Non-occupational risk factors for adult soft-tissue sarcoma in northern Italy

The role of socioeconomic and anthropometric indicators, tobacco, alcohol consumption, dietary habits, and medical history in the etiology of soft-tissue sarcoma (STS) was examined in a hospital-based case-control study, conducted in the Friuli-Venezia Giulia region of northeast Italy, between 1985 and 1990. A total of 88 STS cases (53 males and 35 females; median age: 52 years) and of 610 controls (306 males and 304 females; median age: 54 years) were interviewed. There were significant excess risks associated with a history of herpes zoster infection (odds ratio [OR]=2.4,95 percent confidence interval [CI]=1.1–5.3), chicken pox (OR=2.2, CI=1.2–4.3) and mumps in childhood (OR=2.0, CI=1.1–3.9). History of diabetes was also linked to a nonsignificant increase in STS risk (OR=1.8, CI=0.6–5.4), whereas exposure to radiation for diagnostic or therapeutic purposes was not related to the probability of developing STS. None of the investigated socioeconomic and anthropometric indicators seemed to affect STS risk; neither did tobacco smoking, nor consumption of alcohol, coffee, and tea beverages. Conversely, among the dietary habits investigated, a significant positive association emerged with an increasing frequency of consumption of dairy products (% MathType!MTEF!2!1!+-% feaafeart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXafv3ySLgzGmvETj2BSbqefm0B1jxALjhiov2D% aebbfv3ySLgzGueE0jxyaibaiiYdd9qrFfea0dXdf9vqai-hEir8Ve% ea0de9qq-hbrpepeea0db9q8as0-LqLs-Jirpepeea0-as0Fb9pgea% 0lrP0xe9Fve9Fve9qapdbaqaaeGacaGaaiaabeqaamaabaabcaGcba% Gaae4XdmaaCaaaleqabaGaaGOmaaaaaaa!3DA2!\[{\rm{\chi }}^2\]for trend=6.8, P<0.01) and oil (% MathType!MTEF!2!1!+-% feaafeart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXafv3ySLgzGmvETj2BSbqefm0B1jxALjhiov2D% aebbfv3ySLgzGueE0jxyaibaiiYdd9qrFfea0dXdf9vqai-hEir8Ve% ea0de9qq-hbrpepeea0db9q8as0-LqLs-Jirpepeea0-as0Fb9pgea% 0lrP0xe9Fve9Fve9qapdbaqaaeGacaGaaiaabeqaamaabaabcaGcba% Gaae4XdmaaCaaaleqabaGaaGOmaaaaaaa!3DA2!\[{\rm{\chi }}^2\]for trend=4.3, P<0.05), while a negative association was seen for intake of whole grain bread and pasta (OR for highest cf lowest tertile=0.4, CI=0.2–0.9).Support for this project was contributed by the Italian Association for Cancer Research, Milan, and the Italian National Research Council (CNR Applied Project Oncology, Contract 87.01544.44).     

What's new in neuromuscular disorders? The congenital myopathies.

The congenital myopathies are a heterogeneous group of early-onset neuromuscular conditions with characteristic findings on muscle biopsy, comprising central core disease, minicore myopathy (multi-minicore disease), nemaline myopathy and myotubular myopathy. Recent years have seen genetic resolution of a proportion of these conditions. The following review summarizes recent genetic findings in the congenital myopathies and outlines implications for our understanding of their pathophysiological basis and their relation to other neuromuscular disorders.     

Skeletal muscle involvement in infantile systemic hyalinosis

Infantile Systemic Hyalinosis is a rare autosomal recessive entity, characterised by deposition of hyaline material in skin and bone, often complicated by visceral involvement. The characteristic features are marked delay in motor milestones attributed to severe progressive flexion contractures of proximal and distal joints, and skin and mucosal hypertrophy and thickening, followed by failure to thrive. Pain secondary to osteolytic lesions is also a predominant feature. We report a patient with Infantile Systemic Hyalinosis, confirmed by the clinical findings, who also displayed clear evidence of proximal muscle weakness. Muscle biopsy revealed myopathic changes, which have not been reported previously. We suggest that skeletal muscle is involved in Infantile Systemic Hyalinosis and contributes to the characteristic poor outcome of these patients.     

Enhancement of in vivo antitumor activity of classical anticancer agents by combination with the new, glutathione-interacting DNA minor groove-binder, brostallicin.

PURPOSE: Brostallicin (PNU-166196) is a alpha-bromoacrylic DNA minor groove binder, currently in clinical evaluation. This drug has the peculiarity of showing enhanced antitumor activity in cells with high glutathione S-transferase (GST)/glutathione content. The purpose of the study was to study multiple combinations of brostallicin with classical anticancer agents. EXPERIMENTAL DESIGN: The cis-dichloro-diammine-platinum (cDDP)/brostallicin combination was tested in the human colon carcinoma (HCT-116) model transplanted in nude mice. Two treatment schedules were tested: cDDP followed by brostallicin 48 h after or brostallicin followed by cDDP. These two schemes were selected from the observation that tumor cells in vitro show an increased activity of GST 48 h after cDDP treatment. The HCT-116 model was used also to test the irinotecan (cPT-11)/brostallicin combination. The effect of brostallicin in combination with doxorubicin (DX) was studied in the i.v. injected murine L1210 leukemia. Three administration schedules were tested. The antitumor activity of brostallicin and Taxotere was tested on the A549 lung cancer xenografts. RESULTS: In line with the increased GST activity observed after treatment with cDDP, the cDDP/brostallicin interaction was sequence-dependent, leading to a more than additive antitumor effect, without additional toxicity, only when cDDP was given before brostallicin. The antitumor effect of CPT-11 was enhanced significantly by brostallicin cotreatment. A more than additive antitumor effect, without additional toxicity, was observed when DX/brostallicin were sequentially administered in L1210-bearing mice. Finally, additivity was observed when brostallicin/Taxotere simultaneous combination was tested. CONCLUSIONS: Although the precise molecular mechanism of interaction between brostallicin and the other tested cytotoxics has not yet been identified, a clear therapeutic gain is observed in preclinical models when brostallicin is combined with anticancer agents such as cDDP, DX, CPT-11, and Taxotere. These results indicate the potential therapeutic value of brostallicin in cancer combination treatment therapy.     

Epilepsy in Duchenne and Becker muscular dystrophies.

Duchenne and Becker muscular dystrophies are X-linked allelic disorders in which the association of central nervous system dysfunction, typically in the form of mental retardation, is a well recognized feature. They are both due to mutations in the dystrophin gene, whose corresponding protein products are expressed both in the muscle and central nervous system. We have observed an increased frequency of epilepsy in children with Duchenne and Becker muscular dystrophy attending our clinic. Out of 254 boys with this condition (201 Duchenne and 53 Becker), eight children, four in the Duchenne and four in the Becker group, had a confirmed diagnosis of epilepsy (cumulative incidence 3.14%, with a subgroup incidence of 1.99% in the Duchenne and 7.54% in the Becker group). Statistical analysis indicated that only the incidence of epilepsy in Becker muscular dystrophy was significant (p < 0.007). Our data suggests that epilepsy may be a rare associated feature in children with muscular dystrophy secondary to dystrophin deficiency.     

An early onset muscular dystrophy with diaphragmatic involvement, early respiratory failure and secondary alpha2 laminin deficiency unlinked to the LAMA2 locus on 6q22.

We present four subjects from one family and one subject (with an affected sibling who had died) from a second, unrelated family, with early onset, Duchenne-like, muscular dystrophy who presented with proximal girdle weakness, calf and generalized muscle hypertrophy, selective wasting of the sternomastoid muscles, rigidity of the spine and contractures of the tendo Achilles. Intellect was normal. Serum creatine kinase was grossly elevated and the muscle biopsies showed a dystrophic picture. All five subjects have developed early respiratory failure due to severe diaphragmatic involvement; two have already died aged 4 and 7 years of age and the remaining three are dependent on night time ventilation. There has been very little deterioration over time in the skeletal muscle function, and the survivors remain ambulant, the oldest being 11 years. Immunocytochemical studies of the muscle biopsy showed a normal pattern for dystrophin and the dystrophin-associated glycoproteins, but a reduction of the laminin alpha2 chain of merosin. Magnetic resonance imaging of the brain was normal. The disease did not link to the LAMA2 locus for laminin alpha2 on chromosome 6q, so that these families seem to represent a new form of autosomal recessive muscular dystrophy with a secondary merosin deficiency. The primary protein deficiency has not yet been identified.     

DEFB-1 genetic polymorphism screening in HIV-1 positive pregnant women and their children.

OBJECTIVE: In our study we evaluated the frequency of three SNPs (-52 G/A, -44 C/G; -20 G/A) in the 5' UTR of DEFB-1 gene, in a cohort of 130 HIV-1 infected mothers and their children, collected by the Italian group SIGO in Obstetrics and Gynecology. METHODS: The three SNPs (-52 G/A, -44 C/G; -20 G/A) in the 5' UTR of DEFB-1 gene were genotyped by direct sequencing of PCR products. RESULTS: The C allele at position -44 was shown to be significantly different in both HIV-1 positive mothers and their children when compared to the healthy controls. The odds ratio for -44 C allele in children born to HIV-1 infected mothers is 7.09 (confidence interval 3.38-15.3) while the odds ratio for this allele in HIV-1 infected mothers is 6.42 (confidence interval 3.14-13.4). CONCLUSIONS: Our results evidence a high frequency of the -44 CC allele in HIV-1 infected mothers and their children with augmented potential risk of maternal fetal transmission. This potential vertical transmission risk has been successfully prevented by antiretroviral drug treatment and cesarian section of the HIV-1 positive mothers.