Nephrectomy as a component of systemic treatment for renal cell carcinoma patients.
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Biomedical subjects
Publications and source records attributed to C Porta.
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Hydrochlorothiazide (HCTZ) was shown to inhibit the transepithelial NaCl transport and the apical Na(+)-Cl- symport and to depolarize the apical membrane potential in the rabbit gallbladder epithelium. The depolarization was likely related to the opening of a Cl- conductance. To better understand whether an apical Cl- leak is involved in the mechanism of action of HCTZ, the transapical Cl- backflux was measured radiochemically by the washout technique. The gallbladder wall, pretreated with pronase on the serosal side to homogenize the subepithelium, was loaded with 36Cl- on the luminal side; mucosal and serosal 36Cl- effluxes (Jm, Js) were then measured every 2 min. The pretreatment with pronase did not alter the membrane potentials and the selectivity of the epithelium. Under control conditions and the tissue in steady-state, Jm and Js time courses were each described by two exponential decays (A, B); the rate constants, kA and kB, were 0.71 +/- 0.03 and 0.16 +/- 0.01 min-1, respectively, and correspondingly the half-times (tA1/2, tB1/2) were 1.01 +/- 0.05 and 5.00 +/- 0.44 min (n = 10); these parameters were not significantly different for Jm and Js time courses. Js was always greater than Jm (Js/Jm = 2.02 +/- 0.22 and 1.43 +/- 0.17 for A and B decays). Under SCN- treatment in steady-state conditions, both Jm and Js time courses were described by only one exponential decay, the component B being abolished. Moreover tA1/2 was similar to that predictable for the subepithelium. It follows that it is the component B which exits the epithelial compartment. Based on the intracellular specific activity and 36Cl- JBm at 0 min time of the washout experiment, the cell-lumen Cl- backflux in steady-state was calculated to be equal to about 2 mumol cm-2hr-1, in agreement with the value indirectly computable by other techniques. The experimental model was well responsive to different external challenges (increases in media osmolalities; luminal treatment with nystatin). HCTZ (2.5 x 10(-4) M) largely increased 36Cl- JBm. The increase was abolished by luminal treatment with 10(-4) M SITS, which not only brought back the efflux time courses to the ones observed under control conditions but even increased Js/Jm of the cellular component, an indication of a reduced JBm. It is concluded that HCTZ opens an apical, SITS-sensitive Cl- leak, which contributes to dissipate the intracellular Cl- accumulation and to inhibit the NaCl transepithelial transport.(ABSTRACT TRUNCATED AT 400 WORDS)
This study was aimed at assessing the efficacy of allopurinol mouthwashes in the treatment of 5-fluorouracil-induced stomatitis. A randomized double-blind, placebo-controlled trial was thus designed to test its efficacy to treat oral mucositis in advanced cancer patients receiving 5-fluorouracil-containing chemotherapy. There were 44 patients randomized to receive allopurinol mouthwashes, or placebo, as soon as mucosal lesions were observed during any treatment cycle. Stomatitis was evaluated at the end of each 5-day treatment cycle. Allopurinol mouthwashes resolved stomatitis in 9 of 22 treated patients (40.9%), and diminished its intensity in 10 more patients (45.4%); stomatitis resolved completely in none of the 22 patients, and partially in 3 patients in the placebo group (p < .001 by chi 2 test). Duration of symptoms was also significantly different between the two groups (median: 4 days for the allopurinol group, 7.5 days for the control group; p < .0005 by Student's t-test). In conclusion, our results suggest that allopurinol mouthwashes can be effective to treat 5-fluorouracil-induced stomatitis.
Testicular cancer and Hodgkin's disease are two malignancies sharing many epidemiological similarities, including age class and geographical distribution. However, the association of these tumours in the same patient is an exceptional event; to date, only 14 metachronous and three synchronous cases have been described in the literature. We report on a case of testicular seminoma and Hodgkin's lymphoma association, with the additional occurrence, nearly 20 years later, of a colon carcinoma.
Among all the patients treated by the Italian Cooperative Group for TTP, we retrospectively reviewed the results obtained using vincristine (VCR) in 8 TTP patients (4 men and 4 women, average age: 39.25 years, range: 23-48) who did not respond to combined apheretic and pharmacologic treatment. All patients, after failing to respond to treatment, were started on VCR at the dose of 2 mg, i.v., once a week. Despite this treatment, 4 patients (50%) died 1, 7, 12 and 25 days after the first VCR dose, respectively. The other 4 patients who received VCR achieved complete remission 24, 30, 40 and 50 days from the beginning of the treatment. Total doses of VCR ranged from 2 to 6 mg in the decreased group, and from 6 to 14 mg in the cured patients. In our experience, VCR is a promising agent to treat TTP patients resistant to conventional plasma-exchange and pharmacologic therapy.
The aim of this study was to establish whether a preoperative evaluation of cerebral haemodynamic reserve, carried out by means of transcranial Doppler and single photoemission computed tomography with a provocative test (acetazolamide) is able to select those patients who require carotid shunting to avoid cerebral ischaemia during clamping. All patients were monitored during operation by means of somatosensitive evoked potentials. Those patients who required shunting because of abnormal evoked potentials were also those who had a poor cerebral reserve with a perfusion and velocity increase below 15%. Only one neurological deficit developed in patients who were not shunted.
We treated 13 Hairy Cell Leukemia patients with rIFN a 2b. In case of complete/partial response, the patients were submitted to maintenance treatment, while, in case of minimal/no response, a second induction cycle was administered, followed by a maintenance one. The patients were followed, on an outpatients basis, for 18 months at least, obtaining a 100% overall response rate; one patient had complete response, 7 had partial response, and 5 only minimal response. Six patients (46%) relapsed an average of 13 months after the end of the treatment. The utility of a maintenance therapy is discussed.
We report the results of a phase III trial in which we compared 5-fluorouracil (5-FU) to 5-FU and folinic acid (FA) in 150 previously untreated metastatic colon cancer patients. Patients were randomized in the ratio of 1:2 to receive 5-FU (370 mg/m2, i.v., for 5 days) in arm A or equidose 5-FU plus FA (200 mg/m2, i.v., for 5 days) for arm B, each cycle being repeated every 4 weeks. Five of 49 evaluable arm A patients (10.2%) and 31 of 97 arm B (31.9%) achieved a complete or partial response (p < or = 0.01). Median survival time of arm A patients was 6 months (mean: 6.18), while it was 8 months (mean: 9.01) for arm B cases (p < or = 0.05). In conclusion, our data indicate that FA can enhance 5-FU activity and that this combination is an effective palliative treatment for metastatic colon cancer patients.
Even though plasma-exchange (PE), either alone or combined with cortisone or platelet anti-aggregating substances is the treatment of choice for TTP, 10-15% of patients is resistant to treatment. Since immunoglobulin (IgG) infusion was reported to cure the clinical symptoms of PE-resistant TTP, and vincristine (VCR) has been recently successful in treating TTP, we reviewed the results obtained with both drugs in 20 PE-resistant patients. Of 12 patients receiving IgG and 8 receiving VCR, 3 (25%) and 4 (50%), respectively, achieved complete remission. Even though no conclusions can be drawn from such results, if complete remission can be achieved in a however small number of PE-resistant patients, the use of these drugs is suggested as a salvage treatment for TTP.
Behçet's disease is a chronic, heterogeneous, multisystem disorder caused by a vasculitis involving arterial and venous vessels of all sized. In 1990, a new set of diagnostic criteria has been proposed as a guide to diagnosis of Behçet's disease, requiring the presence of oral ulcerations plus two of the following symptoms or signs: genital ulcerations, characteristics eye lesions, typical skin lesions, and a positive pathergy test. Nevertheless, both clinic and pathologic diagnosis of Behçet's disease remains sometimes very difficult. Diagnostic procedures and therapeutic implications in a case of Behçet's disease are reported and discussed.
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Fifteen patients with chronic obstruction of leg arteries (mean length: 6 cm) were treated with the Kensey catheter and then with PTA. In 11 cases the procedure was successful (74%) and in 2 it was interrupted--in one case for dissection and in the other for vessel perforation. Two maneuvers, after dissection, were ended with PTA and stent placement (overall success rate: 87%). Emergency surgery was never needed. In the cases solved with the Kensey catheter, the cumulative patency rate was 51% at 6, 12 and 24 months. The Kensey catheter did not improve the results of conventional PTA, which means its role is complementary to that of PTA and an alternative to more expensive laser systems, if PTA fails.
The aim of this study is to establish whether a preoperative evaluation of the Cerebral Hemodynamic Reserve, carried out by means of transcranial Doppler and SPECT with provocative test (acetazolamide) can single out those patients who, because they are supplied with a poor cerebral reserve, are truly in need of intraoperative shunting after carotid clamping. All patients were intraoperatively monitored by means of Somato Sensitive Evoked Potentials (SSEPs). Those patients who were shunted due to abnormalities in SSEPs were also those who showed a perfusion and velocity increase below 15%, and therefore supplied, in our opinion, with a scanty cerebral reserve. No, but one, neurological deficit appeared on awakening in patients who were not shunted.
The aim of this study is to present a relatively rare case of paradoxical arterial embolism, found in a patient who was sent to us for serious pulmonary embolism. Taking into account that the foramen ovale, despite being functionally competent, remains anatomically patent in 30% of the adult population, we cannot neglect the possibility of a paradoxical embolism, in the presence of a sudden embolic limb ischemia unless heart pathology or aortic lesions can be held responsible. Furthermore it must not be forgotten that deep venous thrombosis in the lower limbs or in the pelvic plexus may go unobserved on a purely clinical evaluation.
Biological processes frequently require the formation of multi-protein or nucleoprotein complexes. Some of these complexes have been produced in homogeneous form, crystallized, and analysed at high resolution by X-ray crystallography (for example, see refs 1-3). Most, however, are too large or too unstable to crystallize. Individual components of such complexes can often be purified and analysed by crystallography. Here we report how the coordinated application of cryoelectron microscopy, three-dimensional image reconstruction, and X-ray crystallography provides a powerful approach to study large, unstable macromolecular complexes. Three-dimensional reconstructions of native cowpea mosaic virus (CMPV) and a complex of CPMV saturated with a Fab fragment of a monoclonal antibody against the virus have been determined at 23 A resolution from low-irradiation images of unstained, frozen-hydrated samples. Despite the nominal resolution of the complex, the physical footprint of the Fab on the capsid surface and the orientation and position of the Fab have been determined to within a few ångstroms by fitting atomic models of CPMV4 and Fab (Kol)5 to reconstructed density maps.
Transepithelial fluid transport was measured gravimetrically in rabbit gallbladder (and net Na+ transport was calculated from it), at 27 degrees C, in HCO(3-)-free bathing media containing 10(-4) M acetazolamide. Whereas luminal 10(-4) M bumetanide or 10(-4) M 4-acetamido-4'-iso-thiocyanostilbene-2,2'-disulfonate (SITS) did not affect fluid absorption, 25 mM SCN- abolished it; hydrochlorothiazide (HCTZ) in the luminal medium reduced fluid absorption from 28.3 +/- 1.6 (n = 21) to 8.6 +/- 1.6 microliters cm-2 hr-1 (n = 10), i.e., to about 30%. This maximum effect was already obtained at 10(-3) M concentration; the apparent IC50 was about 2 x 10(-4) M. The residual fluid absorption, again insensitive to SITS, was completely inhibited by SCN- or bumetanide. Cl- influx at the luminal border of the epithelium, measured under the same conditions and corrected for the extracellular space and paracellular influx, proved insensitive to 10(-4) M bumetanide, but was slowly inhibited by 10(-3) M HCTZ, with maximum inhibition (about 54%) reached after a 10-min treatment; it subsequently rose again, in spite of the presence of HCTZ. However, if the epithelium, treated with HCTZ, was exposed to 10(-4) M bumetanide during the measuring time (45 sec), inhibition was completed and the subsequent rise of Cl- influx eliminated. Intracellular Cl- accumulation with respect to the predicted activity value at equilibrium decreased significantly upon exposure to 10(-3) M HCTZ, reached a minimum within 15-30 min of treatment, then rose again significantly at 60 min. Simultaneous exposure to HCTZ and bumetanide decreased the accumulation to a significantly larger extent as compared to HCTZ alone, already in 15 min, and impeded the subsequent rise. Intracellular K+ activity rose significantly within 30 min treatment with HCTZ; the increase proved bumetanide dependent. The results obtained show that Na(+)-Cl- symport, previously detected under control conditions, is the HCTZ-sensitive type; its inhibition elicits bumetanide-sensitive Na(+)-K(+)-2Cl- cotransport. Thus, the three forms of neutral Na(+)-Cl(-)-coupled transport so far evidenced in epithelia, Na+/H+, Cl-/HCO3- double exchange (in the presence of exogenous bicarbonate), HCTZ-sensitive Na(+)-Cl- symport and bumetanide-sensitive Na(+)-K(+)-2Cl- cotransport, are all present in the apical membrane of rabbit gallbladder.
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Latex beads coated with secretory immunoglobulin (IgA) instilled into mouse intestinal loops are taken up by M cells present in Peyer's patch follicle-associated epithelial tissue. Bead adsorption and uptake is greater at the edge compared with the apex of follicle domes. Coating beads with bovine serum albumin (BSA) causes a fourfold reduction in adsorption and a twentyfold reduction in uptake. Results demonstrate selectivity between adsorption and uptake and between the ability of different proteins to facilitate uptake.