Biomedical subjects

M Kalmanti

Publications and source records attributed to M Kalmanti.

At least 37 records · Page 2Linked to original sources

PubMed2000

Immediate free flap mandibular reconstruction in osteosarcoma of the mandible in childhood.

Mandibular osteogenic sarcoma (OS) is a very rare entity in childhood. Adequate surgical rejection with a wide margin of normal tissue is the mainstay of treatment of this site, while the role of adjuvant chemotherapy remains uncertain. A case is presented of a 15 1/2-year-old male with a huge OS of the mandible. The boy underwent surgical resection of the mandible with immediate fibula free flap reconstruction and is alive and free of disease 6 1/2 years following unitial diagnosis. This case suggests that immediate bone reconstitution with vascularized grafts have good functional and morphological results for osteosarcoma of the lower jaw.

Adolescent↗

PubMed1999

Insulin-like growth factor-I and binding protein-3 in relation to childhood leukaemia.

The aetiology of most cases of childhood leukaemia remains unknown, but several studies have indicated that increased birthweight and height are risk factors for the disease. Since insulin-like growth factor-I (IGF-I) mediates the effect of growth hormone and has been positively associated with prostate cancer, we have evaluated the role of this hormone and its principal binding protein, IGFBP-3, in the aetiology of childhood leukaemia. Incident cases of childhood leukaemia from those recorded by a national network of childhood oncologists were enrolled in our study. Controls were children hospitalised for acute conditions of no more than moderate severity with matching for gender, age and maternal place of residence. Blood measurements of IGF-I and IGFBP-3 were undertaken using commercially available radioimmunoassays. Serum IGF-I values decreased by about 1.7% per month, and the rate of decline was higher, though not significantly so, among cases (2.1% per month) than among controls (1.4%). There was no significant association between IGF-I and the likelihood of childhood leukaemia, but an increment of 1 microg/ml of IGFBP-3 was associated with a substantial and statistically significant reduction of childhood leukaemia by 28% (95% confidence interval 7% to 45%). Because IGFBP-3 is essentially a binding protein, we interpret our findings as indicating that bioavailable IGF-I may play an important role in the aetiology of childhood leukaemia. The much smaller quantities and the inherent instability of IGF-I in the blood in comparison to those of IGFBP-3 are likely to hinder documentation of an underlying positive association of IGF-I with the disease.

Acute Disease↗

PubMed1999

Gonadal function in young patients successfully treated for Hodgkin disease.

BACKGROUND: Gonadal function in pediatric and young adult survivors of Hodgkin disease is not very well defined. This study evaluates the outcome following the Multiple Drug Protocol (MDP) and the results are compared to the published experience. PROCEDURE: Ovarian and testicular function was assessed in 65 patients (36 males) with Hodgkin disease in first or second complete remission after treatment with either radiation (RT, n = 13), chemotherapy (CT, n = 9), or both (n = 43). Chemotherapy consisted of six cycles of the MDP (doxorubicin, procarbazine, prednisone, vincristine, and cyclophosphamide). Median age at diagnosis was 13.1 years (range, 2.4-22.6) and median age at evaluation was 22.6 years (range, 15.1-33.7), which was 6.7 years (range, 2.0-19.8) after the completion of all treatments. For the purpose of analysis, patients were divided into three groups: group A, patients who received only RT that did not include the pelvis (8 females, 5 males); group B, patients who received CT but no pelvic RT (15 females, 25 males); and group C, patients who received CT plus pelvic RT (6 females, 6 males). RESULTS: All patients progressed spontaneously through puberty and evaluable patients were found to be sexually mature (Tanner stage IV and V). Serum follicle stimulating hormone (FSH) was increased in 0/5, 13/25, and 5/6 and testicular volume was decreased in 1/3, 4/11, and 2/3 group A, B, and C male patients, respectively. Leydig cell dysfunction was uncommon; 91% and 88% of males had normal serum concentrations of luteinizing hormone (LH) and testosterone, respectively. FSH and LH were increased in 0/8, 3/15, and 2/6 group A, B, and C female patients, respectively, at last follow-up, indicating a 17% prevalence of ovarian dysfunction. Serial data in seven females whose initial levels of FSH/LH were elevated revealed normalization in four. Six females delivered eight normal children. CONCLUSIONS: The majority of males who received CT +/- RT have evidence of germ cell dysfunction, while Leydig cell function is unaffected in most. In females, although abnormal function early after the end of treatment was observed, ovarian function remained or returned to normal in most young women. Thus, in females the results of hormone testing performed early after treatment may not be predictive of their eventual reproductive potential.

Adolescent↗

PubMed1999

Prevalence of chronic idiopathic neutropenia of adults among an apparently healthy population living on the island of Crete.

The aim of the present study was to investigate the prevalence of chronic idiopathic neutropenia of adults (CINA) among an apparently healthy population born and living on the island of Crete. The study was carried out with 778 subjects, 392 men aged 16-78 years (median 43 years) and 386 women aged 15-79 years (median 40 years). All were employees of the Medical School or the adjacent University hospital and members of their families. Among these there were 64 subjects (8.23%) who fulfilled the diagnostic criteria of CINA applied in our department. Mild neutropenia (neutrophils 1700-2499/microl) accounted for 6.81% and moderate neutropenia (neutrophils 600-1699/microl) for the remaining 1.41%. No cases of CINA with severe neutropenia (neutrophils below 600/microl) were found. CINA was more frequent in women, with a women to men ratio of about 3:2. Approximately two thirds of the cases appeared in patients aged 30-59 years. Concomitant thrombocytopenia was found in three of the 64 subjects with CINA. Neutropenic subjects had chronic (perennial) rhinitis 3.4 times more frequently than non-neutropenics. No influence of occupation, use of insecticides and pesticides, contact with industrial chemicals, or administration of nonsteroidal anti-inflammatory drugs on the development of CINA was documented. We conclude that, despite the biased character of the study (population not randomly selected), our data provide a valuable estimation of the prevalence of CINA in the general population, given that our sample was sufficiently large, was derived from all major regions of the island, and was composed of subjects of both genders and of all age-groups from 15 to 79 years.

Adolescent↗

PubMed1999

Infantile myofibromatosis: a case study and review of literature.

Infantile myofibromatosis is an unusual condition generally presenting in the newborn period. The case being reported is that of a female newborn who had multiple lesions that involved skin, subcutaneous tissue, skeletal muscles, bone, and lungs. The disease was diagnosed because of the easily palpable skin tumors and subcutaneous nodules that were obvious immediately after birth. The diagnosis was established by histopathological examination of one nodule that showed a spindle-celled mesenchymatogenic lesion demonstrating the morphological and immuno-phenotype characteristics of myofibroblastic differentiation. The histologic picture, combined with the clinical manifestations and the imaging findings, are consistent with infantile myofibromatosis. The physical condition of the newborn was excellent and remains so six months later. The tumors of the skin and the subcutaneous nodules have gradually regressed without therapy. At the age of six months, four (4) nodules are palpable; the infant is under continuous observation.

Bone Neoplasms↗

PubMed1998

Phenotypic characteristics of cord blood hemopoietic cells.

Bone marrow transplantation is limited due to the lack of HLA-matched donors and to the frequent occurrence of GvHD. Hemopoietic transplants using cord blood cells are being increasingly used in pediatric patients. In this study, the immunophenotypic characteristics of cord blood cells have been investigated by one or two-color flow cytometric analysis. The CB cells were characterized by a low proportion of CD3+ T-cells, increased CD4/CD8 and CD45RA/CD45RO ratios, minimal expression of HLA-DR, increased proportion of CD5CD19 double positive B-cells, while CD3- CD8+ and CD3- CD7+ subsets, not usually found in adult PB, were detected. These data reflect the immaturity of CB cells as assessed by immunophenotypic analysis suggesting that it could be a valuable alternative source of transplantable hematopoietic progenitor cells and might alleviate some of the problems associated with bone marrow or peripheral blood transplantation.

Antigens, CD↗

PubMed1997

High sensitivity of leukemic peripheral blood lymphocytes to triethyllead action.

In a previous study we reported that triethyllead (Et3Pb+) inhibits cell proliferation of normal human lymphocytes. To further characterize this interaction, we studied herein the effects of Et3Pb+ on the cell viability of normal and leukemic human lymphocytes and analysed the expression and dynamics of the monomer/polymer equilibrium of tubulin in these cells. Short- and long-term cell culture experiments demonstrated significantly different dose-dependent effects of Et3Pb+ on cell viability of leukemic compared to normal lymphocytes. Indeed, in the presence of increasing concentrations of Et3Pb+ (10(-12)-10(-5) M), primary cultures of chronic lymphocytes (CLL) and acute lymphoblastic (ALL) leukemic human Lymphocytes were much more sensitive to Et3Pb+ treatment when compared to normal peripheral blood lymphocytes (PBL). The IC50 values were approximately 5 x 10(-6) M for PBL and 8 x 10(-10) M for both CLL and ALL respectively, when cells were preincubated for 3 h with this agent. These experiments revealed a 1000-fold higher responsiveness of leukemic cells to Et3Pb+ treatment. Quantitative immunoblot analysis showed that leukemic cells express up to 4-fold higher total tubulin amounts. However, the proportion of polymerized tubulin in leukemic compared to normal lymphocytes increased only slightly (up to 1.4-fold). These findings reveal a significant decrease in the polymeric to total tubulin ratio in leukemic lymphocytes, indicating important modifications in tubulin dynamics and reorganization of the microtubular structures. Our results demonstrate that leukemic cells are much more sensitive than normal lymphocytes to Et3Pb+ action. This effect may be due to the altered monomer/polymer dynamic equilibrium of tubulin shown in leukemic cells. It is, therefore, worthwhile exploring future applied uses of Et3Pb+ as a potential suppressor of leukemic cell growth.

Animals↗

PubMed1997

Electrical power lines and childhood leukemia: a study from Greece.

Residential proximity to electrical power lines of different voltage in relation to childhood leukemia was investigated through a case-control study undertaken in Greece during 1993-1994. The study comprised 117 incident cases of childhood leukemia and 202 age-, gender- and place-of-residence-matched controls. Four measures of exposure to magnetic fields were developed, using data provided by the Public Power Corporation of Greece: Voltage (V) divided by the distance (d), V/d2, V/d3 and an adaptation of the Wertheimer-Leeper code. Conditional-logistic-regression modeling was used to adjust for potential confounding influences of 18 variables. No significant trends of childhood leukemia risk with increasing exposure levels were noted, nor were there statistically significant elevations of disease risk at the higher exposure levels in each measure of exposure. These results do not support a causal link between residential proximity to electrical high-voltage wires and childhood leukemia risk, but in themselves do not refute a weak empirical association.

Adolescent↗

PubMed1997

Merocyanine 540 mediated photolysis of normal bone marrow, committed hemopoietic progenitors and neoplastic cells. implications for bone marrow purging.

The effect of merocyanine 540 (Mc 540) mediated photoirradiation on both neoplastic and normal hemopoietic progenitor cells was studied. Bone marrow (BM) cells from children with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) at initial diagnosis, ALL in remission, neuroblastoma and normal children as well as cells of Reh-6 and HL-60 cell lines were incubated with Mc 540 in the presence of human albumin (HA) and exposed to different argon laser 514 nm doses. Cell survival was estimated using Trypan Blue supravital stain following a 24-h incubation and leukemic cell lines were studied in continuous cell cultures of 4 weeks duration. Our results showed that HA protects normal BM cells from Mc 540 mediated phototoxicity. A 99.9999% inhibition of Reh-6 and HL-60 was noted at irradiation doses where the corresponding mean survival of normal BM cells was 77.4 +/- 12 and 70.3 +/- 10%, respectively. BM leukemic cells from children with ALL and AML were also very sensitive to Mc 540 photoirradiation in contrast to neuroblastoma cells where only a three-fold reduction was observed. Finally, the survival of normal BM progenitors was 38% for colony forming unit erythroid CFU-E, 37% for burst forming unit erythroid BFU-E, 55% for CFU-GM and 29% for CFU-GEMM. In conclusion it seems that Mc 540 mediated photoirradiation in neoplastic cells exerts selective cytotoxicity and can be used in ex vivo purging of malignant cells in BM.

Bone Marrow↗

PubMed1997

The risk profile of childhood leukaemia in Greece: a nationwide case-control study.

The risk profile of childhood leukaemia in Greece was studied through a case-control investigation that included all 153 incident cases of the disease, ascertained throughout the country during 1993 and 1994, and two hospital controls for every case matched for gender, age and place of residence. The data were analysed using conditional logistic regression and the associations are expressed in terms of adjusted odds ratios (OR) and their 95% confidence intervals. Cases were born to mothers of a higher standard education, the OR for an increment of four schooling years being 1.48 (1.17-1.87) and had higher birth weight, the OR for an increment of 500g being 1.36 (1.04-1.77). Pet ownership and birth after a pregnancy with anaemia were associated with increased risk, the ORs being 2.18 (1.14-4.16) and 2.60 (1.39-4.86) respectively. From the frequency analyses, indicative inverse associations were found with birth order, household crowding and previous hospitalization with allergic diseases, whereas indicative positive associations were found with diabetes mellitus during pregnancy and with neonatal jaundice. Substantial or significant elevations were not found with respect to maternal smoking and coffee drinking during pregnancy, diagnostic radiography and ultrasonographic examinations or blood transfusions. A significant inverse association with maternal consumption of alcohol could be due to multiple comparisons, but a detrimental effect can probably be excluded. A non-significant positive association with total shots of viral vaccinations and a weak non-significant inverse association with breast feeding were also found. We interpret the findings of this study as being compatible with acute childhood leukaemia being linked with delayed development of herd immunity to fairly common infectious agents, in conjunction with accelerated perinatal and early post-natal growth.

Adolescent↗

PubMed1997

Isolated intracranial metastasis of neuroblastoma 2 years after completion of therapy.

Metastatic neuroblastoma in the brain without evidence of intracranial or extracranial disease elsewhere, is a very rare event. The pattern of spread is believed to be via the hematogenous route or cerebrospinal fluid. A child with a cystic neuroblastoma mass in the right temporal lobe 23 months following completion of therapy for the initial disease is described here. Chemotherapy with the protocol 'eight drugs in 1 day' was initially effective for this patient.

Adrenal Gland Neoplasms↗

PubMed1997

Severe anemia due to Kell alloimmunization.

A case of alloimmunization in pregnancy caused by antibody to Kell red blood cell antigen is described. The baby was born prematurely with severe anaemia (HB 3g/dL). He was the 5th child of the family. The mother, who was found blood group O, Rh D positive, received at the age of 18 years a blood transfusion. This case emphasizes the importance of serological screening for low frequency red cell antigens, particularly in the case of a positive indirect Coomb's test in Rh positive pregnant mothers.

Anemia, Hemolytic↗

PubMed1997

Congenital systemic Langerhans cell histiocytosis (report of two cases).

Two cases of congenital systemic Langerhans cell histiocytosis (LCH), diagnosed and treated in our department from June 1995 until May 1996, are described. The cases concern two neonates (one female and one male) born with necrotic lesions and skin nodules. The diagnosis was confirmed by skin biopsy which showed diffuse infiltration by CD1 antigen and S-100 protein positive histiocytes. The babies didn't present with anemia, hepatosplenomegaly or lymphadenopathy. Hepatic and renal function were normal. In both infants skeletal survey showed no lytic lesions but chest X-rays and high resolution computerized tomography (HRCT) scan revealed diffuse mottling of both lung fields. Bone marrow aspiration showed the presence of histiocytes in percentages of 6% and 10%, respectively. Both babies were treated with prednisolone 1 mg/kg body weight for three months. The first child who is 20 months old, is now well with resolution of skin and pulmonary lesions occurring within one month of the initiation of steroids, while the second, who presented spectacular resolution of skin lesions within the first three weeks of therapy, is also in excellent condition five months after completion of treatment. We conclude that congenital LCH has to be suspected in neonates with persisting skin lesions. If the disease is systemic but without organ dysfunction, treatment with steroids may be beneficial.

Antigens, CD1↗

PubMed1996

Altered actin polymerization dynamics in various malignant cell types: evidence for differential sensitivity to cytochalasin B.

Using the DNase I inhibition assay, fluorimetric measurements, and immunoblot analysis, we studied quantitatively changes in the actin polymerization dynamics in primary cultures of normal and malignant human lymphocytes, normal human endometrial cells, and in various leukemic and endometrial adenocarcinoma cell lines. The G/total-actin ratio of malignant cells was found to be 1.37 to 1.81-fold higher compared to normal cells, indicating that malignant cells express reduced amounts of polymerized actin. The above findings were corroborated by fluorescence measurements of the amounts of rhodamine-phalloidin-labeled F-actin in normal and neoplastic cells, which showed significantly lower F-actin content in malignant cell preparations. Moreover, the total actin content, as quantitated by the DNase I inhibition assay and by immunoblot analysis, was found to be significantly decreased in the primary cultures of malignant human lymphocytes and endometrial cells when compared to the total actin levels in corresponding normal cells. Proliferation and viability measurements of normal and neoplastic cells in culture, treated equally with cytochalasin B (CB), revealed an increased susceptibility of malignant cells to this anticytoskeletal agent. This was not due to increased CB incorporation in neoplastic cells, as indicated by 3H-CB uptake experiments. In addition, fluorescence microscopy, in the presence of graded concentrations of CB, showed destabilization of microfilaments in the poorly differentiated endometrial adenocarcinoma HEC-50 cells, compared to the well-differentiated Ishikawa cells. In conclusion, all investigated malignant cells are characterized by: (a) higher G/total-actin ratio; (b) decreased F- and total-actin content; and (c) lower resistance to CB treatment. These quantitatively determined parameters may represent potential biochemical indicators reflecting malignant transformation. Moreover, it seems worthwhile to explore whether or not the differential sensitivity of malignant cells to anticytoskeletal drugs may provide a valuable approach to the manipulation of malignant cells.

Actins↗

PubMed1996

Infant leukaemia after in utero exposure to radiation from Chernobyl.

There has been no documented increase in childhood leukaemia following the Chernobyl accident. However, different forms of childhood leukaemia may not be equally susceptible to radiation carcinogenesis. Infant leukaemia is a distinct form associated with a specific genetic abnormality. Outside the former Soviet Union, contamination resulting from the Chernobyl accident has been highest in Greece and Austria and high also in the Scandinavian countries. All childhood leukaemia cases diagnosed throughout Greece since 1 January 1980 have been recorded. Here we report that infants exposed in utero to ionizing radiation from the Chernobyl accident had 2.6 times the incidence of leukaemia compared to unexposed children (95% confidence interval, 1.4 to 5.1; P approximately 0.003), and those born to mothers residing in regions with high radioactive fallout were at higher risk of developing infant leukaemia. No significant difference in leukaemia incidence was found among children aged 12 to 47 months. Preconceptional irradiation had no demonstrable effect on leukaemia risk at any of the studied age groups.

Adolescent↗

PubMed1996

Merocyanine 540 mediated photoirradiation of leukemic cells. In vitro inference on cell survival.

In order to evaluate the selective killing of merocyanine 540 (MC 540) mediated photoirradiation in neoplastic cells, bone narrow cells from children with leukaemia or neuroblastoma and normal children as well as peripheral blood cells and Reh-6 and HL-60 cell lines were studied. Cell suspensions were incubated with MC 540 and exposed to various argon laser 514 nm doses. Cell survival was estimated with trypan blue supravital stain following a 24 h incubation and has been followed in continuous cell cultures of 4 weeks duration. Our results showed that the inhibition of survival of neoplastic haemopoietic cells by laser in the presence of MC 540 is proportional to the MC 540 and photoirradiation doses. A 99.9999% inhibition of Reh-6 and HL-60 was noted at irradiation doses where the corresponding mean survival of normal bone narrow cells was (33.6 +/- 15.5)% and (50.6 +/- 10.7)% respectively. Peripheral blood mononuclear cells were not sensitive to MC 540 mediated photoirradiation. The inhibition of survival of bone marrow metastatic neuroblastoma cells was (69.9 +/- 4.1)%. In conclusion, it seems that MC 540 mediated photoirradiation in neoplastic cells exerts selective cytotoxicity and can be used in ex vivo purging of malignant cells in the bone marrow.

Bone Marrow↗

PubMed1996

Morphologic differences between latent membrane protein-1 (LMP-1)-positive and negative tumour cells in Epstein-Barr virus (EBV)-related childhood Hodgkin's disease. A morphometric study.

The values of five cellular morphometric parameters (longest and shortest cytoplasmic axis, cellular circumference, area and roundness coefficient) were compared between 20 Latent Membrane Protein 1 (LMP-1)-positive and an equal number of LMP-1-negative Reed-Sternberg and Hodgkin (HRS) cells for each of 13 cases of Hodgkin's disease (HD) occurring in children (aged 3-15 years); the presence of Epstein-Barr virus (EBV) encoded EBER mRNAs had previously been detected in all cases using RNA in situ hybridisation (RISH), while the presence of LMP-1 was immunohistochemically detected using the alkaline phosphatase-antialkaline phosphatase (APAAP) method. The longest and shortest axis, circumference and area were larger in LMP-1-positive than in LMP-1 negative HRS cells, while the roundness coefficient of LMP-positive HRS cells was smaller than that of LMP-1 negative cells. All differences were statistically highly significant when univariate (paired comparisons) t-test were used. Multivariate analysis (Hotelling's T2 test) showed all differences (except the roundness coefficient) to be significant both at the 5% and 1% level of significance. These results provide a numerical basis for the alteration brought by the expression of LMP-1 in the cellular skeleton of tumour (HRS) cells in EBV-related childhood HD cases.

Adolescent↗

PubMed1994

Frequent detection of Epstein-Barr virus (EBV), EBER transcripts and latent membrane protein-1 (LMP-1) in tumor cells in Hodgkin's disease arising in childhood.

Paraffin sections from 22 cases of Hodgkin's disease (HD) and 30 cases of non-Hodgkin's lymphomas (NHL) occurring in childhood (3-15 years old) were examined for the presence of Epstein-Barr Virus (EBV) encoded EBER mRNAS and Latent Membrane Protein-1 (LMP-1) using RNA in situ hybridization (RISH) and immunohistochemistry, respectively. In 12/22 (54%) cases of HD the EBER transcripts were detected in most Reed-Sternberg and Hodgkin (HRS) cells as well as in some scattered smaller lymphoid cells. In all these cases the LMP-1 protein was detected exclusively in HRS cells. Three additional cases of HD were found to be EBER RISH positive only in a few scattered small lymphoid cells, the LMP-1 staining being negative in these cases. The EBER and LMP-1 positivity in HRS cells were present in 0/1 of lymphocyte predominant, 4/10 (40%) of nodular sclerosis and 8/11 (72%) of mixed cellularity of HD. No EBER RISH signal was found in tumor cells of the 30 cases of NHL. In four of them only a few scattered small lymphoid cells were EBER RISH positive. LMP-1 reactivity was not detected in any NHL. These results provide evidence for an association between EBV and a sizeable proportion of childhood Hodgkin's disease and show that this association is more frequent in mixed cellularity subtype. Furthermore, the detection of the LMP-1 protein in HRS cells in view of the LMP-1 transforming potential, suggests that EBV may be involved in the pathogenesis of a substantial proportion of cases of HD occurring in childhood.

Adolescent↗