Molecular screening: why haven't we started yet?
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Cell Transformation, Neoplastic↗
Biomedical subjects
E Villa
Publications and source records attributed to E Villa.
Timing for surgical treatment in native infective endocarditis. A seven-year experience.
BACKGROUND: Early surgical intervention in infective endocarditis is performed only when there is persistence of sepsis, hemodynamic instability or when arterial embolism has occurred, otherwise a 4-week antibiotic therapy before surgery is considered necessary. Our 7-year experience in the surgical treatment of native endocarditis in 28 patients, is here revised focusing on the timing of surgery. METHODS: Patients were retrospectively divided into group A (n. 16) with blood cultures that became negative before surgery and group B (n. 11) with blood cultures positive at the time of urgent surgery. One patient with constantly negative blood cultures was not assigned to any group. In group A antibiotic therapy was administered until 3 consecutive blood cultures became negative and the patients were then operated on the basis of echocardiographic findings after a mean duration of antibiotic therapy of 17.4 +/- 6.3 days. RESULTS: Twenty-six patients out of 28 underwent replacement of the infected valve (mechanical bileaflets in 16 patients, porcine stented in 7 and porcine stentless in 3). Valve repair was performed in 2 patients. Overall operative mortality was) 7.1% (2/28); death occurred in 2 patients of group B, operated on for cardiogenic shock. Two/26 patients died (1 acute renal failure and 1 stroke) at a mean follow-up of 32.5 +/- 24.8 (range 3-95) months. CONCLUSIONS: Patients who underwent surgery for infective endocarditis after blood culture negativization showed no mortality and no recurrence of disease even if a 4 weeks antibiotic course was not completed. This experience suggests that earlier operations can be performed safely, lowering the incidence of hemodynamic impairment and arterial embolism.
Endocarditis, Bacterial↗
Type of estrogen receptor determines response to antiestrogen therapy.
Failure of tamoxifen treatment for unresectable hepatocellular carcinomas (HCCs) might be caused by variant estrogen receptors (ERs) in some of these tumors. We therefore planned a study in which antihormonal therapy was done with 80 mg/day tamoxifen or 160 mg/day megestrol according to the presence of wild-type or exon 5-deleted variant ER transcripts. Growth rate (evaluated by MRI) of HCCs characterized by variant ER transcripts was 4 times more rapid than that of HCCs with wild-type ERs. Tumor volume in all patients with wild-type ERs was halved after 9 months of tamoxifen treatment, whereas megestrol in patients with variant ERs only slowed down tumor growth. Choosing antihormonal treatment according to the presence of wild-type or variant ERs in the tumor definitely improves the response rate to tamoxifen; in patients with tumors bearing variant ERs, megestrol causes only a temporary inhibition of tumor growth.
Adult↗
Importance of complete staging in non-Hodgkin's lymphoma presenting as a cerebral mass lesion.
BACKGROUND: The high incidence of local failure and the lack of evidence of systemic dissemination of primary central nervous system lymphoma (PCNSL) has led some authors to conclude that complete staging with extensive tests is not necessary in patients with a lymphomatous cerebral mass who present with a focal neural syndrome. Moreover, De Angelis emphasizes that there is no report in the literature of systemic lymphoma presenting as a cerebral mass lesion, whereas others conclude that an extensive systemic evaluation is unnecessary or that the staging should be limited to physical examination, routine blood studies, and a chest radiography. METHODS: In 16 PCNSL patients observed between 1982 and 1992, we found two patients showing systemic involvement of lymphoma after staging workup with chest X-ray, total body computerized tomographic (CT) scan, cerebrospinal fluid cytology examination, and bone marrow biopsy. In one patient, a CT abdominal scan showed retroperitoneal and pelvic lymphonodal involvement, whereas in the second patient, bone marrow biopsy was positive. These systemic onsets were found no later than 2 months after the diagnosis of central nervous system involvement, which is sufficient time to conclude that these locations were present at the diagnosis of the cerebral mass. RESULTS: In the present study, complete staging demonstrated widespread dissemination (lymph nodes or bone marrow) in two patients with initial neurologic symptoms and a cerebral mass lesion. CONCLUSIONS: In our experience, complete staging allowed detection of systemic lymphoma in two patients initially considered to have PCNSL.
Brain Neoplasms↗
Alpha but not beta interferon is useful in chronic active hepatitis due to hepatitis C virus. A prospective, double-blind, randomized study.
Interferon-alpha has been widely used in chronic hepatitis C, but controlled studies with intramuscular interferon-beta are lacking. We therefore performed a prospective, double-blind, randomized study comparing intramuscular IFN-alpha and -beta in patients with chronic hepatitis C. Sixty patients were randomly assigned to receive 3 MU thrice weekly intramuscularly of either recombinant IFN-alpha or leukocyte IFN-alpha or fibroblast IFN-beta for six months. Nine of 20 patients (45.0%) in the recombinant IFN, 5/19 (26.3%) in the leukocyte IFN, and none in the IFN-beta group had a complete response during therapy (recombinant IFN vs IFN-beta: P < 0.01). Only in IFN-alpha-treated patients, was infection with a single HCV genotype (type 2a or 2b) associated with significantly better long-term outcome. IFN-alpha is useful in chronic hepatitis C while intramuscular IFN-beta interferon does not exert any beneficial effect. This is probably due to an insufficient bioavailability of IFN-beta when given intramuscularly.
Adolescent↗
Effects of L-arginine infusion on renal hemodynamics and sodium excretion during hypo-, normo-, and hyperinsulinemia, as studied in dogs.
The response of renal hemodynamics and sodium excretion (NaU) to an infusion of L-arginine, in the presence (experiment I) or absence (experiment II) of endogenous insulin secretion and during a sustained hyperinsulinemic euglycemic state (experiment III), was studied in 10 age-matched beagle dogs. The experiments were preceded by a standard oral glucose tolerance test (OGTT), performed 1 week before experiment I. One week resting periods were allowed between experiments I, II, and III. No differences in renal hemodynamics and NaU were observed between basal (experiment I) and insulin secretion suppressed states (experiment II). L-Arginine infusion increased renal plasma flow (RPF), glomerular filtration rate (GFR), and NaU to a similar extent in both experiments. The hyperinsulinemic-euglycemic state (experiment III) induced a decrease in renal hemodynamics and NaU. In this situation, the infusion of L-arginine increased NaU, but was unable to increase RPF and GFR. Our data suggest that a sustained hyperinsulinemic state can interact with the physiological vasoactive mechanisms involved in the regulation of renal vasculature. These results may be pertinent to human disease, especially in pathological conditions in which insulin resistance is present.
6-Ketoprostaglandin F1 alpha↗
Identification of subjects at risk for colorectal carcinoma through a test based on K-ras determination in the stool.
BACKGROUND & AIMS: The gold standard for screening for colorectal carcinoma is colonoscopy. The aim of this study was to compare endoscopic results with those obtained using the noninvasive screening test of K-ras determination in the stool in a large population of patients undergoing colonoscopy. METHODS: Two hundred thirty consecutive patients were studied by K-ras amplification on stool-derived DNA using polymerase chain reaction and oligomer-specific hybridization. RESULTS: Wild-type K-ras was amplified in 103 of 230 patients (44.8%), the rate of amplification being directly proportional to the presence of an organic disease of the intestine characterized by hyperproliferating mucosa. In 30 of these 103 patients (29.1%), a K-ras mutation was found. Four of 5 with early colorectal carcinoma, all who had K-ras mutations in the tumor, were identified. In first-degree relatives of patients with colorectal carcinoma, all subjects either carrying adenomas > 1 cm in diameter or multiple smaller adenomas were identified. In patients with inflammatory bowel disease, the test identified the only patient with neoplastic transformation. CONCLUSIONS: The sensitivity and specificity of K-ras determination on stool-derived DNA in patients with colorectal carcinoma, in first-degree relatives of patients with colorectal carcinoma, and in patients with inflammatory bowel disease support the opportunity of a large-scale trial to validate its use as a screening test.
Adenoma↗
Variant liver estrogen and response to tamoxifen.
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Antineoplastic Agents, Hormonal↗
Insulin resistance in patients with a recent diagnosis of coronary artery disease.
OBJECTIVE: To elucidate whether insulin resistance is present in coronary artery disease (CAD) at diagnosis and to study its relationship with other known cardiovascular risk factors. METHODS: We evaluated the incidence of insulin resistance in 40 newly diagnosed CAD patients. Fifteen healthy subjects were used as a control group. The patients and controls had no previous history of metabolic disorders, and were not being administered any medication that might have affected their insulin sensitivity. Immediately after diagnosis of CAD, a standard 75 g oral glucose-tolerance test (OGTT) and an insulin suppression test (IST) were performed on separate days. The IST consisted of a constant infusion of glucose, insulin and somatostatin for 150 min; insulin resistance was estimated by determining the steady-state plasma glucose (SSPG) concentrations during the last 60 min of the test. The insulin sensitivity index (ISI) was calculated by the formula ISI = (glucose infusion rate/SSPG]x10(3). RESULTS: Insulin resistance, defined by an ISI below the normal range derived from the control group, was present in 82.5% of the CAD patients. As a group, the patients with CAD displayed lower ISI (means +/- SD:29.23 +/- 11.23 versus 50.33 +/- 9.37 dl/kg per min, P < 0.001) than did controls. Serum triglycerides and uric acid were higher and high-density lipoprotein cholesterol levels were lower in patients than they were in controls. No differences were observed in fasting plasma insulin, glucose, total and low-density lipoprotein cholesterol concentration. An abnormal OGTT result was observed in 27 patients. The ISI was low in 88.8% of the patients with an abnormal OGTT result and in 69% of the 13 patients with a normal OGTT result. CONCLUSIONS: Insulin resistance and even impaired glucose tolerance are common findings in CAD at diagnosis. The changes in the lipid profile and in uric acid levels paralleled the changes in insulin sensitivity. These results suggest that insulin resistance might play a role in the development of coronary atherosclerosis and that its early diagnosis might be important in the prophylaxis of CAD.
Aged↗
Effects of indomethacin and iloprost on contraction of the afferent arterioles by endothelin-1 in juxtamedullary nephron preparations from normotensive Wistar-Kyoto and spontaneously hypertensive rats.
The contractile effects of endothelin-1 on the afferent arterioles of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) and the modulation of these responses by cyclooxygenase blockade or by the prostacyclin analog iloprost were investigated. For this, the preglomerular vasculature was visualized by using the juxtamedullary nephron preparation. Endothelin-1 (100 pM-1 microM) induced concentration-dependent reduction of afferent diameters either in WKY and SHR kidneys, which were inhibited by 1 microM nifedipine, indicating its dependence on extracellular calcium. After incubation with 20 microM indomethacin, the endothelin-1-induced contractions were potentiated in WKY but abolished in SHR vessels. These results could be explained if endothelin-1 is releasing vasodilator prostanoids in WKY, whereas in SHR preparations, vasoconstrictor prostanoids predominate. The prostacyclin analog iloprost (1 nM-1 microM) did not modify basal diameters of the WKY afferent arterioles, whereas a weak vasodilatatory effect was observed in the SHR afferent vasculature. Both in WKY and SHR preparations, iloprost (10 nM-1 microM) abolished the afferent contractility by endothelin-1, this effect being more prominent in SHR. We conclude that a defective production of vasodilator prostanoids or an enhanced release of vasoconstrictor cyclooxygenase derivatives may determine the renovascular effects of endothelins in SHR kidneys.
Animals↗
Scheduling effectively and efficiently.
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Appointments and Schedules↗
Variant estrogen receptor messenger RNA species detected in human primary hepatocellular carcinoma.
The development of hepatocellular carcinoma (HCC) in addition to cirrhosis affects males in a significantly higher proportion than females. Liver estrogen receptors increase when HCC develops in males; however, these tumors usually respond poorly to antiestrogens. We have, therefore, hypothesized that, similar to breast cancer, estrogen receptors in males with HCC may be mutated. Variant estrogen receptor transcripts (lacking exon 5 of the hormone binding domain) were investigated by reverse transcription-PCR in 14 patients (7 males and 7 females) with HCC. While females mostly displayed the wild-type transcript (both in peritumoral and in tumor liver tissue), males showed both transcripts in the cirrhotic tissue and almost only the variant in the tumor. As the variant ER transcripts when translated could give rise to truncated receptors still able to constitutively activate transcription, they may be key factors in favoring deregulated proliferation in the male liver.
Blotting, Northern↗
Selection of more pathogenic hepatitis C virus genotype II during long-term follow-up of interferon-treated patients.
The behavior of hepatitis C virus (HCV) infection with regards to type and number of HCV genotypes (tested with genotype-specific nested polymerase chain reaction) was evaluated in 60 patients with anti-HCV-positive chronic active hepatitis without cirrhosis [17 untreated and 43 subjects undergoing single or repeat courses of interferon (IFN) therapy] during a mean follow-up period of 76 +/- 18 months. In untreated patients (2 genotype I, 6 genotype II, 9 mixed infections) 4 out of 9 mixed infections selected for genotype II at the end of follow-up. Of the 43 treated patients 10 were long-term responders with histological remission, 6 were short-term responders, and 22 did not respond. Fifteen of the latter patients received another course of IFN therapy, and only 3 patients responded. Eight of the 10 responders had infection with a single genotype (4 gt I, 3 gt II, 3 gt III). After IFN therapy, all but 2 patients cleared the HCV infection. The responders to the second IFN course (1 gt I, 1 gt II, 1 gt III) remained viremic. Of the short-term responders, 2/6 patients had genotype II and 4 had a mixed infection (3 gt II +/- I and 1 gt II +/- III); gt III became prevalent in the latter in all but one patient. Of the nonresponders 18/24 had more than one genotype, 5 were genotype II at baseline and one had genotype I. At the end of the follow-up period 15/18 with mixed infection had selected for gt II (P < 0.01 vs. untreated patient).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Evidence for hepatitis B virus infection in patients with chronic hepatitis C with and without serological markers of hepatitis B.
To assess the influence of HBV infection on anti-HCV-positive chronic liver disease, we performed a prospective case-control study comparing 19 HBsAg-positive, anti-HCV-positive patients with 38 HBsAg-negative, anti-HCV-positive patients, pair-matched for age, sex, and ALT levels. HBV and HCV infections were investigated by standard serology and polymerase chain reaction. HCV RNA was found in all patients with CAH and in 90.0% with cirrhosis (33% HBsAg-positive). HBV DNA sequences were found, in the HBsAg-positive subjects, in 71.4% of CAH and in 83.3% of cirrhotics; in the HBsAg-negative ones, only 10% of CAH but 77.7% of cirrhotics had demonstrable HBV DNA sequences. Consequently, 80.0% of cirrhotics had evidence of both HBV and HCV infection. Conventional serology gives partial information on the true occurrence of HBV infection in HBsAg-negative patients, while PCR defines more accurately the HBV status. When the rate of double infection is defined in this way, it correlates with the presence of cirrhosis.
Case-Control Studies↗
Primary central nervous system lymphoma in immunocompetent patients.
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Aged↗
Combined therapy for primary central nervous system lymphoma in immunocompetent patients.
A retrospective series of 13 immunocompetent patients with histological diagnosis of primary central nervous system lymphoma (PCNSL) is presented. The series was divided into Group A, 6 patients treated with radiotherapy alone, and Group B, 7 patients treated with chemotherapy and radiotherapy. Clinicopathological patterns were similar for the two groups. In Group A, 4 patients achieved complete remission after radiotherapy (45-59.4 Gy) but relapsed within 9 months and died within 21 months of diagnosis. 4 Group B patients received chemotherapy followed by radiotherapy, and three who received a methotrexate-containing regimen are alive and disease-free at 34, 42 and 45 months, while the fourth died after 11 months. The other 3 subjects in this group were treated with radiotherapy followed by chemotherapy, and died within 15 months of diagnosis. Although radiotherapy is the standard treatment, chemotherapy has potentially an important role in the management of PCNSL. The sequence of combined treatment could be crucial to improvement of outcome.
Adolescent↗
[Invaginating colonic lipoma as a cause of intestinal occlusion].
The authors describe three cases of single invaginating colon lipoma, causing ileus. They review the literature and make some remarks.
Colonic Neoplasms↗
Long-term follow-up of hepatitis C virus (HCV) infection in liver transplant patients.
Chronic hepatitis represents a frequent event after orthotopic liver transplantation (OLT). To ascertain the influence of HCV infection on the clinical and histological outcome of these patients, we have investigated the long-term outcome of 22 patients with end-stage chronic liver disease undergoing liver transplant focusing the attention on the role of different HCV genotypes in determining recurrence and severity of post-OLT liver disease. For all patients blood samples taken before OLT and 3 months, 1, 2 and 3 years after OLT were tested for antiHCV antibodies by two different enzyme-linked immuno-assays and by recombinant immuno-blot II and for the presence and type of HCV RNA by nested PCR (5' untranslated region and core gene primers). Of the 16 pre-OLT antiHCV-positive patients, 14 (87.5%) had recurrence of HCV infection while 2 cleared HCV. Pre-OLT genotype recurred in 11 of these 14 patients (2 genotype I) 8 genotype II - in 1 case associated with genotype III - and 1 genotype IV). Of the 6 pre-OLT antiHCV-negative patients, only 1 (16.6%) became persistently HCV-infected, with genotypes I and II. The recurrence of genotype II strictly related with development of severe chronic hepatitis while genotype I and IV were associated with milder forms of liver disease and were more easily cleared.
Chronic Disease↗