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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
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↗
PubMed1979

Epidemiologic survey of juvenile-onset diabetes in Montreal.

Active search of hospital records was used to survey insulin-dependent juvenile-onset diabetics younger than 17 years resident in General Montreal at the time of onset of symptoms during a seven-year period (1971-1977). A mean annual incidence of 8.8/100,000 was found with variation from year to year (5.8 to 10.3). Eighty percent were five years of age or more at time of diagnosis, and the increase with advancing age was similar to that seen in other studies including the somewhat earlier increase in incidence among females. Seasonal peaks were noted in some but not all years and were more marked in years of high incidence and among males. More cases occurred in areas of high socioeconomic level as measured by average family income. The estimated incidence among siblings of diabetics is 15 times the incidence in the general population. Ten percent of diabetics have a first degree relative who is insulin dependent.

Adolescent↗
PubMed1978

Late effect of nocturnal mist tent therapy related to the severity of airway obstruction in children with cystic fibrosis.

To evaluate the long-term effect of nocturnal mist tent therapy on the progression of airway obstruction in children with cystic fibrosis (CF) of varying severity, two matched groups each consisting of 24 children with CF were studied during 18 months on mist tent therapy and 18 months of therapy. The progression in airway obstruction was measured by change in serial measurements of maximal midexpiratory flow (MMEF), from which a regression equation of MMEF against time was obtained for each individual. Changes in MMEF value with or without therapy were compared in patients matched for severity of disease as indicated by initial MMEF values. For the group as a whole no differences were found in the progression of the airway obstruction whether the patients received mist tent therapy or not. This therapy failed to benefit any of the groups of children with CF who had early, moderate, or advanced airway obstruction as judged from their initial MMEF value. It is concluded that nocturnal mist tent therapy neither decreases airway obstruction nor prevents its progression in children with CF.

Adolescent↗
PubMed1976

Juvenile diabetes mellitus, optic atrophy, sensory nerve deafness, and diabetes insipidus--a syndrome.

Four patients with diabetes mellitus, optic atrophy, and high-frequency neurosensory hearing loss, two of whom also had diabetes insipidus, are described. The frequency of this syndrome among patients with juvenile diabetes appears to be between 1/148 and 1/175. Because of the progressive nature of the disabilities and the autosomal recessive mode of inheritance, careful monitoring of all juvenile diabetic patients for other signs of the syndrome is warranted.

Adolescent↗
PubMed1971

Variability of NPH insulin preparations.

In 1968-69 certain juvenile diabetics receiving NPH insulin began having pre-breakfast glucosuria and mid-morning hypoglycemic reactions. A mail survey of our clinic population and a study done at the Quebec camp for diabetic children in 1969 revealed that certain lot numbers were associated with poor control and that a change to new lot numbers or alternate insulin preparations resulted in better control. "Suspect" insulin preparations and non-suspect insulins were given to newly diagnosed diabetics, and plasma insulin and glucose levels were measured over a 24-hour period. The data confirmed that the "suspect" insulins were causing early hypoglycemia and failing to control hyperglycemia during the latter hours of the 24-hour period. The lower glucose levels were associated with higher plasma insulin levels. The "suspect" insulins were further found to have elevated levels of free insulin in the supernatant fluid.The requirements for quality control of modified insulin preparations are reviewed and suggestions are offered for their improvement.

Blood Glucose↗