Cytotoxic activity of Fagonia cretica against human breast cancer cells

In many parts of the world, plants are directly utilised for their medicinal properties. Traditional medicine from Pakistan, India and the Far East is well documented and its history is embedded in folklore. It has been documented that an aqueous extract of the desert shrub, Fagonia cretica, is a popular treatment for breast cancer in Pakistan. The administration of an aqueous extract of Fagonia cretica is reported effective at reducing tumour size and improving the quality of life of breast cancer patients, is well tolerated and does not exhibit adverse effects like vomiting, diarrhoea or alopecia which are common side effects of standard cytotoxic therapy. In the past, many pharmacologically active and chemotherapeutic compounds have been isolated from plants which subsequently have proven to be successful in clinical trials and been used as primary compounds in therapeutic regimes. Fagonia cretica has historical use as a treatment for breast cancer, yet there is little scientific evidence which shows chemotherapeutic potential towards breast tumours. Preparation and analysis of an aqueous extract of Fagonia cretica may reveal novel chemotherapeutic agents that can be used to effectively target cancer cells. An understanding of the mechanism of any activity may improve our understanding of cancer cell biology and reveal novel therapeutic targets. This thesis describes for the first time that an aqueous extract of Fagonia cretica shows potent in vitro cytotoxic activity towards breast cancer epithelial cell lines which was not seen towards normal mammary epithelial cells. Elucidation and characterisation of the cytotoxic mechanism was undertaken by analysing DNA damage, cell cycle status, apoptosis, metabolic state and expression of transcription factors and their targets. Finally, methods for the isolation and identification of active compound(s) were developed using various chromatographic techniques. An aqueous extract of Fagonia cretica was able to reduce cell viability significantly in two phenotypically different breast cancer cell lines (MCF-7 and MDA-MB-231). This activity was markedly reduced in normal mammary epithelial cells (HMEpC). Further investigation into the mode of action revealed that extract treatment induced cell cycle arrest and apoptosis in both MCF-7 and MDA-MB-231 cell lines. This coincided with the formation of DNA double stranded breaks and the DNA repair marker ?-H2AX. In MCF-7 cells, ATM/ATR activation resulted in increased p53 expression and of its transcriptional targets p21 and bax, suggesting a role for a p53-mediated response. Furthermore, inhibition of extract-induced p53 expression with siRNA reduced the cytotoxic effect against MCF-7 cells. Extract treatment was also associated with increased FOXO3a expression in MCF-7 and MDA-MB-231 cells. In the absence of functional p53, siRNA knockdown of extract-induced FOXO3a expression was completely abrogated, suggesting that FOXO3a plays a vital role in extract-induced cytotoxicity. Isolation and characterisation of the active compound(s) within the extract was attempted using liquid chromatography and mass spectrometry in conjunction with a cell viability assay. Multiple fractionations generated an active fraction that contained four major compounds as detected by mass spectrometry. However, none of these compounds were identified structurally or chemically due to constraints within the methodology.

Investigating the prevalence of Salmonella in dogs within the Midlands region of the United Kingdom

Background - The intimate relationship between dogs and their owners has the potential to increase the risk of human exposure to bacterial pathogens. Over the past 40 years, there have been several reports on transmission of salmonellae from dogs to humans. This study therefore aimed to determine the prevalence of Salmonella in the faeces of dogs from the Midlands region of the United Kingdom to assess exposure risk and potential for zoonotic transmission. Results - A total of 436 apparently healthy dogs without diarrhoea from households (n = 126), rescue centres (n = 96), boarding kennels (n = 43), retired greyhound kennels (n = 39) and a pet nutrition facility (n = 132) were investigated for Salmonella shedding. Faecal samples were processed by an enrichment culture based method. The faeces from one dog (0.23 %; 95 % confidence limit 0.006 %, 1.27 %) was positive for Salmonella. The species was S. enterica subspecies arizonae. Conclusion - This study showed that the prevalence of Salmonella from faeces from apparently healthy dogs from a variety of housing conditions is low; however, Salmonella shedding was still identified.

Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial.

BACKGROUND: EGFR overexpression occurs in 27-55% of oesophagogastric adenocarcinomas, and correlates with poor prognosis. We aimed to assess addition of the anti-EGFR antibody panitumumab to epirubicin, oxaliplatin, and capecitabine (EOC) in patients with advanced oesophagogastric adenocarcinoma. METHODS: In this randomised, open-label phase 3 trial (REAL3), we enrolled patients with untreated, metastatic, or locally advanced oesophagogastric adenocarcinoma at 63 centres (tertiary referral centres, teaching hospitals, and district general hospitals) in the UK. Eligible patients were randomly allocated (1:1) to receive up to eight 21-day cycles of open-label EOC (epirubicin 50 mg/m(2) and oxaliplatin 130 mg/m(2) on day 1 and capecitabine 1250 mg/m(2) per day on days 1-21) or modified-dose EOC plus panitumumab (mEOC+P; epirubicin 50 mg/m(2) and oxaliplatin 100 mg/m(2) on day 1, capecitabine 1000 mg/m(2) per day on days 1-21, and panitumumab 9 mg/kg on day 1). Randomisation was blocked and stratified for centre region, extent of disease, and performance status. The primary endpoint was overall survival in the intention-to-treat population. We assessed safety in all patients who received at least one dose of study drug. After a preplanned independent data monitoring committee review in October, 2011, trial recruitment was halted and panitumumab withdrawn. Data for patients on treatment were censored at this timepoint. This study is registered with ClinicalTrials.gov, number NCT00824785. FINDINGS: Between June 2, 2008, and Oct 17, 2011, we enrolled 553 eligible patients. Median overall survival in 275 patients allocated EOC was 11.3 months (95% CI 9.6-13.0) compared with 8.8 months (7.7-9.8) in 278 patients allocated mEOC+P (hazard ratio [HR] 1.37, 95% CI 1.07-1.76; p=0.013). mEOC+P was associated with increased incidence of grade 3-4 diarrhoea (48 [17%] of 276 patients allocated mEOC+P vs 29 [11%] of 266 patients allocated EOC), rash (29 [11%] vs two [1%]), mucositis (14 [5%] vs none), and hypomagnesaemia (13 [5%] vs none) but reduced incidence of haematological toxicity (grade ≥ 3 neutropenia 35 [13%] vs 74 [28%]). INTERPRETATION: Addition of panitumumab to EOC chemotherapy does not increase overall survival and cannot be recommended for use in an unselected population with advanced oesophagogastric adenocarcinoma. FUNDING: Amgen, UK National Institute for Health Research Biomedical Research Centre.

The enteropathogenic Escherichia coli effector NleH inhibits apoptosis induced by Clostridium difficile toxin B

Clostridium difficile is a leading cause of nosocomial infections, causing a spectrum of diseases ranging from diarrhoea to pseudomembranous colitis triggered by a range of virulence factors including C. difficile toxins A (TcdA) and B (TcdB). TcdA and TcdB are monoglucosyltransferases that irreversibly glycosylate small Rho GTPases, inhibiting their ability to interact with their effectors, guanine nucleotide exchange factors, and membrane partners, leading to disruption of downstream signalling pathways and cell death. In addition, TcdB targets the mitochondria, inducing the intrinsic apoptotic pathway resulting in TcdB-mediated apoptosis. Modulation of apoptosis is a common strategy used by infectious agents. Recently, we have shown that the enteropathogenic Escherichia coli (EPEC) type III secretion system effector NleH has a broad-range anti-apoptotic activity. In this study we examined the effects of NleH on cells challenged with TcdB. During infection with wild-type EPEC, NleH inhibited TcdB-induced apoptosis at both low and high toxin concentrations. Transfected nleH1 alone was sufficient to block TcdB-induced cell rounding, nuclear condensation, mitochondrial swelling and lysis, and activation of caspase-3. These results show that NleH acts via a global anti-apoptotic pathway.

Impact of Cryptosporidium spp. interaction with co-occurring microorganisms on moderate-to-severe diarrhea in the developing world

Diarrheal illness is responsible for over a quarter of all deaths in children under 5 years of age in sub-Saharan Africa and South Asia. Recent findings have identified the parasite Cryptosporidium as a contributor to enteric disease. We examined 9,348 cases and 13,128 controls from the Global Enteric Multicenter Study to assess whether Cryptosporidium interacted with co-occurring pathogens based on adjusted odds of moderate-to-severe diarrhea (MSD). Cryptosporidium was found to interact negatively with Shigella spp., with multiplicative interaction score of 0.16 (95% CI: 0.07 to 0.37, p-value=0.000), and an additive interaction score of -9.81 (95% CI: -13.61 to -6.01, p-value=0.000). Cryptosporidium also interacted negatively with Aeromonas spp., Adenovirus, Norovirus, and Astrovirus with marginal significance. Odds of MSD for Cryptosporidium co-infection with Shigella spp., Aeromonas spp., Adenovirus, Norovirus, or Astrovirus are lower than odds of MSD with either organism alone. This may reduce the efficacy of intervention strategies targeted at Cryptosporidium.

Protocolo para el uso y aplicación racional de productos químicos, microbiológicos y antibióticos en la producción de camarón marino de cultivo en El Salvador

Este protocolo tiene por objeto establecer los requisitos y medidas sanitarias de prevención y control de la dispersión de enfermedades de alto impacto y para el uso adecuado y racional de fármacos de uso específico en la acuicultura, específicamente para la producción camaronera y de los laboratorios de producción de nauplios y post larvas del país. Este documento es resultado del proyecto de investigación denominado Muestreo y diagnóstico de la calidad microbiológica del agua durante un ciclo de cultivo de camarón marino en estanques de cooperativas de San Hilario, Bahía de Jiquilisco, Usulután, ejecutado por la Escuela Especializada en Ingeniería ITCA-FEPADE, Centro Regional La Unión. En este proyecto se determinó cualitativa y cuantitativamente la presencia de coliformes totales, coliformes fecales (Es-cherichia coli) y bacterias Heterótrofas que constituyen los bioindicadores estándar de contaminación orgánica del agua. Se determinó además la presencia de Vibrio sp., Pseudomonas sp., y Aeromonas sp. en el área de estudio identificados como los principales agentes causantes de enfermedades infecciosas en el camarón marino. El muestreo ayudó a conocer la influencia de parámetros físico-químicos en la presencia de los microorganismos estudiados y servirá de marco para elaborar una propuesta para un programa de monitoreo de la acuicultura en todas sus etapas del encadenamiento productivo. Se realizó un taller con la Cooperativa Senderos de Paz sobre los resultados de TCBS de la calidad del agua en el canal reservorio y el estanque número 3 de dicha cooperativa.

Bacterial and pathological study of caudal fin rot in brood stocks of Salmo trutta caspius from the propagation and breeding center of Shahid Bahonar of Kelardasht region

In order to study caudal fin rot with emphasis on Aeromonas hydrophila and Pseudomonas fluorescens in Salmo trutta caspius from the salmonids propagation and breeding center of Shahid Bahonar of kelardasht region, One hundred and eighty brood stocks having fin damage symptoms were chosen. Two bacterial samples from each fish were cultured on Aeromonas and Pseudomonas specific media. Biochemical tests, API2OE identification system and antibiogram test using six antibiotic disks were performed for diagnosing isolates bacteria and finding suitable antibiotic. Thirty samples from caudal fin of damaged fishes were fixed in 10% formalin and 51.tm microscopic sections were prepared using standard scatological methods and then stained by Haematoxylin-Eosin staining method to observe the pathological changes and also Maccallum-Goodpasture staining method to observe the bacterial colonies. In second stage of the study, bacterial samples were taken from thirty brood stocks using similar method at the first stage of sampling. For isolation and biochemical diagnosis of Aeromonas and Pseudormonas genus, the samples were analyzed by molecular research included PCR amplification (using 16S rDNA genes of the genus pseudomonas and 16S-23S rDNA intergenic spacer of the genus Aeromonas) and restriction analysis by four restriction enzymes for each genus. The results of biochemical tests showed that isolated bacteria were belonged to Aeromonas caviae and Aeromonas hydrophila (subspecies anaerogenes), Pseudomonas fluorescens, Pseudomonas putida and Pseudomonas alcaligenes while the results of API2OE identification system showed that the isolated bacteria belonged to Aeromonas hydrophila, Pseudomonas fluorescens, Pseudomonas putida and Pseudomonas aeruginosa. Restriction analysis of Aeromonas samples with Hin6l, Csp6I, Taql, and Tasl revealed three samples were different from others while restriction analysis of Pseudomonas samples with Alul, Hinfl, Rsal, and Trull showed at least five species or biovars. The results of antibiogram test showed all Aeromonas samples were sensitive to Trimethoprim, Chloramphenicol and Nitrofurazone, mostly to Nalidixic acid and Chloramphenicol, while most of samples were resistant to Erythromycin and Oxytetracycline. Pseudomonas samples were only sensitive to Nitrofurazone and mostly resistant to Oxytetracycline, Nalidixic acid, Erythromycin, Trimethoprim and Chloramphenicol. The results of light microscope study showed hyperplasia and spongiosis of the malpigian cells of epidermis, increasing of melanin pigments underlying epidermis; sever necrosis in both epidermis and dermis and also sloughing the epidermis in some cases. Occurrence of clefts through the epithelium, neovascularization, hyperemia and mild inflammatory response in dermis and separation of the fin rays also were observed. No bacterial colonies were found in the sections.

Common fish diseases and parasites affecting wild and farmed tilapia and catfish in central and western Uganda

Intensification of aquaculture production in Uganda is likely to result into disease out-breaks leading to economic losses to commercial fish farms and associated natural aquatic ecosystems. This survey assessed health profiles of selected commercial fish farms and adjacent natural aquatic ecosystemsto identify fish diseases and parasites affecting Nile tilapia (Oreochromis niloticus) and African catfish (Clarias gariepinus) in aquaculture systems in Uganda. Fish farms encounter disease out-breaks that cause low survival rates (0 - 30%), especially catfish hatcheries. Health management issues are not well understood by fish farmers, with some unable to detect diseased fish. Current control strategies to control aquatic pathogens include use of chemotherapeutants and antibiotics. Bacterial pathogens isolated included Flavobacterium columnare, Aeromonas sp., Edwardsiella sp., Psuedomonus sp., Steptococcus sp., Staphylococcus sp., Proteus sp., and Vibrio sp. A high occurrence of Flavobacterium columnare exists in both asymptomatic and symptomatic fish was observed. Parasites included protozoans (Ichthyopthirius multiphilis, Trichodina sp. and Icthyobodo sp.) and trematodes (Cleidodiscus sp. and Gyrodactylus sp.). Diagnosis and control of diseases and parasites in aquaculture production systems requires adoption of a regional comprehensive biosecurity strategy: the East African (EAC) region unto which this study directly contributes.

Cryptosporidiosis in farm livestock

Although diarrhoea caused by Cryptosporidium is prevalent in livestock species throughout the world relatively little is known about the species and subtypes of Cryptosporidium found in cattle on Scottish farms. In particular, little is known about the shedding profiles (age when calves become infected and duration of shedding) of the different species found in cattle and how calves become infected. There are several theories about how neonatal calves first become infected with the parasite but the role which adult cattle play in the transmission of the parasite has not been fully addressed. It was previously thought that adult cattle did not become infected with the same species of Cryptosporidium which causes disease in the young calves. Some studies have shown that this may not be true and with the advance of new techniques to discriminate species this is an area which should be revisited. In addition, it is known that it is possible for humans to become infected with Cryptosporidium and show clinical disease early in life and then again later in adulthood. In livestock however, diarrhoea caused by the parasite is generally only seen in neonatal livestock while older animals tend to be asymptomatic. It is not known if this resistance to clinical disease at an older age is due to changes in the host with an increase in age or if prior infection “immunises” the animal and provides protection against re-infection. It is also not known if infection with one isolate of C. parvum will provide protection against infection with another or if the protection formed is species/isolate specific. The main aims of this thesis were to: determine the species and subtypes of Cryptosporidium found in calves on a study farm over a one year period from birth; assess the role which adult cattle play in the transmission of the parasite to newborn calves; develop new typing tools to enable the rapid and easy differentiation of Cryptosporidium species found in cattle and to examine the host-pathogen interactions in animals given serial experimental challenges with distinct Cryptosporidium parvum isolates to determine if the resistance seen in older animals on farms is due to an increase in age or as a result of prior infection. iii A variety of different approaches were taken to achieve these aims. Longitudinal experiments carried out on a study farm revealed that in calves <9 weeks of age the most common species of Cryptosporidium is C. parvum and that all calves in the group became infected with Cryptosporidium within the first two weeks of life. Sample collection from the same animals later in life (at 6 months of age) showed that contrary to most previous studies the most common species detected at in this age group was also C. parvum although, interestingly, the subtype which the calves were shedding was not the same subtype that they were shedding previously. The longitudinal study which investigated the role of adult cattle in the transmission of Cryptosporidium also yielded some interesting results. It was found that most of the adult cattle on this farm were shedding Cryptosporidium albeit intermittently. Speciation of the positive samples revealed that, on this farm, the most predominant species of Cryptosporidium in adult cattle was also C. parvum. This is very unusual as most previous studies have not found this level of infection in older cattle and C. parvum is not usually found in this age group. A number of different subtypes were found in adult cattle and some animals shed more than one subtype over the course of the study. This contradicts prior findings which demonstrated that only one subtype is found on a single farm. The experimental infection trial involving infection of young (<1 week old) and older (6 week old) lambs with distinct C. parvum isolates demonstrated that an increase in age at primary infection reduces the effect of clinical disease. Animals which were infected at <1 week of age were re-challenged at 6 weeks of age with either a homologous or heterologous infection. Results revealed that previous exposure does not protect against re-infection with the same or a different isolate of C. parvum. This study also demonstrated that an increase in infective dose leads to a shorter pre-patent period and that there are variations in the clinical manifestations of different isolates of the same Cryptosporidium species.

Severe and Symptomatic Calcium Disorders Caused by Secondary Bone Disease in a Patient with a Thyroid Storm

A patient with Graves’ disease was admitted with a thyroid storm. She had severe hypercalcaemia caused by thyrotoxicosis. Treatment was complicated by vomiting and diarrhoea. With intravenous ondansetron, hydration and bisphosphonates, GI symptoms improved and oral thyreostatics could be started. This, combined with bisphosphonate administration, resulted in a mild hungry bone syndrome.

Associations between exposure to viruses and bovine respiratory disease in Australian feedlot cattle

Bovine respiratory disease (BRD) is the most important cause of clinical disease and death in feedlot cattle. Respiratory viral infections are key components in predisposing cattle to the development of this disease. To quantify the contribution of four viruses commonly associated with BRD, a case-control study was conducted nested within the National Bovine Respiratory Disease Initiative project population in Australian feedlot cattle. Effects of exposure to Bovine viral diarrhoea virus 1 (BVDV-1), Bovine herpesvirus 1 (BoHV-1), Bovine respiratory syncytial virus (BRSV) and Bovine parainfluenza virus 3 (BPIV-3), and to combinations of these viruses, were investigated. Based on weighted seroprevalences at induction (when animals were enrolled and initial samples collected), the percentages of the project population estimated to be seropositive were 24% for BoHV-1, 69% for BVDV-1, 89% for BRSV and 91% for BPIV-3. For each of the four viruses, seropositivity at induction was associated with reduced risk of BRD (OR: 0.6–0.9), and seroincrease from induction to second blood sampling (35–60 days after induction) was associated with increased risk of BRD (OR: 1.3–1.5). Compared to animals that were seropositive for all four viruses at induction, animals were at progressively increased risk with increasing number of viruses for which they were seronegative; those seronegative for all four viruses were at greatest risk (OR: 2.4). Animals that seroincreased for one or more viruses from induction to second blood sampling were at increased risk (OR: 1.4–2.1) of BRD compared to animals that did not seroincrease for any viruses. Collectively these results confirm that prior exposure to these viruses is protective while exposure at or after feedlot entry increases the risk of development of BRD in feedlots. However, the modest increases in risk associated with seroincrease for each virus separately, and the progressive increases in risk with multiple viral exposures highlights the importance of concurrent infections in the aetiology of the BRD complex. These findings indicate that, while efficacious vaccines could aid in the control of BRD, vaccination against one of these viruses would not have large effects on population BRD incidence but vaccination against multiple viruses would be expected to result in greater reductions in incidence. The findings also confirm the multifactorial nature of BRD development, and indicate that multifaceted approaches in addition to efficacious vaccines against viruses will be required for substantial reductions in BRD incidence.

Study of bacterial agents on external lesions of cultured Sturgeons in Sngar zone of Gilan Province

This study was carried out to isolate and determine bacterial agents in outer lesions of sturgeons in Shahid Dr. Beheshti sturgeon propagation and rearing center in Gilan province. Five species of sturgeons were studied from viewpoint of lesions. A number of 167 specimens of Beluga, 76 specimens of Persian sturgeon, 27 specimens of Russian sturgeon, 42 specimens of stellate and finally 23 specimens of ship had bacterial lesions in different outer parts of their bodies. After sampling and purification, bacterial cultures and biochemical tests were done. After the isolation of bacteria from lesions, Edwardsiella tarda was selected by means of PCR. To obtain molecular acceptance, a pair of E. tarda special primer, forward primer ETa2-351 and reverse primer (Edwsp-780r) were reproduced. A number of 12 E. tarda DNA sample were identified by PCR. After molecular diagnosis, Persian sturgeon challenged with E. tarda for determination of pathogenesis. Challenge method was done by means of injection of different dilutes of E. tarda into dorsal muscle. Sampling of hematopoietic organs (kidney, spleen and liver) were carried out and located in Boin's fixator to perform pathology survey. Also, in order to survey of existence and effect of E. tarda, sampling of kidney for bacterial culture was done by molecular and biochemical methods. Results showed that the most lesions in all five species belonged to abdominal surface. Skin and scutes of this part were involved in comparison with other parts. Also, It was removed some samples from lesions to pathological survey. Microscopic observations showed some levels of destruction of epidermis layers, necrosis of dermis cells and destruction of muscular layer of skin. On the other hand, invasion of inflammatory cells and haemorrhagic in dermis were clear. Based on biochemical results, Aeromonas sobria, A cavia . A. hydrophila , Acinetobacter lowffii , A.baumanni , A.cakoaceticus, Pseudomonas putida , P fluorescens , P.aeruginosa , Serratia marcescens , Escherichia coli , Enterobacter aerogenes , Edwardsiella tarda , Proteus mirabilis , kelebsiella oxytoca and Staphylococcus sp. were isolated from outer lesions. Results of PCR confirmed that E. tarda was before and after challenge in 200 bp range. LD50, 96h was determined 1.2 x 10^5 (CFU/ml). Pathological experiments showed lesions in the kidney, including hemorrhages, degeneration of glumeruli and tubular epithelia, degeneration and necrosis of interestitium tissue, accumulation of protein casts in the tubular lumen. It was observed haemorhages, engorged blood vessels, congestion of sinusoids, increased of melanine, melano macrophage centers, degeneration and necrosis of hepatocytes in the liver. In the spleen, it was recorded congestion, degeneration, necrosis changes in the white and red pulpa, blood engorged and detachment of ellipsoid wall.

Biochemical and epidemiological investigations of non-steroidal anti-inflammatory drug usage and related side effects in equids

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in equine veterinary practice. These drugs exert their effect by inhibiting cyclooxygenase (COX) enzymes, which control prostaglandin production, a major regulator of tissue perfusion. Two isoforms of COX enzymes exist: COX-1 is physiologically present in tissues, while COX-2 is up-regulated during inflammation and has been indicated as responsible for the negative effects of an inflammatory response. Evidence suggests that NSAIDs that inhibit only COX-2, preserving the physiological function of COX-1 might have a safer profile. Studies that evaluate the effect of NSAIDs on COX enzymes are all performed under experimental conditions and none uses actual clinical patients. The biochemical investigations in this work focus on describing the effect on COX enzymes activity of flunixin meglumine and phenylbutazone, two non-selective COX inhibitors and firocoxib, a COX-2 selective inhibitor, in clinical patients undergoing elective surgery. A separate epidemiological investigation was aimed at describing the impact that the findings of biochemical data have on a large population of equids. Electronic medical records (EMRs) from 454,153 equids were obtained from practices in the United Kingdom, United States of America and Canada. Information on prevalence and indications for NSAIDs use was extracted from the EMRs via a text mining technique, improved from the literature and described and validated within this Thesis. Further the prevalence of a clinical sign compatible with NSAID toxicity, such as diarrhoea, is reported along with analysis evaluating NSAID administration in light of concurrent administration of other drugs and comorbidities. This work confirms findings from experimental settings that NSAIDs firocoxib is COX-2 selective and that flunixin meglumine and phenylbutazone are non-selective COX inhibitors and therefore their administration carries a greater risk of toxicity. However the impact of this finding needs to be interpreted with caution as epidemiological data suggest that the prevalence of toxicity is in fact small and the use of these drugs at the labelled dose is quite safe.

A demonstration of mobile phone deployment to support the treatment of acutely ill children under five in Bushenyi district, Uganda.

Background: Benefits of mobile phone deployment for children <5 in low-resource settings remain unproven. The target population of the current demonstration study in Bushenyi District, Uganda, presented with acute fever, pneumonia, or diarrhoea and were treated by community health workers (CHWs) providing integrated community case management (iCCM). Methods: An observational study was conducted in five parishes (47 villages) served by CHWs well versed in iCCM with supplemental training in mobile phone use. Impact was assessed by quantitative measures and qualitative evaluation through household surveys, focus group discussions, and key informant interviews. Results: CHWs in targeted sites improved child healthcare through mobile phone use coupled with iCCM. Of acutely ill children, 92.6% were correctly managed. Significant improvements in clinical outcomes compared to those obtained by CHWs with enhanced iCCM training alone were unproven in this limited demonstration. Nonetheless, qualitative evaluation showed gains in treatment planning, supply management, and logistical efficiency. Provider confidence and communications were enhanced as was ease and accuracy of record keeping. Conclusion: Mobile phones appear synergistic with iCCM to bolster basic supportive care for acutely ill children provided by CHWs. The full impact of expanded mobile phone deployment warrants further evaluation prior to scaling up in low-resource settings.

Diarrea crónica por Salmonella typhimurium en paciente inmunocompentente

La diarrea crónica de origen infeccioso en pacientes inmunocompetentes es un cuadro poco frecuente en países desarrollados, aunque ciertos patógenos, generalmente parásitos (Giardia lamblia, Isospora belli, Cryptosporidium, Cyclospora, Strongyloides, Ameba, Trichuris y Schistosoma) y algunas bacterias (Aeromonas, Plesiomonas, Campylobacter, Clostridium difficile, Salmonella o Mycobacterium tuberculosis) pueden ser causantes de diarrea persistente. Se presenta un caso de un paciente que presentó Salmonella typhimunium en el coprocultivo y se recuperó tras tratamiento con levofloxacino durante 7 días.