Trends in cancer mortality sex ratios in Europe, 1950-1989.

A study was carried out to analyse trends in cancer mortality sex differentials. This study compared age-standardized sex ratio values for mortality from 18 cancers (or groups of cancers), and total cancer mortality over the period 1950-1989 in 24 European countries, for 4 age groups (all ages, 20-44 years, 45-64 years, and 65 years and over). For lung cancer and other tobacco-related neoplasms, appreciable rises in sex ratio values were observed until the late 1970s, particularly in Southern and Eastern Europe, before levelling off in recent years, particularly among the younger age groups. In the late 1980s, the range of variation in overall age-standardized sex ratios for lung cancer was between 2 and 3 in the United Kingdom and in Nordic countries, and around or over 10 in Southern Europe. In young adults, the decline in sex ratio values observed in Denmark and Sweden (unity), and in other Nordic countries and in the United Kingdom (around or below 2) reflects a levelling of lung cancer in young males and an increase in young females. This clearly indicates that young women are a priority target group for smoking control interventions in Europe. Appreciable cohort effects were also observed for stomach cancer: rises in sex ratio values were greater in, or restricted to, middle- and older age groups, whereas in the young there was some tendency towards a levelling in sex differentials. The overall sex ratio values for stomach cancer were around 2 in most areas of Europe in the late 1980s. For intestinal cancer, sex ratio values showed some tendency to rise, reaching a level of 1.3-1.7 in the late 1980s; steady rises were also registered in sex ratio values for melanoma (skin cancer), reaching 1.5-1.8 in the late 1980s in most countries. These upward trends which were minor or inconsistent at younger ages in several countries became progressively stronger with advancing age. Sex ratio values were below unity for cancers of the gallbladder and the thyroid. Sex ratio values tended to rise also for leukaemia (from 1.2-1.5 to 1.5-1.7), but showed no noticeable trend for lymphomas or myeloma. The overall sex ratio values for total cancer mortality in the 1950s were between 1.2 and 1.4 in most European countries. Thereafter, they rose appreciably in several countries, reaching 1.9 in Czechoslovakia, Italy and Poland, and 2.3 in France.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of dipyridamole with or without aspirin on urine protein excretion in patients with membranous glomerulonephritis

Summary The antiproteinuric effect of the antiplatelet agent dipyridamole has been assessed after inhibiton of thromboxane B₂ (TxB₂) synthesis in 8 patients with confirmed membranous glomerulonephritis. There were three study periods, each of 30 days, and 45 days apart, namely a washout period, treatment with dipyridamole 300 mg/d, and dipyridamole 225 mg/d plus aspirin 150 mg/d. On Days 1 and 30 of each study period serum and urine creatinine, 24-h excretion of protein, creatinine clearance, platelet aggregometry on whole blood and serum TxB₂ were measured. Treatment with dipyridamole alone or with aspirin produced significant inhibition of platelet aggregation and a fall in 24-h protein excretion; the latter amounted to 54% with dipyridamole alone and 56 % with dipyridamole plus aspirin (NS). Dipyridamole plus aspirin caused an 82 % reduction in serum TxB₂.     

Evidence that tolerance to cultured thyroid allografts is an active immunological process. Protection of third-party grafts bearing new antigens when associated with tolerogenic antigens.

We studied the tolerance phenomenon that develops in long-term recipients of cultured thyroid allografts. Allogeneic mouse thyroids were cultured under hyperbaric oxygen or acidic conditions and then transplanted beneath the kidney capsule of C57BL/6 recipients. Donors differed from the recipients in minor antigens alone, major histocompatibility complex antigens alone, or both. At 35-77 weeks after the first cultured graft, recipients received two more cultured grafts under the capsule of the opposite kidney and were immunized with donor spleen cells (SC). At 5 weeks after the second transplantation, we observed that whereas second grafts carrying new antigens alone were rejected, second grafts carrying new antigens in association with antigens in the first graft were significantly protected. In another set of experiments, normal mice became tolerant to cultured allografts after 2 weeks in parabiosis with tolerant individuals. Tolerant mice showed reduced specific in vivo and in vitro cytotoxic T lymphocyte responses. However, the frequency of CTL precursors of tolerant mice was the same as in normal mice. The reduced in vitro CTL responses were restored to normal levels by the addition of a lymphokine rich medium. Also, we observed that the injection of specifically activated immune SC caused the rejection of cultured allografts in normal but not in tolerant recipients. We conclude that the tolerance that develops in recipients of cultured allografts is an active immunological process that affects the activation and effector function of CTL.     

Magnetic resonance in the staging of multiple myeloma]

The authors retrospectively reviewed the MR examinations of 46 patients with clinical and laboratory findings of monoclonal gammopathies (MG). All cases had been submitted to radiographic examination which had shown skeletal involvement in 22 cases and osteoporosis in 11, with rupture of the vertebral body in 3 patients. Scintigraphy had been performed on all patients and CT on 12; 36 patients were subsequently submitted to follow-up (at 6, 12 and 24 months). MR examinations were performed with dedicated coils and standard sequences for the subjects with skeletal localizations on X-ray images. The extant cases, with no radiographic evidence of skeletal involvement, were submitted to MRI of the spine, skull and pelvis. In agreement with clinical and laboratory findings and with follow-up results (in 36 patients), MRI diagnosed MG with no skeletal involvement in 13 cases, osteoporosis in 8 (with rupture of the vertebral body in 2), asymptomatic non-progressive myeloma in 4, solitary myeloma in 3, and multiple myeloma in 18 cases. The good identification of bone marrow and its multiplanarity make MRI the method of choice in the study of patients with suspected or known gammopathies. If compared with other modalities, MRI is more sensitive and accurate in depicting the tumor, its size and relationship to periskeletal tissues, and its possible multifocality. Moreover, the technique has proven to be a valid tool during the follow-up, showing tumor response to therapy.     

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.     

Variation at 10 protein coding loci in the mbenzele pygmies from the central african republic and a comparison with microsatellite data

Ten protein coding loci (6‐PGD, A1‐AT, ACP1, CaII, ESD, GC, GPX1, Hbβ, PGM1, and TF) were analyzed in the Mbenzele Pygmies from the Central African Republic. The frequency data were used to calculate the genetic distances between Mbenzele Pygmies and other African groups. In the principal coordinate plot of F_ST genetic distances, the Mbenzele cluster together with other Pygmies of the western cluster, the Biaka from C.A.R., Gielli from Cameroon, and Babinga from Congo. By contrast, they are considerably distanced from other Pygmy groups of the eastern cluster (Twa from Rwanda, Mbuti from Zaire). Genetic distances obtained using protein loci were compared with those based on microsatellite loci. The two distance matrices are insignificantly correlated (r = 0.268; one tail probability = 0.332), and the main difference is in the higher genetic affinity between the Mbenzele and Biaka Pygmies observed at the protein level. Although reasons underlying the discrepancy between inter‐populational variation at protein and DNA loci are not established with certainty, the comparison suggests that the genetic distance between the Mbenzele and Biaka Pygmies at microsatellite loci could have been shaped by genetic drift. Am. J. Hum. Biol. 14:9–14, 2002.© 2002 Wiley‐Liss, Inc.     

Cancer risk in farmers: Results from a multi-site case-control study in north-eastern italy

The relationship between farming and cancer risk was investigated in an integrated series of case-control studies conducted from 1985 to 1991 in the Friuli Venezia Giulia region, north-east Italy. Patients with cancer of the oral cavity and pharynx, larynx, oesophagus, colon and rectum, pancreas, breast, thyroid gland, kidney and urinary tract, bladder, prostate, soft-tissue sarcomas, Hodgkin's diseases, non-Hodgkin's lymphomas and multiple myelomas, and controls admitted to hospital for acute, non-neoplastic conditions, were interviewed. For males, a significantly elevated relative risk was seen for oral cavity and pharynx. Farming, however, was associated with a significant protection against cancer of the colon and rectum and bladder. In females, only one significant association emerged, for multiple myeloma. A few significant interactions between cancer risk and year of birth (i.e., before 1930 or 1930 and after) were observed. The risk of cancer of the larynx was significantly elevated in younger male farmers but not in older ones. Our multi-site case-control study confirms that farmers have, for some cancer sites, a distinctive pattern. Excesses of cancer of the oral cavity and pharynx in farmers are characteristic of the present study area and, possibly, of similar European rural populations who have in common high levels of alcohol consumption and, at least in the past, unbalanced diets.     

Female hormone utilisation and risk of hepatocellular carcinoma.

The relationship between female hormone use and primary liver cancer was analysed using data from a case-control study conducted between 1984 and 1992 in Milan on 82 female incident cases with histologically or serologically confirmed hepatocellular carcinoma and 368 controls admitted to hospital for acute non-neoplastic, non-hormone-related diseases. An elevated relative risk (RR) or primary liver cancer was observed in oral contraceptive (OC) users (RR 2.6, for ever versus never users, 95% confidence interval, CI 1.0-7.0). The RR was directly related to duration of use (RR 1.5 for < or = 5 years and 3.9 for > 5 years) and persisted for longer than 10 years after stopping use (RR 4.3%, 95% CI 1.0-18.2). The RR were below unity, although not significantly, for women ever using oestrogen replacement therapy (RR 0.2, 95% CI 0.03-1.5) and female hormones for indications other than contraception and menopausal therapy (RR 0.4, 95% CI 0.1-1.5). The long-lasting, association between risk of hepatocellular carcinoma and OC use has potential implications on a public health scale, since primary liver cancer is a relatively rare disease among young women, but much more common at older ages. This study provides limited but reassuring evidence on the possible relationship between oestrogen replacement treatment and subsequent risk of hepatocellular carcinoma.