Biomedical subjects

E Villa

Publications and source records attributed to E Villa.

At least 73 records · Page 4Linked to original sources

PubMed1998

Characteristics of hepatocellular carcinoma in Italy.

BACKGROUND/AIMS: This study aimed to assess the main features of hepatocellular carcinoma at the time of diagnosis in Italy, particularly in relation to the presence or absence of underlying cirrhosis, hepatitis virus marker patterns, age of the subjects and alpha-foetoprotein values. METHODS: A total of 1148 patients with hepatocellular carcinoma seen at 14 Italian hospitals in the 1-year period from May 1996 to May 1997 were the subjects of this prevalence study. Both newly diagnosed cases (incident cases) and cases diagnosed before May 1996 but still attending the hospitals during the study period (prevalent cases) were included. RESULTS: We found that 71.1% of cases were positive for hepatitis C virus antibodies but negative for HBsAg; in contrast, 11.5% were negative for anti-HCV but positive for HBsAg; 5.3% were positive for both markers; and 12.1% were negative for both viruses. The mean age of detection was over 60 years, with a younger mean age in HBsAg-positive compared to anti-HCV-positive patients (59.3 years vs. 65.6 years, p<0.01). The male-to-female ratio among HBsAg-positive patients was 10.4:1, in contrast to 2.8:1 among anti-HCV-positive patients (p<0.01). The majority of cases (93.1%) had underlying cirrhosis. Cirrhotic patients were more likely to be anti-HCV positive than non-cirrhotic cases (73.2% vs 43.9%; p<0.01); conversely, absence of hepatitis virus markers was more frequently observed in the non-cirrhotic than in the cirrhotic population (40.9% vs. 10.0%; p<0.01). Overall, the alpha-foetoprotein level was altered (>20 ng/ml) in 57.9% of patients; only 18% of cases presented diagnostic (>400 ng/ml) values. Anti-HCV positivity (O.R. 2.0; CI 95%=1.3-3.1) but not HBsAg positivity (O.R. 1.0; CI 95%=0.6-1.8) was shown to be an independent predictor of the likelihood of altered alpha-foetoprotein values by multivariate analysis. CONCLUSIONS: These findings point to differences in the characteristics of the populations infected by hepatitis B and hepatitis C. Factors other than the hepatitis viruses are important in non-cirrhotic patients. A change in the relative prevalence of hepatitis virus markers among hepatocellular carcinoma cases was demonstrated, reflecting a significant change in the rate of HBV endemicity in the Italian population. Finally, the increased trend in the mortality rate from liver cancer in Italy from 4.8 per 100,000 in 1969 to 10.9 in 1994 may reflect the large cohort of subjects infected with HCV via the iatrogenic route during 1950s and 1960s when glass syringes were commonly used for medical treatment.

Adult↗

PubMed1998

Effects of chronic combined treatment with captopril and pravastatin on the progression of insulin resistance and cardiovascular alterations in an experimental model of obesity in dogs.

Obesity is a metabolic disorder in which multiple clinical and biochemical alterations coexist. However, the progression of these alterations in relation to weight gain has not been investigated in detail. Therefore, we studied the evolution of insulin resistance and associated risk factors in a model of experimental obesity in dogs. We also studied whether chronic exposure to these pathogenic factors could induce cardiac and vascular alterations. Twenty male age- and body weight-matched beagle dogs were divided into four groups (n = 5), according to diet and pharmacologic therapy received, and followed for 2 years. Control animals were maintained with a regular diet, while the 15 remaining animals were fed a high-fat diet. The Obese group of dogs received no therapy, whereas the Capto group received 25 mg/12 h captopril, and the Prava+Capto was treated with 10 mg/24 h pravastatin plus the same dose of captopril throughout the study. Periodical determinations of clinical and biochemical parameters were made, and the degree of insulin resistance was also estimated. After the 2-year follow-up, the dogs were killed and vascular thickening in the aorta and the coronary arteries was evaluated. In addition, cardiac hypertrophy was estimated by heart weight and free-wall left ventricular width. Chronic pravastatin plus captopril treatment, together with decreasing weight gain rate, ameliorated the progression of insulin resistance and associated risk factors (hyperinsulinemia, hypercholesterolemia) related to this severe model. In addition, this combined therapy showed cardioprotective action, as cardiac and vascular hypertrophy observed in the Obese group was prevented. These positive results seems to emerge from the synergistic effects of both drugs, as captopril as monotherapy induced only a slight benefit on these parameters.

Animals↗

PubMed1998

Effects of hyperinsulinemia on the regulation of regional blood flow and blood pressure in anesthetized dogs: hemodynamic role of nitric oxide.

The purpose of this study was to investigate whether acute hyperinsulinemia induces selective hemodynamic effects in the mesenteric, renal, and iliac vascular beds, and to determine whether nitric oxide (NO) plays a role in the regulation of blood flow and mean arterial pressure (MAP) during acute hyperinsulinism. In eight anesthetized dogs (Group A), the response to a hyperinsulinemic test was determined before and after NO inhibition, with L-nitro-arginine methyl esther (L-NAME), during the last 45 min of the experiment. In seven dogs (Group B), NO inhibition was induced before and maintained throughout hyperinsulinemia. In Group A, the hyperinsulinemic test did not alter MAP, but induced a significant reduction in both renal and mesenteric blood flow without a significant change in iliac blood flow. In contrast, the administration of L-NAME in Group B was followed by a significant decrease in mesenteric, renal, and iliac blood flow, but mean arterial pressure remained unchanged. In this group, hyperinsulinemia instituted after the blockade of NO was followed by a significant elevation in blood pressure levels, concomitant with reductions in blood flow to the three vascular beds. In summary, acute hyperinsulinemia induced a redistribution of blood supply, which preserves skeletal muscle irrigation while reducing blood flow to the kidney. Nitric oxide participates in this redistribution because L-NAME infusion abolishes the compensatory influence on skeletal muscle blood flow.

Animals↗

PubMed1998

Pancreatic cancer resection in elderly patients.

BACKGROUND: Pancreatic cancer resection is considered a high-risk procedure in patients aged 70 years or older. METHODS: Some 398 patients with pancreatic adenocarcinoma, observed between 1990 and 1995, were reviewed. Operative outcome and survival of 33 patients aged 70 years or more were compared with findings in 85 younger patients who underwent resection. RESULTS: Resectability was not significantly different between the elderly and younger patients; neither were mortality or overall morbidity. However, patients aged 70 years or more had more relaparotomies (P < 0.01) and more haemorrhagic complications (P < 0.001). Nutritional recovery after resection was satisfying even for elderly patients (body-weight gain and increase in serum albumin concentrations, P < 0.05). Univariate analysis showed a moderately poorer survival in the elderly (P = 0.09). Multivariate analysis demonstrated that tumour diameter, grading and Union Internacional Contra la Cancrum stage were independent prognostic factors, whereas age was not. CONCLUSION: Patients aged 70 years or more can benefit from pancreatic cancer resection similarly to younger patients.

Adenocarcinoma↗

PubMed1998

Endogenous dopaminergic activity in Child-Pugh A cirrhosis: potential role in renal sodium handling and in the maintenance of clinical compensation.

BACKGROUND: We studied the main determinants of aldosterone secretion in a group of 20 patients with biopsy-proven Child-Pugh A cirrhosis without previous ascites or diuretic consumption. METHODS: We evaluated the plasma levels of adrenocorticotrophic hormone (ACTH), active renin and aldosterone (both supine at 07.00 h and after 30 min of upright posture),and active renin and aldosterone responses 30 min and 60 min after the administration of metoclopramide, a dopamine DA2 antagonist (10 mg e.v.). Nine normal subjects were also submitted to the metoclopramide stimulation test. RESULTS: Compared with control subjects, the patients showed significantly greater incremental aldosterone responses both 30 min and 60 min after metoclopramide (+30 min: 157.5+/-73.3 vs. 83.5+/-32.2 pg mL(-1), P< 0003; +60 min: 142.1+/-87.2 vs. 36.8+/-39.0 pg mL(-1), P < 0-001). We found significant positive correlations between amplitude of aldosterone response 30 min after metoclopramide and 24-h urinary fractional excretion of sodium (r=0.61, P < 0.01) and basal morning aldosterone levels (r=0.69, P < 0.001). CONCLUSIONS: The higher incremental aldosterone responses observed after metoclopramide in cirrhotic patients are expressions of increased dopaminergic activity in these patients compared with control subjects. Moreover, the correlation we found between the degree of dopaminergic activity and 24-h urinary fractional excretion of sodium suggests a role for endogenous dopamine as a relevant mediator of natriuresis in cirrhosis, at least in patients with compensated disease.

Adrenocorticotropic Hormone↗

PubMed1998

Low sensitivity of computed tomography in the staging of gastric lymphomas of mucosa-associated lymphoid tissue: impact on prospective trials and ordinary clinical practice.

The natural history and management of gastric lymphomas of mucosa-associated lymphoid tissue (MALTomas) are not completely understood. Most stage I cases are now entered into prospective trials to confirm the excellent results obtained with conservative treatment, whereas current therapeutic policies are based on accumulated experience. The limits of staging work-ups may have a significant impact on prospective trials and ordinary clinical practice. The authors explore the sensitivity of computed tomography scanning in detecting perigastric adenopathy in 20 patients with gastric MALToma treated by gastrectomy. Clinical staging identified 17 patients as having stage I MALTomas and three patients as having stage II1 MALTomas. Histopathologic staging showed that 8 of 17 patients formerly diagnosed with stage I MALToma had perigastric nodal involvement, whereas the three patients with clinical stage II1 were confirmed as such. Computed tomography scanning has low sensitivity in detecting perigastric lymphadenopathy in gastric MALTomas. This leads to understaging, with a significant impact on therapeutic decision, and distorts newly acquired knowledge about the disease's natural history and management, introducing a bias in prospective clinical trials. Endoscopic ultrasonography should be tested as a staging procedure both in prospective trials and in ordinary clinical practice.

Adolescent↗

PubMed1998

Beneficial hemodynamic effects of dipyridamole on portal circulation in cirrhosis.

OBJECTIVE: Dipyridamole is a vasodilator that inhibits the cellular uptake of adenosine, which physiologically reduces the resistance to hepatic arterial flow inside the liver. This study aims at assessing the acute effect of dipyridamole on functional liver plasma flow (measured as the extrarenal sorbitol clearance) and on the Doppler US Congestion Index of the portal vein (the ratio between the cross-sectional area of this vein and the mean velocity of portal flow), which correlates with the severity of portal hypertension. METHODS: We have determined the extrarenal sorbitol clearance (14 cases) and the Congestion Index (seven cases) before and at 30, 60, and 90 min after the oral administration of 25 mg dipyridamole in patients with liver cirrhosis. We also measured the effect of dipyridamole on functional liver plasma flow in six healthy subjects. RESULTS: Dipyridamole increased the extrarenal sorbitol clearance in controls (+17%, p < 0.01) and in cirrhotic patients (+15%, p < 0.01). The drug decreased the portal Congestion Index in all patients, averaging -24% (p < 0.05) 90 min after its oral administration. CONCLUSIONS: This result was due both to a mean decrease of the portal sectional area and to a mean increase in portal flow velocity. In conclusion, these data suggest that dipyridamole should decrease the vascular resistance to portal flow in cirrhosis; this effect may be mediated by an adenosine-dependent vasodilation in the intrahepatic site or along the portosystemic collaterals.

Administration, Oral↗

PubMed1998

Therapeutic management with adriamycin-containing chemotherapy and radiotherapy of monostotic and polyostotic primary non-Hodgkin's lymphoma of bone in adults.

The best treatment of primary lymphoma of bone (PLB) remains undefined. We reviewed 15 patients with monostotic PLB and 8 with polyostotic PLB. Twenty of the patients were suitable for analysis. All patients but 1 received adriamycin-containing chemotherapy in association with radiation therapy. Radiotherapy for monostotic cases consisted of 40 Gy to long bones, followed by a boost to 45 Gy to bulky lesions or 40-45 Gy to whole flat bones. In cases of polyostotic PLB, bulky sites, fractured lesions, or sites with a high risk of fracture were irradiated with a median dose of 38 Gy. All patients with monostotic disease achieved complete remission (CR): 10 patients were alive and relapse-free at the time of this writing, 1 other patient was alive following a relapse, and 1 patient died while relapse-free. The survival rate for the patients in the study at the time of this writing was 92% at 50 months. Four patients with polyostotic disease achieved CR. Three of them had only two adjacent sites of disease and were treated as cases of monostotic PLB. Two of these 3 patients are alive and relapse-free. Four patients with polyostotic disease achieved PR, relapsed rapidly, and died of progressive disease. The relapse site was invariably the skeleton. The survival rate for patients with polyostotic PLB at the time of writing was 25% at 40 months. No severe late treatment-related toxicity was observed. The treatment of patients with monostotic PLB with adriamycin-containing chemotherapy and whole-bone irradiation with 40 Gy, followed by a boost to 45 Gy to bulky sites, prevented local relapse and produced a more favorable outcome than the use of radiotherapy (RT) alone. Patients with multiple adjacent lesions that can be included within a single radiation field with acceptable toxicity should be treated as cases of monostotic PLB.

Adolescent↗

PubMed1997

Primary cardiac lymphoma in immunocompetent patients: diagnostic and therapeutic management.

BACKGROUND: Primary cardiac lymphoma (PCL) is extremely rare in immunocompetent patients. Different definition criteria have been employed in published series. Prognosis is poor due to diagnostic delay and relevance of the site of disease. METHODS: Two cases observed at the study institution are reported, with a review of 48 cases published in the literature from 1980 to 1996. Only patients with lymphoma confined to the heart and/or pericardium and those with a single and asymptomatic extracardiac site were considered for analysis. RESULTS: Eight patients had minimal extracardiac disease. The most common presentation was unresponsive heart failure. Electrocardiography findings were not specific. PCL usually arose in the right chambers as a mass, with or without pericardial effusion (> 80%). Chest X-rays, transthoracic echocardiography, and computed tomography scans are standard in diagnostic workup, but transesophageal echocardiography (TEE) and magnetic resonance imaging (MRI) showed a sensitivity > 90%. Cytology of pericardial effusion was diagnostic in 67% of cases. Thoracotomy was diagnostic in all cases, whereas less invasive procedures had high false-negative rates. Gross resection has no role. Early anthracycline-containing chemotherapy appears to improve survival, whereas the role of radiotherapy has not yet been defined. CONCLUSIONS: The diagnosis of PCL should be considered in patients with a cardiac mass and/or unexplained refractory pericardial effusion. Adequate diagnostic workup, including TEE and MRI, allows confirmation of the early suspicion of PCL. In the absence of a diagnostic cytology, an open biopsy may be indicated to avoid treatment delay. There is no evidence that PCL should be treated differently from other bulky aggressive lymphomas arising at other anatomic sites.

Adolescent↗

PubMed1997

Intraoperative and postoperative radiotherapy in pancreatic cancer.

In the 1985-1994 period, 101 patients underwent resection for ductal pancreatic adenocarcinoma. In 27 patients, the resection was not associated with adjuvant therapies, whereas in 74 patients, it was. Intraoperative radiation therapy (IORT) was performed in 54 patients. Operative mortality and morbidity were similar in patients undergoing IORT (1.8 and 29.6%) to those undergoing resection alone (2.1 and 27.6%). Median survival of the IORT group was 17 vs 14 mo of the non-IORT group (irrespective of postoperative treatments) (ns); the local recurrence rates were 38 and 54%, respectively. The group of 74 patients undergoing adjuvant therapies had a greater survival than 27 patients with no adjuvant treatment, both at the univariate (p < 0.01) and the multivariate analyses (p < 0.05) (covariates tumor stage and radicality). The subgroup of patients undergoing only radiotherapy (RT) and/or chemotherapy (CT) did not show significantly better survival than patients with no additional therapies, whereas the group of patients undergoing IORT + CT + RT showed a significantly better survival (p < 0.05). In conclusion, adjuvant therapies seem to improve survival in patients undergoing resection for pancreatic cancer.

Combined Modality Therapy↗

PubMed1997

Effects of cicaprost and fosinopril on the progression of rat diabetic nephropathy.

We have studied the effects of chronic therapy with cicaprost (a PGI2 analog), fosinopril (a converting enzyme inhibitor), and the combination of both drugs on the progression of experimental diabetic nephropathy. Uninephrectomized streptozotocin-induced diabetic rats were maintained for 8 months with plasma glucose between 13.7 and 22.0 mmol/L to hasten renal damage. Systemic and renal parameters were measured periodically, and at sacrifice structural and morphometrical renal studies were performed to evaluate diabetic injury. Control rats exhibited characteristic features of this model, such as high blood pressure and plasma creatinine and urinary albumin excretion, together with prominent alterations in the kidney (renal and glomerular hypertrophies, mesangial matrix expansion, and tubular alterations). The three therapies attenuated equivalently the progression of diabetic renal injury, as estimated by lower urinary albumin excretion, renal and glomerular hypertrophies, and a better renal architectural preservation. No synergistic action was appreciated with the combined therapy. However, renal preservation achieved with cicaprost was not linked to reductions in systemic blood pressure, whereas in the groups treated with fosinopril the hypotensive effect of this drug could have contributed to the positive outcome of the therapy. Therefore, nephroprotection exerted by this PGI2 analog in this model seems more related to the derangement of renal local mechanisms than to systemic blood pressure control. Finally, the possibility that an impaired prostacyclin synthesis or bioavailability is involved in the pathogenesis of the diabetic nephropathy in this model underlies our results.

Albuminuria↗

PubMed1997

Effects of UP269-6, a new angiotensin II receptor antagonist, and captopril on the progression of rat diabetic nephropathy.

To estimate the effects of UP269-6, a nonpeptide angiotensin II receptor antagonist, and captopril, a converting enzyme inhibitor, on the progression of nephropathy, 77 uninephrectomized diabetic rats were maintained for 8 months with plasma glucose levels from 300 to 500 mg/dL. Systemic and renal parameters were periodically measured, and, at the time of death, a histological evaluation of renal damage was performed. Control rats (no additional treatment but insulin) showed increased blood pressure and urinary albumin levels, together with prominent alterations in the kidney (renal and glomerular hypertrophies, tubular atrophy, and 19% of sclerotic glomeruli). Captopril (50 mg/kg/day) and UP269-6 (10 mg/kg/day) reduced blood pressure and albumin excretion levels, and improved histological renal preservation (lower renal and glomerular hypertrophies, tubular atrophy, and percentage of sclerotic glomeruli: 5% and 7%, respectively). Finally, a low dose of UP269-6 (1 mg/kg/day), which induced an intermediate level of blood pressure between control and the other treated groups, produced an equivalent degree of nephroprotection. Our data demonstrate the efficacy of this new angiotensin II receptor antagonist on the progression of diabetic renal damage. These results also reinforce the role attributed to angiotensin II in the development of renal derangement in this model, as UP269-6 is devoid of agonistic effect on the kinin system.

Albuminuria↗

PubMed1997

Primary brain lymphomas in patients with a prior or concomitant malignancy.

The increased incidence of second malignancies among cancer survivors is well documented. Thus, differential diagnosis between metastatic spread from a prior malignancy and the occurrence of a new neoplasm should be considered. This is particularly difficult for brain lesions due to their poor prognosis that often discourages diagnostic work-up. In some cases diagnosis of a second primary neoplasm, such as primary central nervous system lymphomas (PCNSL), could change the therapeutic management and the prognosis. About 8% of PCNSL occurs as a second malignancy. Homogeneous and intense tomographic enhancement, deep location of lesions and dramatic response to corticosteroids are suggestive for PCNSL and should be carefully considered before the start of treatment for cerebral lesions. Prognosis and standard management of brain metastases and PCNSL are almost completely different. In addition, while treatment of brain metastases often has a palliative purpose the goal in PCNSL treatment is the cure. Four patients with PCNSL as a second malignancy are reported and literature is reviewed. Diagnosis of PCNSL changes the strategy of treatment which could have a critical therapeutic and prognostic impact.

Adult↗

PubMed1997

Therapeutic management of primary central nervous system lymphoma in immunocompetent patients: results of a critical review of the literature.

BACKGROUND: The optimal treatment for primary central nervous system lymphomas (PCNSL) has not been defined. PATIENTS AND METHODS: Therapeutic results of 1180 immunocompetent patients (pts) with PCNSL reported in 50 series published in English between 1980 and 1995 were analysed. The impact on survival of age, treatment strategy, radiation field and doses, systemic and intrathecal chemotherapy (CHT) and treatment sequence was evaluated. RESULTS: Univariate analyses showed a longer survival in pts of < or = 60 years (P < 0.00001): pts treated with > 40 Gy to whole brain (WB) (P = 0.02): pts receiving > 50 Gy to the tumor bed after a WB dose > 40 Gy (P = 0.02): pts submitted to a combined treatment as opposed to CHT alone (P = 0.007) or radiotherapy alone (P < 0.00001): pts receiving CHT followed by radiotherapy rather than in the reverse sequence (P = 0.05); pts treated with high-dose methotrexate (HDMTX) (P = 0.04) and pts receiving intrathecal CHT (P = 0.03). Multivariate analysis confirmed the independent prognostic value of age, WB dose, HD-MTX and intrathecal CHT. CONCLUSIONS: Current data confirm the prognostic value of age and appear to support the use of systemic CHT consisting of HD-MTX and intrathecal drug administration followed by 41-50 Gy to WB and > 50 Gy to the tumor bed in the treatment of PCNSL in immunocompetent pts.

Adolescent↗

PubMed1997

Hemodynamic and renal effects of cross-linked hemoglobin infusion.

It is well known that hemoglobin binds nitric oxide (NO) and produces a pronounced vasoconstriction in isolated arteries. However, it is debatable whether such an effect takes place in whole animals, because hemoglobin also catalyzes the formation of prostaglandins from arachidonic acid. Short-term studies were performed to evaluate the effects induced by intravenous infusion of cross-linked hemoglobin (XL-Hb) on blood pressure (BP) and renal, iliac, and mesenteric flows, and on renal function in six anesthetized dogs. A similar volume-matched expansion with 6% dextran was used as a control (n = 6). Glomerular filtration rate (GFR), urinary flow, and total and fractional sodium excretion were measured before and after XL-Hb or dextran infusion to evaluate possible renal function changes. XL-Hb administration resulted in a 29% elevation in BP and a significant decrease of blood flow (30-37%) to the three vascular beds. XL-Hb did not alter GFR or sodium excretion, despite the increase in BP. In contrast, the administration of dextran did not significantly alter BP but induced a significant increase (6-13%) of blood flow in the three vascular beds. These changes were accompanied by threefold increases in urinary flow and sodium excretion without alterations in GFR. The binding effect of XL-Hb on NO was studied in isolated renal arteries in organ chambers. These in vitro studies showed that XL-Hb blunted the endothelium-mediated vasodilator response to calcium ionophore A-23187 and to acetylcholine. Our results demonstrate that XL-Hb administration is followed by hypertension, vasoconstriction, and blunted natriuresis. All these effects are compatible with the scavenging effect on NO attributed to XL-Hb.

Acetylcholine↗

PubMed1997

Comparative effect of PGE2 and PGI2 on renal function.

Rapid degradation of prostacyclin (PGI2) inherent to its molecular structure has long been a major limitation in assessing the natriuretic effect of this prostaglandin. The recent availability of the stable PGI2 analogue iloprost now allows for a comparative study with prostaglandin E2 (PGE2). In the present study conducted in six anesthetized dogs, the intrarenal effects of two consecutive doses (1 and 4 ng x kg(-1) x min(-1)) of PGE2 on renal blood flow, glomerular filtration rate, and urinary sodium excretion were compared with the effects of two identical doses of iloprost. The selected doses of PGE2 were those producing a maximal natriuretic and vasodilator response without affecting mean arterial pressure. A washout period was allowed between administration of PGE2 and iloprost. PGE2 infusion significantly increased fractional sodium excretion from 0.69+/-0.1 to 2.79+/-1.1% and 4.27+/-1.2%% (P<.05), respectively. These changes in fractional sodium excretion induced by PGE2 were associated with significant increases in renal blood flow from 151.1+/-62 to 185+/-64.3 and 185.6+/-64.3 mL/min (P<.05), respectively; however, no significant alterations were seen in glomerular filtration rate, from 29.5+/-9.4 to 35.2+/-12.2 and 32.7+/-7.8 mL/min (NS), and mean arterial pressure, from 117.6+/-26 to 113.9+/-24.1 and 112.3+/-24.1 mm Hg (NS) during control and PGE2 infusion. At identical doses, sequential infusion of PGI2 had no effect on renal blood floww and glomerular filtration rate, producing natriuresis only at the highest dose, a fractional sodium excretion from 0.69+/-0.1 to 0.8+/-0.28 mm Hg (NS) and 1.05+/-0.34% (P<.05), respectively. In conclusion, the present study confirms that PGE2 exerts a natriuretic effect during increases in renal blood flow. In contrast, PGI2 had no hemodynamic effect, and the natriuresis was markedly blunted.

Animals↗

PubMed1997

Cardiac involvement in acromegaly: specific myocardiopathy or consequence of systemic hypertension?

To evaluate the relative contributions of past or present GH hypersecretion and of hypertension to the cardiac abnormalities present in acromegaly, we have studied the serum GH and insulin-like growth factor I concentrations, systolic and diastolic blood pressures, and morphological and functional cardiac indexes as measured by echocardiography-Doppler, in 39 patients with active or cured acromegaly, 16 hypertensive controls, and 17 normotensive controls. Hypertension was present in 42.8% of patients with active acromegaly and in 28.0% of patients in which acromegaly was cured. Hypertension was independently related to an increase in indexes of cardiac morphology (left ventricular mass, left ventricular posterior wall thickness, interventricular septum thickness, relative wall thickness with respect to the diastolic diameter of the left ventricle, and left atrial end-systolic diameter), systolic function (stroke volume, fractional shortening, and end-systolic stress), and diastolic function (isovolumic relaxation time and maximal late diastolic flow velocity) and to a reduction in the early to late maximal diastolic flow velocity ratio. Acromegaly was related to an increase in left ventricular mass, stroke volume, cardiac output, and isovolumic relaxation time, which were independent from the presence of hypertension. End-systolic stress was reduced by acromegaly. In the five patients in which active acromegaly was successfully treated, left ventricular mass and left ventricular posterior wall thickness were reduced 1 yr later. In conclusion, the asymptomatic morphological and functional cardiac abnormalities present in acromegalic patients are independently related to acromegaly and hypertension, pointing to the existence to a specific acromegalic myocardiopathy that might be aggravated by the coexistence of hypertension.

Acromegaly↗

PubMed1997

Lack of effectiveness of adjuvant alternating chemotherapy in node-positive, estrogen-receptor-negative premenopausal breast cancer patients: results of a multicentric Italian study. The Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group (GROCTA).

A multicentric randomized trial was performed in premenopausal women with node-positive, estrogen-receptor-negative breast tumors to assess the potential superiority of alternating adjuvant chemotherapy over 'standard' CMF chemotherapy. Between January 1989 and June 1992, 107 patients were entered into the study and randomly allocated to receive either cyclophosphamide 100 mg/m2 per as on days 1-14, methotrexate 40 mg/m2 and 5-fluorouracil 600 mg/m2 intravenously (i.v.) on days 1, 8 (CMF), every 4 weeks for a total of 6 cycles, or the following regimens: CMF as previously; epidoxorubicin 75 mg/m2 i.v. on day 1 and vincristine 0.75 mg/m2 i.v. on days 1, 8 (EV); mitomycin-C 10 mg/m2 i.v. on day 1 and vindesine 2 mg/m2 i.v. on days 1, 8 (MVs). The three regimens were given every 4 weeks for a total of 6 cycles according to the following schedule: CMF, EV, MVs, CMF, EV, MVs. At a median follow up of 48 months (range 30-72), 40 patients have relapsed and 17 have died overall. More patients in the triple-combination arm have relapsed and more have died, the latter difference tending toward statistical significance (p = 0.06). There was no statistical difference in the site of relapse between the two groups. Total duration of adjuvant therapy was similar in the two arms (312 chemotherapy cycles in the triple arm and 308 in the CMF arm). Treatment toxicity was also comparable, although more patients in the triple-combination arm were still regularly menstruating 6 months after the completion of chemotherapy. This study failed to show any advantage ensuing from the use of alternating chemotherapy in patients with early breast cancer.

Adult↗