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Biomedical subjects

M M Belmonte

Publications and source records attributed to M M Belmonte.

At least 19 recordsLinked to original sources
PubMed2001

Biocompatibility and osseointegration in osteoporotic bone.

We implanted nails made of titanium (Ti6Al4V) and of two types of glass ceramic material (RKKP and AP40) into healthy and osteopenic rats. After two months, a histomorphometric analysis was performed and the affinity index calculated. In addition, osteoblasts from normal and osteopenic bone were cultured and the biomaterials were evaluated in vitro. In normal bone the rate of osseointegration was similar for all materials tested (p < 0.5) while in osteopenic bone AP40 did not osseointegrate (p < 0.0005). In vitro, no differences were observed for all biomaterials when cultured in normal bone-derived cells whereas in osteopenic-bone-derived cells there was a significant difference in some of the tested parameters when using AP40. Our findings suggest that osteopenic models may be used in vivo in the preclinical evaluation of orthopaedic biomaterials. We suggest that primary cell cultures from pathological models could be used as an experimental model in vitro.

Alloys↗
PubMed2000

The effect of osteopenia on the osteointegration of different biomaterials: histomorphometric study in rats.

The osteointegration of Hydroxyapatite (HA), Titanium (Ti-6Al-4V: Ti), Zirconia (ZrO2), Alumina (Al2O3) and 2 biological glasses (AP40 and RKKP) was comparatively investigated in normal and osteopenic rats by means of histomorphometry. Thirty-six Sprague Dawley female rats were left intact (Group C) while 36 were ovariectomized (Group OVX). Group C and OVX were further divided into 6 subgroups. After 16 weeks all animals were submitted to the femoral implant of nails made of the above-mentioned materials. Eight weeks after implantation the animals were euthanized, the femurs were harvested for histomorphometric analysis. The data showed that: (1) all the tested materials were biocompatible in vitro; (2) no significant differences existed in Affinity Index (AI) of Group C; and (3) results from paired comparison applied to the AI showed significant differences among the Groups C and OVX. The AI did not significantly change among intact groups, while it significantly decreased when some materials were implanted in OVX subgroups (AP40, ZrO2 and Ti-6Al-4V: p < 0.0005, p < 0.05 and p < 0.01). It is confirmed that bone mineral density is a strong predictor of the osteointegration of an orthopedic implant and that the use of pathological animal models is necessary to completely characterize biomaterials.

Journal Article↗
PubMed1998

Bioactivity modulation of bioactive materials in view of their application in osteoporotic patients.

The application of bioactive ceramic coatings to prostheses confers strength to a material (ceramic or biological glass) that exerts beneficial effects on bone-tissue growth but that itself lacks the toughness and stability required of an implant device. The rate of bioactivity is related to the chemical reactivity of the material and causes interface dissolution, precipitation and ion-exchange reactions. Ceramics may differ in sintering temperature and thus exhibit differences in their in vitro dissolution features and in vivo performance. To test these effects, in vitro and in vivo studies were carried out on two biocompatible biological glasses and a ceramic of proven bioactivity in view of their potential utilization as covering materials. In addition, a modified chitosan was adsorbed on the surface of a series of hydroxyapatite (HA) samples. Human fibroblasts and/or osteoblasts were used for the in vitro tests, and normal (INT) and osteoporotic (OVX) rats, normal rabbits and sheep for the in vivo studies. Similar chemical changes were observed in both glasses, suggesting that these materials underwent modifications directly dependent on their biological environment. The in vivo tests point to the possibility of improving the bioactivity of ceramic substrates with chitosan. However, the different behaviour of the materials in vitro and in vivo suggests that these tests should be conducted in parallel.

Journal Article↗
PubMed1994

A biochemical-morphological study on microvillus plasma membrane development.

The microvillus plasma membrane of the human placental syncytiotrophoblast at term has been extensively studied, while little is known about the characteristics of its development. The aim of the present work was to compare functional and structural properties of this membrane at early and term gestational age. Ten normal term placentas (40 weeks) and ten placentas at 10 weeks of gestational age were studied. The Na+/K+-ATPase activity is significantly decreased in the syncytiotrophoblast plasma membrane obtained from term placentas as compared to the early ones, with significant variation of maximum velocity (Vmax). The microviscosity, evaluated by the P parameter of DPH and Sn parameters of 5- and 16-NS, is increased in the term placentas compared to the early placentas. This alteration is accompanied by an increased cholesterol to phospholipids ratio in term placentas, while there is a decreased unsaturated to saturated fatty acid ratio. As follows from morphological studies, an increased mean diameter in the E face was observed in the term placenta with respect to the early placenta. The distribution factor DF, which indicates the particle aggregation state, decreased in the E face in the term placenta as compared to the early one. The present biochemical morphological study shows that a deep modification of the membrane is at the basis of the syncytiotrophoblast plasma membrane development.

Female↗
PubMed1994

Antithrombin III infusion suppresses the hypercoagulable state in adult acute lymphoblastic leukaemia patients treated with a low dose of Escherichia coli L-asparaginase. A GIMEMA study.

Thrombotic events have been reported in acute lymphoblastic leukaemia patients, especially during or after L-asparaginase administration. A so-called L-asparaginase associated coagulopathy has been well recognized, being characterized by a hypercoagulable state (decrease of antithrombin III, plasminogen, protein C, protein S and increase of prothrombin fragment F1 + 2, thrombin-antithrombin complexes and fibrinopeptide A). The aim of this study was to determine whether the supplementation of antithrombin III (AT-III) concentrates could improve the L-asparaginase associated coagulopathy, thereby blocking the activation of the haemostatic system. In 25 adult patients with acute lymphoblastic leukaemia (M 19, F6, mean age 34 years) antithrombin III (AT-III) concentrates were administered at daily doses of 50 U/kg for 10 consecutive days from the beginning of L-asparaginase therapy (6,000 U/m2/day s.c. for 7 days), given according to the GIMEMA ALL 0288 trial. A marked increase of antithrombin III was recorded on days IV-VIII-XI (P < 0.001). No changes in protein C, protein S, plasminogen, alpha 2-antiplasmin, factor VII and platelet count were observed and there was no increase in markers of hypercoagulability. There was no evidence of disseminated intravascular coagulation. In conclusion, AT-III concentrate supplementation during L-asparaginase therapy, by the achievement of high levels of antithrombin III, is associated with a lack of activation of the haemostatic system and appears to overcome the complex coagulopathy associated with L-asparaginase.

Adolescent↗
PubMed1993

Evidence of a hypercoagulable state in patients with acute lymphoblastic leukemia treated with low dose of E. coli L-asparaginase: a GIMEMA study.

Blood coagulation abnormalities induced by administration of E. coli L-asparaginase were investigated in 25 patients with acute lymphoblastic leukemia treated according to the GIMEMA ALL 0288 trial. Dosage of L-asparaginase was relatively low (6,000 U/m2/day for 7 days total dose 42,000 U/m2) as compared to the conventional dosages (120,000-140,000 U/m2 over 10-14 days). A significant decrease in fibronogen, plasminogen, alpha2-antiplasmin and antithrombin III was observed from day IV of L-asparaginase and it was maximum on day VIII, with return to the baseline levels on day XV. Protein C levels had only a borderline reduction, while no modification of protein S or factor VII was observed. Two of the patients investigated developed thrombosis. The presence of a prothrombotic state induced even by this low dosage of E. coli L-asparaginase was suggested by a significant increase of sensitive markers of hypercoagulability such as fibrinopeptide A, thrombin-antithrombin complexes, and prothrombin fragment F1 + 2.

Adolescent↗
PubMed1993

Recombinant alpha-interferon 2b in the treatment of HIV-related thrombocytopenia.

OBJECTIVE: To assess the efficacy and the mechanism of action of alpha-interferon (alpha-IFN) in the treatment of HIV-related thrombocytopenia. METHODS: Thirteen HIV-positive subjects [nine men and four women with severe thrombocytopenia (platelets, < or = 30 x 10(9)/l)] were treated with alpha-IFN 2b alone at a dose of 3 x 10(6) U three times a week for 5 weeks. Haematological parameters, platelet kinetic and bone-marrow myeloid progenitor cultures [megakaryocyte colony-forming units (CFU-MK); granulocyte macrophage CFU (CFU-GM) and erythroid burst-forming units (BFU-E)] were evaluated before and after treatment in responsive subjects. RESULTS: Seven out of 13 subjects showed a partial response (platelets, 50-149 x 10(9)/l) after alpha-IFN 2b therapy. Platelet survival as evaluated by 111In-oxine significantly increased, while platelet turnover showed a slight but not statistically significant increase after treatment. The growth of bone-marrow myeloid progenitor cells decreased after alpha-IFN 2b therapy, again without statistical significance. CONCLUSION: alpha-IFN 2b may increase the platelet count in HIV-positive subjects with severe symptomatic thrombocytopenia by prolonging platelet survival. The immunomodulatory and antiviral action of this drug may be responsible for prolonged platelet survival.

AIDS-Related Complex↗
PubMed1993

Increased serum levels of transforming growth factor beta-1 in patients affected by thrombotic thrombocytopenic purpura (TTP): its implications on bone marrow haematopoiesis.

In this study we evaluated the effect of serum collected from seven thrombotic thrombocytopenic purpura (TTP) patients, either in the acute phase of the disease or in clinical remission, on the in vitro growth of bone marrow haematopoietic progenitor cells, obtained from the same TTP patients in clinical remission and from normal donors. The addition to the cultures of autologous sera collected from TTP patients in acute phase of the disease showed a clear-cut dose-dependent inhibition of immature haematopoietic progenitor cells (BFU-E, CFU-meg and 14th day CFU-GM). On the other hand, no inhibitory effects were observed on more mature 7th day CFU-GM. Interestingly, also sera collected from TTP patients in clinical remission still maintained some inhibitory activity on the growth of immature progenitor cells. A similar inhibitory activity was noticed when TTP sera were tested on normal bone marrow haematopoietic progenitor cells. Such inhibitory activity was significantly reduced in blocking experiments by the addition of a polyclonal neutralizing anti-TGF-beta 1 antibody and the presence of increased levels of both bioactive and latent TGF-beta 1 in TTP sera was confirmed in a bioassay on CCL64 cells. These data contribute to explain the lack of a clear compensatory haematopoiesis observed in some patients with active TTP and add further evidence to the notion of the existence of a state of latent platelet activation in TTP patients in clinical remission.

Acute Disease↗
PubMed1991

Essential thrombocythemia: impaired regulation of megakaryocyte progenitors.

In this paper, the in vitro growth of bone marrow early (megakaryocyte burst-forming units, BFU-meg) and late (megakaryocyte colony-forming units, CFU-meg) progenitors was evaluated in 18 essential thrombocythemia (ET) patients and 22 normal control subjects. BFU-meg clonality was demonstrated both in normal and ET bone marrows, cultivating these primitive progenitors at limiting dilutions in plasma clot assay: 1 to 7 BFU-meg/2.5 x 10(4) mononuclear non-adherent cells were observed, with a strong correlation in ET [r = 0.955 stimulated by recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) plus recombinant human interleukin (rhIL) 3], as well as in normal controls (r = 0.969). In order to clearly elucidate the in vitro response of ET megakaryocyte (meg) progenitors to recombinant growth factors, the interference of accessory cells (i.e., monocytes, T lymphocytes, and natural killer cells) and human serum were avoided by performing experiments on CD34+ cells in a serum-free fibrin clot assay. The number of both early and late meg progenitors in ET was significantly increased in response to rhIL-3, rhIL-3 plus rhIL-6, and rhIL-3 plus rhGM-CSF, but not in response to rhGM-CSF alone. Furthermore, both meg progenitors were investigated for their response to rh transfer growth factor (TGF)-beta 1, tested at concentrations from 0.01 to 10 ng/ml. rhTGF-beta 1 was able to inhibit CFU-meg and BFU-meg in a dose-response manner normal, whereas ET CFU-meg appeared less sensitive to the lower doses investigated (p less than 0.05) and ET BFU-meg were slightly reduced in number only at the higher concentrations of rhTGF-beta 1 (p less than 0.01). Our data suggest that the increased thrombopoiesis in ET may depend on an increased sensitivity of meg progenitors to some of the physiological growth factors and to a disrupted sensitivity to at least one negative regulator of megakaryocytopoiesis. Since these abnormalities involve both meg progenitors, this can be considered a demonstration that the neoplastic event hits the most primitive hemopoietic progenitors.

Cell Division↗
PubMed1991

The risk of developing disease for siblings of patients with insulin dependent diabetes mellitus.

We analyzed the risk of developing insulin-dependent diabetes mellitus (IDDM) in 411 siblings of patients with IDDM. We found that siblings who had a positive test for antibodies against islet cells (ICA) at the time of diagnosis of the index case had a higher risk of developing IDDM than did those who had negative tests. However, of the ten siblings who developed IDDM, only four were positive at the initial testing. The period of time elapsing from a negative test at screening to a positive test at diagnosis varied but was less than one year in one child. Two of the ten siblings who developed IDDM had negative tests both at screening and at diagnosis. Amongst siblings who were negative at the initial screening, those in whom the index case was diagnosed at a young age had a higher risk of developing IDDM than did those in whom the index case was diagnosed at an older age. The age of the sibling at the time of screening, the sex of the sibling, and a positive family history (one which includes in addition to the index case one or more first-degree relatives with IDDM) did not confer increased risk. Our data suggest that screening for ICA will have to be done often and will have to be continued into adult life in order to identify the 70-80% of diabetics who will be positive at some time in the evolution of their disease.

Adolescent↗
PubMed1989

In vivo and in vitro inhibitory effect of alpha-interferon on megakaryocyte colony growth in essential thrombocythaemia.

Megakaryocyte (MK) colony growth of bone marrow mononuclear non-adherent cells was evaluated in 28 patients with essential thrombocythaemia (ET) and in 26 normal controls. The number of MK-colony forming units (CFU-MK per 3 x 10(5) plated cells) was similar in ET (68 +/- 33) and in controls (63 +/- 37), independently of bone marrow accessory cells. On the contrary, the size of the MK colonies was significantly (P less than 0.01) greater in ET patients. Human recombinant alpha-interferon 2a (alpha-IFN), administered to 10 patients at a dose of 3 x 10(6) IU/d s.c. for 11 +/- 3 weeks, was capable of inducing a significant (P less than 0.01) decrease in the number (from 72 +/- 16 to 31 +/- 14) and size of bone marrow CFU-MK, together with a significant reduction of the platelet count (from 1031 +/- 325 to 378 +/- 75 x 10(9)/l). When added in vitro at time 0 to the culture dishes, alpha-IFN inhibited the CFU-MK growth of both normal and ET bone marrow samples, even at very low concentrations (1 and 10 IU/ml). This study demonstrates that alpha-IFN, both in vivo and in vitro, exerts an inhibitory effect on the growth of MK progenitors, which appears to correlate with the clinically documented antiproliferative effect of this cytokine.

Adolescent↗
PubMed1989

Case-control study of IDDM.

Insulin-dependent diabetes mellitus (IDDM) may be caused by a combination of genetic predisposition and environmental insults. However, there are few solid leads concerning human diabetogenic environmental agents. A case-control study was carried out to investigate the possible relationships between IDDM and various biological, chemical, and psychological factors. All 161 cases of IDDM among children aged 0-17 yr occurring in Montreal from 1983 to 1986 were included. The parent of each newly diagnosed diabetic subject was asked to provide the names of two of the child's friends or neighbors who would be age and sex matched to serve as controls. For those unable to do so, matched controls were selected from a hospital emergency room. Parents of cases and controls were interviewed concerning many factors. There was little or no difference between cases and controls with regard to parental smoking habits, exposure to pets, and consumption of meat products high in nitrosamines. In univariate analyses, there was some indication of elevated risk for children who had not been breast-fed, who attended day care or nursery before age 5 yr, who lived in a crowded household at age 3 yr, or who had a history of asthma or eczema, although in multivariate analyses the only variables that had any effect were crowding and day-care attendance. In univariate and multivariate analyses, there was high risk of IDDM among children who had experienced selected stressful life events during the 12 mo preceding onset of IDDM or who had exhibited symptoms of social or psychological dysfunction during that time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Incidence of IDDM in Montreal by ethnic group and by social class and comparisons with ethnic groups living elsewhere.

We examined the incidence of insulin-dependent diabetes mellitus (IDDM) among children aged 0-14 yr in Montreal by social class and by ethnic group from 1971 to 1985. There was a slightly higher risk in wealthier as opposed to poorer classes. This income gradient was more marked in younger than in older children. Children of French extraction had about two-thirds the risk of IDDM of children of other origins, mainly British and other European. This mimics the patterns of risk in Europe, where France is reported to have lower rates than does Britain and Scandinavia. The absolute levels of risks among French Canadian and Jewish Canadian children were about double those reported from France and Israel, respectively. These various results are compatible with the hypothesis that both genetic and environmental factors influence IDDM risk.

Adolescent↗
PubMed1988

Impact of SMBG on control of diabetes as measured by HbA1. 3-yr survey of a juvenile IDDM clinic.

Three hundred twelve diabetic children and adolescents were seen in our diabetic clinic and instructed to test their capillary blood glucose (CBG) twice daily and to use an algorithm to adjust their short-acting insulin. Of this group, 219 youngsters had a full 3-yr period of observation. At each clinic visit, blood was obtained for fasting blood glucose and HbA1 and, once a year, cholesterol and triglycerides were also measured. Patient and parent accuracy in measuring CBG was found to be adequate. The changes over time in HbA1 were nondifferential across age and sex, and there was no difference in the level of HbA1 between age and sex groups, the number of tests reported to have been done by the patients, the number of injections of insulin per day, or the serum cholesterol. There was a significant relationship between the HbA1 and the fasting blood glucose (P less than .001) measured by the laboratory as well as with the serum triglyceride (P less than .01). The failure to improve diabetic control, despite measures that would have been expected to do so, was believed to relate more to a lack of compliance than to a flaw in the therapeutic approach. It was interesting to note that the adolescent patients in the study were in no worse control than the younger children in the group. Although better technical skills are available today to manage diabetes, the psychosocial approach to patient motivation requires improvement.

Adolescent↗
PubMed1986

The distribution of type I (insulin-dependent) diabetes mellitus by age, sex, secular trend, seasonality, time clusters, and space-time clusters: evidence from Montreal, 1971-1983.

The etiology of insulin-dependent diabetes mellitus remains obscure. In an attempt to clarify some aspects of the epidemiology, including its compatibility with an acute infectious process, the authors undertook in-depth analyses of childhood cases accumulated in a population-based register in Montreal during the period from 1971-1983. Incidence rates increased with age until puberty, at which point they plateaued and decreased. There was no overall difference in incidence between males and females; however, the rate for females peaked approximately two years before the rate for males. While there was some variation over time, there was no evidence of a long-term trend, nor was the yearly variation impressive in magnitude. The findings further indicate that the disease is not characterized by explosive outbreaks. There was slight seasonality, with a 28% higher rate of onset in fall and winter than in spring and summer. There was some evidence of space-time clustering in 1971-1973, but not thereafter. Taken as a whole, these findings do not support the hypothesis that a significant portion of insulin-dependent diabetes is caused by an acute infectious process.

Adolescent↗
PubMed1983

Feasibility of strict diabetes control in insulin-dependent diabetic adolescents.

Nineteen insulin-dependent diabetic adolescents who had poor control on twice daily injections and home glucose monitoring participated in a study assessing the feasibility of improved control. Using a randomized crossover protocol, we examined the relative efficacy of continuous subcutaneous insulin infusion and of intensive conventional therapy with three or four daily injections of insulin. Both therapies were regulated with home glucose monitoring. A marked improvement in control with both therapies was observed when mean blood glucose and glycosylated hemoglobin A1 were compared with conventional therapy. However, pump therapy resulted in significantly lower HbA1 than intensive therapy (P less than 0.05), despite a significantly lower total insulin dose (P less than 0.01). We conclude that in adolescents with type I diabetes, continuous subcutaneous insulin infusion is more effective in achieving improvement of diabetes control than is intensive conventional therapy in the outpatient setting.

Adolescent↗
PubMed1982

Comparison between continuous subcutaneous insulin infusion and multiple injections of insulin. A one-year prospective study.

Twenty insulin-dependent diabetic patients participated in a 1-yr prospective randomized cross-over study comparing multiple subcutaneous injections (MSI) and continuous subcutaneous insulin infusion (CSII) complemented by home blood glucose monitoring. While 4 patients dropped out early, 16 patients completed the study. Patients had severe insulin deficiency documented by absent C-peptide response to glucagon stimulation. A marked improvement in control was observed when mean blood glucose and glycosylated hemoglobin A1 were compared with conventional therapy. No significant differences in the degree of metabolic control achieved, as measured by mean fasting, preprandial, and postprandial capillary blood glucose (CBG), M values, glycosylated hemoglobin A1 concentration, cholesterol and triglyceride levels were seen between MSI and CSII in the sixteen patients who completed the study. However, individual comparisons showed that fasting CBG and M-values were lower under CSII than MSI in seven patients (P less than 0.05). In contrast, two patients exhibited lower M values under MSI than under CSII (P less than 0.01), while for the remaining seven patients the results were similar. After completion of the study, two patients went back to conventional insulin therapy, seven patients remained on the pump, and seven patients chose to stay on MSI. In conclusion, on a long-term basis, the two methods can produce comparable levels of blood glucose and glycosylated hemoglobin in ambulatory insulin-dependent diabetics.

Adolescent↗