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PubMed2005

Speech perception with mono- and quadrupolar electrode configurations: a crossover study.

OBJECTIVE: To study the effect of two multipolar electrode configurations on speech perception, pitch perception, and the intracochlear electrical field. STUDY DESIGN: Crossover design; within subject. SETTING: Tertiary referral center. PATIENTS: Eight experienced adult cochlear implant users. INTERVENTION: Each subject used each of three experimental processors for 3 weeks. The following processors were compared that differed only in electrode configuration: 1) monopolar; 2) hybrid quadrupolar, in which half of the current returned to the extracochlear reference electrode and half to two electrodes immediately to the left and right of the active electrode; and 3) flat tripolar +2, which directed all the current to four reference electrodes (two on each side), separated from the active electrode by two inactive electrodes. All the processors used the standard Advanced Bionics HiRes speech-processing strategy, 12 channels, 1,220 pulses per second per channel, and with a pulse width of 33 (micros/phase). RESULTS: The monopolar processors had the largest stimulation efficiency and the smallest dynamic range in linear current units. The reverse was true of flat tripolar +2 processor, whereas the hybrid quadrupolar processor fell in between. Insufficient loudness growth prevented the use of the flat tripolar +2 processor in three subjects. Word recognition did not differ between the clinically used 16-channel monopolar processor and the experimental monopolar processor, regardless of the differences in the number of channels, pulse rate, and duration of experience. Word recognition with the flat tripolar +2 processor was significantly poorer than with the monopolar and hybrid quadrupolar processors; monopolar and quadrupolar processors did not differ. There was no significant interaction between processor type and competing noise type (stationary or fluctuating), but performance at the higher level of fluctuating noise was best with the hybrid quadrupolar processor in almost all the subjects. Pitch scaling showed ceiling performance in five subjects and differed between processors in the two other subjects with imperfect tonotopy. Intracochlear current spread was considerable with the monopolar configuration; it was reduced with the hybrid quadrupolar configuration and virtually absent beyond the active electrodes with the tripolar configuration. CONCLUSION: More confined configurations reduced the longitudinal width of the electrical field, which was expected to enhance channel separation, but no improvement in word recognition was found. More research is needed to test confined configurations that have enhanced efficiency and to evaluate the fundamental effects of configuration on channel discriminability.

Acoustic Stimulation↗

PubMed2005

Changes in the mechanical environment of stenotic arteries during interaction with stents: computational assessment of parametric stent designs.

Clinical studies have identified factors such as the stent design and the deployment technique that are one cause for the success or failure of angioplasty treatments. In addition, the success rate may also depend on the stenosis type. Hence, for a particular stenotic artery, the optimal intervention can only be identified by studying the influence of factors such as stent type, strut thickness, geometry of the stent cell, and stent-artery radial mismatch with the wall. We propose a methodology that allows a set of stent parameters to be varied, with the aim of evaluating the difference in the mechanical environment within the wall before and after angioplasty with stenting. Novel scalar quantities attempt to characterize the wall changes inform of the contact pressure caused by the stent struts, and the stresses within the individual components of the wall caused by the stent. These quantities are derived numerically and serve as indicators, which allow the determination of the correct size and type of the stent for each individual stenosis. In addition, the luminal change due to angioplasty may be computed as well. The methodology is demonstrated by using a full three-dimensional geometrical model of a postmortem specimen of a human iliac artery with a stenosis using imaging data. To describe the material behavior of the artery, we considered mechanical data of eight different vascular tissues, which formed the stenosis. The constitutive models for the tissue components capture the typical anisotropic, nonlinear and dissipative characteristics under supra-physiological loading conditions. Three-dimensional stent models were parametrized in such a way as to enable new designs to be generated simply with regard to variations in their geometric structure. For the three-dimensional stent-artery interaction we use a contact algorithm based on smooth contact surfaces of at least C-continuity, which prevents numerical problems known from standard facet-based contact algorithm. The proposed methodology has the potential to provide a scientific basis for optimizing treatment procedures and stent geometries and materials, to help stent designers examine new stent designs "virtually," and to assist clinicians in choosing the most suitable stent for a particular stenosis.

Adult↗

PubMed1994

Utility of transesophageal echocardiography in the diagnosis of disease of the thoracic aorta.

PURPOSE: Transesophageal echocardiography (TEE) offers a rapid, minimally invasive method for diagnosing thoracic aortic disease. High-resolution images are possible because of the close proximity of the esophagus and vascular structures within the chest. Lung and chest wall components have little influence on the image quality and a virtually unobstructed view of the heart, thoracic aorta, and pulmonary vasculature is seen. The role of TEE in diagnosing diseases of the thoracic aorta is rapidly developing. The purpose of this study is to define the role of TEE in the diagnosis of thoracic aortic disease. METHODS: Between July 1, 1989 and December 31, 1992, 1005 TEEs were performed at our center. Of these, 199 (125 men, 74 women) were entered into our aortic disease registry. Indications for the studies included 37 referrals to rule out aortic dissection, 18 to assess aortic aneurysm, 55 to assess for an intraaortic source of embolus, 9 to rule out intraaortic thrombus, and 13 with familial hyperlipidemia being followed to mark response to low-density lipoprotein apheresis. In 67 cases, subclinical aortic plaquing was found incidentally. No complications from the TEE procedure were encountered. RESULTS: In cases of suspected aortic dissection, TEE was equal to computed tomography (CT) scanning in identifying the type (DeBakey) and extent of thoracic aortic dissection. In addition, TEE provided information regarding functional status of the aortic valve, identified interluminal communications, and assessed blood flow and thrombus burden in the false lumen. TEE correctly identified true aneurysms, intraluminal thrombus, and plaques as possible sources of emboli. One false-positive CT scan result for aortic dissection was seen and was ruled out both by TEE and angiography. CONCLUSION: Biplane TEE can be considered the method of choice in diagnosing disease of the thoracic aorta. Information from TEE can be obtained at the patient's bedside or in the operating suite, to assess surgical results before procedure termination and afterward for follow-up. Adjunctive magnetic resonance imaging, CT scanning, or aortography may be needed to assess extension of the disease process into the abdomen or pelvis or to plan surgical intervention.

Adult↗

PubMed2006

Plaque composition in the left main stem mimics the distal but not the proximal tract of the left coronary artery: influence of clinical presentation, length of the left main trunk, lipid profile, and systemic levels of C-reactive protein.

OBJECTIVES: We sought to investigate whether plaques located in the left main stem (LMS) differ in terms of necrotic core content from those sited in the proximal tract of the left coronary artery. BACKGROUND: Plaque composition, favoring propensity to vulnerability, might be nonuniformly distributed along the vessel, which might explain the greater likelihood for plaque erosion or rupture to occur in the proximal but not in the distal tracts of the coronary artery or in LMS. METHODS: A total of 72 patients were included prospectively; 48 (32 men; mean age 57 +/- 11 years; 25 with stable angina and 23 affected by acute coronary syndromes) underwent a satisfactory nonculprit vessel investigation through spectral analysis of intravascular ultrasound radiofrequency data (IVUS-Virtual Histology, Volcano Corp., Rancho Cordova, California). The region of interest was subsequently divided into LMS and LMS carina, followed by 6 consecutive nonoverlapping 6-mm segments in left anterior descending artery in 34 patients or in circumflex artery in 14 patients. RESULTS: Necrotic core content (%): 1) was minimal in LMS (median [interquartile range]: 4.6 [2 to 7]), peaked in the first 6-mm coronary segment (11.8 [8 to 16]; p < 0.01), and then progressively decreased distally; 2) was overall greater in patients with acute coronary syndromes (11.4 [5.5 to 19.8]) than stable angina (7.3 [3.2 to 12.9]; p < 0.001); 3) was largely independent from plaque size; and 4) did not correlate to systemic levels of C-reactive protein or lipid profile. CONCLUSIONS: Plaques located in the LMS carry minimal necrotic content. Thus, they mimic the distal but not the proximal tract of the left coronary artery, where plaque rupture or vessel occlusion occurs more frequently.

Adult↗

PubMed1999

Recent advances in platelet-polymorphonuclear leukocyte interaction.

Epidemiological evidence suggests a positive correlation between the number of PMN and the risk of ischemic vascular disease. The observation that activated PMN induce platelet activation my provide some biological plausibility to the role of PMN in thrombogenesis. Between other PMN products, cathepsin G, a protease released during PMN activation, is a potent platelet agonist. However, the antiproteinases present in plasma could virtually abolish its activity. Indeed it was shown that, when PMN were stimulated after interaction with platelets in mixed cell population, P-selectin-mediated platelet-PMN adhesion may result in the formation of a sequestered microenvironment in which cathepsin G activity is protected by antiproteases. P-selectin-mediated adhesion was also shown to facilitate the transcellular metabolism of arachidonic acid, resulting in increased production of both thromboxane B2 and leukotriene C4. PMN adhesion to activated platelets in mixed cell suspensions subjected to high shear rate can be modeled as an adhesion cascade involving a P-selectin-dependent recognition step followed by an adhesion-strengthening interaction mediated by the beta(2)-integrin Mac-1. Moreover, an intermediate tyrosine-kinase-dependent signal regulating beta(2)-integrin adhesiveness is required. Indeeed activated platelets express not only P-selectin but also different beta(2)-integrin ligands including fibrinogen and ICAM-2. Some of the functional responses elicited by P-selectin on PMN could be prevented by specific antibody to the P-selectin glycoprotein ligand-1, indicating that this adhesive receptor is able to transduce an 'outside-in' signal when engaged by the ligand. By using activated platelets, P-selectin-expressing CHO cells and soluble recombinant P-selectin, P-selectin was shown to trigger protein tyrosine phosphorylation in PMN and the tyrosine kinase-dependent function of Mac-1. In conclusion, adherence of activated platelets to PMN may be a key event in the sequence of thrombus formation. The recognition of the essential contribution of PMN beta(2)-integrins in addition to P-selectin in platelet-PMN adhesion provides an additional evidence to the broad range of function and mechanisms in which PMN integrins are involved and may be potential targets for pharmacological intervention.

Animals↗

PubMed2002

Immediate administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: a prospective randomized study.

OBJECT: By pursuing a policy of very early aneurysm treatment in neurosurgical centers, in-hospital rebleeds can be virtually eliminated. Nonetheless, as many as 15% of patients with aneurysm rupture suffer ultraearly rebleeding with high mortality rates, and these individuals are beyond the reach of even the most ambitious protocol for diagnosis and referral. Only drugs given immediately after the diagnosis of subarachnoid hemorrhage (SAH) has been established at the local hospital level can, in theory, contribute to the minimization of such ultraearly rebleeding. The object of this randomized, prospective, multicenter study was to assess the efficacy of short-term antifibrinolytic treatment with tranexamic acid in preventing rebleeding. METHODS: Only patients suffering SAH verified on computerized tomography (CT) scans within 48 hours prior to the first hospital admission were included. A 1-g dose of tranexamic acid was given intravenously as soon as diagnosis of SAH had been verified in the local hospitals (before the patients were transported), followed by doses of 1 g every 6 hours until the aneurysm was occluded; this treatment did not exceed 72 hours. In this study, 254 patients received tranexamic acid and 251 patients were randomized as controls. Age, sex, Hunt and Hess and Fisher grade distributions, as well as aneurysm locations, were congruent between the groups. Outcome was assessed at 6 months post-SAH by using the Glasgow Outcome Scale (GOS). Vasospasm and delayed ischemic neurological deficits were classified according to clinical findings as well as by transcranial Doppler (TCD) studies. All events classified as rebleeding were verified on CT scans or during surgery. CONCLUSIONS: More than 90% of patients reached the neurosurgical center within 12 hours of their first hospital admission after SAH; 70% of all aneurysms were clipped or coils were inserted within 24 hours of the first hospital admission. Given the protocol, only one rebleed occurred later than 24 hours after the first hospital admission. Despite this strong emphasis on early intervention, however, a cluster of 27 very early rebleeds still occurred in the control group within hours of randomization into the study, and 13 of these patients died. In the tranexamic acid group, six patients rebled and two died. A reduction in the rebleeding rate from 10.8 to 2.4% and an 80% reduction in the mortality rate from early rebleeding with tranexamic acid treatment can therefore be inferred. Favorable outcome according to the GOS increased from 70.5 to 74.8%. According to TCD measurements and clinical findings, there were no indications of increased risk of either ischemic clinical manifestations or vasospasm that could be linked to tranexamic acid treatment. Neurosurgical guidelines for aneurysm rupture should extend also into the preneurosurgical phase to guarantee protection from ultraearly rebleeds. Currently available antifibrinolytic drugs can provide such protection, and at low cost. The number of potentially saved lives exceeds those lost to vasospasm.

Adolescent↗

PubMedDate not supplied

Medical management of antimicrobial-associated diarrhea and colitis.

Gastrointestinal complications, including diarrhea, may occur with virtually all antimicrobial agents. Such diarrhea may represent either a common, nonspecific adverse effect, or it may be one of the manifestations of antimicrobial-associated colitis (AAC), a potentially fatal complication. Clostridium difficile and a cytotoxin neutralized by Clostridium sordellii antitoxin has been isolated from the stools of nearly all patients with antibiotic-associated pseudomembranous colitis, many patients with AAC, and approximately 20% of those with antimicrobial-induced diarrhea. Demonstration that C. difficile is responsible for cytotoxin production has allowed for specific therapy for these disorders. General treatment measures include discontinuation of the causative antimicrobial agent(s), bowel rest, and supportive care with fluids, electrolytes and colloids, if necessary. Antiperistaltic agents and corticosteroids are not recommended. Various antimicrobials demonstrate potential efficacy in treating AAC in humans. Oral vancomycin is the most widely tested and is currently the treatment of choice. It achieves high concentrations in the feces and is very active against C. difficile in doses of 125-500 mg by mouth every six hours. Other potentially useful but inadequately tested antimicrobials include metronidazole (500 mg by mouth every eight hours) and bacitracin (25,000 units by mouth every six hours). Tetracycline has been employed with some success in nonspecific antibiotic-associated diarrhea, although it is as yet untested in humans with AAC and may induce diarrhea itself. Both miconazole and rifampin are highly effective against C. difficile in vitro but have not been evaluated in AAC. Anion-exchange resins bind the cytotoxin found in stools of patients with AAC. Cholestyramine has been used with variable response in oral doses of 4 g every six to eight hours. Since these resins may also bind vancomycin, resulting in lowered vancomycin concentrations in the stool, combination therapy should be used cautiously. With specific therapy directed against the toxin and aggressive supportive therapy, surgical intervention is rarely necessary. More recently, investigations have been directed at using bacterial preparations to suppress C. difficile by restoring the normal flora. The development of immunological agents (i.e., vaccines, toxoids, antitoxins) for the prevention or treatment of AAC would be a significant advance in therapy.

Anion Exchange Resins↗

PubMed1996

T-cell dysfunctions in hu-PBL-SCID mice infected with human immunodeficiency virus (HIV) shortly after reconstitution: in vivo effects of HIV on highly activated human immune cells.

The state of activation of the immune system may be an important factor which renders a host more receptive to human immunodeficiency virus (HIV) and more vulnerable to its effects. To explore this issue with a practical in vivo model, we developed a modified protocol of HIV infection in hu-PBL-SCID mice. First, we assessed the time course of activation of human peripheral blood lymphocytes (hu-PBL) in the peritoneal cavity of SCID mice. At 2 to 24 h after the intraperitoneal injection into SCID mice, there was a clear-cut increase in the percentage of hu-PBL expressing early activation markers (CD69), concomitant with the release of soluble intercellular adhesion molecule-1 (sICAM-1) and the soluble interleukin-2 receptor (sIL-2R) and with the accumulation of mRNAs for a number of human cytokines. At 2 weeks, virtually all of the hu-PBL expressed the memory phenotype (CD45RO) and HLA-DR antigens as well. Cells collected from the SCID mouse peritoneum at 2 and 24 h after transplantation were fully susceptible to in vitro infection with HIV type 1 (HIV-1) in the absence of either IL-2 or mitogens. The injection of HIV into hu-PBL-SCID mice at 2 h after reconstitution resulted in a generalized and productive HIV infection of the xenochimeras. This early HIV-1 infection resulted in a dramatic depletion of human CD4+ cells and in decreased levels of sICAM-1 (in the peritoneal lavage fluid) as well as of sIL-2R and immunoglobulins M and A (in the serum). Enzyme-linked immunosorbent assay and/or reverse transcriptase PCR analysis showed higher levels of IL-4, IL-5, and IL-10 in the HIV-infected animals than in control hu-PBL-SCID mice, while gamma interferon levels in the two groups were comparable. When we compared the current model of HIV-1 infection at 2 weeks after the intraperitoneal injection of the hu-PBL in the SCID mice with the model described here, we found that the majority of immune dysfunctions induced in the 2-h infection of the xenochimeras are not inducible in the 2-week infection. This supports the concept that the state of activation of human cells at the moment of the in vivo infection with HIV-1 is a crucial factor in determining the immune derangement observed in AIDS patients. These results show that some immunological dysfunctions induced by HIV infection in AIDS patients can be mimicked in this xenochimeric model. Thus, the hu-PBL-SCID mouse model may be useful in exploring, in vivo, the relevance of hu-PBL activation and differentiation in HIV-1 infection and for testing therapeutic intervention directed towards either the virus or the immune system.

Animals↗

PubMed2006

[Coronary artery plaque assessment using Volcano Therapeutics' Virtual Histology intravascular ultrasound and temperature guide wire].

OBJECTIVES: This study investigated the tissue characterization of human coronary artery plaque using Virtual Histology intravascular ultrasound (VH-IVUS) and temperature guide wire. METHODS AND RESULTS: Between August 2005 and December 2005, VH-IVUS examination and guide wire based measurement of coronary temperature were performed in 66 patients: 39 with stable angina pectoris (SAP), and 27 with unstable angina pectoris(UAP). Patients in the acute myocardial infarction with necrotic tissue and thrombus were excluded. After measurement of distal coronary pressure and coronary temperature, the following tissue types of atherosclerotic plaque were evaluated by VH-IVUS: fibrotic, fibro-fatty, dense calcium and necrotic core. Occurrence of fibro-fatty tissue was significantly higher in UAP patients than in SAP patients (17.4 +/- 7.0% vs 11.2 +/- 5.2%, p = 0.04), and coronary temperature was significantly higher in UAP patients than in SAP patients (0.08 +/- 0.05 vs 0.03 +/- 0.02 degrees C, p = 0.01). CONCLUSIONS: These results suggest that the combination of VH-IVUS analysis and measurement of coronary temperature may be able to predict the progression of lesions.

Aged↗

PubMed1998

Endolaryngeal high-frequency ultrasound.

High-frequency ultrasound can provide high-resolution imaging for diagnosing diseases of the head and neck. Over the last few years, a virtual technical evolution has led to the development of small and flexible ultrasound transducers with even greater anatomic resolution. The aim of the present study was to evaluate the efficacy of this new technique for imaging normal and altered anatomical structures of the endolarynx. Specially developed high-resolution, real-time ultrasound transducers (10 and 20 MHz) placed on the tip of endoluminal catheters were inserted into 20 autopsied larynges and five laryngectomy specimens. In a standardized examination process the endolarynx was analyzed in a real-time mode. Using this technique, exact 360 degrees cross sections of the larynx were obtained, demonstrating that it was possible to image the structures of the endolarynx with ultrasonography. Depending on the frequency used, all anatomical structures could be visualized up to a depth of 2 cm. In laryngeal cancer the depth of tumor as well as its relationship to the laryngeal framework could be clearly recognized. These findings suggest that this new endoluminal sonographic procedure represents a potentially important diagnostic tool in the assessment of laryngeal carcinoma.

Anatomy, Cross-Sectional↗

PubMedDate not supplied

Clinical utility of three-dimensional US.

Three-dimensional (3D) ultrasonography (US) is rapidly gaining popularity as it moves out of the research environment and into the clinical setting. This modality offers several distinct advantages over conventional US, including 3D image reconstruction with a single pass of the US beam, virtually unlimited viewing perspectives; accurate assessment of long-term effects of treatment; and more accurate, repeatable evaluation of anatomic structures and disease entities. In obstetric imaging, 3D US provides a novel perspective on the fetal anatomy, makes anomalies easier to recognize, facilitates maternal-fetal bonding, and helps families better understand fetal abnormalities. Three-dimensional pelvic US allows volume data sets to be acquired with both transvaginal and transabdominal probes. Viewing multiple 3D power Doppler US images in a fast cine loop has proved useful in angiographic applications. Three-dimensional prostate US can help make accurate volume assessments for dosimetry planning or for estimating prostate-specific antigen levels. In breast imaging, 3D US has the capacity to demonstrate lesion margins and topography, thereby helping differentiate benign from malignant masses. Three-dimensional US can also help determine the need for biopsy and help facilitate needle localization and guidance during biopsy. With recent advances in computer technology and display techniques, 3D US will likely play an increasingly important role in medicine.

Biopsy↗

PubMed2006

Development of the new group of indole-derived neuroprotective drugs affecting oxidative stress.

1. The role of oxidative stress, and accordingly uncontrolled reactive oxygen species generation/action, have been widely documented in a number of different neuronal pathologies. However, the concept of pharmacological interventions in prevention and therapy of oxidative stress-related diseases has not found adequate application in clinical practice. This may be due to the insufficient efficacy of drugs available, their unsuitable pharmacokinetics, side effects, toxicity, etc. 2. Based on stobadine, (--)-cis-2,8-dimethyl-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole, a well-known antioxidant, free radical scavenger, and neuroprotectant, it was attempted to develop new stobadine derivatives with improved pharmacodynamic and toxicity profiles, on applying molecular design, synthesis and adequate tests. Stobadine molecule was modified mostly by electron donating substitution on the benzene ring and by alkoxycarbonyl substitution at N-2 position. A total of >70 derivatives were prepared. 3. In a mice model of head trauma, some of the new stobadine derivatives administered i.v. immediately after the trauma, significantly improved sensomotoric outcome in the animals assessed 1 h later. Accordingly, decrease in brain edema was proved histologically as well as by brain wet weight assessment. 4. Putative neuroprotective action of the compounds was confirmed on rat hippocampal slices exposed to reversible 6 min hypoxia/low glucose by analysis of synaptic transmission in CA1 region neurons. Irreversible impairment of neurotransmission resulting from the hypoxia was significantly reduced by the presence of SMe1EC2, one of the new compounds, in concentration range 0.03-10.0x10(-6) mol l(-1). Both the neuroprotective and antioxidant effect of the compound closely resembled those of stobadine, melatonin, 21-aminosteroids, alpha-phenyl-tert-butylnitrone and others, all well-established antioxidants, except the range of effective concentrations was by 1-2 orders lower in SMe1EC2. 5. A remarkable antioxidant efficacy was observed in the new compounds in rat brain homogenates exposed to iron/ascorbate system by protection of lipids and creatine kinase against the oxidative impairment. A link between the neuroprotective and antioxidant/ scavenger properties in the compounds can be assumed. 6. Acute toxicity of some of the new pyridoindoles was diminished compared to stobadine. That might be due to the virtually full elimination of stobadine's undesired alpha (1)-adrenolytic activity attained by appropriate modifications of its molecule. 7. The new pyridoindoles extend the range of available neuroprotectants interfering with oxidative stress in neuronal tissue.

Animals↗

PubMed1999

Treatment of myeloma.

Survival for myeloma has improved from a median of 7 months in the 1950s to about 30 months today. Progress in chemotherapy has contributed a great deal to this improvement, although it may also, in part, reflect the improved treatment of infections, renal failure and hypercalcaemia as well as earlier diagnosis. For over 30 years, the gold standard of treatment has been oral melphalan and prednisolone, producing a clinical response in approximately 60% of patients and a median survival of around 36 months. Relapse is unfortunately inevitable in all but a handful and, for the majority, treatment can only hope to produce significant periods of remission with minimal treatment-related morbidity and mortality. Recently, improved results have been seen with the introduction of aggressive chemotherapy and bone-marrow transplantation. Marrow ablative therapies produce remissions in virtually all patients, with complete remissions in approximately 1/3. The best response is seen in those with a lower tumour burden, which will reduce the development of secondary resistance. Current treatment is moving towards an approach using sequential therapy. This involves induction chemotherapy with VAD or a similar regimen such as VAMP (vincristine, adriamycin and methylprednisolone), proceeding to high-dose therapy, often with some form of stem-cell rescue. This ensures minimal tumour burden prior to high-dose treatment as well as reducing graft infiltration, improving general performance status and allowing recovery of renal function. Relapse remains a problem, although the use of IFN may reduce this by prolonging the plateau phase. High-dose therapy should be given early, before prolonged use of alkylating agents induces stem-cell dysplasia, before significant complications arise from the myeloma, and before drug resistance is significant. Unfortunately, these treatments come at a price, in terms of increased treatment-related toxicity. There also remains uncertainty as to the extra benefits of high-dose treatment with marrow rescue over high-dose chemotherapy alone. We await the current MRC trial with interest. For a very few, there is the tantalising possibility of cure with allografting. For those in complete remission after first-line induction therapy, allogeneic bone-marrow transplantation offers the best hope of survival, but comes at a greatly increased risk of toxicity, and it is uncertain if it is superior to autografting for the majority of patients. It may soon be possible to identify those poor prognosis patients in whom an allogeneic transplant should be offered at an early stage. Candidate biochemical markers include serum beta 2 microglobulin, neopterin, IL-6, plasma cell labelling index, CRP or LDH and prognostic clinical features include IgD myeloma or stage III disease at presentation. Many patients will have primary refractory of relapsing disease in whom survival is short despite all current therapeutic modalities. They should therefore be considered for trials of newer agents, drug combinations and therapeutic interventions such as cytokine manipulation or gene therapy. The lack of effective, curative treatment options for patients with myeloma places great importance on effective palliation. While improving survival duration remains elusive in this condition, all possible efforts must be made to ensure quality of life is maximized.

Antineoplastic Agents↗

PubMed2005

Geometrical validation of intravascular ultrasound radiofrequency data analysis (Virtual Histology) acquired with a 30 MHz boston scientific corporation imaging catheter.

Recently, the plaque characterization field was explored with the use of the substrate (frequency domain analysis) rather than the envelope (amplitude or gray-scale imaging) of the intravascular ultrasound (IVUS) radiofrequency data. However, there is no data about the agreement of quantitative outcome between the two methods. The aim of this study was to assess the correlation and agreement between quantitative coronary ultrasound and the geometrical measurements provided by the spectral analysis of ultrasound radiofrequency data [IVUS-Virtual Histology (IVUS-VH), Volcano Therapeutics). Twenty-five patients were included in this study. The IVUS catheter used was a commercially available mechanical sector scanner (Ultracross 2.9 Fr 30 MHz catheter, Boston Scientific) covered with an outer sheath. IVUS-VH significantly underestimated lumen [relative difference (RD)=14.8+/-5.6; P<0.001], vessel (RD=14.1+/-4.8; P<0.001), and plaque (RD=11.5+/-10.8; P<0.001) cross-sectional areas (CSAs). Nevertheless, when adjusted for the ultrasound propagation delay caused by the sheath, relative differences of measurements were remarkably low (0.49%+/-6.3%, P=0.64 for lumen; 2.33%+/-4.6%, P=0.007 for vessel; and 4.2%+/-10.4%, P=0.005 for plaque CSA). These data suggest that the volumetric output of the IVUS-VH software underestimates measurements when acquired with a 30 MHz catheter. However, after applying a mathematical adjustment method for the ultrasound propagation delay caused by the outer sheath of the 30 MHz catheter, relative differences of direct measurements were negligible. These results suggest that ultrasound radiofrequency data analysis could provide, aside from precise compositional data, an accurate geometrical output.

Cardiac Catheterization↗

PubMed1996

[Indications for transmyocardial laser therapy].

In symptomatic endstage coronary artery disease after full medical therapy (antianginal drugs, betablockers and ACE-inhibitors) further therapeutical options both for the interventional cardiologist with little hope for improvement by PTCA, stent, rotablation and atherectomy and for the cardiac surgeon with bypass surgery and endarterectomy are not available by definition due to the diffuse arteriosclerotic vessel morphology. In those patients one can therefore consider transmyocardial laser therapy (TMR) as the ultimate treatment option. It then is primarily a palliative measure to reduce the patient's symptoms. Improving perfusion and prognosis remains the most important goals, however. TMR can be utilized as the only revascularizing treatment measure or in combination with CABG or PTCA. According to data from international registries, few controlled and several non controlled studies and our own registry in Marburg with now 101 patients improvement of angina and/or dyspnoea can be expected in more than 60% of patients with end stage coronary artery disease (CAD). The patient cohort comprises symptomatic individuals after CABG or multiple PTCAs or with diffuse CAD in diabetes mellitus or with most severe hypercholesterinemia. We consider these above mentioned criteria as the only validated criteria to enter patients with endstage CAD in our controlled study. Hypothetical options for treatment by TMR such as vasculopathies after heart transplantation, cardiomyopathies under the notion of a possible but not proven microangiopathy are not accepted in our institution at present. Before TMR all patients are assessed for their angina class according to the Canadian Cardiac Society (CCS I-IV)) and their exercise capacity according to the New York Heart Association classification (NYHA I-IV) and reassessed regularly after 3, 6 and 12 months. Thallium/Te MIBI scans at rest- and whenever possible at exercise as well as stress echocardiography are carried in the patients to assess symptomatic improvement, alterations in myocardial perfusion and functional efficacy by TMR. By intermediate analysis the 101 patients of our registry more than 60% of the patients had improved their angina class by at least one classe, some patients have improved perfusion as assessed by scintigraphy, which makes at present a trend but not yet a significant difference, whereas central hemodynamics and ejection fraction remained virtually unchanged in most patients reassessed after TMR. In our analysis mortality of the 101 TMR patients was assessed and plotted on Kaplan Meier survival curves. Mortality at 6 months was 11%. When compared to a historical group of patients with identical CCS and comparable NYHA classes, who were worked up in the manner of a case control study, the TMR mortality was marginally but not yet significantly lower than one would expect from these control patients with terminal CAD treated purely by medication: Their 6 months mortality was 14%. Remarkably but not unexpectedly patients with comparable CCS classes, who could still be treated by PTCA and/or CABG had a significantly lower 6 months mortality than TMR patients or patients on antianginal drugs only. The pathophysiological mechanisms for the symptomatic improvement by laser therapy are not yet fully understood. The 1 mm transmyocardial channels created by the CO2 laser have been postulated to permit perfusion from the ventricular cavity and to seek connection to capillaries and vessels present in the malperfused myocardium thus improving the perfusion by newly created connections and sinusoids from the ventricular cavity. Although there is clear evidence for the presence of open channels acutely and within a few days after TMR therapy little evidence in man is as yet available on the question whether the channels remain open in the long run and, if so, whether they can actually improve perfusion to a substantial degree...

Angioplasty, Balloon, Coronary↗

PubMed2006

Post-mortem tissue sampling using computed tomography guidance.

PURPOSE: Currently, in forensic medicine cross-sectional imaging gains recognition and a wide use as a non-invasive examination approach. Today, computed tomography (CT) or magnetic resonance imaging that are available for patients are unable to provide tissue information on the cellular level in a non-invasive manner and also diatom detection, DNA, bacteriological, chemical toxicological and other specific tissue analyses are impossible using radiology. We hypothesised that post-mortem minimally invasive tissue sampling using needle biopsies under CT guidance might significantly enhance the potential of virtual autopsy. The purpose of this study was to test the use of a clinically approved biopsy needle for minimally invasive post-mortem sampling of tissue specimens under CT guidance. MATERIAL AND METHODS: ACN III biopsy core needles 14 gauge x 160 mm with automatic pistol device were used on three bodies dedicated to research from the local anatomical institute. Tissue probes from the brain, heart, lung, liver, spleen, kidney and muscle tissue were obtained under CT fluoroscopy. RESULTS: CT fluoroscopy enabled accurate placement of the needle within the organs and tissues. The needles allowed for sampling of tissue probes with a mean width of 1.7 mm (range 1.2-2 mm) and the maximal length of 20 mm at all locations. The obtained tissue specimens were of sufficient size and adequate quality for histological analysis. CONCLUSION: Our results indicate that, similar to the clinical experience but in many more organs, the tissue specimens obtained using the clinically approved biopsy needle are of a sufficient size and adequate quality for a histological examination. We suggest that post-mortem biopsy using the ACN III needle under CT guidance may become a reliable method for targeted sampling of tissue probes of the body.

Biopsy, Needle↗

PubMed2006

In vivo plaque characterization using intravascular ultrasound-virtual histology in a porcine model of complex coronary lesions.

OBJECTIVE: To determine the accuracy of detection of different tissue types of intravascular ultrasound-virtual histology (IVUS-VH) in a porcine model of complex coronary lesions. METHODS AND RESULTS: Coronary lesions were induced by injecting liposomes containing human oxidized low-density lipoprotein into the adventitia of the arteries. IVUS-VH imaging was performed in vivo at 8.2+/-1.6 weeks after injection. A total of 60 vascular lesions were analyzed and compared with their correspondent IVUS-VH images. Correlation analysis was performed using linear regression models. Compared with histology, IVUS-VH correctly identified the presence of fibrous, fibro-fatty, and necrotic tissue in 58.33%, 38.33%, and 38.33% of lesions, respectively. The sensitivity of IVUS-VH for the detection of fibrous, fibro-fatty, and necrotic core tissue was 76.1%, 46%, and 41.1% respectively. A linear regression analysis performed for each individual plaque component did not show strong correlation that would allow significant prediction of individual values. CONCLUSIONS: In a porcine model of complex coronary lesions, IVUS-VH was not accurate in detecting the relative amount of specific plaque components within each individual corresponding histological specimen.

Animals↗

PubMed2000

MRI guided percutaneous abdominal biopsy in a closed magnet: assessment in an animal study.

MRI guided percutaneous abdominal biopsy was evaluated in an animal model, using a closed magnet and different types of needles. Thirty-six single pass biopsies were performed in 6 piglets with 6 types of MR compatible needles. Virtual targets of a diameter of 2 cm were drawn on the images of the right and left lobe of the liver and the upper and lower poles of both kidneys. FMPSPGR sequences were applied during an apnea of 19 to 23 seconds in axial, sagittal, coronal or axial oblique planes using a closed 1.0 T magnet and the body coil. Piglets were autopsied 1 hour after the procedure. Mean duration of the procedure was 16.9 (11-37) minutes; mean number of acquisitions per procedure was 5.9 (3-12); mean number of redirections of the needle was 0.6 (0-4). Pathological samples from the liver and kidneys of good quality were obtained in 22/36 (72.2%) cases. A subcapsular hematoma was observed in 18/24 (75.0%) cases of renal biopsies and in 1/12 (8.3%) of hepatic biopsies. No statistically significant correlation could be established between duration of the procedure and site of biopsy and between the type of biopsy needle and complication (p = 0.18 to 0.85). In conclusion, MRI guided percutaneous needle biopsy in the abdomen is a reliable technique in piglets using a closed magnet.

Abdomen↗