Assessment of renal viability by high-field phosphorus-31 magnetic resonance spectrometry.
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Biomedical subjects
Publications and source records attributed to S Pomer.
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Noninvasive investigation of renal metabolic changes is possible with 31P-MR, which is characterized by the determination of amounts of "free" phosphorus metabolites and intracellular pH and the possibility of measuring enzyme kinetics by the 31P-MR magnetization transfer method. 31P-MR has been extensively used to monitor such alterations in response to kidney ischemia, in which the ratios of anorganic phosphate to ATP and phosphomonoesters change drastically. The stages of ultrastructural ischemic renal damage can already be accurately classified with reference to a scale of 31P-MR-spectrum-derived renal function predictors. The recent application of MR high-resolution imaging may allow further improvement of organ viability assessment. The clinical use of combined MR imaging and spectroscopy is an essential and imminent step.
In a prospective study we investigated the association of kidney graft rejection with pre- and posttransplant B cell responses in vitro after stimulation with pokeweed mitogen, Staphylococcus aureus Cowan I (SAC I), or donor lymphocytes. B cell differentiation was assessed in a reverse hemolytic plaque assay. Elevated pretransplant PWM- or SAC I-stimulated B cell responses were found to define patients with a high incidence of rejection episodes in the first 30 days posttransplant (P less than 0.005 and P less than 0.05, respectively). Elevated pretransplant donor cell-stimulated B cell responses were associated with a high risk of irreversible rejection (P less than 0.005). A posttransplant rise in donor cell-stimulated B cell responses was associated with an increase risk of a subsequent rejection crisis (P less than 0.05). Our data suggest that patients at risk of early rejection may identified by pretransplant testing of B cell responses.
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In order to evaluate the possible differences in response to two currently preferable inotropic-vasodilator drug combinations, the hemodynamic effects of automated infusions of nitroprusside-dobutamine and nitroprusside-dopamine were studied in two clinically similar groups of patients with low-output syndrome after aorto-coronary bypass surgery. Nitroprusside, when infused in combination with dopamine, was effective in lowering filling pressures of both ventricles and systemic and pulmonary arterial pressures reflecting the reversal of deleterious rise of these parameters including determinants of myocardial oxygen consumption (mean arterial pressure rate by +6%, heart rate by +20%) caused by dopamine (6 micrograms/kg/min) infused alone. The combination of the more cardioselective catecholamine dobutamine with nitroprusside brought about similar increase in cardiac output by 50%, but derived its hemodynamic efficiency from the sum of separate effects of components and produced less in the way of elevation of determinants of oxygen consumption. Dobutamine when infused alone (6 micrograms/kg/min) has not affected systemic and pulmonary arterial pressures and stroke index rose more markedly (+9%) as a result of more moderate heart rate increase (+13%). Nitroprusside contributed in an additive manner to the achieved overall reduction of SVR and PVR by 43% and 50%, resp., the automated infusion being helpful in maintaining these values within close tolerances.
In low-output cardiac failure with hypertension developing early after aortocoronary surgery, the currently preferred vasodilators nitroglycerin and nitroprusside proved to be equally successful and safe for the closed-loop control of mean arterial pressure. With NP- and NTG-induced MAP reduction to the present level of 80 mm Hg cardiac index increased similarly from 2.0 +/- 0.35 to 2.4 +/- 0.3 l/min/m2 (p less than 0.05) and from 1.9 +/- 0.29 to 2.2 +/- 0.26 l/min/m2 (p less than 0.05), respectively. Once adequate blood pressure fall was obtained, the addition of dobutamine at 6 micrograms/kg/min resulted under maintenance doses of NP and NTG averaging 1.6 +/- 0.4 and 4.6 +/- 1.8 micrograms/kg/min, respectively. A further improvement of cardiac performance manifested itself by cardiac index rise to 3.4 +/- 0.4 l/min/m2 (p less than 0.005) and 3.3 +/- 0.3 l/min/m2 (p less than 0.001), respectively. The NP-Db and NTG-Db regimens induced comparable reductions of rate - pressure-products reflecting a decrease of myocardial oxygen demands and facilitation of myocardial work.
In the study of hemodynamics of hypertensive patients with low-output syndrome after open-heart surgery (the closed loop control of mean arterial pressure with nitroprusside, n = 14), evidence was obtained that the baseline SVR is a valuable index for predicting the response to vasodilation. Patients with markedly elevated SVR (n = 11) (1800 dyn. s. cm-5) responded favorably to vasodilation with SVR fall (from 2300 +/- 500 dyn X cm-5 to 1400 +/- 300 dyn X cm-5, p less than 0.005, -37%), cardiac index rise (from 2.1 +/- 0.3 to 2.4 +/- 0.4 l/min. m2, p less than 0.05 + 14%), or stroke volume index elevation (from 23.4 to 26.7 ml/m2, p less than 0.05, +14%). In patients with slightly raised SVR close to the normal range a mild SVR reduction (by 10%) occurred but no cardiac index increase with vasodilation alone. These patients derived their hemodynamic benefit from a combination of NP with preload augmentation and possibly direct inotropic stimulation. By assessing SVR before and during treatment with nitroprusside we were able to monitor more closely the course of automated afterload reduction and provide an additional important parameter for this regulation.
Sixteen patients with severe intractable haemorrhagic cystitis following radiotherapy, two of them with bleeding tumours, were treated surgically by cutaneous ureterostomy with or without contralateral nephrectomy. They had undergone various forms of conservative treatment and were treated by surgery only when conservative therapy had failed. In these poor risk patients a cutaneous ureterostomy was employed as a lesser procedure than an ileal loop. Of the 16 who underwent urinary diversion 11 were completely free of haemorrhage and three continued to have slight intermittent haematuria.
Our experience with the urinary diversion especially the end cutaneous ureterostomy with or without contralateral nephrectomy as the last resort option to control the otherwise intractable life threatening bladder post-irrediation hemorrhage is the subject of this study. Among our patients who have undergone various forms of conservative treatment for severe hemorrhagic cystitis following radiotherapy, 17 had to be treated surgically. Of the 17 who underwent urinary diversion 15 responded favourably and 12 were completely free of bleeding. 3 experienced temporary symptomatic relief. It was the underlying disease however, that determined finally the fate of these patients.
The diagnosis and management of 12 patients with spontaneous urinary extravasation due to ureteral calculous obstruction are described. Contrary to the "frank" rupture most cases can be managed without surgical intervention. The presistence of extravasation must be the reason for tumour exclusion. The renal fibrolipomatosis was seen as the possible late result of the extravasation.
The hypertension immediately after open heart surgery for coronary heart disease was chosen to evaluate the suitability of computer-controlled infusion sodium nitroprusside, to improve the circulatory state in heart failure by reducing the impedance to the left ventricular ejection. Sodium nitroprusside produced a prompt reduction of MAP to a preset level and a rise in cardiac index from an average of 2.1 +/- 0.3 to 2.4 +/- 0.4 when infused alone and to 3.1 +/- 0.5 1/min m2 (p less than 0.05, + 48%) after volume was infused to maintain LAP at a constant level to eliminate the effects of preload. The rise in cardiac index was associated with marked decrease in systemic vascular resistance from 2260 +/- 530 to 1415 +/- 280 and 1130 +/- 1130 +/- 270 dyns (p less than 0.005, 63%) respectively. The initial values of SVR correlated well with the fall of SVR (r = 0.78). Our results suggest that systemic vascular resistance is a strong indicator of the vascular responsiveness to vasodilation, the computer-controlled infusion of sodium-nitroprusside being suitable for the "titration" of the high systemic vascular resistance.
The hepatitis C-virus (HCV) is the main etiologic agent of posttransfusion hepatitis (PTH). Most patients depending on hemodialysis need transfusion of blood before kidney transplantation. Of 272 patients after kidney transplantation, 27 (10%) were found to be anti-HCV-ELISA-positive (HCV-Antibody-ELISA, Ortho Diagnostics). The antibodies could be neutralized by HCV C-100-3 antigen. Eight of 22 patients (36%) who had more than one kidney transplantation were classified anti-HCV positive [30% (8/27) of all anti-HCV positive patients]. The number of transfused blood units ranged from 0 to 99 BU. Receiving more than one kidney graft or the transfusion of more than 5 units of blood increased the risk for HCV infection 3.5 or 4.1 times, respectively, compared with one transplantation or less than 5 units of blood. No significant interactions were seen between these two variables. Of the anti-HCV positive patients, 48% were anti-HBc negative as well as HBs-antigen negative, 52% were anti-HBc positive.
We have used the tetracycline (tet)-regulated system as described previously to evaluate the applicability of controlled gene expression in cancer gene therapy. As a model gene, we used the human interleukin-2 (IL-2) gene, which has been placed under the transcriptional control of the tetO/promoter. Human melanoma cells were transduced by two modified retroviral tet vectors containing the transactivator regulatory unit and the IL-2 gene driven by the tetO/promoter, respectively. In the absence of tet, IL-2 expression in the target cells was stable over several months. IL-2 production was in the range of 40 U/10(6) cells/24 hours. A fine tuning of IL-2 expression could be achieved by culturing the transduced cells with increasing doses of tet, whereby a concentration of 500 ng/mL tet in the culture medium abrogated IL-2 expression. Most importantly for clinical application, IL-2 expression by the transduced melanoma cells could also be regulated in vivo. When nu/nu mice were inoculated with the transduced tumor cells, they failed to develop tumors. Instead, the inhibition of IL-2 expression in the transduced tumor cells by oral administration of tet led to subcutaneous tumor growth; this growth rate was comparable with the growth rate of subcutaneously inoculated untransduced parental cells. The finding demonstrates the applicability of the tet-regulated system in cancer gene therapy.