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Biomedical subjects

D Russo

Publications and source records attributed to D Russo.

At least 37 records · Page 2Linked to original sources
PubMed1996

Some sodium, potassium and water changes in the elderly and their treatment.

Creatinine clearance decreases with age by 1 ml/min/year after 40 years of age, although serum creatinine remains constant because of reduction of muscle mass. Reduction of water intake may occur in the elderly because of a reduced sensation of thirst; this is associated with a tendency to lose water with urine. The capacity to respond to sodium load is impaired in aged kidneys, thereby leading to ECV expansion and hypertension. But there is also, in the elderly, a reduced capacity for retaining sodium (FENa is higher than in young subjects), making old subjects sensitive to salt depletion and ECV contraction. Hypernatraemia (Nas > 150 mmol/l) is not infrequent in the elderly (1%) and is usually due to water deficiency (old subjects should be forced to drink), and rarely to iatrogenic excess of sodium. It is the abrupt occurrence of severe hypernatraemia that causes neurological symptoms due to dehydration and brain shrinking, which may lead to cerebral haemorrhage and death. Hyponatraemia (Nas < 130 mmol/l) is frequent among the elderly (7-11%) and is mainly due to water overload, which is usually iatrogenic. Hypovolaemic hyponatraemia occurs when salt depletion causes ECV contraction > 10%, and is due to water retention in an attempt to normalize ECV. Hypervolaemic hyponatraemia is due to ADH hypersecretion because of a decrease in 'effective' circulating blood volume. 'Pseudohyponatraemia' may occur because of hyperlipidaemia or hyperproteinaemia. It is the abrupt occurrence of severe hyponatraemia that causes neurological symptoms (water intoxication), secondary to the oedomatous swelling of the brain within the skull. While rapidly occurring hyponatraemia may be lethal, slowly occurring hyponatraemia is usually asymptomatic. Rapid correction of hyponatraemia may cause cerebral dehydration and 'osmotic demyelination syndrome' ('central pontine myelinosis'). Decrease (e.g. by diuretics) or increase (e.g. by ACE-inhibitors, non-steroidal anti-inflammatory drugs, beta-blockers) or serum potassium may occur in the elderly. Diuretics should be used with caution in elderly subjects to avoid salt depletion, hypotension and renal function impairment.

Aging↗
PubMed1996

Iris indocyanine green videoangiography in diabetic iridopathy.

AIMS/BACKGROUND: Iris fluorescein angiography (IFA) is not commonly used in clinical practice, although its value has been demonstrated especially in cases of diabetic disease. IFA is able to show neovascular tufts in order to guide the laser treatment, and it is highly recommended in diabetic patients who need cataract surgery or vitrectomy. Nevertheless, IFA fails to demonstrate the iris vascular pattern in heavily pigmented iris and conspicuous leakage cases. The aim of the study was to evaluate the feasibility of iris indocyanine green videoangiography (IICGV) and to correlate its findings with those of IFA in diabetic iridopathy. METHODS: Thirty six patients affected in varying degrees by diabetic retinopathy underwent an ophthalmic examination including retinal fluorescein angiography, IFA, and IICGV. IICGV was performed using IMAGEnet System H1024. RESULTS: The results demonstrated that IICGV allows precise visualisation of the iris vascular pattern, also in cases of heavily pigmented iris. CONCLUSIONS: Three main findings seemed to be evident: firstly, iris neovascularisations are detected with IFA far more easily than IICGV; secondly, capillary dilatations and iris hypoperfusion are identified far more clearly using IICGV; thirdly, there is no evident relation between capillary dilatation or iris hypoperfusion, and degree of diabetic retinopathy.

Aged↗
PubMed1996

Thyrotropin receptor gene alterations in thyroid hyperfunctioning adenomas.

Forty-four thyroid autonomously hyperfunctioning adenomas were analyzed to assess the frequency of mutations occurring in the TSH receptor (TSHR). PCR-amplified fragments encompassing the entire exon 10 of the TSHR gene were obtained from the genomic DNA extracted from the tumors and their adjacent normal tissues and were examined by direct nucleotide sequencing. Point mutations were found in 9 of the 44 adenomas examined (20%). One mutation occurred in codon 619 (Asp to Gly), four in codon 623 (three were Ala to Ser, one Ala to Val substitution), two in codon 632 (both Thr to Ile), and two in codon 633 (Asp to Tyr or His). All the alterations were located in a part of the gene coding for an area including the third intracellular loop and the sixth transmembrane domain of the TSH receptor. All mutations were somatic and heterozygotic, and none was simultaneous with alterations of ras or gsp oncogenes. Thus, our data show that in our series of 44 hyperfunctioning thyroid adenomas, a somatic mutation of the TSHR, responsible for the constitutive activation of the cAMP pathway, occurs in 20% of the tumors.

Adenoma↗
PubMed1996

Constitutive activation of the Gs alpha protein-adenylate cyclase pathway may not be sufficient to generate toxic thyroid adenomas.

In toxic thyroid adenomas, mutations in the TSH receptor (TSH-R) gene or the gene encoding the alpha-subunit of the stimulatory guanine nucleotide-binding protein (Gs alpha) have been demonstrated to constitutively activate the cAMP cascade, which subsequently stimulates the growth and function of these tumors. However, the widely varying thyroid phenotypes in patients with TSH-R germline mutations, ranging from only slightly enlarged diffuse to multinodular goiters, suggest that additional mechanisms may be effective in the pathogenesis of toxic adenomas. We have investigated the levels of stimulatory and inhibitory G protein alpha-subunits together with basal and TSH-stimulated adenylate cyclase (AC) activity in toxic adenomas with or without activating mutations and in nodular and extranodular tissues of a toxic goiter due to a germline mutation in the TSH-R gene. Augmented expression of Gs alpha protein was detected in all toxic adenomas, independent of the presence of mutations, and in the nodular tissue of the toxic goiter, but not in the nonnodular hyperplastic tissue of the toxic goiter with the mutated TSH-R. Analogously, the expression of the alpha-subunit of the inhibitory G protein (Gi alpha) was also increased in all adenomas and the nodular tissue of the goiter, but, again, not in the hyperplastic goiter tissue. Basal AC activity was high in all tissues with mutations, but was only slightly increased in adenomas without detected mutations. No correlation was detectable between basal or TSH-stimulated AC activity and the levels of Gs alpha and Gi alpha. Our data suggest that mutational activation of the cAMP cascade may not be sufficient to generate toxic nodules and adenomas, but far more complex mechanisms, including alterations of G protein signaling, may be effective in the pathogenesis of these tumors.

Adenoma↗
PubMed1996

Renal adaptation to dietary sodium restriction in moderate renal failure resulting from chronic glomerular disease.

The renal response to sodium restriction was evaluated, and the concurrent changes of the plasma levels of aldosterone (ALDO) and atrial natriuretic peptide (ANP), in healthy patients (NOR), in normotensive patients with non-nephrotic chronic glomerulonephritis and normal renal function (GN), and in patients with glomerulonephritis and moderate renal failure (GFR, 41 +/- 4 mL/min; CRF). The three groups were studied for 1 wk after changing from a normal-sodium diet (NSD, 235 mEq NaCl/day) to a low-sodium diet (LSD, 35 mEq NaCl/day). All patients reached a steady sodium balance within the 4th and 5th day of LSD with an analogous cumulative loss of sodium. After salt restriction, the fractional urinary sodium excretion diminished by the same extent in the three groups, whereas the fractional free-water generation, measured during water diuresis, did not vary in NOR and markedly decreased in GN and CRF. Plasma levels of ALDO were similar in all groups at NSD and similarly increased during LSD. In GN and CRF, as compared to NOR, ANP levels were higher at NSD and decreased by a minor extent during LSD. Notably, in GN and CRF, but not in NOR, the attainment of the new sodium balance after sodium restriction was preceded by a significant parallel reduction of blood pressure and GFR; the GFR decline was secondary to a major decrement of RPF so that filtration fraction (FF) increased. It was concluded that in NOR, distal tubular effects of ANP and ALDO account for the attainment of sodium balance during LSD. As a difference, both GN and CRF patients achieve the new sodium balance primarily through hemodynamic changes: the renal hypoperfusion secondary to a decrease in blood pressure that diminishes the filtered load of sodium, and the increase of FF that enhances the proximal tubular sodium reabsorption. This abnormal response seems related to both the minor suppression of ANP and the increased salt-sensitivity of blood pressure that are likely the result of the presence of volume expansion.

Adaptation, Physiological↗
PubMed1996

Screening for multidrug resistance in leukemia: cell reactivity to MRK-16 correlates with anthracycline retention and sensitivity of leukemic cells.

The biologic and clinical importance of the multidrug resistance (MDR) that is related with the overexpression of the P170 glycoprotein (Pgp) is widely recognized. However, a major issue that has not yet been solved is the definition of the degree of Pgp expression which is associated with a significant decrease of the sensitivity of the cells to chemotherapy. For this reason we studied the leukemic cells from 83 cases of acute leukemia. Leukemic cells were fixed in PLP and treated with saponine. Pgp expression was assayed by flow cytometry, using the anti Pgp monoclonal antibody MRK-16. Results were expressed both as the number of positive cells and by the intensity of the reaction as defined by the mean fluorescence index (MFI), i.e. the ratio between the mean fluorescence intensity of the MRK-16 incubated cells and of the IgG2a incubated cells. Thus, Pgp expression was compared with the results of two in vitro tests of cell sensitivity to anthracyclines, daunorubicin (DNR) cell retention and DNR cytotoxicity. We found that it was not the number of MRK-16 positive cells, but the degree of the reaction with MRK-16 (MFI) that significantly related to the anthracycline toxicity tests. Therefore, we propose that for clinical purposes a quick and cheap determination of Pgp-related MDR in leukemic cells may be obtained by measuring the MFI with MRK-16 in a standard flow cytometry assay and that the assay may indeed be sufficient to estimate Pgp expression as well as the influence of Pgp on cell sensitivity to anthracyclines.

Anthracyclines↗
PubMed1995

Activating mutations of the TSH receptor in differentiated thyroid carcinomas.

A series of 14 thyroid carcinomas, characterized for their basal adenyl cyclase activity (ACA), was examined for the presence of activating point mutations in the TSH receptor (TSHR) gene. Sequencing of the carboxyl-part of this gene revealed the presence of a somatic and heterozygotic point mutation in codon 623 in three out of six tumors showing a constitutively enhanced ACA and a poor response to TSH stimulation. The mutation determines the substitution of a serine for an alanine in the third intracellular loop of the receptor, in a region critical for signal transduction. One tumor bearing a TSHR mutation presented also a N-ras point mutation. Both mutations were detected also in a lung metastasis of this tumor. Our data represent the first report of alterations in the TSHR gene in thyroid malign neoplasia. TSHR mutations may indeed participate, as well as the G alpha s protein (gsp oncogene), in the oncogenesis of some differentiated thyroid carcinomas presenting increased basal levels of cAMP and a poor response to TSH.

Adenocarcinoma, Follicular↗
PubMed1995

Solitary plasmacytoma of bone and extramedullary plasmacytoma: two different entities?

BACKGROUND: The objective of this study was to evaluate the similarities between solitary plasmacytoma of bone (SPB) and extramedullary plasmacytoma (EP). PATIENTS AND METHODS: The clinical features, treatment and survival of 54 patients with localized plasmacytoma (LP) 1990 were carefully reviewed. Follow-up was expected to continue until June 1993. RESULTS: Thirty-two patients were classified as having SPB and 22 EP. Most of the patients were males. particularly those in the SPB group. Their median age at diagnosis was 54 years and no significant difference between the two groups was observed. SPB occurred most frequently in the vertebral column (42%) and EP in the upper respiratory tract (73%). Fifteen patients with SPB and 2 with EP had paraproteinemia at diagnosis, multiple myeloma (MM) became evident in 75% of the patients with persistent paraprotein after therapy, and in only 22% of those in whom it disappeared. Four patients in the SPB group had immunoparesis, and 3 developed MM. Disease progression toward MM was significantly different (p=0.003) in the two groups, while overall survival differences were not significant (p=0.07) unless unrelated causes were excluded (p=0.02). Adjuvant chemotherapy did not seem to limit diffusion of the disease. CONCLUSIONS: Although EP and SPB are both localized forms of plasma cell dyscrasias, SPB seems to have a greater tendency to progression MM. It appears, however, that the apparent stronger propensity of SPB to progress is actually due to the great number of cases that at diagnosis conceal an occult MM.

Adult↗
PubMed1995

Molecular analysis of PML-RAR alpha fusion mRNA detected by reverse transcription-polymerase chain reaction assay in long-term disease-free acute promyelocytic leukaemia patients.

By use of RT-PCR of PML/RAR alpha, we evaluated bone marrow aspirates in 10 patients with APL in long-term disease-free status after induction chemotherapy and consolidation (median 54 months: range 33-101 months from complete remission). All patients were in clinical and cytogenetic remission at the time of molecular evaluation (range 32-96 months from CR). All patients but one were found to be RT-PCR negative at the molecular level for the expression of PML-RAR alpha transcript, confirming that the majority of the patients with long-term survival of APL are characterized by the eradication of the neoplastic clone.

Bone Marrow↗
PubMed1995

Genetic alterations in thyroid hyperfunctioning adenomas.

Thirty-seven thyroid autonomously hyperfunctioning adenomas were screened for mutations in the TSH receptor (TSHR), G alpha s (gsp), and ras genes. Polymerase chain reaction-amplified fragments of the TSHR C-terminal part (exon 10), the G alpha s (exons 8 and 9), and the three ras genes were obtained from the genomic DNA extracted from 37 tumors and their adjacent normal tissues and were studied by direct nucleotide sequencing and hybridization with synthetic probes. A point mutation in the third intracellular loop (codon 623) of the TSHR was found in 3 of 37 adenomas studied. This mutation codes for a change (Ala to Ser) in the TSHR structure and is somatic and heterozygotic. Constitutive activation of the TSHR was demonstrated by an increase in basal cAMP levels after transfection of Chinese hamster ovary cells with a mutated Ser623-TSHR complementary DNA. Nine gsp[00ae]MDRV[00af]- and one ras-activating mutations were also detected. No simultaneous alteration of the studied genes was present. Thus, in hyperfunctioning thyroid adenomas, our data suggest that a mutational activation of the TSHR and gsp genes may play a tumorigenic role through constitutive activation of the cAMP pathway.

Adenoma↗
PubMed1995

Early effects of contrast media on renal hemodynamics and tubular function in chronic renal failure.

The pathophysiology and prevention of contrast media (CM)-induced nephropathy in chronic renal failure (CRF) are still ill defined. GFR, RPF, endothelin-1 (ET-1) levels, urinary sodium concentration, and fractional excretion of sodium were measured in CRF patients undergoing water diuresis in basal conditions and 20 to 120 min after an iv bolus of either the high-osmolar CM diatrizoate (D) or the low-osmolar CM iopamidol (I). The two CM induced an immediate and progressive decline of both GFR and RPF in the absence of hypovolemia, more pronounced in D (-36% at 120 min) than after I (-19% at 120 min; P < 0.05 versus D). Both CM determined a marked and steady increase of the fractional excretion of sodium. The natriuresis could not be totally ascribed to a CM-induced osmotic diuresis as because the urinary sodium concentration markedly increased. In two further groups of patients receiving D, we studied the effects of pretreatment with a single dose of either captopril or nifedipine. Both drugs, although not preventing the increase of natriuresis, partially antagonized D-induced renal hypoperfusion: GFR and RPF were equally reduced by 20% in D/captopril and D/nifedipine (P < 0.05 versus D). In unpretreated patients receiving either D or I, plasma ET-1 did not change but urinary levels increased; these changes were, however, dissociated from those observed in renal hemodynamics. Both plasma and urinary levels of ET-1 did not vary in pretreated groups. The 72-h follow-up evidenced a significant reduction of renal function only in the unpretreated D group. Therefore, the main findings after CM administration in CRF patients are: (1) an immediate GFR decline proportional to the osmolarity of CM and secondary to the renal hypoperfusion that is neither caused by hypovolemia nor mediated by ET-1, (2) an early tubular dysfunction at the level of the proximal nephron, and (3) a protective effect of single-dose pretreatment with either captopril or nifedipine on D-induced acute and short-term GFR changes.

Contrast Media↗
PubMed1995

Does the type of BCR/ABL junction predict the survival of patients with Ph1-positive chronic myeloid leukemia?

The prognostic value of the site of DNA rearrangement within the M-BCR on chromosome 22 or of the type of transcript has been debated in the last years. The majority of the studies do not support the hypothesis of a predictive value of such molecular parameters. Results coming from a multicentric, prospective trial, based on alpha-IFN therapy, seem to indicate a better karyotypic response in 3' rearranged patients. The possibility of evoking a cytotoxic immune response directed towards peptides originating from each of the different BCR/ABL junctions constitute an important challenge for the future.

Fusion Proteins, bcr-abl↗
PubMed1995

P170 glycoprotein expression and impaired anthracycline retention in chronic myeloid leukaemia.

Chronic myeloid leukaemia (CML) is a well known model of a disease refractory to chemotherapy, including anthracyclines and other drugs that are believed to be pumped out of the cells by a 170 Kd transmembrane glycoprotein (P170). In 35 cases of Ph+ CML we investigated the reactivity of leukaemic cells to a P170-directed monoclonal antibody (MRK-16), by means of flow cytometry. P170 overexpression was found in 4/14 (29%) chronic phase CML cases and in 16/23 (70%) accelerated and blastic phase CML cases (P = 0.01). The same cells were assayed for their ability to retain Daunorubicin and Idarubicin after 2-hours in vitro incubation with 1000 ng/ml of either drug. It was found that anthracycline cell concentration was negatively related with the degree of the reactivity to MRK-16. In accelerated and blastic phase, CML cells simultaneously expressed P170 and the stem cell related marker, CD34. These data confirm that Ph+ leukaemic cells overexpress P170, show that P170 overexpression is functionally relevant, and suggest that P170-related multidrug resistance may be an important factor for chemotherapy failure in Ph+ CML.

ATP Binding Cassette Transporter, Subfamily B, Mem↗