A Galeazzi fracture is defined as a fracture of the radius associated with dislocation of the distal radio-ulnar joint (DRUJ). The conventional surgical technique of nailing does not give enough stability and open reduction, internal fixation with the plate is associated with numerous complications. The stacked nailing for the management of these injuries provides adequate stability, maintains the relationship of the DRUJ and promotes uneventful union by closed technique. The purpose of this study is to evaluate the results of simple, user-friendly, low cost elastic stacked nailing for the management of Galeazzi fracture dislocation.We treated 22 young adults with fresh Galeazzi fracture-dislocation of the forearm, from January 2004 to January 2008, by percutaneous fixation of fracture by stacked elastic nailing at our institute. There were 19 males and three females and the age group ranged from 20-56 years (average 35 years). Surgery was performed within 48 to 72 hours under the guidance of image intensifier. Medullary cavity was filled with two elastic titanium nails having unequal lengths and diameter. One nail acts as a reduction nail and the other acts as a stabilizing nail. The results were evaluated using Mikic criteria based on union, alignment, relationship of the DRUJ, and movements at the inferior radio ulnar joint, elbow and wrist.In six cases, following radiological union, nails in the radius were extracted between six to nine months after operation because of discomfort complained by the patient at site of insertion. After one year follow-up, 18 patients had excellent, four had fair results.Closed reduction and internal fixation of Galeazzi fracture by two elastic rods re-establishes the normal relationship of the fractured fragments and the DRUJ without repair of the ligaments. The stability is achieved by the flexibility and elasticity of the nails, crowding of the medullary canal and anchorage they gain in the radial diaphysis. Elastic nailing can produce excellent clinical results for Galeazzi fracture-dislocation. It has the advantages of technical simplicity, minimal cost, user-friendly instrumentation, and a short learning curve. The fracture of the radius and dislocation of the distal radio-ulnar joint (DRUJ), described by Sir Astley Cooper in 1824, is a very unstable and a rare injury.9Plating of the fracture of the radius is most suitable in these cases and if correctly done it provides rigid internal fixation of the bone and stable reduction of the DRUJ in most cases.10The purpose of this article is to evaluate a simple, low-cost, elastic stacked intra medullary nailing for the management of Galeazzi fracture dislocation. and the stability it can provide in this inherently unstable injury.Twenty two patients with fresh Galeazzi fracture dislocations treated from January 2004 to January 2008 at our institute constitute the study. The mean age of a patients was 35 years (range 20-56 years). Most fractures occurred at the junction of the middle and distal third of the shaft of the radius ; 11 fracTwo fractures were Grade I open injuries as per Gustilo and Anderson’s classification. Nineteen fractures were operated under brachial block and the rest three were given general anesthesia. For open fractures, reduction was undertaken after debridement of the wound. All fractures were operated under tourniquet. The fracture was reduced under C-arm guidance with manual traction exerted on the hand by the assistant after abducting the arm and flexing the elbow with the help of elbow attachment . Each ofA 2-3 mm pre bent elastic titanium nail  was introduced through the styloid process of the radius utilizing a stab incision and negotiated till it reached the subchondral bone of radial head. This acts and behaves as a reduction nail. Another nail of different size and length was then passed across the fracture site into the medullary canal till further negotiation was not possible and the stability of the construct was assured by manual rotation of the construct under C arm. The forearm was then rotated to assess for any DRUJ instability. The entry site was dressed and a compression dressing was given. We had to stitch the entry wound in only two cases during the early part of this study.n=2), just proximal to the articular surface. In a case of fracture of the base of ulnar styloid, plaster immobilization was continued for a period of six weeks.If the DRUJ was found to be stable in supination, splintage in a long arm splint was given in supination for six weeks. If the DRUJ was reducible in supination but unstable, stabilization was achieved by placing 2 mm kirschner wires (K-wires) from the ulna into the radius . The follow-up period in our series was twelve months to 18 months with an average of 14 months. Our results were excellent in 18 cases and fair in four cases as per Mikic criteria.We had one case of superficial infection at the site of the nail entry which responded well to regular dressings and healed up uneventfully. In four cases subluxation of the DRUJ with restricted pronation and supination was noticed during the follow-up period. In two cases it was noted after the cast removal, although it had a stable fixation and a normal alignment in the immediate post operative period. There was loosening of the cast in these two cases in the early part of the study. In the remaining two cases there was a progressive collapse of the radial fracture and the subluxation of the DRUJ was noticed three months after the surgery. All these four cases healed uneventfully and the patients regained good functional range of movement without necessitating further surgery. Complications were recorded in these four patients with fair results.No patient had delayed union or nonunion and nerve injury. Six patients reported discomfort at site of insertion of nail hence the nail was extracted in less than 9 months. The earliest time period necessitating nail removal was after 6 months of operation, following union of the fracture There was no difference in clinical outcome of the patient with fracture of the ulnar styloid process.Galeazzi fractures are inherently unstable injuries. They are estimated to account for six to seven per cent of all forearm fracture in adults. The brachioradialis muscle and the extensors and abductors of the thumb tend to shorten the radius while the pronator quadratus rotates the distal fragment towards the ulna.4133The radius is a curved bone with its concavity towards the ulna. The medullary canal of the radius is funnel-shaped in the distal third, and curved and narrow in the middle thirdIn order to address the issue, a pre bent triangular metal nail sufficiently elastic and resilient while it traverses the canal from the point of insertion, but rigid enough to withstand the torsional, rotational, and angulatory forces while progressing to union was devised which gave fewer instances of malunion and non-union compared with other methods of open reduction and internal fixation.Internal fixation by square nail in Galeazzi fracture of the distal third of the radius not only permits rotatory motion at the fracture site, but also substantial lateral movement, which may predispose to delayed union and non union. It might lead to subsequent instability at the DRUJ. The end-of-the-rush nail acts as a potential irritant to the tendons around the wrist, necessitating early removal.Open reduction and rigid internal fixation of the fracture of the radius re-establishes the normal relationship of DRUJ without repair of the ligaments. Fixation with a plate and screw is superior to square nail fixation in these fracture.Early compression-plating with a six-hole plate will give satisfactory results for most fractures. Grafting is usually not necessary, and four weeks of immobilization in neutral pronation-supination or mild supination is adequate. Resection of the distal end of the ulna or temporary fixation of the distal radio-ulnar joint with a pin through the radius and ulna is rarely, if ever, required after compression plating of a fresh unstable fracture.2The radius is usually bowed in two planes- one in the frontal plane having a lateral convexity and the other in the saggital plane with posterior convexity.1718In our series, no nerve injuries were found. A single medullary nail within the radius has no inherent stability to withstand the muscle forces. Therefore a second nail of a shorter length, engaging into the narrowest part of the radius prevents the rotation of the fracture fragments and imparts fixation on the principle of three-point fixation and Kuntschner’s principle of crowding of the medullary canal. Similarly, Hackethal who had proposed nailing for the forearm fractures and achieved excellent results based the utility of his nailing on the four premises, especially the jamming of the nails in the cortical window, jamming the waist of the medullary cavity, spreading the bunch of nails in the metaphysis and filling up the conus of the medullary cavity with short nails.19An above elbow plaster cast in full supination avoids opening and repair of the inferior radioulnar joint complex.5The use of elastic stable intramedullary nailing for displaced and unstable fractures of the radius and ulna in children is a well established method,2224Elastic stable intramedullary nailing of the radius is technically simple, cost effective with user friendly instrumentation, short learning curve and a cosmetic method with minimal risk of infection, delayed union, or tendon rupture, obeying and respecting the integrity of the soft tissues around the injured site. It provides anatomical reduction with preservation of normal curves of the radius and provides a stable fixation in both angulatory and rotational planes. The stability is achieved by the flexibility and elasticity of the nails and crowding of the medullary canal and anchorage they gain in the radial diaphysis. Our method of percutaneous insertion of the nail through the styloid process avoids injury to tendinous and the neurovascular structures of the lower end radius. This study aims to address the alternative surgical modality available for the management of these difficult injuries.


The European Childhood Leukaemia - Lymphoma Incidence Study (ECLIS) is designed to address concerns about a possible increase in the risk of cancer in Europe following the nuclear accident in Chernobyle in 1986. This paper reports results of surveillance of childhood leukaemia in cancer registry populations from 1980 up to the end of 1991. There was a slight increase in the incidence of childhood leukaemia in Europe during this period, but the overall geographical pattern of change bears no relation to estimated exposure to radiation resulting from the accident. We conclude that at this stage of follow-up any changes in incidence consequent upon the Chernobyl accident remain undetectable against the usual background rates. Our results are consistent with current estimates of the leukaemogenic risk of radiation exposure, which, outside the immediate vicinity of the accident, was small.


Morphological identification of cell multiplication (mitosis) and cell deletion (apoptosis) within the lobules of the "resting" human breast is used to assess the response of the breast parenchyma to the menstrual cycle. The responses are shown to have a biorhythm in phase with the menstrual cycle, with a 3-day separation of the mitotic and apoptotic peaks. The study fails to demonstrate significant differences in the responses between groups defined according to parity, contraceptive-pill use or presence of fibroadenoma. However, significant differences are found in the apoptotic response according to age and laterality. The results highlight the complexity of modulating influences on breast parenchymal turnover in the "resting" state, and prompt the investigation of other factors as well as steroid hormones and prolactin in the promotion of mitosis. The factors promoting apoptosis in the breast are still not clear.


Kashmir valley located in the northern division of India, surrounded by Himalayas has an unique ethnic population living in a temperate environmental conditions having distinctive food habits which play an overwhelming role in the development of GIT cancers over the genetic factors.-3 The foColorectal cancer being the commonest cancer, is the major cause of mortality and morbidity worldwide, there are nearly one million new cases of colorectal cancer diagnosed world-wide each year and half a million deaths. The inci13Here we have presented three cases of colorectal cancer in form of images, obtained from the patients who visited Department of General Surgery of SKIMS, for the resective surgery for the immediate treatment of the cancer.


Variations in formation of the superficial palmar arch are common. A classic superficial palmar arch is defined as direct continuity between the superficial branch of the ulnar artery and superficial palmar branch of the radial artery. During routine dissection classes to undergraduate medical students we have observed formation of superficial palmar arch solely by superficial branch of ulnar artery without any contribution from the radial artery or median artery. Knowledge of the anatomical variations of the arterial pattern of the hand is crucial for safe and successful hand surgery. Superficial palmar arch (SPA) is an arterial arcade which lies beneath the palmar aponeurosis and in front of the long flexor tendons, lumbrical muscles and palmar digital branches of the median nerve. SPA is the major blood supply to the hand. Additional circulation for the palm may come from the median artery or interosseous arterial system. The radial and ulnar arteries form four circuits in the hand, the anterior and posterior carpal arches at the level of the carpal bones and the superficial and deep palmar arches at the mid palmar level . The anaDuring routine dissection of the right upper limb of a 45-year-old South Indian male cadaver, we observed SPA formed exclusively by superficial branch of the ulnar artery . The supSuperficial branch of ulnar artery solely forming SPA is reported -7. McCorThe use of radial arteries as an arterial bypass conduit is an invasive procedure which is becoming popular among various medical centers. The greatest risk associated with harvesting the radial artery is ischemia of the soft tissues of the hand. But in patients where ulnar artery is the main blood supply to the first web space the least number of complications may be expected.The SPA is the center of attraction for most of the surgical procedures and traumatic events in the hand. The hand surgeon should keep in mind this kind of variations before performing surgical procedures such as, arterial repairs, vascular graft applications, and free and/or pedicled flaps. SPA is an anastomosis fed mainly by the ulnar artery. When ulnar artery is occluded, the viability of the structures in palm supplied by the ulnar artery depends on the efficacy of the collateral circulation. In our finding there was no anastomosis between the ulnar artery and radial or median or interosseous arteries. So ulnar artery occlusion in cases like ours there will be no collateral flow of blood to meet the metabolic demands of the palmar tissue i.e., results in acute ischaemia, manifested by rest pain and / or gangrene.During surgical procedures of thumb in the cases similar to ours ligation of radial artery may not be sufficient to stop the profuse bleeding since major blood supply was coming from the superficial palmar arch. Several techniques are used to identify and locate any unusual vessel in the upper limb, including Doppler ultrasound, the modified Allen test, pulse oximetry and arterial angiography.


Individual equilibrium binding constants (KB) have beendetermined from spectroscopic titrations employing the hypochromism induced in the visibleabsorbance of the cations on interaction with the nucleic acid. These demonstrate both stereo- andenantioselectivity in the binding interactions. These KB data, together with induced circulardichroism and DNA thermal denaturation results, are all indicative of selective intercalation of thebidentate components of the cations into the nucleobase stack of the duplex. Supportiveevidence for a secondary binding mode for the picchxn complexes is provided by the differentmutagenicity profiles obtained for related cations.A study of the interaction with calf thymus DNA is described of a novel set of chiral ternary complex cations of general form [Ru(N


Differences between the sexes in time trends of colorectal cancer incidence 1962-87 and mortality 1960-91 in England and Wales are examined in relation to changes in female hormonal factors. There was a trend in the sex ratio of this tumour, particularly marked for the descending colon, whereby the female excess in risk at young ages has almost disappeared but the male excess at older ages has increased. This trend started for cohorts born since the 1920s and coincided with the increase in the use of oral contraceptives and, to a lesser extent, with increases in fertility. The decline has been particularly pronounced for women at young ages born since 1935-39, coinciding with the spread of oral contraceptive use to younger age groups. These results are consistent with the hypothesis that female hormonal factors may play a role in the aetiology of colorectal cancer and with the possibility that oral contraceptive use might exert a protective effect in the descending colon.


Sir,Transcutaneous gas monitoring is a noninvasive technique of measurement of oxygen and carbon dioxide tension across the skin. Several studies have validated the accuracy of the values obtained from this monitor.2 TranscuA total of 48 patients who had cardiac surgery during April-July 2008 in our center, underwent transcutaneous gas tension monitoring measured with TINA TCPM4 . During the monitoring, two patients were noticed during routine clinical examination, to have developed vesicles at the site/s of use of the sensor for the equipment on the chest Figures  and b. TThe concept of transcutaneous measurement of respiratory gases looks promising because of its noninvasive nature. The manufacturers, in their product brochure mention the potential for the occurrence of burn injuries at the site of sensor application and recommend the use of sensor at 44°C to minimize the potential risk of burn injury and pressure-induced necrosis. In two of our patients, the application of probes led to blister formation despite adhering to these instructions. The possibility of contact dermatitis was ruled out by the non-inflammatory nature, absence of itching and the occurrence of blisters within 4 hours of application of the probes. Possible mechanisms of blister formation in the patients were thermal injury caused by the increased local skin temperature and the negative pressure within the well of the sensor while the gas expelled via the skin is sampled.In the light of our experience, we recommend that clinicians wishing to use the transcutaneous measurements may need to restrict the usage time of sensor at any site for less than 3 hours and at temperatures less than 44°C. The sensors need to be applied on aesthetically less significant areas. Further, the possibility of developing such vesicles may be informed to patients during informed consent.


Preterm birth remains the leading cause of perinatal mortality and morbidity. Evidence suggests that intrauterine infection plays an important role in the pathogenesis of preterm labor. This article reviews the clinical data supporting this theory and the cellular and biochemical mechanisms by which intrauterine infection may initiate uterine contractions. The clinical and laboratory methods of diagnosing clinical chorioamnionitis and asymptomatic bacterial invasion of the intraamniotic cavity are also reviewed. Finally, the management of clinical chorioamnionitis and asymptomatic microbial invasion of the amniotic fluid and the use of adjunctive antibiotic therapy in the treatment of preterm labor are presented.


Retinopathy of prematurity (ROP) is one of the leading causes of preventable blindness in childhood. Early posterior pole vascular signs of severe ROP have been studied since the first description of the disease. The progressive changes that take place in the posterior pole vessels of an extremely premature baby occur in a predictable fashion soon after birth. These vascular changes are described as plus disease and are defined as abnormal dilation and tortousity of the blood vessels during ROP that may go on to total retinal detachment. The ophthalmological community now has a better understanding of the pathology and cascade of events taking place in the posterior pole of an eye with active ROP. Despite many years of scientific work on plus disease, there continue to be many challenges in defining the severity and quantification of the vascular changes. It is believed that understanding of the vascular phenomenons in patients with ROP will help in designing new treatment strategies that will help in salvaging many of the eyes with severe ROP. Their work defined the differentiation between two clinical forms of ROP which differed in prognosis and potential timing of the treatment. The international classification of ROP described in 1984 and its revision in 2005 used the term plus disease to signify the vascular features of ROP that may alert the attending ophthalmologist to for consider treatment of the premature avascular retina. The purpose of this review is to describe the current understanding of the clinical presentation, pathophysiology, value of diagnostic tools, and discuss treatment options in the management of patients with ROP/plus disease.34Retinopathy of prematurity (ROP) results from important changes occurring in the posterior retinal vessels of eyes of pre-mature infants. Since the initial classification of retrolental fibroplasia in 1953, many attempts have been made to identify those eyes that may progress to retinal detachment and blindness if not treated in a timely fashion.There are many studies focused on the potential etiologic factors contributing to ROP. The introduction of pulmonary oxygen therapy for preterm infants in the 1940s, played a major role in an epidemic of ROP that subsequently occurred.67Mesenchymal cells (such a primitive astrocytes), of the ischemic, nonvascularized peripheral retina produce vascular endothelial growth factor (VEGF) which in the absence of any regulation, stimulate the production of neovascularization in ROP.8The premature retina responds dramatically to the presence of VEGF. The presence of VEGF results in the remodeling of vessels as a direct response to fluctuations in oxygen from an ischemic bed.2112214plus disease.pre-plus changes of ROP.Different mechanisms have been proposed to explain the cascade of vascular events taking place in the posterior pole in the presence of ROP. Arteriovenous shunts develop because of the reduced capillary resistance from the remodeling of cells combined with an increase in retinal blood flow.1A wide spectrum of posterior retinal vascular changes exists in ROP. Plus disease describes the most severe vascular changes of dilation and tortuosity and is associated with severe ROP and visual morbidity if left untreated. The diagnosis of plus disease is historically a dichotomous decision based on subjective comparison to reference images.1219162122et al.,et al.,et al.26According to current protocols and international standards for screening for ROP, all infants with a birth weight less than 1500 g and/or less than 32 weeks of gestational age, are required to have weekly bedside retinal examination by a specialist with experience in ROP.21Apart from the classic ROP presentation which is fairly predictable in timing of progression and regression, there is a newly recognized form of ROP called “aggressive posterior ROP” (AP-ROP). AP-ROP represents the most severe active form of the disease. AP-ROP occurs in the youngest and smallest infants and does not progress through the stages of severity of disease as in the classic form. AP-ROP is posterior in location and may occur in zone I or the posterior aspect of zone II. Plus disease develops early and is pronounced in all four quadrants. Often there is no ridge at the junction between vascularized and nonvascularized retina and only a flat network of neovascularization may be present. This can be difficult to view using indirect ophthalmoscopy; however, the massive, early and unusual presence of plus disease may be a major marker of this virulent form of ROPRecent research has addressed potential quantitative approaches to the diagnosis of vascular changes in ROP. There is disagreement among experts on both the diagnosis of pre-plus and plus disease showing discrepancies among observers.216282611283132et al. to our knowledge were the first group to attempt a grading system for the vessel changes of ROP,et al.2et al.The posterior pole changes may be more easily seen than zone or stage of ROP.192As explained, the inconsistencies and subsequent anxieties placed on the ROP examination could be alleviated by a quantifiable system of ROP screening, potentially to be performed automatically by computer image analysis tools. One of the initial semi-automated programs available for assessing the retinal vessel changes in preterm infants was developed by Martinez-Perez at Imperial College London.3637Subsequent to retinal image search and analysis (RISA), computer-aided image analysis of the retina (CAIAR) was developed at Imperial College London. The user input necessary was reduced to helf by more intuitive vessel location abilities based on maximum likelihood model-fitting in a scale space framework. The estimated model of Gaussian profile with parameters of height, width, and orientation are computed at each location in the image as illustrated in Figures Concurrently, ROPtool has been under development at Dukes University, North Carolina, an extrapolation of a technique for measuring tubular objects in three-dimensional images initially used for locating the intracerebral vasculature from magnetic resonance angiography (MRA) images.3Other programs have been adapted from diabetic retinal image analysis techniques for analysis of images from preterm infants. Vasculomatic a la Nicola (IVAN) is one such program. IVAN measures retinal vessel diameters of the six largest arterioles and six largest venules located 0.5–1.0 disc diameters from the disc margin . Each im39Recently, a completely automated system, RetVas has been developed to detect the retinal blood vessels of images from preterm infants at risk of developing ROP. A sensitivity of 97% for locating one arteriole and one venule in each quadrant of 75 images has been reported. The software is based on a model reverse engineered from human vision, using the same processes as the human visual cortex to observe images and select features. Pre- and postautomated analysis images are illustrated in Figures 34et al.et al using the same principle of measuring a series of points along each vessel to calculate vessel tortuosity, Wallace et al.23939Each vessel localization program uses its own algorithm in calculating the width and or tortuosity of the blood vessel, it has segmented. For example, CAIAR uses a multi-scale approach successively subdividing the vessel sections into two parts. The geometric concept involves perpendicular bisection of the vessel chord at its midpoint and subsequent reapplication of the subdivision on the resultant segments until the segment lengths fall below a specified value (four pixels).Despite great advancements in the area, there are many barriers to the implementation of new concepts for real-time screening at bedside. Firstly, most of these programs are not fully automated and require a trained operator to select a vessel. Secondly, the degree the accuracy of such a system requires rigorous testing in the form of multicenter clinical trials to ensure the small changes between normal and abnormal vessels are adequately and repeatedly detected in infants with and without ROP. Third, images—specifically high quality images, may not be widely available due to equipment restrictions.2The goal of treatment of Type I ROP is to remove the stimulus for abnormal neovascularization due to an ischemic retina.12229Most recently, the Early Treatment Trial for ROP (ET-ROP) has defined the severity of ROP into two types, Type I and Type II, recommending the guidelines for treatment as outlined in 2435With our understanding of the pathophysiology of retinopathy of prematurity from the role of proangiogenic factors to the cascade of events ending with dilation and tortuosity of posterior vessels, it is possible to predict the natural history of ROP and its close relationship to salvaging the eye as the disease progresses. Plus disease has been described as a factor of prognostic significance in determining stage, diagnosis, and signs of severity of the disease. Our access to current technology and the availability of objective diagnostic tools may lead us to earlier recognition and appropriate treatment. The presence of plus disease has now become an indication of severity and for determining the adequate moment of treatment. Although zones and stages of ROP are noted, they are of secondary importance in determining whether laser treatment is needed.42


Canada's federal government has once again failed to shut North America's only authorized supervised injection facility: Insite. A majority ruling issued by the BC Court of Appeal on 15 January 2010 upheld an earlier British Columbia Supreme Court ruling in 2008 that protected the rights of injection drug users (IDUs) to access Insite as a health facility as per the Charter of Rights and Freedoms component of the Constitution of Canada. The majority decision from Honourable Madam Justices Rowles, Huddart and Smith also established a jurisdictional victory safeguarding Insite as most appropriately run under the authority of the province of British Columbia rather than the federal Government of Canada. The Federal Government has appealed the case to the Supreme Court of Canada. A hearing date has been set for 12 May 2011. The appeal will be a legal one but even more so, it will be an appeal to humanity. Canada's federal government has once again failed to shut North America's only authorized supervised injection facility: Insite. A majority ruling issued by the BC Court of Appeal on 15 January 2010 upheld an earlier British Columbia Supreme Court ruling in 2008 that protected the rights of injection drug users (IDUs) to access Insite as a health facility as per the Charter of Rights and Freedoms component of the Constitution of Canada.The majority decision from Honourable Madam Justices Rowles, Huddart and Smith also established an important jurisdictional victory emerging from the cross appeal by the operators of Insite: the PHS Community Services Society (PHS). The ruling further safeguards Insite as most appropriately run under the authority of province of British Columbia rather than the federal Government of Canada.Insite opened on 21 September of 2003 under an exemption granting it status as a scientific pilot study until 12 September 2006. The primary goals of the program are: (1) to reach a marginalized group of IDUs with healthcare and supports who would otherwise be forced to use drugs in less safe settings (2) to reduce dangerous injection practices (syringe sharing) thereby reducing the risk of infectious diseases like HIV and HCV; and (3) to reduce fatal overdoses in the population of people that use the facility. The program also aims to provide referrals to treatment and detoxification, reduce public disorder (public injection) and validate the personhood of a deeply stigmatized target population[The legal battle began near the end of Insite's three-year exemption for scientific study when a minority conservative government was elected in Canada on 6 February 2006. The new government voiced opposition to the program during and after the election. On 1 SeControlled Drugs and Substances Act until 30 June 30 2008. A looming threat of closure by the conservative led government led the PHS to take the Government of Canada to court in late 2007[Controlled Drugs and Substances Act (CDSA) in Canada is unconstitutional as it pertains to Insite because the closure of the program under the Act would impede people with addictions from receiving life saving healthcare. BC Supreme Court Justice Ian Pitfield ruled that the use of the CDSA to shut Insite would undermine the fundamental right, under Canada's Charter of Rights and Freedoms to life, liberty and security of the person[On 2 October 2007, the project was given an additional exemption to operate under the late 2007. The outSince its inception, Insite has been subject to an independent review by a team of physicians and scientists put in place to provide an "arm's length" evaluation of the program. The results of this scientific evaluation have been published in peer-reviewed academic journals and have indicated that Insite has reduced unsafe injection practices, public disorder, overdose deaths and HIV/Hepatitis while increasing uptake of addiction services and detox. To dateDespite this support from the scientific and medical community, the Conservative government of Canada remains entrenched in its position having served the PHS with court documents indicating their intention to appeal the case of Insite to the highest court in the country: the Supreme Court of Canada. A courtThe author declares that they have no competing interests.


A study of 2072 children who developed cerebral or spinal cord tumours of varying degrees of malignancy before 15 years of age has shown that there is equally good representation of fatal and non-fatal cases in official registrations. Attack rates are higher for boys than girls and the prognosis is better for girls than boys. The risk of an early death is negatively correlated with age at diagnosis, and the risk of a late death shows the opposite relationship. These observations and a relatively high incidence of hindbrain tumours are suggestive of an embryonic origin for most of the cases.


Electrochemotherapy (ECT) is a novel anticancer therapy that is currently being evaluated in human and pet cancer patients. ECT associates the administration of an anti-tumor agent to the delivery of trains of appropriate waveforms. The increased uptake of chemotherapy leads to apoptotic death of the neoplasm thus resulting in prolonged local control and extended survival. In this paper we describe the histological features of a broad array of spontaneous tumors of companion animals receiving pulse-mediated chemotherapy. Multivariate statistical analysis of the percentage of necrosis and apoptosis in the tumors before and after ECT treatment, shows that only a high percentage of necrosis and apoptosis after the ECT treatment were significantly correlated with longer survivals of the patients . Further studies on this topic are warranted in companion animals with spontaneous tumors to identify new molecular targets for electrochemotherapy and to the develop new therapeutical protocols to be translated to humans. Local management of solid neoplasms in humans generally involves multimodality approaches whose cornerstones are surgery combined with radiation therapy ,2. The uThe high rate of local control in our preliminary investigation  that accMany tumor histotypes show a marked responsiveness to pulse-mediated chemotherapy, leading to tumor shrinkage and clinical remission. In particular, ECT seems promising at controlling oral mucosal melanomas either as a single modality therapy or in conjunction with surgical cytoreduction . MoreoveDespite the consistent number of preclinical and clinical publications on this topic, there are few data on the histopathological modifications induced by this therapy . Mir andThe lack of extensive investigation in this field prompted us to run a thorough revision of our histological samples to gather a broader picture of patterns of tumor response and eventually to identify possible prognostic factors.A total of 127 companion animals with spontaneous tumors were enrolled in different phase II ECT trials over a 7 years period and biopsies were collected at presentation, after the first session of ECT and at the completion of the treatment  were collected before the beginning of ECT, after one session (one week after the treatment) and at the completion of the protocol (two weeks after the end of the protocol). More than 370 specimens were analyzed. Histopathology specimens embedded in paraffin have been cut into 6 μm sections and stained following standard protocols, using Hematoxylin/Eosin, Hematoxylin/Van Gieson, and toluidine blue staining (to identify poorly differentiated mast cell tumors) . The TUNHistopathological patterns were tested for significance regarding response to first treatment, response to second session of ECT and the recurrence within the first six months of follow-up. Patients died of unrelated disease were censored in the analysis. Variables tested were: percentage of necrosis, apoptotic index. All analyses were performed following an intention to treat analysis method. The time to progression was calculated as the period from the date of starting treatment to the first observation of disease progression or to death from any cause. Survival plot were performed by Kaplan-Meier product-limit method . The difThe review of more than 370 bioptic specimens allowed to determine different features of tumor histopathology following ECT. Patterns of response in the early phases of the treatment (after 1 session of ECT) involved an acute inflammatory response made up of neutrophils, lymphocytes and plasmacells, followed by extensive necrosis. At the completion of the treatment (after two weeks), the tumor samples showed a dramatic decrease in cell number, with the majority of the remaining cells in apoptosis with no inflammatory response, while most of the residual tumor mass was made up of scar tissue. In three cases of feline sarcomas that experienced local failure, the tumor recurred as a less aggressive histotype: a neurofibroma-like lesion rather than an high grade sarcoma. Interestingly, we always detected lack of sufferance in the normal tissues surrounding the neoplasm. Table ECT has several advantages on other anti-tumor techniques: ease of administration, low cost, minimal toxicity , and high response rate. Our morphological study shows on a broad selection of tumors of companion animals a progressive and highly selective destruction that frequently allowed conservative surgeries in the case of extensive tumors. The histopathological analysis of the treated tumor revealed that cancer cells did not undergo the typical response to bleomycin consisting with enlargement and polynucleation , but eviOn the other hand, this pattern of tumor lysis seems to play a key role in the prevention of local recurrence and distant dissemination for melanomas treated with this technique. In fact, we recently described a vitiligo-like lesion in canine malignant melanomas of the oral cavity where the absence of any pigment at the treatment site in the long term survivors might imply the aiming of the immune system to melanin and other deep melanoma antigens . AnotherTo the best of our knowledge, this is the most extensive description of histopathological patterns of response to electrochemotherapy in tumors of companion animals, showing previously undescribed mechanisms of response. The morphological analysis further confirm the efficacy and selectivity of this novel anticancer treatment as evidenced by the lack of sufferance elicited in the normal tissues surrounding the neoplasms. Studies are currently ongoing at our laboratory to further define the nature of the immune response elicited by the ECT treatment, in order to refine and ameliorate the efficacy of our protocols.Spontaneous tumors of pets share striking clinical, histopathological and molecular similarities with their human counterparts, thus providing an invaluable bench to clinic bridging .The results of our studies are being currently translated to humans . Indeed,The author(s) declare that they have no competing interests.All authors read and approved the final manuscript. EPS set up the ECT protocols and treated the animals; FB, PM, FF and ADA prepared the histological samples and described the histopathological patterns; GC gave advise on the work and helped in the interpretation of the data; FB and BV performed the statistical analysis; AB supervised all the work and wrote the paper together with EPS.


The properties of human benign prostatic hyperplasia (BPH) and rat prostate were compared after culture in the absence of insulin and testosterone. Quantitative methods were used to assess changes in tissue composition and the height of the epithelial cells. BPH appeared less sensitive than rat prostate to withdrawal of hormone support, and the changes which occurred during culture of BPH were more typical of a repair mechanism to injury than of a castration effect. Cell kinetics was investigated using [125I] iododeoxyuridine and vincristine. Both approaches demonstrated a spontaneous surge in proliferative activity of BPH reaching a peak at about Day 4. In contrast, proliferative activity in rat prostate tended to fall over the period of 2-8 days of culture. The significance of these findings in terms of age linked effects is discussed.


Despite the rising interest in homeotic genes, little has been known about the course and pattern of evolution of homeotic traits across the mammalian radiation. An array of emerging and diversifying homeotic gradients revealed by this study appear to generate new body plans and drive evolution at a large scale.This study identifies and evaluates a set of homeotic gradients across 250 extant and fossil mammalian species and their antecedents over a period of 220 million years. These traits are generally expressed as co-linear gradients along the body axis rather than as distinct segmental identities. Relative position or occurrence sequence vary independently and are subject to polarity reversal and mirroring. Five major gradient modification sets are identified: (1)–quantitative changes of primary segmental identity pattern that appeared at the origin of the tetrapods ; (2)–frame shift relation of costal and vertebral identity which diversifies from the time of amniote origins; (3)–duplication, mirroring, splitting and diversification of the neomorphic laminar process first commencing at the dawn of mammals; (4)–emergence of homologically variable lumbar lateral processes upon commencement of the radiation of therian mammals and ; (5)–inflexions and transpositions of the relative position of the horizontal septum of the body and the neuraxis at the emergence of various orders of therian mammals. Convergent functional changes under homeotic control include laminar articular engagement with septo-neural transposition and ventrally arrayed lumbar transverse process support systems.Morotopithecus that are still seen in humans supports establishment of a new “hominiform” clade and suggests a homeotic origin for the human upright body plan.Clusters of homeotic transformations mark the emergence point of mammals in the Triassic and the radiation of therians in the Cretaceous. A cluster of homeotic changes in the Miocene hominoid  At the dawn of modern genetics, William Bateson's Among the questions that Bateson sought to address by studying homeotics was the way in which genetic change could lead to the emergence of new body plans. Neither classical morphology nor standard Darwinian analysis has provided truly satisfying explanations of such major body plan innovations as the origin of the Bilaterians by symmetric right/left replication of the organism or the origin of the vertebrates by body axis inversion of the original Bilaterian design The discovery of the homeobox in the 1970s It is now reasonable to return to Bateson's project. Evolutionary change in the system of homeotic genes seems to be involved in body plan transformation. Modularity theory Can the study of homeotic change help show how morphogenetic evolution relates to the emergence of new body plans This report examines the question of whether duplications and homeotic changes have played a role in new body configuration change in three events of special biological interest-the emergence of mammals among the synapsid amniotes, the diversification of mammal groups in the Late Cretaceous, and the emergence of “hominiforms” among the catarrhine primates in the Early Miocene.The study of axially arrayed serial homeotic characters in a group such as the mammals necessitates the study of vertebrae. This is a topic that has been relegated to limited sub-specialist and medical interest for more than 150 years. However, before Darwin, many of the major attempts to assemble a biological explanation for similarity among animals involved vertebrae explicitly. Most prominently, the widely attended zoological works of Goethe Hox, Pax and other Bilaterian homeotic and morphogenetic gene families have further increased the relevance of attention to evolution of axial structures In addition to the progress of axial skeletal fossil discoveries, the remarkable advances in our understanding of the embryologic development of axial structures and their relationships to The hominiform example is particularly compelling. Proconsulid hominoids differed from old world monkeys in having a Y-5 pattern of molar cusps but were otherwise similar to them in body form and ecological niche–most appear to have been generalized quadrupeds Morotopithecus bishopiProconsul nyanzaeOreopithecus bamboliiPierolapithecus catalaunicusFor most of the past two hundred years, models of the origin of human upright posture and bipedalism have been based primarily on evidence from the appendicular and cranial skeleton, but evidence from the spine has played little or no role in our understanding. A series of discoveries of axial skeletal fossils from species including Homo sapiens lumbar vertebra in UMP 67-28, a hominoid fossil from 21.6 million years ago Given the many unique aspects of load bearing and movement requirements, it is not at all surprising that the lumbar vertebrae of modern humans are strikingly different in structure and function from typical mammalian vertebrae. However, the appearance of most of the unique features of the Morotopithecus. Upright bipedalism plays a significant role in all the species of a clade that share the morphogenetic transformation with Morotopithecus.For a variety of reasons, the term “human” has been applied to a clade of hominoids commencing at the split from the chimpanzee lineage about six million years ago The significance of the anatomical adaptations to upright posture and varying degrees of bipedalism seem among the hominoids has been a matter of ongoing interest However, when the various components of axial anatomical specialization in hominoids are fully identified, and their context in the broader setting of mammalian homeotic evolution is made clear, an alternate sequence of events becomes increasingly compelling. This is the possibility that a distinct and ancient clade within the hominoids can be identified that share a major modification of axial architecture that underlies the upright posture and primary bipedalism of modern humans. This morph appears to persist across the succeeding 21 million yeas to be preserved in primitive form in modern humans. The various other types of specialized locomotion seen among existing hominoids are made possible by comparatively minor secondary and tertiary modifications of the original primitive upright, bipedal architecture. This is the basis for asserting a homeotic transformation is the basis of the origin of humanity.This study revealed that body configuration modification in the Mammalia often involves emergence and change of homeotic gradients. In a number of instances clusters of multiple different homeotic gradient changes occurred at the stem of a major systematic radiation .These clusters of homeotic change generally qualify as body plan changes and often relate to significant alterations in the adaptive zone of the descendant groups. These clusters of changes are often preserved as a fixed homeotic set in the descendant group across tens of millions or hundreds of millions of years.Within individual lineages many of the gradients demonstrate alterations on a sporadic basis (at the level of species or higher level clades). Some lineages  show a very high frequency of homeotic change for some gradients. Other lineages show little or no homeotic change over hundreds of millions of years (Monotremata).Some homeotic alterations appear to be relatively highly conserved–they fluctuate in their expression among more ancient lineages but eventually become fixed (e.g. lumbar rib suppression). A few homeotic features never change after their initial appearance .At a finer level, some gradients clearly are subject to independent alteration in rate and tempo of expression along the body axis–some progress incrementally along the segmental series, some commence abruptly and then progress slowly and these properties vary across taxa. The gradients may respect medio-lateral and dorso-ventral positional relationships relative to each other or they may cross as they progress down the body axis. The segmental locations of onset of gradient change do not follow rigidly fixed sequences relative to each other.Once established, the expression pattern of these gradients and of the morphological substrates upon which the gradients act then diversify . Some apOne remarkable aspect is the mirroring and duplication of homeotic gradients. A gradient series usually seen with a given polarity and location recurs with opposite polarity at a different location. New gradients may act along the entire body axis or in replicated form within each segment. The emergence of new types of structures by duplication with subsequent diversification of the new version mimics the pattern of change often seen with gene duplication at the level of the genome.The basic homeotic distinction of five major spinal regions  is apparThe thoraco-lumbar transition within the vertebral series of mammals, however, depends on a variety of gradients that defy simple counting and categorization –this issThe lumbo-sacral boundary collectively affects multiple gradients in concert and is therefore a discreet phenomenon like the cervico-thoracic boundary. The recent advent of a molecular resolution to the deep relationship of mammalian groups Scutisorex provides the most dramatic example of morphogenetic disruption of the homeotic system among the mammals Scutisorex has twelve lumbar vertebrae.Petrodromus tetradactylus (USNM 241593)–a species with a remarkably accelerated rate of morphological evolution Another informative homeotic character state is the replication of the “diaphragmatic” thoraco-lumbar transition vertebra in a specimen of the macroscelid Reduction in the number of dorsal (thoracic+lumbar) segments is relatively uncommon. It is typical of the Order Chiroptera and the Order Cingulata. Among hominoids this occurs in all of the species of the hominiform clade , 4 but nThe initial reduction in number of lumbar vertebrae in the hominiforms appears to be a shift from the catarrhine modal number of seven down to a modal number of five or six . Modern Pongo, then Gorilla, and then Pan, with the longer more flexible lumbar spine retained in primitive form in hominines such as Australopithecus and Homo  can have mobile ribs on all of their lumbar vertebrae. In fact, many groups of Mesozoic mammals also have mobile uniarticulate ribs on their lumbar vertebrae. It is only among the therian mammals that lumbar ribs are lost definitively Monotremes  part of the vertebra that was revealed and characterized by this study. Some of these gradients appear to have profound functional significance, others seem to be best valued as windows into the morphogenetic mechanisms in play in mammalian evolution. The neomorphic element can be termed the The neomorph appears to arise by a medio-lateral duplication on the lamina of the vertebra. A single primitive extension or process seen in most tetrapods (the diapophysis) becomes two side by side extensions , 10, 11.Once established it actually becomes more constant than the primitive extension that it replicates. In the posterior thoracic region of many mammals, the diapophysis is suppressed along with the dorsal rib head, but the laminapophysis still appears. It is therefore clear that its morphology is determined by a new homeotic gradient that is not necessarily subject to events that alter the old homeotic gradient responsible for the diapophysis.The laminapophysis disassociates most of the trunk musculature from the ribs, thus significantly disengaging the rib cage from the locomotor musculature of the body . This isAt its earliest appearance there are no additional homeotic gradients affecting it. In monotremes it proceeds with monotonous uniformity of shape through all dorsal vertebrae . Independiaphragmatic” joint  along the spine (reverse polarity)  in additHystrix, Hydrochoerus) and almost certainly reflects an entirely independent genetic event.Anterior mirroring also occurs in most carnivores, all pholidotans (pangolins), many artiodactyls and some perissodactyls suggesting that this is an echo of a single homeotic gene-based replication event in an ancient clade within the Laurasiatheria which took place after the divergence of the Chiroptera and the Eulipotyphyla . A similMirroring or replication of homeotic gradients also occurs in regard to several features in the Xenarthra resulting in multiple facet pairs at each articulation between lumbar vertebrae. In some species, the primary articulation takes on an unusual cylindrical shape, so the appearance of a mirror image cylinder is highly suggestive of a duplicated morphogenetic instruction .Mammalian groups appear to display a virtual collapse of the homology paradigm when their different types of lumbar transverse processes (LTPs) are examined in detail. More than fifteen different types of lumbar transverse process serial homology were observed  and therThe explanation appears to be a morphological field that that varies in the site of contact of its induction point upon the vertebra. The variation affects both dorso-ventral location and antero-posterior position within the segment as it can apparently coopt a variety of different axial structures to form the lumbar transverse process (LTP) depending on the location of where its induction point impacts the forming vertebra.Nemegtbaatar (Multituberculata) A few similar antecedents appear in occasional non-mammalian synapsids Large LTPs can structurally support large body size  [37] so Cetacea display two distinct types –one typehominiform” clade within the Hominoidea. The resulting relocation of the LTP structural support is the fundamental functional change that underlies upright posture in hominiforms. This character is first seen at 21.6 million years ago in the lumbar vertebra of Morotopithecus bishopiThe transition in LTP homology is a key basis for the proposal in this paper to establish a “Division of the chordate body into dorsal and ventral portions is defined by a rib-bearing horizontal septum in vertebrates and by dorsal and ventral divisions of the ramifying segmental spinal nerves. It is conventional to appreciate that vertebrate bilaterians have their neural tube dorsal to the horizontal septum while invertebrate bilaterians have the neural axis ventral to it. Overall, this is an issue of the fundamental patterning mechanisms of the dorso-ventral gradients of morphogenesis as well as a key point in the systematics of the Bilateria.Oddly enough, in humans the horizontal septum is actually dorsal to the neural axis in the lumbar region. In fact, this situation occurs sporadically in groups appearing in various lineages scattered throughout the therian mammal phylogeny , 17A, 18Dorso-ventral transposition of the horizontal septum and of the neuraxis occurs at a crossing point that may be termed the “septo-neural inflexion point” and reflects the crossing of two somewhat independent morphogenetic gradients see .The ancestral synapsid condition The details are still unclear for some Mesozoic mammal groups, but for all therian mammals there is a major shift of the pararthrum  to a position near the dorsal margin of the vertebral body , 7A. ThiEmbryologically and evolutionarily, the ribs arise at intersection lines between the horizontal septum and segmental myosepta. Because of this, the relatively dorsal or relatively ventral position of the attachment point of a costal derived process or lumbar transverse process on the vertebra reveals the relative position of the septal and neural horizontal body planes in the animal.In Archosaurs, there is a very abrupt and complete inflexion and transposition . In the The particular type of transition seen in archosaurs almost never occurs in mammals because the synapsid/mammalian primary rib articulation tends not to cross the “neuro-central suture” of the vertebra . In mammals, when the horizontal septum becomes transposed to a position dorsal to the neuraxis, there may be non-costal lumbar transverse processes (as in humans) but there are almost never ribs dorsal to neuraxis. Exceptions to this occur in the form of rib articulations on the pedicles in Superorder Xenarthra (Order Pilosa)  and in tSepto-neural inflexion patterns have not been previously appreciated as an important aspect of tetrapod morphologic and functional evolution. Nonetheless, they may play an important role in the emergence of large cursorial mammals at the close of the Mesozoic, the emergence of the Carnivora from the ungulates at the Cretaceous-Tertiary boundary and in the origin of the anatomical basis of upright posture in humans in the stem hominiform hominoids of the Early Miocene.th gradient set that specifies the dorso-ventral position of the diarthrum relative to the neuraxis as well as its relation to the horizontal septum.A different type of change in horizontal body planes occurs in most australodelphian metatherians. This is the transposition of the ancient more dorsal rib articulation plane  to become ventral to the neuraxis in the lumbar region , 20. ThiIn australodelphians, there is never any further dorsal shift of the horizontal septum. Many eutherians including the Eulipotyphla in the Superorder Laurasiatheria show a similar stable relation of the horizontal septum and the neuraxis.Dorsal repositioning of the horizontal septum is typical of the superorder Afrotheria. In proboscideans, some members of the group display a full transposition Dorsal repositioning of the septum is universal in the Ferungulata , 22, 23.In Perissodactyls, the septum apparently undergoes a secondary and partial ventral descent. The result is the obliteration of the neural foramina since the septum and the neuraxis become co-linear. The nerve roots in perissodactyls exit the spinal canal through perforations in the pedicle and they do not have intervertebral neural foramina as in most vertebrates .Some artiodactyl groups that have secondary ventral shifting of the horizontal septum also have co-linearity with the neuraxis and thus have parallel evolution of the pedicle perforations for the nerve roots instead of intervertebral foramina . Nerve eIn the eutherian Superorder Euarchontoglires, the horizontal septum is parallel to or just ventral to the neural canal . HoweverMorotopithecus bishopi dated at 21.6 million years ago  so this event may literally be the anatomic determinant of “humanity”. Although it is conventional to apply these criteria only to a “hominine” clade originating about six million years ago, the understanding of the impact of this septo-neural transposition event is a formidable challenge to that framework. If the same feature and same genetic event that underlies human upright posture and bipedalism is simply preserved in its primitive form in the stem hominines of six million years ago, how do we exclude the original species in which it appears–There is a common functional requirements of the spine in quadrupedal therians to resist hyperextension due to gravity while allowing dorso-ventral flexibility in locomotion. It is therefore not surprising that there are multiple convergent anatomical structural solutions. Most of these have not been appreciated in earlier attempts to model the mammalian spine on a global engineering basis without adequate attention to the context and detail of the specific anatomical structures actually involved Universally in the Ferrungulata, Paenungulata, Xenarthra and Ameridelphia where septo-neural transposition takes place, there are supplementary modifications of the lumbar spine that relate to resistance against extension of the spine . TypicalHystrix cristata (porcupine with weight up to 30 kg–and note much larger extinct related species such as Neosteiromys pattoni)  . Among pIn a number of mammalian groups including both therians and metatherians These and other types of arrays with the tip of the LTP ventral to the effective axis of rotation for lumbar extension participate in a dynamic, elastic, ligamentous system that supports the lumbar region and resists extension . This apIn this elastic system, as the vertebral column passes into extension, LTPs whose tips are below the effective intervertebral axis of rotation begin to separate from each other . This apPongo and Gorilla have bony blocks to lumbar hyperextension that mimic the situation in ungulates  in Pan is not supported by bony rigidification of the lumbar region. However, Pan differs from other hominiforms such as Morotopithecus and Homo in having thin flat lumbar transverse processes held under tension by heavy ilio-lumbar ligaments suspended between high iliac crests  share them because they emerged in a common hominiform ancestor and are preserved as a synapomorphic character set of the group.Many of the features attributed here to the hominiform pattern of lumbar vertebral architecture do occur more or less sporadically in other mammalian superorders although they are rare in the Superorder Euarchontoglires and are not seen in any non-hominiform primate group. It is worth considering that each of the hominiform lineages could have undergone the septo-neural transposition and consequent loss of the styloid and the ventrally tensioned LTP array on a homoplastic basis. However, this is no more convincing than the more parsimonious suggestion that all the hominiforms known to display these features  provided the basis for large body size in therians of the Late Cretaceous. Changes in three homeotic gradient systems  mark the Early Miocene establishment of a body plan committed to upright postures in the hominiform hominoids.Homeotic change can have major adaptive effects. When a diverse radiation of taxa shares the homeotic innovations of the stem group, there is a Morotopithecus at 22 million years (hominiform/proconsulid divergence) so it is clear that these changes happened with some temporal proximity to each other if not simultaneously. Future discoveries from the fossil record of this time period will no doubt reveal further details about the sequence and tempo at which this body plan generating event took place.The hominiform homeotic transformation is bracketed between the cercopithecoid/hominoid divergence around 24 million years ago and the appearance of Duplication of homeotically determined structures and gradients in the Theria clearly relate to a remarkable explosion of new mammalian body plans. Based on divergence patterns, there is considerable evidence that this took place during the ten to fifteen million years prior to the Cretaceous-Tertiary Boundary and not after it.This is an excellent candidate explanation for the odd pattern of total absence in the fossil record of any mammals much larger than one or two kilograms for the first 160 million years of the existence of this group Therian mammals deploy symmetrical gaits for rapid locomotion The appearance of large mammals at the close of the Cretaceous is at least coincident with the appearance of two major types of architectural transformation of the lumbar spine to provide non-muscular support against extension in the lumbar region. These are convergent class of rigid locking systems in groups with septo-neural transposition , and 26 These data also support the concept of a threshold effect in diversification of the mammals–progress awaited morphogenetic innovation. This supports an enlarged role for a mutational view A comparative evaluation of serially repeating structures and homeotic patterning in 250 extant mammalian species and fossil forms was carried out. For extant forms, specimens in the collections of the Harvard University Museum of Comparative Zoology (MCZ), Harvard Peabody Museum, Smithsonian Museum (USNM) and Chicago Field Museum (FMNH) were selected to provide coverage of all mammalian families except for the order Chiroptera and Rodentia where coverage was at the level of the superfamily. Specimens were selected based on preparations in which a complete naturally articulated spine in which all details could be observed. The objective was to obtain a representative overview across the Class Mammalia but variation within species was not addressed extensively. In essence there simply is not sufficient material available to provide any real comprehensive assessment of variation if the full systematic array of mammals is to be covered. In addition the vertebral nomenclature of Owen


The concept of using a stent to maintain patency of a lumen is not new. As early as 1969, stents werebeing investigated in the peripheral arterial system as a means of preventing restenosis after dilatationby balloon angioplasty . Since then, numerous reports have demonstrated the useof stents in both the peripheral and coronary artery systems . Concomitant with the investigation of expandable endovascularmetal prosthesis has been the development of prosthetic devices for management of tracheobronchial,gastrointestinal, and genitourinary diseases. We will review the use of endoscopicallyplaced prosthetic devices in the management of diseases affecting these systems.


We have reported in the preceding paper that the treatment of plateau phase mouse EMT6 tumour cells with a combination of hyperthermia  and trifluoperazine  greatly enhances the cytotoxicity of the antitumour drug belomycin (BLM). The cytotoxic action of BLM is thought to arise from the induction of DNA damage in a manner which reflects chromatin accessibility. Thus we have studied the effects of the two modifiers (HT and TFP) on chromatin structure and BLM-induced DNA damage. Co-treatment of cells with HT and TFP altered chromatin organisation by the formation and slow resolution of new DNA attachment sites at the nuclear matrix. HT increased drug-induced DNA damage  by the general depression of repair rather than through the generation of new sites for drug action. TFP produced a more discrete block in the repair of alkali-labile lesions in DNA. Both processes appear to occur for the combination of BLM, HT and TFP, and we propose that the novel chromatin configuration permits the accumulation of potentially lethal DNA strand breaks. Our study indicates the potential value of chromatin/DNA repair modifying regimens for overcoming the poor responsiveness of some tumour cells to chemotherapeutic drugs and provides a rational basis for the use of calmodulin inhibitors in thermochemotherapy.


The data in the columns "No. of Cases," "No. of Controls," and "Unadjusted Odds Radio" for the Rosiglitazone rows are duplicates of the equivalent data for Pioglitazone. Please view the corrected Table 4 here:


In Vitro equivalent of the pale and intermediate electronlucentepithelial cells located in the inner zone of the trout thymus, constituting indirectevidence of the phylogenetical relationships of the inner zone of the teleost thymus withthe thymic cortex of higher vertebrates.We present an enzyme- and immuno-cytochemical, and ultrastructural characterization oftrout thymic nurse cells (TNCs). Our data suggest that isolated trout thymic multicellularcomplexes are epithelial cells with acidic compartments that may be involved in the processingof antigens and in the generation of the MHC-II proteins that these cell express, andalso that isolated TNCs are the


Sir,Periodontitis is a destructive inflammatory disease of the supporting tissues of the teeth and is caused by specific microorganisms or group of specific microorganisms resulting in progressive destruction of periodontal ligament and alveolar bone with periodontal pocket formation, gingival recession, or both.2 The hos


Foodborne illness of microbial origin is the most serious food safety problem in the United States. The Centers for Disease Control and Prevention reports that 79% of outbreaks between 1987 and 1992 were bacterial; improper holding temperature and poor personal hygiene of food handlers contributed most to disease incidence. Some microbes have demonstrated resistance to standard methods of preparation and storage of foods. Nonetheless, food safety and public health officials attribute a rise in incidence of foodborne illness to changes in demographics and consumer lifestyles that affect the way food is prepared and stored. Food editors report that fewer than 50% of consumers are concerned about food safety. An American Meat Institute (1996) study details lifestyle changes affecting food behavior, including an increasing number of women in the workforce, limited commitment to food preparation, and a greater number of single heads of households. Consumers appear to be more interested in convenience and saving time than in proper food handling and preparation.


This report describes the first pathologic and immunohistochemical recognition in Australia of a rabies-like disease in a native mammal, a fruit bat, the black flying fox . A virus with close serologic and genetic relationships to members of the Lyssavirus genus of the family Rhabdoviridae was isolated in mice from the tissue homogenates of a sick juvenile animal.


The family histories of 131 patients with histologically defined Hodgkin's disease (HD) were studied and 2,517 first and second degree relatives and spouses were identified and followed-up. The causes of death in deceased relatives were ascertained from death certificates. The numbers of deaths from selected causes were compared with the numbers that would be expected if the relatives had suffered the same mortality rates as the Scottish national population. A 4-fold increase in deaths due to HD was found among first and second degree relatives of patients with the disease (6 cases observed compared with 1.4 expected). Five of the 6 familial cases were related to index patients with the mixed cellularity form of the disease, the remaining case was the brother of a patient with the lymphocyte-depleted form of the disease. The increased risk was seen among relatives of both young and older patients and there was no consistent intrafamilial similarity in age of onset or time of onset of disease.


Two patients with mucosal cancer of the periampullary region were treated with papillocholedochectomy,which entails removal of the papilla of Vater and the whole length of the common bile duct. The neoplasm is dissected out through the plane between the duodenal circular and longitudinal muscles, deep to the sphincter of Oddi and the fibromuscular layer of the bile duct. Pathological examination showed that cancer was confined to the mucosal layer without stromal invasion, and that the operation achieved radical cure. For mucosal cancer, papillo-choledochectomy isan alternative to pancreatoduodenectomy, provided that repeated frozen-section studies confirm thecompleteness of excision.


Peers and Linsell (1973) demonstrated a significant association between the incidence of primary liver cancer and ingested aflatoxin in a study in the Muranga district of Kenya. A study of hepatitis B antigen in the same district showed no significant differences between the low altitude area, with a relatively high incidence of primary liver cancer, and the high altitude area with a lower incidence of the tumour. Current evidence is more in favour of aflatoxin playing an important role in the aetiology of primary liver cancer but hepatitis B antigen may play an ancillary role.


In the BUPA Study, a prospective study of 22,000 men attending a screening centre in London, serum samples were collected and stored. The concentration of beta-carotene was measured in the stored serum samples from 271 men who were subsequently notified as having cancer and from 533 unaffected controls, matched for age, smoking history and duration of storage of the serum samples. The mean beta-carotene level of the cancer subjects was significantly lower than that of their matched controls . The difference was apparent in subjects from whom blood was collected several years before the diagnosis of the cancer, indicating that the low beta-carotene levels in the cancer subjects were unlikely to have been simply a consequence of pre-clinical disease. Men in the top two quintiles of serum beta-carotene had only about 60% of the risk of developing cancer compared with men in the bottom quintile. The study was not large enough to be able to indicate with confidence the sites of cancer for which the inverse association between serum beta-carotene and risk of cancer applied, though the association was strongest for lung cancer. The association may be due to beta-carotene affecting the risk directly or it may reflect an indirect association of cancer risk with some other component of vegetables or with a nonvegetable component of diet that is itself related to vegetable consumption.


Copper(II) complexes of amino acids and peptides containing the chelating bis(imidazolyl) residues havebeen reviewed. The results reveal that bis(imidazolyl) analogues of these biomolecules are very effectiveligands for metal binding. The nitrogen donor atoms of the chelating agent are the major metal binding sitesunder acidic conditions. In the presence of terminal amino group the multidentate character of the ligandsresults in the formation of various polynuclear complexes including the ligand and the imidazole bridgeddimeric species. The most intriguing feature of the coordination chemistry of these ligands is that thedeprotonation of the coordinated imidazole-N(1)H groups results in the appearance of a new chelating site inthe molecules. It leads to the formation of stable trinuclear complexes via negatively charged imidazolatobridges.


Data were examined to determine trends in survival from cancers of the oral cavity and pharynx in Scotland between 1968 and 1987, and to analyse survival rates and the previously noted increases in the incidence of such cancers according to the level of social deprivation. Incidence data on oral cavity and pharyngeal cancer and survival rates following diagnosis were obtained from the Information and Statistics Division of the Common Services Agency for the National Health Service in Scotland, covering the period 1968-92. It was found that survival rates for cancers of the tongue, mouth and pharynx diagnosed among persons less than 65 years of age decreased between 1968-72 and 1983-87. Five year relative survival rates fell from 47% to 39% over this period, while the equivalent rates among persons older than 65 years have shown a modest improvement from 34% to 38%. When considered by level of social deprivation, survival is lower among persons from the most deprived areas, and it is among such persons that the recent increases in occurrence of cancers of the oral cavity and pharynx have primarily occurred. The poorer survival among those from more socially deprived areas, and the evidence that the largest increase in incidence has occurred in such areas may to some extent explain the non-favourable trends in mortality. More importantly it emphasises the potential benefits of targeting such a population for oral health information. An educational campaign should include both information on the risk factors for developing oral cancer, and also the importance of seeking an early professional consultation in the case of symptoms.


A pathological review was carried out on 600 patients with breast carcinoma entered into the 'Nolvadex' Adjuvant Trial Organisation (NATO) study. The tumours were graded histologically and these results were compared with the oestrogen receptor (ER) status of the tumours, the numbers of recurrences and the length of survival of the patients. It was found that histological grading was predictive both in terms of events and survival, and correlates significantly with oestrogen receptor status; within histological grades I and II, patients receiving 'Nolvadex' had fewer events and deaths compared with patients in the control group. For patients with grade III tumours qualitatively it was in the same direction as the benefit obtained in patients with grade I and II tumours.


One hundred and thirteen biopsies of the palate in people accustomed to smoking cigars, most of them with the burning end of the cigar inside the mouth, have been studied.Thirty-eight of these showed mild to severe atypical changes in the epithelium. There were 19 lesions showing orthokeratosis and 53 showing hyperorthokeratosis.The earliest atypical change is seen in the mouths of the ducts of the glands.There were 3 cases showing microinvasive carcinomas.Pigmentation is a prominent feature in these cases.The papules with umbilication could be due to hyperplasia of the mucous glands.It is suggested that stomatitis nicotina occurring in men and women with the habit of reverse smoking is probably precancerous because of the presence of atypical changes in the epithelium and also the finding of 3 microinvasive carcinomas without any macroscopic evidence.There is no acceptable explanation why the soft palate escapes getting either stomatitis nicotina lesion or carcinoma in reverse smokers.


An attempt has been made to reverse cachexia and to selectively deprive the tumour of metabolic substrates for energy production by feeding a ketogenic regime, since ketone bodies are considered important in maintaining homeostasis during starvation. As a model we have used a transplantable mouse adenocarcinoma of the colon (MAC 16) which produces extensive weight loss without a reduction in food intake. When mice bearing the MAC16 tumour were fed on diets in which up to 80% of the energy was supplied as medium chain triglycerides (MCT) with or without arginine 3-hydroxybutyrate host weight loss was reduced in proportion to the fat content of the diet, and there was also a reduction in the percentage contribution of the tumour to the final body weight. The increase in carcass weight in tumour-bearing mice fed high levels of MCT was attributable to an increase in both the fat and the non-fat carcass mass. Blood levels of free fatty acids (FFA) were significantly reduced by MCT addition. The levels of both acetoacetate and 3-hydroxybutyrate were elevated in mice fed the high fat diets, and tumour-bearing mice fed the normal diet did not show increased plasma levels of ketone bodies over the non-tumour-bearing group despite the loss of carcass lipids. Both blood glucose and plasma insulin levels were reduced in mice bearing the MAC16 tumour and this was not significantly altered by feeding the high fat diets. The elevation in ketone bodies may account for the retention of both the fat and the non-fat carcass mass. This is the first example of an attempt to reverse cachexia by a diet based on metabolic differences between tumour and host tissues, which aims to selectively feed the host at the expense of the tumour.


Sir,The study of virulence traits among the bacteria represents an upcoming focus in the field of bacterial pathogenesis, where another serious emerging health concern today is the appearance and spread of resistant bacterial stains. It has bCurrent knowledge on pathogen’s effects on host cell function, induction of secretory pathway that many pathogenic bacteria use to export virulence-related proteins, regulation of virulence genes and identification of these by analysis of bacterial DNA sequence data are the proof of revolution in modern science and advanced technology. It has gAnother important issue that needs serious attention is the understanding of evolution of pathogens, considering their phylogenetic distribution, while the genetic and evolutionary factors that have contributed to their emergence are important to find out spatial virulence. The comparison of spatial virulence worldwide will definitely solve related mechanism of virulence to discover the strategies used by bacteria to subvert immune defences and cause disease. A detail


Murine embryonal carcinoma cells, the pluripotent stem cells of teratocarcinoma were injected simultaneously into caudal and cranial sites on the back of syngeneic recipients in order to determine whether regional anatomical differences affect their take and growth rate and differentiation. The overall tumour take rate was higher in caudal than cranial sites, but the initial weight of tumours was higher in the cranial than caudal sites. Tumours developing in the two anatomical sites grew at the same rate with a linear increase in volume. At the end of the 4-week experimental period the differences in the size of anterior and posterior tumours were negligible and no histological differences were noted between the two groups. Our data indicate that regional factors significantly affect the take rate and the initial growth of this murine teratocarcinoma, i.e. the establishment of solid tumours from injected stem cells. The growth rate of established tumours was not affected by regional factors.


A model has been developed for studying the capability of cells from primary murine mammary tumours to establish colonies in distant organs. The model involves the i.v. inoculation of disaggregated tumour cells into autologous and syngeneic recipients. The results show that the metastatic colonization potential of cells from a given tumour is consistent within the animals of an inoculated batch. Also, the findings are uniform in the autologous host and the syngeneic recipients. Tumours vary in their colonization potential and can be classified in 2 main groups designated high and low. These findings indicate that: (i) cells from 37% of mammary tumours can heavily colonize the lungs when inoculated i.v., even though the incidence of metastatic spread of these tumours in the undisturbed animal is almost zero. Thus, the relative infrequency of spontaneous metastasis from murine mammary tumours is not due to inability of the tumour cells to survive and colonize once free in the blood stream; and (ii) the colonization potential of the tumours is an intrinsic property of the tumour cells rather than of the host, whose prior acquaintance with the cells does not seem to confer resistance to colonization. The model presents opportunities for identification of possible differences between tumours of high and low colonization potential, and is being used to study cellular properties which favour colonization of distant organs by comparison of observations in vitro with the behaviour of cells from the same tumour in vivo.


Oestrous ovis deposits its larvae in the conjunctival eye sac of human. The present paper reports a case study of ocular myasis among sheep farm workers caused by Oestrous ovis. The ocular myasis and the associated mucopurulent conjunctivitis are occupationally acquired in these cases. This study also suggests the treatment of patients and the recovery of the larvae.Ocular myasis and associated mucopurulent conjunctivitis in human eyes is a rare phenomenon. However, if the sheep bot fly abounds and poor hygienic environment prevails, the  Cyclorhapid and Oestridae may produce myasis. The Oestrous ovis, the common sheep bot fly breeds in the nasal cavity and sinuses of sheep. The fly enters the nostrils and deposits its larvae. The larva crawls and reaches the brain cavities, they mature and fall on the ground and become adult. In the sheep farm the standard of hygiene is always very low and there are no techniques adopted to stop the activities of these insects.[In India, agriculture is a major profession. In the agricultural sector, the laborers engaged in field activities may be exposed to several organisms causing zoonotic diseases. The breeding and rearing of sheep or goats is also one such agricultural based activity in India. An unorganized labor force is deputed by the farmers for taking care of animals in sheep farm. These laborers may have the chances of zoonosis due to insects in the vicinity of sheep farm. There has been prevalence of ocular myasis associated with mucopurulent conjunctivitis among these workers. Ocular myasis is due to the infestation of the eye with maggots or bots of certain flies. The infe insects.3 We haveThe present paper describes the case study on the pathology, treatments and associated microbes for the development of mucopurulent conjunctivitis acquired occupationally in the sheep farm workers.Oestrous ovis in eye and eye discharge due to mucopurulent conjunctivitis were the cases examined. The infected eye was observed by ophthalmoscope. The collected discharge namely serous, mucopurulent was analyzed for the presence of pathogens by culture techniques. The bacterial strains isolated and characterized by staining techniques. Antibiotic sensitivity pattern of the organism was studied by Kirby-Bauer method.The sheep farm worker infected with first stage larvae of in question was done by immobilizing with the topical application of 1% xylocaine and grasped with the help of forceps. The diseased eyes were treated with suitable anti-inflammatory drugs and antibiotics determined out of the culture studies.The antibiotics such as garamycin, neomycin, erythromycin, tetracycline, ofloxacin, norfloxacin and sulfacetamide were tested. The recovery and the removal of insect larvae Oestrous ovis. These larvae caused tissue damage over the eye ball and conjunctival sac. The movement of the larvae was affected by the body bristles and barbs [Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas and Moraxella sp. The important observation was the presence of Chlamydiae trachomatis in certain cases.The observation on the infected eyes of cases (workers of sheep farm) through the slit lamp revealed the presence of larvae of nd barbs . There wnd barbs  and 3. FOestrous ovis larvae is associated with mucopurulent conjunctivitis causing eye pathogens. The degree of mucupurulent conjunctivitis depends on the nature of tissue damage caused by the larva. The results of antibiotic disc sensitivity test exhibited the sensitivity to various antibiotics [These results suggested that the infection with ibiotics . Among tOestrous ovis is abound, there may be chances of deposition of larvae in the conjunctival sac of the human eyes. The incidences of ocular myasis associated with mucopurulent conjunctivitis described in the present cases may be occupationally contracted. The erosion of epithelial tissues on the eye ball as well as conjunctival cavity may be prone for the infection of microbes.[The ocular myasis due to the infection of first stage larvae of sheep bot fly associated with mucopurulent conjunctivitis in human eyes is a rare occurrence. However if the sheep bot fly microbes. This is The treatment suggested out of the present study for the recovery and eradication of the conjunctivitis may be curative. The occupationally acquired mucopurulent conjunctivitis among the sheep farm workers may be the first of this kind. It has been known that the activities of the said fly are high in sheep farm. The fly repellents (or) fumigation of insecticides are not very effective. It has been suggested that injection of ivermectin, doramectin or moxidectin into the nostril of the sheep may be effective against the larvae and the control of adult flies.Chlamydiae trachomatis which is recently known for causing blindness.[The significant observation in this context is the presence of lindness. It is de