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S Casanova

Publications and source records attributed to S Casanova.

At least 19 recordsLinked to original sources

A statistical model predicting high hepatocyte proliferation index and the risk of developing hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis.

BACKGROUND: Incidence of hepatocellular carcinoma in hepatitis C virus-related cirrhosis is 4% per year. Although cost-effective, current screening could be improved. AIM: To develop a statistical model including non-invasive parameters able to identify patients at high risk of developing hepatocellular carcinoma. METHODS: One hundred and fifty-eight patients (73F:85M) with compensated chronic hepatitis C virus liver disease underwent evaluation, including argyrophilic nucleolar organizer regions proliferation index, and were followed up for 56.18 +/- 1.44 months. RESULTS: Fifty-six patients had chronic hepatitis without cirrhosis and low argyrophilic nucleolar organizer regions proliferation index (< or =25%), 65 had hepatitis C virus-related cirrhosis and low argyrophilic nucleolar organizer regions proliferation index and 37 had hepatitis C virus-related cirrhosis and high argyrophilic nucleolar organizer regions proliferation index (>25%). Groups were similar for gender and viral genotype distribution. None of the patients with chronic hepatitis without cirrhosis developed hepatocellular carcinoma, compared with 6.1% of low argyrophilic nucleolar organizer regions proliferation index and 30.6% of high argyrophilic nucleolar organizer regions proliferation index (P = 0.002). By multivariable logistic regression analysis, the following parameters were independently associated with hepatocellular carcinoma development and used for the development of the statistical model: platelets (OR 0.98), gamma-globulins (OR 0.111), alanine aminotransferase/aspartate aminotransferase ratio (OR 0.07), serum ferritin (OR 1.0) and ultrasonographic pattern (coarse OR 2.9, coarse nodular OR 10.12). The statistical model properly allocated 95.9% of patients with low argyrophilic nucleolar organizer regions proliferation index and 72.2% of patients with high argyrophilic nucleolar organizer regions proliferation index. CONCLUSIONS: The model, to be validated in large prospective studies, may help tailoring screening according to the risk of hepatocellular carcinoma development.

Adult↗

Inadequacy of the new Response Evaluation Criteria in Solid Tumors (RECIST) in patients with malignant pleural mesothelioma: report of four cases.

Unidimensional Response Evaluation Criteria in Solid Tumor (RECIST) has been recently proposed in the attempt to simplify the standardized bidimensional World Health Organization (WHO) criteria. The complete accord between these two measurement systems was established in a large comparative study [J. Natl. Cancer Inst. 92(3) (2000) 205] that demonstrated the validity and the good performance of RECIST criteria. We report four cases of inadequacy of RECIST criteria in the evaluation of response to chemotherapy in patients with malignant pleural mesothelioma. These four patients were enrolled in two consecutive multicenter phase II clinical trials investigating the activity of a novel chemotherapy regimen in advanced pleural mesothelioma. They were judged as having an objective response to chemotherapy according to WHO criteria. Reassessed according to both methods, we found that results obtained with RECIST criteria do not correspond to WHO underestimating response to chemotherapy. Our data raise doubts about the applicability of unidimensional RECIST response criteria to mesothelioma and, possibly, to any tumor involving the chest wall.

Aged↗

Heterogeneity of diabetes phenotype in patients with 3243 bp mutation of mitochondrial DNA (Maternally Inherited Diabetes and Deafness or MIDD).

OBJECTIVE: In patients with maternally inherited diabetes and deafness (MIDD), due to 3 243 A > G mutation of mitochondrial DNA (mtDNA), diabetes may present with variable phenotypes. OBJECTIVE: To ascertain the existence of two distinct phenotypes, MIDD1 and MIDD2, in a series of patients with MIDD. DESIGN: Multicenter prospective study. PATIENTS: 77 patients with diabetes and the mtDNA 3243 mutation and 139 control patients with type 1 (T1D) or type 2 (T2D) diabetes, matched according to initial presentation of diabetes, age at onset, sex, and duration of diabetes (24 T1D and 115 T2D, including 55 treated with insulin). MEASUREMENTS: Anthropometric characteristics (height, body weight, body mass index [BMI], sex), family history of diabetes, and characteristics of diabetes (age at onset, treatment, hemoglobin A1c [HbA1c]), extrapancreatic manifestations. RESULTS: In 13 cases (17%, MIDD1), diabetes presented as insulin-dependent from the onset, with ketoacidosis in 6 cases. In 64 cases (83%, MIDD2), diabetes resembled T2D, and was treated with diet in 12 cases, oral hypoglycemic agents in 21 cases, or insulin in 31 cases. Compared with patients with MIDD2, patients with MIDD1 were characterized by lower age at onset of first manifestation of MIDD (25.4 +/- 9.6 vs 33.7 +/- 13.2 Years, P<0.0005), lower body weight (49.1 +/- 7.4 vs 56.3 +/- 10.9 kg, P<0.0025), lower BMI (18.2 +/- 2.3 vs 20.9 +/- 3.6 kg/m2, P<0.0005), and higher HbA1c levels (9.5 +/- 2.0 vs 7.5 +/- 1.6%, P<0.0005). Frequency of family history of diabetes and of extrapancreatic manifestations was the same in both MIDD subtypes. No difference was found within the MIDD2 subtype when comparing patients treated with or without insulin. Compared with matched controls, patients with MIDD had a lower BMI (MIDD1/T1D 18.2 +/- 2.3 vs 24.0 +/- 3.6 kg/m2 and MIDD2/T2D 20.9 +/- 3.6 vs 30.2 +/- 5.9 kg/m2, P<0.0025). Lastly, male patients with MIDD had a shorter height than controls (MIDD1/T1D: 166.1 +/- 3.2 vs 177.3 +/- 6.6 cm and MIDD2/T2D: 168.4 +/- 7.2 vs 173.6 +/- 6.6 cm P<0.025). CONCLUSIONS: These results confirm the existence of two different phenotypes in MIDD, MIDD1 and MIDD2, which may be related to the severity of the mitochondrial disease. The role of other genetic and/or environmental factors in the variable phenotype of MIDD remains to be elucidated.

Adult↗

Clinical and prognostic value of serial renal biopsies in lupus nephritis.

Little information is available about the role of repeated renal biopsies in lupus nephritis. We analyzed retrospectively the prognostic significance of serial renal biopsies in patients with lupus nephritis. Thirty-one patients with lupus nephritis underwent two or more renal biopsies during follow-up. The indications for repeated biopsy were as follows: improvement of renal disease but persistence of nonnephrotic proteinuria (group A, 7 patients); persistent or relapsing nephrotic syndrome (group B, 12 patients); and worsening of renal function (group C, 19 patients). After a median follow-up of 10.5 years, 17 patients reached the end point (persistent doubling of plasma creatinine level). At repeated renal biopsy, there was a correlation between improved clinical and histological features for group A. In these patients, treatment was reduced or stopped successfully. Histological features remained almost unchanged in group B. All patients showed an improvement of proteinuria after reinforcement of therapy. In group C, the worsening of renal function was associated with a variable and clinically unpredictable combination of active and chronic lesions. Only the few patients with an elevated activity index and moderate chronicity index showed a favorable and persistent improvement of renal disease after reinforcement of therapy. At multivariate analysis of clinical and histological data at presentation, only male sex was predictive of an adverse outcome (P = 0.015). At repeated renal biopsy, crescents in more than 30% of glomeruli (P = 0.0009) and chronicity index of 5 or greater (P = 0.00006) were associated with the probability of reaching the end point at multivariate analysis. Repeated renal biopsy may be helpful for establishing the prognosis in patients with lupus nephritis, particularly in the presence of worsening of renal function.

Adolescent↗

[Diabetic coronary disease and risk of myocardial infarction].

The raised incidence of myocardial infarction and sudden death in diabetics was explained over 20 years ago by the increase in prevalence and severity of coronary atherosclerosis. Coronary angiographies of 820 consecutive patients admitted to hospital for coronary artery disease were analysed. One hundred and fifteen of these patients (14%) were diabetic. In 77.4% of diabetics and 72.6% of non-diabetics, coronary angiography showed coronary lesions which were usually distal and three vessel in diabetics. When the three coronary arteries were analysed globally, the percentage of patients with at least one mild stenosis was much higher in diabetics than in non-diabetics (50.6% vs 30.3% respectively, p < 0.001), but there was no statistical difference in the number of severe stenoses or occlusions. The increase in mild stenosis in the diabetic population could indicate an anatomical predisposition to future rupture of a plaque. This result could explain the increased frequency of myocardial infarction and sudden death in diabetes, not necessarily preceded clinically by angina pectoris.

Aged↗

Prevalence of lymphocytic infiltrate in 1400 pituitary adenomas.

To evaluate the prevalence of lymphocytic infiltrate in a large series of pituitary adenomas, we retrospectively studied tumor tissues from 1400 patients. Based on immunocytochemical data, tumors were classified as PRL (n=411), multihormonal (n=310), immunonegative (n=275), ACTH (n=166), GH (n=137), alpha subunit (n=44), FSH and/or LH, (n=42), and TSH (n=15) adenomas. The lymphocytic infiltrate was diagnosed on histological examination and investigated by immunostaining with anti LCA (human leucocyte common antigen), anti CD45RO (human T cell) and anti CD20 (human B cell) antibodies. Lymphocytic infiltrate was present in 40 adenomas (2.9%), 26 females and 14 males, aged 18 to 77 years (mean+/-SD, 37+/-14 years). The tumors were 19 PRL, 8 multihormonal, 4 GH, 4 alpha subunit, 3 ACTH, and 2 immunonegative adenomas. In PRL adenomas, the sex ratio (female/male) and the age were similar in patients with and without lymphocytic infiltrate (2.8 vs. 4.6 and 29+/-6 years vs. 32+/-11 years, respectively). The frequency of lymphocytic infiltrate was similar in PRL, GH, ACTH and multihormonal adenomas, but lymphocytic infiltrate was significantly more frequent in PRL adenoma than in immunonegative adenoma, and in alpha subunit adenoma than in immunonegative, ACTH and multihormonal adenomas. The lymphocytic cells were almost exclusively T cells. We conclude that lymphocytic infiltrates are rare in pituitary adenomas. Their frequency is not statistically different in major categories of secreting adenomas (PRL, GH, ACTH, multihormonal). Their pathophysiological significance remains to be established.

Adenoma↗

Increased incidence of moderate stenosis among patients with diabetes: substrate for myocardial infarction?

Persons with diabetes are at higher risk for myocardial infarction and sudden death than are persons without diabetes. It has been demonstrated that the artery that occludes during acute myocardial infarction generally had less than 75% stenosis on a previous angiogram. The extent of coronary artery stenosis was analyzed for 820 consecutively examined patients who underwent coronary angiography at our institution. The patients were categorized according to the presence or absence of diabetes mellitus. The severity of stenosis was taken into consideration. Patients with diabetes had moderate (50% to 75% narrowing) stenosis much more frequently than patients without diabetes (50.6 versus 30.3%, p < 0.001). Moreover diabetes mellitus was an independent risk factor for moderate stenosis. The lesions were more frequently located on distal arteries, more frequently had a pattern of three-vessel disease, and had a trend toward more diffuse disease than described 25 years ago. This greater amount of moderate stenosis may be considered a substrate for future acute plaque rupture. It may explain the high prevalence of acute myocardial infarction and sudden death among patients with diabetes without an increase in the incidence of angina pectoris.

Aged↗

Uptake and killing of Lyme disease and relapsing fever borreliae in the perfused rat liver and by isolated Kupffer cells.

In situ-perfused rat livers were infused with a single dose of 1.5 x 10(7) radiolabeled borreliae. Significant (P < 0.00005) differences in the liver uptake of the agents of Lyme borreliosis, Borrelia burgdorferi IRS, Borrelia afzelii VS461, and Borrelia garinii PBi, and that of the agents of relapsing fever, Borrelia hermsii, Borrelia parkeri, and Borrelia turicatae, were observed. The liver uptakes ranged between 65.9% for B. burgdorferi IRS and 40.5% for B. turicatae. Neither relapsing fever nor Lyme disease borreliae were recovered from infected livers when the livers were cultured in Barbour-Stoenner-Kelly II medium. The in vitro uptake of B. burgdorferi IRS by isolated rat Kupffer cells was rapid, and within 30 min of the infection, large intracellular aggregates of amorphous material were detectable by immunofluorescence with specific anti-B. burgdorferi antibody. The reculturing of B. burgdorferi IRS from Kupffer cells incubated for 24 h in RPMI medium before inoculation with bacteria was negative. The results obtained in this study indicated that borreliae are efficiently taken up and killed by rat hepatic macrophages in the absence of serum factors.

Animals↗

[Nocturnal hypoglycemia in insulin-dependent diabetics].

OBJECTIVES: Repeated hypoglycaemia has been reported to impair recognition of subsequent hypoglycaemia with a high risk of severe hypoglycaemia. This intensified insulin therapy may be dangerous in insulin-dependent diabetes mellitus (IDDM) patients with unawareness of hypoglycaemia. METHODS: We assessed the incidence of nocturnal hypoglycaemia and the benefit of an additional bedtime snack in IDDM patients treated by 2 or 3 daily injections. Capillary blood glucose was measured by finger strip at 10 p.m. and plasma venous glycaemia was determined at 0, 2, 4 and 8 a.m. RESULTS: The study was composed of two phases. In the first phase, patients (n = 93) did not receive any snack at bedtime. Blood glucose fell to 2.75 mmol/l or less in 33%. Among the 40 patients with a 10 p.m. glycaemia of 9 mmol/l or less, 57.5% experienced nocturnal hypoglycaemia vs 15% of the 53 others. The second phase concerned 106 IDD patients. An additional bedtime snack was given when 10 p.m. blood glucose was 9 mmol/l or less. The incidence of hypoglycaemia fell to 32% (14 of 44 IDDM) i.e. a significant benefit of 44% (p < 0.01). However patients who received this additional bedtime snack had a slightly higher 8 a.m. glycaemia than those with 10 p.m. glycaemia at 9 mmol/l or less during the first phase (9.61 +/- 5.67 mmol/l vs 7.75 +/- 4.30 mmol/l) but this result is not significant. CONCLUSION: Prevention of nocturnal hypoglycaemia may be achieved in IDDM patients by bedtime glucose determination and an additional snack when glycaemia is 9 mmol/l or less.

Adult↗

Pattern of glomerular involvement in human immunodeficiency virus-infected patients: an Italian study.

Renal biopsy specimens from 26 adult human immunodeficiency virus (HIV)-infected patients with glomerular involvement were reviewed from the files of three hospital pathology services in Northern Italy. All the patients were Italian and most (19 of 26 patients) were intravenous drug addicts. The types of glomerular lesions were as follows: minimal-change glomerulopathy (two cases), mesangial proliferative glomerulonephritis (GN) with scanty immunoglobulin deposits (four cases), and various patterns of immune complex-mediated glomerulonephritis, including postinfectious GN (six cases), membranoproliferative GN (one case), membranous GN (three cases), immunoglobulin (Ig) A nephropathy (four cases), a mixed membranous and proliferative (three cases) and diffuse proliferative lupus-like pattern with subendothelial deposits, and intraluminal thrombi (two cases) or subepithelial and subendothelial deposits (one case). None of the patients had evidence of HIV-associated nephropathy. Our study confirms previous observations on the low incidence of HIV-associated nephropathy among white HIV-infected patients in Europe, where immune complex-mediated GN seems to predominate. Apart from the frequent electron microscopic observation of endothelial tubuloreticular structures, none of the reported lesions could be distinguished on morphologic grounds from those occurring in uninfected patients. The high variability of the glomerular lesions upholds the need for accurate diagnosis for the clinician confronted with an HIV-positive patient with suspected glomerular involvement.

Adult↗

[Endocrine diseases in POEMS syndrome. Apropos of 4 cases].

POEMS syndrome is a rare systemic multi-organ disease usually reported in Japanese patients. The clinical course is slow with a 5-year survival of 60%. Death is caused by polyneuropathy and or anasarka. We observed four cases in our ward (all males, aged 39, 57, 54 and 54 years) who all presented at least four characteristic clinical signs. Gynecomasty together with impotency was seen in all patients. All had hypogonadism and borderline hyperprolactinaemia. Hyperoestrogenism was seen in two. In three patients, rare endocrinopathies were part of the POEMS syndrome. One patient had diabetes mellitus. The clinical course was variable and a function of the effectiveness of plasmocyte dyscrasia therapy. Little work has been done on endocrinopathies in POEMS syndrome. In most cases, gonadotrope function is impaired with gynecomasty and impotency in men, amenorrhoea in women. Generally the hypogonadism is hypogonadotropic. Hyperoestrogenism is frequent and prolactin levels are normal or high with an exaggerated response to thyroid releasing hormone stimulation. The aetiology of POEMS syndrome is unknown. Current research is based on an immunologic theory based on the discovery of high levels of interleukin 6 in POEMS patients with or without Castleman's disease. The cytokine would affect the different organs and lead to clinical expression. Corticosteroids are usually effective in most patients, particularly in reducing the oedema and controlling the polyneuropathy.

Adult↗

Treatment of chronic sporadic-type non-A, non-B hepatitis with lymphoblastoid interferon: gamma GT levels predictive for response.

The aim of this study was to evaluate the efficacy of human lymphoblastoid interferon-alpha treatment in chronic sporadic-type non-A, non-B hepatitis. We also aimed to determine if histological or liver function data could predict either response or relapse. Sixty patients with chronic sporadic-type non-A, non-B hepatitis were randomized in two groups of 30. One group was treated with interferon-alpha (3 MU thrice weekly) for one year; the other group was untreated controls. The treated group was followed for another year after interferon withdrawal. Liver function tests were performed during treatment. Liver biopsy was carried out before and a year after randomization. We evaluated rate of response [normalization of alanine aminotransferase (ALT) levels for at least three consecutive months] and rate of relapse (ALT rebound after therapy suspension). We also looked at possible predictive factors for response and relapse. In the treatment group the rate of response was 55% (16/29). No control patient exhibited ALT normalization. Among the responders, 31% (5/16) relapsed after interferon withdrawal. Low gamma GT and female sex are positive predictive factors of response (P < 0.01 and P < 0.02 respectively). Presence of portal and periportal inflammation at the second liver biopsy was correlated with relapse (P < 0.05). In conclusion, human lymphoblastoid interferon-alpha treatment for one year is beneficial in patients suffering from chronic sporadic-type non-A, non-B hepatitis. Low pretreatment gamma GT levels and female sex are positive predictors of response in this patient population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Establishment and characterization of a new cell line from primary human breast carcinoma.

A new cell line (BRC-230) was established from surgical material of primary ductal infiltrating breast carcinoma. The epithelial nature of this cell line was confirmed by ultrastructural analysis and demonstrated the retention of structural properties characteristic of the original tumor. The BRC-230 cell line induced tumor in athymic Cr1:nu/nu(CD-1)BR nude mice, it possessed an abnormal karyotype with a modal chromosome number between 60-61 with eight recurrent marker chromosomes, and it presented a doubling time of 30.5 hr. Scatchard analysis demonstrated that both primary tumor and BRC-230 cells were estrogen and progesterone receptor negative. Immunoenzymatic and radioimmunoassays showed a production of marker antigens (CEA, TPA, CA125, CA15-3, CA19-9) which was similar in the patient's serum and BRC-230 cells. The in vitro drug sensitivity assay of the cell line and of the parental tumor tissue showed overlapping results to all tested antiblastic drugs. BRC-230 cells were resistant to 4-Idroperoxy-cyclophosphamide, Idarubicinol, Mitoxantrone, Etoposide, 4'Epidoxorubicin, and Doxorubicin, showing a multiple drug resistance phenotype. Amplification or rearrangement of Her-2neu, Ha-ras, and C-myc genes was observed neither in the original tumor nor in BRC-230 cells; the mdr-1 gene was also present in a single copy. We conclude from these studies that the BRC-230 cell line maintains the same characteristics as the original tumor and may provide us with a good model to study in vitro the biology of drug resistance of breast cancer.

Aged↗