Neuron-specific enolase and response to initial therapy are important prognostic factors in patients with small cell lung cancer.
The prognostic factors for the survival of small cell lung cancer (SCLC) patients are still widely debated. The aim of this study was to identify the clinical features and prognostic factors in SCLC patients. A retrospective study was conducted on SCLC patients who were treated in our hospital between July 2010 and July 2015. Comparison of overall survival (OS) was performed using the Kaplan-Meier method. Prognostic factors for OS were identified by multivariate Cox regression models. A total of 523 patients with complete data and ECOG 0-2 were enrolled in our study. A total of 383 patients (73.2%) were diagnosed with ES-SCLC (extensive-stage SCLC) and 140 patients (26.8%) were diagnosed with LS-SCLC (limited-stage SCLC). In all patients, early disease stage, good ECOG, normal neuron-specific enolase (NSE), thoracic radiotherapy, ≥4 cycles of chemotherapy, prophylactic cranial irradiation, good response to initial therapy were independent favorable prognostic factors for OS, along with gender, age, CEA and CA125. In LS-SCLC patients, normal NSE, normal CEA, good response to initial therapy and surgery were independent favorable prognostic factors for OS. In ES-SCLC patients, good ECOG, normal NSE, thoracic radiotherapy, ≥4 cycles of chemotherapy, prophylactic cranial irradiation and good response to initial therapy were independent favorable prognostic factors for OS. Remarkably, NSE and response to initial therapy were independent prognostic factors for OS in all SCLC patients, LS-SCLC patients and ES-SCLC patients. The normal NSE and good response to initial therapy predicted a better survival for SCLC patients, regardless of disease stage.


Clinical examination of saccadic eye movements in hemianopia.
We used two simple bedside tests of saccadic eye movements between two fingers as targets to study 23 hemianopic patients. With these tests, we could provide confirmation or, in malingering, exclusion of a hemianopia. Furthermore, the amount of ocular motor compensation for the loss of one half of the visual field could be estimated, and visual hemineglect was demonstrated. The findings in some cases with chronic homonymous hemianopia suggested "extrastriate vision."


Fresh osteochondral allografts for patellofemoral arthritis: long-term followup.
Treatment of patellofemoral osteoarthritis in young patients is a challenge for orthopaedic surgeons. Concern about loosening and wear in active young people render arthroplasty more suitable for older patients. Osteochondral allografts may be a good alternative, but reports of experience with such grafts in patellofemoral joints are limited. We retrospectively reviewed our results with fresh osteochondral allografts. Our hypothesis was that these grafts provide relief from osteoarthritis, improve knee function, and delay prosthetic knee replacement. From 1986 to 1999, 14 fresh patellofemoral or patellar allografts were implanted in knees of 11 patients younger than 55 years and diagnosed with advanced secondary osteoarthritis. At last followup (average, 10 years; range, 2.5-17.5 years), eight grafts were in place, four for more than 10 years and two for more than 5 years. Of the nonsurviving allografts, three survived more than 10 years. Radiographs of the knees with intact allografts showed mild or no degenerative changes. Average Knee Society scores improved (preoperative to last followup), with knee scores improving from 46 points (range, 38-60 points) to 82 points (range, 35-100 points) and functional scores from 30 points (range, 10-60 points) to 75 points (range, 20-100 points). Fresh osteochondral allografts can provide relief from the arthritic condition, improve knee function, and delay prosthetic knee replacement. Therapeutic study, Level IV (case series). See the Guidelines for Authors for a complete description of levels of evidence.


Role of the potassium chloride cotransporter isoform 2-mediated spinal chloride homeostasis in a rat model of visceral hypersensitivity.
Visceral hypersensitivity represents an important hallmark in the pathophysiology of irritable bowel syndrome (IBS), of which the mechanisms remain elusive. The present study was designed to examine whether cation-chloride cotransporter (CCC)-mediated chloride (Cl(-)) homeostasis of the spinal cord is involved in chronic stress-induced visceral hypersensitivity. Chronic visceral hypersensitivity was induced by exposing male Wistar rats to water avoidance stress (WAS). RT-PCR, Western blotting, and immunohistochemistry were used to assess the expression of CCCs in the spinal cord. Patch-clamp recordings were performed on adult spinal cord slices to evaluate Cl(-) homeostasis and Cl(-) extrusion capacity of lamina I neurons. Visceral sensitivity was estimated by measuring the abdominal withdrawal reflex in response to colorectal distension (CRD). After 10 days of WAS exposure, levels of both total protein and the oligomeric form of the K(+)-Cl(-) cotransporter isoform 2 (KCC2), but not Na(+)-K(+)-2Cl(-) transporter isoform 1 (NKCC1), were significantly decreased in the dorsal horn of the lumbosacral spinal cord. The downregulation of KCC2 resulted in a depolarizing shifted equilibrium potential of GABAergic inhibitory postsynaptic current and impaired Cl(-) extrusion capacity in lamina I neurons of the lumbosacral spinal cord from WAS rats. Acute noxious CRD disrupted spinal KCC2 expression and function 2 h after the final distention in sham rats, but not in WAS rats. Pharmacological blockade of KCC2 activity by intrathecal injection of a KCC2 inhibitor [(dihydroindenyl)oxy] alkanoic acid enhanced visceral nociceptive sensitivity in sham rats, but not in WAS rats. These results suggest that KCC2 downregulation-mediated impairment of spinal cord Cl(-) homeostasis may play an important role in chronic stress-induced visceral hypersensitivity.


Clinical practice, ethics and economics: the physician at the crossroads.
In recent years health services have faced the challenge of increasingly complex services and rising costs, thus the consideration of costs is a key factor in health policy decisions. The introduction of an economic perspective has sometimes been viewed as conflicting with the ethics of the health care system, especially at the physician-patient level. this article explores the important role of the physician from the ethical and economic perspective in the distribution and allocation of services. An understanding of economic and ethical principles reveals that these two perspectives are compatible with good clinical practice: more efficient health care implies better care for the individual patient and makes it possible to increase the resources available to improve care for the population as a whole. Thus, being efficient is an ethical objective. The selective elimination of ineffective services would free resources to care for those who need effective diagnostic or therapeutic procedures. This requires a better understanding of the determinants and outcomes of clinical practice, physician motivation, the appropriate design and application of incentives, and the best use of limited resources. The physician can play a key role in increasing the efficiency, equity, and quality of the health system without restricting the provision of effective services.


Carbocyclic analogues of xylofuranosylpurine nucleosides. Synthesis and antitumor activity.
(+/-)-4 alpha-Amino-2 alpha,3 beta-dihydroxy-1 alpha-cyclopentanemethanol (6), the carbocyclic analogue of xylofuranosylamine, was synthesized from the previously reported 4 alpha-acetamido-2 alpha,3 alpha-epoxycyclopentane-1 alpha-methanol. Amine 6 was converted to (+/-)-4 alpha-[(5-amino-6-chloro-4-pyrimidinyl)amino]-2 alpha,3 beta-dihydroxy-1 alpha-cyclopentanemethanol (7) by condensation with 5-amino-4,6-dichloropyrimidine. From 7, the carbocyclic analogues of xylofuranosyladenine and xylofuranosyl-8-azaadenine were prepared. In contrast to 9-beta-D-xylofuranosyladenine and its 8-aza analogue, the corresponding carbocyclic nucleosides were resistant to deamination by adenosine deaminase. The carbocyclic 8-aza derivative 10 exhibited significant in vivo antitumor activity which varied according to treatment schedule.


The effect of ribose 5-phosphate and 5-phosphoribosyl-1-pyrophosphate availability on de novo synthesis of purine nucleotides in rat liver slices.
The effect of increasing cellular ribose 5-phosphate (ribose-5-P) availability by methylene blue-induced acceleration of the oxidative pentose phosphate pathway on the rate of 5-phosphoribosyl-1-pyrophosphate (P-ribose-PP) generation, was studied in slices of rat liver at varying Pi concentration. It was found that at Pi concentration prevailing in the tissue of extracellular physiological Pi concentration, ribose-5-P availability is saturating for P-ribose-PP generation, as gauged by the rate of adenine incorporation into tissue nucleotides. The effect of altering P-ribose-PP availability on the rate of de novo purine production gauged by the rate of formate incorporation into purines, was also studied. It was found that the physiological P-ribose-PP concentration in rat liver tissue is limiting for purine synthesis de novo. Depletion of cellular P-ribose-PP, achieved by increase of P-ribose-PP consumption, decelerated purine synthesis, while increase of P-ribose-PP availability, achieved by activation of P-ribose-PP synthetase occurring at elevated Pi concentration, resulted in acceleration of purine synthesis.


The prostacyclin agonist iloprost aggravates fibrosis and enhances viral replication in enteroviral myocarditis by modulation of ERK signaling and increase of iNOS expression.
Enteroviruses, such as coxsackieviruses of group B (CVB), are able to induce a chronic inflammation of the myocardium, which may finally lead to the loss of functional tissue, remodeling processes and the development of fibrosis, thus affecting the proper contractile function of the heart. In other fibrotic diseases like scleroderma, the prostacyclin agonist iloprost was found to inhibit the extracellular signal-regulated kinase (ERK, p44/42 MAPK), a mitogen-activated protein kinase, and consecutively, the expression of the profibrotic cytokine connective tissue growth factor (CTGF), thereby preventing the development of fibrosis. As CTGF was found to mediate fibrosis in chronic CVB3 myocarditis as well, we evaluated whether the in vivo application of iloprost is capable to reduce the development of ERK/CTGF-mediated fibrosis in enteroviral myocarditis. Unexpectedly, the application of iloprost resulted in a prolonged myocardial inflammation and an aggravated fibrosis and failed to reduce activation of ERK and expression of CTGF at later stages of the disease. In addition, viral replication was found to be increased in iloprost-treated mice. Notably, the expression of cardiac inducible nitric oxide synthase (iNOS), which is known to aggravate myocardial damage in CVB3-infected mice, was strongly enhanced by iloprost. Using cultivated bone marrow macrophages (BMM), we confirmed these results, proving that iloprost potentiates the expression of iNOS mRNA and protein in CVB3-infected and IFN-gamma stimulated BMM. In conclusion, these results suggest a critical reflection of the clinical use of iloprost, especially in patients possibly suffering from an enteroviral myocarditis.


Adult Dental Anxiety: Recent Assessment Approaches and Psychological Management in a Dental Practice Setting.
Dental anxiety of patients is a common feature of the everyday experience of dental practice. This article advocates the use of regular assessment of this psychological construct to assist in patient management. Various tools, such as the Modified Dental Anxiety Scale (MDAS), are available to monitor dental anxiety that are quick to complete and easy to interpret. Patient burden is low. A new mobile phone assessment system (DENTANX) is being developed for distribution. This application and other psychological interventions are being investigated to assist patients to receive dental care routinely. Clinical relevance: This article provides evidence and expert opinion on the worth of regular dental anxiety assessment in dental practice using structured tools, such as the Modified Dental Anxiety Scale, and consideration of psychological intervention development.


Equity is out of fashion? An essay on autonomy and health policy in the individualized society.
It is widely recognized that there is a discrepancy between principle and practice with respect to the health equity aim of public policy. This discrepancy is analyzed from two theoretical perspectives: the individualization of society and the fact that individual beliefs and values are connected to one's position in the social structure. These mechanisms influence both the choice of health policy measures and the normative judgements of preventive efforts, both of which tend to be consonant with the views of dominant social groups. In particular, we focus on the treatment of the ethical principle of autonomy and how this is reflected in health policy aimed at influencing health-related behaviour. We examine the current trend towards targeting health information campaigns on certain socio-economic groups and argue that it entails an ethical dilemma. The dominant discourse of the welfare state is contemplated as a means to understand why there tend to be a lack of emphasis on measures that are targeted at socio-economic inequalities. It is argued that there is no substantive basis in the individualized society for perceiving health equity as an independent moral principle and that the driving force behind the professed health equity goal may be in essence utilitarian.


Colorectal cancer and bowel habits.
In a retrospective case-control study comparing 100 colorectal cancer patients with 100 age-, race-, and sex-matched hospital controls and 51 spouse controls, no significant differences were observed in the historical frequency of bowel movements, presence of constipation, or use of laxatives between cases and controls. There is a suggestion of greater suppository or enema use in both control groups as compared to patients with colorectal cancer.


The role of tadpoles and frogs as paratenic hosts in the life cycle of Dracunculus insignis (Nematoda: Dracunculoidea).
The possibility exists that paratenic hosts play a role in the life cycle of various Dracunculus species. In the present study, we established that tadpoles of 2 genera of frogs (Xenopus and Rana) were capable of ingesting copepods infected with third-stage larvae (L3) of Dracunculus insignis. Once ingested, the L3s migrated from the gut to the somatic tissues of the tadpoles. In Xenopus, the dracunculid larvae persisted through the metamorphosis of the tadpoles into adult frogs. These observations confirm the concept that paratenic hosts, such as tadpoles or frogs, may be important means of transporting infective larvae of Dracunculus species up the food chain and facilitate transmission to the definitive hosts.


Marek's disease virus-induced transient paralysis in chickens. 2. Ultrastructure of central nervous system.
Ultrastructural changes of the central nervous system (CNS) were compared in inbred White Leghorn chickens that are genetically resistant or susceptible to Marek's disease virus (MDV)-induced transient paralysis (TP). Widened extracellular spaces, containing granular material resembling protein were found in brains of TP-affected chickens. Demyelination was absent in all chickens and intramyelinic oedema was rare, present only in TP-affected chickens. Both MDV-inoculated TP-resistant and TP-susceptible chickens had CNS perivascular mononuclear cell cuffs at all sampling periods, but the TP-affected chickens also had endothelial cell hypertrophy, a greater quantity of intramural phagocytized chromatin debris, and intramural heterophils. Such findings suggest vasculitis as the causative lesion. No open endothelial cell tight junctions, endothelial cells discontinuities, or transendothelial channels were morphologically evident to explain the vasogenic oedema, but an apparent suggestive increase in coated micropinocytotic vesicles in CNS endothelial cells is a possible mechanism to explain the altered blood-brain-barrier.


Genetic ablation of the t-SNARE SNAP-25 distinguishes mechanisms of neuroexocytosis.
Axon outgrowth during development and neurotransmitter release depends on exocytotic mechanisms, although what protein machinery is common to or differentiates these processes remains unclear. Here we show that the neural t-SNARE (target-membrane-associated-soluble N-ethylmaleimide fusion protein attachment protein (SNAP) receptor) SNAP-25 is not required for nerve growth or stimulus-independent neurotransmitter release, but is essential for evoked synaptic transmission at neuromuscular junctions and central synapses. These results demonstrate that the development of neurotransmission requires the recruitment of a specialized SNARE core complex to meet the demands of regulated exocytosis.


Serum enzyme, myoglobin and muscle strength relationships in polymyositis and dermatomyositis.
Strength of the quadriceps and hamstring groups was biomechanically assessed in terms of isometric torque production in 14 patients with inflammatory myopathy. Eleven had polymyositis and 3, dermatomyositis. Determinations of serum creatine kinase, lactate dehydrogenase, transaminase, and myoglobin were simultaneously obtained over an average period of observation of 1.8 years. In certain individual patients, there were significant correlations between laboratory indices and strength during the entire course of illness. In others, this was not the case. In the total group of patients, absolute values of the laboratory indices did not correlate well with strength except in the case of serum myoglobin, where there a significant inverse relationship. Logarithmic transformations of the laboratory data increased the inverse correlations. High strength and low myoglobin were related to high prednisone dose. Since laboratory guides are not always related to disease activity, quantitative assessment of muscle strength is necessary.


Role of cytosolic calcium diffusion in cardiac purkinje cells.
The Cardiac Purkinje cells (PCs) exhibit distinct calcium (Ca2+) homeostasis than that in ventricular myocytes (VMs). Due to lack of t-tubules in PCs, the Ca2+ ions entering the cell have to diffuse through the cytoplasm to reach the sarcoplasmic reticulum (SR) before triggering Ca2+-induced-Ca2+-release (CICR). In recent experimental studies PCs have been shown to be more susceptible to action potential (AP) abnormalities than the VMs, however the exact mechanisms are poorly understood. In this study, we utilize morphologically realistic detailed biophysical mathematical model of a murine PC to systematically examine the role intracellular Ca2+ diffusion in the APs of PCs. A biphasic spatiotemporal Ca2+ diffusion process, as observed experimentally, was implemented in the model which includes radial Ca2+ wavelets and cell wide longitudinal Ca2+ diffusion wave (CWW). The AP morphology, specifically plateau, is affected due to changes in intracellular Ca2+ dynamics. When Ca2+ concentration in sarcolemmal region is elevated, it activated inward sodium Ca2+ exchanger (NCX) current resulting into prolongation of the plateau at faster diffusion rates. Our results demonstrate that the cytosolic Ca2+ diffusion waves play a significant role in shaping APs of PCs and could provide mechanistic insights into the increased arrhythmogeneity of PCs.


Problems in the assessment of psychosomatic conditions in Social Security benefits and related commercial schemes.
The medical community must recognize that support of claims for Incapacity Benefit and related commercial schemes places the patient in a small and special sub-population of clinical practice which may require specialist investigation, treatment, and documentation. Determination of functional capacity and of disability requires knowledge either not available or unfamiliar to most physicians with caring and therapeutic roles, especially of legal or contractual provisions and occupational data. However, it is not necessary for them to determine disability and they should not be asked to do so. The new, medical assessment procedures for Incapacity Benefit in the UK do not require this, and the largest provider of related commercial schemes (Long Term Disability; Permanent Health Insurance) has already eliminated this requirement from its application process. When such application is anticipated or requested, the medical record should be prepared and appropriate consultation obtained. Subjective issues should be identified and addressed. Comprehensive psychiatric evaluation, especially in subjective impairment, is critical in chronic incapacity. The estimation of functional capacities in the absence of objective data is particularly troublesome, but, clinicians can provide the Disability Medical Analyst with appropriate medical documentation.


[Gastric lipoma case report].
We report a case of gastric lipoma, a rare benign stomach tumor. There are approximately 200 cases previously described in literature. A male, 62-year-old patient with no clinical complaint presented a tumor lesion in the stomach antrum found in a routine upper endoscopy. A surgical resection (subtotal gastrectomy) was done and the histological examination showed submucosal lipoma without signs of malignancy. This report points to the growth of routine examination in the current clinical practice and the dilemma brought by overdiagnosis.


Transplantation of hepatomas induced in the avian liver by MC29 leukosis virus.
A hepatomatous growth derived from primary liver tumors induced in chickens by i.v. inoculation with MC29 leukosis virus has been established and maintained in the avian host. Hepatoma tissue transplanted into the abdominal cavity in a total of 278 chicks in 35 experiments yielded tumors in 222 animals (80%). The i.m. implantation in 69 birds in 7 experiments resulted in growth in 67 chicks (97%). Tumor tissue introduced inadvertently into the s.c. tissue likewise grew very rapidly. Histological and cytological features of the transplants in all sites showed preservation of the morphological characteristics of the original primary liver tumors through repeated passages. The properties of this first transplantable hepatoma derived from virus-induced primary liver tumors are compared with those of other transplantable hepatomas.


Comparative degradation and regeneration of polymer solar cells with different cathodes.
A comparative degradation study of solar cells based on a bulk-heterojunction (BHJ) blend of poly(3-hexylethiophene) (P3HT) and phenyl [6,6] C61 butyric acid methyl ester (PCBM) with two different cathodes is reported. Poly(ethylene-dioxythiphene):poly(styrene sulfonate) (PEDOT:PSS) coated ITO electrodes were used as the anode, whereas Ca/Al and Ca/Ag electrodes were used as cathodes. Fully degraded devices were subjected to thermal annealing under inert atmosphere. The performance of degraded solar cells with a Ca/Al cathode exhibited no improvement after treatment. However the solar cells with a Ca/Ag cathode exhibited a considerable recovery in their performance following annealing under a nitrogen atmosphere. Indeed, these solar cells could be subjected to many degradation and regeneration cycles. Current density-voltage (J-V) characteristics and X-ray photoelectron spectroscopy (XPS) studies show that this behavior arises from the complex chemical thermodynamics of the reactions that can occur at the cathode/active layer interface. In particular, the recovery of device performance for solar cells with a Ca/Ag cathode is due to the reversible oxidation of Ag upon thermal annealing.


Estrogen modulates in vitro T cell responses in a concentration- and receptor-dependent manner: effects on intracellular molecular targets and antioxidant enzymes.
Estrogen is a key hormone in facilitating ovulation and maintenance of pregnancy in young females and subsequent decline in its production contributes to the development of age-associated disorders such as hormone-dependent cancer, osteoporosis, and cardiovascular diseases. The mechanisms through which estrogen promotes female-specific diseases with advancing age are unclear especially, its effects on immune system which is vital for the maintenance of homeostasis and health. Although the diverse effects of estrogen on Th immunity (Th1 vs. Th2) have been characterized in several cell-types and animal models, there is no direct mechanistic study to understand its immunomodulatory actions. The purpose of this study is to investigate whether the in vitro effects of 17β-estradiol on lymphocytes from the spleen influence cell-mediated immune responses based on its concentration and type of estrogen receptors (ERs) and to assess its mechanism of action at the cellular level. Lymphocytes from the spleens of young Sprague-Dawley rats were isolated and incubated with various concentrations of 17β-estradiol (10(-6)-10(-14)M) and specific ERα- and β-agonists (10(-6)M, 10(-8)M and 10(-10)M) without or with concanavalin A (Con A) to measure T lymphocyte proliferation, IFN-γ and IL-2 production, p-ERK 1/2, p-CREB, and p-Akt, activities of antioxidant enzymes[superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)], and nitric oxide (NO) production. The specificity of ER-mediated actions in lymphocytes was examined by coincubation with nonspecific ER antagonists ICI(182,780) or tamoxifen. Lower concentrations of 17β-estradiol enhanced proliferation of T lymphocytes and IFN-γ production without or with Con A stimulation but had no effect on IL-2 production. ERα and ERβ agonists induced an increase in T cell proliferation and IFN-γ production and these effects were inhibited by tamoxifen. ERβ agonist alone enhanced IL-2 production by the lymphocytes. Coincubation with 17β-estradiol and ERα- and β-agonists augmented p-ERK 1/2, p-CREB, and p-Akt expression in the lymphocytes and tamoxifen reversed the ER agonist-induced effects on these molecular targets. Estrogen increased the activities of SOD, CAT, and GPx in both non-stimulated and Con A-stimulated splenocytes in a concentration-dependent manner. Both ERα- and β-agonists enhanced CAT and GPx activity while ERα-agonist decreased SOD activity and ERβ-agonist increased SOD activity. The effects of ER agonists on the antioxidant enzymes were reversed by ICI(182,780). Coincubation of lower doses of 17β-estradiol with Con A and both ER agonists enhanced NO production while higher dose of estrogen with Con A and ERα agonist suppressed its production and these effects were reversed by tamoxifen. Taken together, these results suggest that the effects of estrogen on the cell-mediated immune responses are dependent upon its concentrations and mediated through specific estrogen receptors involving intracellular signaling pathways and antioxidant enzymes.


Mirror-attenuator-mosaic diffuser performance.
The diffuse radiance outgoing from mirror-attenuator-mosaic diffusers is with in certain limits independent from the angle of the incident light. Such diffusers are useful as calibration sources for the Scanner for Radiation Budget radiometer and for similar purposes as well. Two techniques of production of directional diffusers (etching and diamond drilling) are compared. To measure the performance of the samples, a new measurement setup is introduced that permits the direct comparison of incoming and outgoing light with an accuracy of better than 0.5%. The diamond drilling technique shows a much better performance than the etching.


[Clinical trial of parenteral trimethoprim-sulfamethoxazole].
The combination of trimethoprim-sulfamethoxazole has been used successfully in various infections. However the use of the combination was limited, due to the lack of a parenteral form of the drug. In this study a parenteral (i.m.) form of trimethoprim-sulfamethoxazole was given to 35 patients with various infections due to susceptible bacteria to the drug. Twenty-four patients had urinary tract infections, and 7 had various infections with gram negative organisms, and 4 had staphylococcal infections. In patients with urinary tract infection the cure rate was 62.5%. Twenty five per cent of the patients had persistent infection after treatment, and 12,5% had superinfection. The overall cure rate was 71,4% in 35 patients. No side effect was observed.


Use of the female condom among sex workers in China.
To introduce the female condom (FC) among sex workers (SWs) in China. We adopted the intervention study method. The 315 participating SWs were randomly assigned to an intervention group (155 SWs) or a control group (160 SWs). The rate of SWs who reported liking FC increased from 60.0% pre-intervention to 93.5% post-intervention, and the rate of SWs who considered that their clients could accept FC increased from 27.1% to 92.3%. After the intervention, 93.5% expressed that their sexual satisfaction had increased with their familiarity with FC and 97.4% expressed that they would use it in the future. The understanding and use of FC can be greatly improved through active intervention-i.e. medical workers providing SWs with FC.


Monoclonal antibody-recognizing cone visual pigment.
Monoclonal antibodies were raised to a crude photoreceptor-membrane suspension from chicken retinas. Clones producing antibodies against cone outer segments were selected by screening with immunocytochemistry on semithin sections of the retina. One monoclonal antibody, called COS-1, specifically labelled outer segments of double cones and one type of single cones; outer segments of rods and several single cones were not stained. On immunoblots of retinal photoreceptor membranes, this antibody recognized a protein with an apparent molecular mass of 33,000. The visual pigment character of the 33,000 protein was indirectly established by another monoclonal antibody, OS-2, which labelled all outer segments on semithin sections and four bands (33,000-, 36,000-, 38,000-40,000- and a composite band between 66,000-72,000 MW) on immunoblots. Of these, the 36,000- and the 72,000 MW protein bands were identified with an anti-rhodopsin polyclonal antibody as rhodopsin monomer and dimer. Monoclonal antibody OS-2 is assumed therefore to represent an antibody against a common epitope of all visual pigments of the chicken. The monoclonal antibody COS-1 was found to bind to certain cone outer segments of many other vertebrate species as well.


An audit of implanted penile prostheses in the UK.
To assess whether the outcome of implanting penile prostheses is related to the number of prostheses implanted by surgeons, as several reports showed that the outcome of a urological procedure is directly related to the experience of the surgeon. We conducted a retrospective audit of 413 penile prostheses implanted over a 2-year period in the UK by 76 surgeons. About 80% of the surgeons implanted only one or two prostheses per year, usually of the malleable type, and usually on patients in the private sector. Only four surgeons implanted >20 prostheses per year. The overall revision rate for implantation in the UK, at 24%, is far higher than the worldwide average. Guidelines are needed on the number of prostheses a surgeon should implant per year so that revision rates will decline to more acceptable levels and patients will be offered a genuine choice of product.


[An unusual cause of sinusitis].
Larvae of the sheep botfly (Oestrus ovis) normally have sheep or goats as host. In humans the larvae can survive for a short time in the nose or under the eyelids, after which they die or are sneezed out. We describe a 47-year-old woman who during a stay in the Cape Verde Islands developed symptoms of sneezing, a swollen face and an itchy feeling in her nose. These symptoms were due to an infestation of three fully-developed larvae of the O. ovis species in her sinus maxillaries which were later evacuated by endoscopy. In exceptional cases larvae of the O. ovis species can fully mature in a healthy person after a visit to an endemic area. Development into the mature stage has only been described in patients with a poor mucosal immune response.


The herpes simplex virus type 2 protein ICP10PK: a master of versatility.
Herpes simplex viruses types 1 (HSV-1) and 2 (HSV-2) are associated with a wide range of diseases related to infection of epithelial or neuronal tissues. The two viruses evidence distinct pathogenesis aspects, which are likely mediated by distinct viral genes. One such gene is UL39, which codes for the large subunit of ribonucleotide reductase (R1, also known as ICP6 and ICP10 for HSV-1 and HSV-2 respectively). The HSV-2 R1 has serine-threonine protein kinase (PK) activity, which is located within the first 411 amino acids (ICP10PK). ICP10PK is a constitutively activated growth factor receptor (GFR) that signals through the Ras/MEK/ERK pathway. It has transforming activity in immortalized cells, mitogenic (but not transforming) activity in normal diploid cells, and anti-apoptotic (survival) activity in post mitotic neurons in the central nervous system (CNS). In addition to the Ras/MEK/ERK, ICP10PK also activates the PI3-K/Akt pathway, upregulates the Ras family member Rap-1 and adenylate cyclase and activates the B-Raf kinase activity. ICP10 PK appears to have a cellular origin. Its conservation is most likely to reflect the ability to impart an evolutionary advantage, particularly in the face of pro-apoptotic viral genes. Indeed, activation of the Ras/MEK/ERK pathway by ICP10PK is required for virus growth.


Impaired distractor inhibition on a selective attention task in unmedicated, depressed subjects.
Impaired distractor inhibition may contribute to the selective attention deficits observed in depressed patients, but studies to date have not tested the distractor inhibition theory against the possibility that processes such as transient memory review processes may account for the observed deficits. A negative priming paradigm can dissociate inhibition from such a potentially confounding process called object review. The negative priming task also isolates features of the distractor such as colour and location for independent examination. A computerized negative priming task was used in which colour, identification and location features of a stimulus and distractor were systematically manipulated across successive prime and probe trials. Thirty-two unmedicated subjects with DSM-IV diagnoses of non-psychotic unipolar depression were compared with 32 age, sex and IQ matched controls. Depressed subjects had reduced levels of negative priming for conditions where the colour feature of the stimulus was repeated across prime and probe trials but not when identity or location was the repeated feature. When both the colour and location feature were the repeated feature across trials, facilitation in response was apparent. The pattern of results supports studies that found reduced distractor inhibition in depressed subjects, and suggests that object review is intact in these subjects. Greater impairment in negative priming for colour versus location suggests that subjects may have greater impairment in the visual stream associated with processing colour features.


Radiologists, communication, and Resolution 5: a medicolegal issue.
Resolution 5, adopted by the American College of Radiology, sets forth principles of direct communication that are important to every radiologist. This article reviews pertinent court decisions that affect radiologists and illustrates the importance of Resolution 5. In recent cases in state courts, liability standards have focused on four areas: negligence based on failure to personally inform clinicians of the diagnosis, ability of the jury to decide whether the radiologist's actions were appropriate, provision of information to the correct person, and necessity for expert testimony to define urgency. An important factor in liability cases appears to be the judgment of the radiologist in selection of the correct individual to receive the radiology report. The authors believe that electronic communication devices (eg, voice mail and fax machines) may potentially breach confidentiality and that such devices should therefore be used sparingly. Verbal communication by the radiologist to the referring physician, in addition to a written report, should avoid liability and improve quality of care for the patient.


Sensitive and rapid visual detection of Salmonella Typhimurium in milk based on recombinase polymerase amplification with lateral flow dipsticks.
Salmonella Typhimurium (S. Typhimurium) can cause serious foodborne diseases. In this study, an assay combining recombinase polymerase amplification (RPA) with lateral flow dipsticks (LFD) was developed to detect S. Typhimurium in milk. The RPA forward primers STF1, STF2, STF3, the reverse primer STR labeled with digoxin, and the probe STProb labeled with FAM were designed and screened to produce RPA products for LFD detection. The RPA reaction volume, temperature, and time were then optimized, and the sensitivity and specificity of the developed method were analyzed. Finally, the RPA-LFD method was evaluated using milk artificially contaminated with S. Typhimurium. Results indicated that the primer pair STF1/STR is the optimal combination for detecting the bacterium. The minimum volume, shortest time, and optimal temperature of the RPA reaction were 10 μL, 10 min, and 40-42 °C, respectively. The limit of detection of RPA-LFD for detecting the genomic DNA of S. Typhimurium was 1 fg, which is 5 and 10 times lower than the corresponding limits of RPA-agarose gel electrophoresis (AGE) and PCR-AGE, respectively. Testing with 29 other foodborne bacteria as controls revealed that RPA-LFD was highly specific for S. Typhimurium. RPA-LFD can detect S. Typhimurium at concentrations as low as 1.95 CFU/mL in artificially inoculated milk samples and is thus 10 times more sensitive than PCR. Hence, the RPA-LFD assay established in this study could be a potential point-of-care/need test for S. Typhimurium, especially in areas with limited resources.


Influence of Strain Preservation Methods on Fruiting Body Growth and Metabolite Production by the Medicinal Mushroom Cordyceps militaris (Ascomycetes).
Cordyceps militaris is a highly valued edible and medicinal fungus because of its production of various metabolites including adenosine, cordycepin, and N6-(2-hydroxyethyl)-adenosine. Fruiting bodies of this fungus have been used successfully in industrial production and widely as a substitute for Ophiocordyceps sinensis (syn. C. sinensis) in traditional Chinese medicine and health supplements. Strain degeneration occurs with high frequency during the subculturing and preservation of C. militaris strains, which leads to significant losses during industrial production. In this study, we evaluated the effects of different strain preservation methods on fruiting body growth and metabolite production. We found that strain degeneration affects not only fruiting body differentiation but also metabolite production, and suitable preservation methods can avoid degeneration. Preservation in sterile water has a similar effect as cryopreservation in liquid nitrogen at -196°C with regard to maintaining the characteristics of C. militaris strains for at least 1 year, and it is a practical and satisfactory method for preserving C. militaris strains that can be used in factories. Ultracold freezing at -80°C is not suitable for this fungus. Lyophilization, which causes C. militaris strains to retain their inherent characteristics and avoid degeneration, is suitable for long-term preservation (at least 4 years). This study provides practical preservation methods for C. militaris strains over the short and long term and will be helpful to achieve stable and superior-quality production of C. militaris fruiting bodies.


The A (3Pi1) State of ClF.
The A(3Pi1) state of ClF is studied (1) in emission from the beta(1(3)P2) ion-pair state in a high-pressure discharge, (2) from its role in perturbations of the B(3Pi0(+)) and A'(3Pi2) states, and (3) in direct absorption from the X(1Sigma+) ground state. The last of these is obtained via a UV-labeling technique and represents the first observation of the A <-- X transition. The emission spectrum yields extensive assignments for the 0-4, 0-5, and 1-4 bands of beta --> A, with both e and f lines identified. The well-known perturbation in v = 7 of the B state is attributed to interaction with v = 9 of A. A newly identified perturbation in B(6) involves coupling with A(8). The known perturbation in B(8) may involve A(11), but other assignments cannot be ruled out. Approximate potential curves are derived for all three valence states and used to compute the vibrational factors for the perturbations, permitting extraction of the electronic coupling strengths. The B-A coupling elements are within approximately 10% of expectations for rotation-electronic coupling within a Hund's case (a) 3Pi manifold, but the strength of the perturbation between A(5) and A'(6) is only about 30% of predictions for this model. Copyright 1999 Academic Press.


Effects of in vitro potassium on ammoniagenesis in rat and canine kidney tissue.
Decreased ammonium (NH4+) excretion is associated with hyperkalemia. To determine if potassium could directly influence renal ammonia production, we investigated ammoniagenesis by rat and canine renal cortical tissues in vitro at different potassium concentrations. Renal tissue from normal and acidotic rats and normal dogs incubated in glutamine, lactate, and 7 to 10 mEq/liters of potassium or 25 mEq/liters of potassium produced significantly less ammonia than slices incubating in glutamine, lactate, and 4 to 5 mEq of potassium. Glutamate accumulation, which follows glutamine deamidation, did not decrease and even increased at 25 mEq/liters of potassium. With glutamine as the sole substrate, decreased ammoniagenesis was seen only at higher potassium concentrations (greater than 16 mEq/liters) than when lactate was also present. The depression to glutamine ammoniagenesis by high concentrations of potassium was partially obliterated in an anaerobic environment. When glutamate replaced glutamine as the precursor, renal ammonia produced by slices in 7 and 25 mEq/liters was again significantly lower than by slices incubating in 4 mEq/liters. We blocked glutamine synthesis by rat kidney slices with dl-methionine dl-sulfoximine when glutamate was the renal ammonia precursor. This essentially allows glutamate deamination to produce ammonia. Potassium depressed glutamate deamination significantly at 7 mEq/liters (decreases 13%) and at 25 mEq/liters of potassium (decreases 35%) as compared to 4 mEq/liters. The above findings are consistent with a major depressive effect of in vitro potassium on glutamate deamination in rat and canine kidneys. Other evidence, especially from rat tissue studies, suggests that potassium also may affect glutamine deamination directly. Rat kidney slices incubating in the high potassium medium of 7 mEq/liter or greater also consumed less oxygen in the presence of glutamine (P less than 0.01), oxidatively decarboxylated less glutamine (P less than 0.02) and produced less glucose from glutamine (P less than 0.01).


[Statins: possibly more than just lowering of the lipid level].
Clinical trials have demonstrated that treatment of hypercholesterolemia with HMG-CoA reductase inhibitors (statins) is beneficial in primary and secondary prevention of vascular diseases. The observed reduction in cardiovascular morbidity and mortality cannot only be explained by lipid-lowering only. Apart from lowering cholesterol, statins conceivably also exert effects on the vascular wall that may directly contribute to decrease of vascular incidents: (a) a favourable influence on endothelial dysfunction through stimulation of nitrous oxide synthetase: (b) stabilization of plaques by reducing influx of macrophages into the vascular wall and decreasing the production of matrix metalloproteinases, that may affect the connective tissue cover of the plaque: (c) inhibition of the initiation and progression of atherosclerosis by reducing adhesion of leukocytes to the vascular wall: (d) reducing the haemorrhagic diathesis by increasing the fibrinolytic capacity and inhibiting tissue factor expression on macrophages. All these effects of statins independent of the lowering of the cholesterol level might contribute to primary and secondary prevention of vascular incidents. While most nonlipid mechanisms of statins are being studied in vitro and in animals, the clinical relevance is still to be determined.


[Asbestosis of the bladder neck and prostate. Reflections on 2 cases].
Ingested asbestos is mainly excreted in the urine. Marked impregnation of bladder neck in a patient working in an asbestos factory was diagnosed initially as a tuberculosis lesion on the granulomatous histologic appearance. Asbestos fibers were counted by electron microscopy. This appears to be the first case of this type reported and possible causal relations and histopathologic findings are discussed. Also reported is a patient with prostatic cancer, and chronic pulmonary asbestosis, treated by adenomectomy using an upper approach 15 years previously. The cancer was of the prostate transitional cell type. A causal relation could not be proved but other such cases should be investigated, to determine a possible link between the lesion and industrial fibers.


[Electron microscopic and electron histochemical study of mitochondrial inclusions in insect intestine epithelial cells].
The electron microscope investigation of the midgut epithelial cells of Chaoborus obscuripes revealed special membrane formations in mitochondria. The mitochondrial inclusions (MI) look like small membranous whorls about 0.2--0.3 microns in diameter. In a certain period of functional activity, MI start leaving the mitochondria and appear in cytoplasm. Later, large multimembrane structures (MS) composed of parallel membranes in concentric or whorl--like arrangement are observed in the cytoplasm. At first MS are situated in the vicinity of mitochondria, then they gather near the base of the villus. The relationship between appearance of MI and MS in the cytoplasm and the digestion process was revealed. Treatment of ultrathin sections with H202 or H5J06 showed MI and MS to be composed mainly of lipids. This suggests that MI and MS,probably, take part in the lipids metabolism of the midgut epithelial cells of insect.


Effects of resource availability on seedling recruitment in a fire-maintained savanna.
The herbaceous ground cover of the longleaf pine ecosystem harbors the highest plant species richness in North America, with up to 50 species per square meter, but the mechanisms that regulate this diversity are not well understood. In this system, variability in seedling recruitment events may best explain the extremely high small-scale species richness and its relationship to soil moisture and system net primary productivity. To understand the potential mechanistic controls on species richness, we used a long-term resource manipulation study across a natural soil moisture gradient to assess environmental controls on seedling recruitment. We considered the availability of resources to be an indicator of seedling safe-site supply, and also manipulated seed availability to examine the relative importance of recruitment limitations on seedling diversity. We found that water availability regulated the number of species in the seedling community regardless of the underlying natural moisture gradient, and that this effect may result from differential responses of seedling guilds to resource availability. Water supply was more important than seed supply in determining seedling establishment, suggesting that appropriate sites for regeneration are a factor limiting seedling success. This is the first study that shows that the episodic supply of microsites for recruitment could influence species richness in the highly threatened and biodiverse longleaf pine savanna.


[Secondary gout and pseudo-Bartter syndrome in females with laxative abuse].
Four females (27-54 y), presenting with a history of long-term laxative abuse, were admitted to the Medizinische Poliklinik for evaluation of generalized weakness. Laboratory findings revealed signs of Bartter's syndrome, including hypokalemia, systemic alkalosis and normal blood pressure. Three of the four females showed impaired renal function and elevated serum uric acid levels, two of them suffered from recurrent gouty attacks. In our patients the incidence of hyperuricemia and impaired renal function, as a consequence of chronic hypokalemia, was much higher than known from patients with Bartter's syndrome. Hyperuricemia is related to some pathophysiological features of Pseudo-Bartter's syndrome, (e.g. systemic alkalosis, elevated angiotensin) and combined with additional factors (e.g. catabolism, reduced plasma volume) may lead to gouty attacks. Gallstones were found in two of the four females. Long term surreptitious laxative ingestion frequently is observed in females. Hypokalemia, induced by the laxatives, causes reduced intestinal motility and leads to augmented laxative intake. These patients are prone to develop Pseudo-Bartter's syndrome, causing eventually a hyperuricemia and gouty attacks.


Self-reporting versus clinical scrutiny: the value of adding questionnaires to the routine evaluation of seizure disorders. An exploratory study on the differential diagnosis between epilepsy and psychogenic nonepileptic seizures.
Questionnaires or symptom lists have proved effective for differentiating epileptic seizures (ES) from psychogenic nonepileptic seizures (PNES). However, monitoring the events, corroborated by medical history gathered by experts, remains the gold standard. We directly compared symptoms and characteristic of the events self-reported by patients/eyewitnesses (Questionnaire A/B) with the information contained in the clinical charts of 50 patients with undefined diagnosis undergoing long-term monitoring. Data extracted from medical records were reformatted to fit the questionnaires' templates (A1/B1) for comparison. Quantitatively, self-reported information was considerably greater and more complete. Calculating sensitivity (SE) and specificity (SP) of all variables in the group with confirmed diagnosis, we identified those above the preset thresholds with the potential to discriminate between ES and PNES. Eight predictive variables were common to both methods: head injury, physical/emotional abuse, chronic fatigue (A); talked out of seizures, eyes closed, apnea, and collapsing (B). Eleven predictive variables were specific to direct questioning: preictal headache, bright light, feeling overwhelmed, heart racing, tingling and numbness, postictal trouble speaking, physical pain, history of gastro-esophageal reflux disease (GERD), self-inflicted injuries (A); on/off shaking, and side-to-side head movements (B). Thirteen predictive variables were generated by chart review: sleep deprivation, strong emotions/anxiety, preictal headache (warning), nausea/vomiting, history of PNES, cholecystectomy, depression, medications for behavioral problems (A1), sudden start/sudden stop of shaking, both sides shaking, falling during the seizure, feeling confused and disoriented postictally (B1). CONCLUSION: Self-reporting and clinical scrutiny are complementary. Structured questionnaires increase the range of predictive variables and should be utilized routinely to facilitate clinicians' quest for the correct diagnosis.


Radiation therapy versus radical prostatectomy in the PSA era: a urologist's view.
In the absence of a randomized trial directly comparing outcomes in men with localized prostate cancer treated by radical prostatectomy with treatment by radiation therapy, only an approximate answer regarding the relative efficacies of these modalities can be achieved. However, retrospective studies which examined outcomes based on pretreatment parameters intrinsic to the tumors have demonstrated that when stratified by grade and prostate specific antigen (PSA), the rates of cancer control for these therapies are similar at 5 years posttreatment. These modalities differ in other important ways, including acute toxicity, patient satisfaction, posttreatment quality of life, and ease of salvage of treatment failures. A consideration of all of these factors is necessary to arrive at the appropriate choice of therapy for each patient.


Effect of visual input on postural stability in young adults with chronic motion sensitivity: A controlled cross-sectional study.
Chronic motion sensitivity (CMS) has been defined as a feeling of un-wellness elicited by either actual or perceived motion. CMS is a common condition and is more prevalent in females than in males. In addition to a variety of symptoms, young adults with CMS have less postural stability than those without CMS. To determine whether dependence on visual cues for postural stability is different between young adults with and without CMS, and whether it differs by gender within each group. Sixty young adults (30 females and 30 males) were assigned to one of two groups (CMS or non-CMS) using the Motion Sickness Susceptibility Questionnaire-Short Form. Postural stability was measured for all participants using the Bertec Balance Advantage-Computerized Dynamic Posturography with Immersion Virtual Reality. A significant difference was found in mean postural stability scores during immersion virtual reality between the CMS and non-CMS groups (p < 0.001); however, no significant difference was shown in mean postural stability between males and females within the CMS and non-CMS groups (p = 0.10 and p = 0.97, respectively). The results suggest that young adults with CMS are over-reliant on visual cues for postural stability, and that visual dependence is not influenced by gender.


Use of cytosolic triacylglycerol hydrolysis products and of exogenous fatty acid for the synthesis of triacylglycerol secreted by cultured rat hepatocytes.
The fatty acyl moieties incorporated into triacylglycerol (TAG) secreted by rat hepatocytes are derived from diacylglycerol (DAG) that is synthesized de novo through the phosphatidate pathway or derived from endogenous, cytosolic TAG after hydrolysis to DAG and re-esterification. We have used a dual-labeling technique (overnight labeling of cell TAG with [3H]oleate, followed by 3 h incubation with [14C]oleate) to quantify the contributions of the two sources towards TAG secretion by cultured rat hepatocytes. A wide range of TAG secretion rates was achieved by short-term incubation of the cells under a variety of conditions. There was no correlation between the overall amount of exogenous 14C-labeled fatty acid metabolized and the rate of either [14C]- or [3H]TAG secretion. By contrast, there was a strong positive correlation between the fraction of newly synthesized [14C]TAG that was secreted (the fractional secretion rate, FSR) and the absolute rate of TAG secretion. This suggests that the partitioning of DAG between (re)synthesis of cytosolic TAG and synthesis of secreted TAG is an important locus for the control of the rate of TAG secretion. Comparison of the ratio: oxidation/TAG secretion for 3H- and 14C-labeled acyl moieties indicated that, for all conditions studied, approximately half the acyl moieties already esterified to the glyceroyl backbone within cytosolic TAG remain unavailable for oxidation when this pool of TAG is mobilized for the synthesis of secreted TAG. The data provide evidence that hydrolysis of cytosolic triacylglycerol (TAG) does not proceed fully to the constituent fatty acids and glycerol, but only to the level of diacylglycerol, followed by re-modelling of approximately half of its acyl chains, before re-esterification to form secretory TAG.


Absence of JAK2 V617F mutation in thalassemia intermedia patients.
JAK2 is a cytoplasmic tyrosine kinase that has a vital role in signal transduction from several hemopoietic growth factor receptors. The JAK2 V617F mutation has been implicated in a variety of diseases mainly related to myeloproliferative disorders including polycythemia Vera, essential thrombocythemia, and idiopathic Myelofibrosis but has not been previously described in Thalassemia patients. We studied 36 Lebanese patients diagnosed with thalassemia intermedia and assessed the presence or absence of the JAK2 V617F mutation using JAK2 activating mutation assay (In VivoScribe Technologies) and Polymerase Chain Reaction (PCR). None of the thalassemia intermedia patients were positive for this mutation. To our knowledge, this study is the first to determine the status of JAK2 V617F mutation in thalassemia intermedia patients and expands the international published literature on JAK2. The latter's V617F mutation does not seem to play a role in this hematologically important clinical entity.


Development and evaluation of a questionnaire instrument for chemical intolerance, based on the International Classification of Functioning, Disability and Health.
Purpose: The purpose was to develop a questionnaire instrument to measure difficulties in activities and participation, and impact of environmental factors in chemical intolerance, based on the International Classification of Functioning, Disability and Health, and to assess its validity and reliability. Method: Development in three steps: (1) choosing items of relevance for chemical intolerance with an expert group, (2) conducting interviews with persons with chemical intolerance, using sampling to redundancy, (3) conducting a survey with 112 respondents at a first assessment and 91 at a second assessment for test-retest. Results: The final version of the instrument consists of 57 items divided in three parts, which showed good internal consistency in each part, Cronbach alpha: 0.73-0.87. It had good content validity, readability and face validity. Test-retest showed good to very good (≥0.61) Kappa agreement for 37 items, and moderate (0.41-0.60) for 17 items. Three items had poor or fair (<0.41) Kappa agreement. Conclusion: The instrument was found to be valid and reliable. It can be used as a clinical tool to help persons with chemical intolerance to receive the best suited help and support for each individual, identify key points in rehabilitation, measure rehabilitation outcome and establish priority for treatment. IMPLICATIONS FOR REHABILITATION The questionnaire instrument based on the International Classification of Functioning, Disability and Health which was developed and evaluated in this study, can be used to measure difficulties in activities and participation, and impact of environmental factors in chemical intolerance. Persons with chemical intolerance report lack of support from healthcare and society. Using this questionnaire instrument can help forming the best suited help and support for each individual based on his/her preconditions. This questionnaire instrument can be used to identify key points in rehabilitation and measure rehabilitation outcome.


[Human "pancreatic" bladder. Two case reports].
The aim of this study is to report two similar cases with an "accessory biliary duct" confluent to the main pancreatic duct. There was pancreatic juice inside the "gallbladder". There was no connection between "accessory biliary duct" and intra or extrahepatic biliary ducts. This anomalous junction of the "cystic duct" and the main pancreatic duct may be explained by embryology. These two cases could be the first human "pancreatic" bladders reported.


Transactional sex, condom and lubricant use among men who have sex with men in Lagos State, Nigeria.
Men who have unprotected sex with men may also have unprotected sex with women and thus serve as an epidemiological bridge for HIV to the general population. This cross sectional descriptive study assessed condom and lubricant use and practice of transactional sex among men who have sex with men (MSM) in Lagos state. Simple random sampling was used to select three community centres and snowball sampling technique was used to recruit 321 respondents. Almost half (50.9%) had received payment for sex while 45.4% had paid for sex in the past. Consistent condom use was practiced by 40.5% of respondents during the last 10 sexual encounters, 85.6% used lubricants mostly with condom, products used were KY jelly, body cream, saliva and Vaseline. There is need for behavioural change to reduce risky practices which predisposes this group of MSM to HIV and sexually transmitted infections.


Role of light in the mediation of acute effects of a single afternoon melatonin injection on steroidogenic activity of testis in the rat.
Young adult male rats, maintained either in an LD 12 : 12 or in continuous illumination (LL) for one week, were given a single injection of 25 microg melatonin/100 g body wt or ethanolic-saline (control) at 17.00 h. Animals from each group were sacrificed at 11.00 h on the following day. The activity of two important steroidogenic enzymes, 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) and delta(5)-3 beta-hydroxysteroid dehydrogenase (delta(5)-3 beta-HSD), and serum concentrations of testosterone, were measured following highly specific and sensitive spectrophotometric techniques and RIA, respectively. A significant decrease in the activity of both the steroidogenic enzymes was noted in the testes of melatonin-treated rats maintained under normal light-dark schedules, but this response was found to be lacking in the LL rats. However, no significant changes in the level of serum testosterone were noted in either group of melatonin-treated rats from the values in respective groups of ethanolic saline-administered LD and LL rats. Exposure of ethanolic saline-injected rats to continuous light also did not cause any change in the steroidogenic activity of the testis from those in LD rats. The study indicates that continuous light as such does not affect the endocrine function of testis but abolishes suppressive effects of melatonin on the steroidogenic activity of the testis in rat.


Reinvent, reorganise and reform.
The OCTOBER spending review set out the government's plans for the country in the coming years. The review is one of the most challenging we have seen and will affect us all. This, along with the proposals in the white paper on NhS reform and efficiency and public sector job losses, paints a difficult picture of uncertainty. In addition, we are midway through a review of pension reform and as yet undecided funding plans for sustaining public pensions.


"Multi-scan single shot" quantitative 2D NMR: a valuable alternative to fast conventional quantitative 2D NMR.
Quantitative Ultrafast (UF) 2D NMR is a very promising methodology enabling the acquisition of 2D spectra in a single scan. The analytical performances of UF 2D NMR have been highly increased in the last few years, however little is known about the sensitivity of ultrafast experiments versus conventional 2D NMR. A fair and relevant comparison has to consider the Signal-to-Noise Ratio (SNR) per unit of time, in order to answer the following question: for a given experiment time, should we run a conventional 2D experiment or is it preferable to accumulate ultrafast acquisitions? To answer this question, we perform here a systematic comparison between accumulated ultrafast experiments and conventional ones, for different experiment durations. Sensitivity issues and other analytical aspects are discussed for the COSY experiment in the context of quantitative analysis. The comparison is first carried out on a model sample, and then extended to model metabolic mixtures. The results highlight the high analytical performance of the "multi-scan single shot" approach versus conventional 2D NMR acquisitions. This result is attributed to the absence of t(1) noise in spatially encoded experiments. The multi-scan single shot approach is particularly interesting for quantitative applications of 2D NMR, whose occurrence in the literature has been greatly increasing in the last few years.


Countercurrent liquid-liquid extraction on paper.
Proof-of-concept is shown for two-phase countercurrent flow on paper. The device consists of two paper layers, one of which has been modified with a sizing agent to be hydrophobic. The layers exhibit different wetting behavior for water and octanol. Both phases dominate wetting in one of the layers and can be made to move in different directions along the interface to achieve liquid-liquid extraction.


Audiovisual speech segmentation in post-stroke aphasia: a pilot study.
Background: Stroke may cause sentence comprehension disorders. Speech segmentation, i.e. the ability to detect word boundaries while listening to continuous speech, is an initial step allowing the successful identification of words and the accurate understanding of meaning within sentences. It has received little attention in people with post-stroke aphasia (PWA).Objectives: Our goal was to study speech segmentation in PWA and examine the potential benefit of seeing the speakers' articulatory gestures while segmenting sentences.Methods: Fourteen PWA and twelve healthy controls participated in this pilot study. Performance was measured with a word-monitoring task. In the auditory-only modality, participants were presented with auditory-only stimuli while in the audiovisual modality, visual speech cues (i.e. speaker's articulatory gestures) accompanied the auditory input. The proportion of correct responses was calculated for each participant and each modality. Visual enhancement was then calculated in order to estimate the potential benefit of seeing the speaker's articulatory gestures.Results: Both in auditory-only and audiovisual modalities, PWA performed significantly less well than controls, who had 100% correct performance in both modalities. The performance of PWA was correlated with their phonological ability. Six PWA used the visual cues. Group level analysis performed on PWA did not show any reliable difference between the auditory-only and audiovisual modalities (median of visual enhancement = 7% [Q1 - Q3: -5 - 39]).Conclusion: Our findings show that speech segmentation disorder may exist in PWA. This points to the importance of assessing and training speech segmentation after stroke. Further studies should investigate the characteristics of PWA who use visual speech cues during sentence processing.


Acute effects of different types of oil consumption on endothelial function, oxidative stress status and vascular inflammation in healthy volunteers.
Consumption of different types of oil may have different effects on cardiovascular risk. The exact role of maize oil, cod liver oil, soya oil and extra virgin olive oil on endothelial function, oxidative stress and inflammation is unknown. We evaluated the effect of acute consumption of these types of oil on endothelial function, oxidative stress and inflammation in healthy adults. Thirty-seven healthy volunteers were randomised to receive an oral amount of each type of oil or water. Endothelial function was evaluated by gauge-strain plethysmography at baseline and 1, 2 and 3 h after consumption. Oxidative stress status was determined by total lipid peroxides (PEROX), while inflammatory process was estimated by measuring the soluble form of vascular adhesion molecule 1. Serum levels of the two previous markers were measured at baseline and 3 h after oil consumption. Reactive hyperaemia (RH) was significantly decreased after maize oil consumption compared with controls (P < 0.05). However, the consumption of cod liver oil and soya oil induced a significant improvement of RH after 1 h, compared with controls (P < 0.05). There was no significant effect of any type of oil consumption on endothelium-independent dilatation, total lipid PEROX and vascular adhesion molecule 1 serum levels. Consumption of maize oil leads to impaired endothelial function, while soya oil and cod liver oil slightly improve endothelial function. However, all types of oils did not affect inflammatory process and systemic oxidative stress, suggesting that their effect on endothelial function may not be mediated by free radicals bioavailability.


Facial paediatric desmoid fibromatosis: a case series, literature review and management algorithm.
Desmoid fibromatosis (also known as infantile or aggressive fibromatosis) is a rare soft tissue tumour that is occasionally seen in children. Although histologically benign, its growth pattern is highly aggressive often showing invasion of surrounding musculature and bone. Frequently found in cosmetically sensitive areas, complete excision can present a challenging problem. However, incomplete surgical excision is associated with high recurrence rates and although the disease responds to chemo and radiotherapy, both carry significant risks in young children. The management of four paediatric desmoid fibromatoses occurring in the midface is discussed. The recent and pertinent literature is comprehensively reviewed and an algorithm for the management of paediatric desmoid fibromatoses is proposed.


A nomogram predicting long-term biochemical recurrence after radical prostatectomy.
Men who undergo radical prostatectomy (RP) are at long-term risk of biochemical recurrence (BCR). In this report, the authors have described a model capable of predicting BCR up to at least 15 years after RP that can adjust predictions according to the disease-free interval. Cox regression was used to model the probability of BCR (a prostate-specific antigen level>0.1 ng/mL and rising) in 601 men who underwent RP with a median follow-up of 11.4 years. The statistical significance of nomogram predictors was confirmed with a competing-risks regression model. The model was validated internally with 200 bootstraps and externally at 5 years, 10 years, and 15 years in 2 independent cohorts of 2963 and 3178 contemporary RP patients from 2 institutions. The 5-year, 10-year, 15-year, and 20-year actuarial rates of BCR-free survival were 84.8%, 71.2%, 61.1%, and 58.6%, respectively. Pathologic stage, surgical margin status, pathologic Gleason sum, type of RP, and adjuvant radiotherapy represented independent predictors of BCR in both Cox and competing-risks regression models and constituted the nomogram predictor variables. In internal validation, the nomogram accuracy was 79.3%, 77.2%, 79.7%, and 80.6% at 5 years, 10 years, 15 years, and 20 years, respectively, after RP. In external validation, the nomogram was 77.4% accurate at 5 years in the first cohort and 77.9%, 79.4%, and 86.3% accurate at 5 years, 10 years, and 15 years, respectively, in the second cohort. Patients who undergo RP remain at risk of BCR beyond 10 years after RP. The nomogram described in this report distinguishes itself from other tools by its ability to accurately predict the conditional probability of BCR up to at least 15 years after surgery.


Donor Dopamine Does Not Affect Liver Graft Survival: Evidence of Safety From a Randomized Controlled Trial.
Treatment of donation after brain death (DBD) donors with low-dose dopamine improves the outcomes after kidney and heart transplantation. This study investigates the course of liver allografts from multiorgan donors enrolled in the randomized dopamine trial between 2004 and 2007 (clinicaltrials.gov identifier: NCT00115115). There were 264 hemodynamically stable DBDs who were randomly assigned to receive low-dose dopamine. Dopamine was infused at 4 μg/kg/minute for a median duration of 6.0 hours (interquartile range, 4.4-7.5 hours). We assessed the outcomes of 212 liver transplantations (LTs) performed at 32 European centers. Donors and recipients of both groups were very similar in baseline characteristics. Pretransplant laboratory Model for End-Stage Liver Disease score was not different in recipients of a dopamine-treated versus untreated graft (18 ± 8 versus 20 ± 8; P = 0.12). Mean cold ischemia time was 10.6 ± 2.9 versus 10.1 ± 2.8 hours (P = 0.24). No differences occurred in biopsy-proven rejection episodes (14.4% versus 15.7%; P = 0.85), requirement of hemofiltration (27.9% versus 31.5%; P = 0.65), the need for early retransplantation (5.8% versus 6.5%; P > 0.99), the incidence of primary nonfunction (7.7% versus 8.3%; P > 0.99), and in-hospital mortality (15.4% versus 14.8%; P > 0.99). Graft survival was 71.2% versus 73.2% and 59.6% versus 62.0% at 2 and 3 years (log-rank P = 0.71). Patient survival was 76.0% versus 78.7% and 65.4% versus 69.4% at 1 and 3 years (log-rank P = 0.50). In conclusion, donor pretreatment with dopamine has no short-term or longterm effects on outcome after LT. Therefore, low-dose dopamine pretreatment can safely be implemented as the standard of care in hemodynamically stable DBDs.


Outcome measurement in clinical genetics services: a systematic review of validated measures.
This systematic review aimed to inform researchers and policymakers about what validated outcome measures are available to evaluate clinical genetics services (CGS) and the need for new measures. Validated outcome measures used to evaluate CGS were identified from a systematic literature review. Subjective outcome measures were assumed to have been validated only if some form of psychometric assessment was reported. A total of 1688 titles and abstracts were identified, and 61 articles met the inclusion criteria for the final review, which covered 67 validated outcome measures. There were 37 nongenetics-specific and 30 genetics-specific measures identified. No single validated outcome measure encompassed all potential patient benefits from using a CGS. A variety of different domains were identified, including anxiety and depression, coping, decision-making, distress, family environment, health status, knowledge, mood, perception of risk, perceived personal control, psychological impact, quality of life, satisfaction and expectations, self-esteem, spiritual well-being, and worry. Some important aspects of patient benefit from CGS are not covered by existing outcome measures. New research is necessary to develop the array of outcome measures required to quantify the benefits CGS offer patients living with the effects of genetic conditions. These need to be suitable for use in prospective evaluation studies to provide robust evidence for decision-makers to inform service development and commissioning. This includes prioritization of the existing validated outcome measures in terms of their usefulness and relevance to the measurement and valuation of patient benefits from a CGS.


Topical versus oral carbonic anhydrase inhibitor therapy for pediatric glaucoma.
Our purpose was to compare, in a crossover design,the hypotensive effect of oral acetazolamide (Diamox) and topical dorzolamide (Trusopt) in patients with pediatric glaucoma. All patients less than 18 years old who were switched from acetazolamide to dorzolamide without other intervention were reviewed. Intraocular pressures were obtained with either a Tono-Pen (Mentor Ophthalmics, Santa Barbara, Calif.) or applanation tonometer. Minimum follow-up times on acetazolamide and on dorzolamide were 1 month (mean 12.2 +/- 19.7 months) and 2 months (mean 8.2 +/- 5.1 months), respectively. The average dose of acetazolamide was 9.9 +/- 1.8 mg/kg/day. Eleven eyes (11 patients) were included. Indications for crossover from oral to topical carbonic anhydrase inhibitor (CAI) therapy were intolerance to acetazolamide (6 eyes) and surgical intervention in the fellow eye (5 eyes). The mean age at the time of crossover was 7.4 +/- 3.0 years. A comparison of intraocular pressure (IOP) before addition of a CAI was made in 8 eyes. The mean IOP off of a CAI was 27.8 +/- 4.9 mm Hg. The mean 10P was reduced to 18.5 +/- 4.3 mm Hg on acetazolamide (mean percent IOP reduction 35.7% +/- 15.6%, p < 0.01) and to 22.2 +/- 5.4 mm Hg on dorzolamide (mean percent IOP reduction 27.4% +/- 17.1%, p < 0.01). All 11 eyes showed an increase in IOP when switched from acetazolamide to dorzolamide, with a mean increase of 3.7 +/- 2.5 mm Hg (20.2% -/+ 13.7%, p < 0.01). Five eyes have remained controlled on dorzolamide and a topical beta-blocker. Five eyes required further intervention for the control of glaucoma. One eye was switched back to acetazolamide for better IOP control. Although not as effective as oral acetazolamide, topical dorzolamide causes a significant IOP reduction in this group of pediatric glaucoma patients and appears to be well tolerated.


Antithrombotic treatment for pregnancy complications: which path for the journey to precision medicine?
Haemostatic and vascular biology mechanisms appear to play an important role in the pathogenesis of placenta-mediated pregnancy complications. Although low-dose aspirin (LDA) has a modest effect in preventing preeclampsia, antithrombotic interventions, LDA and low molecular weight heparin (LMWH) have not definitively proven their effectiveness in women with placenta-mediated pregnancy complications selected by previous pregnancy outcome alone. Given the heterogeneous aetiology of placenta-mediated pregnancy complications, it is critical to stratify patients according to maternal and fetal characteristics and disease mechanisms rather than simply by pregnancy outcome, such as miscarriage. Such stratification could identify those who could benefit from antithrombotic interventions in pregnancy. We lack data on genome-wide association studies, biomarkers and trials of interventions applied to specific homogeneous populations. Future studies should focus on elaborating different disease mechanisms and examining antithrombotic interventions in specific and more homogeneous groups, such as thrombophilic women with well-characterized placenta-mediated pregnancy complications, stratified by disease severity and pathological findings. Because of fetal safety concerns with new anticoagulants, the intervention should focus on heparins alone or in combination with LDA. Thus, placenta-mediated pregnancy complications deserve precision medicine, defining disease by mechanism rather than outcome with interventions focused on a more personalized approach.


Cultural and religious components in Nigerian parents' perceptions of the aetiology of cleft lip and palate: implications for treatment and rehabilitation.
The present study was conducted to find out the perceptions of mothers from two Nigerian ethnic groups who had children with cleft lip and palate (CLP) about the aetiology of the defect. Mothers of 16 children with CLP from the Yoruba ethnic group who attended the maxillofacial clinic of the Obafemi Awolowo University teaching hospital in southern Nigeria and 20 children with CLP from the Hausa/Fulani ethnic group who attended the maxillofacial clinic of the University of Maiduguri teaching hospital in northeastern Nigeria were interviewed over an 8-month period. We used standardised interviews including questions with ethnographic components to allow us to collect information about traditional beliefs about clefts. Interviews were recorded on tape for later analysis. Thirteen of the 16 parents from the Yoruba group attributed the aetiology of CLP to supernatural forces (evil spirits and ancestral spirits), while 16 of the 20 Hausa/Fulani parents attributed it to the "will of God". Twelve of 16 Yoruba parents had consulted traditional healers for treatment before coming to the hospital. Various plants and animal products were used to treat clefts and 10 of the Yoruba parents were referred to the hospital for further treatment by the traditional healers. Cultural and religious factors seem to have an important role in the explanations, labels and treatment that followed the birth of a child with CLP in this environment. There is a need for greater collaboration and sharing of information between modern medical practitioners and traditional healers.


New sensitive liquid chromatography method coupled with tandem mass spectrometric detection for the clinical analysis of vinorelbine and its metabolites in blood, plasma, urine and faeces.
A new sensitive and specific liquid chromatographic method coupled with tandem mass spectrometric detection was set up and validated for the simultaneous quantitation of vinorelbine, its main metabolite, 4-O-deacetylvinorelbine and two other minor metabolites, 20'-hydroxyvinorelbine and vinorelbine 6'-oxide. All these compounds, including vinblastine (used as internal standard) were deproteinised from blood, plasma and faeces (only diluted in urine), analysed on a cyano column and detected on a Micromass Quattro II system in the positive ion mode after ionisation, using an electrospray ion source. Under tandem mass spectrometry conditions, the specific product ions led one to accurately quantify vinorelbine and its metabolites in all biological fluids. In whole blood, linearity was assessed up to 200 ng/ml for vinorelbine and up to 50 ng/ml for the metabolites. The limit of quantitation was validated at 250 pg/ml for both vinorelbine and 4-O-deacetylvinorelbine. In the other biological media, the linearity was assessed within a same range and the limit of quantitation was adjusted according to the expected concentrations of each compound. This method was initially developed in order to identify the metabolite structures and to elucidate the metabolic pathway of vinorelbine. Thanks to its high sensitivity, this method has enabled the quantitation of vinorelbine and all its metabolites in whole blood over 168 h (i.e., 4-5 elimination half lives) whilst the previous liquid chromatographic methods allowed their measurement for a maximum of 48-72 h. Therefore, using this method has improved the reliability of the pharmacokinetic data analysis of vinorelbine.


Developmental extinction of liver lipoprotein lipase mRNA expression might be regulated by an NF-1-like site.
The molecular mechanism underlying the extinction of lipoprotein lipase (LPL) expression in rat liver during development was investigated. A mouse (BWTG3) and a rat (7777) hepatoma, both of which exhibit characteristics of fetal hepatocytes, were found to contain LPL mRNA, whereas the more differentiated human (Hep G2 and Hep 3B) or rat (Fa32) hepatoma cell lines did not. Somatic cell hybrids between LPL-producing hepatoma cells and non-LPL-producing cells, such as adult rat hepatocytes or fibroblasts, exhibited extinction of LPL gene expression. Assay of expression of nested deletions in the 5' regulatory sequences of the LPL gene in the Hep G2 cell line and in BWTG3 cells localized sequences involved in the suppression of LPL production to a region between -591 and -288 relative to the transcription initiation site. A site with sequence homology to a glucocorticoid responsive element (GRE) was shown not to play an important role in the extinction process. A novel transcription factor, termed RF-1-LPL, was shown to bind to an NF-1-like site in this region. In contrast to neonatal animals, in adult animals an additional protein complex (RF-2-LPL), was formed on the NF-1-like site, suggesting that this sequence might recruit a trans-acting factor involved in the extinction of LPL gene expression in adult rat liver.


Delphinidin-induced autophagy protects pancreatic β cells against apoptosis resulting from high-glucose stress via AMPK signaling pathway.
Hyperglycemia, a diagnostic characteristic of diabetes mellitus, is detrimental to pancreatic β cells. Delphinidin, a member of the anthocyanin family, inhibits glucose absorption, increases glucagon-like peptide-1 (GLP-1) secretion, and improves insulin secretion in diabetes. However, whether delphinidin plays a protective role in pancreatic β-cell mass and function is not clear. In this study, delphinidin was found to decrease the high-glucose-induced apoptosis of RIN-m5F pancreatic β cells. In addition, delphinidin induced autophagy in RIN-m5F cells under the normal and high-glucose conditions, while 3-methyladenine (3-MA) inhibition of autophagy significantly diminished the protective role of delphinidin against high-glucose-induced apoptosis of pancreatic β cells. Delphinidin also decreased the level of cleaved caspase 3 and increased the phosphorylation level of AMP-activated protein kinase α (AMPKα) Thr172. Compound C, an AMPK inhibitor, was found to decrease the ratio of LC3-II/LC3-I, and the apoptotic rate of high-glucose-injured cells was increased after treatment with delphinidin, indicating that delphinidin attenuated the negative effects of high-glucose stress to cells. In conclusion, our data demonstrate that delphinidin protects pancreatic β cells against high-glucose-induced injury by autophagy regulation via the AMPK signaling pathway. These findings might shed light on the underlying mechanisms of diabetes and help improve the prevention and therapy of this common disease.


Differences in rejection grading after simultaneous pancreas and kidney transplantation in pigs.
Clinical observations suggest that recipients of multiorgan transplants from the same donor can have disparate immunological reactions to each organ. We studied this phenomenon in 36 diabetic (streptozotocin-induced), bilaterally nephrectomized, immunosuppressed (cyclosporine, azathioprine, prednisone) pig recipients of simultaneous (same donor) pancreas (bladder drained) and kidney allografts by grading the histological intensity of rejection in biopsies of each organ at defined intervals posttransplant. Graft function was monitored by plasma glucose (PG) and urine amylase (UA) for the pancreas and serum creatinine (Cr) for the kidney. Interstitial rejection was graded as absent, mild, moderate, and severe in, respectively, 8%, 25%, 42%, and 25% of pancreas vs. 4%, 12%, 27%, and 57% of kidney biopsies at 1 week; and 0%, 43%, 29%, and 29% of pancreases vs. 10%, 0%, 30%, and 60% of kidneys at two weeks. Although the distribution of grades was similar in the two organs (P > 0.1), the grade of rejection for each pair at 1 week (n = 24) was discordant in 75% (42% differed by one and 33% by > or = 2 grades) and at 2 weeks (n = 7) in 57% (29% by 1 and 29% by > or = 2 grades). The inability to use the severity of interstitial rejection in one organ to predict the findings in the other is exemplified by the fact that for the two pancreases without interstitial rejection at one week, the corresponding kidney showed moderate or severe rejection, and for the 1 kidney without rejection the corresponding pancreas showed moderate rejection. Vascular rejection grades (absent, mild, moderate, severe) also showed a similar distribution for the pancreas (57%, 30%, 9%, 4%) vs. kidney (50%, 38%, 0%, 12%) at 1 week, and at 2 weeks (57%, 29%, 0%, and 14% for the pancreas vs. 78%, 11%, 0%, and 11 for the kidney) (P > or = 0.64). However, the grading of vascular rejection in organ pairs was dyssynchronous in 54% at 1 week (n = 22) and 29% at 2 weeks (n = 7). No vascular rejection in the pancreas with rejection in the kidney was seen in 5 pairs at 1 week (23%) and 0 at 2 weeks (0%), while no rejection in the kidney with rejection in the pancreas was seen in 5 pairs at 1 week (23%) and 2 pairs at 2 weeks (29%).(ABSTRACT TRUNCATED AT 400 WORDS)


Mycobacterium marinum infection in a renal transplant recipient.
Infections with atypical mycobacteria occur more frequently in patients with solid organ transplants than in the normal host. We report a case of cutaneous Mycobacterium marinum infection in a renal transplant recipient. The patient presented with nodules on the forearm after returning from a fishing trip and was treated for cellulitis without success. Cultures of a biopsy of the lesion grew M. marinum. The patient was treated with ethambutol and ciprofloxacin with a good response; however, 9 months of treatment were required for complete resolution. Immunosuppressive therapy for renal transplantation increases susceptibility to a variety of opportunistic infections. A patient who presents with nodules on the extremities should be questioned regarding contact with fish, aquatic environments, or fish tank water, in which case infection with M. marinum should be considered. The diagnosis and treatment of this infection in transplant recipients is discussed.


Extracorporeal Photopheresis for Non-skin GvHD.
Graft versus host disease (GvHD) is one of the most feared adverse events of allogeneic hematopoietic stem cell transplantation. In severe grades of GvHD patients die from infections due to impairment of their immune defense or therapy-refractory involvement of intestines, liver and lung. Extracorporeal photopheresis is an effective treatment for acute and chronic graft versus host disease without severe impairment of the recipient's immune system. It is generally better known for its effect on skin GvHD but all other manifestations of GvHD can respond as well. Herein we report a brief review of its history and give an overview of the current knowledge of extracorporeal photopheresis in non-skin GvHD.


Investigating the risk of cancer in 1990-1991 US Gulf War veterans with the use of state cancer registry data.
The purpose of this study was to determine whether proportional cancer incidence is greater among Gulf War veterans compared with non-Gulf War veterans. Files obtained from the Defense Manpower Data Center included data for 621,902 veterans who were deployed to the Persian Gulf during the 1990 to 1991 Gulf War (August 2, 1990, to March 1, 1991) and 746,248 non-Gulf War veteran controls. Identification of veterans who received a cancer diagnosis between 1991 and 2006 was accomplished through record linkage of the Defense Manpower Data Center dataset with files from 28 state cancer registries and the Department of Veterans Affairs Central Cancer Registry. By the use of logistic regression, proportional incidence ratios adjusted for demographic and military characteristics were calculated by comparing the proportion of a specific cancer among all cancers in the Gulf War veterans to the proportion of that specific cancer among all cancers in the non-Gulf War veterans. Only lung cancer showed a statistically significant relative excess among Gulf War veterans compared with non-Gulf War veterans (adjusted proportional incidence ratios, 1.15; 95% confidence interval, 1.03-1.29). When adjusted for race, age, and sex, the overall proportion of cancers among Gulf War and non-Gulf War veterans was similar (odds ratio, 0.99; 95% CI, 0.96-1.02). With the exception of lung cancer, there is little evidence of excess risk of cancer associated with Gulf War deployment. A follow-up study is warranted to confirm this finding and to evaluate the role of greater smoking rates among deployed personnel.


Design and reach of a primary care weight management program.
To report the reach of Take Charge Lite (TCL), a lifestyle weight management program. Eight months of data were used to determine prescription reach (number of patients receiving a TCL prescription divided by total eligible), visit reach (number of patients with a TCL visit divided by total receiving a prescription), and total reach (number of patients with a TCL visit divided by total eligible). TCL prescription reach was 42.3% (1,071 prescriptions/2,528 eligible). There were 411 TCL first visits for an average visit reach of 38% (411/1,071). Total reach for the full period was 16% (411/2,528). Total reach was highest among female, middle-aged, and Black patients. There is potential for public health impact from such efforts but issues of reach require further planning and evaluation.


Pound 25 m investment to accelerate growth.
Undeterred by the current economic downturn, and determined to give its customers even better service and reduced order lead times via a more efficient manufacturing and distribution operation, Spirax Sarco, one of the UK's leading steam engineering specialists, is investing pound 25 million in its Cheltenham manufacturing operations in a move which it explains will bring together onto one enlarged site its entire production, distribution, and R&D activities. Jonathan Baillie reports.


Structure and dynamics of the human pleckstrin DEP domain: distinct molecular features of a novel DEP domain subfamily.
Pleckstrin1 is a major substrate for protein kinase C in platelets and leukocytes, and comprises a central DEP (disheveled, Egl-10, pleckstrin) domain, which is flanked by two PH (pleckstrin homology) domains. DEP domains display a unique alpha/beta fold and have been implicated in membrane binding utilizing different mechanisms. Using multiple sequence alignments and phylogenetic tree reconstructions, we find that 6 subfamilies of the DEP domain exist, of which pleckstrin represents a novel and distinct subfamily. To clarify structural determinants of the DEP fold and to gain further insight into the role of the DEP domain, we determined the three-dimensional structure of the pleckstrin DEP domain using heteronuclear NMR spectroscopy. Pleckstrin DEP shares main structural features with the DEP domains of disheveled and Epac, which belong to different DEP subfamilies. However, the pleckstrin DEP fold is distinct from these structures and contains an additional, short helix alpha4 inserted in the beta4-beta5 loop that exhibits increased backbone mobility as judged by NMR relaxation measurements. Based on sequence conservation, the helix alpha4 may also be present in the DEP domains of regulator of G-protein signaling (RGS) proteins, which are members of the same DEP subfamily. In pleckstrin, the DEP domain is surrounded by two PH domains. Structural analysis and charge complementarity suggest that the DEP domain may interact with the N-terminal PH domain in pleckstrin. Phosphorylation of the PH-DEP linker, which is required for pleckstrin function, could regulate such an intramolecular interaction. This suggests a role of the pleckstrin DEP domain in intramolecular domain interactions, which is distinct from the functions of other DEP domain subfamilies found so far.


A five-step approach to digital image manipulation for the radiologist.
Digital manipulation of images plays a key role in development of multimedia presentations. Five basic steps to digitizing images and preparing them for publication and computer presentation are scanning, correction, editing and labeling, saving files, and producing final output. These steps can be completed with commercially available hardware and image manipulation software (eg, Photoshop). The higher the quality of the original scanned image, the more image data there will be to edit: A good image cannot be created from an inferior scan. The most important functions for properly scanning images are size, resolution, and color. Resolutions of 300 ppi and 72 ppi should be used for print publication and computer presentations, respectively. The higher resolution image has the larger file size. The scanned image should be saved as a TIFF (tagged image file format), which is an uncompressed file type used for printed images. The Joint Photographic Experts Group (JPEG) format compresses the size of the image file but also reduces image quality. The JPEG format is a good choice if a small file size is needed, such as in Web and PowerPoint presentations. If the user needs to save an image as a JPEG file, the image should be edited first and then saved once in JPEG format. With Photoshop, the user can rotate and crop an image; adjust its brightness, contrast, and color; remove unwanted patient information, dust, and scratches; and add text and symbol labels to enhance images for teaching purposes. Digital manipulation can be fast and effective if the user has some basic knowledge and tools.


Appropriate surgical margin for odontogenic myxoma: a review of 12 cases.
Odontogenic myxoma (OM) is a rare benign tumor that is frequently nonencapsulated and invades the surrounding bone, resulting in a high risk of recurrence. However, the optimal surgical technique and appropriate surgical margin remains controversial. Here, we report our clinical investigation of 12 patients with OM diagnosed histopathologically. We retrospectively reviewed the records of 12 patients treated at our institution. Osteotomy or bone shaving with enucleation was generally performed with 5-mm bony margins from the radiologic extent of the tumor. One half of the cases occurred in the maxilla and the other half in the mandible. Treatment for maxillary OM was enucleation in 2 patients and maxillectomy in 4 patients. Treatment for mandibular OM was enucleation with shaving of the surrounding bone in 1 patient and segmental mandibulectomy in 5 patients. Radiographs of surgical specimen removed by segmental mandibulectomy indicated that the mean distance between the tumor and the margin was 5.4 (range 3.4-7.0) mm. Tumor recurrence was noted in 1 patient who had undergone enucleation alone. The 1-cm surgical margin for OM, as reported conventionally, might not be necessary. A prospective study is needed to determine the appropriate surgical margin for OM.


Lyme neuroborreliosis-epidemiology, diagnosis and management.
Lyme disease, caused by the Borrelia burgdorferi bacterium, is the most common vector-borne disease in the northern hemisphere. The clinical presentation varies with disease stage, and neurological manifestations (often referred to as Lyme neuroborreliosis) are reported in up to 12% of patients with Lyme disease. Most aspects of the epidemiology, clinical manifestation and treatment of Lyme neuroborreliosis are well known and accepted; only the management of so-called chronic Lyme disease is surrounded by considerable controversy. This term is used for disparate patient groups, including those who have untreated late-stage infection (for example, late neuroborreliosis), those with subjective symptoms that persist after treatment (termed 'post-treatment Lyme disease syndrome' [PTLDS]), and those with unexplained subjective complaints that may or may not be accompanied by positive test results for B. burgdorferi infection in serum (here called 'chronic Lyme disease'). The incidence of PTLDS is still a matter of debate, and its pathogenesis is unclear, but there is evidence that these patients do not have ongoing B. burgdorferi infection and, thus, do not benefit from additional antibiotic therapy. Chronic Lyme disease lacks an accepted clinical definition, and most patients who receive this diagnosis have other illnesses. Thus, a careful diagnostic work-up is needed to ensure proper treatment.