Molecular biomonitoring of a population of nurses handling antineoplastic drugs

Many antineoplastic drugs have been found to have carcinogenic, mutagenic and teratogenic activity and so hospital personnel handling these substances are potentially exposed to health risk. Understanding this risk derived from protracted occupational exposure has great relevance even if the workers normally adopt individual and environmental protective measures. To address this question we have studied the presence of DNA and chromosome damage in a population of nurses employed in Italian oncology units and in matched controls. We used the comet assay to evidence the presence of DNA strand breaks, due to both acute and chronic exposure, and the micronucleus (MN) test, which is a measure of clastogenic and aneugenic events. Furthermore, since the individual response to the exogenous insults may be genetically determined, we studied the possible influence of single nucleotide polymorphism in XRCC1 and XRCC3 DNA repair genes on induced genetic damage. We also considered the effects of confounding factors like smoking, age and gender. The results indicated that the exposed subjects had significantly high levels of genetic damage. Age and gender were associated with increased values in MN, both in control and in exposed groups; the smoking habit affects MN frequency in controls, but not in workers. Furthermore we found that exposed subjects bearing at least one XRCC1 variant allele (399Gln) show higher values of MN. The present data provide the evidence to show that occupational exposure to antineoplastic drugs, even if in safety controlled conditions, represents a serious health risk. Furthermore we have shown that the presence of XRCC1 genetic polymorphism could contribute to increase the genetic damage in susceptible individuals who are occupationally exposed to dangerous substances.     

Assessment of annual health insurance reimbursement for oncology drugs in Hungary

The aim of our study is to analyse the health insurance reimbursement of oncology drugs in outpatient care, inpatient care and named patient system. Data were derived from the database of the National Health Insurance Fund Administration (OEP). The analysis covers data of pharmaceuticals with health insurance reimbursement between 1 January and 31 December, 2008. We performed the analysis according to the ATC group "L" and ICD codes C00-C99 and D00-D48. Within "L" ATC group, for ICD codes C00-C99 and D00-D48 the annual health insurance expenditure for outpatient and named patient drugs were 36.3 billion Hungarian Forints (HUF) (144.5 million EUR, 211.3 million USD). For drugs used in the acute inpatient care, we found 22.59 billion HUF (89.9 million EUR, 131.5 million USD) annual health insurance expenditure. The Hungarian National Health Insurance Fund Administration (OEP) spent altogether 58.9 billion HUF (234.4 million EUR, 342.8 million USD) for the reimbursement of oncological drugs in outpatient, named patient and inpatient care. The reimbursement of oncological drugs represents a significant expenditure for the Hungarian National Health Insurance Fund Administration (OEP). Boncz I, Donka-Verebes é, Oberfrank F, Kásler M. Assessment of annual health insurance reimbursement of oncology drugs in Hungary.     

Acatalasemia and diabetes mellitus

The enzyme catalase catalyzes the breakdown of hydrogen peroxide into oxygen and water. It is the main regulator of hydrogen peroxide metabolism. Hydrogen peroxide is a highly reactive small molecule formed as a natural byproducts of energy metabolism. Excessive concentrations may cause significant damages to protein, DNA, RNA and lipids. Low levels in muscle cells, facilitate insulin signaling. Acatalasemia is a result of the homozygous mutations in the catalase gene, has a worldwide distribution with 12 known mutations. Increased hydrogen peroxide, due to catalase deficiency, plays a role in the pathogenesis of several diseases such as diabetes mellitus. Diabetes mellitus is a disorder caused by multiple genetic and environmental factors. Examination of Hungarian diabetic and acatalasemic patients showed that an increased frequency of catalase gene mutations exists among diabetes patients. Inherited catalase deficiency may increase the risk of type 2 diabetes mellitus, especially for females. Early onset of type 2 diabetes occurs with inherited catalase deficiency. Low levels of SOD and glutathione peroxidase could contribute to complications caused by increased oxidative stress.     

The frequency of induced premature centromere division in human populations occupationally exposed to genotoxic chemicals

Premature (early) centromere division (PCD, i.e., the separation of centromeres during the prometaphase/metaphase of the mitotic cycle) seems to be a possible manifestation of chromosome instability in human chromosome-breakage syndromes. Chromosome instability also frequently occurs in the peripheral blood lymphocytes (PBL) of humans occupationally exposed to clastogenic agents, and is considered an etiologic factor of neoplastic diseases. In order to investigate the importance of PCD in cancer risk assessment, we studied the frequency of PCDs in PBL of 400 Hungarian subjects. The various groups comprised 188 control donors and 212 subjects occupationally exposed to different genotoxic chemicals, such as acrylonitrile (ACN) and/or dimethylformamide (DMF), benzene, cytostatic drugs, ethylene oxide (ETO), mixed exposure in the rubber industry, mixed organic solvents including CCl4, hot oil-mist, bitumen, and polychlorinated biphenyls (PCB). Data were compared with chromosomal aberration frequencies determined in the same samples. PCD yields are significantly higher in populations exposed to mixed chemicals, crude oil and cytostatic drugs, compared with controls. PCDs involving more than three chromosomes are also more frequent in ETO- and oil mist-exposed groups than in the others. The results indicate that the induction of PCDs is neither incidental nor artificial. As a consequence, we suggest that PCD can be developed into a new, exposure-related cytogenetic biomarker for a more adequate occupational cancer risk assessment. A further, follow-up epidemiological and cytogenetic investigation of PCD is in progress.     

Micronucleus induction and FISH analysis in buccal cells and lymphocytes of nurses administering antineoplastic drugs

A genotoxic effect for antineoplastic drugs, in particular micronucleus induction, has been shown in several studies. The aim of our study was to assess genotoxic effects in nurses administering different mixtures of antineoplastic drugs in an oncology hospital by evaluating the frequency of micronuclei in exfoliated buccal cells and blood lymphocytes by use of the standard micronucleus (MN) test and by identifying, by means of FISH analysis with centromeric probes, the mechanism of micronucleus induction (clastogenic or aneugenic). The study group comprised 23 nurses, 10 of whom worked in the day-care hospital and 13 in the ward. Twenty healthy subjects were selected as controls. Pan-centromeric FISH analysis was performed on lymphocytes from a selected group of nurses (12/23 subjects) characterized by higher MN frequencies as observed by standard Giemsa staining. A significant increase of micronucleus frequency compared with controls was found in exfoliated buccal cells of both groups of nurses: day-care hospital nurses 0.92 versus 0.45 (p=0.034) and ward nurses 0.94 versus 0.45 (p=0.051). An increase, although not statistically significant, of mean MN frequency was also found by the MN standard test on lymphocytes of the day-care hospital nurses (10.9 versus 7.5; p=0.056), while no differences were found in ward nurses (8.15 versus 7.5; p=0.56). We found that the administration of antineoplastic drugs by nurses in ward units induced a higher frequency of FISH MN+ (43% of subjects) than in the day-care hospital (20%). This was associated with the micronucleus size percentage. This finding could be correlated with the different compositions of administered mixtures of antineoplastic drugs: in ward units the mixtures contained drugs, such as vinorelbine, that were absent in the mixtures administered in the day-care hospital. Our results show genetic damage induced by administration of antineoplastic drugs, particularly in exfoliated buccal cells. This result suggests the useful application of this non-invasive sampling to evaluate genotoxic effects of occupational exposure to mixtures of inhalable chemicals at low doses.     

The complexities of obesity and diabetes with the development and progression of pancreatic cancer

Pancreatic cancer (PC) is one of the most lethal malignant diseases with the worst prognosis. It is ranked as the fourth leading cause of cancer-related deaths in the United States. Many risk factors have been associated with PC. Interestingly, large numbers of epidemiological studies suggest that obesity and diabetes, especially type-2 diabetes, are positively associated with increased risk of PC. Similarly, these chronic diseases (obesity, diabetes, and cancer) are also a major public health concern. In the U.S. population, 50 percent are overweight, 30 percent are medically obese, and 10 percent have diabetes mellitus (DM). Therefore, obesity and DM have been considered as potential risk factors for cancers; however, the focus of this article is restricted to PC. Although the mechanisms responsible for the development of these chronic diseases leading to the development of PC are not fully understood, the biological importance of the activation of insulin, insulin like growth factor-1 (IGF-1) and its receptor (IGF-1R) signaling pathways in insulin resistance mechanism and subsequent induction of compensatory hyperinsulinemia has been proposed. Therefore, targeting insulin/IGF-1 signaling with anti-diabetic drugs for lowering blood insulin levels and reversal of insulin resistance could be useful strategy for the prevention and/or treatment of PC. A large number of studies have demonstrated that the administration of anti-diabetic drugs such as metformin and thiazolidinediones (TZD) class of PPAR-γ agonists decreases the risk of cancers, suggesting that these agents might be useful anti-tumor agents for the treatment of PC. In this review article, we will discuss the potential roles of metformin and TZD anti-diabetic drugs as anti-tumor agents in the context of PC and will further discuss the complexities and the possible roles of microRNAs (miRNAs) in the pathogenesis of obesity, diabetes, and PC.     

铁与2型糖尿病发病的最新进展

糖尿病对人类健康的威胁日益加重,近年来大量的实验、临床及流行病学资料显示体内铁过载与糖尿病发生存在密切关联。作为机体必需的营养元素,铁在机体组织中的稳态平衡对维持正常的生理功能至关重要。同时铁还是一种极强的促氧化剂,机体铁含量升高往往导致氧化压力增强,进而加大罹患2型糖尿病的风险;膳食中血红素铁摄入量增加以及机体铁代谢紊乱都可能导致2型糖尿病及其并发症发生。此外,其他胰岛素抵抗疾病如代谢综合征、妊娠糖尿病以及多囊卵巢综合征都与铁过载呈显著关联,过量铁是诱发这些疾病的主要原因,并直接导致胰岛素抵抗。治疗中可通过铁螯合剂的使用来有效降低机体铁水平,并改善胰岛素抵抗。这些研究成果为2型糖尿病的干预治疗提供了新思路。对铁代谢与2型糖尿病及其并发症的最新研究做简要综述。     

Narrative review of ferroptosis in obesity

Obesity is widely recognized as a major global health problem caused by a chronic energy imbalance resulting from a combination of excess caloric intake and insufficient energy expenditure. Excessive energy intake and physical inactivity are traditional risk factors for obesity. Obesity is a risk factor for many diseases, including hypertension, diabetes and tumours. Recent studies have found a strong link between ferroptosis and obesity. Ferroptosis is an iron-dependent regulated cell death caused by iron overload and reactive oxygen species-dependent excessive accumulation of lipid peroxidation. Ferroptosis is involved in many biological processes, such as amino acid metabolism, iron metabolism and lipid metabolism. Some potential strategies to reduce the adverse effects of ferroptosis on obesity are suggested and future research priorities are highlighted.     

Urinary cyclophosphamide excretion and micronuclei frequencies in peripheral lymphocytes and in exfoliated buccal epithelial cells of nurses handling antineoplastics

In this study, urinary cyclophosphamide (CP) excretion rate, as well as micronuclei (MN) in peripheral lymphocytes and in buccal epithelial cells were determined for 26 nurses handling antineoplastics and 14 referents matched for age and sex. In urine samples of 20 out of 25 exposed nurses CP excretion rate was found in a range of 0.02-9.14 microg CP/24 h. Our results of the analyses of CP in urine demonstrates that when the nurses were handling CP (and other antineoplastic drugs) this particular compound was observed in urine. The mean values (+/-SD) of MN frequencies (%) in peripheral lymphocytes from the nurses and controls were 0.61 (+/-0. 32) and 0.28 (+/-0.16), respectively (p<0.01). The mean value (+/-SD) of MN frequency (%) in buccal epithelial cells of nurses was 0.16 (+/-0.19) and also mean MN frequency in buccal epithelial cells for controls was found to be as 0.08 (+/-0.08), (p>0.05). Age, sex and smoking habits have not influenced the parameters analyzed in this study. Handling time of antineoplastics, use of protective equipment and handling frequency of drugs have no effect on urinary and cytogenetic parameters analyzed. No correlation was found between the urinary CP excretion and the cytogenetic findings in nurses. Neither could we find any relationship between two cytogenetic endpoints. Our results have identified the possible genotoxic damage of oncology nurses related to occupational exposure to at least one antineoplastic agent, which is used as a marker for drug handling. As a whole, there is concern that the present handling practices of antineoplastic drugs used in the several hospitals in Ankara will not be sufficient to prevent exposure.     

Iron in infectious diseases friend or foe?: The role of gut microbiota

Iron is a trace element involved in metabolic functions for all organisms, from microorganisms to mammalians. Iron deficiency is a prevalent health problem that affects billions of people worldwide, and iron overload could have some hazardous effect. The complex microbial community in the human body, also called microbiota, influences the host immune defence against infections. An imbalance in gut microbiota, dysbiosis, changes the host's susceptibility to infections by regulating the immune system. In recent years, the number of studies on the relationship between infectious diseases and microbiota has increased. Gut microbiota is affected by different parameters, including mode of delivery, hygiene habits, diet, drugs, and plasma iron levels during the lifetime. Gut microbiota may influence iron levels in the body, and iron overload and deficiency can also affect gut microbiota composition. Novel researches on microbiota shed light on the fact that the bidirectional interactions between gut microbiota and iron play a role in the pathogenesis of many diseases, especially infections. A better understanding of these interactions may help us to comprehend the pathogenesis of many infectious and metabolic diseases affecting people worldwide and following the development of more effective preventive and/or therapeutic strategies. In this review, we aimed to present the iron-mediated host-gut microbiota interactions, susceptibility to bacterial infections, and iron-targeted therapy approaches for infections.     

Maternal diseases and isolated orofacial clefts in Hungary

BACKGROUND: Isolated orofacial clefts (OFCs) are likely to be caused by gene-environment interaction; therefore, the objective of the current study was to evaluate the possible association between all maternal diseases during pregnancy and isolated cleft lip with or without cleft palate (CL+/-CP) and posterior cleft palate (PCP) in the offspring. METHODS: The database of the large population-based Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996, was evaluated. The database includes 1374 cases with isolated CL+/- CP and 601 with PCP, plus 38,151 matched population controls (without defects) and 20,868 patient controls with other defects. Data collection was based on prospective medical records, retrospective maternal data via a self-reported questionnaire, and home visits of nonresponding families. RESULTS: An increased risk for isolated CL+/- CP was found for children born to mothers with influenza, common cold, orofacial herpes, and gastroenteritis during pregnancy. Risk for isolated PCP was increased in children of mothers with influenza, sinusitis, and bronchitis. Among chronic maternal diseases, epilepsy and angina pectoris showed a higher prevalence in the mothers of children born with isolated OFCs (cases). CONCLUSIONS: Some maternal diseases are risk factors for the pathogenesis of isolated OFCs. It is worth considering the prevention of possible harmful effects of influenza by vaccination during the expected epidemic period.     

The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action

Vitamin D, the sunshine vitamin, is important for childhood bone health. Over the past two decades, it is now recognized that vitamin D not only is important for calcium metabolism and maintenance of bone health throughout life, but also plays an important role in reducing risk of many chronic diseases including type I diabetes, multiple sclerosis, rheumatoid arthritis, deadly cancers, heart disease and infectious diseases. How vitamin D is able to play such an important role in health is based on observation that all tissues and cells in the body have a vitamin D receptor, and, thus, respond to its active form 1,25-dihydroxyvitamin D. However, this did not explain how living at higher latitudes and being at risk of vitamin D deficiency increased risk of these deadly diseases since it was also known that the 1,25-dihydroxyvitamin D levels are normal or even elevated when a person is vitamin D insufficient. Moreover, increased intake of vitamin D or exposure to more sunlight will not induce the kidneys to produce more 1,25-dihydroxyvitamin D. The revelation that the colon, breast, prostate, macrophages and skin among other organs have the enzymatic machinery to produce 1,25-dihydroxyvitamin D provides further insight as to how vitamin D plays such an essential role for overall health and well being. This review will put into perspective many of the new biologic actions of vitamin D and on how 1,25-dihydroxyvitamin D is able to regulate directly or indirectly more than 200 different genes that are responsible for a wide variety of biologic processes.     

Evaluation of genotoxic effects induced by exposure to antineoplastic drugs in lymphocytes and exfoliated buccal cells of oncology nurses and pharmacy employees

The continuous introduction of new antineoplastic drugs and their use as complex mixture emphasize the need to carry out correct health risk assessment. The aim of this study was to evaluate genotoxic effects of antineoplastic drugs in nurses (n=25) and pharmacy technicians (n=5) employed in an oncology hospital. The nurses administered antineoplastic drugs in the day-care hospital (n=12) and in the wards (n=13), and pharmacy technicians prepared the drugs in the central pharmacy. We performed the micronucleus (MN) test with lymphocytes and exfoliated buccal cells and conducted traditional analysis of chromosomal aberrations (CA). Thirty healthy subjects were selected as controls. Monitoring of surface contamination with cyclophosphamide, 5-fluorouracil, ifosfamide, cytarabine, and gemcitabine showed the presence of detectable levels only for cyclophosphamide, 5-fluorouracil and ifosfamide. In addition, we measured the 5-fluorouracil metabolite alpha-F-betaalanine in the urine of all subjects and found significant concentrations only in 3 out of 25 nurses. The micronucleus assay with lymphocytes did not show significant differences between exposed and control groups, while the same test with exfoliated buccal cells found higher values in nurses administering antineoplastic drugs than in pharmacy employees. In the CA analysis, we detected in exposed groups a significant increase (about 2.5-fold) of structural CA, particularly breaks (up to 5.0-fold). Our results confirm the genotoxic effect of antineoplastic drugs in circulating blood lymphocytes. Moreover, in exfoliated buccal cells the data show more consistent genetic damage induced during administration of the antineoplastic drugs than during their preparation. The data also stress the use of this non-invasive sampling, to assess occupational exposure to mixture of chemicals at low doses.     

Vitamin D deficiency in children with cerebral palsy: A narrative review of epidemiology,contributing factors,clinical consequences and interventions

Sufficient vitamin D levels are necessary, not only for mineralization, normal growth and development of bones, but also for the prevention of fatal chronic diseases like diabetes mellitus, metabolic syndrome and cancer. This is of particular importance in children with neuro- and musculoskeletal disorders, especially cerebral palsy (CP). CP is a heterogeneous group of childhood developmental disability disorders described by uncharacteristic posture, balance, and movement. Patients with CP are at an increased risk of vitamin D deficiency and as a result reduced bone mineral density, bone fragility, osteopenia, and rickets. The present review aims to combine and summarize available evidence, regarding the epidemiology, underlying contributing factors, clinical consequences, and treatment interventions of vitamin D deficiency in children with CP.     

Screening drug effects in patient‐derived cancer cells links organoid responses to genome alterations

Cancer drug screening in patient‐derived cells holds great promise for personalized oncology and drug discovery but lacks standardization. Whether cells are cultured as conventional monolayer or advanced, matrix‐dependent organoid cultures influences drug effects and thereby drug selection and clinical success. To precisely compare drug profiles in differently cultured primary cells, we developed DeathPro, an automated microscopy‐based assay to resolve drug‐induced cell death and proliferation inhibition. Using DeathPro, we screened cells from ovarian cancer patients in monolayer or organoid culture with clinically relevant drugs. Drug‐induced growth arrest and efficacy of cytostatic drugs differed between the two culture systems. Interestingly, drug effects in organoids were more diverse and had lower therapeutic potential. Genomic analysis revealed novel links between drug sensitivity and DNA repair deficiency in organoids that were undetectable in monolayers. Thus, our results highlight the dependency of cytostatic drugs and pharmacogenomic associations on culture systems, and guide culture selection for drug tests.     

Olfactory ferric and ferrous iron absorption in iron-deficient rats

The absorption of metals from the nasal cavity to the blood and the brain initiates an important route of occupational exposures leading to health risks. Divalent metal transporter-1 (DMT1) plays a significant role in the absorption of intranasally instilled manganese, but whether iron uptake would be mediated by the same pathway is unknown. In iron-deficient rats, blood (59)Fe levels after intranasal administration of the radioisotope in the ferrous form were significantly higher than those observed for iron-sufficient control rats. Similar results were obtained when ferric iron was instilled intranasally, and blood levels of (59)Fe were even greater in the iron-deficient rats compared with the amount of ferrous iron absorbed. Experiments with Belgrade (b/b) rats showed that DMT1 deficiency limited ferric iron uptake from the nasal cavity to the blood compared with +/b controls matched for iron deficiency. These results indicate that olfactory uptake of ferric iron by iron-deficient rats involves DMT1. Western blot experiments confirmed that DMT1 levels are significantly higher in iron-deficient rats compared with iron-sufficient controls in olfactory tissue. Thus the molecular mechanism of olfactory iron absorption is regulated by body iron status and involves DMT1.     

孕妇维生素D缺乏与妊娠期糖尿病的相关性分析

目的:调查孕妇妊娠早期维生素D水平及其影响因素,探讨维生素D缺乏与妊娠期糖尿病的相关性。方法:选取2012年7月至2013年4月在上海交通大学医学院附属新华医院产科正规产检并分娩的非孕前糖尿病孕妇,在其建卡初检时采用电化学发光免疫技术测定血清25(OH)D3水平;妊娠24-28周行糖筛查及糖耐量试验,诊断是否为妊娠期糖尿病GDM。收集并整理孕妇年龄,孕前体重指数BMI、维生素D测定孕周与测定季节、孕期维生素D补充情况等信息。结果:1000例孕妇中,GDM发病率为11.5%,维生素D缺乏比例占67.4%;其中,约有54%孕妇常规补充复合维生素,约含维生素400 IU/天,10%孕妇常规补充维生素D。GDM孕妇25(OH)D3水平显著低于正常对照组(P=0.007)。维生素D缺乏孕妇发生GDM的风险是维生素D水平较高组的1.944倍,且在秋冬季更易发生GDM。可以考虑在孕14-16周进行维生素D水平的早期测定。结论:孕妇维生素D缺乏十分普遍。妊娠早期孕妇低维生素D水平可能增加孕妇胰岛素抵抗及孕期发生GDM的发生风险。     

Use of mean platelet volume improves detection of platelet disorders

Classification of platelet disorders has been based on the platelet count. Addition of a second variable, mean platelet volume (MPV), to the routine blood count allows classification of patients into 9 categories: high, low, or normal MPV, and high, low or normal platelet count. We studied 1,244 adult inpatients. 1,134 had both platelet values normal. 11 patients had high MPV and low platelet count: all had hyperdestructive causes. 15 patients had high MPV and normal platelet count: 12 had heterozygous thalassemia, and three had iron deficiency. Seven patients had high MPV and high platelet count: causes included myeloproliferative disorders, inflammation, iron deficiency, and splenectomy, 25 patients had high platelet counts and normal MPV: the causes were inflammation, infection, sickle cell anemia, iron deficiency, or chronic myelogenous leukemia. 52 patients had an MPV that was inappropriately low for the platelet count (high, normal, or low). All had sepsis, splenomegaly, aplastic anemia, chronic renal failure, or a disease being treated with myelosuppressive drugs. High MPV thus appears correlated with myeloproliferative disease or thalassemia; and low MPV, with cytotoxic drugs or marrow hypoplasia. Addition of MPV to the platelet count allows subtler disorders to be detected (when the platelet count is normal), and allows distinction of the cause of thrombocytopenia.     

Population-based case-control study of isolated congenital cataract

BACKGROUND: The aim of this study was to detect possible etiological factors in the origin of isolated congenital cataracts. METHODS: The data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-2002, contains 111 cases of isolated congenital cataract and 111 matched control pairs without the defect, 37,837 population controls without any defects, and 22,744 malformed controls with other nonocular abnormalities. Exposure data and family history are based on prospective medical records, retrospective maternal information, and information obtained by regional nurses during a home visit with nonrespondent mothers. RESULTS: A positive family history indicated an autosomal-dominant origin in 10% of cases. Rubella infections occurred more frequently in case mothers than in control mothers before vaccination against rubella virus was instituted. A higher prevalence of influenza or common cold during pregnancy was found in the case group (55.9%) than in the population control group (18.5%; adjusted odds ratios [ORs], 5.8; 95% confidence interval (CI), 4.0-8.4) or in the malformed control group (21.7%; adjusted OR, 4.7; 95% CI, 3.2-6.9). The prevalence of acute infectious diseases of the respiratory system during pregnancy was also higher in the case group (26.1%) than in the population control group (9.1%; adjusted OR, 3.8; 95% CI, 2.5-5.8), or the malformed control group (9.3%; adjusted OR, 3.4; 95% CI, 2.3-5.3). The higher risk for isolated congenital cataract in cases of mothers with influenza or common cold and acute infectious diseases of the respiratory system during pregnancy was not found after administration of antifever therapy. CONCLUSIONS: Some isolated congenital cataracts are preventable by rubella vaccination and probably by influenza vaccination in the epidemic period. In addition, our results suggest that using antifever therapy for fever-related respiratory diseases may restrict the teratogenic risk of hyperthermia.