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Biomedical subjects

M Ibrahim

Publications and source records attributed to M Ibrahim.

At least 19 recordsLinked to original sources
PubMed2006

Synergistic activity of R207910 combined with pyrazinamide against murine tuberculosis.

In previous studies, the diarylquinoline R207910 (also known as TMC207) was demonstrated to have high bactericidal activity when combined with first- or second-line antituberculous drugs. Here we extend the evaluation of R207910 in the curative model of murine tuberculosis by assessing the activities of one-, two-, and three-drug combinations containing R207910 and isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), or moxifloxacin (MXF) in the setting of a high initial bacillary load (7.2 log(10) CFU). Two months of treatment with the combinations R207910-PZA, R207910-PZA-INH, R207910-PZA-RIF, or R207910-PZA-MXF resulted in culture-negative lung homogenates in 70 to 100% of the mice, while mice treated with INH-RIF-PZA (the reference regimen) or RIF-MXF-PZA remained culture positive. Combinations including R207910 but not PZA (e.g., R207910-INH-RIF and R207910-MXF-RIF) were less active than R207910-PZA-containing regimens administered either alone or with the addition of INH, RIF, or MXF. These results reveal a synergistic interaction between R207910 and PZA. Three-drug combinations containing these two drugs and INH, RIF, or MXF have the potential to significantly shorten the treatment duration in patients, provided that these results can be confirmed in long-term experiments including periods of relapse.

Animals↗
PubMed2006

Scleral melting 16 years after pterygium excision with topical Mitomycin C adjuvant therapy.

PURPOSE: To report a case of scleral melting noted 16 years after pterygium excision with postoperative adjuvant topical Mitomycin C (MMC). METHOD: Case report. RESULTS: A 61-year-old Malay gentleman underwent right nasal pterygium excision using bare sclera technique followed by topical MMC 0.1% for a week, 16 years ago. He was noted to have a right nasal scleral thinning with calcified plaque and granuloma. He was successfully treated conservatively without further progression of the scleral melting. CONCLUSION: Long-term complication of pterygium excision with adjuvant topical Mitomycin C may occur. The case shows that early detection and recognition of the complication can be sight saving.

Humans↗
PubMed2006

Iodine supplementation for the prevention of mortality and adverse neurodevelopmental outcomes in preterm infants.

BACKGROUND: Parenteral nutrition solutions, formula milks, and human breast milk contain insufficient iodine to meet recommended intakes for preterm infants. Iodine deficiency may exacerbate transient hypothyroxinaemia in preterm infants and this may be associated with adverse respiratory or neurological outcomes. OBJECTIVES: To assess the evidence from randomised controlled trials that dietary supplementation with iodine reduces mortality and morbidity in preterm infants. SEARCH STRATEGY: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2005), MEDLINE (1966 - November 2005), EMBASE (1980 - November 2005), CINAHL (1982 - November 2005), conference proceedings, and previous reviews. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared a policy of supplementing enteral or parenteral feeds with iodine (more than 30 micrograms per kilogram per day) versus placebo or no supplementation in preterm infants. DATA COLLECTION AND ANALYSIS: The standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two reviewers, and synthesis of data using relative risk, risk difference and weighted mean difference. The primary outcomes for this review were neonatal mortality, death before hospital discharge, and longer term neurodevelopmental outcomes including severe neurodevelopmental disability. MAIN RESULTS: We found only one randomised controlled trial (N = 121) that fulfilled the review eligibility criteria (Rogahn 2000). The participants were infants born before 33 weeks' gestation (but most were of birth weight greater than 1000 grams). The primary aim of this trial was to assess the effect of iodine supplementation on thyroid function. The investigators did not detect any statistically significant effects on the plasma levels of thyroxine (free and total), triiodothyronine, or thyrotrophin in preterm infants (measured up to 40 weeks' post-conceptional age). Only one infant died and the trial was therefore underpowered to detect an effect on mortality. The trial did not assess the effect of the intervention on neurodevelopmental morbidity. There was not a statistically significant difference in the incidence of chronic lung disease. AUTHORS' CONCLUSIONS: There are insufficient data at present to determine whether providing preterm infants with supplemental iodine (to match fetal accretion rates) prevents morbidity and mortality in preterm infants. Future randomised controlled trials of iodine supplementation should focus on extremely preterm and extremely low birth weight infants, the group at greatest risk of transient hypothyroxinaemia. These trials should aim to assess the effect of iodine supplementation on clinically important outcomes including respiratory morbidity and longer term neurodevelopment.

Developmental Disabilities↗
PubMed2006

VLCAD deficiency: pitfalls in newborn screening and confirmation of diagnosis by mutation analysis.

We diagnosed six newborn babies with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) through newborn screening in three years in Victoria (prevalence rate: 1:31,500). We identified seven known and two new mutations in our patients (2/6 homozygotes; 4/6 compound heterozygotes). Blood samples taken at age 48-72 h were diagnostic whereas repeat samples at an older age were normal in 4/6 babies. Urine analysis was normal in 5/5. We conclude that the timing of blood sampling for newborn screening is important and that it is important to perform mutation analysis to avoid false-negative diagnoses of VLCADD in asymptomatic newborn babies. In view of the emerging genotype-phenotype correlation in this disorder, the information derived from mutational analysis can be helpful in designing the appropriate follow-up and therapeutic regime for these patients.

Acyl-CoA Dehydrogenase, Long-Chain↗
PubMed2006

Evidence for population level declines in adult HIV prevalence in Kenya.

The HIV/AIDS epidemic in Kenya has been tracked through annual sentinel surveillance in antenatal clinics since 1990. The system started with 13 sites and now has over 35. Behaviours have been measured through national Demographic and Health Surveys in 1993, 1998, and 2003. The surveillance data indicate that prevalence has declined substantially starting in 1998 in five of the original 13 sites and starting in 2000 in another four sites. No decline is evident in the other five original sites although the 2004 estimate is the lowest recorded. Nationally, adult prevalence has declined from 10% in the late 1990s to under 7% today. Surveys indicate that both age at first sex and use of condoms are rising and that the percentage of adults with multiple partners is falling. It is clear that HIV prevalence is now declining in Kenya in a pattern similar to that seen in Uganda but seven or eight years later. Although the coverage of preventive interventions has expanded rapidly since 2000 this expansion was too late to account for the beginnings of the decline in prevalence. More work is needed to understand fully the causes of this decline, but it is encouraging to see Kenya join the small list of countries experiencing significant declines in HIV prevalence.

Adolescent↗
PubMed2004

Mouse strains that lack spinal dynorphin upregulation after peripheral nerve injury do not develop neuropathic pain.

Several experimental models of peripheral neuropathy show that a significant upregulation of spinal dynorphin A and its precursor peptide, prodynorphin, is a common consequence of nerve injury. A genetically modified mouse strain lacking prodynorphin does not exhibit sustained neuropathic pain after nerve injury, supporting a pronociceptive role of elevated levels of spinal dynorphin. A null mutation of the gamma isoform of protein kinase C (PKCgamma KO [knockout]), as well as an inbred mouse strain, 129S6, also does not manifest behavioral signs of neuropathic pain following peripheral nerve injury. The objective of this study was to extend our observations to these genetic models to test the hypothesis that elevated levels of spinal dynorphin are essential for the maintenance of abnormal pain. In PKCgamma wild-type mice and the outbred mouse strain ICR, ligation of the L5 and L6 spinal nerves (SNL) elicited both tactile hypersensitivity and thermal hyperalgesia. Both strains showed a significant elevation in dynorphin in the lumbar spinal dorsal horn following SNL. Spinal administration of an anti-dynorphin A antiserum blocked the thermal and tactile hypersensitivity in both strains of mice. However, the PKCgamma KO mice and the 129S6 mice (which express PKCgamma) did not show abnormal pain after SNL; neither strain showed elevated levels of spinal dynorphin. The multiple phenotypic deficits in PKCgamma KO mice confound the interpretation of the proposed role of PKCgamma-expressing spinal neurons in neuropathic pain states. Additionally, the data show that the regulation of spinal dynorphin expression is a common critical feature of expression of neuropathic pain.

Animals↗
PubMed2004

Lung transplantation for cystic fibrosis.

BACKGROUND: Lung transplantation is a robust therapeutic option to treat patients with cystic fibrosis. PATIENTS AND METHODS: Since 1996, 109 patients with cystic fibrosis were accepted onto our waiting list with 58 bilateral sequential lung transplants performed in 56 patients and two patients retransplanted for obliterative bronchiolitis syndrome. RESULTS: Preoperative mean FEV(1) was 0.64 L/s, mean PaO(2) with supplemental oxygen was 56 mm Hg, and the mean 6-minute walking test was 320 m. Transplantation was performed through a "clam shell incision" in the first 29 patients and via bilateral anterolateral thoracotomies without sternal division in the remaining patients. Cardiopulmonary bypass was required in 14 patients. In 21 patients the donor lungs had to be trimmed by wedge resections with mechanical staplers and bovine pericardium buttressing to fit the recipient chest size. Eleven patients were extubated in the operating room immediately after the procedure. Hospital mortality of 13.8% was related to infection (n = 5), primary graft failure (n = 2), and myocardial infarction (n = 1). Acute rejection episodes occurred 1.6 times per patient/year; lower respiratory tract infections occurred 1.4 times per patient in the first year after transplantation. The mean FEV(1) increased to 82% at 1 year after operation. The 5-year survival rate was 61%. A cyclosporine-based immunosuppressive regimen was initially employed in all patients; 24 were subsequently switched to tacrolimus because of central nervous system toxicity, cyclosporine-related myopathy, or renal failure, obliterative bronchiolitis syndrome, gingival hyperplasia, or hypertrichosis. Ten patients were subsequently switched to sirolimus. Freedom from bronchiolitis obliterans at 5 years was 60%. CONCLUSIONS: Our results confirm that bilateral sequential lung transplantation is a robust therapeutic option for patients with cystic fibrosis.

Cystic Fibrosis↗
PubMed2003

Iodine deficiency associated with parenteral nutrition in extreme preterm infants.

Infants are in negative iodine balance on current standard regimens of total parenteral nutrition, with a mean iodine intake of 3 micro g/kg/day (150 ml/kg/day). The recommended enteral intake of iodine for preterm infants is 30 micro g/kg/day. Gastrointestinal absorption of iodine is high, suggesting that parenteral intakes should approach enteral recommendations.

Age Factors↗
PubMed2003

Community-based river management in Southeast Sulawesi, Indonesia: a case study of the Bau-Bau River.

In this paper we explain the current condition of the Bau-Bau River, examine community participation for management of the river system, and consider options for improving the institutional capacity for a community-based approach. This assessment is based on a research project with the following objectives: (1) analyse the biophysical and socio-economic condition of the river as a basis for future planning; (2) identify current activities which contribute waste or pollution to the river; (3) assess the status and level of pollution in the river; (4) analyse community participation related to all stages of river management; and (5) identify future river management needs and opportunities. Due to the increasing population in Bau-Bau city, considerable new land is required for housing, roads, agriculture, social facilities, etc. Development in the city and elsewhere has increased run-off and erosion, as well as sedimentation in the river. In addition, household activities are generating more solid and domestic waste that causes organic pollution in the river. The research results show that the water quality in the upper river system is still good, whilst the quality of water in the vicinity of Bau-Bau city, from the mid-point of the watershed to the estuary, is not good, being contaminated with heavy metals (Cd and Pb) and organic pollutants. However, the levels of those pollutants are still below regulatory standards. The main reasons for pollution in the river are mainly lack of management for both liquid and solid wastes, as well as lack of community participation in river management. The government of Bau-Bau city and the community are developing a participatory approach for planning to restore and conserve the Bau-Bau River as well as the entire catchment. The activities of this project are: (1) forming institutional arrangements to support river conservation; (2) implementing extension initiatives to empower the community; (3) identifying a specific location to establish an urban forest; (4) implementing demonstration projects for liquid system management; (5) promoting coordination amongst the different organisations and agencies in the catchment; (6) improving domestic waste transportation; and (7) recycling waste to create compost material to become an income source for the community.

Agriculture↗
PubMed2003

Annual risk of tuberculous infection in Khammam a tribal district of Andhra Pradesh.

A tuberculin survey to estimate annual risk of tuberculosis was conducted in Khammam tribal district during 2001-2002. A total of 8637 children were test-read--2991 without BCG scar and 5442 with BCG scar. The tests were performed using ITU PPD RT23 and the maximum size of induration was recorded at about 72 hours after the test. Based on the frequency distribution of reaction size, cut-off point for infection with tubercle bacilli was considered at 12 mm. Using this criterion, the prevalence of infection was estimated at 11.8% among children without BCG scar and 10.6% among children with BCG scar. This difference was found to be statistically insignificant. ARTI rates computed from the prevalence estimates among children without and with BCG scar were 1.6% and 1.5% respectively. It was computed as 1.5% from the prevalence in the combined group i.e. irrespective of BCG scar status.

Child↗
PubMed2002

[Delayed cerebral radionecrosis following radiation therapy of cutaneous squamous cell carcinomas of the head].

INTRODUCTION: Three cases of cerebral radionecrosis occurring after radiation therapy for squamous cell carcinomas of the scalp are reported. This rare and poorly documented complication of radiotherapy is discussed. CASE REPORTS: Three patients presenting with squamous cell carcinomas of the scalp were treated with surgery and radiotherapy for recurrent or incomplete resection of squamous cell carcinomas of the head. X-ray doses range were 50 to 60 Grays in 22 to 24 fractions. Cerebral radionecrotic lesions were diagnosed 6 months to 14 years after irradiation, and were inconstantly associated with clinical symptoms. The patients were treated with systemic steroids, which were of limited efficacy in one of our patients. DISCUSSION: Little is known of cerebral radionecrosis following radiotherapy. This may be related to their rare occurrence and/or to the difficulties in establishing diagnosis. The delay of occurrence after radiotherapy can vary between a few months and several years, and the lesions are directly correlated with the doses and the fractionning of the X-rays. Intracerebral localization of the tumour is the main differential diagnosis. Localized and cystic forms of cerebral radionecrosis can be treated by surgery. Treatment otherwise relies on systemic steroids.

Aged↗
PubMed2001

Molecular characterisation of mouse and human TSSC6: evidence that TSSC6 is a genuine member of the tetraspanin superfamily and is expressed specifically in haematopoietic organs.

Previous analyses of the murine and human TSSC6 (also known as Phemx) proteins were not carried out using the full length sequence. Using 5'-RACE and cDNA library screening, we identified an additional 5' sequence for both the murine Tssc6 cDNA and its human homologue TSSC6. This novel sequence encodes a 5' exon encoding an in frame, upstream start codon, an N-terminal cytoplasmic domain and a transmembrane domain. The deduced, and now full length, murine and human TSSC6 proteins contained four hydrophobic regions together with other features characteristic of the tetraspanin superfamily. Computational analyses of the full length sequences show that TSSC6 is a genuine, albeit relatively divergent member of this superfamily. Using RNA from a number of mouse tissues, we identified seven splice variants of Tssc6. Splice variants of the human gene were also detected. Tssc6 expression was detected early in embryogenesis in primitive blood cells and was confined to haematopoietic organs in the adult mouse. Tssc6 expression was detected in many haematopoietic cell lines and was highest in cell lines of the erythroid lineage.

Alternative Splicing↗
PubMed2001

Exposure of Blastocystis species to a cytotoxic monoclonal antibody.

A recently described cytotoxic monoclonal antibody (mAb 1D5) raised against Blastocystis hominis isolate B, was tested for reactivity with 13 different isolates of Blastocystis. The isolates used were previously isolated from humans, rats and reptiles and were maintained as axenised cultures throughout the course of this study. Five B. hominis isolates (B, C, E, G and H) were found to react with mAb 1D5 in immunoblotting studies and the indirect fluorescence antibody test. The pattern of fluorescence observed for all five isolates was diffuse and patchy. Immunoblotting studies revealed that mAb 1D5 reacted with a 29-30-kDa protein found in all five isolates. Results of a cytotoxic assay showed that the mAb exhibited a complement-independent cytotoxic effect on all the exposed isolates. Microscopic observations showed differences in morphology between the Blastocystis cells exposed and unexposed to mAb. Acridine orange staining performed on both exposed and unexposed cells showed similar internal structures when viewed under fluorescence microscopy.

Animals↗
PubMed2001

Identification and characterisation of Toxoplasma gondii protein farnesyltransferase.

Prenylated proteins are involved in the regulation of DNA replication and cell cycling and have important roles in the regulation of cell proliferation. Protein farnesyltransferase and protein geranylgeranyltransferase are the two enzymes responsible for catalysing isoprene lipid modifications. Recently these enzymes have been targets for the development of cancer chemotherapeutics. Using metabolic labelling we identified isoprenylated proteins which suggests the presence of protein farnesyltransferase in Toxoplasma gondii. T. gondii protein farnesyltransferase is heat-labile and requires Mg(2+) and Zn(2+) ions for full activity. Peptidomimetic analogues as well as short synthetic peptides were tested in vitro as possible competitors for farnesyltransferase substrates. We found that the synthetic peptide (KTSCVIA) specifically inhibited T. gondiiprotein farnesyltransferase but not mammalian (HeLa cells) farnesyltransferase. Therefore this study suggests the possible development of specific inhibitors of T. gondiiprotein farnesyltransferase as an approach to parasitic protozoa therapy.

Alkyl and Aryl Transferases↗
PubMed2001

Pelviscopic reversal of tubal sterilization with the one- to two-stitch technique.

STUDY OBJECTIVE: To describe 28 pelviscopic proximal reversals of tubal sterilization. DESIGN: Cohort study (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: Twenty-eight women. INTERVENTIONS: Twenty-two women underwent bilateral and six unilateral tubal end-to-end anastomosis through a catheter introduced through the working channel of a hysteroscope for a combined hysteroscopic-laparoscopic operation. MEASUREMENTS AND MAIN RESULTS: In the two-stitch technique the first stitch adapted the mesosalpinx and the second (4-0 or 6-0 material) to unite the tube muscularis. In some cases a third stitch was applied to either the muscularis or mesosalpinx. In all cases the wound was sealed with tissue col at the end of the procedure. Tubal patency was achieved in 95% of bilateral anastomoses and 100% of unilateral ones. Seventeen pregnancies (61%) were achieved within a minimum of 6 months and a maximum of 4 years. Fifteen patients (54%) had an intrauterine pregnancy with normal delivery and two (7%) had a tubal pregnancy. No abortions occurred. CONCLUSION: Laparoscopic end-to-end anastomosis is a suitable surgical alternative to tubal end-to-end anastomosis by laparotomy and has all the advantages of a laparoscopic procedure.

Adult↗
PubMed2001

Selective enhancement of gene transfer by steroid-mediated gene delivery.

The incorporation of transgenes into the host cells' nuclei is problematic using conventional nonviral gene delivery technologies. Here we describe a strategy called steroid-mediated gene delivery (SMGD), which uses steroid receptors as shuttles to facilitate the uptake of transfected DNA into the nucleus. We use glucocorticoid receptors (GRs) as a model system with which to test the principle of SMGD. To this end, we synthesized and tested several bifunctional steroid derivatives, finally focusing on a compound named DR9NP, consisting of a dexamethasone backbone linked to a psoralen moiety using a nine-atom chemical spacer. DR9NP binds to the GR in either its free or DNA-crosslinked form, inducing the translocation of the GR to the nucleus. The expression of transfected DR9NP-decorated reporter plasmids is enhanced in dividing cells: expression of steroid-decorated reporter plasmids depends on the presence of the GR, is independent of the transactivation potential of the GR, and correlates with enhanced nuclear accumulation of the transgene in GR-positive cells. The SMGD effect is also observed in cells naturally expressing GRs and is significantly increased in nondividing cell cultures. We propose that SMGD could be used as a platform for selective targeting of transgenes in nonviral somatic gene transfer.

Active Transport, Cell Nucleus↗