanism. Intracellular SAM levels increase drastically by exogenously added methionine. This increase predicts that mutants exhibiting methionine revertible phenotypes can be indicative for mutations in proteins exhibiting SAM-dependent functions. In agreement with this prediction, we show that mutant pmt2-5 has this phenotype and that gene pmt2 encodes a potential SAM-dependent enzyme.

Amino Acid Sequence↗
PubMed2000

Iron complexes of the cardioprotective agent dexrazoxane (ICRF-187) and its desmethyl derivative, ICRF-154: solid state structure, solution thermodynamics, and DNA cleavage activity.

This study investigates the solution thermodynamics of the iron complexes of dexrazoxane (ICRF-187, (+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane), [Fe(ADR-925)](+/0), and its desmethyl derivative ICRF-154, [Fe(ICRF-247)H2O](+/0). The solid state structure of [Fe(ICRF-247)H2O]+ is also reported. [Fe(ICRF-247)H2O]Br x 0.5NaBr x H2O crystallizes in the P42(1)2 space group with Z = 4, a = 14.9851(8), b = 14.9851(8), c = 8.0825(9) A and R = 0.03(2) for 1839 reflections and exhibits a pentagonal bipyramidal geometry with a labile water molecule occupying the seventh coordination site. Potentiometric titrations (FeL = 8.5 mM, 0.1 M NaNO3, 25 degrees C) reveal stable monomeric complexes (log Kf = 18.2 +/- 0.1, [Fe(ADR-925)]+, and 17.4 +/- 0.1, [Fe(ICRF-247)H2O]+) exist in solution at relatively low pH. Upon addition of base, the iron-bound water is deprotonated; the pKa values for [Fe(ICRF-247)H2O]+ and [Fe(ADR-925)]+ are 5.63 +/- 0.07 and 5.84 +/- 0.07, respectively. At higher pH both complexes undergo mu-oxo dimerization characterized by log Kd values of 2.68 +/- 0.07 for [Fe(ICRF-247)H2O]+ and 2.23 +/- 0.07 for [Fe(ADR-925)]+. In the presence of an oxidant and reductant, both [Fe(ICRF-247)H2O]+ and [Fe(ADR-925)]+ produce hydroxyl radicals that cleave pBR322 plasmid DNA at pH 7 in a metal complex concentration-dependent manner. At low metal complex concentrations (approximately 10(-5) M) where the monomeric form predominates, cleavage by both FeICRF complexes is efficient while at higher concentrations (approximately 5 x 10(-4) M) DNA cleavage is hindered. This change in reactivity is in part accounted for by dimer formation.

Cardiovascular Agents↗
PubMed2000

Bioavailability investigation of two different oral formulations of Tetrazepam.

Two different oral tetrazepam (CAS 10379-14-3) formulations (Tetrazepam-ratiopharm film-coated tablets as test preparation and tablets of a reference preparation marketed in France) were investigated in 20 healthy volunteers in order to prove bioequivalence between these preparations. A single 50 mg oral dose was given according to a randomised two-way crossover design in the fasted state. Blood samples for determination of tetrazepam plasma concentrations were collected at pre-defined time points up to 96 h following drug administration. A washout period of 14 days separated both treatment periods. Tetrazepam plasma concentrations were determined by means of a validated LC-MS/MS method. Values of 3873.08 ngh/ml (test preparation) and 3930.69 ngh/ml (reference preparation) for the parameter AUC0-infinity demonstrate an nearly identical extent of drug absorption. Maximum concentrations (Cmax) of 482.08 ng/ml and 465.14 ng/ml were achieved for test and reference preparation. Time to reach maximum plasma concentration (tmax) was 1.39 hours for both preparations. Cmax and AUC0-infinity-values were tested parametrically by an analysis of variance (ANOVA). Bioequivalence was concluded if the 90% confidence intervals of the T/R-ratios were in the range of 80%-125% for AUC0-infinity and 70%-143% for Cmax. Based on the results obtained in this study, bioequivalence between the test and the reference preparation was demonstrated.

Administration, Oral↗
PubMed2000

Langevin equations with multiplicative noise: resolution of time discretization ambiguities for equilibrium systems

A Langevin equation with multiplicative noise is an equation schematically of the form dq/dt=-F(q)+e(q)xi, where e(q)xi is Gaussian white noise whose amplitude e(q) depends on q itself. Such equations are ambiguous, and depend on the details of one's convention for discretizing time when solving them. I show that these ambiguities are uniquely resolved if the system has a known equilibrium distribution exp[-V(q)/T] and if, at some more fundamental level, the physics of the system is reversible. I also discuss a simple example where this happens, which is the small frequency limit of Newton's equation &quml;+e(2)(q)&qdot;=-nablaV(q)+e(-1)(q)xi with noise and a q-dependent damping term. The resolution does not correspond to simply interpreting naive continuum equations in a standard convention, such as Stratonovich or Itoinsertion mark.

Journal Article↗
PubMed2000

Symmetric path integrals for stochastic equations with multiplicative noise

A Langevin equation with multiplicative noise is an equation schematically of the form dq/dt=-F(q)+e(q)xi, where e(q)xi is Gaussian white noise whose amplitude e(q) depends on q itself. I show how to convert such equations into path integrals. The definition of the path integral depends crucially on the convention used for discretizing time, and I specifically derive the correct path integral when the convention used is the natural, time-symmetric one whose time derivatives are (q(t)-q(t-Deltat))/Deltat and coordinates are (q(t)+q(t-Deltat))/2. (This is the convention that permits standard manipulations of calculus on the action, like naive integration by parts.) It has sometimes been assumed in the literature that a Stratonovich Langevin equation can be quickly converted to a path integral by treating time as continuous but using the rule straight theta(t=0)=1 / 2. I show that this prescription fails when the amplitude e(q) is q dependent.

Journal Article↗
PubMed2000

Glucagon-producing neuroendocrine tumour associated with hypoaminoacidaemia and skin lesions.

A nine-year-old neutered female crossbred Bernese mountain dog was diagnosed with superficial necrolytic dermatitis and a glucagon-producing islet cell tumour. Laboratory findings included hyperglucagonaemia and hypoaminoacidaemia. The dog was euthanased because of progression of the disease, and necropsy revealed liver metastases of a neuroendocrine carcinoma with immunohistochemical expression of glucagon and somatostatin. This report represents a case of canine glucagonoma syndrome; the previously reported cases in dogs are also briefly described.

Adenoma, Islet Cell↗
PubMed2000

Severe disability at hospital discharge in ischemic stroke survivors.

BACKGROUND: Several studies have attempted to identify criteria for predicting functional prognosis after stroke, but often with contradictory results. The purpose of this study was to predict the functional outcome at discharge of first-time stroke patients included consecutively in the Lausanne Stroke Registry. METHODS: We studied 3,628 sequential patients with first-ever stroke who were admitted consecutively to the Centre Hospitalier Universitaire Vaudois. Functional status was evaluated using the Rankin disability scale at discharge. We studied the prognostic value of historical, clinical and instrumental variables related to functional outcome at discharge. The factors studied were age, sex, risk factors, ECG results, occurrence of transient ischemic attacks (TIAs), extension of cerebral infarction, presumed cause of stroke, clinical findings and demographic characteristics. Univariate analysis was performed on each variable by comparing the number of functionally independent with that of dependent patients at the moment of discharge. The significant variables of the univariate analysis were subjected to multivariate analysis with a backward logistic regression procedure to find those with an independent effect on the outcome. RESULTS: A total of 3,156 patients, excluding 117 patients with ischemic stroke who died during hospitalization and 355 with brain hemorrhage, were included; 2,867 patients belonged to the nil, mild or moderate disability groups (modified Rankin score 1-4; functionally at least partially independent patients), while 291 patients belonged to the severe disability group (modified Rankin score 5; functionally dependent patients). The mean duration of stay in hospital of the severe disability group was 31.2 days (SD = 16.2). Multivariate analysis showed that impaired consciousness on admission, limb weakness, progressive worsening, infarct in the superficial and deep territory of the middle cerebral artery, ischemic heart disease and cardiac arrhythmia were predictors of severe disability at discharge. Age was not an independent predictor of poor outcome. Hypercholesterolemia was significantly related to a better outcome. CONCLUSIONS: Some prognostic indicators associated with functional outcome at discharge are available during the first few hours after onset of stroke. This is important for the management of the individual stroke patient and for organizing suitable rehabilitation planning.

Adult↗
PubMed2000

Coil occlusion of the parent artery for treatment of symptomatic peripheral intracranial aneurysms.

BACKGROUND AND PURPOSE: Peripheral intracranial aneurysms can be difficult to treat with traditional surgical or embolization techniques that spare the parent vessel. We report the results of our use of coil occlusion of the parent vessel for the treatment of nine peripheral intracranial aneurysms. METHODS: During approximately a 4-year period, nine patients (six men and three women, 27 to 68 years old; average age, 42 years) presented to our institution with peripheral intracranial aneurysms. The aneurysms were located on branches of the right posterior inferior cerebellar artery (n = 2), the right superior cerebellar artery (n = 1), the right anterior inferior cerebellar artery (n = 1), the right posterior cerebral artery (n = 3), the left middle cerebral artery (n = 1), and the left anterior cerebral artery (n = 1). Parent vessel occlusion was performed using microcoils after test injection with amobarbital (Amytal) in eight of the nine cases (one patient was comatose and could not be tested before occlusion). RESULTS: Angiography immediately after the procedure showed aneurysmal occlusion in every patient. Follow-up arteriography, performed in six patients 2 to 12 months after treatment, documented continued aneurysmal occlusion in every case. Three patients exhibited mild, nondisabling neurologic deficits after coil placement; the rest had no new deficits, although one patient was severely disabled from the initial hemorrhage and one patient died of an unrelated cause. CONCLUSION: Our results lend support to the use of parent vessel occlusion for peripheral aneurysms that are difficult to treat surgically or that are not amenable to intra-aneurysmal coil placement.

Adult↗
PubMed2000

[Radiation therapy in two cats with pituitary tumors].

Two cats with large pituitary neoplasms (adenoma and adenocarcinoma) were treated with fractionated radiation therapy. Total doses of 40 Gy, respectively 36 Gy, were applied in 10 fractions of 4 Gy, and 3.6 Gy respectively. Side effects were minimal and transient. Anesthesia was well tolerated. Improvement of clinical signs could be observed during radiation therapy in both cats. One cat had a complete, the other a partial tumor response. One cat (suspicion of adenoma) was euthanized 1 3/4 years after therapy due to unrelated disease. No tumor was found on histopathology, however a small focal necrosis of brain tissue in the irradiated field was observed. The second animal with a pituitary adenocarcinoma was euthanized because of tumor recurrence 1 1/2 years after therapy. Radiation therapy was effective, despite the low total doses of radiation applied.

Adenocarcinoma↗