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Biomedical subjects

J Martin

Publications and source records attributed to J Martin.

At least 73 records · Page 4Linked to original sources

Myocardial blood flow and flow reserve in response to hormone therapy in postmenopausal women with risk factors for coronary disease.

Estrogen has beneficial effects on markers of coronary heart disease (CHD) risk, but may increase overall CHD events. The effects of hormone therapy on vascular endothelial function have been mixed, and require further assessment. We studied the myocardial blood flow (MBF) response to postmenopausal combination hormone therapy (CHT) in postmenopausal women with risk factors for CHD. We performed dynamic [13N]ammonia positron emission tomography in 15 postmenopausal women in a 7-month placebo-controlled crossover trial of continuous conjugated equine estrogen/cyclical micronized progesterone. MBF was measured at rest, after sympathetic stimulation with the cold pressor test (CPT), and after i.v. adenosine infusion, to determine baseline, endothelium-dependent, and maximal flows, respectively. Response to CPT was neutral in all women at baseline (-0.51 +/- 27%). Adenosine induced a marked increase in MBF (161 +/- 111%). Treatment with 3 months of combined estrogen/progestin CHT did not change CPT or adenosine MBF responses. Myocardial flow reserve was unchanged as well. In this group of postmenopausal women at higher cardiovascular risk, no association was found between CHT assignment and change in MBF. Further study is needed to clarify the effects of CHT on the endothelium of women with presumably diseased vasculature.

Aged↗

Comparison of the pharmacological properties of rat Na(V)1.8 with rat Na(V)1.2a and human Na(V)1.5 voltage-gated sodium channel subtypes using a membrane potential sensitive dye and FLIPR.

A novel, membrane potential sensitive dye and a fluorescence imaging plate reader (FLIPR) have been used to characterize the pharmacological properties of rat Na(v)1.8 voltage-gated sodium channels (VGSC) in parallel with rat Na(v)1.2a and human Na(v)1.5 VGSC subtypes, respectively. The sensitivity of recombinant Na(v)1.2a-CHO, Na(v)1.5-293-EBNA, and Na(v)1.8-F-11 cells to VGSC activators was subtype dependent. Veratridine evoked depolarization of Na(v)1.2a-CHO and Na(v)1.5-293-EBNA cells with pEC(50) values of 4.78 +/- 0.13 and 4.84 +/- 0.12, respectively (n = 3), but had negligible effect on Na(v)1.8-F-11 cells (pEC(50) < 4.5). Type I pyrethroids were without significant effect at all subtypes. In contrast, the type II pyrethroids deltamethrin and fenvalerate evoked direct depolarization of Na(v)1.8-F-11 and Na(v)1.5-293-EBNA cells. Deltamethrin potentiated the veratridine-evoked response in Na(v)1.8-F-11 cells by > or =20-fold, in contrast to a <or =3-fold potentiation of the response in Na(v)1.2a, and Na(v)1.5 cells. Tetrodotoxin (TTX) inhibited VGSC activator-evoked depolarization of Na(v)1.8-F-11 cells with a biphasic concentration-response curve. The calculated pIC(50) values were 8.05 +/- 0.25 (n = 4) and 4.32 +/- 0.21 (n = 4), corresponding to TTX inhibition of endogenous TTX-sensitive (TTX-S), and recombinant Na(v)1.8 TTX-resistant (TTX-R) VGSCs, respectively. With the exception of TTX, the potencies of a number of ion channel blockers for the Na(v)1.8, Na(v)1.2a, and Na(v)1.5 VGSC subtypes were similar. In summary, these high-throughput FLIPR assays represent a valuable tool for the determination of the relative potencies of compounds at different VGSC subtypes and may prove useful for the identification of novel subtype-selective inhibitors.

Animals↗

[MRI evaluation of primary chemotherapy response in breast cancer].

The aim of this work was to evaluate the value of contrast enhanced MRI for determination of response to neoadjuvant chemotherapy (type FEC) in breast cancer according to two parameters: size of the enhancing tumor and the maximum relative enhancement curve (MRC) in the same tumor area. Twenty women with breast cancer (15 invasive ductal carcinomas and 5 invasive lobular carcinomas) T2 (n = 8) or T3 (n = 12) were evaluated by physical examination and MRI after a minimal of three courses of FEC and prior to surgery. Data from physical examination and imaging studies were compared to histopathological findings. Physical examination estimated correctly the residual tumor size in 45% of cases and MRI in 60% with 3 false negative cases. Among evaluated patients with MRI measurable residual tumor, tumor size was underestimated in 69% of the cases and overestimated in 31% of the cases. A MRC flattening was observed in 5 cases among the patients with a partial response or clinical stable disease correlated with a poor cellular density in the microscopic findings. MRI monitoring of chemotherapy response can be useful for guiding surgery. Therefore, underestimation of the residual tumor size and false negative rate are remaining problems.

Breast Neoplasms↗

UK Back pain Exercise And Manipulation (UK BEAM) trial--national randomised trial of physical treatments for back pain in primary care: objectives, design and interventions [ISRCTN32683578].

BACKGROUND: Low back pain has major health and social implications. Although there have been many randomised controlled trials of manipulation and exercise for the management of low back pain, the role of these two treatments in its routine management remains unclear. A previous trial comparing private chiropractic treatment with National Health Service (NHS) outpatient treatment, which found a benefit from chiropractic treatment, has been criticised because it did not take treatment location into account. There are data to suggest that general exercise programmes may have beneficial effects on low back pain. The UK Medical Research Council (MRC) has funded this major trial of physical treatments for back pain, based in primary care. It aims to establish if, when added to best care in general practice, a defined package of spinal manipulation and a defined programme of exercise classes (Back to Fitness) improve participant-assessed outcomes. Additionally the trial compares outcomes between participants receiving the spinal manipulation in NHS premises and in private premises. DESIGN: Randomised controlled trial using a 3 x 2 factorial design. METHODS: We sought to randomise 1350 participants with simple low back pain of at least one month's duration. These came from 14 locations across the UK, each with a cluster of 10-15 general practices that were members of the MRC General Practice Research Framework (GPRF). All practices were trained in the active management of low back pain. Participants were randomised to this form of general practice care only, or this general practice care plus manipulation, or this general practice care plus exercise, or this general practice care plus manipulation followed by exercise. Those randomised to manipulation were further randomised to receive treatment in either NHS or private premises. Follow up was by postal questionnaire one, three and 12 months after randomisation. The primary analysis will consider the main treatment effects before interactions between the two treatment packages. Economic analysis will estimate the cost per unit of health utility gained by adding either or both of the treatment packages to general practice care.

Adult↗

Pattern of reaction diffusion fronts in laminar flows.

Autocatalytic reaction between reacted and unreacted species may propagate as solitary waves, namely, at a constant front velocity and with a stationary concentration profile, resulting from a balance between molecular diffusion and chemical reaction. The effect of advective flow on the autocatalytic reaction between iodate and arsenous acid in cylindrical tubes and Hele-Shaw cells is analyzed experimentally and numerically using lattice Bhatnagar-Gross-Krook simulations. We do observe the existence of solitary waves with concentration profiles exhibiting a cusp and we delineate the eikonal and mixing regimes recently predicted.

Animals↗

Primary diagnosis and REAL/WHO classification of non-Hodgkin's lymphoma by fine-needle aspiration: cytomorphologic and immunophenotypic approach.

The Revised European American lymphoma (REAL) and World Health Organization (WHO) classification of non-Hodgkin's lymphoma (NHL) relies on the constellation of cytologic, phenotypic, genotypic, and clinical characteristics of NHL. For the most part, the classification does not rely on architectural pattern for classification of neoplasms. This classification makes it possible to diagnose and classify lymphomas by fine-needle aspiration (FNA). In this study, we attempted to evaluate the accuracy of FNA in diagnosing and classifying NHL within the context of the REAL/WHO classifications. Cases included only those in which FNA was the primary diagnosis, followed by a surgical biopsy for confirmation. Flow cytometry (FCM) for phenotyping was carried out whenever material was available. Two groups of pathologists were identified. Group A consisted of pathologists with background training in cytopathology and/or hematopathology (three pathologists). Group B consisted of experienced surgical pathologists with no training in cytopathology and/or hematopathology (four pathologists). Seventy-four cases were included in the study. FCM phenotyping was performed in 53 cases (71%). Large cell lymphoma constituted 63% of the cases. The remaining lymphomas included Burkitt's, small lymphocytic, lymphoblastic, follicle center cell, Ki-1, mantle cell, marginal zone, and natural killer cell lymphoma. The diagnosis of lymphoma was rendered for all cases. The correct classification was seen in 63% of the cases. Classification was more accurate in immunophenotyped than in nonimmunophenotyped cases (84% vs 33%; P = 0.00004). Group A pathologists showed higher incidence of proper classification than group B (80% vs 56%; P = 0.046). The diagnosis and classification of NHL can be achieved in a large number of cases on FNA material. This accuracy can be increased if cytomorphologic criteria are established for different entities of NHL aided by FCM for phenotyping.

Biopsy, Needle↗

[Peripartum cardiomyopathy. Perioperative anaesthesiological management of a rare complication of pregnancy].

Peripartum cardiomyopathy is a rare disorder with an incidence from 1:3,000 to 1:15,000 live births and thus not often described in the anaesthesiology literature. The etiology of this disease is still not known but the symptoms are similar to idiopathic dilated cardiomyopathy. Echocardiographic findings show a dilatation of the left ventricle in addition to abnormal wall motion with a severe reduction of the cardiac function. Despite the rarity of this disorder, the anaesthesiologist or ICU physician should consider peripartal cardiomyopathy as a differential diagnosis to ensure an adequate perioperative management. There seems to be an increased incidence in pregnant women who are elderly (age >30 years),who have a history of gestosis/hypertension,have a gemini pregnancy or are of black origin. The prognosis depends on the recovery of the left ventricular contractility within the first 6 months after onset of the disease. The mortality rate is reported to vary between 25% and 50%. Heart transplantation is regarded as the last resort which has successfully been performed with several patients. This case describes the perioperative management of a 32-year-old women with peripartum cardiomyopathy.

Adult↗

Identification of the pocket factors in a picornavirus.

Bovine enterovirus (BEV), along with other enteroviruses and the rhinoviruses, has a hydrophobic pocket within structural protein VP1. In the crystal structures of these viruses there is electron density commensurate with a non-protein molecule within the pocket. These molecules, termed pocket factors, have been shown to stabilise the capsid and their removal from the pocket is a necessary prerequisite to uncoating. The pocket factors have been proposed, from the electron densities and uncoating studies, to be short chain fatty acids. In order to identify the pocket factor of BEV, we have grown and purified the virus in an identical manner to that used for the crystal structure determination and have performed a lipophilic extraction. Palmitic acid, C(16:0), was the most abundant accounting for 40.8% by mass of the lipophilic extract (39.3 mol%). Myristic acid C(14:0), was next most abundant at 18.5% by mass (20.0 mol%). In addition, we have identified other fatty acids in smaller proportions. We have therefore shown that BEV contains saturated fatty acid pocket factors of varying chain length. We have also compared the profile of the fatty acyl chain composition of BEV with those for uninfected BHK-21 cell plasma membrane and endoplasmic reticulum extracts.

Animals↗

The Jarvik 2000 is associated with less infections than the HeartMate left ventricular assist device.

OBJECTIVES: Device-related infections remain a considerable problem of left-ventricular support. We compared the device-related-infections between the HeartMate left ventricular assist device (LVAD) and the Jarvik 2000 permanent LVAD, a device with a novel retroauricular power-supply. METHODS: Between December 2000 and September 2002 we implanted the HeartMate-vented, electrical-system in 11 patients and the permanent Jarvik 2000 in six patients. Total support time was 1626 patient-days (HeartMate, 26-271 days) versus 1246 patient-days (Jarvik 2000, 8-411 days). As potential risk factors for infection we analyzed age, preoperative hospital-days, total protein, cardiac index, maximal oxygen uptake, use of inotropes, LVAD risk-score-index and Aaronson-Mancini-score, intubation time, and intensive care unit stay. We used the Center of Disease Control definitions for surgical site infections. RESULTS: HeartMate-patients were younger than Jarvik 2000 patients (46+/-13 versus 58+/-6 years, P=0.056), there were no other differences in the risk factors. Four HeartMate-patients needed late (>or=48 h) surgical revisions for bleeding/hematomas versus no revisions in the Jarvik 2000 patients. In the HeartMate-patients, there were seven (64%) driveline-infections, five (45%) device-pocket infections, and three (27%) bloodstream-infections, or 0.43 device-related infections/100 patient-days. Infections occurred early (34+/-31 days). Three patients required urgent transplantation due to bloodstream infection. There were no adverse outcomes in the HeartMate-group due to infection. In the Jarvik 2000 patients, there was one driveline-infection (16%) after 270 days of support (0.08 device-related infections/100 patient-days), significantly less than in the HeartMate-group (P=0.044). Driveline infections resolved with antibiotics and local wound care in the Jarvik 2000 patient, but only in one of seven HeartMate-patients. CONCLUSIONS: Implantation of the Jarvik 2000 is associated with less device-related infections than the HeartMate-LVAD. The power-supply of the permanent Jarvik 2000 is suitable for long-term mechanical support.

Anti-Bacterial Agents↗

Genetic polymorphisms in Spanish rheumatoid arthritis patients: an association and linkage study.

HLA polymorphism accounts only for approximately one-third of the genetic predisposition to rheumatoid arthritis (RA). To investigate the role of other loci in the susceptibility to RA, we have performed an analysis of several polymorphisms in genes of immune-related function: IL-10 -1082, -819, -592 promoter single nucleotide polymorphisms (SNPs), IL-10G and IL-10R microsatellites, IL-6 -622 promoter SNP, FcgammaRIIIA Val/Phe-158 polymorphism, IL-1 receptor antagonist VNTR, and the IKBL+738 T/C mutation. The analysis has been performed on a case-control study and also on RA trios. IL-10G12 was found to be associated with RA in the case-control study (18% in RA patients vs 9% in controls: P=0.001; pc<0.05). This allele was also more often transmitted than not transmitted (10 vs 5). No other allele in the present study is found to be associated to RA. Our data suggest that most of the loci studied play no major role in the susceptibility to RA, the IL-10 gene being the sole exception.

Arthritis, Rheumatoid↗

Assessment of the Ventrix parenchymal intracranial pressure monitoring probe (NL950-P) and Monitor (NL950-100) in a 3 Tesla magnetic resonance scanner.

Magnetic resonance (MR) imaging and spectroscopy provide important information in patients with acute head injury. However, optimal patient management requires intracranial pressure (ICP) monitoring. There are few reports on the use of ICP sensors in an MR environment. We tested the Ventrix parenchymal intracranial pressure monitoring probe and monitor (Integra Neurosciences, USA), modified by the use of a fibre-optic extension cable, within a 3 Tesla MR system. The device performed well in the MR environment, but one element within the fibre-optic extension was significantly ferromagnetic. The ICP probe produced a small susceptibility artefact on spin echo images, and a larger artefact on gradient echo images. The MR safety of the integrated system is probably acceptable, but could be easily improved with minor modifications. Although the system is MR compatible and produces generally acceptable imaging even at 3 Tesla, there is significant degradation of image quality during gradient echo sequences.

Artifacts↗

The two-level ulnar collateral ligament injury of the metacarpophalangeal joint of the thumb.

Ulnar collateral ligament injuries of the thumb may present as avulsion fractures of the bone or as ligamentous tears. Displaced fracture fragments or Stener lesions demand operative management. Occasionally, both fracture and ligamentous tears may occur simultaneously, and the management of the ligamentous aspect may be overlooked in cases with undisplaced fractures leading to failure of non-operative treatment. It is important in cases with a relatively undisplaced fracture fragment to exclude a simultaneous ligamentous tear and Stener lesion by careful clinical examination and by examining the radiographs for telltale displaced flecks of bone.

Adult↗

Endoscopic balloon dilation of gastroenteric anastomotic stricture after laparoscopic gastric bypass.

BACKGROUND AND STUDY AIMS: Laparoscopic gastric bypass is a recently introduced treatment option for morbid obesity, with promising initial results. Stenosis of the gastroenterostomy is a recognized complication. The efficacy and safety of endoscopic balloon dilation for the management of this type of anastomotic stenosis has not been studied. PATIENTS AND METHODS: 450 patients who underwent laparoscopic gastric bypass at our institution were followed prospectively. All patients had a 15 ml gastric pouch and either a 75 cm or 150 cm jejunal Roux limb depending on whether obesity was morbid (body mass index (BMI) < 50 kg/m 2) or super-morbid (BMI > 50 kg/m 2). Patients who developed symptoms compatible with stenosis of the gastrojejunostomy were referred for upper gastrointestinal endoscopy. RESULTS: 14 patients, 11 women and three men, underwent a total of 27 endoscopies, with 23 balloon dilations. Their average age was 46 years (range 33 - 59 years), average preoperative BMI was 47 kg/m 2, and they presented an average of 2.7 months after surgery (range 0.3 - 15.7 months). Of the 14 patients, 13 had a stricture of the gastrojejunostomy and one patient had edema. For initial dilation, a 15 mm hydrostatic balloon was used in 12 patients and an 18 mm balloon in two patients. There was response to treatment with the 15 mm balloon in seven of the 12 patients (58 %), and they required no further dilation; in one there was a response to a further 15 mm balloon dilation; in three patients a response to subsequent 18 mm balloon dilation; and one patient required 18 mm and 25 mm balloon dilations. The two patients treated with an initial 18 mm balloon dilation required no further dilations. The average length of follow-up after successful dilation was 18 months (range 7 - 30 months). There were no complications with any of the 23 dilations performed. CONCLUSION: Stenosis of the gastroenterostomy after laparoscopic gastric bypass occurred in 3.1 % of the patients in this series. It can be successfully and safely treated with endoscopic balloon dilation with good long-term follow-up.

Adult↗

Viability of the myocardium after twenty-four-hour heart conservation--a preliminary study.

BACKGROUND: Orthotopic heart transplantation following ischemic times beyond four hours is associated with increased risk of early graft failure. The use of modern myocardial preservation strategies could enable safe transplantation after long-term conservation. In this study, we tested a new myocardial protection regime in an experimental model of 24 h storage. METHODS: Orthotopic heart transplantations (n=15) were performed in a pig model. Donor hearts were flushed with Bretschneider solution, excised, and stored for 24 hours at 4 degrees C. During implantation, controlled reperfusions with substrate-enriched leukocyte-depleted blood cardioplegia were performed after each anastomosis. Blood cardioplegia contained 1 mmol/l of the Na(+)-H(+)-exchange inhibitor HOE 642 and 100 mg/l of adenosine. Controlled reperfusion was continued with leukocyte-depleted blood for 20 min. A microaxial pump was inserted after heart transplantation and circulatory assistance was maintained for five hours to prevent right heart failure. RESULTS: No initial graft failure could be observed. Thirteen hearts could be weaned from extracorporeal circulation. Due to bleeding problems, kidney and lung failure only five hearts could be included in the final analysis. Hemodynamics of these hearts remained stable with epinephrine at 0.1 micro g/kg/min. Myocardial oxygen consumption 20 min after start of reperfusion (5.3+/-2.0 ml/100 g/min) did not differ significantly versus baseline (6.8+/-2.0 ml/100 g/min). Oxygen extraction six hours after heart transplantation was also well preserved compared to baseline (58.0+/-10.2 versus 49.2+/-8.8 %). Histological examination six hours after transplantation using luxol fast blue staining revealed that only 1.0 % of the myocytes were irreversibly damaged. CONCLUSIONS: The data indicate full viability of the myocardium after 24 h conservation. The preservation technique described could contribute to the extension of conservation times in heart transplantation and enable transplantation of marginal donor hearts.

Animals↗

[Mechanical circulatory assist devices in acute and chronic heart failure].

The clinical use of mechanical circulatory assist devices as bridge to transplantation has been proved as life-saving therapy in a large population of patients. Learning from the clinical experience the construction of the blood pumps has been markedly improved over the last years. The better outcome of the patients has enabled a broader use of ventricular assist devices. The novel axial pumps are designed for long-term circulatory support. After further reduction of device related complications (first of all thromboembolic events) these systems may provide a future alternative to heart transplantation.

Contraindications↗