Recently, three new polyomaviruses  have been reported to infect humans. It has also been suggested that lymphotropic polyomavirus, a virus of simian origin, infects humans. KI and WU polyomaviruses have been detected mainly in specimens from the respiratory tract while Merkel cell polyomavirus has been described in a very high percentage of Merkel cell carcinomas. The distribution, excretion level and transmission routes of these viruses remain unknown.Here we analyzed the presence and characteristics of newly described human polyomaviruses in urban sewage and river water in order to assess the excretion level and the potential role of water as a route of transmission of these viruses. Nested-PCR assays were designed for the sensitive detection of the viruses studied and the amplicons obtained were confirmed by sequencing analysis. The viruses were concentrated following a methodology previously developed for the detection of JC and BK human polyomaviruses in environmental samples. JC polyomavirus and human adenoviruses were used as markers of human contamination in the samples. Merkel cell polyomavirus was detected in 7/8 urban sewage samples collected and in 2/7 river water samples. Also one urine sample from a pregnant woman, out of 4 samples analyzed, was positive for this virus. KI and WU polyomaviruses were identified in 1/8 and 2/8 sewage samples respectively. The viral strains detected were highly homologous with other strains reported from several other geographical areas. Lymphotropic polyomavirus was not detected in any of the 13 sewage neither in 9 biosolid/sludge samples analyzed.This is the first description of a virus isolated from sewage and river water with a strong association with cancer. Our data indicate that the Merkel cell polyomavirus is prevalent in the population and that it may be disseminated through the fecal/urine contamination of water. The procedure developed may constitute a useful tool for studying the excreted strains, prevalence and transmission of these recently described polyomaviruses. Polyomaviridae family that persistently infect humans and cause disease in immunocompromised individuals. These viruses have been potentially implicated in certain cancers .The nucleotide sequences obtained were deposited in GenBank [GenBank: None of the 22 sewage, sludge and biosolid samples tested positive for LPyV although typical concentrations of JCPyV and HAdV indicated human fecal contamination (data not shown). The nPCR assay showed a sensitivity of 1-10 genomic copies/reaction when the complete LPyV genome  cloned iThe observation that MCPyV DNA was much more frequently detected than that of KIPyV or WUPyV might reflect that MCPyV is a more prevalent infection or that it is a highly excreted virus.Our results on MCPyV in urine, urban sewage and river water strongly support the notion that this virus shows an excretion pattern that resembles that of JCPyV and BKPyV. Human excretion of new polyomaviruses, especially MCPyV, may lead to fecal (urine) contamination of water and food.in vitro culture of the new polyomaviruses because no cell culture systems for these viruses are available at present. Furthermore, for other human polyomaviruses, such as JCPyV, the regulatory regions of strains excreted in urine present an archetypal structure and are inefficiently cultured.In this study we did not attempt the To our knowledge, this is the first report of the presence of a virus strongly related to human cancer in sewage and river water samples. We propose that the methodology reported here is suitable to study the prevalence, excretion pattern and genetic variability of recently discovered human polyomaviruses in environmental matrices.The authors declare that they have no competing interests.SBM coordinated the study, concentrated urine samples and nucleic acid extractions of the urine samples, collaborated in PCR assays, typed the amplicons detected and drafted the manuscript. JRM concentrated the sewage and biosolid samples and performed the nucleic acid extractions; he also collaborated in the PCR analysis and in the sequencing of the resulting amplicons. BC concentrated river water samples and performed nucleic acid extraction of the same samples. AC collaborated in the production of standards for the quantification of HAdV and JCPyV and in the nucleotide sequence comparisons. RG participated in the development of the methodology, conception and coordination of the study and helped to draft the manuscript. All authors read and approved the final manuscript.SBM is an assistant professor at the Department of Microbiology of the Faculty of Biology, University of Barcelona. Her main research interests are the epidemiology of human and animal polyomaviruses. She addresses their transmission through the environment and their potential as indicators of the presence of human or/and animal fecal contamination.


Although transmissible spongiform encephalopathies (TSE) or prion diseases are neurodegenerative disorders, the immune system is also involved, at least in the early stages of their pathogenesis. Extensive studies have focused on cells targeted by the TSE agent for its replication but few on the possible involvement of macrophages in its clearance, as in more conventional diseases. This review summarises some of the experiments aimed at demonstrating a role for macrophages in TSE and presents the application to TSE of the macrophage "suicide" technique, which has been used to clarify the implication of these cells in the early steps of TSE pathogenesis.


The death certificate only (DCO) index, which quantifies the proportion of patients for whom the death certificate provides the only notification to the registry, is a widely used measure of incompleteness of population-based cancer registration. This paper provides an algebraic assessment and a quantitative illustration of the relationship between the DCO index and incompleteness of cancer registration. It is shown that the relationship between the DCO index and incompleteness of registration is strongly dependent on the case fatality rate and the misclassification rates of cancer deaths among unregistered patients. Therefore, the DCO index is a very poor indicator of incompleteness. Similar limitations apply to the DCN index (proportion of cases first notified by death certificate), which has been proposed as an alternative measure of incompleteness.


Esophageal resection remains the only curative option in high grade dysplasia of the Barrett esophagus and non metastasized esophageal cancer. In addition, it may also be an adequate treatment in selected cases of benign disease. A wide variety of minimally invasive procedures have become available in esophageal surgery. Aim of the present review article is to evaluate minimally invasive procedures for esophageal resection, especially the approach performed through right thoracoscopy. Esophagus resection may be the adequate treatment in selected cases of benign esophageal diseases, but the most frequent indications for esophageal resection are the high grade dysplasia of the Barrett esophagus and the non metastasized esophageal cancer.Prognosis of patients with esophageal cancer remains poor: only 56% of the patients presented with esophageal cancer have resectable disease with an overall five-years survival rate of 10% while the five-years survival rate among operated patients is still only 18%.3 The adv4There is still controversy about the approach and extent of necessary resection. A recent prospective randomized study, in which en bloc esophageal resections with systematic abdominal and mediastinal lymph node dissection (two fields lymphadenectomy) has been compared with the classical transhiatal approach, showed that the transhiatal approach carries lower morbidity than through right thoracotomy performed extended en-bloc lymphadenectomy. Moreover, a trend was observed with advantage for the transthoracic approach in tumors located in the mid-esophagus, for the most frequent lower esophageal cancer the median survival, disease free and quality-adjusted survival were not statistically different.In an attempt to lower the mortality and morbidity rates of the conventional esophagectomy, advantages in minimally invasive instrumentation and gained experience in minimally invasive surgery make a minimal invasive approach possible. Several minimal invasive approaches mimic the conventional procedures for esophagectomy: 1) transhiatal esophageal resection by laparoscopy; 2) esophagectomy by right thoracoscopy, the so called three-stage operation and 3) esophageal resection by means of endoscopic microsurgical mediastinal dissection.–11 MoreoThe aim of the present review article is to evaluate this minimal invasive approach for esophagus resection, especially the approach performed through right thoracoscopy.Benign esophageal diseases are an infrequent indication for esophageal resection. Nevertheless, important caustic and peptic stenosis not suitable for treatment by balloon dilatation may finally be considered indications for resection. End stage motility diseases of the esophagus like achalasia and Chagas's disease with important mega-esophagus and the presence of multiple esophageal epiphrenic diverticula may also be an indication for resection. Also, borderline high grade dysplasia of the Barrett esophagus may be a good indication for resection by minimal invasive techniques.Cancer of the esophagus is the most frequent indication for resection. Once diagnosed, it is important to establish a good preoperative assessment of the resectability. Enhanced CT scan of thorax and abdomen and an endoscopic ultrasonography can determine the lymph node involvement, local growth in other organs and existence of metastases. Positron emission tomography (PET's scan) is currently under evaluation in order to assess the capacity to properly exclude distant metastases. Moreover, treatment of the esophageal cancer needs a multidisciplinary approach and usually patients with a locally advanced cancer will be treated by neo-adjuvant chemo-radiation, making surgery perhaps more difficult.All operable cancers in any location can be approached by minimal invasive surgery. For distal tumors the transhiatal or the right thoracoscopic approaches seem both a good option whereas for higher tumors, in the proximal esophagus and around the carina the right thoracoscopic approach is the only possibility.Resection of the esophagus (and lymphadenectomy) through a right thoracoscopy. Mobilization of the stomach and creation of gastric conduit can be performed by laparotomy or by laparoscopy followed by a cervical anastomosis (three stage technique).Ivor Lewis operation: right thoracoscopy (esophagectomy and lymphadenectomy) followed by laparoscopic gastric mobilization and intrathoracic anastomosis between mediastinal esophagus and gastric tube.Transhiatal approach, total laparoscopic or laparoscopic assisted dissection of the esophagus up to the carina followed by mobilization of the stomach, creation of the gastric conduit and subsequent cervical anastomosis.Esophageal resection through mediastinoscopy: endoscopic microsurgical dissection.Robot assisted procedureset al., described in 1992 the first combined thoracoscopic and laparoscopic approach for esophageal resection for cancer with reconstruction by means of a gastric conduit anastomosed to the neck The Theet alThe authors conclude that RTE was feasible, providing an effective lymphadenctomy with low blood loss. Standardization of the technique should reduce the complication rate, which is in the range of the rate for open resection.et al., comparing the standard transhiatal (and lymphadenectomy of the celiac trunk) approach with the transthoracic approach (and lymphadenectomy of the mediastinum and celiac trunk) has not demonstrated a significant difference between the groups concerning survival at five years. An important trend exists in favour of the transthoracic group, but not for the tumors located in the distal esophagus and cardia. In order to increase visualization during the mediastinal dissection of the esophagus decreasing the operative trauma and postoperative complications, different minimal invasive approaches have been developed first as imitation of the conventional procedures: the three stage procedure , the Ivor-Lewis procedure  and the transhiatal approach. Later on, but also initiated early in the nineties by Cuschieri, the right thoracoscopic approach in prone position is becoming increasingly used because the reduction of postoperative pulmonary complications. In the beginning, all procedures had long operative times and the postoperative complications rates were similar to the conventional approach. More experience of surgeons with advanced minimally invasive procedures, the introduction of more sophisticated devices for dissection and sealing of tissues, such as Ligasure, Ultracision and endostaplers and the general acceptance that oncological procedures can be performed by minimally invasive procedures without oncological disadvantage for the patient, has stimulated importantly further developments. The enthusiasm of different Japanese groups and the systematically standardization of the Pittsburgh's group of Luketich have demonstrated that the three stage procedure can be performed not only safely, but also in an comparable operating time with important advantages in the postoperative recovery of the patients and a good oncological outcome, at least as good as after conventional surgery. One of the problems of this approach will be the difficulty of the double endotracheal tube and the collapse of the right lung to visualize adequately the mediastinum. With short operative time, the produced shunt by the collapse is to overcome; nevertheless in elderly people and longer thoracoscopic time, pulmonary complications may rise. Luketich et al., described an incidence of 7.7% of pneumonia and 1,8% of acute respiratory disease as major complications along with 4.5% atelectasis with mucus plug requiring bronchoscopy as minor complications. Moreover these problems do not affect the hospital stay of seven days and the very low mortality rate of 1.4%. To overcome these complications, the right thoracoscopic esophageal dissection performed in prone position will permit a reasonable partial ventilation of the right lung with as consequence less postoperative pulmonary complications. Palanivelu et al., have an incidence of 1.54% of pneumonia and 0.77% of acute respiratory disease. Moreover their operative time is comparable with the standard conventional and right thoracoscopic procedures. Concerning oncological parameters, R0 -R1 resections, number of lymph nodes resected and finally the survival according to stage, the two most important series of Luketich et al. and Palanivelu et al., are similar to the published with conventional procedures. The role of the promising robotic assisted esophageal resection has to be defined in a near future.Surgical treatment of esophageal cancer, with important dissections at abdominal, thoracic and cervical spaces means a tremendous operative trauma for the patient with high postoperative discomfort and a high morbidity and mortality. The approach of the esophagus through a right thoracotomy in combination with a laparotomy and cervical incision has an important rate of complications, especially the pulmonary, that will account for the long intensive care stay. Transhiatal approach, according to Orringer will reduce this complication rate by avoiding opening of thoracic cavity and therefore reducing the number of pulmonary complications. Drawback of this approach is the blind character of the mediastinal dissection that can only be performed with some displacement of the heart with consequent hemodynamic repercussions. A randomized study from Hulscher et al., compares recently the outcomes between open and minimally invasive esophagectomy and concluded that minimally invasive techniques to resect the esophagus in patients with cancer were confirmed to be safe and comparable to an open approach with respect to postoperative recovery and cancer survival.[Smithers survival.Another important point is to define the role of the laparoscopic transhiatal approach. Important advantage will be the avoidance of the thoracoscopic stage with theoretically less respiratory complications. As for the conventional transhiatal, the approach is ideal for the very distal esophageal and gastro-esophageal junction tumors. These tumors are the most frequent in the western world. Important advantage for this approach will be the initial assessment of the abdomen for metastases, the dissection of the tumor between distal esophagus and stomach, with a good view of both sides of the tumor, the hiatus and both pleuras. The dissection can be accomplished very adequately in the anatomical planes up to the carina. The dissection and construction of the gastric conduit will be performed at the same stage without changing the positioning of the patient. Drawback of this procedure is the lack of carinal lymphadenectomy. The results obtained by our group with this approach in an unselected group of 50 patients are very promising with a sConcerning the survival of the patients, new protocols will give more insight in the role of chemoradiation as neoadjuvant treatment for these tumors. Probably the combination of a preoperative precise stagimg of the tumor, the use of efficacious neoadjuvant therapy and the minimally invasive surgical resection will be the adequate approach for these patients, producing less postoperative complications and a better survival.


Rana tigerina and thereby reduce the complications involved in the sepsis.Frog skin has been sequentially and scientifically evaluated by our group for its wound healing efficiency. Owing to the complex structure of skin, attempts were being made to analyse the role of individual constituents in different phases of healing. Our earlier papers have shown the significance of frog skin not only in wound healing but also enhancing the proliferating activity of the epidermal and dermal cells which are instrumental for normal healing process. We also have identified for the first time novel antimicrobial peptides from the skin of The current study envisages the role of frog skin lipids in the inflammatory phase of wound healing. The lipid moiety of the frog skin dominated by phospholipids exhibited a dose dependent acceleration of healing irrespective of the mode of application. The efficiency of the extract is attributed partially to the anti-inflammatory activity as observed by the histochemical and immunostimulatory together with plethysmographic studies.Thus, frog skin for the first time has been demonstrated to possess lipid components with pharmaceutical and therapeutic potential. The identification and characterization of such natural healing molecules and evaluating their mechanism of action would therefore provide basis for understanding the cues of Nature and hence can be used for application in medicine. Hoplobatrachus sp.) skin was found to be very effective. Acceleration of wound healing by the application of several biological membranes is very common owing to their efficacy in preventing infection and sepsis. However, frog skin plays a complex role in addition to helping in the haemostasis and mechanical protection to wound site as described by Purna Sai et al., [et al., [et al, [Rana tigerina. The healing or repair process can be classified into three main overlapping and interrelating phases [Wound healing is a complex phenomenon involving a highly dynamic integrated series of cellular, physiological and biochemical processes. In our search for wound healing mechanisms, a Naga based technique of using frog  according to Folch The total extract obtained from the frog skin was analyzed to study the amounts of neutral lipids, phospholipids, free fatty acids, cholesterol, cholesterol esters, diglycerides and triglycerides present.2) was created under mild anaesthesia as described in detail by Purna Sai et al., [Female albino rats of Wistar strain weighing 120 g were selected. Open excision type of wounds of a standard size  and Elson and Morgan(1993), respectively ,9. Uroni61 and ElFemale albino rats of the Wistar strain (120 g) were used in groups each comprising of 6 for the study. Pedal oedema was produced by injecting 0.05 ml of freshly prepared suspension of 1% carrageenan in the plantar surface of the right hind paw. Foot pad thickness was measured plethysmographically at regular intervals after the injection of carrageenan.In one set of experiments, the lipid extract was administered intraperitoneally 1 hour before carrageenan injection as a suspension in polysorbate 80 which serves as a vehicle. In the second set of experiments, the lipid extract was injected 1 hour after the injection of carrageenan. Three doses of the lipid extract  were selected for evaluating the anti-inflammatory effect and were compared with similar doses of known anti-inflammatory agent hydrocortisone.At specific intervals (1 and 4 hrs) after the carrageenan induction of oedema, both the experimental and control rats were sacrificed and the plantar region of the paw was fixed in (10%) formalin, processed by routine histological procedures and subsequently embedded in paraffin. Serial sections were cut at 8-10 μ thickness and were stained with haematoxylin and eosin.et al., [9 SRBC/ml for immunization and challenge.The antigen was prepared according to Sharma et al., . Sheep e9 SRBC/ml into the right hind foot pad on day 0 and challenged 7 days later by injecting intradermally the same amount of SRBC into the left hind foot pad. Thickness of the left hind foot pad was measured with a vernier callipers at 4 and 24 hours after challenge. Frog skin lipid extract was injected intraperitoneally in doses of 6 and 12 mg/Kg body weight on each of 2 days prior to immunization, on the day of immunization and on each of the 2 days after immunization  in the experimental group, while the control group was injected similarly with polysorbate 80.Hypersensitivity reaction to SRBC was induced in rats following the method of Doherty . Groups 9 SRBC on day 0. Blood samples were collected from individual animals by the retro-orbital puncture on day 7 and day 14. Frog skin lipid extract was administered intraperitoneally on days  in the group forming the experimental series, while the control group was similarly injected with polysorbate 80. Antibody response was observed by the haemagglutination technique.Two groups of six rats each were immunized by injecting intraperitoneally 0.5 ml of 5 × 10The composition of the lipid extract as determined by us in our earlier paper  is indicLipid extracts treated rats both topically and intraperitoneally healed completely by 12 days while the control rats took 20 days for healing. The wound healing observed was found to be dose dependent.The contraction measurements indicate a dose dependent reduction of the wound area. The rate of contraction in the experimental series was much faster and regular compared to the control group Figures  and 2.The hydroxyproline and hexosamine content was found to increase gradually up to the 8th day and then decreased gradually. The increase in the hydroxyproline Figure , hexosamA dose related decrease in the pedal oedema was observed as measured plethysmographically. The decrease in the oedema was significantly greater when the extract was injected prior to the injection of carrageenan. The reduction in pedal oedema was more in the lipid extract treated animals in comparison with the response to hydrocortisone which in turn was more efficient than the control Tables  and 4.Histological and histochemical studies of the rat paws showed stratified squamous epithelium with the underlying sub-epidermal region consisting of capillaries and muscles. The onset of inflammation upon the injection of carrageenan is indicated in the control, hydrocortisone, lipid extract treated animals Figure . An inteIntraperitoneal administration of lipid extract  for 5 days around immunization produced a dose related increase in early (4 hrs) and delayed (24 hrs) hypersensitivity reactions in rats  [Oedema induced by carrageenan is a model of exudate inflammation and agents effective in decreasing carrageenan induced oedema can be used as anti-inflammatory agents in acute inflammation. Carrageenan induced oedema is mediated through histamine and serotonin in the first hour followed by kinin release up to two and half hours and lastly by prostaglandins from two and half to six hours ,16. The , (1973)  support Immunostimulatory studies indicated that lipid extract stimulates both the humoral and cell mediated responses in the experimental animals. Increase in the DTH reaction in rats in response to thymus dependent antigen revealed the stimulating effect of lipid extract on lymphocytes and accessory cell types required for the expression of the reaction.The augmentation of the humoral response to SRBC by the lipid extract as evidenced by the increased haemagglutination indicated the enhanced responsiveness of macrophages and lymphocytes involved in the antibody synthesis. In view of the key role played by macrophages in co-ordinating the processing and presentation of antigen to lymphocytes, the augmentation of the humoral response to SRBC reveals that lipid extract may enhance the effect by facilitating these processes.These studies suggest that any agent capable of accelerating any of the phases of wound healing  would result in more rapid healing thereby reducing scar formation.in toto. Hence, exploring the mechanisms of the bioactive constituents would enable the use of these cues to achieve multilayered cell engineering regimens to produce more complex tissue architectures. This would lead to an increase in sophisticated biotechnological strategies for the improvement of techniques to engineer bio-artificial grafts and implants for burns and wound injuries in particular.In conclusion, the frog skin lipid extract irrespective of the mode, whether topically applied or injected intraperitoneally accelerate healing. The influence of the lipid extract on acute inflammation and immunostimulatory response indicated that the mechanism of quickened healing could be attributed partly to the reduction in the inflammatory phase that corresponds to the prime phase in wound healing. Thus, the frog skin lipid extract enhances the healing by playing a pivotal role in the first two phases of healing although it did not possess any significant antimicrobial effect. These studies therefore confirm the scientific significance of frog skin and its constituents in wound healing. This may be attributed to the fact that the amphibians being the first true land vertebrates connecting land and water obviously developed certain evolutionary specializations for regeneration and repair so as to withstand the onslaught of predators causing frequent injuries if not killing them DTH: Delayed Type Hypersensitivity; SRBC: Sheep Red Blood Cells.The authors declare that they have no competing interests.VK carried out the experiments and involved in drafting the manuscript. MB was involved in reviewing the manuscript. RR is the head of the department involved in general scientific discussions and PK conceived, designed the study and was instrumental in coordinating as well as drafting the manuscript. All the authors read and approved the final manuscript.


Arabidopsis Stock Centre (NASC).This review explores the UK CropNet site. The project is aimed at aiding the comparative mapping of cereal and other crop genomes. The site provides software tools for use by those working on genome mapping, and access to an array of databases that will be of interest to all members of the plant genomics research community, using several ACeDB interfaces. All screen views from the website are reproduced with the kind permission of Dr Sean May, Director, Nottingham


Minisatellite DNA probes which can detect a large number of autosomal loci dispersed throughout the human genome were used to examine the constitutional and tumour DNA of 35 patients with a variety of cancers of which eight were of gastrointestinal origin. Somatic changes were seen in the tumour DNA in ten of the 35 cases. The changes included alterations in the relative intensities of hybridising DNA fragments, and, in three cases of cancers of gastrointestinal origin, the appearance of novel minisatellite fragments not seen in the corresponding constitutional DNA. The results of this preliminary study suggests that DNA fingerprint analysis provides a useful technique for identifying somatic changes in cancers.


The ascorbyl radical concentration has been observed, by means of electron spin resonance spectroscopy, in the blood and spleen of female Wistar rats carrying a Yoshida tumour. The ascorbyl radical concentration of the tumour tissue itself was studied as the tumour was developing, and as it was regressing after treatment with methylene dimethane sulphonate. Changes in the concentration of this radical may be related to host tumour reactions.


If the chloride level exceeds 250 mg l-1, then the sweetness of the beer is enhanced, but yeast flocculation can be hindered. An excess of sulphate can give a sharp, dry edge to hopped beers and excessive amounts of nitrate have been found to harm the yeast metabolism after conversion to the nitrite form. As water is a primary ingredient within beer, its quality and type is a fundamental factor in establishing many of the distinctive regional beers that can be found in the United Kingdom and is thus monitored carefully.The majority of anions found in beer are a consequence of impurities derived from the water used during the brewing process. The process of beer manufacture consists of malting, brewing and fermentation followed by maturation before filtration and finally storage. Strict quality control is required because the presence of certain anions outside strictly defined tolerance limits can affect the flavour characteristics of the finished product. The anions present were quantified using the technique of ion chromatography with the Metrohm modular system following sample preparation. The analysis produced a result of the order 200 mg l


The specificity of action of mature blood cell extracts on their own progenitor cells was investigated by measuring their effects on the structuredness of the cytoplasmic matrix (SCM) using the technique of fluorescence polarization. Changes in SCM induced by the various extracts are probably closely related to the proliferation state of the cells.Saline extracts of lymphocytes, granulocytes and erythrocytes  have been partially purified by ultrafiltration into selected molecular weight ranges and each tested against proliferative populations of lymphoid, granulocytic and erythroid cells. In all cases, complete specificity of effect on SCM was found, LNEs affecting only lymphoid cell populations, GCEs affecting only the granulocytic cell populations and RCEs affecting only erythroid cells. In each case, with the possible exception of the RCEs, the active fractions reside in the molecular weight ranges reported in the literature for cell extracts possessing proliferation inhibitory properties.


Although the rhomboid lip is a well-known structure constructing the foramen of Luschka, less attention has been directed to the structure for posterior fossa microsurgeries. The authors report two cases of the hemifacial spasm (HFS) with a large rhomboid lip, focusing on the importance of the structure during microvascular decompression.A 59-year-old female presenting with left HFS was admitted to our hospital. A preoperative magnetic resonance image demonstrated an offending artery at the root exit zone of the VII nerve. The patient underwent microvascular decompression through the lateral suboccipital approach. The intraoperative findings showed that a large rhomboid lip adhered to the IX and X cranial nerves and prevented the exposure of the root exit zone of the VII cranial nerve. The rhomboid lip was meticulously separated from the cranial nerves so that the choroid plexus of the foramen of Luschka and the rhomboid lip could be safely lifted with a spatula, and the offending artery was successfully detached from the root exit zone. In another case of a 60-year-old male, the rhomboid lip was so large that it needed to be incised before separating it from the lower cranial nerves. In each case, the HFS was resolved following surgery without any new deficits.The large rhomboid lip adhering to the cranial nerves should be given more attention in the posterior fossa surgeries and should be managed based on the microsurgical anatomy for preventing unexpected lower cranial nerve deficit. The choroid plexus protruding from the foramen of Luschka is an important landmark of the root exit zone of the VII cranial nerve during microvascular decompression surgery for hemifacial spasm (HFS).45101213 45101236A 59-year-old female presenting with left-sided HFS for 2 years was admitted to our hospital. Neurological examinations demonstrated typical HFS; it is characterized by twitching tonic spasm and synkinesis of the facial muscles. There were no other symptoms. The preoperative magnetic resonance (MR) angiogram revealed that the left posterior inferior cerebellar artery (PICA) formed a rostral loop at the level of the internal acoustic meatus . MR imagMicrovascular decompression of the left VII cranial nerve was performed through the lateral suboccipital approach. Auditory brainstem evoked response (ABR) and facial electromyography were used for intraoperative neurophysiological monitoring. The patient was placed in a lateral park bench position and craniotomy was performed below the posterior end of the incisura mastoidea along the medial boarder of the inferior half of the sigmoid sinus. After dural opening, dissection of the arachnoid membrane around the lower cranial nerves was started. When the inferolateral margin of the cerebellum and the flocculus were gently elevated, a large rhomboid lip was found at the dorsal side of the IX and X cranial nerves . The rhoA 60-year-old male presenting with right-sided HFS for 15 years was admitted to our hospital. Neurological examinations demonstrated typical HFS. The preoperative MR angiogram revealed that the right PICA formed a rostral loop at the level of the internal acoustic meatus. MR images revealed that the PICA compressed the root exit zone of the VII cranial nerve .Microvascular decompression of the right VII cranial nerve was performed through the lateral suboccipital approach with the aid of the same intraoperative monitoring as in Case 1. Intradurally, a large rhomboid lip prevented the visual tract for the root exit zone of the VII cranial nerve and adhered to the dorsal side of the IX and X cranial nerves . The surThe lateral recesses are narrow, curved pouches formed by the union of the roof and the floor of the fourth ventricle. They extend laterally below the cerebellar peduncles and open through the foramina of Luschka into the cerebellopontine angles. The ventral wall of each lateral recess is formed by the floor of the fourth ventricle and the rhomboid lip, which is a sheet-like layer of neural tissue that extends laterally from the floor and unites with the tela choroidea to form a pouch at the outer extremity of the lateral recess .611] Th11 Th611]36lateral suboccipital infrafloccular approach, in which the flocculus is gently retracted in a caudorostral direction perpendicular to the VIII cranial nerve  To our knowledge, adhesion of the large rhomboid lip to the lower cranial nerves has not been mentioned in the literature on microvasular decompression although the situation does not seem uncommon. One of the possible reasons is that surgeons can mistake the rhomboid lip for part of the arachnoid membrane even when the rhomboid lip is large. The rhomboid lip is a slightly thicker and tougher structure than the arachnoid membrane, and usually does not seem as transparent as the arachnoid membrane. It may still be difficult to distinguish between the arachnoid membrane and the rhomboid lip, especially without anatomical knowledge of the rhomboid lip. Another possible reason for the large rhomboid lip, which has not been mentioned, is that the identification of the rhomboid lip might be difficult especially through the lateral route to the root exit zone of the VII cranial nerve. The infrafloccular approach seems suitable for identifying the large rhomboid lip from the anatomical aspect Figure ,c, and tThis report sheds light on the clinical importance of the rhomboid lip during microvascular decompression. The anatomical knowledge of the rhomboid lip and the adjacent area may facilitate safer exposure of the root exit zone of the VII cranial nerve. Further studies on the anatomical variation of the rhomboid lip in its size or distance to the cranial nerves are needed to reinforce the importance of the structure for microvascular decompression.


The use of DNA microarrays opens up the possibility of measuring the expression levels of thousands of genes simultaneously under different conditions. Time-courseexperiments allow researchers to study the dynamics of gene interactions. Theinference of genetic networks from such measures can give important insights for theunderstanding of a variety of biological problems. Most of the existing methods forgenetic network reconstruction require many experimental data points, or can onlybe applied to the reconstruction of small subnetworks. Here we present a method thatreduces the dimensionality of the dataset and then extracts the significant dynamiccorrelations among genes. The method requires a number of points achievable incommon time-course experiments.


Resection of large lipomatous tumours in the subdeltoid region remains technically challenging due to the risk of injury to the axillary neurovascular bundle. We describe a novel deltoid release and reinsertion technique for resection of large lipomatous tumours of the sub-deltoid region and report the functional and oncologic outcomes of six patients who underwent this procedure. Three cases were diagnosed histologically as atypical lipoma and three cases were diagnosed as lipoma. There was one local recurrence in a case of an atypical lipoma. Rotator cuff function was comparable to that of the contralateral side in all cases and the average Constant Score adopted by the European Shoulder and Elbow Society was 84 (range 81 to 92) out of 100. We conclude that patients with large sub-deltoid lipomatous tumours who undergo resection through a previously undescribed deltoid release and reinsertion technique have excellent functional outcome with a low risk for recurrence. The upper extremity is affected by bone and soft tissue neoplasms one-third as often as the lower extremity . When soLipomatous tumours of the soft tissues are the most common soft tissue tumours and these lesions can occur at every age and at almost any anatomical location , 3. The The deltoid muscle has a multipennate origin from the lateral third of the clavicle, the acromion process and the spine of scapula, and is the largest muscle of the shoulder girdle. Its function is of paramount importance in abduction and flexion. The axillary nerve exits in the quadrangular space below the lower border of teres minor, where it passes around posterior and lateral to the humerus on the deep surface of the deltoid muscle. The nerve then splits into anterior and posterior trunks, both of which run intimately with the deep surface of the deltoid muscle. Tumours in the sub-deltoid region are therefore particularly difficult to resect due to the risk of injury to the axillary nerve . VariousThe aim of this study is to report the surgical and functional outcomes of our patient population with sub-deltoid low-grade lipomatous tumours who underwent marginal resection of their tumours though extensive deltoid mobilization with preservation of the axillary nerve branches.A retrospective review of a prospectively maintained database was performed. Review of the database was approved by our institution's Research Ethics Board. We identified seven cases of large lipomatous tumours located in the subdeltoid region treated at our institution between March 1997 and July 2007. One patient was lost to follow-up, therefore a total of six patients were included in the follow-up section of the study. Patient demographics, indication for surgery, pathology and operative records were reviewed. Functional shoulder assessment was performed using the Constant scoring system adopted by the European Society for Shoulder and Elbow Surgery , 9. The With the patient under general anaesthesia and placed in a beach-chair position, we utilized a standard anterior deltopectoral approach to the shoulder. After the incision was made through skin and subcutaneous tissue, dissection was carried out through the delto-pectoral interval after isolation of the cephalic vein medially. A section of the anterior deltoid was sacrificed with the vein if necessary. Exposure was carried proximally to the clavicle and distally to the insertion of the deltoid.Mobilization of the deltoid was performed by releasing its multipennate origin with the use of a reciprocating saw from the anterior and lateral surface of the clavicle and laterally from the lateral edge of the acromion, and extending posteriorly to the quadrangular space as deemed necessary. The deltoid was also partially released from its insertion onto the humerus if necessary. The muscle was then reflected approximately 90 degrees  to allowClosure was completed with reinsertion of the deltoid muscle to the acromion and lateral clavicle using multiple drill holes and attachment using nonabsorbable suture . The insThe operative arm was placed in a shoulder immobilizer for three weeks, with limited active abduction and flexion. Progressive active assisted and active exercises were then initiated and progressed gradually to deltoid and rotator cuff strengthening exercises.From 1997 to 2007, seven patients with sub deltoid lipomas or well-differentiated liposarcomas  underwent excision of the tumour . One patThere were no wound complications. Minimal atrophy of the anteromedial deltoid fibres was present in all six patients. One patient who required sacrifice of axillary nerve fibres had incomplete motor and sensory deficit of that nerve. A second patient had sensory dysfunction with persistent numbness and parasthesias in the distribution of the axillary nerve. The average Constant Score was 84 , compared to 90  in the nonoperative shoulder . All sixLocal recurrence was documented in one case after nine years of the initial surgery. Final pathologic diagnosis in this case was atypical lipoma.Lipomatous tumours are the most common soft tissue neoplasms. These tumours can occur at every age and at almost any anatomical location in the body. The shoulder is one of the most common sites where these tumours may occur. Tumour excision at this site is challenging for the surgical oncologist in terms of proximity of the tumour to vital neurovascular structures and the subsequent need to balance the oncological resection and optional functional outcome.The deltoid muscle has a multipennate origin from the clavicle, acromion, and the scapula. The axillary neurovascular bundle lies in close proximity to the muscle's under surface, rendering the approach to tumours of the sub-deltoid space at risk for neurovascular injury. The use of a conventional anterior or posterior approach to resect sub deltoid lipomatous tumours may not be adequate for complete resection of a tumour which extends beneath the muscle and adheres to the axillary nerve, or extends posteriorly to the quadrilateral space.Martini  was the All patients included in the current study had minor anteromedial deltoid atrophy. The deltoid atrophy is likely the result of minor denervation or interference with vascular supply of the muscle. However, the atrophy did not result in cosmetic or functional deficits. Two patients had axillary nerve dysfunction; one of them had a large tumour involving branches of the axillary nerve which were sacrificed in order to obtain adequate resection. Therefore, an unexpected axillary nerve injury occurred in 1 of 5 patients. These results are comparable to those of Tamai et al., who reported normal axillary nerve function in both patients reported [Functional assessment unitizing the Shoulder Constant Score adopted by the European Society for Shoulder and Elbow Surgery showed that all six patients were free of pain and able to return to full activities. While the range of motion in forward flexion, lateral elevation, and external rotation was normal in all patients; five patients had limitation of internal rotation up to the T12 vertebra and one had symmetrical internal rotation to the interscapular at the T7 level. Minimal deltoid muscle weakness evidenced by difference in abduction strength compared to the contra-lateral side was present in half of the patients, but was not functionally significant as evidenced by the Constant Score.In conclusion, we present a novel surgical approach to resection of lipomatous tumours of the sub-deltoid region. Our proximal-release approach results in excellent functional outcomes with a low risk of local recurrence and injury to the axillary nerve.


It has been claimed that publicity surrounding popular celebrity Jade Goody's experience of cervical cancer will raise awareness about the disease. This study examines the content of newspaper articles covering her illness to consider whether 'mobilising information' which could encourage women to adopt risk-reducing and health promoting behaviours has been included.Content analysis of 15 national newspapers published between August 2008 and April 2009In the extensive coverage of Goody's illness (527 articles in the 7 months of study) few newspaper articles included information that might make women more aware of the signs and symptoms or risk factors for the disease, or discussed the role of the human papilloma virus (HPV) and the recently introduced HPV vaccination programme to reduce the future incidence of cervical cancer. For example, less than 5% of articles mentioned well-known risk-factors for cervical cancer and less than 8% gave any information about HPV. The 'human interest' aspects of Goody's illness  were more extensively covered.Newspaper coverage of Goody's illness has tended not to include factual or educational information that could mobilise or inform women, or help them to recognise early symptoms. However, the focus on personal tragedy may encourage women to be receptive to HPV vaccination or screening if her story acts as a reminder that cervical cancer can be a devastating and fatal disease in the longer term. Her seven-month battle with cancer attracted intense media coverage across the world. In the UK, this publicity coincided with the introduction in September 2008 of the Human Papillomavirus (HPV) vaccination programme aimed at protecting girls from cervical cancer. The timing of the coverage of Goody's experience of cervical cancer is thus potentially crucial as uptake of vaccines depends on perceptions of the balance between any putative adverse effects of a vaccine and the perceived severity and consequences of contracting the disease, . Altious year The publious year. Whilst ious year these daThe diagnosis and experience of illness amongst other celebrities, such as Olivia Newton John (breast cancer), Lance Armstrong (testicular cancer), Michael J Fox (Parkinson Disease) and Katie Couric (Colon Cancer) have also been credited with raising public awareness about their illnesses-34. HoweIn the articles covering Jade Goody's cervical cancer story there was almost no mention of her sexual history or behaviour. The media's coyness about discussing the association between cervical cancer risk and sexual behaviour in these articles is in stark contrast to the negative scrutiny of Goody's personal life prior to her diagnosis with cancer. It also contrasts with recent newspaper coverage of cervical cancer 'framed'  around tThe coverage of Goody's illness focussed more on one young woman's experience of diagnosis, treatment and death from cervical cancer and is likely to contribute to a general public awareness that cervical cancer can be a devastating and fatal disease. This knowledge could mobilise women to take action and encourage them to be more receptive to screening or HPV vaccination, as research on vaccine decision-making suggests that the perceived risk posed by the disease to be prevented is weighed against the perceived risk of the vaccines-4. The nOur study has limitations. It only considered coverage in 15 newspapers, and was not able to examine other popular media  which may have covered different topics or been more widely accessed by young women. Our analysis of coverage ran up to the date of Goody's funeral, and it is plausible that any later coverage or her illness may have emphasised different aspects of the causes, consequences and experience of cervical cancer. Furthermore, it was not designed to examine audience reception and understanding of the coverage.The extent to which any 'Goody Effect' contributes to saving lives in the longer term depends on how long her story acts as a reminder of the potentially devastating impact of this disease to all women including those in the highest risk groups, and whether it motivates 'hard to reach' groups to believe that actions such as attending for cervical screening and follow up treatments can make the difference between life and death. However, the failure of newsprint coverage of her illness and death to include basic information on the signs and symptoms of cervical cancer, common risk factors for the disease, and the possibility of protecting young women against contracting the viral agent which causes cervical cancer through vaccination presents an ongoing challenge to cancer researchers and specialists in cancer education. Lewison et al highlight cancer researchers' increasing reliance on the "diverse media for informing and engaging the public". They suggest that "If the aim is to achieve a 'public understanding of cancer', then we need to ask how this current interface works and whether it is achieving the aspirations of both the public and the research community". Our anaThe authors declare that they have no competing interests. The Medical Research Council (MRC) funded this research. SH and KH are funded by the MRC.SH, KH participated in the design, analysis of the data and to the writing and redrafting the final version of the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/10/368/prepub


In rats with 2-week obstructive jaundice the sensitivity to endotoxin was studied and the effect of a single dose of endotoxin on histological development in the kidney, liver and spleen was also investigated. We were tested the effect on accumulation and distribution within organs, of fibrinogen labelled with radioactive iodine 125. We showed an increased sensitivity to endotoxin in obstructive jaundice. The cause of death in most rats was acute circulatory failure during the course of endotoxic shock, without clinical features of disseminated intravascular coagulation. In the isotope study, after endotoxin administration there was a specific dynamic increase of fibrinogen accumulation in the kidneys of rats with obstructive jaundice. We proposed, that the cause of the kidney changes during the course of obstructive jaundice could be the local activation of intrarenal coagulation.


The metabolic pathway called the arachidonic acid cascade produces a wide range of eicosanoids, such as prostaglandins, thromboxanes and leukotrienes with potent biological activities. Recombinant DNA techniques have made it possible to determine the nucleotide sequences of cDNAs and/or genomic structures for the enzymes involved in the pathway. Sequence comparison analyses of the accumulated sequence data have brought great insights into the structure, function and molecular evolution of the enzymes. This paper reviews the sequence comparison analyses of the enzymes involved in the arachidonic acid cascade.


Over the years, there has been a tremendous increase in the use of fluoroscopy in orthopaedics. The risk of contracting cancer is significantly higher for an orthopedic surgeon. Hip and spine surgeries account for 99% of the total radiation dose. The amount of radiation to patients and operating surgeon depends on the position of the patient and the type of protection used during the surgery. A retrospective study to assess the influence of the radiation exposure of the operating surgeon during fluoroscopically assisted fixation of fractures of neck of femur (dynamic hip screw) and ankle (Weber B) was performed at a district general hospital in the United Kingdom.Sixty patients with undisplaced intertrochanteric fracture were included in the hip group, and 60 patients with isolated fracture of lateral malleolus without communition were included in the ankle group. The hip and ankle groups were further divided into subgroups of 20 patients each depending on the operative experience of the operating surgeon. All patients had fluoroscopically assisted fixation of fracture by the same approach and technique. The radiation dose and screening time of each group were recorded and analyzed.The radiation dose and screening time during fluoroscopically assisted fixation of fracture neck of femur were significantly high with surgeons and trainees with less than 3 years of surgical experience in comparison with surgeons with more than 10 years of experience. The radiation dose and screening time during fluoroscopically assisted fixation of Weber B fracture of ankle were relatively independent of operating surgeon's surgical experience.The experience of operating surgeon is one of the important factors affecting screening time and radiation dose during fluoroscopically assisted fixation of fracture neck of femur. The use of snapshot pulsed fluoroscopy and involvement of senior surgeons could significantly reduce the radiation dose and screening time. The use of fluoroscopy has increased tremendously in field of orthopedics.14346The aim of the study was to assess the effect of surgical experience on the radiation exposure and screening time during fluoroscopically assisted fixation of undisplaced fractures of neck of femur (dynamic hip screw) and ankle (Weber B).A retrospective study was conducted at a district general hospital in the United Kingdom from 2003 to 2005. The surgeons were divided into three different groups based on their years of operative experience . SurgeonA total of 700 patients with fixation of fracture of neck of femur underwent fluoroscopically assisted fixation of hip (dynamic hip screws), and 225 patients with ankle fracture underwent fluoroscopically assisted fixation during 2003–2005. Only patients with undisplaced intertrochanteric fracture were included in the hip group. Patients with multiple fractures, communited fracture, compound fracture, and significant morbidity were excluded.Patients with a fracture of lateral malleolus without communition was included in the ankle group. Patients with polytrauma, compound fracture, medial malleolar fracture, and communition were excluded.In each subgroup of the hip group, 20 consecutive patients who satisfied the inclusion criteria and were operated by the appropriate surgeon were included . The age and sex of the patients were comparable in the hip and ankle group.Similarly in the ankle group, in each subgroup, 20 consecutive patients who satisfied the inclusion criteria and were operated by the appropriate surgeon were included .All screening was performed using a mobile C arm fluoroscopy unit . The total filtration of the x-ray tube was 6.35 mm; the focus to detector distance was 99.5 cm, and the diameter of the routinely used input field of view was 17 cm. The dose of the patient was routinely monitored and recorded in accordance with the requirements of Regulation 7 of The Ionising Radiation  Regulations [IR(ME)R] 2000 by means of a dose area product (DAP) meter permanently built into the x-ray tube housing.72. The DAP meter was calibrated following the procedure described in the National Protocol for Patient Dose Measurement in Diagnostic Radiology.8DAP is the currently accepted method of assessing the radiation exposure in complex diagnostic x-ray procedures and is measured in Gy cmIn addition to the DAP value, the overall fluoroscopic screening time (minutes) was recorded for each patient.All the patients with fracture neck of femur underwent dynamic hip screw fixation by lateral approach. The patients with Weber B fracture of ankle underwent fixation of lateral malleolus using a one-third tubular plate using a lateral approach.t test, and P values were calculated.The radiation dose and screening times of the various groups were compared using Student P = 0.0005).The radiation dose (DAP) and screening time during fixation of a hip fracture were almost three times more with surgeons and trainees with less than 3 years of operative experience (Group I) when compared with that of the surgeons with more than 10 years of surgical experience (Group III)  (P = 0.0P = 0.1015).The radiation dose and screening time during fixation of ankle were not significantly affected by surgical experience of the operating surgeon, and they were comparable among all the three groups   [P = 0.1015) [In this study, overall patient doses as monitored by DAP were reassuringly well below these published values. The radiation exposure during fixation of fractures of hip was significantly higher when they were performed by surgeons with fewer than 3 years of operative experience, and this was statistically significant (0.0005 ) . In pati 0.1015) .This study shows that the experience and training of the operating surgeon is one of the most important factors determining the radiation exposure to patients in fixation of hip fracture. The involvement of senior surgeons in hip fracture fixation is likely to reduce the radiation dose to patients and surgeons. We endorse the practice of using snap shot pulsed fluoroscopy, last image hold, and good set up geometry as a means of dose optimization. The practice of continuous screening during fixation of fractures of neck of femur and ankle must be discouraged.


Reconstruction of the facial hard- and soft tissues is of special concern for the rehabilitation of patients especially after ablative tumor surgery has been performed. Impaired soft and hard tissue conditions as a sequelae of extensive surgical resection and/or radiotherapy may impede common reconstruction methodes. Even free flaps may not be used without interposition of a vein graft as recipient vessels are not available as a consequence of radical neck dissection.We describe the reconstruction of the facial hard- and soft tissues with a free parasacpular flap in a patient who had received ablative tumor surgery and radical cervical lymphadenectomy as a treatment regimen for squamous cell carcinoma (SCC). To replace the missing cervical blood vessels an arteriovenous subclavia-shunt using a saphena magna graft was created. Microvascular free flap transfer was performed as a 2-stage procedure two weeks after the shunt operation. The microvascular reconstructive technique is described in detail. Various reconstructive options have been used in the past for the reconstruction of head and neck tissues. In a high number of patients, mainly treated because of head and neck carcinoma, tissue defects may develop following tumor therapy because of extensive resection or chronic effects of radiotherapy. In the initial years, reconstruction was limited to the use of pedicled flaps such as the pectoralis major, latissimus dorsi, and deltopectoral flap -3. IntroThis report describes the use of a vena saphena magna interposition ateriovenous subclavia-shunt for the reconstruction of complex defect in the head and neck region.In a 61-year-old male with a history of alcohol and nicotin abuse but no other serious diseases the initial diagnosis of a SCC of the right anterior floor of the mouth and cervical lymph node metastases  was made. He underwent former surgery including partial resection of the tongue, the mandible and of the floor of the mouth, radical neck dissection of thr right side, selective lymphadenectomy on the left side, immediate reconstruction of the mandible with a reconstruction plate, and intraoral reconstruction with a pectoralis major flap and irradiation post surgery (60 Gy). As a consequence of woundhealing based on the postoperative radiotherapy a large extraoral soft tissue defect and exposition of the reconstruction plate occurred. In order to reconstruct the soft tissues and to establish conditions for a secondary bony defect reconstruction a vessel reconstruction procedure was performed prior to free flap surgery. The saphena magna vein was taken from the patient's right leg. One end of the vein was anastomosed in an end-to-side fashion to the right subclavia artery and the other end in an end-to-side fashion the to the right subclavia vein thus resulting in an arteriovenous loop fig. . After 1Since the introduction of a microsurgical free flap for the reconstruction of a head and neck defect in 1976 a wide variety of free flaps have been described for the reconstruction of the head and neck region . As sincIn situations when microvascular free flap transfer is impeded as recipient vessels are lacking because of surgical ablation or radiation damage pedicled could be used ,12 or reIn the head and neck region recipient vessels are predominantly branches of the external carotid artery and jugular vein ,14. ContOur patient had undergone previous tumor resection and soft tissue reconstruction, radical neck dissection and post-operative radiation. The usual options for  recipient vessels i.e. branches of the external carotid artery and jugular vein were not available as was revealed by pre-operative angiographic examination. The creation of a saphenous arteriovenous loop using the subclavia artery and vein offered a reliable and practical alternative reconstruction method when no pedicled flap or other recipient vessels were available. The ateriovenous subclavia-shunt for such difficult cases seems to be a reliable alternative because of its advantages in the following aspects: 1. The subclavian vessels are located outside ablative surgical field, zone of radiation or injury. 2. The vessels' size is suitable for microsurgical anastomosis, especially the vein can accept high venous outflow from the graft. 3. Anatomy of the subclavian vessels is constant and offers favorable surgical approach. 4. The two stage approach with a 10- to 14-day interval between loop construction and free tissue transfer allows the vein to thick the vessel wall and to avoid venous collapse even in cases of low venous flow.Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the corresponding author.The authors declare that they have no competing interests.RAD drafted the manuscript and performed the operation. CN drafted the manuscript and performed the operation. UM participated in the planning of the operation and performed it. NRK participated in the planning of the operation and performed it. JGH participated in the planning of the operation and performed it. All authors read and approved the final manuscript.


The toxicity produced by two courses of methotrexate separated by different intervals has been studied in matched groups of rats. The maximum degree of neutropenia reached when courses were separated by 8 days or more was no greater than that seen after a single course of methotrexate. However, when courses of neutropenia following the second course of methotrexate was directly related to the level of depression of bone marrow cell numbers at the time of the second course. Conversely the anti-leukaemic effects of 2 courses of methotrexate, in terms of time of onset of leukaemia and time of death in rats transplanted with a syngeneic T-cell leukaemia, are shown to be similar when courses of methotrexate are separated by between 2 and 12 days. Thus in this system, chemotherapeutic schedules using methotrexate may be designed on the basis of minimal host toxicity without prejudicing anti-leukaemic effects. These results are discussed in relation to toxicity and anti-leukaemic effects observed during UKALL trials of treatment in acute lymphoblastic leukaemia.


The chick embryo was used to study the relationship between the onset of tumour neovascularization and tumour growth. Walker 256 carcinosarcoma was implanted on the chrioallantoic membrane (CAM) of about 600 embryos aged 5-16 days. Tumour diameter and changes in the CAM vasculature in response to the implants were recorded daily. Representative tumours were examined by light microscopy of Epon-embedded tissue and autoradiography after injection of [3H]-thymidine. Tumours remained avascular for 72 h, after which they were penetrated by new blood vessels and began a phase of rapid growth. The rate of growth during this vascular phase was greatest for implants on 5- and 6-day-old embryos and decreased the later the day of implantation. The time of onset of tumour angiogenesis appears to be independent of the immunological state of the chick embryo, although the rate of growth after vascularization may be modified by the onset of immunity. This study suggests that the avascular and vascular phases of tumour growth are separable, and that the avascular tumour population lives under the growth constraints which limit the size of a tumour spheroid growing in soft agar or aqueous humour.


Autofluorescence spectra of neoplastic tissues have been reported to be significantly differentfrom those of normal tissues when excited by blue or violet light. From this concept, a light-inducedautofluorescence endoscopic imaging system for gastrointestinal mucosa  has been newly developed and the clinical evaluation ofthe prototype system has been conducted in hospitals in Canada, Netherlands and Japan.We examined the clinical usefulness of the prototype LIFE-GI system for the detection ofgastrointestinal cancer and high and low grade dysplasia. The LIFE-GI system was alsoapplied to the early detection of remnant lesions after endoscopic treatment of early gastriccancer and to the detection of laterally spreading superficial colonic tumors.This system has potential application for the diagnosis of dysplastic lesions and earlycancers in the gastrointestinal tract as an adjunct to ordinary white light endoscopy. Thissystem, which needs no administration of a photosensitive agent, may be suitable as ascreening method for the early detection of neoplastic tissues.


A symposium discussing collaborative research work on infectious diseases dynamics was held at Queens' College, University of Cambridge on 25 October 2006. The evolution and spread of infectious diseases are determined by dynamic processes occurring at many scales from the within-cell to the host population level. There is a considerable similarity between these different scales, whether considering the colonization and spread of salmonella within a cell or organ  into the Campylobacter infections when Dr Chris Coward  presented some work investigating the dynamics of the disease at the within-host level in chickens, based on findings from some previous in vitro studies of Campylobacter replication.The session then swapped focus from salmonella to Campylobacter species are a major form of human food poisoning, with Campylobacter jejuni the leading cause of bacterial gastroenteritis in humans, responsible for over 40 000 laboratory-confirmed cases a year in England and Wales (http://www.hpa.org.uk/infections/topics_az/campy/data_ew.htm). A major source of human infection is thought to be consumption of contaminated poultry, there being a major reservoir of infection in the poultry industry where the organism behaves as an enteric commensal. Understanding how the numbers of organisms in poultry populations can be reduced provides a strategy for dealing with the problem in humans.Previous research at Cambridge had focused on the identification of bacterial genetic factors important for the colonization of chickens using the technique of Signature Tagged Mutagenesis STM; . In STM,Dr John McCauley from the National Institute for Medical Research at Mill Hill followed this with a presentation describing some of the different mechanisms that underlie the variation in host tropism of different influenza viruses, addressing some of the mechanisms other than just virus binding which might be responsible for both the failure and the success of H5N1 viruses to invade the human population and respiratory tract. Interferon (IFN) responses are important components of host cells' responses to virus challenge. Having described the qualitative differences between different virus approaches to evading a cell's interferon defences, he went on to describe a series of experiments relating to how different NS1 proteins in influenza viruses have their effects. Using a combination of different wild-type virus, as well as several others constructed using reverse genetics techniques, Dr McCauley described the different levels (i) of interferon induced by different human viruses, (ii) of signals induced by different influenza NS1's, and (iii) of sensitivity of different human viruses to the effects of IFN. Interestingly, the human viruses that induced most IFN were the least sensitive to its effects. Finally, experiments were described in which replication of highly pathogenic avian influenza viruses could be markedly enhanced by IFN interfering co-infections or disabling the interferon response of cells. This raised the question of whether more recent viruses, such as the recent H5N1 viruses, had already found a means of subverting this response and whether we should be measuring the host innate immune response when considering the ability of a virus to infect different species.http://www.who.int/csr/disease/avian_influenza/country/cases_table_2006_12_27/en/index.html).The final talk of the morning session was given by Dave Balkissoon, a CIDC supported student based at the BBSRC Institute for Animal Health, who presented results from investigations into the innate immune response to avian influenza in inbred lines of chickens. Another major public health issue, the potential socio-economic effects of avian influenza have been highlighted recently with mass media attention focused on the outbreak of the H5N1 strain of the disease currently moving across Asia, Africa and Europe. The poultry industry in the UK deals with approximately 40 billion chickens per year, including broilers, layers and breeders, as well as feral and wild birds, and the disease is highly contagious within avian populations. In addition, it has a high epizootic potential, and has so far (December 2006) killed 157 people worldwide , but their role as an anti-viral agent specifically with regards to influenza in chickens is unclear. Additional interest lies in determining whether a relationship exists between the Mx gene and particular production traits, synonymous with the intensive selection processes used in commercial poultry lines. This can help to determine the levels of risk among commercial poultry stocks.Of particular interest in this project is the role of the Mx anti-viral allele between different commercial and experimental poultry populations. Various production traits have been identified close to the Mx gene on chromosome 1 such as thigh muscle yield, tarsometatarsal length and leg twisting score, and whether differences are due to co-selection or chance founder effects was being investigated.Initial results suggested a very heterogeneous distribution of the The afternoon session saw the scientific focus change from the biological aspects of infectious diseases highlighted in the morning, to the role that mathematical modelling can play, in both understanding the pathogenesis of diseases at a molecular level and also in aiding investigations into the dynamics of epidemic processes at the population level.The opening talk was given by Dr Olivier Restif, a mathematical modeller working in CIDC, who examined the effect of widespread vaccination policies on the potential re-emergence of diseases due to vaccine-induced antigenic variation. The notion that certain control strategies can have an effect on epidemic development opposite to that intended is a constant concern for those implementing policy in public health. However, there are various recent examples of situations in which countries with high vaccination coverage from certain diseases have experienced increasing number of cases of the disease from new strains of the antigen. The modelling strategy investigated the effects of cross-immunity (i.e. the reduction in susceptibility caused by infection from a different strain) on the invasion and persistence of a novel strain of a disease to a finite population where an original strain of the disease is endemic. A series of stochastic simulations were used to assess the impact of cross-immunity when different levels of vaccination coverage were used.The results from a series of stochastic simulations indicate that there is an important trade-off between invasion and persistence of the novel strain, with high levels of cross-immunity resulting in an increased probability of the invading strain of the disease replacing the existing one. In the presence of vaccination, the growth rate of the novel strain depends on the coverage of the vaccine and the level of cross-protection  conferred by the vaccine. Based on invasion analysis only, the worst case scenario is expected in a situation where there is high coverage of a vaccine that confers little cross-protection to the novel strain. However, stochastic simulations show that epidemiological feedback can prevent the persistence of highly invasive strains in a finite-size population. As a result, the model predicts that the most successful strains (i.e. which can invade and persist) can be either very close to or very far from the vaccine strain in terms of antigenic distances . AccountBeforehand there was a very different and novel application of mathematical techniques to help quantify antigenic variation, this time between rabies virus isolates. Rabies is a lyssavirus from the Rhabdoviridae family. It is a highly contagious epidemic disease that is almost invariably fatal. The standard control procedure used by the World Health Organization is vaccination, although the potential of the virus to mutate over time makes designing and implementing effective and efficient vaccination strategies difficult.Understanding the antigenic variation in lyssaviruses could help to provide important insights into the evolution of the rabies disease and the dynamics of its spread, aiding selection of vaccine strains and prediction and control of its spread. Daniel Horton, another CIDC student, this time based at the international rabies reference laboratory at VLA, presented some work on using antigenic cartography . The maps have also proven to be experimentally robust.Moving on from the application of mathematical modelling at the molecular level to its use at a somewhat larger scale, the next presentation was the first of two concerned with modelling the spatial spread of infectious disease spread across landscapes. Dr Colin Russell  continued the rabies theme and presented results from a stochastic mathematical model for the spatio-temporal spread of the disease in raccoons in northeastern USA  focused instead on modelling the spatial spread of infectious diseases in plants. The previous discussion highlighted the importance of accounting for landscape heterogeneity when modelling epidemics, and due to factors such as population expansion, climate change and changes in farming practices, landscapes are changing dramatically, having a major effect on the extent of epidemic progression. An important point given was that the dynamics of the disease vary over different spatial scales—at the plant, within-field and farm premise levels—and these differences need to be reflected in both the modelling strategy and the control mechanism.These ideas were illustrated with various examples of current work within the Gilligan group, most notably in some investigative work on the effects of different scale control policies on the propagation of rhizomania in sugar beet. This is a particularly persistent disease caused by a virus transmitted through the soil and into the roots by a carrier vector. It causes significant problems with regards to yield and is generally spread over large distances through the movement of agricultural equipment that can carry the virus from infested soil.The traditional response strategy is by a local containment policy, involving removal of the infected crop, prevention of future growth in infested fields and the disinfection of agricultural equipment. A key focus in planning many control policies  is in trying to optimize the level of protection needed to prevent epidemic situations. Some interesting questions arise: for example, is there a minimum effective control neighbourhood, and should preference be given to protecting the more, or less infected regions? The idea that more intuitive control policies are sometimes much less effective than less intuitive ones echoes the results from the earlier presentation by Dr Restif. Some modelling simulations of the spread of disease in a host meta-population suggested that protection of the less infected regions proved more efficacious in controlling disease spread than protection within the infected regions. Additionally, not all sites needed to be protected to prevent an epidemic developing. It was shown that of greater importance is ensuring that the scale of the control policy matches the scale of the epidemic; in the rhizomania model for example, farm level control policies proved a much more effective preventive measure than field level policies.Economic and logistical constraints are also the keys in instigating response strategies, and some additional work was presented linking epidemiological and economic models in order to optimize resources in epidemic situations. This fittingly led to the final presentation of the day, given by Dr Cathy Roth of the Global Outbreak Alert and Response Network (GOARN)— part of the World Health Organization (WHO)—in which she discussed the many problems facing policy makers when developing and implementing response strategies in the face of potential disease outbreaks. This drew together aspects from all the research work presented throughout the day, from the molecular scale right to population level, and the use of this knowledge in the design of coherent and efficient procedures for responding to epidemic situations.The WHO is the principal global body responsible for collating, assimilating and implementing the results of research work and applying them to real-life epidemic situations. Many of the problems facing health officials are less scientific and more practical, such as non-reporting of cases, ignorance of the methods of transmission, the financial costs of developing, producing and distributing drug treatments, limited access to decent sanitation facilities, and difficulties in educating people about important facts of disease control; for example, proper burial procedures in order to aid eradication of the virus.Policy makers are often forced to make quick and difficult decisions based upon the knowledge that they have at the time of an outbreak. Scientific rigour in research plays a vital role in influencing these decisions, by providing better understanding of the biological nature of infectious diseases and the dynamics of their spread. Well-funded research strategies are keys to increase our knowledge of infectious diseases; however, understanding the science is just one component of effective control, and one in which only collaborative effort between scientists and policy makers across many different fields can hope to achieve.The meeting highlighted the scientific benefits that come from collaboration between mathematical and laboratory-based sciences in extending our understanding of both basic infectious disease processes as well as applied issues in disease control; such an approach will continue to provide the focus for research within CIDC.


Lectins are proteins which have the ability to interact specifically with carbohydrate residues of glycoproteins and other glycoconjugates. The staining patterns of 10 fluorescein conjugated lectins  and a protease inhibitor (F-LA) have been studied in histological sections of 11 normal or reactive lymph nodes and 6 nodes and one skin biopsy involved by Hodgkin's disease. On the basis of the patterns of lectin binding, and current knowledge of their saccharide specificities, we found that within germinal centres there is an orderly carbohydrate rich extracellular matrix which contains a higher concentration of GlcNAc and terminal Gal residues than the surface membranes of component cells. This suggests active secretion rather than simple membrane shedding, and it is possible that this pericellular domain plays a part in the regulation of the proliferative response, or controls migration of lymphocytes in and out of the germinal centre. Lectin binding in Reed-Sternberg cells suggests that the huge nucleoli contain glycoconjugates of diverse structure, which may be linked with their failure to undergo cytokinesis.


In the present work the cell cycle of 5 solid human tumours in vitro and the duration of their various intermitotic phases were studied using H3 thymidine and autoradiography. All the cell lines studied showed a longer G2-period than other normal mammalian cells. No relationship between the duration of the cell cycle and the modal chromosome number or malignancy of the tumours was observed.Reports are available on the studies of the cell cycle of several normal cell populations and of neoplastic effusions in man and experimental animals


The use of large-scale microarray expression profiling to identify predictors of disease class has become of major interest. Beyond their impact in the clinical setting (i.e.improving diagnosis and treatment), these markers are also likely to provide clues onthe molecular mechanisms underlining the diseases. In this paper we describe a newmethod for the identification of multiple gene predictors of disease class. The methodis applied to the classification of two forms of arthritis that have a similar clinicalendpoint but different underlying molecular mechanisms: rheumatoid arthritis (RA)and osteoarthritis (OA). We aim at both the classification of samples and the locationof genes characterizing the different classes. We achieve both goals simultaneously bycombining a binary probit model for classification with Bayesian variable selectionmethods to identify important genes.We find very small sets of genes that lead to goodclassification results. Some of the selected genes are clearly correlated with knownaspects of the biology of arthritis and, in some cases, reflect already known differencesbetween RA and OA.


Recently we reported the variable presence of hypoxia adjacent to necrosis in human glioma lines grown as subcutaneous tumours in severe combined immunodeficient (SCID) mice. To assess the basis for this observation, we examined the pattern of oxygenation in M006 and M006XLo glioma spheroids. We found a wide range of binding of [3H]misonidazole to cells adjacent to the necrotic core, analogous to the patterns seen in xenografts, indicating substantial differences in the central oxygen tension of the spheroids. Clonal selection was used to isolate single cell-derived sublines of the M006XLo line. Some sublines gave spheroids that showed narrow distributions of [3H]misonidazole binding to the cells adjacent to necrosis, whereas other sublines showed a range of binding similar to that seen in spheroids of the parent line. After additional passages in monolayer culture, clonal sublines occasionally gave rise to spheroids in which the mean oxygen tension of cells adjacent to necrosis differed substantially from that of the initial spheroids. No relationship was evident between the thickness of the rim of viable cells and the presence or absence of central hypoxia, over a wide range of rim thickness. These results indicate that different oxygenation characteristics of glioma spheroids and tumour microregions are unlikely to arise from stable genetic variants coexisting in the parent line.


The highly effectiveness and robustness of receptor-mediated viral invasion of living cells shed lights on the biomimetic design of nanoparticle(NP)-based therapeutics. Through thermodynamic analysis, we elucidate that the mechanisms governing both the endocytic time of a single NP and the cellular uptake can be unified into a general energy-balance framework of NP-membrane adhesion and membrane deformation. Yet the NP-membrane adhesion strength is a globally variable quantity that effectively regulates the NP uptake rate. Our analysis shows that the uptake rate interrelatedly depends on the particle size and ligand density, in contrast to the widely reported size effect. Our model predicts that the optimal radius of NPs for maximal uptake rate falls in the range of 25–30 nm, and optimally several tens of ligands should be coated onto NPs. These findings are supported by both recent experiments and typical viral structures, and serve as fundamental principles for the rational design of NP-based nanomedicine. Viruses invade living cells via protein-mediated endocytosis The highly effective and robust adhesion-driven process has raised many fundamental questions with regard to the physical principles harnessed by the evolutionary design of viruses. While it has long been known from biochemistry that the molecular recognition of receptors and ligands allows viral invasion to be type specific, it was only recently fully understood from mechanics point of view that viral invasion is also size selective From a fundamental mechanics point of view, adhesion and membrane deformation play the roles of driving force and resistance to NP endocytosis, respectively. A rational biomimetic design of NPs should either reduce the resistance or enhance the adhesion to facilitate NP internalization. Indeed, it has both experimentally In this article, we aim to establish guiding principles for the biomimetic design of NPs with high uptake rate, one of the key parameters that assess the efficacy of NP-based therapeutics. Noting that correlating the biophysical parameters of NPs with the uptake rate may analytically be complex, we circumvent the difficulty by separately deriving the endocytic time of a single NP and the equilibrium cellular uptake when immersing the cell in a solution with dispersed NPs. The endocytic time and cellular uptake together indicate the uptake rate. From thermodynamic analyses, we reveal that particle size and ligand density interrelatedly govern the uptake rate. The interrelated effects can be interpreted from a general framework of energy balance between NP-membrane adhesion and membrane deformation. The interrelation suggests that tailoring only one design parameter may not be effective to achieve high uptake rate. We construct a phase diagram of the uptake rate in the space of particle size and ligand density, which may serve as a design map for NP-based therapeutics. Finally, we extend our discussions by including the effects of other relevant biophysical parameters.R is the NP radius and From an energetics point of view, NP engulfment by cell membrane is driven by adhesion but involves significant membrane deformation cost Wrapping also involves pulling excess membrane area toward the wrapping site, for which work needs to be done to overcome membrane tension, denoted here by Because of the nonlinearity of The total deformation energy at the fully wrapped state indicates a characteristic particle radius Several unique features arise when endocytosis is receptor-mediated. First, as adhesion is supplied by ligand-receptor binding, wrapping of NPs requires diffusing receptors to the binding sites, thereby setting a characteristic time scale of endocytosis and limiting the uptake rate 2. We assume that the receptors are initially uniformly distributed on the cell membrane with an initial receptor density R and coated with ligands of surface density k may be described interchangeably at given K.To reflect the discreteness of receptor-mediated endocytosis, it is convenient to set the cross-sectional area of the receptor as the unit area, denoted by local” energy balance. Such a local consideration ignores the entropic effect of receptors, which represents the “global” aspects of adhesion. Equation (2) also manifests the interrelated effects of particle size and ligand density on NP endocytosis.The dual character of receptors suggests that the adhesion strength in receptor-mediated endocytosis can be decomposed into two components, i.e., in vitro involve immersing biological cells into a solution with dispersed NPs To measure the cellular uptake rate, experiments Unless otherwise mentioned, the following parameter values are used for our analysis: The fact that wrapping necessitates receptors to diffuse from the far field to the wrapping site sets a diffusion-limited endocytic time. The endocytic time can thus be determined by formulating a diffusion problem that involves tracking the wrapping front of the cell membrane R being wrapped by cell membrane, as shown in M is the total membrane area. We consider a general stage of wrapping characterized by the degree of wrapping Similar to crack extension or healing in a crystal lattice −2. At Since t∼D is the diffusivity of the receptors. Solving R, and substituting them into Eq. (8), the characteristic impact length scale and hence the endocytic time can be obtained.Conservation of the receptors in the wrapping zone and the impacted area specifies a characteristic length N, are wrapped by cell membrane with different degrees of wrapping k, one follows We next analyze the cellular uptake of NPs when immersing the cell in a solution with dispersed NPs of bulk density It is noteworthy to point out the close similarities of the adhesion strengths The unified energy-balance framework of adhesion and membrane deformation for the endocytic time and the cellular uptake suggests that one may define the uptake rate asFrom the phase diagram of the uptake rate in The ridge line of the phase diagram in kBT) and receptor-ligand binding energy kBT), our model predicts that the optimal amount of ligands coated onto viruses falls in the range 10–100 irrespective of the virus size. The extensively studied model system, the Semliki Forest virus (SFV), is about 35nm in radius, covered with 80 glycoproteins (ligands) Considering viruses as NPs optimized by nature via evolution, the number of ligands decorated on the surfaces of viruses should obey the optimal number: In addition to the particle size and ligand density, many factors may influence the phase boundaries of the uptake rate, as presented below.Several factors affect the density of receptors expressing on the cell membrane. First of all, receptors internalized by NPs may be recycled back to the host membrane; they may also be degraded in the endosomes and lysosomes. In addition, new receptors may be produced and diffuse to the cell membrane. The precise amount of receptors involved in endocytosis is currently unknown. In addition to ligand-receptor binding, receptor-mediated endocytosis may be assisted by specific proteins, such as clathrin or caveolin One notes that variation of the relative energy scale leads to the change of the enthalpic component of the adhesion strength and/or the membrane deformation energy density. As the lower bound of the uptake rate is enthalpically governed, variation of the relative energy scale modifies the lower bound of the phase diagram. On the other hand, the upper bound is entropically governed, and thus only weakly dependent on The bulk density of NPs in solution appeared as a model parameter only for computing the cellular uptake. A high bulk density yields a high surface concentration of NPs on cell membrane, leading to intensified competition for receptors among adhering NPs Through thermodynamic analyses, we revealed that the endocytic time of a single NP and the cellular uptake when immersing the cell into a solution with dispersed NPs are governed by the unified framework of energy balance between adhesion and membrane deformation. We established phase diagrams in the space of particle size and ligand density for both the endocytic time and the cellular uptake. We identified from the phase diagrams the lower (upper) bounds below (beyond) which the endocytic time goes to infinite or the cellular uptake vanishes. We further revealed that the mechanisms governing the lower and upper bounds of the endocytic time and the cellular uptake are the same: the lower bounds correspond to the enthalpic limit of the NP-membrane adhesion strength, while the upper bounds to the entropic limit.The computed endocytic time and the cellular uptake allow us to define the uptake rate. It should be mentioned that the uptake rate defined here is different from what is typically measured in experiments We further discussed the effects of other relevant biophysical parameters on the uptake rate, including the receptor density, the relative energy scale of ligand-receptor binding energy and membrane bending rigidity, membrane tension, and the bulk density of NPs. All the effects can be coherently interpreted by the variation of the enthalpic and entropic adhesion strength. The phase diagram of the uptake rate in the space of particle size and ligand density thus serves as a design map that guides the rational designs of NP-based bioagents for biosensing We consider a general stage of wrapping at which an area of Corresponding to the wrapping-size distribution k using l receptors. In the present analysis, we assumed that the density of receptors bound to NPs is independent of wrapping size. This simplification does not affect the qualitative conclusions drawn here.The thermodynamic equilibrium, expressed by Eqs. (10) and (11), can be obtained by minimizing the free energy functional with respect to its two independent variables,


Wild-type measles viruses have been divided into distinct genetic groups according to the nucleotide sequences of their hemagglutinin and nucleoprotein genes. Most genetic groups have worldwide distribution; however, at least two of the groups appear to have a more limited circulation. To monitor the transmission pathways of measles virus, we observed the geographic distribution of genetic groups, as well as changes in them in a particular region over time. We found evidence of interruption of indigenous transmission of measles in the United States after 1993 and identified the sources of imported virus associated with cases and outbreaks after 1993. The pattern of measles genetic groups provided a means to describe measles outbreaks and assess the extent of virus circulation in a given area. We expect that molecular epidemiologic studies will become a powerful tool for evaluating strategies to control, eliminate, and eventually eradicate measles.


Almost one tenth of more than 370 hepatectomies, mostly for tumors, involved resection of major parts ofthe caudate lobe, subsegment 1. Five of them were for tumors or hemangiomas here, compressing orinvading the vena cava; two were for metastases of colorectal cancer located very close to the junctions of theright and middle hepatic veins with the vena cava. We would previously have deemed these tumorsunresectable. In these patients the vein was banded above and below the liver, an internal shunt tube placedin preparation for shunting of blood, and the afferent liver blood flow controlled. Control of the vena cavaby tightening of the bands was needed in two cases. Tumor-invaded parts of the vein wall were resected intwo other cases, in whom the presence of the tube facilitated the resection but the bands did not have to betightened. The procedure did not cause morbidity and we conclude that tumors close to the vena cava canoften be resected without complex vascular exclusion techniques, even when they invade the vein.


The 1962-66 cancer mortality of Polish migrants to Australia is compared with the cancer mortality prevailing in Poland and in Australia. Small numbers compel to limit the analysis to the most frequent cancer sites only.The main findings are:(a) Stomach cancer mortality of Polish migrants to Australia is intermediate between the high mortality in Poland and the much lower one in Australia.(b) Intestinal tract and breast cancer mortality of Polish migrants is displaced upwards, from the low Polish level to the much higher Australian one.(c) Lung cancer mortality of Polish male migrants does not differ distinctly from the mortality observed both in the country of origin and of adoption of these migrants.The presented findings are compared with the results of a similar study of Polish migrants to the U.S. Aims for future studies are briefly outlined.


The reduction in size of the experimental ISIS 130 tumour has been investigated in LOU rats under the influence of increasing doses of cytostatic agents belonging to different classes. External temperatures of tumours as well as rectal temperatures have been measured at the same time, twice daily, during the whole experiment. The greater the decrease in the tumour size after drug administration, the larger was the decrease in external temperature of tumour. The rectal temperatures remained fairly stable, thus differences between the tumour and rectal temperatures increased. A possible correlation between the reduction of tumour size and the decrease of external temperature of tumour has been traced for every cytostatic agent, and the same linear relationship has been found to link these two parameters. The decrease in external temperature of tumour may, moreover, predict the decrease in tumour size within a term of 1-2 days. Measurement of the magnitude of the transient tumour hypothermia of ISIS 130, following chemotherapy, would represent a new method for measuring the efficiency and duration of action of cytostatic agents.