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Biomedical subjects

A S Ibrahim

Publications and source records attributed to A S Ibrahim.

At least 37 records · Page 2Linked to original sources
PubMed1994

A classification after radical cystectomy of patients with bladder cancer associated with schistosomiasis.

The aim of this study was to classify the bilharzial bladder cancer patients after radical cystectomy into several prognostic strata with increasing risk of recurrence. 310 patients through the period 1977-1983 at the National Cancer Institute of Cairo were systematically analysed for 12 variables evaluated after radical cystectomy. Eight factors were shown to have a significant influence on the recurrence-free survival curve after radical cystectomy namely: tumour stage, size, grade and location in the bladder, lymph node involvement, metastasis, renal insufficiency and urinary diversion. Using the proportional hazard model, five factors were significantly related to a lower recurrence-free survival, one major prognostic factor, tumour grade (G2 or G3) (relative risk estimate of 5.5), and four minor prognostic factors (relative risk estimates around 2), namely tumour diameter greater than 5 cm, anterior or trigonal location of the tumour, tumour stage (T3 or T4) and presence of renal insufficiency before surgery. Four prognostic strata have been defined in relation to the presence of these prognostic factors. This classification was validated on a second sample of 122 patients by comparing for each prognostic stratum, the recurrence-free survival curve observed on this sample and the corresponding predicted curve by Cox model. No statistically significant difference could be detected. This classification of bladder cancer patients appears to be adequate for bilharzial bladder cancer patients after radical cystectomy, at least in the conditions they presented and were treated for at the NIC in Cairo.

Adult↗
PubMed1994

Sterol composition of Cryptococcus neoformans in the presence and absence of fluconazole.

Analysis of the sterol compositions of 13 clinical isolates of the pathogenic yeast Cryptococcus neoformans obtained from five patients with recurring cryptococcal meningitis showed that, unlike Candida albicans, the major sterols synthesized by this yeast were obtusifoliol (range, 21.1 to 68.2%) and ergosterol (range, 0.0 to 46.5%). There was considerable variation in the sterol contents among the 13 isolates, with total sterol contents ranging from 0.31 to 5.9% of dry weight. The isolates from the five patients who had relapses had different total sterol contents and compositions in comparison with those of the pretreatment isolates, indicating either that the sterols had been changed by therapy or that the patients were infected with new isolates with different sterol compositions. Growth of the cryptococcal isolates in the presence of subinhibitory concentrations of fluconazole (0.25x the MIC) significantly altered the sterol content and pattern. The total sterol content decreased in nine isolates and increased in four isolates in response to pretreatment with fluconazole. Fluconazole had no consistent effect on ergosterol levels. In contrast, fluconazole caused a decrease in obtusifoliol levels and an increase in 4,14-dimethylzymosterol levels in all isolates. These results indicate extensive diversity in sterol content, sterol composition, and sterol synthesis in response to subinhibitory concentrations of fluconazole in C. neoformans strains. We propose that fluconazole inhibits the sterol synthesis of C. neoformans by interfering with both 14 alpha-demethylase-dependent and -independent pathways. No correlation between the sterol compositions of C. neoformans isolates and their susceptibilities to fluconazole was found.

Cholestadienols↗
PubMed1994

Mechanisms by which Candida albicans induces endothelial cell prostaglandin synthesis.

One strategy for improving resistance to opportunistic pathogens is to determine host cellular responses during the invasion process and upregulate those responses that are relevant to host defense mechanisms. Within this context, we have shown previously that invasion of endothelial cells by Candida albicans in vitro causes increased production of prostaglandins. As a prerequisite for modulating endothelial cell prostaglandin production, we now characterize the mechanisms through which this process occurs. Endothelial cell invasion by C. albicans appeared to stimulate the conversion of arachidonic acid into prostaglandins by upregulating the synthesis of endothelial cell cyclooxygenase and increasing the activity of the endothelial cell phospholipase. The enhanced activities of these two enzymes were independent of calphostin C-sensitive protein kinase C and resulted in the increased production and extracellular secretion of prostaglandin I2 (PGI2), PGF2 alpha, and PGE2. The secretion of these prostaglandins had no effect on the amount of endothelial cell injury induced by C. albicans. The role of the increased prostaglandin secretion by endothelial cells is likely related to modulation of the leukocyte response at the candida-leukocyte-endothelial cell interface.

Candida albicans↗
PubMed1993

Interferon-gamma protects endothelial cells from damage by Candida albicans.

Endothelial cells activated with interferon-gamma (IFN-gamma) have been shown to inhibit the replication of Toxoplasma gondii. To determine if this cytokine protects endothelial cells from damage by Candida albicans, human umbilical vein endothelial cells were pretreated with IFN-gamma and infected with C. albicans; endothelial cell damage was measured by the release of 51Cr. Pretreatment with IFN-gamma decreased the extent of endothelial cell injury caused by C. albicans by up to 100% +/- 8.2%. This diminution of endothelial cell damage was confirmed by scanning electron microscopy. The degree of protection was dependent on the concentration of IFN-gamma, with maximum protection occurring at 13 units/mL. Higher concentrations of IFN-gamma were toxic to the endothelial cells. Pretreating the endothelial cells with this cytokine had no effect on candidal germination and growth, suggesting that IFN-gamma stimulates endothelial cells to become resistant to or inhibit the action of candidal virulence factors.

Candida albicans↗
PubMed1993

Fungicidal properties of defensin NP-1 and activity against Cryptococcus neoformans in vitro.

Defensin NP-1, derived from the neutrophils of rabbits, was tested for its fungistatic and fungicidal activity against strains of Cryptococcus neoformans. The MICs for the encapsulated strains tested ranged from 3.75 to 15.0 micrograms of NP-1 per ml. The minimum fungicidal concentrations for these strains were similar to the MICs. An acapsular strain, however, had a lower MIC of 0.93 and minimum fungicidal concentration of 1.88 micrograms/ml. NP-1 demonstrated time-dependent and concentration-dependent killing of C. neoformans. Killing occurred rapidly in the first 20 min of exposure to NP-1 and was maximum at 90 to 120 min. Killing of C. neoformans by NP-1 was concentration dependent with 31% +/- 9% survival at 25 micrograms/ml, 13% +/- 4% survival at 50 micrograms/ml, 9% +/- 5% survival at 75 micrograms/ml, and 5% +/- 3% survival at 100 micrograms/ml. NP-1's fungicidal effect on C. neoformans was also inoculum dependent, with increased activity observed at 10(4) versus 10(5) or 10(6) cells per ml. In addition, stationary-phase C. neoformans was less susceptible to NP-1 killing than yeast cells in the logarithmic phase. Subinhibitory concentrations of both NP-1 (0.25 x MIC) and fluconazole (0.25 x MIC) acted synergistically in inhibiting growth of C. neoformans. Similar combinations of NP-1 and amphotericin B, however, did not yield synergy.

Amphotericin B↗
PubMed1993

Thrombin-induced rabbit platelet microbicidal protein is fungicidal in vitro.

Platelet microbicidal protein (PMP) is released from platelets in response to thrombin stimulation. PMP is known to possess in vitro bactericidal activity against Staphylococcus aureus and viridans group streptococci. To determine whether PMP is active against other intravascular pathogens, we evaluated its potential fungicidal activity against strains of Candida species and Cryptococcus neoformans. Anionic resin adsorption and gel electrophoresis confirmed that the fungicidal activity of PMP resided in a small (approximately 8.5-kDa), cationic protein, identical to previous studies of PMP-induced bacterial killing (M.R. Yeaman, S.M. Puentes, D.C. Norman, and A.S. Bayer, Infect. Immun. 60:1202-1209, 1992). When assayed over a 180-min period in vitro, the susceptibilities of these fungi to PMP varied considerably. Generally, Candida albicans strains (mean survival, 33.5% +/- 6.9% [n = 6]) as well as isolates of Candida glabrata (mean survival, 50.8% +/- 2.9% [n = 2]) were the most susceptible to killing by PMP, while Candida guillermondii and Candida parapsilosis were relatively resistant to PMP-induced killing. Compared with C. albicans, C. neoformans was relatively resistant to the fungicidal activity of PMP, with a mean survival among the isolates studied of 77.4% +/- 12.4% (n = 6). Against C. albicans, PMP-induced fungicidal activity was time dependent (range, 0 to 180 min), PMP concentration dependent (range, 10 to 150 U/ml), and inversely related to the fungal inoculum (range, 5 x 10(3) to 1 x 10(5) CFU/ml). Scanning electron microscopy of PMP-exposed C. albicans and C. neoformans cells revealed extensive surface damage and collapse, suggesting that the site of PMP fungicidal action may directly or indirectly involve the fungal cell envelope.

Amphotericin B↗
PubMed1992

Modulation of interactions of Candida albicans and endothelial cells by fluconazole and amphotericin B.

Using an in vitro model of intravascular infection, we examined the effects of exposure to subinhibitory concentrations of fluconazole and amphotericin B on the ability of Candida albicans to adhere to and damage human umbilical vein endothelial cells. Incubation of the organisms for 18 h in 0.5x the MICs of fluconazole and amphotericin B inhibited endothelial cell adherence by 22 and 91%, respectively (P less than 0.001 for each drug). Candida-induced endothelial cell injury was also decreased by exposing the organisms to the antifungal drugs while in contact with the endothelial cells. Fluconazole inhibited damage by approximately 50% at concentrations ranging from 0.25x to 5x the MIC (P less than 0.01 for each concentration). Exposure to amphotericin B at 0.5x the MIC completely blocked the ability of the organisms to injure endothelial cells. The capacities of the antifungal agents to inhibit endothelial cell injury paralleled their abilities to suppress candidal germination. Organisms exposed to up to 5x the MIC of fluconazole had diminished, but still detectable, germ tube production and elongation, whereas incubation in 0.5x the MIC of amphotericin B completely abrogated germination. In addition to their direct effects on the growth of C. albicans, fluconazole and amphotericin B may decrease the ability of the fungus to disseminate hematogenously by inhibiting the organisms' capacity to adhere to and injure endothelial cells.

Amphotericin B↗
PubMed1992

Susceptibility testing of Cryptococcus neoformans: a microdilution technique.

We studied a series of test conditions in a microtiter system to define the optimal method for determining the susceptibility of Cryptococcus neoformans to antifungal agents. Twenty-one isolates of C. neoformans were grown for 24 or 48 h in four chemically defined media: yeast nitrogen base (BYNB 7); RPMI 1640; synthetic amino acid medium--fungal (SAAMF), buffered at pH 7.0 to select the medium that best supported growth of this fastidious yeast; and yeast nitrogen base, pH 5.4 (YNB 5.4). Maximum growth of C. neoformans, at 35 degrees C, was obtained in YNB 5.4, with the next highest growth levels in BYNB 7, SAAMF, and RPMI. Growth at 24 h was uniformly poor in all media and lacked reproducibility. In contrast, incubation for 48 h gave adequate growth with low standard deviations, and 48 h was selected as the optimal incubation period for this study. Comparison of the relationship between growth kinetics and initial inoculum size for eight cryptococcal isolates showed that 10(4) cells per ml yielded optimal growth in BYNB 7 and YNB 5.4, whereas 10(5) cells per ml was optimal in RPMI and SAAMF. Furthermore, variation of inocula from 10(3) to 10(5) cells per ml showed small but significant inoculum effects in determining MICs of fluconazole, amphotericin B, and flucytosine for C. neoformans. Therefore, 10(4) cells per ml was chosen as the optimal inoculum for susceptibility testing in this study. Mean MICs of fluconazole, amphotericin B, and flucytosine for 21 crytococcal isolates in RPMI and BYNB 7 were low (for example, fluconazole had mean MICs of 1.2 and 1.3 micrograms/ml in RPMI and BYNB 7, respectively) and differed significantly from medium to medium. In contrast, the MICs obtained in SAAMF were significantly higher (e.g., fluconazole had a mean MIC of 2.2 micrograms/ml). Variance in MICs was large with fluconazole and flucytosine but small with amphotericin B, irrespective of the medium used. A microtiter system employing BYNB 7 as the medium, 48 h as the incubation period, and 10(4) cells per ml as the final inoculum is a simple, accurate, and reproducible method for the testing of C. neoformans susceptibility to fluconazole, amphotericin B, and flucytosine.

AIDS-Related Opportunistic Infections↗
PubMed1991

Perception of and concern about sociocultural change and general psychopathology in Saudi Arabian university students.

This study presents data on 280 Saudi Arabian university students regarding their perception of and concern about sociocultural changes in their society and compares their scores on these variables with their responses on psychopathology measures. Subjects wee administered an interview schedule evaluating perception of and concern (upset or not upset) about sociocultural changes, the Multiple Affect Adjective Check List (Zuckerman & Lubin, 1965), the Depression Symptomatology Scale (Schwab, 1974; Schwab, Holzer, Warheit, & Schwab, 1981), and the Symptom Inventory, a measure devised for this study. The results showed that (a) substantial numbers of subjects were aware of the social and cultural transformations in Saudi Arabia, (b) depressive and psychopathological symptoms were reported by extremely higher proportions of Saudis than usually reported in other societies, and (c) higher levels of concern about sociocultural changes obtained the lowest depression scores, indicating that those not upset by social transformation were generally not depressed.

Adaptation, Psychological↗
PubMed1990

Crude oil and hydrocarbon-degrading strains of Rhodococcus rhodochrous isolated from soil and marine environments in Kuwait.

Soil and marine samples collected from different localities in Kuwait were screened for microorganisms capable of oil degradation. Both fungi and bacteria were isolated. The fungal flora consisted of Aspergillus terreus, A. sulphureus, Mucor globosus, Fusarium sp. and Penicillum citrinum. Mucor globosus was the most active oil degrading fungus isolated. Bacterial isolates included Bacillus spp. Enterobacteriaceae, Pseudomonas spp., Nocardia spp., Streptomyces spp.,and Rhodococcus spp. Among these Rhodococcus strains were the most efficient in oil degradation and, relatively speaking, the most abundant. Bacterial and fungal isolates differed in their ability to degrade crude oil, with Rhodococcus isolates being more active that fungin in n-alkane biodegradation, particularly in the case of R. rhodochrous. In addition to medium chain n-alkanes, fungi utilized one or more of the aromatic hydrocarbons studied, while bacteria failed to do so. R. rhodochorous KUCC 8801 was shown by GLC and post-growth studies to be more efficient in oil degradation than isolates known to be active oil degraders.

Journal Article↗
PubMed1990

Combinations of antifungal and antineoplastic drugs with interactive effects on inhibition of yeast growth.

Interactive effects among antifungal and antineoplastic drugs contributed to toxicities when combinations of these drugs were used to inhibit the growth of five Candida spp. Drug interactions were measured by growth inhibition in both liquid and solid media, by viable cell counts and by examination using scanning electron microscopy. Large cooperative effects on toxicity were demonstrated between some antineoplastic and antifungal drugs. For example, positive cooperativity was seen between the antineoplastic drug 5-fluorouracil and combinations of the antifungal agents amphotericin B and miconazole nitrate. Smaller, and often negative, interactions occurred between the antineoplastic drug cyclophosphamide and antifungal drugs. The levels of drugs required for inhibition in combination drug treatments were critically dependent upon the ratios as well as the absolute concentrations of the drugs tested. Drug combinations were selected which inhibit yeast growth at concentrations far below the individual MIC of the drugs. These combinations may prove of value in clinical treatments of cancer patients infected by Candida.

Antibiotics, Antineoplastic↗
PubMed1990

Growth of Candida albicans on hydrocarbons: influence on lipids and sterols.

Candida albicans KTCC 89062 an isolate from a crude oil polluted soil sample in Kuwait grew adequately on n-alkanes with only 12 to 20 carbon chains but not on aromatic hydrocarbons. This isolate grew on glucose better than on any of the alkanes. Alkane-grown cells contained higher proportions of total lipids than glucose-grown cells, and the total lipid content was directly proportional to the alkane chain length. The sterol content also increased in alkane-grown cells; the highest level was with C12 as substrate and progressively lower sterol levels were obtained as the carbon chain length increased. The phospholipid:sterol ratio decreased when the cells were grown on alkanes as compared with glucose grown cells. The ratio of unsaturated:saturated fatty acids was higher in alkane than glucose grown cells and decreased progressively from C12 to C20 as substrates. Growth on alkanes but not on glucose was associated with pseudohyphal formation.

Alkanes↗
PubMed1989

Multifactorial analysis of effects of interactions among antifungal and antineoplastic drugs on inhibition of Candida albicans growth.

Interactions among antineoplastic and antifungal drugs affecting the inhibition of Candida albicans growth are complex functions of the nature of the drugs used in combination, their absolute concentrations, and also their relative concentrations. Studies of drug interactions involving the use of test drugs in fixed concentration ratios can lead to inaccurate conclusions about synergism or antagonism among the drugs. A multifactorial experimental design procedure in which the concentrations of all drugs in test combinations were simultaneously varied has been used to identify and quantify drug interactions. The methods have been applied to combinations of two, three, and four drugs, including antineoplastic drugs, antifungal drugs, and combinations of antineoplastic and antifungal drugs. Results were obtained which allow predictions of effects of combinations and provide maximum effectiveness in growth inhibition with minimum levels of the test drugs.

Antifungal Agents↗
PubMed1987

A model to predict the outcome of the bilharzial bladder cancer patient after radical cystectomy.

The aim of the present study was to evaluate the prognostic factors of bilharzial bladder cancer treated by radical cystectomy: good prognosis is defined as a survival of more than one year, free of local recurrence or metastasis. Two groups of 155 patients, one with a good prognosis (GPG) and the other with a bad prognosis (BPG), through the period 1977-1983 at the National Cancer Institute of Cairo were systematically analyzed for 13 variables evaluated at the commencement of the one year follow-up. Nine factors proved to be of high prognostic value: age, tumour stage, size, grade and location in the bladder, lymph node involvement, metastasis, renal insufficiency and type of urinary diversion. Four variables appeared not to have prognostic value viz: sex, type of tumour (multiplicity), histopathology, and presence of ova of schistosoma haematobium in the specimen. Using a discriminant analysis technique to take into account the inter-relationships between the factors, it was found that tumour grade was the most important prognostic factor followed, in order of importance, by tumour stage, renal insufficiency, size of the tumour and lymph node involvement. Moreover, a simplified score for prognosis was determined: X = 10 grade (1 to 3) +5 stage (1 to 4) +6 renal insufficiency (Y/N) +1 diameter of the tumour (cm) +4 lymph node involvement (Y/N). The larger the score, the poorer the prognosis.

Adult↗
PubMed1983

Normal serum concentrations of uric acid among a Syrian population.

For the accurate interpretation of the effect of age on uric acid concentrations in a local Syrian population a reference value must be used. We found this to be 4.71 (+/- 2SD 2.22-7.19) and 5.16 (+/- 2SD 2.51-7.81) mg/100 ml for apparently normal healthy females and males respectively. No significant differences were found in serum uric acid levels between the age groups for females although for males of 30-40 years there was a significant rise in the concentration.

Adult↗