Mortality in relation to profiles of clinical features in Ghanaian severely undernourished children aged 0-59 months: an observational study.

Severe acute malnutrition (SAM) is associated with a complex pattern of various clinical conditions. We investigated how risk factors cluster in children with SAM, the relationship between clusters of risk factors and mortality as well as length of stay in children with SAM. A prospective observational study design was used. Data were extracted from medical records of 601 infants and children aged 0-59 months admitted and treated for SAM in three Ghanaian referral hospital between June 2013 and June 2018. Among the 601 medical records extracted, ninety-nine died. Three clusters of medical features clearly emerged from data analyses. Firstly, an association was defined by eye signs, pallor, diarrhoea and vomiting with gastrointestinal infections and malaria. In this cluster, pallor and eye signs were related to 2- to 5-fold increased mortality risk. Secondly, HIV, oedema, fast pulse, respiratory infections and tuberculosis; among those features, HIV increased child mortality risk by 2-fold. Thirdly, shock, convulsions, dermatitis, cold hands and feet, weak pulse, urinary tract infections and irritability were clustered. Among those features, cold hands and feet, dermatitis, convulsions and shock increased child mortality risk in a range of 2- to 9-fold. Medical conditions and clinical signs in children diagnosed with SAM associate in patterns and are related to clinical outcomes.

Extranodal non-Hodgkin lymphoma of the sinonasal cavities: A 22-case report.

OBJECTIVE: To determine presenting features, management and prognosis in extranodal non-Hodgkin lymphoma of the sinonasal tract. MATERIAL AND METHODS: A retrospective study between 2004 and 2013 in the University Hospital Center of Nantes (France) recruited patients with lymphoma discovered by sinonasal involvement. Epidemiologic, diagnostic, clinical and prognostic criteria were analyzed, with survival studied on the Kaplan-Meier estimator and Log-rank test. RESULTS: Twenty-two patients were included: 14 male, 7 female, with a mean age of 65 years at diagnosis. All had non-Hodgkin lymphoma, with strong predominance of diffuse large B-cell lymphoma (77%). Seven patients had risk factors for lymphoma (infection by HIV, EBV or chronic lymphocytic leukemia). A majority (68%) had advanced tumor at diagnosis (stage IV on the Ann Arbor classification). Most were located in the craniofacial bones (68%), mainly involving the maxillary or ethmoidal sinuses. The most frequent presenting symptoms were unilateral nasal obstruction, mucopurulent rhinorrhea, recurrent epistaxis or diplopia. Treatment consisted in chemotherapy, in some cases associated to radiotherapy. Overall survival was 82% at 12 months and 73% at 36 months. Recurrence-free survival was 76% at 12 months and 64% at 36 months. CONCLUSION: Lymphoma is an aggressive pathology; revelation by sinonasal involvement is rare. Recommended treatment is chemotherapy, possibly associated to radiotherapy. Prognosis depends on histologic type, Ann Arbor stage at diagnosis and the therapeutic options available for the individual patient.

Antiplasmodial activity and cytotoxicity of 10ß-aminoquinolinylethylethers of artemisinin.

Each year roughly 800 000 people die of malaria, with 95% being African children. The shortcomings of the current drugs and the emergence of P. falciparum resistance to the artemisinin class of compounds warrant the search for new classes or derivatives. In search for such compounds, a series of 10ß-amino-quinolinylethylethers of artemisinin, previously synthesized from this laboratory were screened for antimalarial activity against both the chloroquine-susceptible 3D7 and -resistant K1 strains of P. falciparum. Their cytotoxicity was also assessed against HEK 293 and HepG2 cell lines.The parasitic and mammalian cells were incubated with compounds at various concentrations for 72 h. The antimalarial activity was determined using SYBR Green I-based fluorescence. For cytotoxicity determination, cells were grown to confluence and CellTiter-Glo luminescent cell viability assay was used.All derivatives proved to be active against both strains with good selectivity towards the parasitic cells. The derivative 11 featuring 2 artemisinin moieties and an aminoethylpiperazine linker was the most active of all. It possessed 17- and 166-fold more potency than artemether against 3D7 (EC50: 9.5 vs. 166 nM) and K1 (10.9 vs. 1723.3 nM), respectively, while was found to be as potent as artesunate against both strains.Derivative 11 stands as a good candidate to be further investigated primarily in vitro in comparison with an equimolar combination of chloroquine (CQ) and artemisinin to ascertain its advantages, if any, over the combination.

What predicts failed cannulation and therapy at ERCP? Results of a large-scale multicenter analysis.

UNLABELLED: STUDY BACKGROUND AND AIMS: Predicting outcome at endoscopic retrograde cholangiopancreatography (ERCP) remains difficult. Our aim was to identify the risk factors for failed ERCP. PATIENTS AND METHODS: A prospective multicenter study of ERCP was performed in 66 hospitals across England. Data on 4561 patients were collected using a structured questionnaire completed at the time of ERCP. RESULTS: In total 3209 patients had not had an ERCP prior to the study period. Considering their first ever ERCP, 2683 (84 %) were successfully cannulated, 2241(70 %) had all intended therapy completed, 360 (11 %) had some intended therapy completed, and 608 (19 %) were considered to have had a failed procedure. For first ever ERCP, factors associated with incomplete procedure (odds ratio and 95 % confidence interval) were: Billroth surgery (9.2, 3.2 - 26.7), precutting (2.0, 1.6 - 2.7), common bile duct (CBD) stone size and number (3.2, 2.1 - 4.8 for multiple, large stones), interventions in the pancreatic duct (3.4, 1.6 - 7.0), and CBD stenting (2.8, 2.2 - 3.5). Analysis of the 1352 patients who had undergone an ERCP prior to the study period indicated previous failed ERCP was also predictive of incomplete therapy (1.5, 1.1 - 2.1). The modified Schutz score correlated with ERCP completion, as did the Morriston score, even when modified to include only variables measurable before the procedure. CONCLUSION: This study confirms that patient- and procedure-based variables are key predictors of technical success and validates current methods of rating ERCP difficulty. Of note, a correlation between outcome and institutional factors, such as unit and endoscopist caseload, was not demonstrated.

The use of prebiotics and probiotics in Infant Formula

Gastrointestinal flora influences health; but the composition of flora can be changed with prebiotics or probiotics. The addition of probiotics to powdered infant formula has not been demonstrated to be harmful to healthy term infants. However; evidence of clinical efficacy regarding their addition is insufficient to recommend the routine use of such formula. The administration of probiotic (single or in combination) supplementation in infant or follow-on formula; and given beyond early infancy; may be associated with some clinical benefits; such as a reduction in the risk of nonspecific gastrointestinal infections; a reduced risk of antibiotic use and a lower frequency of colic and irritability. Confirmatory well-designed clinical research studies are necessary

Dietary fumonisin exposure in a rural population of South Africa.

A validated culturally specific dietary assessment method was used to determine the habitual maize intakes of black Xhosa-speaking Africans living in the Centane region of the Eastern Cape Province to assess their exposure to the carcinogenic fumonisin mycotoxins. The mean total dry weight maize intakes of home-grown, commercial or combined (both maize sources) were 474, 344, 462 g day(-1), respectively. When considering the total mean levels of fumonisin in home-grown maize (1142 microg kg(-1)) and commercial maize (222 microg kg(-1)), the probable daily intakes (PDI's), expressed as microg kg(-1) body weight day(-1) were 12.1 (95%CI: 0.3-4926.5) and 1.3 (95%CI: 1.0-1.8) for men and 6.7 (95%CI: 1.0-457.8) and 1.1 (95%CI: 0.9-1.3) for women, consuming home-grown and commercial maize, respectively. Based on the different maize-based beer drinking frequencies the PDI's varied between 6.9 and 12.0 microg kg(-1)/drinking event. Depending on the maize intake patterns an exposure "window" exists where fumonisin exposure is below the recommended group provisional maximum tolerable daily intake (PMTDI) for fumonisins of 2 microg kg(-1)bw day(-1). The assessment of fumonisin exposure and development of preventative strategies depend, not only the accurate determination of total fumonisin levels in maize, but also on the distinct dietary patterns of a specific population.

Guidelines on the management of common bile duct stones (CBDS).

The last 30 years have seen major developments in the management of gallstone-related disease, which in the United States alone costs over 6 billion dollars per annum to treat. Endoscopic retrograde cholangiopancreatography (ERCP) has become a widely available and routine procedure, whilst open cholecystectomy has largely been replaced by a laparoscopic approach, which may or may not include laparoscopic exploration of the common bile duct (LCBDE). In addition, new imaging techniques such as magnetic resonance cholangiography (MR) and endoscopic ultrasound (EUS) offer the opportunity to accurately visualise the biliary system without instrumentation of the ducts. As a consequence clinicians are now faced with a number of potentially valid options for managing patients with suspected CBDS. It is with this in mind that the following guidelines have been written.

Risk factors for complication following ERCP; results of a large-scale, prospective multicenter study.

BACKGROUND AND STUDY AIMS: Analyses of endoscopic retrograde cholangiopancreatography (ERCP) complication are often constrained by the number of endpoints observed. This large-scale study aimed to identify the principal risk factors for ERCP complication. PATIENTS AND METHODS: This was a prospective multicenter study of ERCP complications, based in five English regions. An exploratory univariable analysis of patients' first recorded procedures identified potentially important patient- and procedure-related factors. For overall complications and pancreatitis, variables significant in univariable analysis were included in multiple regression. RESULTS: A total of 66 centers collected data on 5264 ERCPs, performed on 4561 patients. A therapeutic intervention was attempted in 3447/4561 (76%) of patients as part of their first recorded ERCP. Following first recorded ERCP, 230 patients (5.0%) suffered > or = 1 complication: pancreatitis in 74 (1.6%), cholangitis in 48 (1.0 %), hemorrhage in 40 (0.9%), perforation in 20 (0.4%), and miscellaneous in 54 (1.2%). Significant factors from multiple regression were included in a multi-level analysis, which incorporated variables measured at the level of the endoscopist and hospital. For overall complication, risk factors ( P value, odds ratio [OR], 95% confidence interval [CI]) were: cannulation attempts > 1 ( P = 0.094, OR 1.32, 95% CI 0.95-1.83), precut ( P = 0.033, OR 1.55, 95 % CI 1.04-2.32), and suspected sphincter of Oddi dysfunction ( P = 0.121, OR 1.97, 95 % CI 0.84-4.64). For pancreatitis, risk factors ( Pvalue, OR, and 95 % CI) were: cannulation attempts > 1 ( P = 0.0001, OR 3.14, 95% CI 1.74-5.67), female sex ( P < 0.001, OR 2.22, 95% CI 1.43-3.45), age ( P < 0.002, OR 1.09 per 5 year decrease, 95% CI 1.03-1.15), and performance in a district (as opposed to university) hospital ( P = 0.034, OR 2.41, 95% CI 1.08-5.41). CONCLUSION: Careful patient selection combined with skilled cannulation minimizes complications. Higher-risk procedures should be performed in specialist centers.

A brief history of vaccines and vaccination.

Human vaccinology, with its primary focus on the individual, seems far removed from veterinary medicine, with its concern for the health of the herd. Yet several episodes in the past (smallpox, fowl cholera, anthrax, swine erysipelas, rabies, tuberculosis, etc.) serve to illustrate the proximity between research on veterinary and human vaccines. In some cases the human vaccine was developed first, while in other cases it was the animal vaccine. The history of vaccinology clearly demonstrates the importance of these 'two medicines' working together. Foot and mouth disease (FMD) vaccines were among the first vaccines to be developed, beginning at the end of the 19th Century. Thanks to the discoveries of several researchers, including European researchers such as Vallée (French), Waldmann (German), Frenkel (Dutch) and Capstick (British), FMD vaccines began to be produced on an industrial scale from 1950 onwards, making possible vaccination of millions of animals in Europe and beyond. Vaccination strategies against FMD have always been dependent on the properties of the vaccines being used. At the beginning of the 21st Century FMD vaccines are designed in such a way that serological tests can differentiate infected from vaccinated animals, which has affected OIE regulations on international trade in animals and animal products. The history of vaccination against rinderpest, bovine contagious pleuropneumonia, and Marek's disease will also be dealt with.

Antigen and vaccine banks: technical requirements and the role of the european antigen bank in emergency foot and mouth disease vaccination.

Antigen and vaccine banks are stocks of immunogenic materials ready to be formulated into vaccines (bulk antigens) or ready to use (vaccines) in case of need by one or more of the parties of the bank. These stocks were primarily developed by foot and mouth disease [FMD] free European countries to control unexpected severe FMD episodes after the cessation of routine vaccination in the 1990s. For various reasons, including the lack of suitable antigens or of discriminatory tests to be used following emergency vaccination, such banks have so far not been developed to control other transboundary diseases, although over the last few years stocks of vaccines have been collected by the European Community to support control measures for bluetongue or classical swine fever. The FMD virus antigens in the banks are stored at ultra-low temperatures (usually -130 degrees C) to guarantee a shelf life of at least five years compared to a shelf-life of one to two years for vaccines stored at +4 degrees C. When concentrated, a 50 I volume of antigens can contain up to 15 million cattle doses as per the standard potency specifications in the OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. Selecting antigen/vaccine strains for storage in a bank and selecting the appropriate strain(s) to be used in the case of emergency vaccination is the responsibility of FMD disease experts. The paper discusses the role of serological testing for the detection of infected animals in a vaccinated population, which is necessary for the recognition of FMD status. Technical advantages and disadvantages of antigen and vaccine banks in general are also outlined in this article. Finally, the experience of the European Community in organising, renewing, and controlling a sizeable FMD antigen bank since 1993 is discussed, and the use of the European Union (EU) antigen bank for international actions outside the EU is presented.

When is pancreatitis considered to be of biliary origin and what are the implications for management?

Acute pancreatitis is a disease caused by gallstones in 40-60% of patients. Identification of these patients is extremely important, since there are specific therapeutic interventions by endoscopic sphincterotomy and/or cholecystectomy. The combination of trans-abdominal ultrasound (stones in the gallbladder and/or main bile duct) and elevated serum alanine transaminase (circa >60 IU/l within 48 h of presentation) indicates gallstones as the cause in the majority of patients with acute pancreatitis. In the presence of a severe attack this is a strong indication for intervention by endoscopic sphincterotomy. The presence of a significant main bile duct dilatation is also strongly indicative of gallstones and should prompt the use of endoluminal ultrasonography: >8 mm diameter with gallbladder in situ, or >10 mm following cholecystectomy if aged <70 years and >12 mm, respectively, if > or = 70 years. In mild pancreatitis surgically fit patients should be treated by cholecystectomy, and intra-operative cholangiography, as pre-operative biliary imaging is not efficient in this setting. Patients who are not fit for cholecystectomy should undergo prophylactic endoscopic sphincterotomy to prevent further attacks. In the post-acute-phase, pancreatitis patients in whom the aetiology is uncertain should undergo endoluminal ultrasonography. Thisis the most sensitive method for the detection of cholelithiasis and choledocholithiasis and may reveal alternative aetiological factors such as a small ampullary or pancreatic cancer. A number of recent studies have shown that bile crystal analysis, a marker for microlithiasis, increases the yield of positive results over and above endoluminal ultrasonography, and should be considered as part of the modern investigative algorithm.

TIPSS in the treatment of ectopic variceal bleeding.

BACKGROUND/AIMS: Bleeding from ectopic varices is a well recognized life-threatening complication of portal hypertension but the optimal treatment of this problem is yet to be established. METHODOLOGY: We retrospectively reviewed patients with ectopic variceal bleeding who underwent transjugular intrahepatic portosystemic shunting for recurrent bleeding not responding to conservative management. RESULTS: Over an eleven-year period we identified ten patients who underwent TIPSS for ectopic variceal hemorrhage. Six patients bled from rectal varices and four from stomal varices. TIPSS was successful in nine patients. The Childs-Pugh grade of the patients was A=3, B=3 and C=4. The follow-up period ranged from 7 days to 1380 days. Rebleeding occurred in three patients, two of whom died. The remaining patient had a blocked TIPSS and successfully underwent repeat stenting which re-established patency. Four patients (Childs B=2, Childs C=2) died within 60 days. All three patients with Childs A liver disease were alive at one year. CONCLUSIONS: TIPSS can be used effectively to treat ectopic variceal bleeding. Patients with Childs grade A liver disease appear to do well with TIPSS. Those with advanced liver disease (Childs B & C) have a uniformly poor outcome. In these patients ectopic variceal hemorrhage is likely to represent a terminal event.

A study of the role of neuro-glial remodeling in the oxytocin system at lactation.

Under conditions of strong secretion of neurohypophysial hormone, such as during parturition, lactation and dehydration, the hypothalamic oxytocin-system displays a remarkable morphological plasticity such that astrocytic coverage of its neurones diminishes, their surfaces become directly juxtaposed and contacted by an increased number of synapses. A growing body of evidence indicates that these anatomical changes have an impact on glutamatergic neurotransmission in the supraoptic nucleus, and may be therefore of physiological consequence. We here evaluated the consequences of the inhibition of such plasticity on the overall activity of the oxytocin system during lactation. Remodeling was prevented by performing hypothalamic microinjections in gestating rats of endoneuraminidase, an enzyme that removes polysialic acid from the neural cell adhesion molecule. Our earlier studies established that the presence of polysialic acid is a prerequisite for remodeling of the oxytocin system in the supraoptic and paraventricular nuclei. In dams in which polysialic acid was absent in all magnocellular nuclei after bilateral endoneuraminidase injections, parturition was normal and neither the frequency nor the amplitude of suckling-induced reflex milk ejections was different from vehicle-treated dams. The weight gain of pups was also normal as was water intake by the dams. We then assessed the electrical activity of antidromically identified magnocellular neurones in the polysialic acid-free supraoptic nucleus of isoflurane-anesthetized lactating rats. Basal and bursting activity characteristic of oxytocin neurones before each reflex milk ejection was not significantly different from that recorded in the supraoptic nucleus of rats with normal levels of polysialic acid. Our results indicate that neuro-glial remodeling, despite its role on fine modulation of oxytocin neuronal activity, is not essential to parturition and lactation.

Influence of opioid use on surgical and long-term outcome after resection for chronic pancreatitis.

BACKGROUND: The outcome of pancreatic resection for chronic pancreatitis in patients with preoperative opioid use is not well described. METHODS: During 1997 to 2003, 112 of 231 patients referred with chronic pancreatitis underwent pancreatic resection. The outcome of patients who had preoperative opioid use (N=46) was compared with those without (N=66). RESULTS: Patients who used opioids presented at a younger age and had a younger age of symptom onset, longer symptom duration, more hospitalizations, a higher frequency of diabetes mellitus, a higher pain score, and more restriction in daily activity (all P<.05). Twenty-one (46%) patients with opioid use had a total pancreatectomy compared with 9 (14%) without opioid use (P=.0002); the 21 patients also had a higher frequency of postoperative bleeding and early reoperation (8 vs 2, P<.02; 11 vs 3, P=.003, respectively). Mortality and overall morbidity was not significantly different between the 2 groups (4 vs 1, 27 vs 34, respectively). Pain scores improved postoperatively in both groups (P=.001) and was not significantly different between the groups from 12 months onward (median follow-up of 12 months, range, 3-60 months). Twenty percent of patients who used preoperative opioids however reverted to morphine use compared with 6% of patients who had not used opioids. CONCLUSIONS: Patients who used opioids had more advanced disease than patients without opioid use, accounting for part of the postoperative morbidity. Although long-term pain relief was comparable between the 2 groups, maintaining opioid withdrawal was more problematic in those with preoperative opioid use. Earlier referral for resection may be warranted in this group of patients.

Hereditary pancreatic endocrine tumours.

The two main types of hereditary pancreatic neuroendocrine tumours are found in multiple endocrine neoplasia type 1 (MEN-1) and von Hippel-Lindau disease (VHL), but also in the rarer disorders of neurofibromatosis type 1 and tuberous sclerosis. This review considers the major advances that have been made in genetic diagnosis, tumour localization, medical and surgical treatment and palliation with systemic chemotherapy and radionuclides. With the exception of the insulinoma syndrome, all of the various hormone excess syndromes of MEN-1 can be treated medically. The role of surgery however remains controversial ranging from no intervention (except enucleation for insulinoma), intervening for tumours diagnosed only by biochemical criteria, intervening in those tumours only detected radiologically (1-2 cm in diameter) or intervening only if the tumour diameter is > 3 cm in diameter. The extent of surgery is also controversial, although radical lymphadenectomy is generally recommended. Pancreatic tumours associated with VHL are usually non-functioning and tumours of at least 2 cm in diameter should be resected. Practice guidelines recommend that screening in patients with MEN-1 should commence at the age of 5 years for insulinoma and at the age of 20 years for other pancreatic neuroendocrine tumours and variously at 10-20 years of age for pancreatic tumours in patients with VHL. The evidence is increasing that the life span of patients may be significantly improved with surgical intervention, mandating the widespread use of tumour surveillance and multidisciplinary team management.

Highly conserved chromosomes in an Asian squirrel (Menetes berdmorei, Rodentia: Sciuridae) as demonstrated by ZOO-FISH with human probes.

The chromosomes of Menetes berdmorei (Rodentia, Sciuridae, Sciurinae) were studied by ZOO-FISH using whole human chromosome probes. All homoeologies between M. berdmorei and human chromosomes were determined, except for two small chromosome segments. Twelve human chromosomes are conserved in a unique block of synteny; ten are split into two and one into three blocks. Thus, a small number of interchromosomal rearrangements, about twenty, separates human from this squirrel karyotype. Homoeologies between human and the presumed ancestral chromosomes of Sciurinae could also be deduced, as well as those with the presumed ancestral chromosomes of eutherian mammals. Sciurinae chromosomes appear to be much closer to those of non-rodent mammals than those of Muridae and Cricetidae species studied so far. Thus, they provide an interesting tool to link the rodent genome to those of other mammals.

Reconstruction of the ancestral karyotype of eutherian mammals.

Applying the parsimony principle, i.e. that chromosomes identical in species belonging to different taxa were likely to be present in their common ancestor, the ancestral karyotype of eutherian mammals (about 100 million years old) was tentatively reconstructed. Comparing chromosome banding with all ZOO-FISH data from literature or studied by us, this reconstruction can be proposed with only limited uncertainties. This karyotype comprised 50 chromosomes of which 40-42 were acrocentrics. Ten ancestral pairs of chromosomes were homologous to a single human chromosome: 5, 6, 9, 11, 13, 17, 18, 20, X and Y (human nomenclature). Nine others were homologous to a part of a human chromosome: 1p + q (proximal), 1q, 2p + q (proximal), 2q, part of 7, 8q, 10p, 10q and 19p (human nomenclature). Finally, seven pairs of chromosomes, homologs to human chromosomes 3 + 21, 4 + 8p, part of 7 + 16p, part of 12 + part of 22 (twice), 14 + 15, 16q + 19q, formed syntenies disrupted in man.