Metabolic syndrome (MetS) is frequently characterized by elevated liver enzymes, including gamma-glutamyl transferase (GGT) and alanine aminotransferase (ALT). Our objective was to evaluate the range of prevalence of MetS in apparently healthy individuals whose liver enzyme concentrations were all within-normal-range.We have performed a cross sectional analysis on participants of the Tel-Aviv medical center inflammation survey (TAMCIS) recruited between the years 2003-2009. Analyzed were a cohort of 6,561 men and 3,389 women.The prevalence of MetS increased significantly from the first quintile to the fifth for both GGT and ALT, all the five quintiles being in the normal range. Logistic regression analysis for the presence of MetS showed crude odds ratios of 2.7 and 2.4 between the first and fourth quintiles and 3.6 and 3.2 for the fifth quintile in men and women respectively for ALT. For GGT the respective odds being 3.6 and 3.2 for the fourth quintile and 3.9 and 3.4 for the fifth quintile in men and women, respectively.A relatively high prevalence of MetS was noted in a cohort of apparently healthy individuals with liver enzyme concentrations within-normal-limits. Practical consequences include the need to follow up these enzyme concentrations as continuous variables and to take into consideration that even relatively small elevations within the normal range might reflect the presence of dysmetabolism. The metabolic syndrome (MetS) is a constellation of cardiovascular risk factors known to be associated with increased future atherothrombotic events -4. PreviLittle is known however, about the association between the prevalence of the metabolic syndrome among individuals presenting with within-normal-range liver enzymes. To the best of our knowledge, there is only one paper which demonstrated that even 'normal' levels of ALT are associated with the long-term development of multiple metabolic disorders, including the MetS and diabetes mellitus .Since both elevated GGT -18 and AWe have presently analyzed data that has been collected during the last five years in the Tel-Aviv medical center inflammation survey (TAMCIS), a registered data bank of the Israeli ministry of justice -29. ThisResults of the routine health check-up were assessed employing certain definitions in order to recognize atherothrombotic risk factors in individuals. These included diabetes mellitus which was defined as a fasting blood glucose concentration of ≥7.0 mmol/L or the intake of insulin or oral hypoglycemic medications. Hypertension was defined as a blood pressure of ≥ 140/90 mm Hg on two separate measurements or the use of antihypertensive medications. Dyslipidemia was defined as the low density lipoprotein cholesterol (LDL-C) or non-high density lipoprotein cholesterol (non-HDL-C) concentrations, for individuals displaying elevated triglyceride concentrations of > 2.26 mmol/L, above the recommended levels according to the risk profile defined by the updated adult treatment panel III (ATP III) recommendations  or the uAll blood samples were drawn following a 12 hour fasting period. Glucose was measured by the glucose oxidase system . We utilAll data was summarized and displayed as mean (standard deviation [SD]) for the continuous variables and as number of patients (expressed as a percentage) in each group for the categorical variables. Since the triglyceride concentrations displayed irregular distributions, we used logarithmic transformation which converted the distributions to normal ones for all statistical procedures. Therefore all results of triglyceride concentrations are expressed as back-transformed geometrical means. The One-Way Kolmogorov-Smirnov test was used to assess the distributions. In order to characterize the population we divided the patients in each gender into quintiles of each of the two liver function enzymes of relevance, including GGT and ALT, and analyzed all results accordingly. For all categorical variables the Chi-square statistical test was used for assessing the statistical significance between the quintiles, while the One-Way Analysis of Variance was used for all continuous variables. In order to better appreciate the magnitude of the differences in the prevalence of the MetS between the quintiles of the liver enzymes and in order to adjust for differences in age, physical activity, smoking status and use of medications that are not a part of the parameters which define the MetS, we used logistic regression and calculated the odds ratio for having the MetS between the quintiles of each liver enzyme relative to the lower quintile. All above analyses were considered significant at p < 0.05 (two tailed). The SPSS statistical package was used to perform all statistical evaluations .We have presently analyzed the results of a total of 6,561 men and 3,389 women at the mean (SD) age of 44 (11) years. Nine hundred and sixteen men (14%) and 645 women (19%) were characterized as having the metabolic syndrome. Epidemiological data as well as relevant biochemistry for men and women are given in Tables We have presently shown that the MetS is prevalent in individuals who present normal concentrations of liver enzymes. Special attention has been given to two of them (GGT and ALT) for whom epidemiological evidence suggests an association with increased vascular risk. Goessling et al  have recIn our study, we found that the prevalence of the MetS doubles if a comparison is made between the first, second and third quintiles of both GGT and ALT. In these quintiles the concentrations of the enzymes are not only regarded as being absolutely normal, but are actually even in the lower range of the "normal" values. Assuming a link between these enzymes and a potential dysmetabolic state, the finding might suggest a relatively high sensitivity of these biomarkers to reveal the presence of dysmetabolism.Elevated liver enzymes are well documented in individuals with the MetS and are markers of fatty liver changes . To a ceThe present findings are not necessarily of solely theoretical relevance. In fact, the elevations in the concentrations of these liver enzymes might be contributory in the etiopathogenesis of the atherothrombotic inflammatory process. In particular, GGT might have an important role in the extracellular catabolism of glutathione, the principal thiol antioxidant in humans . In addiThe notion that persistently elevated liver enzyme concentrations, even within the so-called "reference" range, is associated with cardiovascular risk factors and future disease has been previously demonstrated . In factWe recognize several limitations in the current analysis. First, our conclusions are of a descriptive nature and are based essentially only on associations between parameters. Based upon its cross sectional design, the present findings are inherently limited in the ability to eliminate causal relationships. Second, since some of the study population had several risk factors, we could not fully eliminate the possible effect of underlying diseases and medications used for these diseases on the present findings. Further prospective population-based studies are needed to investigate the mechanisms in order to answer these questions. Finally, serum GGT is a sensitive indicator of alcohol consumption and/or liver dysfunction such as fatty liver, and is also high in patients with liver disease: chronic viral hepatitis, primary biliary cirrhosis, or drug-induced liver injury. These liver diseases are present in community-dwelling persons and are usually asymptomatic. Thus, these possible confounders could have affected results.We conclude that a relatively high prevalence of the MetS has been noted in a cohort of apparently healthy individuals who have within-normal-limits concentrations of liver enzymes. The relatively high prevalence of the MetS observed could explain, at least in part, the previously noted epidemiological associations between elevated concentrations of GGT and ALT and future vascular risk. Moreover, our findings suggest that even minute changes, still within the so called "normal range" could point towards a potential dysmetabolic state. These observations could therefore lead to avoiding the usage of cut-off values for normalcy for these two biomarkers. In addition, they should encourage the use of both GGT and ALT as continuous biomarkers that could be used for early signaling of dysmetabolism. Finally, our results support the notion that in the era of early detection, prevention and treatment of metabolic disorders, one cannot be confident that relatively low concentrations of liver enzymes exclude the presence of dysmetabolic changes. A practical consequence might therefore be to follow these enzyme concentrations as continuous biomarkers and take into consideration the possibility that even small changes in their concentrations might be of relevance.The authors declare that they have no competing interests.OR and AS have participated in the design of the study, performed the statistical analyses and drafted the paper. SB and IS conceived the study, participated in its design and coordination and helped to draft and review the manuscript. OKB, MC and YV helped in the data organization and retrieval, English editing and final draft preparation. All of the authors have read and approved the final manuscript.


EditorAlterations in the structure and appearance of the nail unit may be seen in association with a variety of dermatological disorders.A 63-year-old woman was referred for the evaluation of a painful enlargement and severe third left finger nail deformity of 2 months’ duration. The lesion started at the dorsal side of the proximal nail fold and migrated distally toward the hyponychium.Clinically, there was a greenish-blue discoloration associated to severe onychodystrophy, massive subungual hyperkeratosis causing uplifting of the nail plate and partially onycholysis at the distal phalanx .The woman was otherwise in good general health, and there was no involvement of other skin areas. A fungal infection of the area was excluded by examination of a potassium hydroxide preparation. Complete general physical and mucocutaneous examination was done. Laboratory evaluation was within normal limits. The patient refused the nail biopsy. The risk of scarring and injuring the nail matrix was unacceptable to her.Ultrasonography US;  with verNail psoriasis can create diagnostic difficulties and may remain undiagnosed for a long time. It occurs in 10% to 50% of psoriasis patients, particularly those with arthritis, and about 1% to 5% of patients manifest nail changes alone.2This is the category of patients in whom the clinician faces a formidable diagnostic challenge because psoriatic nail disease resembles other causes of dystrophic nails. Nail morphology in psoriasis depends upon the anatomical location of the disease process.3The chief complaint of patients with psoriasis is the unsightliness of nails. They also battle lowered self-esteem, feelings of being socially isolated, and the stress associated with the unpredictable intervals of flaring disease and spontaneous remissions leading to significant disfigurement and disability. It is an often persistent disease and frequently refractory to treatment. Topical treatments are barely effective, and possible side-effects of systemic treatments limit their usefulness in uncomplicated nail psoriasis.In our patient, the personal and family history, clinical examination, the X-ray film, dermatological sonography and a strict clinical follow-up led us to make the right diagnosis, thereby avoiding the biopsy. Dermatological sonography of soft tissues should be done more widely for the evaluation of nail psoriasis.


Transient osteoporosis of hip is a condition of unknown etiology, presenting as painful limping, and characterized by osteopenia of the involved joint without preexisting disease or immobilization. Most of the cases were reported in middle-aged men, and one-third of the cases develop in women in the third trimester of pregnancy. The hypothesis that this condition leads to avascular necrosis of the hip has been disproved by various reports and hence does not warrant any surgical interference. This is a self limiting condition, which needs regular follow-up. The authors report a case of migrating transient osteoporosis of the hip in a 30-year-old man successfully treated with antiresorptive treatment. Transient osteoporosis of hip (TOH) or bone marrow edema syndrome (BMES) is a condition of unknown etiology, though many unproved theories have been proposed, affecting women in the third trimester of pregnancy and middle-aged men. The condition is often self-resolving with conservative management, though there are reports of fracture neck of femur and recurrent episodes.21211A 30-year-old man was seen in the Orthopaedic clinic with pain left hip after prolonged traveling. He was of moderate built and had no significant medical history and was not on any medications. He was not addicted to alcohol and never smoked. There was terminal painful restriction of flexion and abduction.He had no neurological deficit, and there were no signs related to the lumbar disc prolapse. X-rays of the pelvis done on initial presentation were normal. Blood parameters including C-reactive protein, ESR, and liver function tests were normal. Clinically, he was found to have normal hormonal function, and his thyroid function tests were also normal. Ultrasound scanning of the abdomen was normal and didn't show hepatomegaly. Ultrasound scanning of the left hip revealed normal study. He was advised non-weightbearing on the left hip. Further review in 2 weeks the X-rays showed osteopenia of the head and neck of left femur, and the diagnosis of transient osteoporosis of the hip (TOH) was thought of and MRI was done. MRI showed marrow signal abnormality , which was extending in the femoral head and neck till the intertrochanteric region Figures .There was minimal effusion in the hip as well. He was subjected to a Tc99 methylene diphosphanate bone scan, which showed increased uptake in the left hip and knee joints. He was managed by non-weightbearing on the left leg and analgesics (diclofenac sodium slow release 100 mg tablets). The patient became asymptomatic after 4 months of treatment and remained symptom-free for 14 months.After 14 months of presentation, he developed pain in his right hip, with terminal restriction of range of movements. X-rays of the hip done this time showed osteopenia of the right proximal femur. Repeated MRI scan showed the same findings as in the previous MRI, with abnormal signal intensities but sparing some parts of the head of femur inferomedially. The previously affected left hip was found normal in this MRI Figures .The patient was started on calcitonin nasal spray and alendronate (Fosamax 70 mg tab once weekly). Calcitonin was initiated for 6 weeks and the oral weekly bisphosphanates were given for 3 months. The symptoms resolved this time within one month of starting the antiresorptive treatment. Follow-up at one year showed complete resolution of the osteopenia and the patient was symptom-free.First described by Curtiss and Kincaid in 1959 as transitory demineralization of the hip in pregnancy, TOH is a self limiting condition, which resolves without leaving any residual effects.34The presentation in the hip is dull aching pain in the hip progressing over a period of time, with terminal limitation of movements. Hip is classically involved, but there are reports of involvement of the knee, ankle, and the foot.10The clinical and radiological features are evaluated in three phases. Phase one, which lasts for 1–2 months, when there is increasing hip pain. The next phase, which shows osteopenia in the proximal femur, lasts for 2–3 months and clinical symptoms becomes more predominant. The third phase, which extends to 6 months, after emergence of the symptoms starts to regress.1315Many theories are proposed, including endocrine dysfunction, local compression of the vessels, and nerves by the gravid uterus,Initial X-rays are most of the times normal because it takes time for the osteopenia to develop. Characteristic radiographic findings are present within 4–8 weeks after onset of symptoms. There is often a delay in diagnosis as the X-rays are normal in the initial period but if suspected an MRI can confirm the diagnosis. Once the disease progresses, the proximal femur including the head and neck up to the intertrochanteric area gets demineralized with preserved joint space.16MRI is diagnostic and excludes other causes of hip pain in the adult. MRI shows characteristic features of bone marrow edema as early as 48 hours after the onset of pain.51819T1-weighted images show ill-defined area of decreased signal intensity when compared with normal intensity of the normal bone marrow in the proximal femur. In T2-weighted images increased signal intensity was observed.18The MRI appearance of TOH was first described by Bloem.20Radiological appearance of TOH and AVN may be strikingly similar,It is possible to differentiate TOH and AVN of head of femur from the plain X-rays and MRI. In TOH, there is diffuse osteopenia of the entire femoral head and neck, without articular erosion or subchondral collapse, unlike in AVN, where the appearance is of mottled radiolucent area surrounded by an area of sclerosis. There is segmental involvement in the anterosuperior subchondral area of the head of femur in AVN.1518517The mainstay of treatment is conservative with protective weightbearing, to prevent pathological fractures.1214421Oral, intravenous bisphosphanates and calcitonin have been used by various authors with beneficial effects.129101011et al.Varenna Core decompression has been performed to prevent progression to osteonecrosis since many authors thought TOH as a precursor of avascular necrosis of head of femur,517Complete resolution takes 2–24 months as per various reports.191121et al.,TOH may have migratory features and both regional migratory osteoporosis (RMO) and TOH are considered part of the same spectrum.26TOH should be considered in the differential diagnosis of painful limping in men and properly treated to prevent development of the disease in the contralateral hip. The authors report a case of migrating TOH after complete resolution in the previously affected side, successfully treated with antiresorptive measures.


The literature rarely describes putaminal haemorrhage producing pure spinothalamic sensory deficit. Here reports a case of putaminal haemorrhage in which selective impairment of the spinothalamic sensory modality was due to the compression of the hematoma.A 57 year old hypertensive man presented with a pure sensory stroke(PSS), and CT scan showed a putaminal haemorrhage. The clinical course was characterized by rapid resolution of the deficits.This case illustrates this rarely of PSS from compression of putaminal haemorrhage of good functional and vital prognosis, and stresses the value of CT scanning for diagnosis and prognosis. Pure sensory stroke is a well-defined clinical entity in which hemisensory symptoms predominate without other major neurological signs . Most paA 57-year-old man with a history of hypertension and cerebral infarction was admitted due to suddenly of numbness on his right hand, arm, leg, and face. He had no headache, vomiting, and other symptoms. On admission, his blood pressure was 180/100 mmHg. He was alert with normal cranial nerves, motor functions, and speech. There was decreased touch and pinprich sense in the right half of his body that worsened in the lower extremity. Position and vibration sense were normal in the right fingers and toes, and stereognosis and graphesthesia were normal. The deep tendon reflexes were normal, and plantar reflexes were flexor. Coordination was intact bilaterally. Routine laboratory tests were normal. Brain computed tomographic scan showed a small hematoma in the left putaminal region occurring in the territory of the posterior branches of lateral lenticulostriate arteries, the area of decreased attenuation surrounding the hematoma represents edema and the posterior horn of the lateral ventricle compressed Fig . No blooHiraga et al  describeThis case illustrates this rarely of PSS from compression of putaminal haemorrhage of good functional and vital prognosis, and stresses the value of CT scanning for diagnosis and prognosis.PSS: Pure sensory stroke; CT: Computed tomographic scan; IV: Intra venousWritten 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 Editor-in-Chief of this journal.The author declares that he has no competing interests.


The inter-hospital transfer of patients is crucial to a well functioning trauma system, and the transfer process may serve as a quality indicator for regional trauma care. However, the assessment of the transfer process requires high-quality data from various sources. Prospective studies and studies based on single-centre trauma registries may fail to capture an appropriate width and depth of data. Thus the creation of inclusive regional and national trauma registries that receive information from all of the services within a trauma system is a prerequisite for high quality inter-hospital transfer studies in the future. In a recent article published in the Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, Professor Katsaragakis and colleagues depict patient flow through what they describe as a non-trauma-system setting in Greece . Their sInclusive trauma systems define roles for all levels and types of health care facilities and personnel that provide care for trauma patients from the scene of injury to rehabilitation. During the last decades of the 20th century, several studies reported increased survival rates after the creation of such dedicated trauma systems [The development of a dedicated trauma system to deal effectively with severely injured patients was initiated in the early 1980's, with the American College of Surgeons (ACS) playing a leading role . The tra systems . A numbe systems -7.The demand for cost reduction and centralisation of advanced health care services has lead to a shift of specialist resources and severely injured patients away from local hospitals towards regional centres and university hospitals. The local hospital has become a potentially hazardous diversion for major trauma patients, thereby necessitating safe and efficient pre-hospital triage and inter-hospital transfer procedures.Organised trauma systems with dedicated trauma centres ensure (at least in theory) that patients in need of specialist resources are brought directly to an appropriate level of care. However, not all injured patients should be brought directly to a trauma centre, and the quality of care prior to reaching the trauma centre may have significant impact on patient outcome . DespiteThroughout the logistically complicated inter-hospital transfer, the patients' wells being relies on optimal inter-disciplinary communication, cooperation and transition of care. The intended positive effect of dedicated trauma systems on patient outcomes might vanish due to suboptimal triage or a lack of routines and competence causing unfavourable treatment delays. Consequently, the inter-hospital transfer process is crucial to the system's efficiency and should be investigated accordingly. The development of performance measures for emergency medical systems have been called for and the appropriateness of triage and transfer processes has been suggested as quality indicators of trauma systems ,10.The North-American trauma research has evolved from expert panel studies, towards trauma registry-based analyses and population-based studies. Administrative registries are designed for purposes other than research and have been criticised due to their lack of important clinical information . Trauma To assess the management of patients who are transferred within a trauma system and to compare their outcomes with other groups of patients without selection bias, investigators must have extensive access to information. Data must be collected from the pre-hospital emergency medical services, the local hospitals, the transferring units and the receiving trauma centres within a region. Further, investigators must be able to track individual patients through these various components that make up the trauma system. A single-centre based trauma registry will therefore struggle to provide all necessary data, making investigators dependent on additional data collection. The aforementioned study from Greece illustrates this limitation. The study is based on prospectively gathered data that was collected to assess the feasibility of developing a national Greek trauma registry . With 40ad hoc documentation process may lead to an unacceptable quality of the gathered data.To our knowledge there are few examples of studies that successfully avoided these limitations. In Oregon, a state-wide trauma registry allowed a population-based study of survival as a function of being transferred to higher level of care . In the So, we are back to the established trauma registries. Using the terms of Dreyer and Garner , we woulThe authors declare that they have no competing interests.HML has had the original idea for the article and has been responsible for the overall outline of the manuscript. HML, TK, MR and KGR have all contributed with literature search as well as original and independent parts of the manuscript. TK has revised and submitted the manuscript. All authors have proof read and accepted final draft of the manuscript.


Dislocation of the shoulder is the commonest of all large joint dislocations. Inferior dislocation constitutes 0.5% of all shoulder dislocations. It characteristically presents with overhead abduction of the arm, the humerus being parallel to the spine of scapula. We present an unusual case of recurrent luxatio erecta in which the arm transformed later into an adducted position resembling the more common anterior shoulder dislocation. Such a case has not been described before in English literature. Closed reduction by the two-step maneuver was successful with a single attempt. MRI revealed posterior labral tear and a Hill-Sachs variant lesion on the superolateral aspect of humeral head. Immobilisation in a chest-arm bandage followed by physiotherapy yielded excellent results. The case is first of its kind; the unusual mechanism, unique radiological findings and alternate method of treatment are discussed. Luxatio erecta[Shoulder dislocations account to 45% of all large joint dislocations. Inferioio erecta,5-7. Its40 year old male athlete presented to the Emergency Department with pain and inability to move right shoulder. His right arm was locked in abduction of 135 degrees. The injury occurred when the patient hyperabducted his arms during a high-jump and presented with the characteristic overhead-abduction of the arm. Examination revealed loss of contour of shoulder, prominence of acromion and presence of subacromion sulcus laterally. Humeral head was palpable in the axilla. There were no neurological deficits. Brachial and radial pulses were palpable. Surprisingly, following analgesia, the patient could rest the arm at less than 90 degrees on a table Figure .Detailed history revealed a similar episode of locking of the arm in the abducted position three years before while playing volleyball. However with manipulation by self, the shoulder reduced and pain subsided. General examination revealed features of generalized ligament laxity. Anteroposterior Figure  and modiUnder general anesthesia, on repeat examination, the humeral head was still palpable in the axilla and not anteriorly in the shoulder. Closed reduction was carried out based on the two-step maneuver described by Nho et al.Patient is positioned supine under sedation or anesthesia. The operator stands on the affected side, by the side of the arm Figure . One armThe proximal hand is placed on the lateral aspect of arm to adduct it against the body, while the other hand holds the forearm and externally rotates the arm Figure . The humPost-reduction radiography Figure  demonstrTrue inferior dislocation of the shoulder was first described in non-traumatic disorders such as septic arthritis, stroke and other neuromuscular disorders. EffusioTwo mechanisms of injury have been described for luxatio erecta - direct and indirect,11. In tSonanis et al first reTraumatic true inferior dislocation is also possibly a hyperabduction injury as both patients described so far and the present case all experienced hyperabduction moment of the arm during the injury. Due to the violent abduction force, the proximal humerus is levered over the acromion and the humerus comes to rest in abduction in such a way that the inferior glenoid rim is impacted on the superolateral aspect of the humeral head in the region of the anatomical neck of humerus. Following analgesia and with reduction of muscle spasm, the humeral head gets levered over the inferior glenoid rim and comes to rest in the infraglenoid region in an adducted position. The impingement of head of humerus over inferior glenoid rim results in a bony defect on the superolateral aspect of humeral head. With higher abduction forces, the proximal shaft of humerus comes to rest in apposition to the inferior glenoid rim. The arm in such patients is always locked in abduction and does not change unless manually reduced.The adducted position of the arm in the present report should not mislead the treating orthopedician to the diagnosis of an anterior dislocation. Attempt to reduce such dislocations by traditional methods for anterior dislocation may result in further trauma. Both the patients described before presented with an adducted arm mimicking anterior dislocation and underwent reduction by the scapulohumeral maneuver developed by Sonanis et al. Nho et al developeMRI revealed a variant Hill-Sachs lesion in the superolateral aspect of humeral head and posterior labral tear. Davids and Talbott describeWe present a case of post-traumatic recurrent luxatio erecta humeri, that later transformed unusually to the adducted posture, reduced by the 'two-step maneuver'. The maneuver was successful with single operator, single attempt and minimal manipulation. Closed reduction and immobilisation followed by range of motion exercises resulted in full shoulder function. The mechanism of this subset of inferior shoulder dislocation is different. The bony lesion on the superolateral aspect of humeral head, possibly called a 'cross' Hill-Sachs lesion due to its anatomical relation to the classic Hill-Sachs, appears to be characteristic of inferior glenohumeral dislocation.Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.SS - Patient recruitment, treatment, acquisition of data and interpretation of dataSS, DKA, DKP, JM - Treatment and revising the paper critically for important intellectual content. All authors have read and approved the final manuscript.


The proposed biosynthetic pathways to ladder polyethers of polyketide origin and oxasqualenoids of terpenoid origin share a dramatic epoxide-opening cascade as a key step. Polycyclic structures generated in these biosynthetic pathways display biological effects ranging from potentially therapeutic properties to extreme lethality. Much of the structural complexity of ladder polyether and oxasqualenoid natural products can be traced to these hypothesized cascades. In this review we summarize how such epoxide-opening cascade reactions have been used in the synthesis of ladder polyethers and oxasqualenoid natural products. Marine polyether natural products, polycyclic molecules of marine origin with regular occurrence of multiple C-O-C motifs, include the distinct families of the ladder polyethers and the oxasqualenoids. Members in both of these families exhibit biological activities ranging from potentially therapeutic properties to extreme lethality. They have received attention from diverse scientific communities owing to their involvement in harmful algal blooms, their devastating effects on marine ecosystems and the industries that depend on their continued health, their impact on public health in coastal areas, their beneficial properties that make them useful probes of protein structure and function, and, in recent years, to their potential to treat the symptoms of cystic fibrosis.via all-endo cascades of epoxide openings , and the application of these reactions to the synthesis of ladder polyethers and oxasqualenoids. The material is organized by the size of the rings that are formed in epoxide-opening cyclizations, tetrahydropyrans and oxepanes. A further distinction is made between the approaches developed for control of regioselectivity in epoxide-opening reactions, i.e., those that rely on electronically biased epoxides and those in which the epoxides may be considered to be electronically unbiased.In this review we provide a summary of various approaches to achieving trans-syn-trans arrangement  or all- polyepoxide. It was consequently suggested that a single promiscuous monooxygenase might be sufficient for all alkene to epoxide oxidations in the biosynthesis of a ladder polyether . T. T125]. Although disappearing directing groups address problems related to the removal of substituents not present in the natural targets, these reactions suffer from the inability to incorporate the methyl substituents found occasionally at the ring junctions of ladder polyethers.endo selectivity in intramolecular epoxide-opening reactions has been approached by several research groups. The first attempt to perform a cascade reaction that does not rely on the effects of directing groups and incorporates only disubstituted epoxides was reported by Murai . I. I163 un228, 229, 231 and 232  complex 239 to the kinetic resolution of 4,5- and 5,6-epoxy alcohols  established that the absence of Lsd19 in the ΔlasB mutant causes a complete switch from the production of lasalocid A in S. lasaliensis to the production of isolasalocid in the ΔlasB mutant [While the work of Leadlay on the biosynthesis of monensin A provided substantial evidence in favor of the Cane-Celmer-Westley proposal , final, in vitro . These sB mutant .With many challenges remaining in the field of epoxide-opening cascades and exciting opportunities in related areas that have not been extensively researched, future progress can be foreseen. The investigations of epoxide-opening cascades in synthesis and those that are proposed to happen in nature will require collaborative efforts of chemists and biologists.


This review deals with the various mechanisms, and possible pharmacological interventions for the prevention of cataract. The article also reviews research on potential anticataractous agents, including aldose reductase inhibitors, glutathione boosters, antiglycating agents, vitamins and various drugs from indigenous sources.Cataractous-opacification of the lens is one of the leading causes of blindness in India. The situation can be managed by surgical removal of the cataractous lens. Various pharmacological strategies have been proposed for the prevention and treatment of cataract. Information on possible benefits of putative anticataract agents comes from a variety of approaches, ranging from laboratory experiments, both  Cataract remains the leading cause of visual disability and blindness worldwide. It is esSeveral risk factors have been identified in the pathogenesis of senile cataract. Apart from aging, smoking, diabetes, gender, steroids and nitric oxide are responsible for the development of cataract. These risk factors have been associated with different morphological types of cataract.Smoking is thought to increase the risk of cataract, at least in part, by increasing the oxidative stress in the lens caused by the generated free radicals. In the presence of tobacco smoke these free radicals may directly damage lens proteins and the fiber cell membrane in the lens.7 TobaccoThere are several ways that diabetes can affect the eyes but the most common cause of loss of vision is cataract. Cataractogenesis is one of the earliest secondary complications of diabetes mellitus, a severe metabolic disorder characterized by hyperglycemia. Some mecA number of epidemiological studies using cross-sectional data have shown an increased prevalence of cataract in women compared with men. The causThe association between steroid use and development of cataract is well established. There seems to be a consensus that higher the dose of steroid and longer the duration of use, the higher will be the risk for posterior subcapsular cataracts. Steroids2− in itself is not highly toxic but it may react with other molecules yielding more reactive compounds. For example, the reaction with nitric oxide (NO) generates peroxynitrite (ONOO−), which causes extensive cell damage and can also have an important role in diabetic cataract formation.[Oormation.15Apart from the above mentioned risk factors, genetic factors, socioeconomic status, illiteracy, malnutrition, diarrhea, myopia, renal failure, hypertension, sunlight, ultraviolet (UV) exposure, obesity, chemical burn, glaucoma and alcohol17 have aLoss of transparency during human cataract formation results from a variety of complex metabolic and physiological mechanisms, which act in combination to change the refractive index. Studies Among the multiple mechanisms proposed for cataractogenesis this article explains the role of the following pathways in cataract development.Non-enzymatic glycationOxidative stressPolyol pathwayUnder hyperglycemic conditions, part of the excess glucose reacts non-enzymatically with proteins or other tissue or blood constituents, thus increasing the physiological rate of non-enzymatic glycation. Chronic,Specific chemical characterization of AGE proteins has been difficult, as Amadori products can theoretically undergo a large number of potential rearrangements. Immunological and chemical evidence indicates that progressive accumulation of AGEs in the diabetic eye lens contributes to accelerate cataractogenesis in hyperglycemic experimental animals and diabetic humans.22The osmotic and exogenous or endogenous oxidative stresses play an important role in the pathogenesis of cataract. Oxidativ2426The mechanism involved in the progression of diabetic cataracts is different from senile cataracts. The accumulation of polyols within the lens is the primary contributing factor. Certain tissues of the body, including the eye lens, do not require insulin for glucose and other simple sugars to enter. In diabetes, sugar is in high concentration in the aqueous humor and can diffuse passively into the lens. The enzyme aldose reductase within the lens converts glucose to sorbitol or galactose to galactitol . These pin vitro, in vivo and in epidemiological studies may be broadly classified in the following categories:Drugs have been developed which are aimed to interact at the level of altered lens metabolism and lens pathophysiology. The anticataract agents claimed to be effective Aldose reductase inhibitorsNon-steroidal anti-inflammatory drugsAgents acting on glutathioneVitamins, minerals, antioxidants and herbal drugsMiscellaneous agentsARI are aimed to block the metabolic pathways of glucose responsible for diabetic vascular dysfunction. Their role in the prevention of diabetic cataract in animals is now well established.29 Numeroin vitro animal lenses incubated in high-sugar mediums have found flavonoids to inhibit aldose reductase.[G. applanatum.[Flavonoids are among the most potent naturally occurring ARI. Several evaluations of eductase.32 In oureductase. The flaveductase. A recentplanatum.et al., demonstrated that administration of pyruvate prevented cataract development by inhibiting the AR in diabetic rats.[Emblica officinalis was investigated and found to be better than quercetin.[Gymnema sylvestre showed potential AR inhibition in sugar-induced cataract and also protected the lens from osmotic damage.[A recent study by Varma tic rats. The AR-iuercetin. Similarluercetin.39 The aqc damage.Among the ARI only sorbinil reached the advanced clinical trial stages in cataract prevention program. However, due to manifestation of skin rashes the trial had to be discontinued. In spite of extensive research input, clinical trials of the sorbitol-lowering agents have not produced convincing proof of their efficacy.Non-steroidal anti-inflammatory drugs (NSAIDs) have emerged as another group of drugs with anticataract potential. The first indication regarding the probable use of NSAIDs as prophylactic anticataract agents came from studies on aspirin use in patients with rheumatoid arthritis and diabetes. SubsequeIn vivo effectiveness of naproxen has also been tested in rat pups developing cataracts under oxidative influence of sodium selenite.[We have earlier shown that naproxen delays the onset and progression of galactose-induced cataract in rats. In vivo selenite. To eluciselenite. It was aselenite. Comparatselenite. The hypoAnticataract activity of aspirin, sulindac, and naproxen eye drops was also studied and they were found to delay both onset and progression of cataract in different models of cataractogenesis, moreover, there were no adverse side-effects even after long-term application. Subsequein vitro and in vivo.[Bendazac, a compound resembling indomethacin in its structure, emerged as a potential radical scavenger and anticataract agent. Bendazac protects lens and serum proteins' denaturation  in vivo.52 5-hydr in vivo. Another  in vivo. Bendazac in vivo. Bendazac2 O2.The most important function of glutathione (GSH) is to deactivate and render excess free radicals and keep them harmless. GSH is composed of the amino acids cysteine, glutamic acid, and glycine, and its synthesis within the lens takes place in two ATP-dependent steps . There aThe concentration of GSH decreases with age in the lens and more markedly in cataract. GSH has 5Clinical trials on Phaken, a preparation containing three constituents of amino acids GSH plus arginine, inostitol, pyridoxine and ascorbic acid have shown to improve visual acuity, but due to a high dropout rate no clear-cut conclusions could be drawn.In vitro evaluations of surgically removed cataracts have confirmed inactivity of glutathione reductase enzyme activity in a significant number of cataracts examined.[The potential role of vitamins in preventing cataract is well documented, especially vitamin C or ascorbic acid which plays an important part in lens biology, both as an antioxidant and as a UV filter. Dietary 58examined. Furthermexamined.The excessive free radical attack implicated in the development of cataract can be prevented by dietary intake of micronutrients such as zinc, copper and manganese. Copper and zinc are required for the catalytic activity of metal protein and SOD. Plasma lIt is widely accepted that oxidative stress is a significant factor in the progression of cataractogenesis.–74 OxidaCarotenoids are natural lipid-soluble antioxidants. It is reported that persons with a high intake of carotene reduce the incidence of risk of cataract and the in vitro and in vivo.[Curcumin, the active principle of turmeric, has been shown to have antioxidant activity  in vivo. The effe in vivo. and stre in vivo. Curcumin in vivo.in vitro it was found to protect bovine serum albumin against glycol-oxidative damage.[Numerous studies proved stobadine, a novel synthetic pyridoindole, to be an efficient antioxidant and in ve damage. Stobadine damage.In recent years, a great emphasis has been laid on exploring the possibility of using our natural resources to delay the onset and progression of cataract. A great number of medicinal plants and their formulations are reported to possess antioxidant properties and offer protection against cataract.et al., have shown that the aqueous extract of Ocimum sanctum possesses potential anticataract activity against oxidative stress-induced experimental cataractogenesis. The protective effect was supported by restoration of the antioxidant defense system.[Pterocarpus marsupium and Trigonella foenum-graceum exerted a favorable anticataract effect.[Emilia sonchifolia modulate the lens opacification and oxidative stress in selenite-induced cataract.[Dregea volubilis is a traditionally used medicinal plant for the treatment of various eye ailments; now its potential anticataract effect has been proved scientifically and it has also been found that the effect is due to drevogenin D, a triterpenoid aglycone.[Vaccinium myritillus or bilberry also has a long history of use for various eye conditions.[Gupta e system. The aquet effect. A recentt effect. Flavonoicataract. Dregea vaglycone. Vacciniunditions. In a clinditions.Ginkgo biloba extract have been found to possess potential therapeutic effect in radiation-induced cataract.[Camellia sinensis) has been studied extensively and the explained antioxidative potential is the major mechanism in the prevention of cataractogenesis. Gupta et al., have shown that green tea protects against selenite-induced cataract and acts primarily by preserving the antioxidant defense system.[E. officinalis, commonly known as amla, used against diabetes, is also effective in delaying the progression of diabetic cataract.[Certain herbal drugs, especially cataract. The antie system. It was ae system. Recentlye system. A recentcataract.Gymnema sylvestre, which is one of its constituents.[The herbal formulation Diabecon  inhibited the sugar-induced lens opacity in organ culture and also demonstrated that the effect is mainly due to tituents. A study tituents.Various substances with diverse chemical structures and properties have been found to have protective effect against cataract in different experimental models. A study was conducted with pyruvate, a compound of metabolic origin and possessing an alpha-keto-carboxyl group. It was found effective in delaying cataract formation in diabetic as well in vitro and found to offer significant protection. The study concluded that the effect might be because of the antioxidant and free radical scavenging activity, as evidenced by a decrease in malondialdehyde in the treated lens.[ACE inhibitors have found to afford protection from free radical damage in many experimental conditions. Recentlyted lens.in vivo universal antioxidant because of its ability to protect against oxidative stress in the lipid phase of biological cellular membranes and in the aqueous environment by a gradual intraocular turnover into L-carnosine. The clinical effects of a topical solution of Can-C on lens opacities were examined in patients with cataracts and in canines with age-related cataracts. These data showed that N-acetylcarnosine is effective in the management of age-related cataract reversal and prevention both in human and in canine eyes.[N-acetylcarnosine  has been found to be effective in the prevention and treatment of age-related cataracts. It protects the crystalline lens from oxidative stress, and in a recent clinical trial it was shown to produce an effective, safe and long-term improvement in sight. When Can-C is administered topically, N-acetylcarnosine functions as a time-release prodrug form of L-carnosine, resistant to hydrolysis with carnosinase. N-acetylcarnosine has potential as an ine eyes.Protective effect of alpha lipoic acid, pantethiStudies on anticataract drugs are advancing on a number of fronts and a few drugs have reached the stage of clinical trials. Various groups are also trying to investigate the anticataract effect of drugs from natural and synthetic origin. Our preliminary studies have shown encouraging results on the use of a special combination of a few antioxidants and herbal drugs. It seems likely that some of these compounds will be shown in future to be effective in delaying or slowing the development of cataract.in vitro and in vivo studies of vitamins, minerals, herbal drugs and nutritional supplementation in the prevention and treatment of cataracts. Although there are several drugs that may have potential for the treatment of cataract, most studies are merely preliminary. However, larger and prospective clinical studies on the use of nutrients and herbal drugs for the treatment of cataract are needed. Similarly, the possibility of toxicity associated with long exposure to most of the drugs limits this intervention. There are positive reports on topical use of these drugs with no or minimum side-effects. A prevention or delay through such an application in humans will prove to be a significant achievement against the cataract blindness in the world.Much research has been done on epidemiological,


Cigarette smoking has been implicated as an important risk factor for the development of respiratory symptoms in adults. The relationship of dyspnea with cigarette smoking has been examined in smokers and ex-smokers and the beneficial effects of smoking cessation have been demonstrated. Recent studies reported that in subjects who smoke cigarettes the risk of developing respiratory symptoms is higher in a dose-dependent way. Environmental tobacco smoke heavily influences the incidence of respiratory symptoms in both adults and in children. Up to the present time, the mechanisms whereby cigarette smoking causes dyspnea perception remain to be defined. Abnormalities in sensory nerves might diminish the perception of bronchoconstriction in smokers. In this regard, it has been postulated that prolonged exposure to cigarette smoke may lead to chronic depletion of sensory nerve neurotransmitters. Eosinophil airway inflammation has been proposed as a determinant of breathlessness via mechanisms affecting either the mechanical pathways that control breathlessness or the afferent nerves involved in perception of dyspnea. An increased number of eosinophils in some smokers implies the possibility that smoking may trigger immunological or other reactions associated with eosinophilia. In conclusion, cigarette smoking is by far one of the greatest risk factors for most respiratory symptoms, including dyspnea. Smoking is associated with the development of symptoms in a dose-dependent way and eosinophilia and airway hyperresponsiveness (AHR) increase the risk of developing dyspnea. The mechanisms responsible for inter-individual differences in dyspnea perception are difficult to clarify due to the wide variation in the perception of breathlessness present in normal subjects  in whom Cigarette smoking has been implicated as an important risk factor for the development of respiratory symptoms in adults . On this1, they have fewer symptoms than consistent smokers who reported more dyspnea at the last survey [Data were similar for male and female subjects. The results of the symptom-analysis of both the initial and last surveys would suggest that although restarters have the steepest rates of decline in FEVt survey . This mit survey . More ret survey   in smoking asthmatics [Neutrophilic airway inflammation and release of neutrophil chemoattractant cytokines, including IL-8, have been observed to be associated with smoke exposure, with sputum IL-8 concentration being related to percent-predicted forced expiratory volume in 1 second . Smoking cessation was shown to have a positive impact on growth of pulmonary function. Young smokers without respiratory symptoms experienced the same longitudinal changes in FEV1 as non-smokers [The presence of respiratory symptoms has been examined as a marker of susceptibility to the detrimental effect of smoking on respiratory function. In an analysis from the Tucson study of data on the growth of pulmonary function between 5.5 and 25 years of age, symptoms and smoking had a negative impact on growth of lung function, using FVC, FEVInterestingly, the habit of smoking may influence dyspnea perception also in fibrotic diseases. De Cremoux and colleagues  examinedIn summary, cigarette smoking is by far one of the greatest risk factors for most respiratory symptoms, including dyspnea. Smoking is associated with the development of symptoms in a dose-dependent way and eosinophilia and AHR increase the risk of developing dyspnea. In short, further studies are necessary in order to establish the exact interaction between cigarette smoking and airway inflammation with dyspnea perception.The authors declare that they have no competing interests.


Although the use of prophylactic granulocyte colony-stimulating factor (G-CSF) in conjunction with myelosuppressive chemotherapy is supported by clinical research evidence and advocated by international clinical guidelines when the consequent risk of febrile neutropenia exceeds 20%, there remains doubt as to the cost-effectiveness of the practice. There are limited economic data, and the data that are available are not necessarily applicable to the management of breast cancer in a European setting. Much of the available evidence on G-CSF in the management of febrile neutropenia is partial, focusing primarily on direct costs to the health service – that is, those related to hospitalisation and drug treatment. A full assessment of the cost effectiveness of G-CSF prophylaxis needs to take account of both costs and outcomes, including mortality, quality of life and patient functioning. As febrile neutropenia has been shown to affect productivity, consideration should also be given to quantifying the indirect costs of neutropenia. Although the rate of breast cancer has increased in recent decades, patient survival has improved largely as a result of effective chemotherapy regimens (Use of granulocyte colony-stimulating factors (G-CSFs) is increasingly being recognised as a means of managing FN without resorting to chemotherapy dose reductions , and itsHowever, there are concerns about the financial implications of the widespread use of G-CSF in early-stage breast cancers  and indirect costs (those incurred by the patient and caregivers). Estimates of the direct costs of managing FN vary substantially. They depend on various factors, including the care setting, the particular cancer and the severity of the episode. Studies from the United States tend to report higher costs than do those from Europe.In a retrospective study from Spain, the estimated cost of FN was €3519 (∼£2360) per episode .Analysis of more than 24 000 patients hospitalised with FN in the United States, conducted as part of an economic evaluation of G-CSF  suggests that the economic case may be less convincing in European settings, because of the lower cost of managing FN episodes. However, as stated earlier, the cost of managing FN has been found to differ across malignancies, and therefore the relevance of this evidence to breast cancer is uncertain.In the United Kingdom, the cost of G-CSF prophylaxis during breast cancer chemotherapy has been estimated at £3100–£5900 per patient, for six cycles .Thus, on the basis of direct costs alone, prophylaxis may not compare favourably with the cost of managing an episode of FN as discussed above . However, this crude financial calculation takes no account of the indirect costs of FN, as well as the benefits of prophylactic treatment in terms of avoiding neutropenic episodes and the resultant impact on the individual patient's mortality and quality of life. A full economic evaluation of prophylactic G-CSF should capture both the direct costs  and consider the indirect costs . A broad perspective that takes account of the full range of costs associated with FN would likely lead to a more favourable conclusion for primary prophylaxis.Best practice guidelines from both North America and Europe recommend selective use of G-CSF for primary prophylaxis of FN. There is consensus across the guidelines, which recommend G-CSF for individuals whose risk of FN exceeds 20%.There is only limited economic evidence for the cost effectiveness of implementing this recommendation, and a great deal of variation between findings from studies in the USA and Europe because of differences in the estimated cost of managing an episode of FN. Further research evidence is needed to allow accurate estimation of the costs of managing FN specifically in patients with breast cancer, in Europe, which seeks to capture the direct, indirect and intangible costs associated with FN. Such research will help to determine the most economically advantageous positioning of G-CSF in the management of breast cancer, so that patients receive the best possible care while scarce health-care resources are allocated appropriately.P Trueman has received consulting fees from Novartis and Wyeth and has equity ownership/stock options with Johnson & Johnson.


Breast reconstruction with autologous tissue transfer is now a standard operation, but abnormalities of the abdominal wall contour represent a complication which has led surgeons to invent techniques to minimize the morbidity of the donor site.®).We report the case of a woman who had bilateral transverse rectus abdominis myocutaneous flap (TRAM-flap) breast reconstruction. The surgery led to the patient developing an enormous abdominal bulge that caused her disability in terms of abdominal wall and bowel function, pain and contour. In the absence of rectus muscle, the large defect was repaired using a combination of the abdominal wall component separation technique of Ramirez et al and additional mesh augmentation with a lightweight, large-pore polypropylene mesh (UltraproThe procedure of Ramirez et al is helpful in achieving a tension-free closure of large defects in the anterior abdominal wall. The additional mesh augmentation allows reinforcement of the thinned lateral abdominal wall. Abnormalities of the abdominal wall contour after breast reconstruction with autologous tissue transfer have previously been reported as problematic, with a lower abdominal bulge being the most frequently reported abnormality . AlthougIn addition to the aesthetic disturbance, these defects can also lead to adverse interference of the abdominal wall functions, as a thrust bearing for the intraabdominal pressure and as an antagonist of the back muscles and part of the respiratory system. To date, these side effects have not attracted attention in the literature and no therapeutic approaches have been reported.Here we present the case of a woman with an extreme bulge of the lower abdominal wall following bilateral transverse rectus abdominis myocutaneous flap (TRAM-flap) breast reconstruction. This was repaired using a combination of the abdominal wall component separation technique of Ramirez et al  and addiin situ. The breast reconstruction was conducted using a non-muscle-sparing pedicled TRAM-flap transposition. The defect created at the donor site within the abdominal wall after harvesting the rectus muscle was closed using a continuous suture with resorbable suture material. An additional augmentation was performed by the implantation of a resorbable polyglactin mesh placed on the fascial suture.We report the case of a 61-year-old woman who was suffering from lower abdominal bulge formation, chronic constipation, as well as a feeling of permanent abdominal constriction and pain. These symptoms appeared eight months after bilateral breast reconstruction, which was performed following subcutaneous mastectomy that was necessary owing to ductal carcinoma The patient presented at the authors' outpatient clinic eight months after reconstruction. At that time her body mass index was 18.9 and she was suffering from a lower abdominal bulge formation  on each side . A subcutaneous suction drain was placed on top of each mesh, after which wound closure was achieved with a continuous intracutaneous suture using non-resorbable material.Following adequate preparations with intestinal irrigation, a re-incision through the midline scar was performed. On entering the peritoneal cavity, several dense adhesions of small intestine to the abdominal wall and interenteric to the colon were found. These were carefully dissolved without causing injury to the intestine. Further exploration revealed a near-total absence of both abdominal rectus muscles; residual muscle fibres could be detected only at the lateral side of the rectus sheath. The initially implanted absorbable mesh was not identified, and the ultrasonographic finding of a diastasis-like defect with lateralization of both lineae semilunares was verified. Following a wide-ranging mobilization of the epifascial subcutaneous tissue, the remaining parts of the anterior rectus sheaths and minimal lateral parts of the rectus muscles were exposed. The herniation sac was partly resected, leaving sufficient material to facilitate a peritoneal closure of the abdominal cavity. In order to reach an adaptation of both lateralized anterior rectus sheaths, a component separation of the abdominal wall (Ramirez procedure) was performed. In the absence of an intact rectus abdominis muscle and anterior rectus sheath, only a vertical incision lateral to the linea semilunaris and separation in the plane between oblique external and internal muscle was used. A two-layer closure of the fascia in the midline was performed using a non-resorbable single-stitch suture of the posterior wall, and a continuous suture with a slowly resorbable suture material for the remaining anterior rectus sheath. The lateral defects between the external oblique muscle and linea semilunaris were covered with a halfmoon-shaped lightweight polypropylene mesh   was not An extensive epifascial preparation might put the blood circulation of the skin at risk. In slim patients, where the subcutaneous layer is not usually pronounced, the additional use of excessive foreign material should be considered carefully. The use of lightweight, large-pore polypropylene meshes appears to reduce the risk of any major foreign-body reaction that might lead to shrinkage of the mesh area or to a reduction in abdominal wall mobility . The texIt has been shown that a reconstruction of the abdominal wall midline is possible and maintainable in the absence of both rectus muscles, using the component separation technique of Ramirez et al. A modification is suggested using additional mesh augmentation to cover the thinned lateral abdominal wall, using a lightweight polypropylene mesh prosthesis.The author(s) declare that they have no competing interests.DAK assisted with the surgery, designed the case report, collated the information, performed the literature search and prepared the manuscript. JC assisted with the surgery, was involved in all investigations and assisted in providing a critical appraisal and review of the manuscript. JO prepared the images, advised on the format and design and assisted in providing a critical appraisal of the manuscript. VS performed the surgery, was involved in all investigations and assisted in the literature search, writing and editing of the manuscript. All authors have reviewed and approved the final manuscript.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 Editor-in-Chief of this journal.


The recognition of neonatal intestinal perforation relies on identification of free gas in the peritoneum on plain abdominal radiographs and the associated clinical signs. The neonatal bowel takes several hours to fill with gas, potentially obscuring one of the radiological signs of bowel perforation in the neonate.+2 weeks of gestation, who was suspected before birth to be at risk of intestinal perforation, based on antenatal ultrasound signs of bowel obstruction. However, the diagnosis of intestinal perforation after birth was initially delayed because the first abdominal radiograph, requested by the neonatal team, was taken too early in the clinical progression of the neonate's condition. As a consequence, this delayed referral to the paediatric surgical team and definitive management.We describe the case of a male, Caucasian neonate, born prematurely at 35This case illustrates how consideration of the timing of abdominal radiographs in suspected intestinal perforation in the neonate may avoid misinterpretation of radiographic signs, thereby avoiding delays in referral and treatment in the crucial first few hours of life. Abdominal distension with bile-stained vomiting in a neonate can potentially represent bowel obstruction. Neonatal bowel obstruction can be complicated by intestinal perforation, hence the necessity for early surgical referral in cases of neonatal bowel obstruction. Intestinal perforation may occur before birth. The preliminary imaging modality of choice to diagnose suspected bowel obstruction and intestinal perforation in a neonate is a plain supine abdominal radiograph. Accurate diagnosis often relies on recognition of abnormal gas patterns within the abdomen. However, the passage of gas through the neonatal intestine takes a number of hours after birth.in utero bowel perforation, which can be associated with postnatal meconium peritonitis. Meconium peritonitis can be treated operatively or non-operatively, since in utero bowel perforations may heal spontaneously. A recent meta-analysis of the literature has helped to clarify the features of meconium peritonitis that are associated with a need for operative management [Peritoneal calcification is indicative of nagement . Cases onagement .+2 week) Caucasian neonate with suspected antenatal bowel obstruction presented to the neonatal unit with mild abdominal distension and bile stained aspirates. The infant was otherwise well at birth. No other abnormal features were detected on examination. Prenatal test for cystic fibrosis was negative.A premature (35An abdominal radiograph was taken by the neonatal team within 1 hour of birth. No dilated loops were demonstrated. A calcified rim was present in the centre of the abdomen, with some irregular calcification in the right upper quadrant. There was no evidence of free gas within the peritoneal cavity (Figure A second radiograph was performed approximately 4 hours after birth because of increasing abdominal distension in the neonate. On this second radiograph, free gas was visible in the peritoneal cavity Figure . The surAt laparotomy, a large perforation was found in the ascending colon. Meconium and calcified material were drained from the peritoneal cavity. A drain was inserted and a stoma formed from the proximal ascending colon. The neonate made a good recovery postoperatively. Hirschprung's disease and cystic fibrosis were excluded as causes of the perforation.The relevance of this case study to the management of neonates with suspected antenatal bowel obstruction is that the first abdominal radiograph placed our neonate in the lowest risk category, suggesting the neonate could be safely managed non-operatively. Conversely, the second abdominal radiograph, demonstrating perforation, placed our neonate in a category that generally requires surgical management ,2.British Medical Journal highlighted the potential dangers of iatrogenic radiation, stressing the imperative for doctors to protect patients from unnecessary exposure [A second issue highlighted in this patient is that this neonate was exposed to an extra dose of radiation that ultimately proved to obscure the diagnosis, therefore it was of no benefit to the patient. A recent article in the exposure .This study illustrates a potential pitfall in the use and interpretation of plain abdominal radiographs in the first few hours of life that may negatively impact on management of neonatal patients.The authors declare that they have no competing interests.MJG wrote the case study, researched and wrote the literature review. MMC critically revised the literature review and advised on radiological aspects of the case. KL was lead consultant who managed the case, instigated the conception of the case study, gave advice on the intellectual content of the case study in relation to clinical practice and obtained consent from the parents. All authors read and approved the final manuscript.Written informed consent was obtained from the parents of the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.


Febrile neutropenia (FN) causes significant morbidity and mortality in patients receiving cytotoxic chemotherapy and can lead to reduced chemotherapy dose intensity and increased overall treatment costs. Antibiotic prophylaxis reduces the incidence of FN. Recent research and meta-analyses confirm that prophylactic fluoroquinolones decrease FN and infection-related mortality in patients with acute leukaemia and those receiving high-dose chemotherapy. Fluoroquinolone prophylaxis also lowers the incidence of FN and all-cause mortality following the first cycle of myelosuppressive chemotherapy for solid tumours. Levofloxacin has been the agent studied most thoroughly in this context. Although there is no convincing evidence that colonisation of individuals with resistant organisms due to antibiotic prophylaxis increases FN or mortality, such concerns must be taken seriously and the use of prophylaxis should be limited responsibly for patients with the greatest chance of benefit. Fluoroquinolone prophylaxis is well tolerated and cost-effective and should be offered to patients receiving chemotherapy for haematological malignancies and high-dose chemotherapy for solid tumours in which prolonged (>7 days) neutropenia is expected. It should also be considered for those receiving chemotherapy for solid tumours and lymphomas during the first cycle of chemotherapy when grade 4 neutropenia is anticipated. For many years, controversy has surrounded the use of prophylactic antibiotics following chemotherapy for malignant diseases. Although effective, the toxicity of the trimethoprim–sulfamethoxazole combination led to a decline in its use, and raised questions about the prophylaxis of febrile neutropenia (FN) in general, particularly as mortality from FN was diminishing. However, as discussed elsewhere in this supplement , data haThe fluoroquinolones, introduced in the 1980s, have transformed this field, becoming the most commonly used prophylactic antibacterial agents in neutropenic patients because of their broad antimicrobial spectrum, preservation of anaerobic gut flora , systemiIn the past 5 years, major randomised trials and meta-analyses have led to significant progress in our understanding of the efficacy of fluoroquinolone prophylaxis, and the categories of patients (and chemotherapy regimens) associated with the greatest risk of FN, and hence those most likely to benefit from prophylactic treatment. The use of granulocyte colony-stimulating factors, with or without antibiotics, in the prophylaxis of FN is described in this supplement by Kelly and Wheatley. Our review summarises the evidence supporting the use of prophylactic antibiotics following chemotherapy and highlights the situations in which the gains are likely to be greatest.Two large, investigator-led, randomised controlled trials published in 2005 provide firm evidence of the efficacy of fluoroquinolone prophylaxis in two distinct contexts: hospitalised patients expecting prolonged neutropenia, and patients receiving cyclical, mainly outpatient-based, chemotherapy causing neutropenia of a short duration.3) was expected to last longer than 7 days. The trial included patients receiving chemotherapy for acute leukaemia, lymphomas or solid tumours. They were randomised to receive oral levofloxacin (500 mg daily) or placebo from the start of chemotherapy until the resolution of neutropenia. Intention-to-treat analysis showed a lower incidence of fever in patients receiving levofloxacin compared with the placebo group . Mortality was lower in the levofloxacin group but the study was not powered to prove this.3) were randomised to receive either levofloxacin (500 mg daily) or placebo for 7 days during the expected neutropenic period in up to six cycles of chemotherapy. A significant reduction in febrile episodes and hospitalisation for treatment of bacterial infection was documented in the levofloxacin group during all cycles of treatment. Thirty-day mortality was lower in the levofloxacin group (1.5%) compared with the placebo group (2.3%), but the difference did not reach statistical significance  Trial  than in later cycles (odds ratio 0.78). However, FN in cycle 1 predicted a much higher risk of subsequent FN and a trend towards continued prophylactic efficacy in later cycles , the data on cycle effects support the practice of offering prophylactic levofloxacin in the first cycle of myelosuppressive cancer chemotherapy, and in subsequent cycles only if there has been a fever in cycle 1. These data also show that prophylactic levofloxacin is effective regardless of the patient's age or performance status, or the type of solid tumour .Fluoroquinolone prophylaxis also significantly reduces FN in patients with solid tumours or lymphoma who are undergoing cyclical standard-dose myelosuppressive chemotherapy (Fluoroquinolones are the most effective agents for prophylaxis of FN, and are cost effective and well tolerated . When chThe main concern relating to the prophylactic use of antibiotics remains the development of resistance. Although it is established that fluoroquinolone prophylaxis can result in increased fluoroquinolone resistance in treatment centres, there is little evidence of a resultant increase in FN or infection-related mortality (There are also important ethical concerns about withholding a proven treatment from current patients for the sake of an unquantified benefit to patients in the future.


Laparoscopic repair of ventral hernia is the standard of care in today’s era. With increasing experience, different theories and techniques have been described by different authors to overcome the intraoperative and postoperative problems. We describe a novel technique for closure of defect in laparoscopic hernia repair which has the added advantage. Along with advances in minimally invasive surgery, the laparoscopic repair of incisional hernia has been gaining popularity. Yet, the absence of recurrence, seroma, and pain eludes the laparoscopic surgeon tackling ventral and incisional hernias laparoscopically–3 Many tMost large published series have defined that the defect is closed by continuous suturing with a No. 1 synthetic monofilament suture or loop before the onlay mesh. Authors Initially in our series we had not sutured the defect before fixing the onlay mesh in order to perform a tension-free repair, which had a very high incidence of visible postoperative impulse along with seroma formation . SubsequWe modified the technique of suturing to interrupted FAR-NEAR-NEAR-FAR vertical mattress sutures. It gave us the benefit of the double-layered repair, with less length of suture used, and handling became easier. Generally we used a No. 1 polypropylene monofilament suture on a 40 mm large round bodied needle, at intervals of 1/1.5cm from each other.Patient is supine, arms tucked at the side. Monitor is at the foot end, surgeon at the head end and the patient 30 degrees head down in case of infra-umbilical hernias and vice versa in case of supra-umbilical hernias. Pneumoperitoneum is created from the palmers point and ports are inserted as shown in Suturing of the edges of the defect is started at the distal end of the defect and proceeded proximally in a far-near-near-far vertical mattress suture technique . BetweenThis modification is beneficial in terms of reduction of operating time from that when continuous suturing is performed with the loop suture, preventing mid-suturing give way as all the sutures and knots were primarily separate with less knot pressure, better handling of smaller length sutures and prevention of subcutaneous foreign body sensation. Otherwise it has all the benefits of suturing the defect, such as, absence of postoperative impulse and significant reduction of seroma formation.


Providing guidelines for testing expected inaccuracy and imprecisionis still a matter under debate. The Expert Panel of the FrenchSociety of Clinical Chemistry has developed a protocol, which wasbased on a comparative multi-centre evaluation of four instruments:the Ciba-Corning 278, the Instrumentation Laboratory 1306, theNova SP 5 and the ABL 330. The purpose was to evaluate theanalytical performance and efficiency of the analysers. Another aimwas to design a valid approach for evaluating any new system. Asbuffered aqueous solutions and fluorocarbon emulsions give onlypartial information, tonometered blood was used at different levelsof gas mixture, even though it is both difficult and time-consuming.Comparisons have been established on patients' blood samples withthe analysers currently used in the evaluation sites. The tests showedthat the four analysers have the same degree of precision, and interinstrumentcomparisons demonstrated a very high degree ofreliability.This analysis emphasizes that the evaluation of instruments forpH and blood gas analysis is neither easy nor is it often done,mainly due to the choice of a quality-control material and thelability of the measured parameters.


The bicuspid aortic valve (BAV) and specific systemic autoimmune diseases are associated with cardiovascular manifestation, including aortic aneurysm. We reported a case of 64 year-old patient with BAV and a history of ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE), and who developed ascending thoracic aortic aneurysm. The patient presented also the homozygosity for genetic variants of MMP9, ACE, MTHFR and PAI-1 genes. Gene-environmental interactions may represent an additional pathogenetic dimension in the still challenging management of the abnormalities of the aortic wall, including dilatation, aneurysm and dissection. The bicuspid aortic valve (BAV) affects 1 to 2% of the population and may be complicated by abnormalities of the aortic wall, including dilatation, aneurysm and dissection [Specific systemic autoimmune diseases are associated with cardiovascular manifestations, including aortic aneurysm ,3.We reported a case of a 64-year-old male with BAV and a history of ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE), and who developed ascending thoracic aortic aneurysm. In addition we have performed a genetic screnning of 5 gene polymorphisms  reported in multiple case control studies to be genetic risk factors for the development of the abdominal aortic aneurysm (AAA) [The patient was a -64 year-old man, who had a 25-year history of hypertension and a 8-year history of hypothyroidism. In 2000, the patient underwent a corrective osteotomy of the spine for ankylosing spondylitis and spondylarthropathy. He had also been diagnosed as having a dilatation of the ascending thoracic aorta associated to BAV. The patients was treated with metilprednisolone along with colchicine, and was followed regularly for progressive aortic dilation.He was admitted at our hospital for further evaluation on December 2008. Transthoracic echocardiography revealed aortic root and ascending aortic dilatation Figures , 2.A computed tomography scan confirmed the presence of the ascending aorta aneurysm (53 mm) and ectasia of the aortic root and arch (respectively 45 mm and 42 mm). The patient was referred to our cardiothoracic surgery service in order to evaluate the need for aortic root replacement. Preoperative coronary angiography and aortography confirmed the presence of ascending aortic aneurysm root without evidence of hemodynamically significant stenosis or regurgitation so the cardiac surgeons decided to postpone surgical treatment at the time when the valve requires replacement.Genetic testing was performed by polymerase chain reaction/restriction fragment length polymorphism analysis in order to identify genotypes patient. The genetic results for the studied polymorphisms are shown in table Patients with AS and SLE may develop cardiovascular manifestations ranging from asymptomatic forms to life threatening conditions, including common cardiovascular manifestation and valvular problems ,3. The mAneurism formation may be more common in patients with the coexistence of BAV. In fact, bicuspid aortic valve is considered to be a cause of intrinsic changes in the aortic wall resulting in aneurysms of the ascending aorta, independent of degree of valvular dysfunction .In addition to the presence of BAV and the inflammatory involvement of the aortic wall by immune diseases and systemic hypertension, genetic factors may contribute significantly to the development of aortic dilation in our patient. Indeed, our observations are in agreement with such hypothesis, reporting the presence of homozygosity for genetic variants of MMP9, ACE, MTHFR and PAI-1 genes that have been previously associated with a significant risk of abdominal aortic aneurysm disease . ExpressAn association between the presence of AAA and elevated MTHFR 677C>T has been indicated, and meta-analysis of these studies reveal a significant increased risk of AAA disease for the T allele variant . RecentlIn the present case report, in addition to inflammatory involvement of the aortic wall by systemic autoimmune diseases, these specific genetic variants may have promoted the development of aortic dilation in this patient.BAV is responsible for a large proportion of patients coming to aortic valve replacement. The mechanism responsible for the associated vascular complications remains controversial. Some patients with BAV have rapidly progressive valve and aortic dysfunction while some remain without complications.Several advances in the molecular genetics of aortic valve disease related to BAV, have recently been made, especially through the use of linkage analysis. These resulted in the discovery of mutations in NOTCH1 gene, a signaling and transcriptional regulator gene on chromosome 9, NOTCH1 and some different loci linked to BAV on chromosomes 18, 5, and 13 .However, genetic basis of BAV remains unclear. Our data suggest, for the first time, that some genetic biomarkers  may predispose BAV patients at an increased risk of aortic dilatation, aneurysm formation, and dissection. Our findings are hypothesis generating and need to be confirmed by further clinical studies.Elucidating the genetic basis for BAV may have substantial implications in clinical practice. Identification of specific genetic markers may helpful for early clinical detection of relatives; genetic markers might be also used to predict the natural progression of the condition and to identify those cases that might have potentially life-threatening complications from BAVTherefore, future studies focusing on the identification of additional disease-causing and susceptibility genes are needed in order to improve understanding of the pathophysiological processes as well as to identify new therapeutic strategies.Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journalThe authors declare that they have no competing interests.IF carried out the molecular genetic studies and helped to draft the manuscript; LA and PLF have been involved in revising it critically for important intellectual content; AM performed the echocardiography; SB give his sugery opinion and has been involved in revising of the manuscript; MGA defined the study design and wrote the manuscript.All authors read and approved the final manuscript.