Trends in zygomycosis in children

Zygomycosis, or mucormycosis, is associated with significant morbidity and mortality in both children and adults. Studies in adults have shown an increase in the incidence of zygomycosis, particularly among haemtopoietic stem cell transplant (HSCT) recipients and patients with haematologic malignancies. There is a paucity of data on the epidemiology of zygomycosis in children. We performed a retrospective analysis to describe trends in zygomycosis between 1 January 2003 and 31 December 2010. We used the Pediatric Health Information System (PHIS) database to identify paediatric patients who were diagnosed with zygomycosis during the study period. Administrative data on diagnoses, demographics, underlying conditions and clinical experiences were collected. Summary statistics were calculated and tests for trend were conducted. We identified 156 unique patients with zygomycosis. The prevalence of zygomycosis did not significantly increase over time (P=0.284). The most common underlying condition was malignancy (58%) and over half received intensive care. Voriconazole utilisation among all hospitalised children significantly increased during the period (P=0.010). Our study demonstrates that the incidence of zygomycosis is not significantly increasing. During the time period there was a significant increase in the use of voriconazole among children.     

Statistical challenges in preprocessing in microarray experiments in cancer

Many clinical studies incorporate genomic experiments to investigate the potential associations between high-dimensional molecular data and clinical outcome. A critical first step in the statistical analyses of these experiments is that the molecular data are preprocessed. This article provides an overview of preprocessing methods, including summary algorithms and quality control metrics for microarrays. Some of the ramifications and effects that preprocessing methods have on the statistical results are illustrated. The discussions are centered around a microarray experiment based on lung cancer tumor samples with survival as the clinical outcome of interest. The procedures that are presented focus on the array platform used in this study. However, many of these issues are more general and are applicable to other instruments for genome-wide investigation. The discussions here will provide insight into the statistical challenges in preprocessing microarrays used in clinical studies of cancer. These challenges should not be viewed as inconsequential nuisances but rather as important issues that need to be addressed so that informed conclusions can be drawn.     

Increased apoptosis in cancer cells in vitro and in vivo by ceramides in transferrin-modified liposomes

Lysosomes are a promising therapeutic target for induction apoptosis in cancer cells due to lysosomal membrane permeabilization (LMP) leading to leakage of hydrolytic enzymes, especially the cathepsins, into the cytoplasm. We hypothesized that with the modification of the ceramide-loaded liposomes with transferrin (Tf), we would achieve both tumor targeting and increased delivery of lysosome-destabilizing agents, such as ceramides to lysosomes, to initiate LMP-induced apoptosis. We prepared Tf-modified (TL) and plain (PL) liposomes and loaded with short (C6)- or long (C16) N-acyl chain ceramides. Uptake, intracellular localization of liposomes, stability of the lysosomal membrane and release of cathepsin D were investigated on Hela cells by fluorescence microscopy and flow cytometry. Apoptosis was evaluated by binding of fluorescently-labeled Annexin V. Antitumor and pro-apoptotic effects of C6Cer-loaded Tf-liposomes were demonstrated in vivo in an A2780-ovarian carcinoma xenograft mouse model. TL were internalized specifically via the TfR-dependent endocytic pathway and localized within the endosome-lysosomal compartment. Ceramide-loaded Tf-liposomes significantly increased apoptosis compared with ceramide-free and ceramide-loaded non-modified liposomes. The treatment of cancer cells with TL led to increased LMP and cytoplasmic relocation of the intralysosomal cathepsin D. A strong antitumor and pro-apoptotic effect of C6Cer-loaded TL was also demonstrated in vivo in an A2780-ovarian carcinoma xenograft mouse model. The lysosomal accumulation of ceramides delivered by Tf-liposomes initiates the permeabilization of the lysosomal membranes required for the release of lysosomal cathepsins into the cytoplasm and initiation of the cancer cell apoptosis both in vitro and in vivo.     

Recent advances in pharmacogenomics in oncology

Progress in understanding the molecular mechanisms of oncogenesis, together with the sequencing of the human genome and the availability of huge databases, bring new tools for the discovery and the evaluation of new potential targets for cancer therapy and for the individualisation of cancer chemotherapy as a function of the molecular characteristics of tumours. Targeting the genetic alterations of cancer cells appears feasible and the first successes of this approach allow to remain optimistic about the renewal of our therapeutic armamentarium. In addition, seeking for correlations between gene expression profiles and chemosensitivity has been performed on the in vitro models of the National Cancer Institute and may allow crucial improvements in the identification of patients who world best take advantage of a specific chemotherapy. Clinical trials, first on a retrospective basis, then performed prospectively, are implemented to validate this approach.     

Dermatomycosis in Goats in India

Summary: In an extensive survey involving 2176 goats 1.56% of goats manifested clinical lesions of ringworm infection. Animals below the age of 6 months were affected most (4.20%). The incidence of infection was higher during the winter months. T. verrucosum, T. mentagrophytes and M. gypseum were isolated from the skin scrapings of 12, 4, and 2 goats respectively. It is suggested that the infected animals could be a source of disease to human population in which the zoophilic dermatophyte invasion is characterized by severe inflammatory lesions of the skin. The zoonotic importance of different dermatophytes is stressed.
Zusammenfassung: In einer ausgedehnten Untersuchung an 2176 Ziegen wurden bei 1,56% klinische Zeichen einer Hautmykose festgestellt. Tiere, die jühger als 6 Monate alt waren, zeigten mit 4,20% am häfigsten Krankheitssymptome. In den Wintermonaten war die Erkrankungshäufigkeit am gröBten. T. vermcosum, T. mentagrophytes and M. gypseum wurden jeweils von 12,4 bzw. 2 Ziegen isoliert. Die inflzierten Tiere köinnen eine Infektionsquelle für die menschliche Bevölkerung darstellen und dort Mykosen mit stark entzündlichen Veränderungen auslösen. Die Bedeutung verschiedener Dermatophyten als Erreger von Zoonosen wird hervorgehoben.     

Hemoglobin in lymphogranulomatosis in children

The peculiarities of hemoglobin content and properties in lymphogranulomatosis were studied in children by different methods. In most patients the content of fetal hemoglobin and methhemoglobin was found to increase and the rate of ferricyanide oxidation of hemoglobin also increases. Simultaneously, the rate of non-homogenicity of basic hemoglobin fractions was observed to increase on account of immunologically different components.     

Socioeconomic factors in cancer in Sweden

It is well known that certain cancers have shown clustering in socioeconomic groups, but limited data are available on recent results and time trends in such clustering. We determined standardized incidence ratios (SIR) for cancer, adjusted for age, period, region, parity and age at first childbirth among men and women in 6 socioeconomic groups based on the Swedish Family-Cancer Database. Persons had to be identified with the same socioeconomic status in the census of years 1960 and 1970, or of years 1960, 1970 and 1980; the comparison group was all people according to the same censuses. Cancers were followed from years 1970 to 1998 or from 1980 to 1998. Both increased and decreased SIRs were found, and a consistent pattern emerged, although the overall SIRs for cancer did not differ much, the lowest being for farmers (0.85) and the highest for professional men (1.07) and women (1.11). At individual sites, manual workers were at risk of tobacco-, alcohol- and occupation- and human papilloma virus-related cancers and at a decreased risk at most other cancers. Manual workers and farmers showed an excess of stomach cancer; professionals had an excess of melanoma and squamous cell skin cancer. Male and female SIRs correlated highly for manual and blue-collar workers and for professionals. The overall population-attributable fraction for selected sites was 16.7% for men and 10.9% for women and it was highest, over 50%, for lung cancer in both genders.     

Sex hormones in women in rural China and in Britain

Plasma concentrations of certain hormones linked to breast cancer risk were measured in age-pooled samples from 3,250 rural Chinese women in 65 counties, and 300 British women, all aged 35-64. In age-groups 35-44, 45-54 and 55-64 respectively, mean oestradiol concentrations were 36% (P = 0.043), 90% (P less than 0.001) and 171% (P = 0.001) higher in the British than in the Chinese women, and mean testosterone concentrations were 48% (P less than 0.001), 68% (P less than 0.001) and 53% (P = 0.001) higher in the British than in the Chinese women. The difference in testosterone concentrations between the two countries appeared to be due largely to the lower average body weight in the Chinese women. Sex hormone binding globulin did not differ significantly between the two countries in age groups 35-44 and 45-54, but was 15% (P = 0.002) lower in the British than in the Chinese women at ages 55-64. Prolactin concentrations did not differ significantly between the two countries in any age group.     

Trends in cervical cancer and carcinoma in situ in Great Britain

Doubts have frequently been expressed about the effectiveness of the screening programme for cervical cancer in Britain. These doubts have been reinforced as a result of recent increases in mortality from this disease among younger women. In this paper we discuss trends in registration and mortality data, relate these to the level of screening, and conclude that screening may in fact have had a considerable impact on mortality rates. There is good evidence that in some age groups there has been a large increase in the incidence of carcinoma in situ of the cervix; it seems likely that the potential increase in cervical cancer incidence and mortality may have been partially prevented as a result of the screening programme. The extent of this effect cannot be quantified precisely because of uncertainties concerning the natural history of cervical cancer, differences in risk for different cohorts, and the possible effects of other factors. It is likely that incidence rates will continue to change, and it will be necessary to monitor these and the screening programme with some care in order to make the best use of the resources available for cervical cytology.     

Temozolomide treatment in glioma--experiences in two university hospitals in Finland

Thirty-two patients with relapsing glioma were treated with temozolomide in two university hospitals in Finland. One patient (3%) had complete response and 9 (28%) partial response, with 8 patients (25%) showing stable disease. Median progression-free survival for these 18 patients (56%) was 7 months (range 2-11+). The remaining either had progressive disease (25%) or only clinical evaluation (19%). Karnofsky score improved in 34% of patients and decreased in 3%. Symptoms were alleviated in 44% and deteriorated in 9%. Grade 3-4 toxicity was detected in 9% of the patients. Only 4% of the days in treatment were spent in hospital. An average 1.8 neuroradiological investigations, 6.9 laboratory visits, and 5.3 visits to the oncologist were made. This study confirms that temozolomide has positive effects on the outcome of often heavily pretreated glioma patients. High drug costs are compensated by prolonged home care and even the possibility to maintain working capacity.     

Hodgkin's disease in children in Kuwait

Between 1968 and 1981, 78 children younger than age 15 years were diagnosed, staged, treated, and followed up for a minimum period of 2 years. Most cases (64%) were in their first decade and the male-to-female ratio was 1.9:1. Mixed cellularity type occurred in 49% and nodular sclerosis in 32%. Lymphocytic depletion type was rare and occurred in only 4% of the cases. More than one half (53%) had Stages III and IV at presentation. The mediastinum was involved in 38%. The treatment of Stages I and II was mainly by radiotherapy, and Stages III and IV by combination of radiotherapy and chemotherapy. The total survival was 75% and relapse-free survival was 53%. Since 1975, lymphography became a routine investigation and staging laparotomy was performed in selected case. The mantle field was extended to include the para-aortic bar and spleen in Stage II with enlarged mediastinum, Stage IIIs after laparotomy, and cases in which laparotomy was thought to be indicated but was not performed. The new policy resulted in marked improvement in survival (from 56% to 87%) and relapse-free survival (from 32% to 70%). The stage at presentation was the main prognostic factor, although in the second period of the study, the difference between Stage I and II disappeared.     

Changes in testicular cancer in Scotland

There are two purposes to this paper. Firstly to describe the temporal pattern of germ-cell testicular cancers in Scotland, both as a single entity and as the histological sub-types (pure) seminoma and teratoma. Incidence rates rose by over 50% between 1959 and 1984, with the rates of seminoma increasing only marginally and the majority of the overall increase accounted for by the substantial increased observed among the sub-type teratoma.Secondly, to investigate the impact of new therapies on the mortality rate from germ-cell testicular cancer in Scotland in the light of improvements in survival rate reported during the last 25 years from clinical trials and clinical series. Noticeable changes have occurred in the temporal pattern of mortality which cannot be explained by changes in incidence. The ever-widening gap between the increasing incidence rate and the declining mortality rate, particularly apparent in the high-risk age group 15–44, indicates an improving prognosis for patients with this malignancy in Scotland.     

Spatial variation in stage distribution in colorectal cancer in the Netherlands

BackgroundIn the Netherlands the incidence of colorectal cancer has increased, mainly in the eastern part of the country. Patient delay due to unawareness or ignorance of symptoms and differences in use of diagnostic tools could have influence on the stage distribution. The aim of this study was to evaluate geographical differences in stage-specific incidence rates of colon and rectal cancer in the Netherlands.MethodsAge-adjusted incidence rates for cancers of the colon and rectum diagnosed in 2001–2005 and registered in the Netherlands Cancer Registry were calculated for each municipality and stage. The incidence for each 500 m by 500 m grid was estimated as a weighted average of the incidence rates of the neighbouring municipalities. The incidence rates and the stage distribution are both presented as maps. Geographic variation in stage-specific incidence was evaluated using spatial scan statistic.ResultsIn both colon and rectal cancer, significant spatial variation in stage-specific incidences was found, except for colon cancer of stages III and IV. The regions with a higher stage-specific incidence were almost all in the south eastern part of the Netherlands, however, these differences were not seen in the stage distribution. There were no differences in stage distribution between large cities and the rest of the country.ConclusionsThese maps give insight into differences in stage-specific incidences of colon and rectal cancer in the Netherlands. Educational interventions to increase the awareness of symptoms of colorectal cancer may be especially useful for the population in regions with high incidence of advanced stages.     

整合素在急性白血病中的研究进展

急性白血病是一种早期造血干/祖细咆的恶性克隆性疾病.微小残留病和耐药被认为是其复发和难治的根源.近来,越来越多的证据显示白血病细胞通过与骨髓微环境中的基质细胞或细胞外基质相互作用促进其存活,并增强其对常规化疗药物的耐药.整合素是介导细胞与细胞外基质（细胞与非细胞成分）粘连的最主要黏附分子,在细胞增殖、存活等生物学过程中发挥关键作用,但作用机制尚不完全清楚.现就目前揭示的整合素及肿瘤微环境在急性白血病发生、发展中的作用进行综述.     

Advances in cancer epidemiology in Japan

Epidemiologists in Japan have been performing calculations to estimate nationwide cancer incidence rates as well as 5‐year survival rates using population‐based cancer registry data. There have been remarkable changes in cancer incidence and/or mortality in cancers of the lung, liver and stomach, which were thought to be attributed to the changing impact of exposure to cigarette smoking, chronic hepatitis C virus infection and Helicobacter pylori infection, respectively. In systematic reviews providing evidence in risk/protective factors for cancer sites using case–control and cohort studies of the Japanese population, there were associations between cancer sites (esophagus, stomach, colo‐rectum, liver, pancreas, lung and breast) and various lifestyle factors. In the past 10 years, a hospital‐based case–control study at Aichi Cancer Center provided valuable evidence of gene‐environment interaction on the development of cancer [i.e., the effects of aldehyde dehydrogenase‐2 (ALDH2) polymorphism and heavy alcohol drinking on esophageal cancer, ALDH2 polymorphism and smoking on lung cancer, methylenetetrahydrofolate reductase polymorphism and heavy alcohol drinking on pancreatic cancer]. The database with stored DNA was also used and identified seven loci containing significant but low‐penetrance polymorphisms associated with the development of breast cancer. These findings together with established risk factors are likely to be useful to predict personalized breast cancer risk in East Asian women. In 2005, the Japan Multi‐Institution Collaborative Cohort (J‐MICC) study was launched to elucidate gene‐environment interactions as well as to confirm preclinical diagnostic biomarkers of cancer. J‐MICC, which has recruited 92,000 healthy individuals by the end of 2012, will follow the individuals until 2025.     

Achievements in systemic therapies in the pregenomic era in metastatic breast cancer

Over the last decades, the introduction of several new agents into clinical practice has significantly improved disease control and obtained some, albeit rare, survival benefits in metastatic breast cancer (MBC). Despite these results, the choice of treatment for the majority of patients is still empirically based, since the only two predictive factors with level 1 evidence for clinical use are hormonal receptor status for endocrine therapy and HER-2 status for trastuzumab therapy. Important improvements in the endocrine therapy of both pre- and postmenopausal women with hormone-responsive disease have been achieved. For premenopausal women, ovarian function suppression with luteinizing hormone-releasing hormone analogs combined with tamoxifen has become the standard treatment, although aromatase inhibitors plus ovarian function suppression are under evaluation. In postmenopausal patients, aromatase inhibitors have proved to be superior to standard endocrine therapies in either first- or second-line treatment and a novel antiestrogen compound, fulvestrant, has been introduced in clinical practice. Chemotherapy remains the treatment of choice for hormone unresponsive or resistant patients. Anthracyclines and taxanes have been used either alone or in combination as first-line chemotherapy, but with the more frequent use of these agents in the adjuvant setting, new standards are needed for first-line chemotherapy, and new and more efficacious treatments are required. In the subgroup of patients with tumors that overexpress HER-2, the use of trastuzumab alone or in combination with chemotherapy has modified the natural history of these tumors, even if only about one out of two patients obtains a clinical response. In this review we summarize the main achievements and the currently available treatment options for patients with MBC.     

Tamoxifen in ductal carcinoma in situ

The widespread adoption of screening mammography has resulted in an increased incidence of ductal carcinoma in situ (DCIS), which now accounts for 20% to 30% of new breast cancer diagnoses. Despite treatment with combined lumpectomy and radiation therapy, up to 15% of women will experience an ipsilateral breast recurrence, with 50% of these recurrences containing invasive disease. There is also a 6% incidence of contralateral breast cancers in women treated for DCIS. The recognition that adjuvant tamoxifen reduces local, regional, and distant disease in women diagnosed with invasive breast cancer led to the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-24 study, which randomized more than 1,800 women undergoing breast-sparing surgery and radiation for DCIS to adjuvant tamoxifen versus placebo for 5 years. At 7 years of follow-up, there was a statistically significant 27% reduction in the annual incidence rate of all breast cancer-related events for those women receiving tamoxifen, including a 48% reduction in invasive breast cancer. The benefit attributable to tamoxifen was confined to those tumors that were estrogen receptor (ER)-positive. However, adverse events, including endometrial cancer, thromboembolic events, and cataracts, are more common in older women. Tamoxifen should be considered as an adjunct to treatment for women undergoing breast-conserving surgery for ER-positive DCIS.     

Foreign bodies in ENT in a teaching hospital in Eastern India

Objective

To evaluate the nature, common sites, modes of presentation of various foreign bodies (FB) in Ear, Nose and Throat (ENT).

Materials and methods

Observational retrospective study carried out at Vivekananda Institute of Medical Sciences, Ramakrishna Mission Seva Pratishthan. The study period was between Jan 2006 to Jan 2007. The information obtained from the hospital record books.

Results

Four hundred and eighty-two patients presented in the Department of Otorhinolaryngology of Vivekananda Institute of Medical Sciences, in the study period with FB in their ENT. Out of 482 pts, the commonest location of FB was to be in throat with 302 pts (62%) followed by ear with 119 pts (25%) and nose 61 pts (13%). Amongst the FB in throat the commonest was fish bone and the commonest site being tonsils. Artificial denture accounted for a significant number of 13 (4.3%). External auditory canal was the commonest site of FB lodgment in ear found in 118 patients (99.16%). Nasal FB were found in 61 patients; more common in pediatric age group (98.36%).

Conclusion

From this study we have found that FB lodgement is a very common complaint with which patients come to otolaryngologist. The commonest site of FB lodgement is in the throat. Most of the FB could be removed in emergency room (ER) with or without Local Anesthesia.