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Biomedical subjects

P Abraham

Publications and source records attributed to P Abraham.

At least 37 records · Page 2Linked to original sources
PubMed2004

Detection and localization of inclusions in plates using inversion of point actuated surface displacements.

A numerical simulation is carried out demonstrating the use of plate surface vibration measurements for detecting and locating inclusions within the structure. A finite element code is used to calculate normal surface displacement for both steel and mortar plates subjected to a monochromatic point force. The data is generated for the homogeneous plate and the identical plate within which exists a small rectangular inclusion. It is observed that when the elastic modulus of the inclusion is orders of magnitude lower than the base material, resonances of the inclusion produce large local displacements that are readily observed in the raw displacement data. For more modest moduli differences, there are no such directly observable effects. In this case, three inverse algorithms are used to process the displacement data. The first two are local inversion techniques that each yield a spatial map of the elastic modulus normalized by density. These algorithms successfully detect and localize the inclusion based on its modulus difference from that of the base plate. The third technique uses a form of the inhomogeneous equation of motion to obtain the induced force distribution connected with the inclusion. The spatial mapping of this force also successfully detects and localizes the inclusion.

Journal Article↗
PubMed2004

Reproducibility of proximal and distal transcutaneous oxygen pressure measurements during exercise in stage 2 arterial claudication.

AIM: Although transcutaneous oxygen pressure measurements (tcpO2) are largely used in the investigation of vascular patients, its reproducibility is still debated. Indeed an unpredictable gradient exists between arterial and transcutaneous oxygen pressure. We hypothesised that indices taking into account changes over time and independent of absolute starting values would be more reproducible than other indices. METHODS EXPERIMENTAL DESIGN: comparative test-retest procedure (1 to 13 days between tests). SETTINGS: institutional practice, ambulatory care. PATIENTS AND PARTICIPANTS: 15 subjects with stage 2 claudication. INTERVENTIONS: tcpO2 recordings at rest and at exercise during the 2 treadmill tests. MEASURES: calculation of the Delta-from-rest of oxygen pressure index (limb tcpO2 changes minus chest tcpO2 changes), of the resting - or minimal values attained during exercise - of absolute tcpO2 and of the regional perfusion index (regional perfusion index: ration of limb to chest). RESULTS: Both absolute tcpO2 and regional perfusion index at rest showed low reproducibility. During exercise the best reproducibility was attained through Delta-from-rest of oxygen pressure index calculation. Equations from the linear regression analysis (test 2 versus test 1) were 0.88 x -4.2 (r(2)=0.82) at the buttock level and 0.82 x -3.8 (r(2)=0.80) at the calf level. CONCLUSION: TcpO2 measurement on the calf or buttock during exercise, is a reproducible measurement in patients with vascular claudication, specifically when corrected for exercise-induced systemic pO2 changes trough Delta-from-rest of oxygen pressure calculation.

Aged↗
PubMed2003

Antithyroid drug regimen for treating Graves' hyperthyroidism.

BACKGROUND: Antithyroid drugs are widely used in the therapy of hyperthyroidism. There are wide variations in the dose, regimen or duration of treatment used by health professionals. OBJECTIVES: To assess the effects of dose, regimen and duration of antithyroid drug therapy for Graves' hyperthyroidism. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Central), MEDLINE, EMBASE, BIOSIS, CINAHL, HEALTHSTAR, Current Controlled Trials and reference lists. We contacted investigators and hand searched conference abstracts. Most recent search: June 2002. SELECTION CRITERIA: Randomised and quasi-randomised trials of antithyroid medication for Graves' hyperthyroidism were used. DATA COLLECTION AND ANALYSIS: Trial allocation to included, excluded and awaiting assessment categories was made by consensus. Two reviewers independently extracted data and assessed trial quality. Pooling of data for primary outcomes, and select exploratory analyses were undertaken. MAIN RESULTS: Nineteen randomised trials involving 2233 participants were included. Overall the quality of trials as reported was poor; specifically in terms of allocation concealment, assessor blinding and loss to follow-up. Four trials examined the effect of duration of therapy on relapse rates of Graves' hyperthyroidism. In one trial using the Titration regimen, longer duration therapy (18 months) had significantly fewer relapses (37% vs 58%) than six month therapy (Odds ratio (OR) = 0.42, 95% confidence interval (CI) 0.18 to 0.96). In one quasi-randomised trial using the Block-Replace regimen, there was no significant difference between the six and 12 month (relapses rates 41% versus 35%) arms of the study. Extending the duration of therapy to over 18 months was not associated with improved relapse rates (Peto OR = 0.75, 95% CI 0.39 to 1.43). Ten trials examined the effect of Block-Replace versus Titration regime. Relapse rates were similar in both groups at 54% in the Block-Replace group and 58% in the Titration group (Peto OR = 0.83, 95% CI 0.63 to 1.10). Participants reporting rashes (11% versus 5%) and withdrawing due to side effects (16% versus 9%) were significantly higher in the Block-Replace group compared to the Titration group respectively. Three studies considered the addition of thyroxine after initial therapy with antithyroid drugs. There was significant heterogeneity between the studies and the difference between the two groups were not significant (Odds ratio = 0.58, 95% CI 0.05 to 6.21). REVIEWER'S CONCLUSIONS: The evidence (based on three studies) suggests that the optimal duration of antithyroid drug therapy for the Titration regimen is 12 to 18 months. The six month Block-Replace regimen was found to be as effective as the 12 month treatment in one quasi-randomised study. The Titration (low dose) regimen had fewer adverse effects than the Block-Replace (high dose) regimen and was no less effective in trials (based on 10 trials) of equal duration. The incidence of hypothyroidism was not reported and there were no deaths in the study populations.

Antithyroid Agents↗
PubMed2003

Prolonged aspirin inhibition of anodal vasodilation is not due to the trafficking delay of neural mediators.

We previously reported that forearm vasodilation to a delivered all-at-once over 5 min or a 1-min repeated monopolar anodal 0.10-mA current application is aspirin sensitive and that a single high-dose aspirin exerts a long-lived effect in the former case. We hypothesized that 1) in the latter case, the effect of aspirin would also be long lived and 2) the time required to resupply nerve endings with unblocked cyclooxygenase through axonal transport could explain this phenomenon. We studied the time course for the recovery of vasodilation to repeated current application after placebo or 1-g aspirin treatment. We then searched for a difference at a proximal vs. distal site in the recovery of the response. Aspirin abolished current-induced vasodilation at 2 h, 10 h, and 3 days, with a progressive recovery thereafter, but no difference between distal and proximal site was observed for the recovery of the response. This suggests that, although neural cyclooxygenase could participate in the response, the time course of aspirin inhibition of current-induced cutaneous vasodilation is not due to the time required through neural transport to resupply nerve endings with unblocked proteins.

Adult↗
PubMed2003

Acute superior mesenteric vein thrombosis associated with factor V 'Leiden' gene mutation.

OBJECTIVES: To study thrombophilia states in Indian patients with acute spontaneous superior mesenteric vein thrombosis (SMVT). METHODS: Two men with this condition, a 56 year old and a 31 year old presenting with acute SMVT, demonstrated on CT scan, were subjected to a thrombophilia screen consisting of Protein C, S, antithrombin levels, lupus anticoagulant, anticardiolipin antibodies, fibrinogen levels, factor VIII levels, factor V 'Leiden' gene mutation, and paroxysmal nocturnal hematuria screen. RESULTS: A thrombophilia screen showed factor V 'Leiden' gene mutation (heterozygous) in both cases. Additionally, the first patient had high fibrinogen levels and the second high factor VIII levels. Both patients are currently on long-term anticoagulation. CONCLUSION: Factor V 'Leiden' gene mutation in association with other thrombophilic factors may predispose to spontaneous superior mesenteric vein thrombosis.

Acute Disease↗
PubMed2002

Break excitation alone does not explain the delay and amplitude of anodal current-induced vasodilatation in human skin.

In iontophoresis experiments, a 'non-specific' current-induced vasodilatation interferes with the effects of the diffused drugs. This current-induced vasodilatation is assumed to rely on an axon reflex due to excitation of cutaneous nociceptors and is weaker and delayed at the anode as compared to the cathode. We analysed whether these anodal specificities could result from a break excitation of nociceptors. Break excitation is the generation of action potentials at the end of a square anodal DC current application, which are generally weaker than those observed at the onset of a same application at the cathode. In eight healthy volunteers, we studied forearm cutaneous laser Doppler flow (LDF) responses to: (1) anodal and cathodal 100 microA current applications of 1, 2, 3, 4 or 5 min; (2) 100 microA anodal applications of 3 min with a progressive ending over 100 s (total charge 23 mC); these were compared to square-ended 100 microA anodal applications of the same total charge (23 mC) or duration (3 min); (3) a 4 min 100 microA anodal application with a 333 msec break at half time. Results (mean +/- S.D.) are expressed as percentage of heat-induced maximal vasodilatation (%MVD). Onset (T(vd)) and amplitude (LDF(peak)) of vasodilatation were determined. We observed that: T(vd) was linearly related to the duration of current application at the anode (slope = 1.01, r(2) = 0.99, P < 0.0001) but not at the cathode (slope = 0.03, r(2) = 0.02, n.s.). Progressive ending of anodal current did not decrease LDF(peak) (63.3 +/- 24.6 %MVD) as compared to square-ending of current application of the same duration (36.9 +/- 22.2 %MVD) or the same total charge (57.1 +/- 23.5 %MVD). A transient break of anodal current did not allow for the vasodilatation to develop until current was permanently stopped. We conclude that, during iontophoresis, anodal break excitation alone cannot account for the delay and amplitude of the vascular response.

Adult↗
PubMed2002

In vitro and in vivo characterization of [125I]iodomethyllycaconitine in the rat.

The in vitro and in vivo binding characteristics of [125I]iodomethyllycaconitine ([125I]iodoMLA) were determined in the rat. [125I]iodoMLA binding to rat cerebral cortex membranes was saturable and reversible and its specific binding represented approximately 70-80% of the total binding. [125I]iodoMLA labeled a single site with Kd = 1.8 +/- 0.4 nM and Bmax = 68 +/- 3 fmol/mg protein. Kinetic analysis revealed a t1/2 for association and dissociation of 10.5 +/- 3.1 and 10.3 +/- 1.6 min, respectively. Pharmacological characterization of [125I]iodoMLA binding indicated that it was specific for the alpha7 nAChR. In vitro brain region binding studies revealed greater binding in regions known to contain high numbers of alpha7 nAChRs. The analysis of the biodistribution of intravenously administered [125I]iodoMLA indicated that it was rapidly cleared and exhibited poor brain penetration; nevertheless, the levels of [125I]iodoMLA in alpha7 nAChR-rich target regions were significantly increased compared to the nontarget region (cerebellum) 60-120 min after administration. No metabolism of MLA by human liver S9 fraction was detected. Our results suggest that [125I]iodoMLA will be a useful radioligand to study the alpha7 nAChR in vitro and in vivo.

Animals↗
PubMed2002

Vasodilatation in response to repeated anodal current application in the human skin relies on aspirin-sensitive mechanisms.

The vasodilatation resulting from prolonged square-wave monopolar current application as used in iontophoresis is assumed to rely on an axon reflex. Involvement of prostaglandins in the anodal current-induced vasodilatation remains unclear. We tested the hypothesis that prostaglandins participate in a sensitisation mechanism to current application rather than as direct vasodilators. In healthy volunteers, laser Doppler flowmetry (LDF) was recorded in the forearm during and following isolated or repeated 0.1 mA transcutaneous anodal current applications, using deionised water as a vehicle. Segmented current applications of 6 or 12 mC resulted in an LDF increase twice that observed following current applications of comparable total charge delivered all at once (P < 0.05). Following a 1 min anodal application, a slow and prolonged LDF drift occurred (slope: 0.3 +/- 0.5 arbitrary units min(-1)). When the same current application was repeated after intervals of 5 and 20 min, an abrupt vasodilatation occurred, with maximal LDF amplitude of 53.5 +/- 34.0 and 48.2 +/- 19.1 arbitrary units, respectively. Pretreatment with 1 g oral aspirin abolished the abrupt vasodilatation to repeated current application but not the initial slow drift. We suggest that vasodilatation occurs through two parallel pathways: (1) a slow progressive drift of LDF of limited amplitude insensitive to aspirin pretreatment, and (2) an abrupt vasodilatation probably resulting from afferent fibre activation, appearing if a preliminary sensitisation by current application is performed. Sensitisation lasts for at least 20 min, and is blocked by aspirin, suggesting participation of prostanoids.

Adult↗
PubMed2002

Oral single high-dose aspirin results in a long-lived inhibition of anodal current-induced vasodilatation.

1 Acetyl salicyclic acid (aspirin) irreversibly blocks cyclo-oxygenase (COX). This effect is short-lived in endothelial or smooth muscle cells due to resynthesis but long-lived in platelets devoid of synthesis ability. Aspirin blocks the anodal current-induced vasodilatation, suggesting participation by prostaglandin (PG). We analysed the time course of the effect of aspirin as an indirect indicator of the origin of the PG possibly involved in anodal current-induced vasodilatation. 2 In healthy volunteers, vasodilatation, estimated from the peak cutaneous vascular conductance (CVC(peak)), was recorded in the forearm during and in the 20 min following 5 min, 0.10 mA transcutaneous anodal current application, using deionized water as a vehicle. CVC(peak) was normalized to 44 degrees C heat-induced maximal vasodilatation and expressed in per cent values. Experiments were performed before and at 2 and 10 h, 3, 7, 10 and 14 days after blinded 1-g aspirin or placebo treatment. 3 CVC(peak) (mean+/-s.d.mean) after aspirin vs placebo was 13.6+/-14.5 vs 65.0+/-32.1 (P<0.05) 14.7+/-4.2 vs 87.5+/-31.9 (P<0.05), 18.1+/-10.2 vs 71.6+/-26.8 (P<0.05), 42.5+/-23.4 vs 73.3+/-26.8 (non significant, NS), 60.2+/-24.3 vs 75.2+/-26.9 (NS), 52.1+/-18.5 vs 67.9+/-32.1 (NS) at 2 and 10 h and at days 3, 7, 10 and 14 respectively. 4 Aspirin inhibition of anodal current-induced vasodilatation persists long after endothelial and smooth muscle cyclo-oxygenases are assumed to be restored. This suggests that the PG involved in this response are not endothelial- or smooth muscle-derived. The underlying mechanism of this unexpected long-lived inhibition of vasodilatation by single high dose aspirin remains to be studied.

Adult↗
PubMed2002

Presentation of a PTHrP-secreting pancreatic neuroendocrine tumour, with hypercalcaemic crisis, pre-eclampsia, and renal failure.

Severe hypercalcaemia during pregnancy is rare and most cases are secondary to hyperparathyroidism. This is the first report of a parathyroid hormone related protein (PTHrP) secreting neuroendocrine tumour of the pancreas manifesting with severe hypercalcaemia during pregnancy. Measurement of PTHrP was useful in both the diagnosis and follow up of our patient and should be considered in the diagnostic workup of patients with unexplained hypercalcaemia. A raised PTHrP concentration is a strong indicator of malignancy.

Acute Kidney Injury↗
PubMed2002

Spectral and profile analysis of Doppler recording following below-knee arterial distal bypasses.

BACKGROUND: Arterial below knee distal bypasses are associated with a high risk of thrombosis as compared to proximal bypasses. We assumed that before the bypass occludes, in the early postsurgical period, measurable velocity changes, and/or the presence of high intensity transient signals (HITS) would occur. METHODS SETTINGS: institutional reference center, hospitalized patients. SUBJECTS: satisfactory Doppler recording was obtained in 51 among 61 consecutive patients (32 males, 19 females, height: 165+/-7 cm, weight: 68+/-12 kg) suffering lower extremity arterial disease, that underwent saphenous (n=33), prosthetic (n=4) or sequential (n=14) below knee bypasses. We performed a spectral and profile analysis of a single postsurgical 2 hour Doppler recording at the ankle level and analyzed Doppler derived indices and clinical risk factors in the evaluation of the risk of bypass occlusion within 7 days following surgery. RESULTS: Primary patency at day 7 was observed in 41 of the 51 operated patients. The presence of HITS was found in approximately 30% of the patients and provided no information on the risk of thrombosis. No clinical variable was significantly associated with an increased risk of thrombosis. Whatever the duration of recording, the presence of a diastolic forward flow and wide systolic velocity changes were poor indicators of bypass thrombosis risk. On 512 beat recordings, a mean systolic velocity below 1630 Hz and a standard deviation of the resistance index >0.095 were associated with a 6.74 [1.6-28.4] (p<0.01) and 14.5 [3.6-58.9] (p<0.001) times increases in the risk of bypass occlusion respectively, compared with subjects that do not fulfill each criteria. CONCLUSIONS: Periods of transient asymptomatic no-flow-reflow events may be observed before the bypass irreversibly occludes. Prolonged Doppler recording should be preferred to short term analyses, to allow for the detection of these transient events and may provide potential indices for future research.

Algorithms↗
PubMed2002

[Very long-term outcome of 68 vena cava filters percutaneously implanted].

Between January 1987 and December 1991, 68 consecutive patients aged 71.5 +/- 12.0 years underwent percutaneous implantation of a vena caval filter, mainly the LGM (N = 64). Fifty seven patients had pulmonary embolism, 61 had deep vein thrombosis of the lower limbs. The average follow-up interval was 4.9 +/- 3.3 years (7.0 +/- 2.7 years for the patients still alive). The follow-up included a telephonic enquiry to determine the date and cause of death, recurrent deep vein thrombosis and/or pulmonary embolism; surviving patients underwent clinical examination, plain abdominal X-ray with a lateral decubitus view and duplex ultrasonography of the lower limb veins to assess the patency of the filter. Fifty three per cent of the patients died. Four predictive factors for mortality were identified: a contra-indication to anticoagulant therapy, chronic post-embolic cor pulmonale, an indication of prophylactic implantation in the elderly and the presence of underlying malignant disease. There were 5.8% recurrences of pulmonary embolism, 26.1% of lower limb deep vein thrombosis and 25% of filter thrombosis. The only predictive factor of thrombosis was a proximal venous thrombus and was associated in 50% of filter thrombosis. Seventy per cent of the plain abdominal X-rays were abnormal with 9 displacements. 9 migrations and 10 closures of the filters. There was a significant correlation between closure on plain abdominal X-ray and caval thrombosis and between recurrent deep vein thrombosis and caval thrombosis. The frequency of long-term complications after implantation of a caval filter in this study suggests that interruption of the vena cava should be reserved for the only validated indications in the presence of a formal contra-indication to or failure of anticoagulant therapy. Other indications require evaluation with prospective randomised trials.

Adult↗
PubMed2001

Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 2-exo-2-(2'-substituted-3'-phenyl-5'-pyridinyl)-7-azabicyclo[2.2.1]heptanes. Novel nicotinic antagonist.

A series of 2'-substituted-3'-phenyl epibatidine analogues were synthesized and evaluated for inhibition of binding at nicotine acetylcholine receptors and for antinociceptive properties in mice. The introduction of a bulky phenyl group at the 3'-position exerted a profound influence on both receptor binding and antinociceptive effects. Substitution of different groups at the 2'-position distinguished between agonist and antagonist properties. These results demonstrate that structural requirements for receptor activities and recognition are distinctively different.

Analgesics↗
PubMed2001

Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 2-exo-2-(2'-substituted 5'-pyridinyl)-7-azabicyclo[2.2.1]heptanes. Epibatidine analogues.

A convenient, high-yield synthesis of 7-tert-butoxycarbonyl-7-azabicyclo[2.2.1]hept-2-ene (5), which involved the addition of tributyltin hydride to 7-tert-butoxycarbonyl-2-p-toluenesulfonyl-7-azabicyclo[2.2.1]hept-2-ene (4) followed by elimination of the tributyltin and p-tolylsulfonyl groups using tetrabutylammonium fluoride was developed. The addition of 2-amino-5-iodopyridine to 5 under reductive Heck conditions provided 7-tert-butoxycarbonyl-2-exo-(2'-amino-5'-pyridinyl)-7-azabicyclo[2.2.1]heptane (6). Compound 6 was the key intermediate used to prepare epibatidine analogues where the 2'-chloro group on the pyridine ring was replaced with a fluorine (1b), bromine (1c), iodine (1d), hydroxy (1e), amino (1f), dimethylamino (1g), trifluoromethanesulfonate (1h), and hydrogen (1i) group. (+)- and (-)-Epibatidine and compounds 1b-d and 1i all possess similar binding affinities at the alpha(4)beta(2) nAChR receptors labeled by [(3)H]epibatidine. Compound 1f has affinity similar to nicotine, whereas compounds 1e, 1g, and 1h have much lower affinity. The binding affinity appears to be dependent upon the electronic nature of the substituent. However, other factors are also involved. None of the compounds possesses appreciable affinity for the alpha(7) nAChR labeled by [(125)I]iodo-MLA. With the exception of 1f and 1g, all the epibatidine analogues are full agonists (tail flick test) in producing antinociception after intrathecal injection in mice.

Analgesics, Non-Narcotic↗
PubMed2001

Dynamics of local pressure-induced cutaneous vasodilation in the human hand.

We recently demonstrated that a pressure-induced vasodilation results from local nonnociceptive stimulation of the skin of the human hand. We aimed to test the hypothesis that this vasodilation was not a short-lived response to a single type of pressure strain, but could be a widely activated and prolonged protective cutaneous response. We studied the dynamics of pressure-induced vasodilation during various ramp changes in local externally applied pressure using laser Doppler flowmetry. Changes from an adjacent control probe were subtracted from pressure-induced local changes. Following an initial transient decrease, continuous 4.4, 5.6, and 11.1 Pa.s(-1) increases of pressure resulted in a secondary increase of blood flow whose amplitude was maximal for 11.1 Pa.s(-1) (22.9 +/- 12.6% above baseline) (mean +/- SEM). The increase in flow was not noted at 16.7 Pa.s(-1). If the 16.7 Pa.s(-1) ramp pressure increase was interrupted at min 2 or 4, a prolonged vasodilation response was found, but not if it was stopped at min 8. When the 16.7 Pa.s(-1) increasing pressure was returned to zero after 4 min of pressure increase (-8.1 +/- 8.9% before pressure removal), vasodilation occurred and reached a maximum of 26.0 +/- 9.6% at 7 min after removal of pressure (P < 0.05 from baseline). Pressure-induced vasodilation is a slow-responding and transient adaptive phenomenon, initiated by a wide range of pressure changes below the range of noxious stimulation. We propose that this response is a protective mechanism without which certain pressure-associated lesions may develop.

Adult↗
PubMed2001

Infra-stellate upper thoracic sympathectomy results in a relative bradycardia during exercise, irrespective of the operated side.

OBJECTIVE: Removal of accessory fibres coming from the sub-stellar thoracic chain to the heart during infra-stellate surgical upper thoracic sympathectomy (ISS) may be responsible for a decreased heart rate to workload relationship during exercise following surgery. We hypothesised that heart rate would decrease not only following right ISS. METHODS: We performed repeated bicycle incremental exercise tests in 11 control subjects (26.9+/-9.5 years, 61.4+/-12.4 kg, 167+/-10 cm), and 11 patients (29.8+/-10 years, 59.3+/-12.0 kg, 168+/-7 cm) referred for bilateral ISS: results are mean+/-standard deviation. Surgery was performed at two distinct times allowing to study the consequences of unilateral and bilateral sympathectomy to confirm whether a significant relative bradycardia was constant and dependent on the operated side. RESULTS: For control subjects, test durations were 13.55+/-3.29, 14.09+/-4.01 and 13.00+/-3.26 min and heart rates were 187+/-7, 187+/-8 and 186+/-7 beats min(-1) at the first, second and third test, respectively. Although time to exhaustion was comparable to controls and unchanged between tests: 12.32+/-2.87, 12.3+/-2.90, 12.33+/-3.76 min, heart rate at maximum exercise decreased significantly from 176+/-16 to 164+/-15, and 148+/-15 beats min(-1), before, following unilateral and bilateral ISS, respectively. The operated side did not allow for the prediction of the effect of unilateral sympathectomy. CONCLUSIONS: Patients should be informed of the exercise bradycardia resulting from ISS, although clinical tolerance seems excellent in endurance exercise. Contrary to previous reports at rest, during exercise no right-sided dominance was observed. These findings are consistent with reports of random distribution of sub-stellate cardiac fibres from anatomical studies.

Adult↗