Natsit kansainvälisen juutalaisuuden uhreina

Kirjallisuusarvostelu

Pius XII:n pyhimystietä tasoittamassa

Elokuva-arvostelu

The effect of the birth hospital and the time of birth on the outcome of Finnish very preterm infants

The purpose of this study was to evaluate the effect of the birth hospital and the time of birth on mortality and the long-term outcome of Finnish very low birth weight (VLBW) or very low gestational age (VLGA) infants. This study included all Finnish VLBW/VLGA infants born at <32 gestational weeks or with a birth weight of ≤1500g, and controls born full-term and healthy. In the first part of the study, the mortality of VLBW/VLGA infants born in 2000–2003 was studied. The second part of the study consisted of a five-year follow-up of VLBW/VLGA infants born in 2001–2002. The study was performed using data from parental questionnaires and several registers. The one-year mortality rate was 11% for live-born VLBW/VLGA infants, 22% for live-born and stillborn VLBW/VLGA infants, and 0% for the controls. In live-born and in all (including stillbirths) VLBW/VLGA infants, the adjusted mortality was lower among those born in level III hospitals compared with level II hospitals. Mortality rates of live-born VLBW/VLGA infants differed according to the university hospital district where the birth hospital was located, but there were no differences in mortality between the districts when stillborn infants were included. There was a trend towards lower mortality rates in VLBW/VLGA infants born during office hours compared with those born outside office hours (night time, weekends, and public holidays). When stillborn infants were included, this difference according to the time of birth was significant. Among five-year-old VLBW/VLGA children, morbidity, use of health care resources, and problems in behaviour and development were more common in comparison with the controls. The health-related quality of life of the surviving VLBW/VLGA children was good but, statistically, it was significantly lower than among the controls. The median and the mean number of quality-adjusted life-years were 4.6 and 3.6 out of a maximum five years for all VLBW/VLGA children. For the controls, the median was 4.8 and the mean was 4.9. Morbidity rates, the use of health care resources, and the mean quality-adjusted life-years differed for VLBW/VLGA children according to the university hospital district of birth. However, the time of birth, the birth hospital level or university hospital district were not associated with the health-related quality of life, nor with behavioural and developmental scores of the survivors at the age of five years. In conclusion, the decreased mortality in level III hospitals was not gained at the expense of long-term problems. The results indicate that VLBW/VLGA deliveries should be centralized to level III hospitals and the regional differences in the treatment practices should further be clarified. A long-term follow-up on the outcome of VLBW/VLGA infants is important in order to recognize the critical periods of care and to optimise the care. In the future, quality-adjusted life-years can be used as a uniform measure for comparing the effectiveness of care between VLBW/VLGA infants and different patient groups

Very preterm infants in Finland - Use of health care services and economic consequences during the first five years of life

The aim of this thesis was to study the health, the hospitalisations, and the use of communal health care services in very preterm children during the first five years of life. In addition, the effect of very preterm birth and prematurity-related morbidities on the costs of hospitalisations, other health care services and the cost per quality adjusted life years (QALY) were studied. This population-based study included all very preterm children (gestational age (GA) <32 weeks or birth weight<1501g, N=2 064) and full-term controls (GA 37+0−41+6, N=200 609) born in Finland during 2000-2003. The data sources included national register data, costing data from the participating hospitals and parental questionnaires. This study showed that most very preterm infants born in Finland survived without prematurity-related morbidities diagnosed during the first years of life. They required relatively little hospital care after the initial discharge, which accounted for the vast majority of the total four-year hospitalisation costs. However, a minority of children born very preterm later developing morbidities had a long initial length of stay and more re-admissions and outpatient visits during the five-year follow-up period. In particular, the number and costs of non-emergency outpatient visits were considerable in individuals with prematurity-related morbidities. The need and costs of hospitalisations decreased clearly with each follow-up year, even in individuals with morbidities. The health-care related costs during the fifth year of life in children born very preterm without prematurity-related morbidities were close to the costs in infants born healthy at term. The cost per QALY of 19,245 € was at an acceptable level already by four years of age in the very preterm population as a whole. Prematurity-related later morbidities and decreasing GA increased the costs per QALY. As the initial hospital stay accounted for a great majority of the total four-year costs, and the costs of hospitalisation decreased with each follow-up year, the cost per QALY is likely to decrease with age. In conclusion, the majority of costs arising after the initial hospitalisation were associated with morbidities related to prematurity. Therefore offering high-quality neonatal care to prevent later morbidities in very preterm survivors has a long-term impact on the cost per QALY. In addition, this study indicates that when estimating the costs of prematurity after the first year of life, one should calculate not only the hospitalisation costs, but also other costs for social welfare services, primary care, and therapies, as these exceed the hospitalisation costs in very preterm infants during the fifth year of life.

Survival and Quality of Life among Patients with Severe Lower Extremity Peripheral Arterial Disease

Lower extremity peripheral arterial disease (PAD) is associated with decreased functional status, diminished quality of life (QoL), amputation, myocardial infarction, stroke, and death. Nevertheless, public awareness of PAD as a morbid and mortal disease is low. The aim of this study was to assess the incidence of major lower extremity amputation due to PAD, the extent of reamputations, and survival after major lower extremity amputation (LEA) in a population based PAD patient cohort. Furthermore, the aim was to assess the functional capacity in patients with LEA, and the QoL after lower extremity revascularization and major amputation. All 210 amputees due to PAD in 1998–2002 and all 519 revascularized patients in 1998–2003 were explored. 59 amputees alive in 2004 were interviewed using a structured questionnaire of QoL. Two of each amputee age-, gender- and domicile-matched controls filled in and returned postal self-administered QoL questionnaire as well as 231 revascularized PAD patients (the amount of these patients who engaged themselves to the study), and one control person for each patient completed postal self-administered QoL questionnaire. The incidence rate of major LEA was 24.1/100 000 person-years and it was considerably high during the years studied. The one-month mortality rate was 21%, 52% at one-year, and the overall mortality rate was 80%. When comparing the one-year mortality risk of amputees, LEAs were associated with a 7.4-fold annual mortality risk compared with the reference population in Turku. Twenty-two patients (10%) had ipsilateral transversions from BK to AK amputation. Fifty patients (24%) ended up with a contralateral major LEA within two to four amputation operations. Three bilateral amputations were performed at the first major LEA operation. Of the 51 survivors returning home after their first major LEA, 36 (71%) received a prosthesis; (16/36, 44%) and were able to walk both in- and outdoors. Of the 68 patients who were discharged to institutional care, three (4%) had a prosthesis one year after LEA. Both amputees and revascularized patients had poor physical functioning and significantly more depressive symptoms than their controls. Depressive symptoms were more common in the institutionalized amputees than the home-dwelling amputees. The surviving amputees and their controls had similar life satisfaction. The amputees felt themselves satisfied and contented, whether or not they lived in long-term care or at home. PAD patients who had undergone revascularizations had poorer QoL than their controls. The revascularized patients’ responses on their perceived physical functioning gave an impression that these patients are in a declining life cycle and that revascularizations, even when successful, may not be sufficient to improve the overall function. It is possible that addressing rehabilitation issues earlier in the care may produce a more positive functional outcome. Depressive symptoms should be recognized and thoroughly considered at the same time the patients are recovering from their revascularization operation. Also primary care should develop proper follow-up, and community organizations should have exercise groups for those who are able to return home, since they very often live alone. In rehabilitation programs we should consider not only physical disability assessment but also QoL.

Late effects of cancer at a young age: Registry-based studies of the health of cancer patients and their off-spring

Modern cancer therapy has resulted in increased survival among patients diagnosed with cancer at a young age. These improvements have led to the investigation of late morbidity and mortality associated with cancer and its treatments. The aim of this study was to evaluate late effects of cancer treated at a young age on the health of patients and their offspring. Utilising the nationwide population-based registries in Finland, we evaluated the risk of hypothyroidism and the probability of parenthood in cancer survivors as well as preterm birth, neonatal outcomes, and the risk of cancer among offspring of patients. The survivor cohort, identified from the Finnish Cancer Registry, consisted of 25,784 cancer patients diag-nosed between ages 0 and 34 in 1953–2004. By linkage to the population register, siblings of these patients were identified for comparison. The prevalence of hypothyroidism was higher among former childhood cancer (aged 0–16) patients than in the general population. The probability of parenthood following early onset cancer was overall significantly reduced compared to siblings. Offspring of female cancer survivors were at an increased risk of preterm birth, this risk being highest among patients diagnosed in childhood and early adulthood (aged 20–34 years). The offspring were not, however, at a significantly increased risk of neonatal death or stillbirth, though they were more likely to need monitoring or intensive care in the neonatal period. The risk of sporadic cancer among offspring of male and female cancer survivors was not elevated in comparison to the general population. The study showed that former cancer patients are at risk of certain adverse endocrine and reproductive health outcomes and should be followed for timely intervention. The offspring of cancer survivors do not appear to be at risk for adverse health outcomes.

Koulutetut maahanmuuttajat työmarkkinoilla. Tutkimus korkeakoulututkinnon suorittaneiden maahanmuuttajien työllistymisestä ja työurien alusta Suomessa

Maahanmuuttajien määrä on Suomessa merkittävämmin lisääntynyt vasta 1990- ja 2000-luvuilla. Vuonna 2010 Suomessa asui lähes 170 000 ulkomaan kansalaista. Tavallisimmin Suomeen muutetaan avioliiton, paluumuuton tai pakolaisuuden vuoksi. Pieni, joskin kasvava joukko muuttaa työn tai opiskelun vuoksi. Myös kansalaisuuksien, koulutustaustojen, ammattien jne. kirjo muuttajien joukossa on suuri. Ulkomaan kansalaisten lisääntyessä Suomessa on jouduttu kohtaamaan monenlaisia maahanmuuttoon liittyviä haasteita, joista työllistymiseen liittyvät kysymykset eivät ole vähäisimpiä. Tutkimuksessa tarkastellaan lähtömaassaan korkeakoulututkinnon suorittaneiden maahanmuuttajien työllistymistä ja työuran alkua Suomessa. Tutkimuksen tarkoituksena on selvittää, miten korkeakoulutetut maahanmuuttajat ovat Suomessa työllistyneet, minkälaisia heidän työuriensa alut ovat Suomessa olleet ja miten he ovat onnistuneet uudessa maassa hyödyntämään lähtömaassa hankkimaansa koulutusta. Lisäksi tutkimuksessa tarkastellaan, miten maahanmuuttajien lähtömaan erilaiset elämäntilanteet, olosuhteet ja valinnat ovat vaikuttaneet työuran muotoutumiseen Suomessa. Tutkimuksen aineisto muodostuu kysely- sekä haastatteluaineistosta. Kyselyaineiston (n=99) tarkoituksena on luoda määrällistä kuvaa korkeakoulutettujen maahanmuuttajien työllistymisestä Suomessa. Numerotietojen taakse jää kuitenkin näkymättömiin tieto maahanmuuttajien yksilöllisistä kokemuksista liittyen työllistymiseen ja työuran muotoutumiseen uudessa maassa. Toisena aineistona hyödynnettävän elämäkerrallisen haastatteluaineiston (n=20) kautta on mahdollista tehdä näkyväksi ne tutkittavien yksilölliset työ- ja koulutusuraan liittyvät valinnat, joita maahanmuuttajat ovat tehneet niin lähtömaassa kuin Suomessa sekä ne tilanteet ja olosuhteet, joissa tutkittavat ovat lähtömaassa eläneet ja joiden pohjalta he ovat tulleet Suomeen ja Suomen työmarkkinoille. Aineistoissa mukana olevat maahanmuuttajat olivat pääosin avioliiton, paluumuuton sekä pakolaisuuden vuoksi Suomeen tulleita. Vain muutama oli tullut työn vuoksi. Maahanmuuttajien työmarkkina-asemaa selitetään usein maahanmuuttajien resursseilla, kuten kielitaidolla, koulutuksella, työkokemuksella, sosiaalisten suhteiden ja verkostojen laadulla ja määrällä jne. Myös maahanmuuttajiin kohdistuvilla syrjivillä ja ennakkoluuloisilla asenteilla on keskeinen merkitys työllistymisessä. Koulutuksen ollessa yksi keskeisimmistä työmarkkina-asemaa määräävistä tekijöistä, tulisi koulutettujen maahanmuuttajien sijoittua hankitun tutkinnon oikeuttamiin tehtäviin. Tutkimuksessa kuitenkin havaittiin, että työllistyminen oli maahanmuuttajilla vaikeaa hyvästä koulutuksesta huolimatta. Kyselyaineistoon vastanneista vain muutama (6 %) oli työssä heti Suomeen muuttovuoden lopussa, kolme vuotta Suomessa asuttuaan työssä oli runsas kolmannes (35 %) ja aineistonkeruuhetkellä eli vuonna 2004 työssä oli 38 % vastaajista. Työsuhteet olivat tutkittavilla useimmiten määräaikaisia ja kestoltaan lyhyitä. Lisäksi työurat koostuivat runsaasta työttömyydestä sekä koulutukseen osallistumisesta. Myönteistä kuitenkin oli, että mikäli korkeakoulutetut maahanmuuttajat onnistuivat Suomessa työllistymään, vastasi työ usein joko kokonaan tai ainakin osittain hankittua korkeakoulututkintoa. Korkeakoulutettujen maahanmuuttajien työuran alut Suomessa voidaan tyypitellä kolmeen ryhmään, joista kukin jakaantui vielä kahteen alaryhmään siten, että kaiken kaikkiaan saatiin kuusi erilaista työuran alun tyyppiä: koulutusta vastaava vakaa ja vakiintuva ura, koulutusta osittain vastaava sekaura ja laskeva ura sekä koulutusta vastaamaton sisääntuloura ja työttömän ura . Haastatteluaineiston kautta tarkastellaan korkeakoulutettujen maahanmuuttajien yksilöllisiä elämänuria lähtien liikkeelle korkeakoulutettujen maahanmuuttajien lähtömaassa tekemistä ura- ja ammatinvalinnoista jatkuen Suomeen muuton kautta aina työuran muotoutumiseen Suomessa. Haastatteluja toisistaan erottelevina keskeisinä teemoina olivat toisaalta pärjääminen Suomessa ja suomalaisilla työmarkkinoilla toisaalta elämän muotoutuminen lähtömaassa ja nimenomaan siellä tehdyt ura- ja ammatinvalinnat ja niihin liittyvät kokemukset ja elämäntilanteet. Näiden kriteerien pohjalta aineisto jakaantui kolmeen ryhmään, jotka nimettiin pärjääjiksi, harhailijoiksi ja sinnittelijöiksi. Pärjääjien kertomukset muotoutuivat tietyllä tavalla myönteisen kehän kautta: niin lähtömaassa tehdyt ammatinvalinnat kuin työuran muotoutuminen Suomessa tapahtuivat suhteellisen vaivattomasti. Useimmiten työt Suomessa vastasivat lähtömaassa hankittua koulutusta. Omiin uravalintoihin oltiin myöhemmin myös tyytyväisiä. Harhailijoille oman paikan löytyminen oli puolestaan hankalampaa. Leimallista tälle ryhmälle oli tietynlainen valintojen vaikeus sekä tyytymättömyys omiin aikaisemmin tehtyihin ratkaisuihin. Jotkut harmittelivat nuorena tekemiään uravalintoja niin, että päättivät Suomessa hankkia kokonaan uuden ammatin. Muutto Suomeen merkitsi useimmille ammatillisen aseman laskua. Sinnittelijät kertoivat jo lähtökohdiltaan kahteen muuhun ryhmään nähden hyvin erilaista tarinaa. Tämän ryhmän lähes koko elämä lähtömaassa oli sodan ja levottomuuksien sävyttämää. Tämä näkyi myös ammatinvalinnassa: opiskelupaikka oli saatettu valita esimerkiksi sen perusteella, missä oli milloinkin turvallista opiskella. Myös Suomeen muutto erosi kahdesta aikaisemmasta ryhmästä, sillä lähtö entisestä kotimaasta oli tapahtunut usein hyvinkin yllättäen vailla etukäteissuunnittelua tilanteiden kärjistyttyä nopeasti. Suomessa työelämään pääseminen oli kaikille sinnittelijöille vaikeaa ja haastatteluhetkellä useilla vielä hyvin alkutekijöissä. Hyväkään koulutus ei aina takaa maahanmuuttajille työtä uudessa maassa, sillä hankittua tutkintoa ja osaamista ei ole helppo siirtää maasta toiseen. Pahimmassa tapauksessa vieraassa maassa suoritettu korkeakoulututkinto voi kokonaan mitätöityä uudessa maassa ja korkeakoulututkinnon myötä hankittu osaaminen menettää täysin arvonsa. Kyse on niin yksilön kuin yhteiskunnankin resurssien tuhlaamisesta tilanteessa, jossa maassa pysyvästi asuvat koulutetut maahanmuuttajat työskentelevät tavalla tai toisella koulutustaan vastaamattomissa epävakaissa töissä, työmarkkinoiden laitamilla tai ovat kokonaan työmarkkinoiden ulkopuolella.

Health Related Quality of Life after Childhood Cancer - A Finnish Nationwide survey

The purpose of this Finnish epidemiological nationwide cross-sectional study was to evaluate the Health Related Quality of Life (HRQL) of young people that have survived childhood cancer at least four years after cancer diagnosis. The study aims were (1) to increase knowledge and understanding about the relationship between childhood cancer and its treatment and HRQL of childhood cancer survivors and (2) to identify survivors who need and could benefit from ongoing long-term follow-up, as well as (3) to identify what kind of aftercare the childhood cancer survivors will possibly need. HRQL and fatigue of currently still young survivors of extracranial childhood malignancies were evaluated with self-reports and parent proxy reports. HRQL was measured with age-appropriate generic instruments: PedsQL™, SF-36, 15D, 16D and 17D. Fatigue for children and adolescents aged below 18 years was measured with the PedsQL™ Multidimensional Fatigue Scale Finnish version. PedsQL™ parent-proxy and the PedsQL™ Multidimensional Fatigue Scale Parentproxy instruments were used to assess the perception of the parents on HRQL and fatigue of their children and adolescents. Postal-survey questionnaires were mailed to 852 childhood cancer survivors aged 11-27 years and their randomly selected gender-, age and living-place matched controls, as well as under 18-year-old children´s parents. A total of 474 survivors, 595 controls, 209 survivor’s parent and 253 control’s parent replied. The mean age of survivors at the time of the study was 18.4 years. The mean length of survival was 12.3 years, and the mean age at diagnosis 5.5 years. The most of the Finnish childhood cancer survivors evaluated that their HRQL as good. Survivors rated their HRQL equal or higher than their controls. The only dimension where the survivors scored poorer than the controls was the 15D mobility dimension. Survivors of childhood cancer did not suffer from significant fatigue. There were subgroups of childhood cancer survivors who had poorer level of HRQL, and suffered from fatigue more than the reference group. The demographic factors that associated with poorer HRQL were female gender, greater weight, living alone, need of remedial education, an additional non-cancer diagnosis, survivors with siblings, and self-reported unhappiness. Disease-related factors that associated with poorer HRQL were higher age at the time of diagnosis, the diagnosis of Wilms tumor, neuroblastoma, or osteosarcoma, and treatment with stem cell transplantation. The factors associated with more fatigue in survivors were male gender, older age at evaluation, the need of remedial education at school, lower overall average grade in the latest school marks report, length of survival more than 10 years, lower HRQL-scores, and a sarcoma diagnosis. However, all the used demographic and disease related factors explained only about one third of the variation in the HRQL scores. In open questions, the survivors were most worried about their physical health, but were also worried about their mental health, cancer inheritance, late-effects, and fertility and relapse issues. It seems that there are subgroups of survivors who need and could benefit from ongoing long-term follow-up. In the future, the survivors of childhood cancer need more information about their physical and mental health, as well as on their cancer inheritance, possible late-effects including fertility issues, and on the risk of relapse.

Exclusão vascular do fígado em lesões venosas hepáticas complexas

Injuries to the main hepatic veins carry a very high mortality rate, regardless of the technique used for repair. Isolated reports of survivors have, for the most part, been managed by hepatic vascular exclusion (EVE) techniques, usually with an atriocaval shunt. Herein we report a case of a severe intrahepatic major hepatic vein injury successfully managed with EVE.

Comparative analysis between identified injuries of victims of fall from height and other mechanisms of closed trauma

OBJECTIVE:to identify predictors of death in blunt trauma patients sustaining pelvic fractures and, posteriorly, compare them to a previously reported series from the same center.METHOD: Retrospective analysis of trauma registry data, including blunt trauma patients older than 14 y.o. sustaining pelvic fractures admitted from 2008 to 2010. Patients were assigned into group 1 (dead) or 2 (survivors). We used Student's t, qui square and Fisher's tests for statistical analysis, considering p<0.05 as significant. Posteriorly, we compared predictors of death between both periods.RESULTS: Seventy-nine cases were included. Mean RTS, ISS and TRISS were, respectively, 6.44 + 2.22, 28.0 + 15.2 e 0.74 + 0.33. Nineteen patients died (24,0%). Main cause of death was hemorrhage (42,1%). Group 1 was characterized by (p<0.05) lower systolic blood pressure and Glasgow coma scale means on admission, higher heart rate, head AIS, extremity AIS and ISS means, as well as, higher frequency of severe head injuries and complex pelvic fractures. Comparing both periods, we notice that the anatomic and physiologic severity of injury increased (RTS and ISS means). Furthermore, there was a decrease in the impact of associated thoracic and abdominal injuries on the prognosis and an association of lethality with the presence of complex pelvic fractures.CONCLUSION: There were significant changes in the predictors of death between these two periods. The impact of thoracic and abdominal associated injures decreased while the importance of severe retroperitoneal hemorrhage increased. There was also an increase in trauma severity, which accounted for high lethality.

Short-term changes in handgrip strength, body composition, and lymphedema induced by breast cancer surgery

PURPOSE: This study investigated short-term changes in body composition, handgrip strength, and presence of lymphedema in women who underwent breast cancer surgery.METHODS: Ninety-five women participated in a cross-sectional study, divided into two groups: Control (n=46), with healthy women, and Experimental (n=49), with women six months after breast cancer surgery . The Experimental Group was subdivided into right total mastectomy (RTM, n=15), left total mastectomy (LTM, n=11), right quadrant (RQ, n=13), and left quadrant (LQ, n=10). It was also redistributed among women with presence (n=10) or absence (n=39) of lymphedema. Presence of lymphedema, handgrip strength, and body composition were assessed.RESULTS: Trunk lean mass and handgrip strength were decreased in the Experimental Group. Total lean mass was increased in the LTM compared to RTM or LQ. Left handgrip strength in LTM was decreased compared to RTM and RQ and in LQ compared to RTM and RQ. Finally, total lean mass, trunk fat mass, trunk lean mass, right and left arm lean mass were increased in women with lymphedema.CONCLUSIONS: Breast cancer survivors have changes in their body composition and in handgrip strength six months after surgery; however, the interaction between the type of surgery and its impact is unclear. Furthermore, women who developed lymphedema in this period showed more significant changes in the body composition, but they were not enough to cause impairment in handgrip strength.

Siiveniskuja vuosimiljoonien takaa

Kirjallisuusarvostelu

HFE gene mutations in coronary atherothrombotic disease

Although iron can catalyze the production of free radicals involved in LDL lipid peroxidation, the contribution of iron overload to atherosclerosis remains controversial. The description of two mutations in the HFE gene (Cys282Tyr and His63Asp) related to hereditary hemochromatosis provides an opportunity to address the question of the association between iron overload and atherosclerosis. We investigated the prevalence of HFE mutations in 160 survivors of myocardial infarction with angiographically demonstrated severe coronary atherosclerotic disease, and in 160 age-, gender- and race-matched healthy control subjects. PCR amplification of genomic DNA followed by RsaI and BclI restriction enzyme digestion was used to determine the genotypes. The frequency of the mutant Cys282Tyr allele was identical among patients and controls (0.022; carrier frequency, 4.4%), whereas the mutant His63Asp allele had a frequency of 0.143 (carrier frequency, 27.5%) in controls and of 0.134 (carrier frequency, 24.5%) in patients. Compound heterozygotes were found in 2 of 160 (1.2%) controls and in 1 of 160 (0.6%) patients. The finding of a similar prevalence of Cys282Tyr and His63Asp mutations in the HFE gene among controls and patients with coronary atherothrombotic disease, indirectly questions the possibility of an association between hereditary hemochromatosis and atherosclerosis.

Long-term outcome of 25 children and adolescents with severe aplastic anemia treated with antithymocyte globulin

Severe aplastic anemia (SAA) is probably an immune-mediated disorder, and immunosuppressive therapy is recommended for patients with no available donor for bone marrow transplant. Between October 1984 and November 1987, 25 consecutive children and adolescents with SAA with no HLA-compatible marrow donor received equine antithymocyte globulin (ATG) (15 mg kg-1 day-1) for 10 days. The patients were evaluated 6 weeks, 6 months, and 12 months after starting ATG treatment. Thereafter, patients were evaluated yearly until July 1998. Median age was 10 years (range, 1.5-20 years), granulocyte counts on referral ranged from 0.032 to 1.4 x 10(9)/l (median 0.256 x 10(9)/l), and 12 patients had granulocyte counts <0.2 x 10(9)/l. At a median follow-up of 9.6 years (range, 8.6-11.8 years), 10 patients (40%) remained alive with good marrow function. No morphologic evidence of hematological clonal disorders has been observed, although two patients probably have acquired clonal chromosomal abnormalities (trisomy 8 and del(6)q21, respectively). Responses to ATG were observed between 6 weeks and 6 months from the start of treatment in 60% of evaluable patients. The response rate was not different in patients whose granulocyte count at diagnosis was <0.2 x 10(9)/l, or in those who were <10 years of age. This study supports the view that, when compared with supportive measures, ATG is an effective treatment for children or adolescents with SAA. Although these results are inferior to those reported for marrow transplantation or more intensive immunosuppressive regimens, these patients who responded to ATG are long-term survivors with stable peripheral blood counts and a low rate of relapse.

alpha-Tocopherol enhances tumour growth inhibition by cis-dichlorodiammine platinum (II)

Present studies indicate that alpha-tocopherol enhances the efficacy of cisplatin as demonstrated by inoculation of Dalton's lymphoma cells incubated with either cisplatin (5 or 10 µg/ml) alone or cisplatin + alpha-tocopherol (25 or 50 µg/ml) into C3H/He mice. Tumour cells (3 x 10(6) cells/mouse) incubated with cisplatin grow slowly in syngeneic mice as indicated by the late appearance of tumour. However, mice failed to develop tumour when inoculated with tumour cells incubated with cisplatin + alpha-tocopherol. When the animals were challenged with tumour cells (3 x 10(6) cells/mouse) on the 15th day after the initial inoculation, 30-50% survived more than 60 days, with 10% tumour-free survivors being observed in some groups. Antitumour activity was higher in mice receiving lymphoma cells (3 x 10(6) cells/mouse) preincubated with cisplatin + alpha-tocopherol compared to cisplatin alone. Tumour-bearing mice receiving cisplatin in combination with different concentrations of alpha-tocopherol exhibited significantly higher (P<0.001) intratumour platinum content (123-306%) but without any change in the kidney platinum content as compared to those receiving cisplatin (5 or 10 µg/ml) alone. Enhancement of cisplatin-induced tumour growth inhibition is probably due to the modulation of tumour cell membrane permeability by alpha-tocopherol. alpha-Tocopherol might increase the influx of cisplatin into tumour cells, causing the DNA repair machinery to be less efficient due to increased efficiency of adduct formation in the DNA molecule. This effect of alpha-tocopherol can render cisplatin more effective as an antitumour agent.