[Zinc, copper, iron, calcium, phosphorus and magnesium content of maternal milk during the first 3 weeks of lactation]. / Contenido de zinc, cobre, hierro, calcio, fósforo y magnesio en leche materna en los primeros días de lactación.

Zinc, Copper, Iron. Calcium Phosphorous and Magnesium contents were determined in early milk samples in 72 mothers from Caracas city. The samples were collected during three different lactation stages: calostro (3 days), transitional (7 days) and mature milk (21 days). The more significant changes in the concentration of the studied elements were observed during the first two weeks, them they stabilize during the third week. The Zn, Cu, Fe, Ca, P and Mg average concentration found in calostro samples were 7.1 +/- 2.5 micrograms/ml; 0.52 +/- 0.15 microgram/ml; 0.49 +/- 0.14 microgram/ml; 214 +/- 62 micrograms/ml, 107 +/- 27 micrograms/ml and 33.3 +/- 7.5 micrograms/ml. respectively. For the transitional milk samples the average concentration found for the studied elements were: 4.0 +/- 1.0 micrograms/ml; 0.50 +/- 0.10 microgram/ml; 0.38 +/- 0.08 microgram/ml, 292 +/- 62 micrograms/ml; 213 +/- 36 micrograms/ml and 30.4 +/- 5.2 micrograms/ml. For the mature milk samples the results were: 2.8 +/- 2.7 micrograms/ml; 0.47 +/- 0.08 microgram/ml; 0.36 +/- 0.09 microgram/ml; 244 +/- 49 micrograms/ml; 175 +/-35 micrograms/ml and 25.2 +/- 3.3 micrograms/ml. The concentration range for all trace elements studied (Cu, Fe and Zn) can be considered normal. For the major elements (Ca, P and Mg) the results obtained in our work are similar to those reported for other countries. These facts allows to conclude that the nutritional state of this mother population is adequate to satisfy the lactate's requirements during their first live stage.

[Tobacco and periodontopathies]. / El tabaco y las periodontopatías.

The purpose of this research, which is part of a study on periodontal disease and its risk factors among workers in Araraquara, São Paulo, Brazil, was to determine the association between smoking and its frequency, on the one hand, and the presence of periodontal cavities on the other. A sample of 528 sugar and alcohol refinery employees from Araraquara between the ages of 18 and 64 was examined in March and April of 1992 by a trained examiner who applied the Index of Periodontal Treatment Needs in the Community. Questionnaires were used to record the individuals' age, smoking habits, and the number of cigarettes smoked daily. An oral examination was also performed to assess the presence of dental plaque and to determine the bacterial colony index. Data analysis revealed a positive association between the presence of periodontal cavities and smoking. After adjusting the data for age, presence of dental plaque, and bacterial colony index, the odds ratio for having periodontal cavities increased directly with the number of cigarettes smoked. These results suggest that smoking and its frequency should be taken into account when planning programs for the primary prevention and treatment of periodontal disease.

Short-term treatment for adult hypergranular and microgranular acute promyelocytic leukemia.

A high hemorrhagic risk and a complete response to the differentiative agent all-trans-retinoic acid (ATRA) are the main clinical features of acute promyelocytic leukemia (APL), two distinct subtypes of which have been recognized, the common hypergranular leukopenic form (M3) and a microgranular hyperleukocytic variant (M3v). We analyzed, with emphasis on both disease- and therapy-related prognostic factors, the results from a 9-year trial in 65 adults with M3 and M3v APL, treated homogenously with a short-term therapy (STT) program excluding maintenance. STT comprised a maximum of six courses with doxorubicin, cytosine arabinoside (ara-C), and 6-thioguanine. Sixty-five APL patients formed the study group, M3v accounting for 25% of cases. In M3v, the absolute blast cell count was significantly higher (p < 0.0001) and early hemorrhagic deaths were more frequent (p = 0.05). The blast count correlated inversely with the probability of remission (p = 0.005), poor-risk patients being those with > 10 x 10(9)/l blast cells. During the study, the median survival improved from 0.1 to 2.7 years (p = < 0.005). In first place, response to chemotherapy increased from 42 to 84% (p = 0.006), by giving daily prophylactic platelet transfusions (to > 30 x 10(9)/l) and no heparin (course I), and by avoiding too toxic high-dose ara-C and deferring treatment in infected/neutropenic patients showing the atypical differentiative bone marrow pattern (course II). Secondly, the probability of first unmaintained remission differed significantly between patients given intentionally more than four total chemotherapy courses or intermediate/high-dose ara-C consolidation (0.59 at 5 years) and those treated less intensively (0.21) (p < 0.005). Intensive STT was very effective for the management of adult APL patients at standard hemorrhagic risk and receiving optimal supportive care. In high-risk patients with hyperleukocytosis and M3v, induction results could be improved by the concomitant use of ATRA. M3v in adults must be recognized promptly because of the very high early hemorrhagic risk.

CPITN: time and cost estimates for periodontal prevention and treatment procedures.

The aim of this study was to estimate the necessary time and cost for periodontal prevention and treatment in a working population from sugar and alcohol refineries in Araraquara, SP, Brazil. A stratified sample of 528 employees aged 18-64 from administrative, industrial and agricultural staffs was examined by one examiner, previously trained, according to the community periodontal index of treatment needs (CPITN). The time required for procedures and the cost was extrapolated to the total worker population. The results showed that the estimated time required for periodontal prevention/treatment was 4527 hours. Of this time, 1783 hours were required for oral hygiene instruction, 2531 for scaling, 151 for surgery and 62 for maintenance. The cost would be US $17,655 for hiring a dentist for 8 hours/day to provide oral hygiene instruction, scaling, surgery and maintenance. However, the cost would be US $9,028 for hiring a dentist for 4 hours/day to provide surgery and maintenance and a dental hygienist for 8 hours/day to provide scaling and oral hygiene instruction. Taking into account epidemiologic, technical and economic aspects, the decision relating to manpower should be this second option.

Hairy cell leukemia: a clinical review based on 725 cases of the Italian Cooperative Group (ICGHCL). Italian Cooperative Group for Hairy Cell Leukemia.

The Italian Registry for hairy cell leukemia (HCL) has recorded 725 patients with HCL diagnosed over 25 years. We analysed this large series of patients with the aim of providing an evaluation of changes in clinical presentation, impact of initial therapy and modifications in prognostic factors over the period of two decades. Over time, a progressive down-staging of the disease at the onset, along with a reduction of patients with severe anemia and marked splenomegaly, has been observed. A second malignancy was found in 3.7% of patients, mostly detected several years after the onset of HCL. A striking improvement of survival rates has been observed, from 58.9% survival at five years for patients diagnosed before 1985 to 87.5% at five years for patients diagnosed after 1985 (p < 0.0001). Before 1985 hemoglobin alone provided prognostic information, whereas after 1985, clinical stage and the number of leukocytes correlated better with patient outcome. Survivals at 5 and 10 years were 34.4% and 29.6% respectively for untreated patients, 58.8% and 44.1% for patients receiving chemotherapy, steroids or other drugs, 64.1% and 56.1% for splenectomized patients and 88.9% (at 5 years) for alpha interferon (IFN)-treated patients (p < 0.0001). Our findings suggest that IFN has improved the prognosis of HCL, and that it must be considered a good initial treatment for patients with HCL.

Reinforced HEAV'D therapy for adult acute lymphoblastic leukemia: improved results and revised prognostic criteria.

Thirty-six adults with acute lymphoblastic leukemia (ALL) were treated with adriamycin, vincristine, prednisolone, and asparaginase for remission induction, followed by vincristine-adriamycin-cyclophosphamide consolidation courses, cranial irradiation, a short ara-C plus VM-26 pulse, and vincristine plus cyclophosphamide rotating weekly with ara-C plus VM-26 for three months (reinforced HEAV'D). Thirty-one patients achieved a complete remission (86 per cent). Compared with historical results from a prior study, age > 30 years, absolute blast count > 15 x 10(9)/l, and CD10-negative immunophenotype were not associated with higher relapse rate and shorter survival, suggesting a positive effect from intensification therapy with ara-C and VM-26 in these poor prognostic categories. However, patients with an abnormal karyotypic pattern or a positive molecular study for BCR-ABL rearrangement detecting t(9;22) had a far greater likelihood of treatment failure (probability of remission at 3 years 0.10) than those with normal karyotype or negative molecular study (probability 0.70), and those not studied or with insufficient methaphases (probability 0.50) (p < 0.05 by log-rank test). These results underline the prognostic importance of chromosomal abnormalities and the usefulness of ara-C and VM-26 in the management of adult ALL.

Determinación de zinc y cobre en leche materna en una muestra de población de Caracas / Determination of zinc and copper in maternal milk in a sample from Caracas population

La importancia de los oligoelementos en el período perinatal ha sido extensamente estudiada en la última década. En la actualidad los datos son muy distintos, lo cual probablemente sea debido a diferencias de orden geográfico, racial, nutricional, etc. De allí la importancia de conocer los valores de cada zona para ir determinando mejor los factores que pueden contribuir a esas diferencias. Se estudiaron 72 gestantes del Hospital Miguel Pérez Carreño de Caracas que tuvieron su parto entre abril y diciembre de 1989. Se les realizó una ficha personal y se tomaron muestras de leche materna, los días 3,7 y 21 del postparto. Se determinaron concentraciones de zinc (Zn) y de cobre (Cu) por el método de espectrofotometría atómica con un espectrofotómetro VARIAN modelo AA-875. La población materna estudiada resultó una muestra homogénea correspondiente a los estratos III-IV-V de Graffar modificado por Méndez. El valor promedio de la concentración de Zn en la leche materna en el 3er. día fue de 650,00 ñ 240,31 ug/dl y la de Cu fue de 57,28 ñ 27,97 ug/dl. El valor promedio de la concentración de Zn en leche materna en el 7mo.día fue de 346,91 ñ 90,14 ug/dl y la de Cu fue de 53,61 ñ 16,15 ug/dl. El valor promedio de la concentración de Zn en leche materna del día 21 fue de 255,35 ñ 90,32 ug/dl y la del Cu fue de 52,24 ñ10,55 ug/dl. Los resultados de este trabajo son la proyección de una muestra normal de embarazadas y recién nacidos, provenientes de una población de estrato socieconoómico medio bajo de la ciudad de Caracas, que goza de un salario fijo y de los beneficios del Seguro Social y que presentó un comportamiento homogéneo, sin déficit de Zn y Cu, lo que pudiera representar los valores normales para utilizarlos como referencia, al estudiar sujetos con características similares a la estudiada

Intensive retreatment of adults and children with acute lymphoblastic leukemia.

Twenty-three patients (16 adults) failing their first or subsequent (n = 8) intensive treatment for de novo acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia lymphoid blast phase (n = 2) were managed with protocol POG 8201, originally introduced in relapsed ALL of childhood. In this programme, a four-drug induction phase is followed by early consolidation with teniposide-cytarabine, intrathecal chemotherapy, continuation weekly chemotherapy alternating teniposide-cytarabine with vincristine-cyclophosphamide, and periodic reinduction courses. Fourteen adults and five children with ALL achieved a complete response (CR) (86 per cent). The highest response rate (100 per cent) was obtained in 12 patients treated at first relapse after an initial CR of greater than 18 months (p = 0.07). Median duration of CR was 8 months in adults and 11 months in children. A longer than previous one CR (inversion) was obtained in four cases. Four ALL patients were successfully transplanted from a matched sibling after 3-11 months from achievement of CR. Median overall survival in adults with ALL was 11 months, significantly longer than for 40 comparable cases treated intensively but without rotational continuation therapy in previous years (p less than 0.001). This regimen is applicable to adults with relapsed ALL, where prolongation of survival may allow time for effective salvage with bone marrow transplantation.

Long-term results of the HEAVD protocol for adult acute lymphoblastic leukaemia.

Between 1979 and 1987, 82 adults (age 14-71 years) with acute lymphoblastic leukaemia (ALL) were treated with a 6-course protocol called HEAVD, the main feature of which was the early postremission administration of escalating doses of doxorubicin (total 405 mg/m2) and cyclophosphamide (total 2.5 g/m2). A complete remission (CR) was attained in 66 patients (80%, 95% confidence intervals, [CI] 71%-89%). Factors affecting favourable CR achievement were age less than 60 years and absence of lymphadenopathy-hepatosplenomegaly at presentation (P less than 0.05). Median duration of CR was 27 months. 26 patients remain in first continuous and unmaintained CR, 18 of whom between 5.9 and 11.1 years, for an estimated 39% prolonged disease-free survival (95% CI 27%-51%). CR duration correlated significantly with absolute blast cell count (15 x 10(9)/l or less compared to more) and age (30 years or under compared to over). Overall, 29 patients are alive with a median follow-up of 6.7 years, the projected long term survival being 35% at 11 years (95% CI 24%-46%). Treatment-related toxicity included 1 lethal case of L-asparaginase-related thromboembolism and 3 toxic deaths among 66 CR patients. Late-onset toxicity was not observed in long-term survivors. The relatively late occurrence of endpoint events (relapse and death) in adult ALL confirms that long-term updating is necessary to determine the curative potential of modern chemotherapy programs for the disease.

Short-term remission induction and consolidation therapy for adult acute myelogenous leukemia.

One hundred and ninety two adults (median age 44 years) with de novo or secondary (n = 17) acute myelogenous leukemia (AML) were managed with a maximum of six intended courses with adriamycin 25 mg/m2/d for three days, plus cytarabine 200 mg/m2/d and 6-thioguanine 200 mg/m2/d for seven days (short-term therapy, STT). Twenty eight patients not in remission after the first course were given cytarabine 2 g/m2/bd for six days, a treatment that was highly toxic and gave a low CR rate. One hundred and twenty-six patients overall (66 per cent) achieved a complete remission (CR), 117/164 (71 per cent) after one to three standard courses (median 1), and 9/28 (32 per cent) after high-dose cytarabine. Median CR duration was 12 months. By multivariate analysis, younger age, blast count less than or equal to 50 x 10(9)/L, and de novo AML were associated with a better outcome (p less than 0.05). CR duration correlated favourably with FAB M3 morphology and total number (five or six) of cycles (p less than 0.05). In patients receiving five or six total courses, median CR length resulted 15.5 months and leukemia-free survival at 3 years 37 per cent. Therapy was curtailed in one fourth of CR patients because of unacceptable toxicity, and there were nine early deaths attributable to therapy-related complications among 126 CR cases. STT may be a worthwhile form of treatment for patients with de novo non-hyperleukocytic AML that are able to tolerate five or six consecutive induction-like chemotherapy courses.

Treatment of Early Stage Hodgkin's Disease According to Risk Factors.

Between January 1981 and December 1987, 95 patients with stage IA (34 patients), IIA (42 patients) and stage IIB (19 patients) Hodgkin's disease (HD) were evaluated in our institution. Thirty patients defined as "high risk" because of either bulky mediastinal disease, systemic symptoms or both were treated with combined modality therapy (CMT). The remaining 65 patients considered as "standard risk" because they presented at diagnosis without any known adverse prognostic factor, received radiotherapy (RT) only. The median follow-up was 39 months. The complete remission (CR) rate was 97% (92/95). The actuarial 3 year overall (OS) and disease free survival (DFS) were 93% and 72% respectively with no differences between the two groups of patients. All 65 "standard risk" patients achieved CR; thirteen (20%) relapsed after a median time of 22 months. Twenty seven of 30 "high risk" patients (90%) achieved CR and six of them (22%) had early relapses. No severe pancytopenia episodes or life-threatening complications occurred during therapy. As far as the risk of second neoplasms is concerned, we observed only a single case of acute non lymphoblastic leukemia 48 months after the completion of CMT. These results indicate that in unfavourable early stage HD, CMT is effective with a probability of more than a 70% DFS 3 years after therapy with an acceptable acute and late toxicity. Patients without "high" risk factors showed the expected response after RT. About 60% of the patients who failed RT could be salvaged by chemotherapy (CT) while refractory cases or patients who relapsed after CMT did poorly with a third line chemotherapeutic regimen. Therefore alternative therapeutic approaches including high dose CT followed by autologous bone marrow transplantation should be considered for this subset of patients.

Thrombotic complications during L-asparaginase treatment for acute lymphocytic leukemia.

We report 2 new cases of thrombosis occurring in a cohort of 21 consecutive patients with acute lymphocytic leukemia treated with L-asparaginase (L-ase), 6,000 U/die s.c. or i.m. days 15-21 from start of chemotherapy, according to the GIMEMA LAL 0288 protocol. The first patient died of massive diffuse thromboembolism (thrombosis of sagittal sinus and of suprahepatic veins and pulmonary arteries; multiple hepatic and splenic infarctions) associated with markedly reduced levels of protein C, antithrombin III and plasminogen. In the second patient, portal vein thrombosis developed soon after the completion of L-ase. Antithrombin III was reduced, whereas protein C level was normal. Therapy with fresh frozen plasma and subcutaneous calcium heparin (12,500 U twice daily) proved successful, and 8 days later abdominal echotomography revealed the complete disappearance of the thrombus. The incidence of thrombosis is similar to that previously found in a cohort of consecutive patients treated at our Department with a different schedule and dosage of L-ase administration, and similar to that reported in previous series.

Fibrinopeptide A changes during remission induction treatment with L-asparaginase in acute lymphoblastic leukemia: evidence for activation of blood coagulation.

L-Asparaginase, a widely used antileukemic agent, inhibits liver protein synthesis leading to hypofibrinogenemia and hypoprothrombinemia together with a severe reduction of antithrombin III and protein C. An increased risk of thrombosis has been reported in leukemic patients treated with this agent. We measured fibrinopeptide A (FPA) changes in 14 patients with acute lymphoblastic leukemia during induction remission treatment with a protocol including L-Asparaginase (10,000 U/m2/daily intravenous for 14 days). At diagnosis, 9/14 patients had FPA level above upper limit of normal range (mean = 4.1 ng/ml). After two days of therapy, FPA rose to 5.2 ng/ml and thereafter showed a slight increase throughout. Antithrombin III, protein C and fibrinogen dropped to its nadir on day 6 and 9. However, the ratio FPA/fibrinogen on a molar basis showed a three-fold increase during this days, demonstrating that the thrombin-dependent consumption of fibrinogen was also increased. In conclusion, our data show that activation of blood coagulation occurs in concomitance with the hemostatic derangement caused by L-Asparaginase. Replacement therapy with the recently available antithrombin III concentrates may be worthy of a clinical trial to test its effectiveness in preventing the thrombotic phenomena reported in these patients.

Clinical significance of fibrinopeptide A in acute lymphocytic and non-lymphocytic leukaemia.

Fibrinopeptide A (FPA) was systematically investigated in 74 patients with acute leukaemia at different stages of the disease (50 with non-lymphocytic leukaemia, ANLL; 24 with lymphocytic leukaemia, ALL). At diagnosis, 75% of the cases had high FPA levels (86% in ANLL and 54% in ALL) with significantly higher levels in ANLL than in ALL (13.4 vs 4.4 ng/ml; p less than 0.001). Patients with DIC (20 cases in ANLL and 1 case in ALL) had significantly higher levels (p less than 0.001). FPA levels were neither correlated with fibrinogen or FDP levels nor with blast cell count. During chemotherapy, median FPA did not show significant changes whereas, at the end of therapy, a return toward normality was generally observed both in ALL and ANLL apart from the group of patients with acute promyelocytic leukaemia. Among the 24 patients who entered post-remission follow-up (13 ANLL and 11 ALL), 10 cases out of the 11 relapsing (6/6 with ANLL and 4/5 with ALL) had increased FPA 1 to 2 months before the ascertainment of the relapse. However, 16% and 9% of the samples obtained on different occasions, respectively from ANLL and ALL cases in maintained first remission, showed FPA above the normal limit. This study demonstrates that subclinical activation of blood coagulation, as indicated by high FPA level, is common both in lymphocytic and non-lymphocytic leukemia and suggests that this phenomenon is related to disease activity.

Cytogenetic and clinical studies in acute promyelocytic leukemia (M3) and cytologic M3 variant (M3V).

Cytogenetic specimens were obtained from bone marrow 24-hour cultured cells in 22 patients with acute promyelocytic leukemia, including six with microgranular variant. A t(15;17) was identified in 10-100% of metaphase cells from 13 patients. We have found no correlation between complete remission percentage and karyotype. Our data suggest that each laboratory, as far as M3 and M3V are concerned, must study its own culture time as it relates to numerous parameters involving tumoral cell kinetics.

A phase II study of idarubicin (4-demethoxydaunorubicin) in advanced myeloma.

Idarubicin (IDA) is an anthracycline analog which differs from the parent compound by the substitution of a C4 methoxyl group with an hydrogen atom in the aglycone moiety. This drug has shown greater potency and activity in experimental and human leukemias and lymphomas by intravenous and oral routes of administration together with less cardiotoxicity than doxorubicin (DX) and daunorubicin (DNR). We have treated 15 patients with advanced multiple myeloma (MM) refractory or relapsed to standard chemotherapy regimens. The treatment schedule consisted of idarubicin 40 mg/m2 orally on day 1 every 3 weeks for 6-8 months. We obtained 8/14 partial response, 4/14 minor response and 2 progressions. One patient was not evaluable for the response because of liver toxicity not related to IDA administration. The median duration of response was 8 months with a minimum of 2 and a maximum of 12 months. Hematologic toxicity occurred in about 20% of patients and no treatment was delayed. Cardiotoxicity, defined as impairement of left ventricular ejection fraction (LVEF), was observed in one case. The major systemic toxicity observed was nausea in 80% of patients and vomiting in 40%. Hair loss resulting was socially acceptable. These results indicate that IDA is useful as a single agent, easy to administer, not cross resistant with DX and recommended for a combination regimen.