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Biomedical subjects

T Paul

Publications and source records attributed to T Paul.

At least 37 records · Page 2Linked to original sources

Intralesional rituximab for cutaneous B-cell lymphoma.

Rituximab, a chimeric anti-CD20 monoclonal antibody, has been approved for systemic treatment of relapsed or refractory CD20-positive B-cell non-Hodgkin's lymphoma. As cutaneous B-cell lymphoma (CBCL) also expresses the CD20 molecule, three patients with histologically and immunohistochemically confirmed CBCL without systemic involvement were treated with low-dose intralesional rituximab in a pilot study. Single doses applied ranged from 10 to 30 mg per lesion, according to lesion extent, with a cumulative dose of up to 350 mg. Injections were given two or three times weekly for 3-5 weeks, with a second cycle after 6 weeks in one patient with incomplete remission. Complete and lasting remission was achieved in each patient; this has persisted for up to more than 1 year. The observed adverse events were of grade 1 severity. Results suggest that intralesional rituximab may be a safe and effective new therapy modality for CBCL.

Adult↗

Detection of melanoma cells in sentinel lymph nodes, bone marrow and peripheral blood by a reverse transcription-polymerase chain reaction assay in patients with primary cutaneous melanoma: association with Breslow's tumour thickness.

BACKGROUND: Tyrosinase reverse transcription-polymerase chain reaction (RT-PCR) has been shown to be highly sensitive in detecting tumour cells in melanoma patients. OBJECTIVE: To assess whether the detection of minimal residual disease by RT-PCR is improved by concomitant analysis of sentinel lymph nodes (SLNs), bone marrow (BM) and peripheral blood (PB) in patients with primary melanoma. METHODS: Thirty-five SLNs, 41 BM samples and 26 PB specimens from 26 patients with primary cutaneous melanoma (tumour thickness > or = 0.75 mm) were examined by nested RT-PCR for tyrosinase and Melan-A. SLNs and BM samples were also analysed by histopathology. RT-PCR findings were related to tumour thickness of the primary melanoma. RESULTS: Overall, melanoma cells were detected by RT-PCR in 13 of 26 patients (50%). Seven patients had positive RT-PCR results in their SLNs (27%), including all patients (n = 4) with histologically positive SLNs, two patients had positive findings in their BM exclusively detected by RT-PCR (8%) and six patients in PB (23%). The presence of tumour cells detected by RT-PCR in SLNs was not related to the presence of melanoma cells in BM and/or PB. The incidence of RT-PCR-positive SLNs was significantly associated with greater tumour thickness (P = 0.004). Both patients with positive RT-PCR findings in their BM had a large tumour thickness (> or = 2 mm). No association between positive RT-PCR findings in PB and greater tumour thickness was observed. CONCLUSIONS: RT-PCR-positive SLNs were strongly associated with greater tumour thickness, underlining the prognostic significance of SLN positivity. Similar to certain epithelial malignancies, molecular investigation of the BM might provide complementary prognostic information in the early stages of melanoma. In contrast, no association between positive RT-PCR results in PB and increasing tumour thickness was found, implying that RT-PCR findings in PB are of doubtful clinical relevance in primary melanoma.

Adult↗

Influence of walking speed on lower limb muscle activity and energy consumption during treadmill walking of hemiparetic patients.

OBJECTIVE: To identify the relationship between treadmill speed and energy consumption and lower limb muscle activity in ambulatory hemiparetic patients. DESIGN: Experimental cohort. SETTING: Inpatient rehabilitation clinic. PARTICIPANTS: Twenty-four ambulatory hemiparetic subjects. INTERVENTION: Subjects walked harness-secured on the treadmill with no body-weight support at self-reported (V SAS), slow (V SAS - 25%), and fast (V SAS + 25%) speed. MAIN OUTCOME MEASURES: Assessment of basic, limb-dependent cycle parameters, lower limb muscle activity, and energy consumption. RESULTS: Cadence (r = .75), stride length (r = .78), relative double-support duration (r = .31), mean muscle activity of the paretic tibialis anterior (r = .12), gastrocnemius (r = .37), vastus lateralis (r =.19), rectus femoris (r = .31), and biceps femoris (r = .45) muscles, as well as heart rate (r = .54), correlated positively with treadmill speed. Mean maximum heart rate was 131 beats/min. Energy (r = -.67) and cardiac cost (r = -.55) correlated negatively with gait speed (ie, patients walked more efficiently at faster velocities). The qualitative muscle activation pattern analysis revealed earlier (more normal) onset of activation of gastrocnemius, vastus lateralis, biceps femoris, and gluteus medius. CONCLUSIONS: Patients should try to walk fast on the treadmill, thereby facilitating relevant weight-bearing muscles and improving gait efficiency.

Aged↗

Experimental preseeding of the STARFlex atrial septal occluder device with autologous cells.

Devices used in interventional cardiology are permanent implants. However, most of the devices fulfill only a temporary function. For example, atrial septal defect (ASD) occluders serve as mechanical shields until complete in- and overgrowth of the occluding device by endogenous tissue from the defect edges has occurred. Thereafter, the foreign body material of the devices is no longer needed and bears potential long-term adverse effects. The concept of "biodegradable" occluder devices that act as transient mechanical shields to close the defects and as scaffolds for overgrowth with autologous tissue is, therefore, tempting. Since rapid and complete ingrowth as well as coverage by firm tissue is a prerequisite for any such "biological" occluder devices, the feasibility and short-term in vivo response to STARFlex devices preceeded with autologous cells was studied in an experimental sheep model. The experiments demonstrated that autologous cell preceeding of cardiovascular implants is technically feasible. Cells survived the mechanical stress of device implantation. A precoating of conventional STARFlex occluders led to an increased cellular density after cell seeding of the device, an increased resistance of the precultured cytolayer against mechanical stress, and a significantly higher poststress viability of "implanted" cells. Experimental closure of ASD using autologous-cell preseeded STARFlex devices was uncomplicated. In the sheep model this led to rapid, complete, and firm ingrowth of the device into the adjacent atrial tissue. A thicker layer of young fibrous granulation tissue in organization was found on the preceeded devices compared with the unseeded control group after 4 weeks in vivo. Currently, an increased thrombogenicity limits in vivo application.

Cell Transplantation↗

Synthesis of stereodefined polysubstituted olefins. 1. Sequential intermolecular reactions involving selective, stepwise insertion of Pd(0) into allylic and vinylic halide bonds. The stereoselective synthesis of disubstituted olefins.

Palladium-catalyzed allylic substitution and cross-coupling reactions have been combined into a sequential procedure to provide a range of disubstituted olefin products starting from two-, three-, and four-carbon common olefin templates. Diverse application of this template strategy is demonstrated in a variety of model studies and in a parallel synthesis (combinatorial) approach to prepare an allylic amine molecular library. An approach toward the preparation of astaxanthin beta-D-diglucoside, an interesting antioxidant whose total synthesis has yet to be reported, using the olefin-template approach is also discussed.

Alkenes↗

Effect of a prolonged superoxide flux on transferrin and ferritin.

The involvement of "free" iron in damage caused by oxidative stress is well recognized. Superoxide generated in a short burst and at a relatively high flux by the xanthine/xanthine oxidase couple is known to release iron from ferritin in the presence of phenanthroline derivatives as iron chelators. However, superoxide generation via xanthine oxidase is accompanied by the simultaneous direct generation of hydrogen peroxide and, in the presence of ferritin, there is also a superoxide-independent release of iron. In this study it was found that the iron chelator employed attenuates superoxide formation from the xanthine/xanthine oxidase couple. The reaction of ferritin and transferrin with a clean chemical source of superoxide, di(4-carboxybenzyl)hyponitrite (SOTS-1) was therefore investigated. The efficiency of superoxide-induced iron release from ferritin increases dramatically as the superoxide flux is decreased, reaching as high as 0.5 Fe per O2*-. Treatment of ferritin for 16 h with SOTS-1 yielded as many as 130 Fe atoms/ferritin molecule, which greatly exceeds the amount of possible "contaminating" iron absorbed on the protein shell.

Animals↗

How should xanthine oxidase-generated superoxide yields be measured?

The rate of formation of superoxide measured by its reduction of tetranitromethane (TNM) and by its reduction of ferric cytochrome c (Fe(III) cc) are in excellent agreement when the superoxide is generated from a simple chemical precursor. In contrast, the rate of formation of superoxide generated in the reaction of xanthine oxidase with acetaldehyde is much higher (up to a factor of 6) when measured with TNM and compared with Fe(III) cc. It is shown that Fe(III) cc measures superoxide that has diffused from the enzyme, and that TNM probably scavenges all the dioxygen that is reduced by one electron by the enzyme. The TNM traps enzyme-bound superoxide in competition with the second-electron transfer and proton transfer, which normally yield hydrogen peroxide. The proton transfer is probably rate determining, k(p) </= 3.8x10(3)s(-1).

Acetaldehyde↗

Strand cleavage of supercoiled DNA by water-soluble peroxyl radicals. The overlooked importance of peroxyl radical charge.

It is well established that the peroxyl radicals formed during the thermal decomposition of 2,2'-azobis(amidinopropane), ABAP, in oxygenated water can cleave double-stranded DNA, from which fact it has been concluded that peroxyl radicals, as a general class, can induce DNA strand scission. However, the ABAP-derived radicals are positively charged, and DNA is a negatively charged polyanion. Moreover, the relatively small and, therefore, free to diffuse peroxyl radicals likely to be formed in vivo will generally be negatively charged or neutral. Plasmid supercoiled DNA [pBR 322, 4361 base pairs (bp)] was reacted with known, equal fluxes of two positively charged peroxyl radicals, a negatively charged peroxyl radical, and a neutral peroxyl radical. The two positively charged peroxyl radicals degraded >/=80% of the supercoiled pBR 322 at a flux of 4 radicals/bp, but the negatively charged and neutral peroxyl radicals had no significant effect even at a flux as high as 24 radicals/bp. The same lack of effect on the DNA was also observed with high fluxes of superoxide/hydroperoxyl radicals. Similar results were obtained with another supercoiled DNA, pUC 19, except that pUC 19 is somewhat more sensitive to strand scission by positively charged peroxyl radicals than pBR 322. We conclude that most of the peroxyl radicals likely to be formed in vivo have little or no ability to induce DNA strand scission and that the potential role of electrostatics in radical/DNA reactions should always be considered.

Animals↗

[Early postoperative dysfunction of a modified Blalock-Taussig shunt: successful therapy with angioplasty and stent implantation in the subclavian artery].

A newborn with pulmonary atresia with ventricular septal defect and transposition of the great arteries was palliated with a modified Blalock-Taussig shunt at 5 days of age. Three days postoperatively arterial oxygen saturations dropped significantly. Thrombosis of the shunt was suspected. Angiography revealed stenosis of the proximal subclavian artery related to the creation of the shunt. The patient was successfully treated with angioplasty and stent implantation into the stenotic subclavian artery. Follow-up angiography 3 months after stent deployment showed a completely patent subclavian artery and unobstructed blood flow across the modified Blalock-Taussig shunt.

Angiography↗

[Antegrade flow in the aorta ascendens despite aortic atresia: 2 case reports with retrograde coronary perfusion through coronary fistulas and sinusoids].

In aortic atresia, coronary perfusion normally occurs through retrograde blood flow in the ascending aorta. We report on two patients with antegrade flow in the ascending aorta despite aortic atresia. In one patient with hypoplastic left heart syndrome (aortic atresia, severe mitral stenosis), an intact interatrial septum/premature closure of the foramen ovale was found. While no other way of left atrial or ventricular decompression was found, echocardiography, angiography and the post-mortem examination showed left ventricular to coronary sinusoids as the sole pathway for systemic oxygenation. In a second patient with complex congenital heart disease, including aortic atresia, antegrade flow in the ascending aorta was through a left coronary fistula with shunt flow originating from the pulmonary trunk. This report describes systemic perfusion depending on retrograde coronary flow due to coronary-cameral (sinusoids) and coronary arterio-venous fistulas leading to the phenomenon of antegrade blood flow in the ascending aorta despite aortic atresia.

Aorta↗

[Atrioventricular nodal reentry tachycardia in children: curative treatment by high frequency catheter ablation].

BACKGROUND: Atrioventricular nodal reentrant tachycardia (AVNRT) is one of the most common forms of supraventricular tachycardia in the pediatric population. PATIENTS AND METHODS: 41 children with a mean age of 9.6 (3.7-16) years with recurrent atrioventricular nodal reentrant tachycardia (AVNRT) refractory to medical treatment (n = 38) and recurrent syncope (n = 3) underwent electrophysiologic (EP) study. In all patients dual AV-nodal physiology could be demonstrated during EP study and typical form of AVNRT (mean heart rate 220/min) could be induced by programmed atrial stimulation. A steerable 7 F ablation catheter was placed at the inferoparaseptal region of the tricuspid valve annulus close to the orifice of the coronary sinus with the intention to record a late fractionated local atrial electrogram during sinus rhythm. Starting at this point radiofrequency current (500 kHz) with a target temperature of 70 degrees C was delivered with the intention to ablate the slow pathway. If a slowly accelerated junctional rhythm (< 120/min) occurred during energy discharge, programmed atrial stimulation was repeated. Otherwise radiofrequency current was delivered step by step up to a septal position next to the tricuspid valve annulus. Slow pathway ablation was defined as lack of evidence of dual AV nodal pathways during repeated atrial stimulation. Slow pathway modulation was defined as maximal one atrial echoimpulse after ablation. RESULTS: The number of energy applications ranged from 1-19 (median 6). In 35/41 patients slow pathway ablation could be achieved; in six patients the slow pathway was modulated. In none of the patients permanent high grade AV block was observed. During follow-up (mean 4.1 years) two patients had a recurrent episode of AVNRT after slow pathway modulation. All other patients are still free of AVNRT without medical treatment. CONCLUSION: Selective radiofrequency current ablation/modulation of the slow pathway is a safe and curative treatment of AVNRT in young patients.

Adolescent↗

[Supraventricular tachycardia in infants, children and adolescents: diagnosis, drug and interventional therapy].

Supraventricular tachycardias are the most frequent forms of symptomatic tachyarrhythmias in infants, children and adolescents. Clinical symptoms depend on age and underlying cardiac anatomy. Newborn babies and infants with paroxysmal atrioventricular reentrant tachycardias usually present with signs of congestive heart failure due to rapid heart rate. In older children and adolescents, palpitations are the leading symptom. Patients with chronic-permanent tachycardias (i.e., atrial ectopic tachycardia, permanent form of junctional reciprocating tachycardia) often develop a secondary form of dilated cardiomyopathy, the so-called "tachymyopathy". Adenosine has evolved as the drug of choice in any age group for the termination of atrioventricular reentrant tachycardia of any origin. In addition, it serves as a diagnostic tool in primary atrial tachycardias. Long-term management of atrioventricular reentrant tachycardia in infancy and childhood is age dependent. In newborn babies and infants, pharmacological therapy is advised due to the high spontaneous cessation rate of those tachycardias at the end of the first year of life. In contrast to this, the probability of spontaneous cessation of tachycardia in children > 1 year of age is very low. Therefore, radiofrequency catheter ablation of the anatomical substrate of the tachycardia is a rational alternative to long-lasting antiarrhythmic therapy. Results in children with a structurally normal heart are comparable to those achieved in adults. In patients with congenital heart disease and supraventricular tachycardias, catheter ablation during preoperative cardiac catheterization is recommended. Atrial reentrant tachycardias have been identified as one major risk factor for late postoperative morbidity and mortality in young patients. Pharmacological therapy is often not sufficient to control the tachycardia. In addition, underlying sinus node dysfunction may be aggravated in a considerable portion of the patients affected. Catheter ablation based on conventional endocardial mapping techniques by multipolar electrode catheters with the aim of identifying the critical region of the reentrant circuit is associated with an impaired success rate and a considerable recurrence rate. It may be assumed that, using the modern mapping techniques currently available (electroanatomical mapping and non-contact mapping), results of radiofrequency catheter ablation of atrial reentrant tachycardias after surgical correction of congenital heart disease will be significantly improved within the next few years.

Acute Disease↗

Anterograde double-balloon valvoplasty for treatment of severe valvar aortic stenosis in a preterm baby weighing 1400 grams.

We describe our treatment of a premature baby born weighing 1400 g with severe aortic stenosis, with a gradient of 80 mmHg across the valve. Efforts to advance a 6 mm angioplasty catheter into the stenotic aortic valve via the left ventricle failed. Anterograde angioplasty, instead, was performed using two 4 mm coronary angioplasty catheters. Six months subsequent to the intervention, the pressure gradient measured 25 mmHg, and there was no hemodynamically significant aortic insufficiency.

Aortic Valve Stenosis↗

A novel procedure for generating both nitric oxide and superoxide in situ from chemical sources at any chosen mole ratio. First application: tyrosine oxidation and a comparison with preformed peroxynitrite.

The first method for generating (*)NO and O(2)(*)(-) at any known, constant ratio has been developed. Spermine NONOate and di(4-carboxybenzyl)hyponitrite decay with first-order kinetics and exactly equal rate constants (half-lives of 80 min) at 37 degrees C and pH 7.5 to give 200 and 40 mol % (*)NO and O(2)(*)(-), respectively. Tyrosine oxidation to dityrosine and 3-nitrotyrosine (the major and minor products under the conditions used in these experiments) has been studied (mainly in the presence of CO(2)) using various different ratios of the rates of formation of (*)NO and O(2)(*)(-). The (*)NO/O(2)(*)(-) = 1.0 product profiles are very similar to those of the products derived from equal amounts of (*)NO and O(2)(*)(-) generated at a (*)NO/O(2)(*)(-) ratio of 1.0 from SIN-1 but are very different from those derived from preformed peroxynitrite. All the experimental results can be explained in terms of free radical chemistry. The product profiles at all the (*)NO/O(2)(*)(-) ratios could be satisfactorily simulated provided an important group of reactions which lead to the consumption of dityrosine was included.

Molsidomine↗

Management of severe traumatic brain injury by decompressive craniectomy.

OBJECTIVE: The beneficial effect of decompressive craniectomy in the treatment of head trauma patients is controversial. The aim of our study was to assess the value of unilateral decompressive craniectomy in patients with severe traumatic brain injury. METHODS: We retrospectively investigated 49 patients who underwent decompressive craniectomy. Intracranial pressure, cerebral perfusion pressure, therapy intensity level, and cranial computed tomographic scan features (midline shift, visibility of ventricles, gyral pattern, and mesencephalic cisterns) were evaluated before and after craniectomy. The gain of intracranial space was calculated from cranial computed tomographic scans. Patient outcome was graded using the Glasgow Outcome Scale. RESULTS: Thirty-one patients (63.3%) underwent rapid surgical decompression within 4.5 +/- 3.8 hours after trauma; in 18 patients (36.7%), delayed surgical decompression was performed 56.2 +/- 57.0 hours after injury. Patients younger than 50 years or patients who underwent rapid surgical decompression had a significantly better outcome than older patients or patients who underwent delayed surgical decompression. Craniectomy significantly decreased midline shift and improved visibility of the mesencephalic cisterns. The state of the mesencephalic cisterns correlated with the distance of the lower border of the craniectomy to the temporal cranial base. Alterations in intracranial pressure, cerebral perfusion pressure, and therapy intensity level were not significant. The overall mortality of the patients corresponded to the reports of the Traumatic Coma Data Bank (1991). CONCLUSION: Although there was a significant decrease in midline shift after craniectomy, this did not translate into decompressive craniectomy demonstrating a beneficial effect on patient outcome.

Adolescent↗

Effects of intracardiac radiofrequency current application on coronary artery vessels in young pigs.

INTRODUCTION: Radiofrequency current is widely used in children to ablate accessory AV pathways. Previous data in a pig model demonstrated coronary artery obstruction adjacent to radiofrequency current lesions 48 hours and 6 months after energy delivery. In the present study, the long-term effects (>6 months) of radiofrequency current application on coronary artery vessels in young pigs are assessed. METHODS AND RESULTS: Radiofrequency current (500 kHz) was delivered over 30 seconds in ten piglets (mean body weight 12.8 kg) using a steerable 6-French catheter with a 4-mm thermistor tip electrode (target temperature 75 degrees C). Lesions were created under fluoroscopic and electrocardiographic guidance at the lateral right atrial (RA) wall above the tricuspid valve orifice, and at the lateral left atrial and left ventricular wall adjacent to the mitral valve orifice. Selective coronary angiography and intravascular ultrasound (IVUS) studies were performed 3, 6, 9, and 12 months after energy application. After 12 months, the lesions were studied pathohistologically. All lesions consisted of compact fibrous tissue. RA lesions extended to the adjacent right coronary artery and led to coronary artery involvement with increased fibrous tissue in the adventitia and media and intimal thickening in three animals. Coronary arterial narrowing was documented by IVUS during follow-up in all three cases 9 months after energy application. Angiography failed to demonstrate coronary pathology in any of the three animals. CONCLUSION: The risk of late coronary artery lesions must be considered when catheter ablation at the RA wall is planned in children with free-wall accessory AV pathways.

Animals↗

Self-reported needlestick injuries in dental health care workers at Armed Forces Hospital Riyadh, Saudi Arabia.

The objective of the present study was to assess the incidence of sharps/needlestick injuries among dental health care workers (DHCWs) at Armed Forces Hospital Riyadh. A questionnaire was distributed among all dental staff, including dentists, hygienists, and dental surgery assistants. Results show that 65 individuals (58%) had sharps/needlestick injuries, and of these, more than half did not report these injuries to the appropriate department. At the time of injury, the majority of the DHCWs were vaccinated or immune, but a few of them were not vaccinated against hepatitis B virus. This study concludes that every DHCW should be immunized against hepatitis B virus to avoid cross-infection from sharps/needlestick injuries, which are quite common in a dental practice. The high frequency of these injuries could be reduced by simple interventions.

Accidents, Occupational↗