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Biomedical subjects

G Gamba

Publications and source records attributed to G Gamba.

At least 19 recordsLinked to original sources
PubMed1996

Thrombin activity and early outcome in unstable angina pectoris.

BACKGROUND: The blood coagulation system is frequently activated in the acute phase of unstable angina, but it is unknown whether the augmented function of the hemostatic mechanism may serve as a marker of increased risk for an early unfavorable outcome. METHODS AND RESULTS: Plasma concentrations and 24-hour urinary excretion of fibrinopeptide A were prospectively determined in 150 patients with unstable angina. All patients underwent 24-hour Holter monitoring, during which time urine was collected; at the end of this period, a blood sample was taken and coronary arteriography was performed. The patients were followed up for the occurrence of cardiac events (death and myocardial infarction) until they underwent coronary revascularization or until they were discharged from the hospital. Fibrinopeptide A plasma levels and 24-hour urinary excretion were found to be abnormally elevated in 50% and 45% of the study population, respectively. During hospitalization, 11 patients developed myocardial infarction and 2 patients died. Kaplan-Meier analysis demonstrated a significantly higher probability of developing cardiac events in patients with abnormal rather than normal plasma levels of fibrinopeptide A (P<.01), whereas no difference in outcome was observed between patients with normal and those with abnormal 24-hour urinary excretion. Cox regression analysis showed that the only variables independently related to an early unfavorable outcome were the presence of persistent ischemia during 24-hour Holter monitoring (P<.0001), the presence of intracoronary thrombosis at angiography (P=.016), and abnormal fibrinopeptide A plasma levels (P=.038). CONCLUSIONS: Patients with unstable angina pectoris and abnormal fibrinopeptide A plasma levels are at increased risk for an early unfavorable outcome.

Aged↗
PubMed1996

Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies: a four-year prospective study from the Italian Registry.

PURPOSE: To assess the natural history and risk factors for thrombosis in a large cohort of unselected patients with antiphospholipid antibodies. PATIENTS AND METHODS: Three hundred sixty consecutive patients (118 males, 242 females, median age 39 years [range 2 to 78]) fulfilling the currently accepted criteria for diagnosis of lupus anticoagulant (LAC) (n = 326) and/or raised immunoglobulin G anticardiolipin antibodies (IgG ACA) (n = 185) were collected from 16 Italian institutions and prospectively observed for a median of 3.9 years (range 0.5 to 5). Main endpoints were the occurrence of arterial or venous thrombosis, the outcome of pregnancies, and any severe complications leading to hospitalization or death. RESULTS: Thirty-four patients developed a thrombotic complication, with a total incidence of 2.5% patient-years. Multivariate logistic regression analysis identified two independent risk factors for thrombotic events: a previous thrombosis (RR 4.9; 95% CI, 1.76 to 13.7; P < 0.005) and IgG ACA titer above 40 units (RR 3.66; 95% CI, 1.24 to 10.8; P < 0.01). A total of 28 pregnancies were observed in 25 women and 11 (39%) were abortive. Adverse pregnancy outcomes were significantly more frequent in women with a history of miscarriage or vascular occlusion (9/16, 56%) than in asymptomatic women (2/12, 17%) (P = 0.035). Four patients developed non-Hodgkin's lymphoma during the follow-up. Eighteen patients died. Vascular events and hematological malignancies represented the most frequent causes of death (n = 5 for each). CONCLUSIONS: The present study shows that: (a) previous thrombosis and ACA titer > 40 U are independent predictors of thrombosis; (b) history of miscarriage or vascular disease is significantly associated with adverse pregnancy outcome; (c) hematological malignancies can develop during follow-up in patients with antiphospholipid antibodies.

Adolescent↗
PubMed1996

The electroneutral Na(+)-(K+)-Cl- cotransport family.

Recently the molecular identification of the major electroneutral sodium-potassium-chloride entry mechanisms present on apical membranes of distal nephron segments of the mammalian kidney, on basolateral membranes of many non-renal epithelial cells and on certain non-epithelial tissues has been achieved. These transporters represent a major pathway for cellular uptake of chloride critical for chloride absorptive and secretory processes and for cell volume regulation following cell shrinkage. In the mammalian kidney, these sodium-coupled chloride cotransporters represent the major target sites for clinically useful diuretics including the "loop" diuretics [furosemide (Lasix) and bumetanide (Bumex)] and thiazides (such as, chlorothiazide, hydrochlorothiazide and metolazone). Although these Na-(K)-Cl cotransporters exhibit functional and pharmacological differences, they clearly evolved from a common ancestral gene and thus form a new gene family. This information is already advancing our understanding of the evolution, structure and function of these transporters both in renal handling of sodium and in hypertension.

Animals↗
PubMed1996

Portal and mesenteric thrombosis in protein S (pS) deficiency.

Portal and/or mesenteric thrombosis is a rare occurrence, and often an underlying hypercoagulable state can be found. We describe a case in which a mesenteric infarction due to mesenteric venous thrombosis occurred as the first manifestation of an inherited type I deficiency of protein S, whereas signs of portal thrombosis emerged later.

Adult↗
PubMed1995

Cloning and functional expression of a rat kidney extracellular calcium/polyvalent cation-sensing receptor.

The maintenance of a stable extracellular concentration of ionized calcium depends on the integrated function of a number of specialized cells (e.g., parathyroid and certain kidney epithelial cells). We recently identified another G protein-coupled receptor (BoPCaRI) from bovine parathyroid that responds to changes in extracellular Ca2+ within the millimolar range and provides a key mechanism for regulating the secretion of parathyroid hormone. Using an homology-based strategy, we now report the isolation of a cDNA encoding an extracellular Ca2+/polyvalent cation-sensing receptor (RaKCaR) from rat kidney. The predicted RaKCaR protein shares 92% identity with BoPCaR1 receptor and features a seven membrane-spanning domain, characteristic of the G protein-coupled receptors, which is preceded by a large hydrophilic extracellular NH2 terminus believed to be involved in cation binding. RaKCaR cRNA-injected Xenopus oocytes responded to extracellular Ca2+, Mg2+, Gd3+, and neomycin with characteristic activation of inositol phospholipid-dependent, intracellular Ca(2+)-induced Cl- currents. In rat kidney, Northern analysis revealed RaKCaR transcripts of 4 and 7 kb, and in situ hybridization showed localization primarily in outer medulla and cortical medullary rays. Our results provide important insights into the molecular structure of an extracellular Ca2+/polyvalent cation-sensing receptor in rat kidney and provide another basis on which to understand the role of extracellular divalent cations in regulating kidney function in mineral metabolism.

Amino Acid Sequence↗
PubMed1995

Consistency of the peritoneal equilibration test in a cohort of nonselected Mexican CAPD patients.

The peritoneal equilibration test (PET) is a useful tool in continuous ambulatory peritoneal dialysis (CAPD) prescription. PET D/P ratios are reproducible in the same patient when performed within a short period. However, peritoneal transport consistency in nonselected patients over longer periods of time is debated. The PET was performed twice in 19 randomly selected patients (13 female) from a cohort of 55 patients on CAPD for 32 +/- 24 months, age 44 +/- 18 years. Mean time between the first and second PET was 9.6 +/- 4 months. All patients were peritonitis-free at least 6 weeks before each PET. Fifteen patients did not change transport type between the two PETs: 3 low (L), 8 low-average (LA), 3 high-average (HA), and 1 high (H). Only 4 changed: 1 H to HA, 2 LA to HA, and 1 L to LA. In these 4 patients the change was centripetal (towards the mean) and less than 1 SD and not considered clinically significant. No differences between both groups in peritonitis rate, gender, age, time on dialysis, and diabetes mellitus status were observed. Transport type, as evaluated by the PET, was consistent over time in our group of patients.

Adult↗
PubMed1994

Molecular cloning, primary structure, and characterization of two members of the mammalian electroneutral sodium-(potassium)-chloride cotransporter family expressed in kidney.

Electrically silent Na(+)-(K+)-Cl- transporter systems are present in a wide variety of cells and serve diverse physiological functions. In chloride secretory and absorbing epithelia, these cotransporters provide the chloride entry mechanism crucial for transcellular chloride transport. We have isolated cDNAs encoding the two major electroneutral sodium-chloride transporters present in the mammalian kidney, the bumetanide-sensitive Na(+)-K(+)-Cl- symporter and thiazide-sensitive Na(+)-Cl- cotransporter, and have characterized their functional activity in Xenopus laevis oocytes. Despite their differing sensitivities to bumetanide and thiazides and their different requirements for potassium, these approximately 115-kDa proteins share significant sequence similarity (approximately 60%) and exhibit a topology featuring 12 potential membrane-spanning helices flanked by long non-hydrophobic domains at the NH2 and COOH termini. Northern blot analysis and in situ hybridization indicate that these transporters are expressed predominantly in kidney with an intrarenal distribution consistent with their recognized functional localization. These proteins establish a new family of Na(+)-(K+)-Cl- cotransporters.

Amino Acid Sequence↗
PubMed1994

Molecular cloning and characterization of the renal diuretic-sensitive electroneutral sodium-(potassium)-chloride cotransporters.

cDNAs encoding the two major electroneutral sodium-chloride transporters present in the mammalian kidney, the bumetanide-sensitive Na(+)-K(+)-Cl- symporter and thiazide-sensitive Na(+)-Cl- cotransporter, were isolated and their functional activity characterized in Xenopus laevis oocytes [2]. Although they differ in sensitivities to bumetanide and thiazides and have different requirements for potassium, these approximately 115-kDa proteins share about 60% sequence similarity and exhibit a topology featuring 12 potential membrane-spanning helices flanked by large hydrophilic domains at the NH2- and COOH-termini. These molecules, together with the Na-Cl cotransporter from the flounder urinary bladder, which exhibits a significant homology suggestive of common ancestry, define a new family of electroneutral Na(+)-(K+)-Cl- cotransporters. Northern blot analysis and in situ hybridization indicate that these transporters are expressed predominantly in kidney with an intrarenal distribution consistent with their recognized functional localization. The kidney-specific distribution of transcripts encoding these cotransporters suggest that other, probably related, genes encode non-renal Na(+)-(K+)-Cl- cotransporters.

Animals↗
PubMed1994

The coronary subclavian steal syndrome: an uncommon sequel to internal mammary-coronary artery bypass surgery.

Coronary subclavian steal syndrome is a possible sequel in patients who have undergone myocardial revascularization with an internal mammary artery. We report a case of this syndrome in a 67-years-old man. In 1990 he underwent a quadruple bypass: aorta-obtuse margin, aorta-right coronary (two sequential), internal artery mammary-descending coronary artery. Three months later he started to have angina pectoris. In April 1992 an aortic arch angiography and a coronary angiography were performed. The examination showed an occlusion of the left subclavian artery at its origin. The artery was opacified countercurrently by the left vertebral artery but the left mammary artery was not opacified. Left coronary angiography showed a very severe disease of left anterior descending coronary artery and retrograde flow through the anastomosis in the left mammary artery. The patient underwent a left common carotid-subclavian artery bypass operation using a 6 mm vascutex graft. Eighteen months later the patient is doing well without angina pectoris and with very little alteration of the perfusion in the left frontal lobe observed by SPECT neuroimaging with a lipophilic tracer (99mTc-HMPAO). We think that the coronary-subclavian steal syndrome can be treated successfully with low risk by means of common carotid-subclavian artery bypass.

Aged↗
PubMed1994

Serum albumin and body surface area are the strongest predictors of the peritoneal transport type.

The peritoneal equilibration test (PET) is used as a tool for dialysis prescription. In order to establish which parameters can predict peritoneal transport type, we studied 55 patients on continuous ambulatory peritoneal dialysis (CAPD), who were subjected to a standard PET. Clinical data (sex, age, calculated body surface area [BS], average time on dialysis [TD], and presence of diabetes mellitus), laboratory variables, (serum creatinine [SCr] blood urea nitrogen [BUN], serum albumin [SA], and residual renal function), and adequacy parameters (dialysate creatinine clearance [CrCl], weekly clearance of urea normalized to total body water [KT/V], protein catabolic rate, and dialysis index), were obtained and recorded at the time of the PET. The study group was composed of 29 males and 26 females, mean age of 43.5 +/- 16 years, and average TD of 25.2 +/- 18 months. PET results: 13 patients were low, 16 low average, 19 high average, and 7 high peritoneal transporters. According to the logistic regression analysis, the factors significantly associated with the type of peritoneal transport were: BS, SA, dialysate CrCl, and TD (coefficients 7.2, -1.23, 0.72, and -0.03, respectively). Greater BS and lower SA directly correlate with high peritoneal transport, and are the strongest predictors for the model.

Adult↗
PubMed1993

Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid.

Maintenance of a stable internal environment within complex organisms requires specialized cells that sense changes in the extracellular concentration of specific ions (such as Ca2+). Although the molecular nature of such ion sensors is unknown, parathyroid cells possess a cell surface Ca(2+)-sensing mechanism that also recognizes trivalent and polyvalent cations (such as neomycin) and couples by changes in phosphoinositide turnover and cytosolic Ca2+ to regulation of parathyroid hormone secretion. The latter restores normocalcaemia by acting on kidney and bone. We now report the cloning of complementary DNA encoding an extracellular Ca(2+)-sensing receptor from bovine parathyroid with pharmacological and functional properties nearly identical to those of the native receptor. The novel approximately 120K receptor shares limited similarity with the metabotropic glutamate receptors and features a large extracellular domain, containing clusters of acidic amino-acid residues possibly involved in calcium binding, coupled to a seven-membrane-spanning domain like those in the G-protein-coupled receptor superfamily.

Amino Acid Sequence↗
PubMed1993

Primary structure and functional expression of a cDNA encoding the thiazide-sensitive, electroneutral sodium-chloride cotransporter.

Electroneutral Na+:Cl- cotransport systems are involved in a number of important physiological processes including salt absorption and secretion by epithelia and cell volume regulation. One group of Na+:Cl- cotransporters is specifically inhibited by the benzothiadiazine (thiazide) class of diuretic agents and can be distinguished from Na+:K+:2Cl- cotransporters based on a lack of K+ requirement and insensitivity to sulfamoylbenzoic acid diruetics like bumetanide. We report here the isolation of a cDNA encoding a thiazide-sensitive, electroneutral sodium-chloride cotransporter from the winter flounder urinary bladder using an expression cloning strategy. The pharmacological and kinetic characteristics of the cloned cotransporter are consistent with the properties of native thiazide-sensitive sodium-chloride cotransporters in teleost urinary bladder and mammalian renal distal tubule epithelia. The nucleotide sequence predicts a protein of 1023 amino acids (112 kDa) with 12 putative membrane-spanning regions, which is not related to other previously cloned sodium or chloride transporters. Northern hybridization shows two different gene products: a 3.7-kb mRNA localized only to the urinary bladder and a 3.0-kb mRNA present in several non-bladder/kidney tissues.

Amino Acid Sequence↗
PubMed1993

Evidence of a hypercoagulable state in patients with acute lymphoblastic leukemia treated with low dose of E. coli L-asparaginase: a GIMEMA study.

Blood coagulation abnormalities induced by administration of E. coli L-asparaginase were investigated in 25 patients with acute lymphoblastic leukemia treated according to the GIMEMA ALL 0288 trial. Dosage of L-asparaginase was relatively low (6,000 U/m2/day for 7 days total dose 42,000 U/m2) as compared to the conventional dosages (120,000-140,000 U/m2 over 10-14 days). A significant decrease in fibronogen, plasminogen, alpha2-antiplasmin and antithrombin III was observed from day IV of L-asparaginase and it was maximum on day VIII, with return to the baseline levels on day XV. Protein C levels had only a borderline reduction, while no modification of protein S or factor VII was observed. Two of the patients investigated developed thrombosis. The presence of a prothrombotic state induced even by this low dosage of E. coli L-asparaginase was suggested by a significant increase of sensitive markers of hypercoagulability such as fibrinopeptide A, thrombin-antithrombin complexes, and prothrombin fragment F1 + 2.

Adolescent↗
PubMed1993

Death risk in CAPD patients. The predictive value of the initial clinical and laboratory variables.

The characteristics, survival rate and risk factors associated with death in patients with end-stage renal failure treated with chronic ambulatory peritoneal dialysis (CAPD) were studied. This is a retrospective study of a cohort of 206 patients, from which the follow-up was complete in 190 patients (92%). Only 16 patients (8%) were lost. The study group is composed of 118 males and 88 females, with a mean age of 39 +/- 15 years. The origin of the renal disease was: unknown in 90 patients (44%); diabetes mellitus in 50 (24%); systemic lupus erythematosus in 16 (8%); obstructive uropathy in 15 (7%); glomerulonephritis in 14 (7%), and miscellaneous in 21 (10%). The average follow-up was 12 +/- 11 months. At the end of study, 66 patients were dead (32%). CAPD was discontinued in 12 (6%). Thirty-eight patients (18%) received kidney transplantation. The survival rate for the whole group was 67 and 48% at 1 and 3 years, respectively. Multivariate survival analysis according to the Cox proportional-hazard model showed that the most powerful predictor associated with high risk of death was low serum albumin levels. According to the Cox model other independent variables significantly associated with increase in the probability of death while on CAPD were advancing age, low serum creatinine concentrations and elevated serum cholesterol levels. These results indicate that the risk factors associated with death in CAPD patients are similar to those observed for hemodialysis patients and suggest that using simple laboratory measurements at the enrollment in CAPD the relative risk of death for each patient can be estimated.

Adolescent↗
PubMed1993

[The aneurysmal degeneration of aortocoronary bypasses. A case report].

A 67-year-old man presenting with oppressive atypical chest pain 13 years after aorto-coronary saphenous vein bypass surgery, was found to have a large left anterior mediastinal mass on chest x-rays. Computerized tomography and digital subtraction angiography showed conflicting evidence on the vascular nature of the structure: the suspect diagnosis was of aortic pseudoaneurysm originating in the area of previous aortic cannulation. Selective coronary and bypass angiography showed extreme irregularity and dilatation of the grafts, and revealed the mediastinal mass to be represented by aneurysmal dilatation of the saphenous vein graft to the obtuse marginal coronary artery, partially filled with thrombus. At operation, another smaller aneurysm was found on the right coronary artery graft. Aneurysmal degeneration of vein grafts in the coronary circulation is exceedingly rare, and in only 6 reported cases has such an aneurysm presented as a mediastinal mass. To our knowledge, this is the first case in which an aneurysmal dilatation involved two saphenous vein coronary grafts.

Aged↗
PubMed1992

Platelet function after in vivo and in vitro treatment with thrombolytic agents.

Whereas in vitro studies showed that plasmin may induce both inhibition and activation of platelets, in vivo and ex vivo investigations suggested that thrombolytic agents are responsible for platelet stimulation. To gain further information on this topic, ex vivo platelet function was studied in 24 subjects with acute myocardial infarction treated with streptokinase or recombinant tissue-type plasminogen activator (rt-PA). Ten patients with acute myocardial infarction who did not receive thrombolytic treatment were also investigated. The data shows that at the end of thrombolytic infusion, the maximal extent of platelet aggregation and adenosine triphosphate release was reduced in treated patients compared with that in untreated ones. In subjects treated with streptokinase, the defect in platelet aggregation derived from both cellular and plasmatic defects. Plasmatic beta-thromboglobulin concentration was significantly reduced after streptokinase, but unchanged after rt-PA. Three days after thrombolytic treatment, platelet aggregation of patients receiving streptokinase or rt-PA was not significantly different from that of untreated subjects. A similar defect in platelet function was obtained in vitro, incubating normal platelet-rich plasma with pharmacologic concentrations of streptokinase. Again, platelet function defect derived from both cellular and plasmatic damages. It cannot be excluded that platelet activation occurs in patients with acute myocardial infarction during the very early phases of thrombolytic treatment. However, it is suggested that a transient defect in platelet function follows both streptokinase and rt-PA infusion.

Adenosine Triphosphate↗