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Biomedical subjects

P Muretto

Publications and source records attributed to P Muretto.

At least 37 records · Page 2Linked to original sources
PubMed1999

Thymidylate synthase protein expression in advanced colon cancer: correlation with the site of metastasis and the clinical response to leucovorin-modulated bolus 5-fluorouracil.

Recently, we have demonstrated that thymidylate synthase (TS) protein expression predicts for the clinical response to a regimen of infusional 5-fluorouracil (5FU) in advanced colorectal cancer patients. Previous studies by other groups that showed a correlation between TS gene expression and response to the fluoropyrimidine also involved infusional regimens. Considering the putatively different mechanism of action of bolus compared with continuous infusion of 5FU, the aim of the present study was to test whether the correlation between TS expression and the clinical response to 5FU is valid for bolus regimens. A secondary aim was to compare TS levels between liver metastases and abdominal recurrences from colon cancer, because these sites have a distinctly different responsiveness to 5FU chemotherapy. The study population consisted of 41 patients (25 males and 16 females; median age, 60 years) with unresectable metastatic or recurrent colon cancer, homogeneously treated with 5FU (420 mg/m2 i.v., days 1-5) and leucovorin (20 mg/m2 i.v., days 1-5); cycles were repeated every 28 days. Twenty-seven patients (66%) showed high levels of TS expression as defined by TS scores equal to 3 and 4. The proportion of cases with high levels of TS expression was significantly higher in abdominal recurrences (18 of 22, 82%) compared with liver metastases (9 of 19, 47%; P = 0.02). Intratumoral TS protein expression was inversely correlated with response to chemotherapy (response rate: 7 of 14, 50%, versus 0 of 27 in patients with low and high levels of TS expression, respectively; P = 0.0001). These results confirm that the level of TS protein expression predicts for response to 5FU, even with a bolus schedule. The higher TS levels observed in abdominal compared with liver metastases may account for their different responsiveness to 5FU chemotherapy. Immunohistochemical quantitation of TS protein levels may thus allow us to change the therapeutic approach to advanced colorectal cancer from a general to an individual treatment strategy at a time when new non TS-targeted drugs have become available for this disease.

Adult↗
PubMed1998

Expression of p53 protein and resistance to preoperative chemotherapy in locally advanced gastric carcinoma.

BACKGROUND: Inactivation of the p53 gene has been reported to be associated with resistance to chemotherapy. The authors evaluated the significance of p53 status to the clinical outcomes of patients with locally advanced, unresectable gastric carcinoma (LAGC) who received chemotherapy. METHODS: Thirty chemotherapy-naive patients with LAGC received weekly administration of cisplatin 40 mg/m2, epi-doxorubicin 35 mg/m2, 5-fluorouracil 500 mg/m2, 6S-leucovorin 250 mg/m2, and glutathione 1500 mg/m2. After eight administrations of these agents, patients were assessed for response. Biopsy specimens of primary tumors were analyzed for p53 status using monoclonal antibody Bp53-12. RESULTS: Characteristics of patients were as follows: The median age was 66 years (range, 44-70 years); 18 were males and 12 were females. Eastern Cooperative Oncology Group performance status was 0 for 14 patients and 1 for 16. Histology was intestinal for 13 patients; for 17, it was diffuse. The site of the primary tumor was the cardia in 8 patients, the body of the stomach in 13, and the antrum in 9. The response rate (assessed with CT scan and endoscopy) for patients with p53 negative tumors was significantly higher than for those with overexpression of p53 (71% vs. 12%, P=0.004). CONCLUSIONS: p53 status analyzed before chemotherapy seems to be associated with response to treatment in patients with LAGC. This may provide a useful guide to selecting neoadjuvant chemotherapy for these patients.

Adult↗
PubMed1998

Treatment of iron overload in the "ex-thalassemic". Report from the phlebotomy program.

After successful marrow transplantation (BMT) iron overload remains an important cause of morbidity in Thalassemia. After BMT, patients have normal erythropoiesis capable of producing a hyperplastic response to phlebotomy so that this procedure can be contemplated as a method of mobilizing iron from overloaded tissues. Forty-one patients (mean age 16 +/- 2.9 years) with prolonged follow-up (range 2-7 years) after BMT were submitted to a moderate intensity phlebotomy program (6 ml/kg blood withdrawal at 14-day intervals) to reduce iron overload. Values are expressed as mean +/- SD or as median with a range (25th-75th percentile). Serum ferritin decreased from 2,587 (2,129-4,817) to 280 (132-920) micrograms/l (p < 0.0001), total transferrin increased from 2.34 +/- 0.37 to 2.9 +/- 0.66 g/l (p = 0.0001), transferrin saturation decreased from 90% +/- 14% to 39% +/- 34% (p < 0.0001). Liver iron concentration evaluated on liver biopsy specimens decreased from 20.8 (15.5-28.1) to 3 (0.9-14.6) mg/g dry weight (p < 0.0001). Alanine amino-transaminase from 5.2 +/- 3.4 to 1.6 +/- 1.2 (p < 0.0001) times the upper level of normality. The histological grading for chronic hepatitis (Histology Activity Index) decreased from 4.2 +/- 2.4 to 2.3 +/- 1.8 (p < 0.0001). Phlebotomy is a safe, efficient, and widely applicable method to decrease iron overload in "ex-thalassemic."

Adolescent↗
PubMed1998

Ultrasound-guided fine needle cutting biopsy for the characterization of diffuse liver diseases in bone marrow transplant patients.

Liver disease is a frequent complication in bone marrow transplant recipients and may occur early or late in the post-transplant period. Using ultrasound-guided fine needle (1.2 mm, 18 G) cutting biopsy, we studied six patients with undefined late post-BMT liver disease. No procedure-related complications occurred and all liver biopsies were informative, leading to changes in therapeutic approach. In our small series, the most frequent cause of hepatic damage was drug toxicity. US-guided fine needle cutting biopsy is a useful and easy tool for the work-up of unexplained post-BMT liver disease.

Adolescent↗
PubMed1998

Immunohistochemical study of tonsils from newborn infants with emphasis on follicular dendritic reticulum cells.

The origin of follicular dendritic reticulum cells (FDRCs) is still debated in the literature, although their derivation from local transformed mesenchymal cells is now generally accepted. The purpose of this immunohistochemical study was to further define the nature of the FDRC, for which an endothelial cell derivation was proposed in previous papers. Palatine tonsils were removed at autopsy from eight newborn infants ranging from a few hours to four days of age. Paraffin embedded tonsil specimens were stained by current histochemical methods and immunohistochemically processed with a panel of antibodies against follicular dendritic reticulum cells (CD21 and CD35), endothelial cells (Factor VIII R. Ag, CD31, CD34), B lymphoid cells (L26, LN1, MB2), T lymphoid cells (UCHL1, DF-T1, OPD4, CD8, CD3), monocytic cells (PGM1 and KP1), interdigitating dendritic cells (S100 Protein, PGM1), intercellular adhesion molecule (ICAM-1 (CD54). Double immunostainings for endothelial markers and for FDRCs were performed. In newborn infant tonsils, lymphoid follicles are absent. T lymphocytes appear to represent the largest component whereas B lymphocytes are seen in small aggregates between blood capillary vessels. Monocytes and interdigitating dendritic cells are also present. The capillary endothelial cells within the B lymphoid aggregates are positive for endothelial and FDRCs markers; double immunostaining for Factor VIII R Ag (or other endothelial markers) and CD21 was present within the same capillary endothelial cells. Further they were positive for ICAM-1. These observations lend further evidence that the derivation of FDRCs may be from transformed endothelial cells and on this way they act as enhancing microenvironment for B lymphocyte expansion.

Animals↗
PubMed1997

Limitations of magnetic resonance imaging in measurement of hepatic iron.

To evaluate the usefulness of magnetic resonance imaging for the quantitative determination of hepatic iron, we examined 43 patients with thalassemia major and assessed the influence of pathologic changes in the liver on the precision of estimates of the hepatic iron concentration. Tissue signal intensities were measured from magnetic resonance T1-weighted images derived from gradient-echo (GE) pulse sequences and the ratio of the signal intensity of liver to muscle calculated. By excluding patients (n = 9) having a signal intensity ratio (SIR) less than or equal to 0.2, a linear relationship with hepatic iron was found and subsequent analyses were limited to these 34 patients. In 27 patients with hepatic fibrosis, an overall correlation of -0.848 was found between hepatic iron and SIR. By contrast, in the seven patients with no fibrosis, the correlation coefficient (-0.993) was significantly greater (P < .0001). Despite the differences in correlation, the regression line between hepatic iron and SIR for the patients with no fibrosis did not differ significantly with respect to either slope or intercept from that of the patients with fibrosis. Thus, the presence of fibrosis did not seem to affect the pattern of the relationship between hepatic iron and the SIR, but rather to increase the variability of the relationship. Clinically, the presence of fibrosis makes estimates of hepatic iron derived from magnetic resonance imaging so variable as to be of little practical use in the management of transfusional iron overload.

Adolescent↗
PubMed1997

Phlebotomy to reduce iron overload in patients cured of thalassemia by bone marrow transplantation. Italian Cooperative Group for Phlebotomy Treatment of Transplanted Thalassemia Patients.

In thalassemia after successful bone marrow transplantation (BMT), iron overload remains an important cause of morbidity. After BMT, patients have normal erythropoiesis capable of producing a hyperplastic response to phlebotomy so that this procedure can be contemplated as a method of mobilizing iron from overloaded tissues. A phlebotomy program (6 mL/kg blood withdrawal at 14-day intervals) was proposed to 48 patients with prolonged follow-up (range, 2 to 7 years) after BMT. Seven patients were not submitted to the program (five because of refusal and two because of reversible side effects). The remaining 41 patients (mean age, 16 +/- 2.9 years) were treated for a mean period of 35 +/- 18 months. All were evaluated before and after 3 +/- 0.6 years of follow-up. Values are expressed as mean +/- standard deviation (SD) or as median with a range (25 to 75 percentile). Serum ferritin decreased from 2,587 (2,129 to 4,817) to 417 (210 to 982) microg/L (P < .0001), total transferrin increased from 2.34 +/- 0.37 to 2.7 +/- 0.58 g/L (P = .0001), transferrin saturation decreased from 90% +/- 14% to 50% +/- 29% (P < .0001). Liver iron concentration evaluated on liver biopsy specimens decreased from 20.8 (15.5 to 28.1) to 4.2 (1.6 to 14.6) mg/g dry weight (P < .0001). Aspartate transaminase decreased from 2.7 +/- 2 to 1.1 +/- 0.6 (P < .0001) and alanine transaminase from 5.2 +/- 3.4 to 1.7 +/- 1.2 (P < .0001) times the upper level of normality. The Knodell score for liver histological activity decreased from 6.9 +/- 3 to 4.9 +/- 2.8 (P < .0001). These data indicate that phlebotomy is safe, efficient, and widely applicable to ex-thalassemics after BMT.

Adolescent↗
PubMed1997

Kaposi's sarcoma after allogeneic bone marrow transplantation.

A case of Kaposi's sarcoma (KS) in an allogenic BMT recipient is reported. A 26-year-old man underwent allogeneic bone marrow transplantation for microdrepanocytosis. He received prolonged immunosuppressive therapy for mild chronic GVHD. Two years after BMT he developed KS localized to the skin. The KS improved rapidly and outcome was complete remission after cessation of immunosuppression.

Adult↗
PubMed1997

Alpha-interferon treatment of chronic hepatitis C after bone marrow transplantation for homozygous beta-thalassemia.

No experience has been reported to date in treating chronic hepatitis C virus (HCV) infection with interferon (IFN) therapy after BMT, mainly due to concerns related to the impact of an immunomodulatory drug in patients who are immunologic and haematologic chimeras. However, chronic inflammatory activity related to HCV infection results in a chronic fibrogenous mechanism potentially leading to liver cirrhosis and hepatocellular carcinoma. Moreover, patients transplanted for beta-thalassemia could be at greater risk because of concomitant iron overload and pre-existing fibrous liver damage. Eleven patients with serological, biochemical, histological and molecular biological evidence of HCV infection were included in the study and treated for 6-12 months with recombinant IFN 24-65 months following BMT. The serum alanine aminotransferase (ALT) was persistently elevated (range 85-1242 U/l; mean 416) for at least 1 year prior to IFN treatment. Ten patients completed the protocol; five were considered as responders to treatment. In these five patients the liver histology showed an overall reduction of inflammation and necrosis: histological inflammatory activity improved from chronic active hepatitis (CAH) to chronic persistent hepatitis (three patients) or minimal residual inflammatory activity (two patients). The Knodell total activity score varied from 5.4 (range 3-9) to 1.4 (range 1-2; P = 0.05). All responding patients revealed negativization of serum HCV-RNA, that has been persistent in four (follow-up 1-3 years). ALT level fell to 15-80 U/l (mean 52; P = 0.0027). No major complications occurred during the therapy and no influence on marrow engraftment parameters were noted. We conclude that IFN therapy does not adversely interfere with engraftment and that it is a feasible therapy for treatment of chronic hepatitis C virus after BMT.

Adolescent↗
PubMed1997

[Could lymph node microangiopathy play a part in the immunodeficiency of diabetes? Histological and immunohistochemical study of lymph nodes from 4 patients with long-term insulin-dependent diabetes mellitus subjected to autopsy examination].

The reason of increased susceptibility to frequent and protracted infections in diabetic patients is still unclear, although a multitude of "in vitro" studies have focused on the metabolic and functional modifications of the immune cells. From the literature immune abnormalities have been demonstrated "in vitro models" in genetic (type 1), autoimmune (type 2) and metabolic (type 1 and type 2) insulin-dependent diabetes mellitus (IDDM), and concisely referred in this paper. Diabetes microangiopathy, which is a peculiar alteration of the disease has been extensively described on many sites such as retina, renal glomeruli, skin etc, but as far as we know, not yet in the lymph-nodes. Therefore we report our histological and immunohistochemical observations in lymph-nodes removed from four patients with long-term IDDM, submitted to autoptic examination. On the clinical history all had shown, in the last years, lymphocytopenia and several infective diseases. The peculiar microangiopatic modifications appear joint to lymphodepletion of B and T cell dependent areas with marked reduction of follicular dendritic reticulum cells. The microangiopathy of thin intranodal capillaries besides compromise the diapedesis and traffic of the T and B lymphocytes could prevent the transformation of endothelial cells into dendritic reticulum cells. Indeed from the recent literature the dendritic reticulum cells should appear derived from transformed endothelial cells. This histological and immunohistochemical report could thence provide some additional knowledge about the complex problem of the immunodeficiency in diabetic patients.

Adult↗
PubMed1996

Mucormycosis after bone marrow transplantation: report of four cases in thalassemia and review of the literature.

We report four cases of mucormycosis that occurred among 711 patients who underwent BMT for thalassemia, and review 18 additional cases among BMT recipients that were reported in the English-language literature. All these patients were polytransfused and were in advanced phase of disease with severe acquired hemochromatosis. The sites of infection were sinonasal, rhinocerebral-pulmonary, pulmonary and pulmonary-central nervous system. Mucormycosis was the primary cause of death in three of four patients. Two infections were detected within the first 100 days after BMT. Only one of the four patients had partial resolution of sinonasal mucormycosis following aggressive antifungal therapy combined with hyperbaric oxygen treatment.

Adolescent↗
PubMed1995

An immunohistochemical study on foetuses and newborns lymph nodes with emphasis on follicular dendritic reticulum cells.

Lymph nodes were withdrawn from twenty foetuses and eighteen newborns. Paraffin embedded tissues were stained by current histochemical methods and immunohistochemically processed with a panel of antibodies against dendritic reticulum cells (DRC) (CD21, CD35), endothelial cells (QBEnd/10-CD34, CD31, Factor VIII RAg), B lymphoid cells (L26, MB2), T lymphoid cells (UCHL1, DF-T1, OPD4), monocytic cells (PGM1, KP1) and interdigitating dendritic cells (S100 protein, PGM1). The immunohistochemistry was focused on determining the initial appearance of DRC whose origin is still debated. They are currently considered to be transformed mesenchymal cells. This study shows that DRC make their appearance in the superficial or subcutaneous lymph nodes just at the beginning of extrauterine life whereas they are identifiable in the mesenteric lymph-nodes already during the foetal life. They acting as an enhancing microenvironment, appear to be related to B lymphocyte expansion. Their derivation from endothelial cells rather than other mesenchymal cells seems more probable.

Antibodies↗
PubMed1994

Bone marrow transplantation in thalassemia: modifications of hepatic iron overload and associated lesions after long-term engrafting.

Among 450 thalassemic patients treated in the Hematologic Department, 50 patients who were disease-free 4-6 years after allogeneic bone marrow transplantation were sequentially studied by liver biopsy. The patients received marrow from siblings who were genotypically HLA identical at A, B, C and DR loci. For evaluation of siderosis and associated lesions, each patient underwent liver biopsy before, and again 6 months and yearly for 4 to 6 years after bone marrow transplant. Spontaneous reversibility of liver iron overload, once the need for transfusions ceased when a functioning graft had been established, was observed in the youngest patients, aged 1-8 years, whereas iron excess remained at the end of follow-up in many patients aged 9-15 years. Hypotheses about the mechanism of the iron decrease are discussed. Several cases also obtained improvement of associated pathologies such as hepatitis, probably through modifications in the mechanisms controlling their immunological status.

Adolescent↗
PubMed1994

Chronic liver disease and active hepatitis C virus infection in patients with antibodies to this virus.

AIMS: To assess the association between active hepatitis C virus (HCV) infection and liver damage in randomly selected patients with antibodies to the virus. METHODS: Thirty three consecutive subjects with serologically confirmed positivity for antibodies to HCV were studied for the presence of liver and circulating viral sequences by using the reverse transcription polymerase chain reaction (RT-PCR) and specific primers for the 5'-untranslated region (5'-UTR) of the HCV genome. Parallel clinical, biochemical, and histological investigations were carried out in all cases. RESULTS: A comparative virological and histological investigation showed the presence of molecular signs of active viral replication and different degrees of liver damage in all cases. Baseline values of liver and plasma samples from all the patients showed (with one exception) the presence of detectable HCV RNA sequences, despite alanine amino transferase activities being within normal values or within 1.5 times the upper limit of normal in 13 of them. Examination of percutaneous liver biopsy specimens showed the presence of confirmed liver damage (ranging from chronic persistent hepatitis to cirrhosis) in all 33 patients. CONCLUSIONS: Circulating HCV RNA sequences (a direct sign of active HCV infection) are associated with liver damage, even in the absence of clinical or biochemical signs of overt liver disease. Parallel molecular, histological, and clinical follow up of these patients is needed to understand precisely the natural history of HCV infection and for correct clinical management.

Base Sequence↗
PubMed1994

Lymphoid follicles in extranodal sites: an immunohistochemical study.

Lymphoid follicles in extranodal sites involved in chronic inflammatory reactions are the subject of this study. Immunohistochemistry was focused on associated lymphoid formations considered as incomplete or prefollicular structures because they were composed only of some types of the germinal centre cells among demonstrated dendritic reticulum cells (DRC) and thin vessels. Paraffin embedded tissues were stained with current histological methods and immunohistochemically processed with a panel of antibodies against DRC (CD21, CD35, IgM); endothelial cells (factor VIII R. Ag., EUA); B lymphoid cells (L26, MB2); T lymphoid cells (UCHL1, MT1): intercellular adhesion molecule (ICAM-1); histiocytic/monocytic cells (KP1, PS100, delta-1-antitrypsin, delta-1-antichymotrypsin); smooth muscle (actin 1A4); basement membranes (collagen IV). Prefollicular structures showed positivity for B cells markers among a network of DRC and thin long processes. Furthermore, scattered T lymphoid and histiocytic cells such as collagen IV fragments and some pericytic cells were demonstrated. Some sections with Emat-eos. were destained and submitted to immunohistochemistry analyses: in prefollicular structures, histologically referred endothelial cells were positive for dendritic reticulum markers and ICAM-1. These findings appear to favor the hypothesis that DRC could be transformed endothelial cells which therefore represent an important component in follicular formation.

Antibodies, Monoclonal↗
PubMed1994

Primary bronchial malignant melanoma. A case report.

A case of primary bronchial malignant melanoma occurred in a 66 years old woman is reported. Because of cough and hemoptysis bronchoscopic examination was performed and and a polypoid mass was found to occlude the right lower bronchus. Histopathologic examination showed the presence of malignant melanoma also confirmed by immuno reactivity with antibodies to S-100 protein and melanoma associated monoclonal antibody HMB45. Clinical history, physical examination and other instrumental investigations failed to find other possible primary sites of the tumour. Primary melanoma of the lung is a very rare condition, but our case seems to satisfy the criteria to be considered in the little group of definite primary melanoma of the lower respiratory tract.

Aged↗
PubMed1993

Fate of iron stores in thalassaemia after bone-marrow transplantation.

After successful bone-marrow transplantation (BMT) in thalassaemia, the individual acquires the pattern of globin synthesis of the donor. We call such an individual "ex-thalassaemic after BMT", a term that underscores the cure of the genetic defect but maintenance of residual signs of organ damage due to iron overload and dysfunction acquired during the pretransplant years. We have analysed the extent and fate of tissue iron overload in 151 ex-thalassaemic patients after BMT, according to the risk factors of hepatomegaly, hepatic portal fibrosis, and inadequate chelation therapy. Serum ferritin concentrations decreased and unbound iron binding capacity (UIBC) increased slowly during the years after the transplant. When analysed according to risk group (assigned at the time of the transplant), ferritin and UIBC returned within the normal ranges in only the low-risk group (without hepatomegaly or portal fibrosis, and with adequate chelation pre-BMT). Ferritin and UIBC were still abnormal 7 years after the transplant in the moderate-risk group (those with one or two risk factors) and highly abnormal in the high-risk group (all three risk factors) indicating persistence of, respectively, moderate and severe iron overload at the time of transplant. In ex-thalassaemic patients who were studied before and yearly after the transplant the extent of haemosiderosis, as judged by staining of liver biopsy samples, decreased during the years after transplant. The degree of iron deposition and rate of post-BMT linear growth seem to influence rate of post-BMT decrease in tissue iron overload in different risk groups at the time of BMT.

Adolescent↗