We studied 41 patients with clinically symptomatic ventricular tachycardia in the absence of coronary artery disease or left ventricular dysfunction to define the extent of right and left heart derangement and their relation to electrophysiologic and clinical data. Individual echocardiographic measurements as well as global assessment scores of the right and left heart demonstrated a wide spectrum of right heart echocardiographic abnormalities. There was much less variation in the left heart, with the majority of patients being close to normal. There was an association between the right heart score, the clinical presentation of arrhythmia, the response to programmed electrical stimulation, and the recurrence of arrhythmia (p < 0.05). Thus echocardiographic findings demonstrate the whole spectrum of right heart involvement in patients with apparent idiopathic ventricular tachycardia and can give insight into clinical history, arrhythmia inducibility, and prognosis.

Adolescent↗

PubMed1993

Determinants of inducible ventricular tachycardia in patients with clinical ventricular tachyarrhythmia and no apparent structural heart disease.

Thirty-seven patients with symptomatic ventricular tachyarrhythmia and no apparent structural heart disease were evaluated with multiple cardiovascular tests to establish the relationship between the results of programmed electric stimulation and other clinical and arrhythmia variables. Of 37 patients, 12 (32%) had inducible sustained ventricular tachycardia. Factors associated with the results of programmed electric stimulation included a history of ventricular tachycardia > or = 30 seconds requiring intervention for termination and global right heart abnormality documented by echocardiography. During treatment for a mean follow-up of 50 months, 29 patients did well, 6 patients had recurrences of major arrhythmia symptoms, 1 was lost to follow-up and 1 had a noncardiac death. Those patients with an adverse outcome were more likely to have inducible ventricular tachycardia. Thus certain clinical and echocardiographic data are associated with the results of programmed electric stimulation, which in turn have important prognostic value in this group of patients. Sustained ventricular tachycardia is unlikely to be induced in patients with no evidence of structural heart disease and clinical nonsustained ventricular tachycardia.

Adolescent↗

PubMed1993

Monte Carlo calculations of ion passages through brain endothelial nuclei during boron neutron capture therapy.

The Monte Carlo technique is used to examine the passage of ions from the (n, p) reaction in nitrogen and the (n, alpha) reaction in 10B through the nuclei of endothelial capillary wall cells of normal white matter. Contributions to the dose from different regions are evaluated, as is the distribution of doses to the nuclei for mean doses from 1 to 100 Gy. Calculation of mean dose to the nuclei is generalized for any neutron fluence and element concentration. The dose-averaged LETs for both reactions are found giving (for the particular conditions of the calculation); 60 keV/microns for the (n, p) reaction and 216 keV/micron for the (n, alpha) reaction in boron limited to the lumen, and 224 keV/micron for a uniform distribution of boron. From a consideration of 'minimal survival' and hit and dose distributions, evidence is presented which suggests that the RBE for the (n, alpha) reaction depends upon the distribution of the boron in the tissue, with the uniform distribution being less effective at cell killing than the boron restricted to the lumen for the same mean dose to the cell nuclei.

Boron Neutron Capture Therapy↗

PubMed1993

Dose modification factors in boron neutron capture therapy.

The effective treatment depth and therapeutic ratio in boron neutron capture therapy (BNCT) depend on a number of macroscopic dose factors such as boron concentrations in the tumor, normal tissue and blood. However, the role of various microscopic dose modification factors can be of critical importance in the evaluation of normal tissue tolerance levels. An understanding of these factors is valuable in designing BNCT experiments and the selection of appropriate boron compounds. These factors are defined in this paper and applied to the case of brain tumors with particular attention to capillary endothelial cells and oligodendrocytes.

Boron Neutron Capture Therapy↗

PubMed1993

Maximum therapeutic depth in thermal neutron capture therapy.

The effective treatment depth in boron neutron capture therapy with thermal neutrons depends on the beam aperture, heavy water concentration, boron concentrations in the tumor, normal tissue and blood, tolerance dose to normal tissue and the capillary dose modification factor. In this study a 15 cm aperture is used and the tolerance dose to normal tissue is evaluated to be 15 Gy. Human pharmacokinetic data are evaluated for BSH and D, L-BPA, the two compounds currently used in thermal BNCT. Results show that the average measured tumor to blood boron ratios and standard deviations are 1.4 (0.4) for BSH and 4.3 (1.8) for subcutaneous melanoma. Experimental dose-depth phantom results for the Musashi Institute of Technology reactor are used with expected boron concentrations to calculate the maximum therapeutic depth in the brain for a thermal neutron beam. For BPA, the subcutaneous melanoma boron concentrations are assumed for intracranial metastases, and no allowance is made for possible enhanced uptake in the dopamine and noradrenaline tracts. Results for BSH are enhanced by inclusion of the capillary dose reduction factor. Calculations show that for expected boron tumor to blood ratios, the modified advantage depth is about 4 cm and the maximum therapeutic depth is about 1.5 cm for both BSH and BPA. Typical heavy water ratios of 15% increase the treatment depth by 0.5 cm, but this is offset by the use of smaller beam aperture in practice.

Boranes↗

PubMed1993

Modern concepts of atrial fibrillation.

Atrial fibrillation (AF) is recognized as a common cardiac arrhythmia associated with significant morbidity and mortality. The mechanism of AF depends on the type, paroxysmal (P) AF is usually secondary to autonomic imbalance and chronic (C) AF is typically secondary to cardiovascular dysfunction. There is significant overlap as most patients with PAF will eventually develop CAF. Therapeutic considerations depend mostly on the clinical situation ranging from emergent electrical therapy for unstable patients to no therapy for asymptomatic patients. Most patients are mildly symptomatic from rapid heart rate (ventricular response) and benefit from drugs designed to create AV block. Anticoagulation is important additional therapy in order to prevent thromboemboli. Reversion of AF and maintenance of sinus rhythm would be the ideal goals of therapy except for the toxicity of available agents. As a result many patients would be best left in AF as the rhythm of choice.

Anti-Arrhythmia Agents↗

PubMed1992

TGF-beta blocks early but not late differentiation-specific gene expression and morphologic differentiation of 3T3 T proadipocytes.

Transforming growth factor-beta (TGF-beta) inhibits morphologic differentiation of BALB/c 3T3 T cells as well as other proadipocyte models. Our prior studies suggested that TGF-beta may act only during the early stages of differentiation induction. However, we did not determine whether TGF-beta was differentially effecting expression of any of the various differentiation-specific genes or if it could cause down-regulation of these genes in differentiated cells. Therefore, in the current study we tested the effects of exogenous TGF-beta (0.01-5.0 ng/ml) on morphologic differentiation and on differentiation-dependent gene expression (Northern and slot blot analyses) at various times during differentiation. When induced to differentiate, 3T3 T cells first undergo predifferentiation growth arrest and from this state molecular, biochemical, and morphological differentiation proceeds. Here it was found that when added prior to the onset of differentiation, TGF-beta was a potent inhibitor or morphologic differentiation as well as of the expression of differentiation-specific genes such as lipoprotein lipase (LPL) and glycerol-3-phosphate dehydrogenase (GPD). However, once morphologic differentiation began, TGF-beta was ineffective in blocking differentiation. In addition, exposure of fully differentiated cells to TGF-beta for up to 72 hours caused no decrease of differentiation-specific genes and even a 7-day treatment caused no morphologic dedifferentiation. Tumor necrosis factor also had no detectable effect on fully differentiated cells.

3T3 Cells↗

PubMed1992

Adjuvant metoprolol improves efficacy of class I antiarrhythmic drugs in patients with inducible sustained monomorphic ventricular tachycardia.

Inducible ventricular tachycardia frequently persists despite solitary class I antiarrhythmic drug therapy. To determine the effect of metoprolol as adjuvant therapy, 19 patients with clinical ventricular tachycardia with baseline inducible sustained monomorphic ventricular tachycardia and persistently inducible ventricular tachycardia despite class I drugs were evaluated. Eight of 19 patients (42%) became noninducible when metoprolol was added to class I drug therapy. Sixteen of 19 patients (84%) were harder to induce or noninducible on a regimen of adjuvant metoprolol therapy. In evaluating the clinical characteristics of the 19 patients, no significant differences were found between patients who were persistently inducible and those rendered noninducible. In evaluating the electrophysiologic characteristics, the group eventually rendered noninducible had a significantly shorter baseline induced cycle length (259 +/- 27 vs 305 +/- 53 msec). Combination class I drug and metoprolol therapy significantly lengthened the ventricular effective refractory period in both groups compared with baseline. The long-term follow-up was excellent in all patients remaining on metoprolol in the noninducible group. Therefore adjuvant metoprolol therapy creates a significant improvement in a number of patients with persistently inducible ventricular tachycardia despite class I drug therapy.

Adult↗

PubMed1992

Ionic biology and ionic medicine in cardiac arrhythmias with particular reference to magnesium.

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Calcium↗

PubMed1992

Local control of subcutaneous murine melanoma xenografts in nude mice by neutron capture therapy.

The systemic administration of enriched [10B]D,L-p-boronophenylalanine results in the selective uptake of boron by Harding-Passey melanoma xenografts in the nude mouse model. The boron-10 located in the tumour cells acts as a radiation sensitizer for thermal neutron irradiation. The nude mouse model can be successfully used to demonstrate that regression and local control of melanoma can be achieved by neutron capture therapy. Control is a manifestation of the high linear energy transfer radiation released after neutron capture by boron-10, and does not result from an equal fluence of neutrons alone. Histological examination of remnant tumour beds 300 days after treatment shows the presence of isolated melanoma cells. However, these cells are few in number and appear incapable of division.

Animals↗

PubMed1991

A total body nitrogen facility for paediatric use.

The design, calibration and evaluation of a facility for in vivo prompt gamma neutron capture analysis of total body nitrogen in children is described. The patient is scanned in both supine and prone positions, across a vertically collimated beam from a 1 GBq 252Cf fission source. Two NaI(T1) detectors are placed on either side of the patient, perpendicular to both the neutron beam and the scanning direction. The effective dose equivalent delivered to a child during an 840 s scan is approximately 0.14 mSv (QF = 10). Correction factors for nitrogen background (width-dependent), hydrogen background (1-4% of hydrogen gamma ray peak) and the differential attenuation of nitrogen and hydrogen gamma rays (width-dependent) can be applied to the measured nitrogen-to-hydrogen gamma ray counts ratio. By using the mass of hydrogen (based on body mass and fat mass) as an internal standard, the nitrogen mass can then be determined. Measurements with a urea-containing box phantom show that the current precision (CV) of the net nitrogen counts and of the nitrogen-to-hydrogen counts ratio is +/- 2.0% and +/- 1.5%, respectively. Using small anthropomorphic and other phantoms, estimation of the mass of nitrogen has a precision of +/- 1.4 to 5.4% and an accuracy of 97.1 to 101.5%.

Australia↗

PubMed1991

Nitrogen deposition in malnourished children with cystic fibrosis.

To determine the protein nutritional status of 21 malnourished children with cystic fibrosis (CF), total body nitrogen (TBN) was measured and the results were compared with 21 control subjects. CF patients demonstrated a lower TBN (P less than 0.001). When matched for height (n = 10) or bone age (n = 13), the CF patients still had a depressed TBN/height or TBN/lean body mass (P less than 0.05). To assess nitrogen deposition during nutritional rehabilitation, repeat TBN measurements were performed on the 21 CF patients. Nitrogen deposition ranged from -230 to 550 g/y and correlated with weight velocity (r = 0.78, P less than 0.001). Increased nitrogen deposition (greater than 150 g/y) was generally associated with normal height gain (height velocity SD score greater than -2.00) and weight gain (greater than 2.0 kg/y). Decreased nitrogen deposition was associated with poor weight gain but did not preclude normal linear growth. These data suggest an important role for TBN estimations in defining protein nutritional status in children and indicate that skeletal growth can continue in the presence of minimal nitrogen deposition.

Adolescent↗

PubMed1991

Monte Carlo study of thermal flux profiles and body correction factors for body protein measurements of obese subjects.

In previous calculations for Total Body Nitrogen measurements of children, the anterior/posterior thermal neutron flux profile with depth was found to be fairly flat after an initial rise. However, for obese adults significant variations are found in the flux profile with the central flux value being as low as 20% of the peak value. The significance of these flux variations is examined. Correction factors are calculated for the varying attenuation of the nitrogen and hydrogen photons by a range of obese bodies. The calculations included the effect of the thermal flux profile as well as that of an outer layer of low nitrogen content adipose tissue. The bodies are assumed to have a homogeneous hydrogen content. A study of four obese body models with varying sex and fat content shows that the correction factors do not vary much between males and females. This is surprising since the female models are assumed to have a surface fat layer twice as thick as for the male models. The correction factors are found to be only slightly sensitive to the thermal flux variations with depth.

Adipose Tissue↗

PubMed1990

Epithermal neutron capture therapy: a new modality for the treatment of glioblastoma and melanoma metastatic to the brain.

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Animals↗