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Determination of the severity of coronary artery disease (CAD) by single photon emission computed tomography (SPECT) imaging has previously been shown to have greater sensitivity, specificity, and accuracy when performed with pharmacologic stress using dobutamine than by standard dose dipyridamole (SDD) or exercise stress testing (EST) prior to SPECT imaging. The use of lung to heart (L:H) ratios has been shown to be valuable in determining the presence or absence of left main (LM) or triple vessel (3V) CAD. No such work has been previously reported for dobutamine. Twenty-one patients were studied using dobutamine (n = 7) or EST (n = 14). These results were compared with results from Part II of this series of studies using high-dose dipyridamole (HDD) pharmacologic stress. In this study, patients underwent L:H ratio analysis following injection of 3 mCi of Tl-201, this provides sufficient time for thallium clearance from the blood pool. Results of the L:H ratios were compared with the results of coronary arteriographic (CA) evaluation. Patients who were "stressed" via EST demonstrated statistically greater (p </= 0.001) L:H ratios in patients with LM/3V CAD when compared with patients who had 0-2 significantly stenosed coronary arteries. Patients stressed with dobutamine demonstrated lower L:H ratios (p = NS) in patients with LM/3V CAD than was seen for patients with 0-2 V CAD. Patients stressed with dobutamine had statistically (p </= 0.05) lower L:H ratios than did similar patients stressed with EST. Increased L:H ratios following EST and HDD, as shown previously in Part II of this series, provide excellent markers for LM/3V CAD following Tl-201 injection. The presence of "normal" L:H ratios in patients with LM/3V CAD following dobutamine stress may suggest the presence of "stunned" or "hibernating" myocardium. The presence of "decreased" L:H ratios following dobutamine after HDD or EST has already shown an increased L:H ratio, might suggest a marker for myocardial viability that deserves further investigation.
Determination of the severity of coronary artery disease (CAD) by single photon emission computed tomography (SPECT) imaging has previously been shown to have greater sensitivity, specificity, and accuracy when performed with pharmacologic stress using high-dose dipyridamole (HDD), than by standard dose dipyridamole (SDD) or exercise stress (EST) prior to SPECT imaging. The use of lung-to-heart (L:H) ratios has been shown to be valuable in determining the presence or absence of left main (LM) or triple vessel (3V) CAD. Fifty-four patients were studied; HDD (n = 40) or EST (n = 14) was used for the study. These patients underwent L:H ratio analysis, in which anterior views were used 5-10 minutes after the injection of 3 mCi of T1-201. Results of the L:H ratios were compared with the diagnosis of epicardial CAD, as determined by coronary (CA) arteriography. Patients who were "stressed" using either HDD or EST demonstrated statistically greater (p < 0.001) L:H ratios if they had LM/3V CAD when compared with patients who had 0-2 significantly stenosed coronary arteries. Though L:H ratios were greater when HDD pharmacologic stress was used, there was no statistical (p = NS) differences between the two groups. Increased L:H ratios with HDD and EST provide excellent markers for LM/3V CAD using T1-201 imaging. Coupled with previously reported SPECT data, the use of HDD shows promise for increasing the diagnostic accuracy of SPECT imaging.
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BACKGROUND: Heel-pad stiffness is an important parameter in clinical assessments of the lower limb and is usually quantified by the slope of the force-deformation curve. However, the data produced is affected by the geometry of the heel, thus making inferences about tissue behaviour difficult. METHOD: With the use of finite element analysis the aim of this study is to explore the possibility of expressing heel-pad stiffness in terms of stress-strain data. An axisymmetric, non-linear and time-dependent representation of the heel was created. The material model, incorporating non-linearity and viscoelasticity, was based on a series of experiments involving healthy, cadaveric specimens and loading at different loading rates (0, 175 and 350 mm/s). The conditions of an in vivo study were then replicated and stress-strain data of the model were compared. Good agreement was achieved (error <5%) at higher strains (>0.2). Probe diameter, loading rate and heel-pad thickness were then varied and heel-pad stiffness, expressed in terms of both force-deformation and stress-strain characteristics, reported. FINDINGS: In terms of the force-deformation characteristics, thin heels are consistently stiffer than thick heels. In terms of stress-strain characteristics, thicker heels are stiffer than thin heels using small probes whereas thinner heels are stiffer than thick heels using large probes. It was possible to predict stress-strain data of the heel-pad that are least-dependent of heel-pad thickness using large probes and slow-rising loads. INTERPRETATION: It is suggested that stress-strain curves derived from large probes under slow loads would provide the most robust and standardized measure of heel-pad stiffness.
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Native forms of asparaginase stem from different biological sources. Previously reported data from children treated with Erwinase showed significantly lower trough levels and pharmacokinetic dose intensity than after E. coli-derived preparations. Hence, schedule optimization was initiated to achieve relevant serum activities. 21 children on reinduction therapy received Erwinase on Mondays, Wednesdays and Fridays for 3 weeks (9 x 20000 IU/m2 i.v.) instead of 4x 10 000IU/m2 of E. coli asparaginase (twice weekly for 2 weeks). Asparaginase trough activities were measured as the primary parameter, targeting 100-200 IU/I after 2 d and >50 IU/l after 3 d. Concurrently, asparagine trough concentrations were monitored. The mean trough activity was 156+/-99 IU/l, with 2/108 samples showing no detectable activity. Regarding trough levels per individual (three or more measurements/patient), means ranged from 52+/-29 to 276+/-114 IU/l (20 patients, 106 samples), with nine, six, and five children inside, below, and above the target range, respectively. The mean 3 d trough activity was 50+/-39 IU/l (20 patients, 51 samples). In 11 of these samples no activity was measurable. Mean trough activities calculated per individual ranged from < 20-84+/-30 IU/l (14 patients, 42 samples) with seven children below the target limit of 50 IU/l and asparagine concentrations <0.2 - 1.5microM. We concluded that an increased dose of 9x20000 IU/m2 of Erwinia asparaginase within 3 weeks resulted in a pharmacokinetic dose intensity comparable to former observations made with 4 x 10 000IU/m2 of the E. coli product Crasnitin which is no longer marketed. High interindividual variability and the phenomenon of 'silent' inactivation necessitate monitoring wherever possible.
The effect of baseline drug resistance mutations on response to zidovudine, lamivudine, and ritonavir was evaluated in zidovudine-experienced persons infected with human immunodeficiency virus type 1 (HIV-1). Presence of the K70R mutation was associated with significantly higher plasma HIV-1 RNA levels at baseline. However, presence of resistance mutations did not affect the increase in plasma HIV-1 RNA during a 5-week drug washout, nor was there any effect on first-phase virus decay rates after initiation of therapy or on the probability of having plasma HIV-1 RNA levels <100 copies/mL at week 48. Polymorphisms at protease codons 10, 36, and 71 were associated with significantly faster second-phase decay rates. Suppression of plasma HIV-1 RNA despite presence of zidovudine resistance mutations implies that the presence of these mutations does not preclude a durable response to treatment with a potent 3-drug regimen.
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The human bocavirus (HBoV) was recently isolated from respiratory tract samples. Within a study collective of children with severe lower respiratory tract disease, the patients testing positive for HBoV (12.8%) had a higher rate of underlying cardiopulmonary disease. Viral loads in respiratory tract specimens varied from 10(2) to 10(10) genome equivalents/ml.
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We analyze our experience in 175 patients with transitional bladder cancer for whom radical cystectomy was indicated. Patients were divided into three groups: one group was managed with radical cystectomy only and the other two with pre-operative radiotherapy: long-term approach and short-term approach. No significant differences have been observed when comparing current survival rate and disease-free intervals of all three groups. It can be deduced from our series that, by the scarce number of local recurrences observed, there is no other measure to be added to surgery directed to improve the tumour's local management. Most metastasis were diagnosed within 18 months after cystectomy. 58.4% patients presented bone dissemination. The risk of distant dissemination increases with the extent of vesical wall invasion, degree of anaplasia and presence of positive glands. The gland stage is not necessary for the metastasis to be present. Death's ratio with distant dissemination is significantly lower in the group managed Without pre-operative radiotherapy than in the others. Of the 11 patients where no tumour was observed in the cystectomy piece, 2 developed metastasis, indicating that this was already present before bladder extraction. Management of patients with infiltrating++ bladder cancer is complex, but no efforts should be spared to advise the most appropriate approach for each particular case. Chemotherapy plays an unquestionable role among the procedures we have to control, since most patients' deaths happen within two years after local-regional treatment of the primitive tumour and nearly all of them as a consequence of metastasis. Cytostatic agents are the only effective therapy for distant dissemination. We believe that every patient with a cancer extended to the perivesical fat or with dissemination to regional glands, whichever the stage, should be treated with chemotherapy after extirpation of the bladder, and starting as early as the patient's general status would allow it.