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1.
Cancer Immunol Immunother ; 73(6): 109, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662232

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a highly immunosuppressive microenvironment. This single-blind, randomized study aimed to evaluate the synergistic immunomodulatory effects of synbiotics (probiotics and inulin prebiotics), as well as their impact on postoperative complications and outcomes, compared to the use of probiotics alone. Ninety patients diagnosed with PDAC were enrolled and randomly assigned into three groups: the placebo group, the probiotics group (receiving a mixture of ten strains of Lactobacillus, Bifidobacterium, and Streptococcus bacteria at a dose of 25 billion CFUs), and the synbiotics group (the same probiotics along with inulin prebiotics). The interventions were administered for 14 days before the surgery and continued for one month postoperatively. Tumor tissue infiltration of CD8 + T cells and the expression of IFN γ were assessed by immunohistochemistry (IHC). Inflammatory cytokines concentrations, including Il 1 B, IL 6, and IL 10, were evaluated as well by ELISA at various time points pre- and postoperative. Furthermore, patients were followed up after the surgery to assess postoperative short-term outcomes. Our results showed a significant elevation of CD8 + T cell proportion and IFN γ expression in the synbiotics group compared to the probiotics group (p = 0.049, p = 0.013, respectively). Inflammatory cytokines showed a significant gradual decrease in the synbiotics group compared to placebo and probiotics-treated groups (p = 0.000 for both). Administration of synbiotics and probiotics significantly decreased the rate of postoperative complications including anastomotic leakage, diarrhea, and abdominal distension (p = 0.032, p = 0.044, p = 0.042, respectively), with a remarkable reduction in bacteremia in the synbiotics group. These results revealed that this synbiotics formulation potentially enhances the immune response and reduces complications associated with surgery.Clinical trial identification: NCT06199752 (27-12-2023).


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Simbióticos , Humanos , Simbióticos/administração & dosagem , Masculino , Feminino , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/patologia , Pessoa de Meia-Idade , Idoso , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/cirurgia , Probióticos/uso terapêutico , Probióticos/administração & dosagem , Método Simples-Cego , Citocinas/metabolismo , Complicações Pós-Operatórias/prevenção & controle , Linfócitos T CD8-Positivos/imunologia
2.
Biology (Basel) ; 13(4)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38666894

RESUMO

Human coronaviruses (HCoVs) are seriously associated with respiratory diseases in humans and animals. The first human pathogenic SARS-CoV emerged in 2002-2003. The second was MERS-CoV, reported from Jeddah, the Kingdom of Saudi Arabia, in 2012, and the third one was SARS-CoV-2, identified from Wuhan City, China, in late December 2019. The HCoV-Spike (S) gene has the highest mutation/insertion/deletion rate and has been the most utilized target for vaccine/antiviral development. In this manuscript, we discuss the genetic diversity, phylogenetic relationships, and recombination patterns of selected HCoVs with emphasis on the S protein gene of MERS-CoV and SARS-CoV-2 to elucidate the possible emergence of new variants/strains of coronavirus in the near future. The findings showed that MERS-CoV and SARS-CoV-2 have significant sequence identity with the selected HCoVs. The phylogenetic tree analysis formed a separate cluster for each HCoV. The recombination pattern analysis showed that the HCoV-NL63-Japan was a probable recombinant. The HCoV-NL63-USA was identified as a major parent while the HCoV-NL63-Netherland was identified as a minor parent. The recombination breakpoints start in the viral genome at the 142 nucleotide position and end at the 1082 nucleotide position with a 99% CI and Bonferroni-corrected p-value of 0.05. The findings of this study provide insightful information about HCoV-S gene diversity, recombination, and evolutionary patterns. Based on these data, it can be concluded that the possible emergence of new strains/variants of HCoV is imminent.

3.
Bioinformation ; 20(2): 91-102, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38497067

RESUMO

Rift Valley Fever (RVF) is a mosquito-borne viral zoonosis caused by RVFV in humans and livestock. Currently, there are no approved vaccines or antiviral therapies available. Additionally, in Saudi Arabia, there is a lack of a routine screening system to monitor RVFV in humans and animals which hinders to design and develop the preventive measures as well as the prediction of future outbreaks and the potential re-emergence of RVFV. Hence, we have performed the cloning, sequencing, and phylogenetic analysis, of nucleocapsid (N) protein gene. The sequence analysis showed high similarities with RVFV isolates reported from humans and animals. The highest similarity (99.5%) was observed with an isolate from Saudi Arabia (KU978775-Human) followed by 99.1% with four RVFV isolates (Human and Bovine) from other locations. A total of 51 nucleotides and 31 amino acid variations were observed throughout the N protein gene sequences. The phylogenetic relationship formed closed clusters with other isolates collected from Saudi Arabia. Thus, we report of the cloning, sequencing, and phylogenetic analysis of the RVFV-N protein gene from Saudi Arabia.

4.
J Obstet Gynaecol India ; 73(Suppl 1): 19-24, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37916005

RESUMO

Background: The aim of this study was to evaluate hyperemesis gravidarum in pregnant women and its psychological impact. Methods: This retrospective study included 109 pregnant females suffering from hyperemesis gravidarum admitted during 2019-2020 at Maternity Ain shams university hospital. Results: Disease severity and laboratory investigations such as Na and K levels (P = 0.007 and < 0.001, respectively) and serum creatinine level (P < 0.001) were significantly positively correlated. Depressive symptoms included guilt feeling for leaving family (49.5% patients), suicidal thoughts (9.2%), crying (56.9%) and lost concentration (33.9%). Conclusions: Medical staff should be aware of psychological impact of the disease and refer to specialists if needed.

5.
Sci Rep ; 12(1): 21723, 2022 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-36522420

RESUMO

Hypericum perforatum and Echinacea are reported to have antiviral activities against several viral infections. In this study, H. perforatum (St. John's Wort) and Echinacea were tested in vitro using Vero E6 cells for their anti-viral effects against the newly identified Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) through its infectious cycle from 0 to 48 h post infection. The hypericin of H. perforatum and the different parts (roots, seeds, aerial) of two types of Echinacea species (Echinacea purpurea and Echinacea angustifolia) were tested for their anti-viral activities to measure the inhibition of viral load using quantitative real-time polymerase chain reaction (qRT-PCR) on cell culture assay. Interestingly, the H. perforatum-Echinacea mixture (1:1 ratio) of H. perforatum and Echinacea was tested as well on SARS-CoV-2 and showed crucial anti-viral activity competing H. perforatum then Echinacea effects as anti-viral treatment. Therefore, the results H. perforatum and Echinacea species, applied in this study showed significant anti-viral and virucidal effects in the following order of potency: H. perforatum, H. perforatum-Echinacea mixture, and Echinacea on SARS-CoV-2 infectious cycle. Additionally, molecular simulation analysis of the compounds with essential proteins (Mpro and RdRp) of the SARS-CoV-2 revealed the most potent bioactive compounds such as Echinacin, Echinacoside, Cyanin, Cyanidin 3-(6''-alonylglucoside, Quercetin-3-O-glucuronide, Proanthocyanidins, Rutin, Kaempferol-3-O-rutinoside, and Quercetin-3-O-xyloside. Thus, based on the outcome of this study, it is demanding the setup of clinical trial with specific therapeutic protocol.


Assuntos
Antineoplásicos , COVID-19 , Echinacea , Hypericum , SARS-CoV-2 , Antivirais/farmacologia , Antivirais/uso terapêutico , Quercetina/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
6.
J Infect Public Health ; 14(6): 803-810, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34044250

RESUMO

BACKGROUND: Dengue virus causes the dengue fever as well as hemorrhagic fever in tropical and sub-tropical countries. It is now endemic in most parts of the South East Asia. Full-genome information of dengue virus 3 is not available from Yemen. METHODS: In this study, the dengue virus 3 was detected by diagnostic tools like serology and RT-PCR in the samples isolated from a patient in Yemen. The full-genome was sequenced, and the identity, phylogenetic relationship and recombination analysis was performed by using BioEdit, MEGA X and RDP4 softwares. RESULTS: The full-genome of the Yemen isolate was found to be 10,643 nt long with 3390 amino acids. The Yemen dengue virus 3 isolate showed the sequence similarity (98.5-92.4%) with dengue virus 3 isolates from China, Pakistan, India and Bangladesh respectively. The significant non-synonymous substitutions of amino acid in Yemen isolate were observed with selected isolates. The phylogenetic tree of Yemen isolate formed a unique clade within genotype III and sub-clade into lineage III. The Dengue virus isolate from Jeddah formed separated cluster with lineage IV. CONCLUSIONS: This reveals the unique genetic variability among DENV-3 serotypes from Jeddah and earlier reported isolates from other regions.


Assuntos
Vírus da Dengue , Dengue , Bangladesh , China , Dengue/epidemiologia , Vírus da Dengue/genética , Genótipo , Humanos , Índia , Paquistão , Filogenia , RNA Viral/genética , Sorogrupo , Iêmen/epidemiologia
7.
Viruses ; 12(5)2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32443401

RESUMO

Hepatitis E Virus (HEV) imposes a major health concern in areas with very poor sanitation in Africa and Asia. The pathogen is transmitted mainly through ingesting contaminated water or food, coming into contact with affected people, and blood transfusions. Very few reports including old reports are available on the prevalence of HEV in Saudi Arabia in humans and no reports exist on HEV prevalence in camels. Dromedary camel trade and farming are increasing in Saudi Arabia with importation occurring unidirectionally from Africa to Saudi Arabia. DcHEV transmission to humans has been reported in one case from the United Arab Emeritus (UAE). This instigated us to perform this investigation of the seroprevalence of HEV in imported and domestic camels in Saudi Arabia. Serum samples were collected from imported and domestic camels. DcHEV-Abs were detected in collected sera using ELISA. The prevalence of DcHEV in the collected samples was 23.1% with slightly lower prevalence in imported camels than domestic camels (22.4% vs. 25.4%, p value = 0.3). Gender was significantly associated with the prevalence of HEV in the collected camels (p value = 0.015) where males (31.6%) were more infected than females (13.4%). This study is the first study to investigate the prevalence of HEV in dromedary camels from Saudi Arabia. The high seroprevalence of DcHEV in dromedaries might indicate their role as a zoonotic reservoir for viral infection to humans. Future HEV seroprevalence studies in humans are needed to investigate the role of DcHEV in the Saudi human population.


Assuntos
Camelus/virologia , Vírus da Hepatite E/imunologia , Hepatite E/epidemiologia , Animais , Feminino , Anticorpos Anti-Hepatite/sangue , Hepatite E/sangue , Hepatite E/transmissão , Humanos , Masculino , Prevalência , Arábia Saudita/epidemiologia , Estudos Soroepidemiológicos , Zoonoses/epidemiologia , Zoonoses/virologia
8.
PLoS Negl Trop Dis ; 9(3): e0003587, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25768090

RESUMO

Mycetoma is a unique neglected tropical disease which is endemic in what is known as the "mycetoma belt". The disease has many devastating impacts on patients and communities in endemic area and is characterised by massive deformity, destruction and disability. Mycetoma is commonly seen in the foot and hand and less frequent in other parts of the body. Mycetoma of the head and neck is a rarity and is associated with high morbidity and even mortality if not treated early. In this communication we report on 49 patients with head and neck mycetoma followed up at the Mycetoma Research Centre in Khartoum. Most of the reported patients had actinomycetoma and the majority were young adult males from mycetoma endemic areas in the Sudan. Most of them were students, farmers and workers. Prior to presentation the majority had long disease duration and the cause was multifactorial. Advanced disease with massive lesion, deformity and disability was the common presentation. There was no obvious history of local trauma, familial tendency or other predisposing factor identified in this group of patients. MRI and CT scan were the most accurate diagnostic tools to determine the disease extent. The treatment outcome was rather poor and characterised by low cure rate, poor outcome and high follows-up dropout. Such a gloomy outcome calls for structured and objective health education programs.


Assuntos
Micetoma/patologia , Adolescente , Adulto , Idoso , Biópsia por Agulha Fina , Criança , Feminino , Cabeça , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Micetoma/etiologia , Micetoma/terapia , Pescoço , Resultado do Tratamento
9.
PLoS Negl Trop Dis ; 8(10): e3271, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25356640

RESUMO

Patients with mycetoma usually present late with advanced disease, which is attributed to lack of medical and health facilities in endemic areas, poor health education and low socio-economic status. With this background, an integrated patient management model at the village level was designed to address the various problems associated with mycetoma. The model was launched in an endemic village in the Sudan, between 2010 and 2013. This model is described in a prospective, descriptive, community-based study, aimed to collect epidemiological, ecological, and clinical data and to assess knowledge, attitude and practice (KAP) in order to design effective and efficient management measures. In this study, the prevalence of mycetoma was 14.5 per 1,000 inhabitants. The patients were farmers, housewives and children of low socio-economic status, and no obvious risk group was detected. All had surgery performed in a mobile surgical unit in the village which encouraged patients to present early with small early lesion leading to a good clinical outcome. The close contact with the Acacia tree thorns, animals and animal dung, walking bare footed and practising poor hygiene may all have contributed to the development of mycetoma in the village. Knowledge of mycetoma was poor in 96.3% of the study population, 70% had appropriate attitudes and beliefs towards interaction with mycetoma patients and treatment methods, and 49% used satisfactory or good practices in the management of mycetoma. Knowledge and practices on mycetoma were found to be significantly associated with age. Based on the KAP and epidemiological data, several health education sessions were conducted in the village for different target groups. The integrated management approach adopted in this study is unique and appeared successful and seems suitable as an immediate intervention. While for the longer term, establishment of local health facilities with trained health staff remains a priority.


Assuntos
Micetoma/terapia , Adolescente , Adulto , Idoso , Criança , Ecossistema , Feminino , Educação em Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Micetoma/epidemiologia , Micetoma/etiologia , Estudos Prospectivos , Sudão
10.
Int J Surg ; 12(2): 181-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24378913

RESUMO

BACKGROUND: Umbilical hernia repair is often accompanied by complications in patients with liver cirrhosis and ascites. It appears that the early elective repair of umbilical hernias in these patients is safer and can be considered for selected patients. The objective of this study is to evaluate the feasibility, safety, complications and technical aspects of sublay mesh repair of umbilical hernia in cirrhotic patients with ascites. METHODS: Between October 2010 and April 2013, 70 patients with non-complicated umbilical hernia, liver cirrhosis and ascites were enrolled in this study. All patients underwent sublay mesh repair. Demographic data, preoperative variables, peri-operative course, and postoperative complications were recorded and analyzed. RESULTS: A total of 38 women and 32 men underwent operation at an average age 51.24 years. The patients mean MELD score was 18 (range 12-25). The mean operative time was 67.45 min and the average hospital stay was 3.8 days. 2 patients had wound infection, 3 patients developed seroma and 1 patient had an ascitic fistula. Recurrence occurred in 1 (1.4%) patient and no mortality related to the procedure. CONCLUSION: elective sublay umbilical hernia mesh repair is a safe approach and feasible technique in selected non-complicated cirrhotic patients with ascites.


Assuntos
Ascite/complicações , Hérnia Umbilical/complicações , Hérnia Umbilical/cirurgia , Herniorrafia/métodos , Cirrose Hepática/complicações , Telas Cirúrgicas , Adulto , Feminino , Herniorrafia/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
11.
J Trop Med ; 2013: 275253, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23634148

RESUMO

Visceral leishmaniasis (VL) is a parasitic disease characterized by immune suppression. Successful treatment is usually followed by immune reconstitution and a dermatosis called post-Kala-azar dermal leishmaniasis (PKDL). Recently, PKDL was described as one of the immune reconstitution syndromes (IRISs) in HIV/VL patients on HAART. This study aimed to present PKDL as a typical example of paradoxical IRIS in non-HIV/AIDS individuals. Published and new data on the pathogenesis and healing of PKDL was reviewed and presented. The data suggested that PKDL is a typical example of paradoxical IRIS, being a new disease entity that follows VL successful treatment and immune recovery. PKDL lesions are immune inflammatory in nature with granuloma, adequate response to immunochemotherapy, and an ensuing hypersensitivity reaction, the leishmanin skin test (LST). The data also suggested that the cytokine patterns of PKDL pathogenesis and healing are probably as follows: an active disease state dominated by IL-10 followed by spontaneous/treatment-induced IL-12 priming, IL-2 stimulation, and INF- γ production. INF- γ -activated macrophages eliminate the Leishmania parasites/antigen to be followed by LST conversion and healing. In conclusion, PKDL is a typical example of paradoxical IRIS in non-HIV/AIDS individuals with anti-inflammatory cytokine patterns that are superseded by treatment-induced proinflammatory cytokines and lesions healing.

12.
Case Rep Med ; 2013: 351579, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23533426

RESUMO

Post-kala-azar dermal leishmaniasis (PKDL) is a known complication of visceral leishmaniasis (VL) caused by L. donovani. It is rare in VL caused by L. infantum and L. chagasi. In Sudan, it occurs with a frequency of 58% among successfully treated VL patients. In the majority of cases, PKDL can be diagnosed on the basis of clinical appearance, distribution of the lesions, and past history of treated VL. The ideal diagnostic method is to demonstrate the parasite in smears, by culture or PCR. Diagnosis is particularly difficult in patients who develop PKDL in the absence of previous history of visceral leishmaniasis. We describe a case of cutaneous leishmaniasis misdiagnosed as PKDL and 3 cases of PKDL who were either misdiagnosed or mistreated as other dermatoses. This caused exacerbation of their disease leading to high parasite loads in the lesions and dissemination to internal organs in one of the patients, who was also diabetic. The latter patient had L. major infection. A fourth patient with papulonodular lesions on the face and arms of 17-year duration and who was misdiagnosed as having PKDL is also described. He turned out to have cutaneous leishmaniasis due to L. major. Fortunately, he was not treated with steroids. He was cured with intravenous sodium stibogluconate.

13.
J Egypt Soc Parasitol ; 42(1): 121-8, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22662601

RESUMO

This study assessed the effect of pancreatico-biliary reflux (PBR) as co-factor in the process of chronic cholecystitis by measurement of the levels of active pancreatic enzyme amylase in gallbladder bile and serum of patients undergoing cholecystectomy. Pancreatic Amylase levels in bile from the gallbladder and serum were measured during surgery in 68 patients with chronic calcular cholecystitis subjected to elective open or laparoscopic cholecystectomy in the National Hepatology and Tropical Medicine Research Institution and Theodore Bilharz Research Institute. Bile amylase was detected in 64 patients (94.1%) indicating pancreatico-biliary reflux. Biliary amylase level ranged from 20-50 IU/L in 42 patients (61.76%), below 20 IU/l in 14 patients (20.59%), over 50 IU/L in 8 patients (11.76%) and undetectable in two patients. According to gallbladder bile amylase, the incidence of Occult PBR in patients operated upon for chronic calcular cholecystitis was 94.1%. The reason should be clarified by further research and wider scale study. Routinely investigating biliary amylase in every patient having cholecystitis can be a method for early detection of precancerous lesions.


Assuntos
Refluxo Biliar/etiologia , Colecistite/complicações , Pancreatopatias/etiologia , Adulto , Colecistite/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
J Egypt Soc Parasitol ; 42(1): 129-34, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22662602

RESUMO

This prospective study was conducted to investigate the efficacy of single-dose Ceftazidime as a prophylactic antibiotic to prevent surgical site infections in low-risk patients undergoing LC. Two hundred patients included in the study were randomly divided into two groups (100 each): G1: patients received intravenous Ceftazidime within 60 minutes prior to surgery and G2: received intravenous placebo (10 ml isotonic sodium chloride 0.9% solution). All patients were invited for examination 10, 20 and 30 days post-operatively and any post-operative complications were recorded and managed. Preoperatively; there was no significant differences existed between the 2 groups regarding sex, age; body mass index and ASA score. Also, the duration of LC surgery, incidence of intra-operative gallbladder perforations and spill of bile or stones, incidents of intra-operative bleeding from either cystic artery or gall bladder liver bed and mean postoperative hospital stay were found not significantly different between the 2 groups. Post operatively there was no statistical difference regarding the surgical site infection between the two groups.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Ceftazidima/administração & dosagem , Ceftazidima/uso terapêutico , Colecistectomia Laparoscópica , Complicações Pós-Operatórias/prevenção & controle , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecção da Ferida Cirúrgica/prevenção & controle , Adulto Jovem
15.
J Egypt Soc Parasitol ; 42(1): 157-64, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22662604

RESUMO

The prevalence and clinical features of the various obstructive lesions in appendectomy specimens studied pathologically with special emphasis on unusualetiological findings were evaluated. The clinic-pathological data of 251 patients who underwent appendectomies for presumed acute appendicitis from January; 2008 to December; 2010; were reviewed retrospectively. Among all appendectomies performed, eleven (4.38%) specimens revealed incidental abnormal pathological diagnoses: Four cases (1.59%) of Enterobiusvermicularis, Ascaris lumbricoides two cases (0.79 %), schistosomiasis eggs in three cases (1.19%), and parasitic amebiasis in two cases (0.79%). None suffered tumor in any appendectomies specimens. Mean age was lower, perforated and gangrenous appendicitis was absent and negative appendectomy rate was higher in patients with unusual appendix pathology.


Assuntos
Apendicite/patologia , Apêndice/patologia , Adolescente , Adulto , Criança , Humanos , Estudos Retrospectivos , Adulto Jovem
16.
J Egypt Soc Parasitol ; 41(3): 675-84, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22435160

RESUMO

Laparoscopic cholecystectomy (LC) had been considered the gold standard treatment for symptomatic gall bladder (GB) stones. Single incision laparoscopic cholecystectomy (SILC) was emerged as a less invasive alternative with better cosmesis and less post operative pain. This study evaluated the feasibility, safety, advantages and complications of SILC using the conventional laparoscopic instruments. A total of 52 patients (47 females and 5 males) with symptomatic GB stones underwent elective SILC using the conventional laparoscopic instruments. The mean operative time was 61.75 min and the mean estimated blood loss was 17.21 ml. Gall bladder perforation occurred in 5 cases (9.6%) in which 3 cases calculi spillage occurred. Troublesome cystic artery bleeding occurred in 2 cases (3.8%) while gall bladder bed bleeding happened in 1 case (1.9%). An intraoperative cholangiogram was performed in 3 cases and a drain was inserted in one case. No conversions of the technique occurred. 49 patients discharged in the first post operative day and 3 patients (5.8 %) in the 2nd day. Three month post operative wound length was an average of 1.58 cm while patient satisfaction of the surgery was an average of 9.32.


Assuntos
Colecistectomia Laparoscópica/métodos , Cálculos Biliares/cirurgia , Adulto , Colecistectomia Laparoscópica/efeitos adversos , Estudos de Viabilidade , Feminino , Hemorragia/etiologia , Humanos , Laparoscópios , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Resultado do Tratamento , Adulto Jovem
17.
Trans R Soc Trop Med Hyg ; 102(1): 58-63, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17963805

RESUMO

Post-kala-azar dermal leishmaniasis (PKDL) is a recognized dermatosis that follows successful treatment of visceral leishmaniasis in the Sudan. This randomized and double-blind study aimed to assess safety, immunogenicity and curative potentials of a novel immunochemotherapy regimen in patients with persistent PKDL. Following informed consent, 30 patients were randomized to receive alum-precipitated autoclaved Leishmania major (Alum/ALM) vaccine+Bacille Calmette-Guérin (BCG) and sodium stibogluconate (SSG) or vaccine diluent and SSG. The SSG+Alum/ALM+BCG proved safe with minimal local adverse events. In the SSG+vaccine group, 87% of the patients were cured by day 60 compared with 53% in the SSG alone group (SSG+vaccine efficacy=71%, 95% CI for risk ratio 0.7-1.16). On day 90 of follow-up there were two relapses in the SSG alone arm and none in the SSG+vaccine arm. Pre-treatment cytokines showed high IFN-gamma or high IFN-gamma/IL-10 levels and leishmanin skin test (LST) non-reactivity, while healing/clinical improvement were associated with LST reactivity and low IFN-gamma levels in both study groups (P=0.004). In conclusion, SSG+Alum/ALM+BCG is safe and immunogenic with significant healing potentials in persistent PKDL lesions. Immunochemotherapy probably augmented IFN-gamma production, which induced healing. Leishmanin skin reactivity is a good surrogate marker of cure in persistent PKDL lesions.


Assuntos
Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/uso terapêutico , Vacina BCG/imunologia , Vacinas contra Leishmaniose/imunologia , Leishmaniose Visceral/prevenção & controle , Adolescente , Adulto , Criança , Método Duplo-Cego , Feminino , Humanos , Interferon gama/sangue , Interleucina-10/sangue , Leishmaniose Visceral/imunologia , Masculino , Pessoa de Meia-Idade , Estatística como Assunto , Sudão , Resultado do Tratamento , Vacinas Combinadas
18.
Ann Trop Paediatr ; 26(4): 357-61, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17132302

RESUMO

BACKGROUND: Untreated visceral leishmaniasis (VL) is an inevitably fatal childhood disease. First-generation candidate vaccines for VL [autoclaved Leishmania major (ALM) + BCG] have been found to be safe and immunogenic but not superior to BCG alone. Modulation of ALM by adsorption to Alum significantly increases the immunogenicity. The Alum-adsorbed ALM vaccine was found to be safe and strongly immunogenic in healthy adult volunteers in a non-VL-endemic area. This study aimed at establishing the safety and immunogenicity of Alum-precipitated autoclaved L. major + BCG vaccine in children under field conditions. METHODS: A total of 544 healthy, leishmanin non-reactive children (<15 y) were randomly allocated to receive either a single intradermal injection of Alum/ALM + BCG or vaccine diluent (placebo). Volunteers were closely followed for 2 years at 6-month intervals for vaccine safety and immunogenicity. RESULTS: The vaccine was well tolerated with minimal side-effects. Leishmanin skin test conversion (>or=5 mm) was seen in 56%, 50%, 25% and 31% at 6, 12, 18 and 24 months post-vaccination, respectively; conversion in the placebo group was 4%, 12%, 3% and 13% at the same follow-up visits. There was no significant increase in anti-leishmanial antibodies in either study arm at any of the follow-up visits. During the study, four patients in the placebo arm developed parasitologically confirmed VL. CONCLUSION: Alum/ALM + BCG vaccine is safe and immunogenic in children under field conditions. Multiple injections might be needed to obtain results similar to those obtained in healthy volunteers.


Assuntos
Vacina BCG/imunologia , Leishmania major/imunologia , Leishmaniose Visceral/prevenção & controle , Vacinas Protozoárias/imunologia , Adolescente , Compostos de Alúmen , Animais , Anticorpos Antiprotozoários/biossíntese , Anticorpos Antiprotozoários/sangue , Vacina BCG/efeitos adversos , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Vacinas contra Leishmaniose , Masculino , Vacinas Protozoárias/efeitos adversos , Testes Cutâneos , Vacinas Combinadas/efeitos adversos , Vacinas Combinadas/imunologia
19.
Eur J Hum Genet ; 12(1): 66-74, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14523377

RESUMO

Genetic susceptibility to visceral leishmaniasis (VL) is indicated by differences in incidence and clinical phenotypes between ethnic groups in Sudan. In mice, innate susceptibility to Leishmania donovani, the etiological agent of VL, is controlled by Slc11a1 (formerly Nramp1). We therefore examined polymorphisms at SLC11A1 in 59 multicase families of VL from the high-incidence Masalit tribe in Sudan. Multipoint nonparametric analysis in ALLEGRO shows a significant linkage across SLC11A1 (Zlr scores 2.38-2.55; 0.008< or =P< or =0.012; information content 0.88). The extended transmission disequilibrium test shows biased transmission of alleles at 5' polymorphisms in the promoter (P=0.0145), exon 3 (P=0.0037) and intron 4 (P=0.0049), and haplotypes formed by them (P=0.0089), but not for 3' polymorphisms at exon 15 or the 3'UTR. Stepwise logistic regression analysis using a case/pseudo-control data set derived from the 59 families was consistent with main effects contributed by the intron 4 469+14G/C polymorphism. Although the two alleles for 469+14G/C lie on haplotypes carrying different alleles for the functional promoter GTn polymorphism, the latter did not itself contribute separate main effects. Sequence analysis of 36 individuals failed to identify new putative functional polymorphisms in the coding region, intron 1, intron/exon boundaries, intron 4/exon 4a, or in the 3'UTR. One novel promoter polymorphism (-86G/A) was located within a putative nuclear factor kappa B binding site that could be functional. Further work will determine whether additional polymorphisms occur upstream in the promoter, which could be in linkage disequilibrium with the intron 4 polymorphism. These studies contribute to knowledge of the role of SLC11A1 in infectious disease.


Assuntos
Proteínas de Transporte de Cátions/genética , Suscetibilidade a Doenças , Leishmaniose Visceral/imunologia , Análise de Variância , Frequência do Gene , Ligação Genética , Marcadores Genéticos , Haplótipos , Humanos , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Sudão
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