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Biomedical subjects

A Castello

Publications and source records attributed to A Castello.

At least 19 recordsLinked to original sources
PubMed2003

The C(-260)>T gene polymorphism in the promoter of the CD14 monocyte receptor gene is not associated with acute myocardial infarction.

CD surface molecules mediates cell activation and signaling. In particular, CD14 on blood monocytes mediate monocyte/macrophage activation by lipopolysaccharide. Lipopolysaccharide and its receptor, CD14, have been implicated in atherogenesis. It has been recently shown that a C(-260)T polymorphism in the promoter of the CD14 receptor may be a risk factor for coronary artery disease. Recently this association has been questioned because no increased risk was found with the T allele, even in the homozygous state. In the present study we investigated a possible association between the C(-260)T polymorphism in the CD14 promoter and acute myocardial infarction. Two hundred and thrteen patients with and acute myocardial infarction 213 healthy controls were included in the study. Genotype frequencies of the C(-260)T polymorphism in the CD14 promoter were determined by polimerase chain reaction and the amplified product was cleaved with HaeIII. The frequency of the T allele was not significantly different in patients compared with controls. In this study we were not able to detect differences of frequency of the allele T (-260) in the promoter of the CD14 receptor gene in survivors of myocardial infarction and controls.

Cytosine↗
PubMed2001

Evaluation of bioavailability of three types of IFNbeta in multiple sclerosis patients by a new quantitative-competitive-PCR method for MxA quantification.

Intracellular expression of human myxovirus protein A (MxA) is exclusively induced by type I IFNs (IFNalpha,beta,omega) or by some viruses and it is strongly increased under IFN treatment. We set up an internally controlled quantitative-competitive polymerase chain reaction (qc-PCR) that quantifies MxA mRNA expressed in human peripheral blood mononuclear cells (PBMC). Our qc-PCR is accurate because the mean ratio of copy number estimated by qc-PCR to that quantified spectrophotometrically is 1.08+/-0.03, moreover it is repeatable with high sensitivity (1 fg MxA/pg GAPDH). MxA mRNA was tested in 47 Relapsing-Remitting Multiple Sclerosis (RR-MS) untreated patients and in 48 patients treated with one of the 3 IFNbeta licensed for MS (24 with Rebif, 14 with Avonex and 10 with Betaferon). All the 48 treated patients were negative to IFNbeta neutralising antibodies (NABs) as tested in our laboratory using a cytopathic assay (CPE). MxA mRNA levels were detectable in all untreated patients (mean 24+/-18 fg MxA/pg GAPDH) and significantly higher levels were found in all the treated patients 12 h after IFNbeta administration (mean 499+/-325 fg MxA/pg GAPDH); furthermore, the three types of IFNbeta showed comparable bioavailability. Our data indicate that the bioavailability of the three available types of IFNbeta can be evaluated by MxA qc-PCR.

GTP-Binding Proteins↗
PubMed2001

Safety and efficacy of thrombolysis with alteplase (50 mg) plus tirofiban versus alteplase (100 mg) alone in acute myocardial infarction: preliminary findings.

BACKGROUND: The goal of therapy in acute myocardial infarction (AMI) is the complete and timely restoration of coronary blood flow. Platelets have a pivotal role in the pathophysiology of AMI. The study was aimed at evaluating the safety and efficacy of the combination of 50 mg alteplase plus tirofiban vs 100 mg alteplase in AMI patients. METHODS: One hundred twenty patients (83 males, 37 females; mean age 54.3 +/- 8 years) were hospitalized for suspected AMI within 6 hours of the onset of symptoms. All patients presented pain and persistent ST-segment elevation, were suitable candidates for thrombolysis (1st episode) and were randomized (double blind) into two groups. Group A (n = 60,42 males, 18 females) received 50 mg alteplase (15 mg as bolus, followed by an infusion of 35 mg over 60 min) in combination with tirofiban (0.4 mcg/kg/min for 30 min followed by an infusion of 0.1 mcg/kg/min for 3 days). Group B (n = 60, 41 males, 19 females) received 100 mg of accelerated-dose alteplase alone. Reperfusion criteria were defined as follows: > 50% reduction in the ST-segment elevation; resolution of chest pain; double marker of creatine kinase (CK) and CK-MB activity 2 hours after the start of thrombolysis; reperfusion arrhythmias within the first 120 min of thrombolysis. The blood pressure, heart rate and ECG were continuously monitored. The mortality, re-AMI, recurrent angina, major and minor bleeding, and emergency bypass surgery or coronary angioplasty were checked. RESULTS: The groups were similar with regard to clinical data, risk factors, time elapsed from the onset of symptoms to thrombolytic therapy and AMI localization. Forty-seven patients (78.3%) from group A showed reperfusion (15-60 min) vs 25 patients (41.7%) from group B (43-105 min after the end of full-thrombolysis, p = 0.01). Group A patients showed an earlier CK peak and lower CK and CK-MB peaks than those in the control group (p = 0.0001, p = 0.011, p = 0.005, respectively). Nine patients (7.5%) died: 6 (10%) in group B and 3 (5%) in group A (p = NS). A non-fatal re-AMI occurred in 8 patients from group A and in 4 patients from group B (p = NS). Recurrent angina occurred in 27 patients (45%) from group A and in 11 (18.3%) from group B (p = 0.037). Twenty-three of these patients underwent urgent coronary angioplasty (17 from group A and 6 from group B) and 3 from group A and 1 from group B underwent urgent coronary artery bypass grafting (p = NS). The frequency of minor bleeding was higher in group A than in group B (56.7 vs 25%, p = 0.033). No major bleeding was observed in the study groups. At the predischarge echocardiogram, the ejection fraction was higher in group A than in group B (50 +/- 9 vs 44 +/- 7%, p = 0.001). CONCLUSIONS: Our data suggest that the combination of glycoprotein IIb/IIIa inhibitors plus alteplase is feasible in AMI patients and that the increased risk of bleeding is an acceptable risk considering the advantage in terms of the reduction in the extent of an AMI. In addition, this combination can allow one to gain time when it is necessary to perform mechanical revascularization in patients admitted to a hospital without an interventional cardiology laboratory or in those who have to be referred to another hospital for urgent coronary artery bypass grafting.

Creatine Kinase↗
PubMed2000

Utility and safety of immediate exercise testing of low-risk patients admitted to the hospital with acute chest pain.

It is common practice to hospitalize patients with chest pain for a period of observation and to perform further diagnostic evaluation such as exercise treadmill testing (ETT) once acute myocardial infarction (AMI) has been excluded. This study evaluates the safety and efficacy of immediate ETT for patients admitted to the hospital with acute chest pain. One hundred and ninety non-consecutive low-risk patients admitted to the hospital from emergency department with acute chest pain underwent ETT using Bruce protocol immediately on admission to the hospital (median time 165+30 min). Fifty-seven (30%) patients had positive exercise electrocardiograms, 44 (77.2%) of whom had significant coronary narrowing by angiography. An uncomplicated anterior non-Q-wave AMI was diagnosed in one patient. One hundred and eleven (58.4%) patients had negative and 22 (11.6%) patients had non-diagnostic exercise electrocardiograms. Of these 133 patients, 86 (64.7%) were discharged immediately after ETT, 19 (14.3%) were discharged within 24 h, and 28 (21%) were discharged after 24 h of observation. There were no complications from ETT. During the 17+/-6 months follow-up no patients died, and only eight (7.2%) patients with negative ETT experienced a major cardiac event (one AMI and seven angina). In conclusion, our results suggest that immediate ETT of low-risk patients with chest pain who are at sufficient risk to be designated for hospital admission, is effective in further stratifying this group into those who can be safety discharged immediately and those who require hospitalization.

Chest Pain↗
PubMed2000

Interferon beta neutralizing antibodies in multiple sclerosis: neutralizing activity and cross-reactivity with three different preparations.

The presence and titer of neutralizing antibodies (NABs) was evaluated by an antiviral biological assay in 387 samples of 111 multiple sclerosis (MS) patients treated with one of the three commercial preparations of interferon beta (IFNbeta). Fifty NAB positive samples were found in 19 patients: 11 treated with IFNbeta-1b (Betaferon(R)) and eight with IFNbeta-1a (five with Avonex(R) and three with Rebif(R)). All the 38 NABs+ samples of patients treated with IFNbeta-1b cross-reacted with IFNbeta-1a of both commercial types. The median level of neutralizing units (NUs) of the sera was higher when tested against IFNbeta-1a than against IFNbeta-1b (p=0.000 vs. Avonexr(R) and p=0.003 vs. Rebif(R)). In line with these data, the NABs+ sera of patients treated with IFNbeta-1a cross-reacted with IFNbeta-1b and the level of NUs were lower when tested against IFNbeta-1b than against IFNbeta-1a (p=0.003). The different amount of NUs against IFNbeta types 1a and 1b could be due to the presence of aggregates in the IFNbeta-1b preparation. The different levels of cross-reactivity of NABs could reduce the bioavailability and therapeutic efficacy of IFNbeta in NABs+ patients switching from IFNbeta-1b to IFNbeta-1a.

Adjuvants, Immunologic↗
PubMed2000

Efficacy of rescue thrombolysis in patients with acute myocardial infarction: preliminary findings.

Thrombolysis reduces mortality in patients with acute myocardial infarction (AMI) who are hospitalized within 6 hours from the onset of symptoms. AMIs involving a small area of myocardium show a lower mortality in comparison with AMI involving a large area. The present study was aimed at evaluating the safety and efficacy of rescue thrombolysis in patients with large AMI who had failed thrombolysis. Ninety patients (69 Males and 21 Females), mean age 56.7 +/- 9 years, hospitalized for suspected AMI within 4 hours from the onset of symptoms, suitable for thrombolysis (First episode), and showing pain and persistent ST segment elevation 120 minutes after starting thrombolysis, were randomized (double-blind) into two groups. Group A (45 patients: 10 females and 35 males) received an additional thrombolytic treatment (rTPA 50 mg), 10 mg as bolus plus 40 mg in 60 minutes. Group B (45 patients: 11 females and 34 males) received placebo. Positive noninvasive markers were defined as follows: (1) resolution of chest pain, (2) > or = 50% reduction in ST segment elevation, (3) double marker of creatine kinase (CK) and CK-MB activity 2 hours after the start of thrombolysis, and (4) occurrence of reperfusion arrhythmias within the first 120 minutes of thrombolytic therapy. Blood pressure, heart rate, and ECG were continuously monitored. An echocardiogram was carried out at entry, and before discharge, to control ejection fraction and segmentary kinetics. Adverse events such as death, re-AMI, recurrent angina, incidence of major and minor bleeding, and emergency CABG/PTCA were checked. The groups were similar in terms of age, sex, diabetes, smoking habits, hypertension, and adjuvant therapy (beta-blockers). No significant difference was observed between the two groups regarding the time elapsed from the onset of symptoms to thrombolysis and AMI localization. Thirty-five patients (77.7%) showed reperfusion (10-50 minutes) after commencement of additional rTPA. Of the patients receiving placebo, 12 (26.6%) showed reperfusion within 35-85 minutes. Group A showed an earlier and lower CK and CK-MB peak than the control group, (respectively, p = 0.0001-0.009 and 0.002). Mortality (17.7%, 16 patients) was higher in group B than in the additional rTPA group, i.e., 6.6% (3 patients) in group A versus 28.8% (13 patients) in Group B (p = 0.041). Seven patients from group A showed nonfatal re-AMI. Angina was observed in 18 patients (40%) from group A and 3 (6.6%) from group B (p = 0.006). Ten of these patients underwent urgent PTCA (9 from group A and 1 from group B), and 3 from group A underwent urgent CABG. Minor bleeding was higher in group A than in group B (44.4% versus 15.5%, p = 0.047). Major bleeding was observed in group A (nonfatal stroke). At predischarge, the echocardiogram ejection fraction was higher in group A than in group B (46 +/- 8% versus 38 +/- 7%, p = 0.0001). Our data suggest that an additional dose of thrombolytic drug in patients with unsuccessful thrombolysis is feasible and also that the bleeding increase is an acceptable risk in comparison with the advantages obtained in reducing AMI extension. Rescue thrombolysis can allow a gain in time to perform mechanical revascularization in patients admitted to hospital without an interventionist cardiology laboratory or in those who have to be referred to another hospital for urgent CABG.

Acute Disease↗
PubMed2000

VP7 and VP4 genotyping of human group A rotavirus in Buenos Aires, Argentina.

Specific and sensitive tests for the detection and typing of group A rotavirus strains are needed for a more comprehensive knowledge of the epidemiology of rotaviral infection. In this study 500 stool specimens taken from 1996 to 1998 from children with acute diarrhea in Buenos Aires were examined. Group A rotavirus was unequivocally demonstrated in 62% of the samples tested by enzyme-linked immunosorbent assay (ELISA) for detection of VP6 antigen, polyacrylamide gel electrophoresis of double-stranded RNA, and reverse transcription-PCR (RT-PCR) for amplification of the VP7:G (1, 062 bp) and VP4:P (876 bp) genes. Only five positive specimens were found by RT-PCR but not by ELISA. G and P typing was carried out by nested amplification of variable sequences of the VP7 and the VP4 genes with six G- and five P-type-specific primers (multiplex PCR). Results obtained by this method showed the prevalence of the following G and P types: G1, 39%; G2, 43%; G4, 4%; P[8], 16%; P[4], 71%. Unexpectedly, the G-P type combination most frequently found was G2P[4] (43%) rather than G1P[8] (12%), which is the most commonly found worldwide. Unusual strains of the type G1P[4] accounted for 14% of the total, while mixed infections with more than one type were found in 10% of the samples. Detection of fecal rotavirus-specific immunoglobulin M (IgM) and IgA antibodies in consecutive samples of two patients taken at daily intervals demonstrated that high levels of IgM and IgA antibodies were detected on day 1 after the onset of disease and that the samples remained positive for about 10 days, after which virus shedding was no longer observed. Multiplex PCR offers a sensitive and specific alternative to determine the prevalence of group A rotavirus G and P types and to identify the emergence of uncommon strains, whereas detection of fecal IgM and IgA antibodies represents a useful supplement to virus detection for the diagnosis of current or recently acquired infections.

Antibodies, Viral↗
PubMed2000

[The safety and efficacy of systemic salvage thrombolysis in acute myocardial infarct].

BACKGROUND: Thrombolysis reduces mortality in patients with acute myocardial infarction hospitalized within 6 hours of the symptom onset. Infarctions involving a small area of the myocardium show a lower mortality in comparison to those involving a large area. The aim of this study was to evaluate the safety and efficacy of rescue thrombolysis in patients with large acute myocardial infarction who had failed standard thrombolysis. METHODS: From January 1995 to December 1997, ninety patients (69 males, 21 females, mean age 56.7 +/- 9 years), hospitalized for suspected acute myocardial infarction within 4 hours of the symptom onset, suitable for thrombolysis (first episode), and who experienced pain and showed persistent ST segment elevation 120 min after starting thrombolysis, were randomized (single blind) into two groups: Group A (n = 45) received an additional thrombolytic treatment (rt-PA 50 mg), 10 mg as a bolus plus 40 mg in 60 min; Group B (n = 45) received conventional therapy. Positive non-invasive markers were defined as follows: resolution of chest pain; > 50% reduction in ST segment elevation; double marker of creatine phosphokinase (CPK) and CK-MB activity 2 hours after the start of thrombolysis; occurrence of reperfusion arrhythmias within the first 120 min of thrombolytic therapy. Blood pressure, heart rate and ECG were continuously monitored. Echocardiogram was carried out at entry and before discharge to control ejection fraction and segmental wall motion. Adverse events such as death, reinfarction, recurrent angina, incidence of major and minor bleeding, and emergency bypass surgery or coronary angioplasty were checked. RESULTS: Thirty-five patients (77.7%) showed reperfusion (10-50 min) after the start of additional rt-PA. In patients who did not receive additional thrombolysis, only 12 (26.6%) showed reperfusion 65-115 min after the end of rt-PA infusion. Group A showed an earlier and lower CK and CK-MB peak than Group B (p = 0.0001, p = 0.009, and p = 0.002, respectively). Mortality (n = 16, 17.7%) was higher in Group B (n = 13) than in Group A (n = 3) (28.8 vs 6.6%, p = 0.041). Seven patients from Group A showed non-fatal reinfarction. Angina was observed in 18 (40%) patients from Group A and 3 (6.6%) from Group B (p = 0.006). Ten of these patients underwent urgent coronary angioplasty (9 from Group A and 1 from Group B) and 3 from Group A urgent bypass surgery. Minor bleeding was higher in Group A than in Group B (44.4 vs 15.5%, p = 0.047). A major bleeding was observed in Group A (non-fatal stroke). At predischarge echocardiogram ejection fraction was higher in Group A than in Group B (46 +/- 8 vs 38 +/- 7%, p = 0.0001). CONCLUSIONS: Our data suggest that an additional dose of a thrombolytic drug in patients with unsuccessful thrombolysis is feasible, and the bleeding increase is an acceptable risk in comparison with the advantages obtained from a reduced infarct extension. Rescue thrombolysis could save time and allow mechanical revascularization to be carried out in patients admitted to a hospital without interventional cardiology laboratory or in those who have to be refereed to other hospitals for urgent bypass surgery.

Aged↗
PubMed1999

Bone marrow changes in heart transplant recipients with peripheral cytopenia.

BACKGROUND: We analyzed bone marrow changes in heart transplant recipients who develop peripheral cytopenia and underwent bone marrow biopsy (BMB). We correlated the changes in bone marrow with survival, acute and chronic rejection, infections, and malignancy. METHODS: The test group was constituted of 64 heart transplant recipients with peripheral cytopenia, in whom 82 BMBs were performed to assess marrow quantitative (cellularity, erythropoiesis, myelopoiesis, megakaryopoiesis, fibrosis, and blast cells) and qualitative (dyserythropoiesis, dysmyelopoiesis, and dysmegakaryopoiesis) changes. The control series was constituted of 217 matchable transplant recipients without cytopenia. Statistical analysis was aimed at assessing whether: (1) cytopenia is an independent risk factor for survival; (2) acute rejection, chronic rejection, infections, and malignancy predict cytopenia; (3) the degree in BMB change allows further stratification of the risk of death; and (4) characteristics and distribution of BMB lesions vary in patients with and without acute and chronic rejection, infections, and malignancy. RESULTS: In the test group, BMB specimens showed reduced cellularity in 68% of patients and dysplastic changes of a mild degree affecting all three marrow lines (erythropoietic in 88%, myelopoietic in 43%, and megakaryopoietic in 79%). At statistical analysis, peripheral cytopenia was an independent risk factor for survival, and malignancy proved to be a risk factor for cytopenia. Of BMB specimen changes, only dysmegakaryopoiesis showed a trend as a negative risk factor for survival. Acute rejection was associated with a high score of erythropoiesis, infections with a low score of dysmegakaryopoiesis, and malignancy with a high score of cellularity. CONCLUSIONS: Peripheral cytopenia is an independent risk factor for survival in heart transplant recipients. Different marrow changes correlate with transplantation-related complications, i.e., acute rejection, infection, and malignancy.

Adult↗
PubMed1998

5D4 keratan sulfate epitope identifies a subset of ramified microglia in normal central nervous system parenchyma.

Microglia expressing keratan sulfate (KS) was studied in normal central nervous system (CNS) and in rat neonatal brain cultures. The majority of KS+ cells are ramified microglia located in the brain parenchyma; positive cells were only exceptionally found in extraparenchymal structures. KS+ cells are ubiquitous, but their density is heterogeneous throughout the CNS. Serial sections incubated with anti-KS MAb and MAb against the complement receptor type 3 (CR3) revealed a higher number of CR3+ cells and double immunofluorescence showed the presence of two microglial populations: the first expressing both KS and CR3, the second expressing only CR3. Two sets of microglial cells were found also in neonatal rat microglial cultures where only a low percentage of microglial cells expressing CR3 was also KS+. KS was not induced by microglia activation.

Animals↗
PubMed1996

[Comparison of the echo-dobutamine-atropine test and ergometric test in the diagnosis of coronary disease].

BACKGROUND: A prospective study has been done on 46 patients with suspected coronary artery disease (CAD). They had no history of myocardial infarction (MI) and a normal basal kinetic echocardiography. This was done in order to evaluate the overall accuracy of dobutamine-atropine stress echocardiography (DAS) compare to exercise stress test (ET) for the diagnosis of CAD. METHODS: All the patients after suspension of coronary therapy, performed a casual sequence with both maximal or symptom limited exercise testing (treadmill-Bruce protocol) and DAS. The dobutamine has been given while monitoring systemic blood pressure, electrocardiography and echocardiography in steps of 10 mcg/kg/min' per 3 min' up to a maximum of 40 mcg/kg/min'. Atropine has been added (0.25-1 mg) in patients who did not reach the theoretical maximal cardiac frequency. The test is considered positive when kinetic segmental left ventricular dysfunction appeared. CAD was defined as 50% luminal area stenosis in at least 1 coronary artery at coronary angiography. RESULTS: Significant CAD was present in 27/46 patients (59%). Compared with ET, DAS had significantly higher sensitivity (59% vs 92%, p = 0.01). The different sensibility between the two tests was higher on these patients with a 1 vessel disease (40% vs 86%, p = 0.02). There were no significant differences in specificity among the two tests (79% vs 84%, respectively). Differences in overall accuracy between ET and DAS were significant (67% vs 89%, p = 0.02). CONCLUSIONS: The results of our study show that the DAS is a safe and feasible technique with high sensibility (especially in patients with single CAD) and specificity. This is a valid alternative to the traditional ET, especially for these patients unable to exercise or these who are poorly motivated to achieve a work load sufficient to make the test interpretable.

Adult↗
PubMed1994

Hepatitis B virus antigens in peripheral blood mononuclear cells during the course of viral infection.

We studied the expression of surface (HBsAg) and core (HBcAg) proteins of hepatitis B virus (HBV) on the surface of peripheral blood mononuclear cells (PBMC) from HBV-infected patients. A total of 122 patients with different liver viral diseases was analyzed by indirect immunofluorescence with monoclonal antibodies. The 35 patients with HBV chronic active hepatitis (CAH) and 38 of 60 patients with acute hepatitis B (63%) expressed HBsAg on the PBMC. No expression was detected on the cells from both normal and HBV-unrelated viral hepatitis control groups. Serial follow-up of patients with acute hepatitis B showed that HBsAg expression by PBMC tended to be undetectable 4 months after the onset of the disease and at the same time the clinical improvement was evident. Cell cultures of EBV-transformed B lymphocytes were established from PBMC of HBV-infected patients; immunoelectron microscopy demonstrated the HBsAg on the cellular membrane. One-third of HBV-infected patients who were studied showed the expression of HBcAg by PBMC. HBcAg was detected in patients with acute hepatitis B at the early stage of infection. The cells of these patients also expressed HBsAg in PBMC. In CAH patients, a positive association was observed between the expression of HBcAg and the presence of serum HBeAg.

Acute Disease↗
PubMed1992

Bone changes of mucolipidosis II at different ages. Postmortem study of three cases.

Bone changes are a constant feature of mucolipidosis II, with striking differences between newborns and older children. Intracellular, membrane-bound vacuoles were found in the chondrocytes, osteoblasts, osteocytes, and stromal fibroblasts of three affected children. Osteoclasts and marrow cells were unaffected. Ricketslike lesions were present at birth in the two younger cases, whereas signs of high bone turnover and defective calcification were no longer present in the older child. Severe abnormalities of the metaphyseal plate with the loss of normal cartilage architecture and the absence of endochondral ossification were the major changes in this age group.

Age Factors↗
PubMed1990

Risk assessment in myelodysplastic syndromes: value of clinical, hematologic and bone marrow histologic findings at presentation.

We analyzed the prognostic value of clinical, hematologic and bone marrow (BM) histologic findings at presentation in 94 patients with myelodysplastic syndromes (MDS) (28 RA; 2 RARS; 34 RAEB; 6 CMML; 24 RAEB-t). With survival as the dependent variable, stepwise multivariate analysis indicated as the prognostically most important factors among the MDS taken as a whole: latency from the first symptoms to diagnosis, age, and percentage of BM blasts. In each main MDS group the most unfavorable initial characteristics were: 1) low Hb, no macro-megaloblastosis, male sex for RA/RARS; 2) low Hb and low platelet levels for RAEB/CMML; 3) granuloblastic hyperplasia and high BM blastosis for RAEB-t. Of the BM histologic parameters, only the percentage of blasts had significant prognostic value. Histologic assessment of BM blastosis, however, did not differ statistically from that based on cytologic examination of BM smears, so that marrow histology seemed not essential for initial prognostic assessment in MDS patients. The finding of abnormal localization of immature precursors (ALIP) in BM biopsies was associated with a negative trend without reaching statistical significance. Using four objective parameters of proven significance (age, Hb, platelets, and BM blasts) we devised a staging system of immediate clinical utility for prognostic stratification and risk-adapted therapeutic choices.

Biopsy, Needle↗
PubMed1990

Therapy of essential thrombocythemia with alpha-interferon: results and prospects.

Conventional treatment of symptomatic essential thrombocythemia (ET) consists of long-term administration of myelosuppressive cytotoxic agents which, although efficacious in most cases, are associated with leukemogenic potential. Alpha-interferon (IFN) exerts a dose-dependent inhibitory influence on thrombopoiesis through a direct antiproliferative effect on megakaryocytic precursors. Therefore, it may provide a biologic, potentially non-mutagenic alternative to conventional cytotoxic treatments. At daily doses ranging from 1 to 5 M.U., alpha-IFN is efficacious in inducing a hematologic response in most patients with ET. Response to IFN is a gradual process. The median time to hematologic response varies from 1 to 3 months and a significant proportion of patients reach and maintain normal platelet counts with low doses (1-3 M.U./d). Normalization of marrow megakaryocytosis requires longer treatment (9-12 months). Also patients resistant to cytotoxic drugs may respond to alpha-IFN, suggesting a lack of cross-resistance between the two treatment modalities. Side-effects, although not severe, represents a limit to the administration of adequate doses of IFN in about 25% of cases. Once hematologic response has been obtained, both low-dose IFN and cytotoxic drugs are effective as maintenance. The full potentialities of alpha-IFN in ET in combination with cytotoxic drugs or with other cytokines need to be further investigated.

Humans↗
PubMed1990

Bone marrow biopsy in monoclonal gammopathies: correlations between pathological findings and clinical data. The Cooperative Group for Study and Treatment of Multiple Myeloma.

Between January 1987 and October 1989, 561 consecutive untreated patients with monoclonal gammopathy of undetermined clinical importance (MGUS) (n = 295) or with multiple myeloma (n = 266) were evaluated in a multicentre trial. Both bone marrow biopsy and aspiration (performed at different anatomical sites) were required at presentation. Bone marrow biopsy data indicated that changes in bone marrow composition from MGUS to early multiple myeloma and to advanced multiple myeloma followed a precise pattern, including an increased percentage of bone marrow plasma cells (BMPC%), a shift from plasmocytic to plasmoblastic cytology, an increase in bone marrow cellularity and fibrosis, a change in bone marrow infiltration (becoming diffuse rather than interstitial), a decrease in residual haemopoiesis and an increase in osteoclasts. In multiple myeloma the BMPC% of biopsy specimens and aspirate were closely related, although in 5% of cases the difference between the two values was greater than 20%. Some histological features were remarkably associated with each other. For example, BMPC% was higher in cases with plasmoblastic cytology, heavy fibrosis, or reduced residual haemopoiesis. Anaemia was the clinical characteristic most influenced by bone marrow histology. The BMPC% was the only histological variable which affected the greatest number of clinical and laboratory characteristics, including, besides haemoglobin concentration, erythrocyte sedimentation rate, radiographic skeletal bone disease, and serum concentrations of monoclonal component, calcium, beta 2-microglobulin and thymidine kinase activity. These data indicate that comparative bone marrow histology in monoclonal gammopathies has clinical importance.

Aged↗