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Biomedical subjects

H Osman

Publications and source records attributed to H Osman.

At least 19 recordsLinked to original sources
PubMed2006

Surveillance of respiratory virus infections in adult hospital admissions using rapid methods.

Both influenza and respiratory syncytial virus (RSV) cause epidemics of respiratory illness of variable severity during the winter season. Influenza in particular has been blamed for hospital winter bed pressures, although it is thought that RSV may also play a role. Human metapneumovirus (hMPV) is a new respiratory virus reported to be important in children; only a limited number of studies are available for adult populations. We aimed to determine initially the burden of virologically confirmed infections, i.e. influenza, RSV and hMPV using polymerase chain reaction (PCR) technology and, in addition, to assess the feasibility of this approach as a surveillance tool for these respiratory viruses. Adult patients admitted to hospital in the previous 24 hours with onset of acute respiratory symptoms in the last 14 days were asked to participate. Informed written consent was obtained and nose and throat swabs taken. Multiplex PCR for influenza A (H1N1 and H3N2), influenza B and RSV A and B were carried out together with a separate PCR for hMPV. A total of 219 patients in 2001-2002 and 216 in 2002-2003 were tested and the combined results for both seasons were: 8 positive for influenza A/H1N1, 14 for influenza A/H3N2, 2 for influenza B, 14 for RSV A and 6 for RSV B. Most patients (261/435) were >65 years and most positives (30/44) were found within this age group. A number of patients aged >65 years who were positive for influenza (12/15) reported having had vaccine. In total, 373 samples were tested for hMPV and 20 were found positive across all age groups except the 45-54 years age group. As influenza activity was low during the study period the impact of infection on admissions could not be assessed. Nevertheless the viruses studied accounted for 15% of hospital admissions for respiratory infection. Most patients were aged >65 years, as expected. In the two years studied RSV and hMPV were each responsible for as many hospitalized cases of respiratory infection as influenza. Influenza infection must be considered even in those who give a history of vaccination. The molecular methods used in this study showed that surveillance of these respiratory viruses can be conducted and may help in the management of patients.

Adult↗
PubMed2004

Human hepatic cell uptake of resveratrol: involvement of both passive diffusion and carrier-mediated process.

This work reports significant advances on the transport in hepatic cells of resveratrol, a natural polyphenol with potent protective properties. First, we describe a new simple technique to qualitatively follow resveratrol cell uptake and intracellular distribution, based on resveratrol fluorescent properties. Second, the time-course study and the quantification of (3)H-labelled resveratrol uptake have been performed using human hepatic derived cells (HepG2 tumor cells) and hepatocytes. The temperature-dependence of the kinetics of uptake as well as the cis-inhibition experiments agree with the involvement of a carrier-mediated transport in addition to passive diffusion. The decrease of passive uptake resulting from resveratrol binding to serum proteins brings to light a mediated mechanism in physiological situation.

Biological Availability↗
PubMed2004

Influence of cytomegalovirus (CMV) sero-positivity on CMV infection, lymphocyte recovery and non-CMV infections following T-cell-depleted allogeneic stem cell transplantation: a comparison between two T-cell depletion regimens.

We compared the incidence and outcome of preemptively treated cytomegalovirus (CMV) infection, lymphocyte recovery and non-CMV infections between two different TCD modalities, one employing CD34+ selection and T-cell add-back (TCAB), preceded by Campath-1H in vivo (CD34+/TCAB group, n=29), and the other using grafts incubated with Campath-1H in vitro (Campath-1H in vitro group, n=32). The probabilities of CMV reactivation and recurrence were 67 and 83.6% in the CD34+/TCAB group and 42.9 and 20% in the Campath-1H group (P=0.07 and 0.02). Donor sero-positivity reduced CMV reactivation in the Campath-1H group, but not in the CD34+/TCAB group. The durations of positive PCR/antigenemia positivity and antiviral therapy were also significantly longer in the CD34+/TCAB group. However, only two patients developed CMV disease in each group. The mean absolute lymphocyte counts (x 10(9)/l) at 30 days (0.27 vs 0.4, P=0.03) and 100 days (0.77 vs 1.4, P=0.01) were significantly lower in the CD34+/TCAB group along with a higher incidence of non-CMV infections in CMV at-risk patients, but not in the CMV low-risk group. These findings suggest that the modality of TCD should be tailored according to the CMV risk status, and CMV sero-positive patients should receive a less extensively T-cell-depleted graft and a CMV sero-positive graft if possible.

Adoptive Transfer↗
PubMed2004

Enterovirus infections following T-cell depleted allogeneic transplants in adults.

Anecdotally, enteroviruses have been reported to cause serious complications post BMT, but the exact impact of these viruses in the post transplant period has not been reported. We prospectively evaluated stool, urine and throat samples for enteroviruses by viral culture together with relevant body fluids by RT-PCR in 64 allograft recipients receiving grafts T-cell depleted by Campath-1H, following both conventional and reduced-intensity conditioning. Seven patients (10.4%) developed nine episodes of enterovirus infections at a median of 146 days post transplant. Four episodes were associated with symptomatic illnesses, which could be attributable to enteroviruses. There was no mortality directly related to enteroviruses. There was no correlation between dose and mode of Campath-1H use, lymphocyte recovery, IgG and IgA levels and enterovirus isolation. Although enteroviruses tended to be more frequent in TBI-based conventional conditioning recipients, the only significant risk factor for enterovirus infection was unrelated donor graft. The low incidence of the severe enterovirus infections could have been related to a low lymphocyte count in this cohort in the absence of GVHD, particularly CD4+ count, which has been implicated in tissue damage in experimental animals. Further studies are needed to define its impact in different allograft settings.

Adolescent↗
PubMed2004

The use of lamivudine for patients with acute hepatitis B (a series of cases).

There are limited data on the use of lamivudine for patients with severe forms of acute hepatitis B. We report our experience with the use of lamivudine in six patients with acute HBV infection. Lamivudine was justified by disease severity for four patients and by concerns about risk of chronicity for two patients. The diagnoses of the treated patients were: fulminant liver failure (two patients), severe acute hepatitis B, protracted acute hepatitis B, and new HBV infection in the renal dialysis setting (two patients, one with severe liver injury). Serum HBV DNA titres ranged from 10(5) to 10(7) copies/mL prior to commencement of lamivudine. Lamivudine treatment was associated with a decline in serum HBV DNA and serum transaminases in all patients. All but one patient survived. A 58-year-old man with fulminant hepatitis and multiple organ failure died despite antiviral treatment. When possible, HBeAg and HBsAg seroconversion was documented during follow-up. In the absence of a randomized, prospective study of lamivudine in patients with severe acute hepatitis B, our data encourage the use of this safe and well tolerated drug.

Acute Disease↗
PubMed2003

Polyoma viruria following T-cell-depleted allogeneic transplants using Campath-1H: incidence and outcome in relation to graft manipulation, donor type and conditioning.

Haemorrhagic cystitis (HC) is an important cause of morbidity following stem cell transplantation (SCT) and has been associated with polyoma virus infection. We studied the incidence and outcome of polyoma virus infection in 58 T-cell-depleted SCT patients. T-cell depletion was carried out using Campath-1H, either 10 or 20 mg in vitro (n=33) or 50 or 100 mg in vivo (n=25) following conventional (n=35) or nonmyeloablative conditioning (n=23). A total of 21 patients (36%) had polyoma viruria at a median of 35 days (5-114); 30% among patients receiving Campath in vitro and 44% among those given in vivo. The only risk factor for polyoma viruria was graft-versus-host disease GVHD grade >or=2. The onset of polyoma viruria coincided with Cytomegalovirus (CMV) reactivation in all six patients who reactivated both viruses. Prolonged viruria (defined as polyoma viruria >2 weeks) was documented in 10 patients (17%) and this was associated with GVHD >or=grade 2. HC occurred in four patients. Prolonged viruria was associated with HC only in patients receiving unrelated donor grafts following conventional conditioning. HC was not observed following nonmyeloablative conditioning despite a higher incidence of prolonged viruria. Thus, HC was uncommon in patients with polyoma viruria following T-cell depletion with Campath, particularly after reduced intensity conditioning.

Adolescent↗
PubMed2003

United Arab Emirates National Newborn Screening Programme: an evaluation 1998-2000.

To evaluate the United Arab Emirate National Newborn Screening Programme we compared coverage, timeliness of programme indicators (age at sampling, recall and treatment initiation, timing of specimen delivery and laboratory results) and specimen quality with international standards. Recall rate, sensitivity, specificity, positive predictive values and relative incidence rates for phenylketonuria (PKU) and congenital hypothyroidism (CH) were calculated. Investigations for hypothyroidism included thyroid function studies (T3, T4, fT4 and TSH), technetium-99m thyroid scan when possible and thyroglobulin and thyroid antibodies when indicated. PKU investigations included plasma amino acids and measurement of biopterin defects. In the 6 years before December 2000, 138,718 neonates were screened. Relative incidences for CH and for classic PKU were 1:1570 and 1:20,050 respectively.

Aftercare↗
PubMed2001

Fatty acids bind to the fungal elicitor cryptogein and compete with sterols.

Cryptogein is a proteinaceous elicitor of plant defense reactions which also exhibits sterol carrier properties. In this study, we report that this protein binds fatty acids. The stoichiometry of the fatty acid-cryptogein complex is 1:1. Linoleic acid and dehydroergosterol compete for the same site, but elicitin affinity is 27 times lower for fatty acid than for sterol. We show that C7 to C12 saturated and C16 to C22 unsaturated fatty acids are the best ligands. The presence of double bonds markedly increases the affinity of cryptogein for fatty acids. A comparison between elicitins and known lipid transfer proteins is discussed.

Algal Proteins↗
PubMed2001

Pre-emptive oral ribavirin therapy of paramyxovirus infections after haematopoietic stem cell transplantation: a pilot study.

Infections with the paramyxoviruses, respiratory syncytial virus (RSV) and parainfluenza virus (PIV) can result in serious morbidity and mortality after haemopoietic stem cell transplant (HSCT). Once pneumonia develops, the outcome of these infections is often poor despite anti-viral therapy. Aerosolised ribavirin has been evaluated as pre-emptive therapy for post-transplant RSV infections with some success. Due to the financial and logistic burden involved with the use of aerosolised ribavirin, we explored the efficacy and toxicity of oral ribavirin for pre-emptive therapy of post-transplant RSV and PIV infections in a dose escalating schedule (15-60 mg/kg/day). Five episodes each of RSV and PIV were treated in seven patients. Five patients were receiving treatment for GVHD and two acquired the infection in the pre-engraftment period. All the episodes of RSV infection improved with oral ribavirin with dose escalation to 30-45 mg/kg in three of them. On the other hand, only two of the five PIV infections improved with oral ribavirin. Of the three non-responders, two infections were acquired in the pre-engraftment period with one death from PIV pneumonia. Reversible anaemia was the only side-effect noted in patients treated for over 2 weeks. Thus, the use of oral ribavirin was well tolerated in the post-transplant period with no untoward toxicities. There was a trend towards better response in RSV infections, which needs to be further explored in controlled studies.

Administration, Oral↗
PubMed2001

Cidofovir as primary pre-emptive therapy for post-transplant cytomegalovirus infections.

Pre-emptive antiviral therapy for CMV infection following allogeneic stem cell transplantation is an effective strategy for preventing CMV disease. This entails the logistic difficulty of daily intravenous therapy with ganciclovir or foscarnet to clinically asymptomatic patients. Cidofovir (CDV) is effective against CMV in vitro and has the practical advantage of weekly administration. However, there are limited data on the pre-emptive use of CDV in CMV infections. We carried out a pilot study exploring the efficacy and toxicity of CDV as primary pre-emptive therapy for CMV infections monitored by PCR-based assays. CDV was used at 5 mg/kg with probenecid and hydration, weekly for a maximum of 4 weeks, followed by fortnightly maintenance treatment. Four patients were treated with CDV and two of them responded. Both the non-responders developed CMV disease. There was no renal toxicity noted in any of the patients, but three patients had severe vomiting and one developed uveitis, which precluded maintenance treatment in the two responders. Following failure of CDV, foscarnet was effective in controlling the CMV infection in both patients, although the infection recurred in both. Thus, larger randomised studies are required before CDV can be recommended as a primary pre-emptive therapy for post-transplant CMV infections.

Adult↗
PubMed2001

Mediation of elicitin activity on tobacco is assumed by elicitin-sterol complexes.

Elicitins secreted by phytopathogenic Phytophthora spp. are proteinaceous elicitors of plant defense mechanisms and were demonstrated to load, carry, and transfer sterols between membranes. The link between elicitor and sterol-loading properties was assessed with the use of site-directed mutagenesis of the 47 and 87 cryptogein tyrosine residues, postulated to be involved in sterol binding. Mutated cryptogeins were tested for their ability to load sterols, bind to plasma membrane putative receptors, and trigger biological responses. For each mutated elicitin, the chemical characterization of the corresponding complexes with stigmasterol (1:1 stoichiometry) demonstrated their full functionality. However, these proteins were strongly altered in their sterol-loading efficiency, specific binding to high-affinity sites, and activities on tobacco cells. Ligand replacement experiments strongly suggest that the formation of a sterol-elicitin complex is a requisite step before elicitins fasten to specific binding sites. This was confirmed with the use of two sterol-preloaded elicitins. Both more rapidly displaced labeled cryptogein from its specific binding sites than the unloaded proteins. Moreover, the binding kinetics of elicitins are related to their biological effects, which constitutes the first evidence that binding sites could be the biological receptors. The first event involved in elicitin-mediated cell responses is proposed to be the protein loading with a sterol molecule.

Algal Proteins↗
PubMed2001

Effects of 12 beticolins, Cercospora beticola toxins, on proliferation of ras-transformed adrenocortical cell.

AIM: To explore different effects of 12 beticolins, Cercospora beticola toxins, on ras-transformed adrenocortical cell growth inhibition and their functional mechanism. METHODS: Beticolin-induced inhibition was measured with survival cell number determined by an automated photocolorimetric method. The penetration of beticolin was examined by confocal microscopy. Ras protein determined by Lowry method were separated by 14 % SDS-PAGE and electroblotted to Immobilon-P transfer membrane and detected with pan-Ras (Ab-3) monoclonal antibody. The Ca2+ chelation by beticolin was investigated using a calcium ionophore. RESULTS: Cell growth inhibition was found dose- and time-dependently at submicromolar level for beticolin-1, -2, and -13 (IC50 </= 250 nmol/L) and for beticolin-0, 6, and -11 (400 nmol/L < IC50 </= 500 nmol/L). The inhibition by beticolin-1 was immediate, independent of cell culture step and not reversible for 3-day treatment. Beticolin-3 and -4 were slightly active (1 micromol/L < IC50 </= 2 micromol/L) and beticolin-7, -9, -12, and -5 were inactive at micromolar level. The beticolin-induced cell growth inhibition was correlated with the hydrophobicity of these compounds. Beticolin-1 fluorescence in RTAC cells was detected by confocal microscopy whereas beticolin-3 and -12 were not even after a 24 h incubation period. Beticolin-1-induced cell growth inhibition was partially reverted by calcium ionophore suggesting a role of intracellular Ca2+ chelation by beticolin-1 on cell growth inhibition. Furthermore, beticolin-1 blocked up Ras p21 translocation to membrane and induced accumulation of Ras in the cytosol as an inactive form by different ways. CONCLUSION: Beticolins with high hydrophobicity inhibit tumorigenic cell proliferation by different ways.

Adrenal Cortex↗
PubMed2000

Varicella zoster meningoencephalitis following treatment for dermatomal zoster in an alloBMT patient.

Herpes zoster infections are frequently observed after allogeneic bone marrow transplantation (alloBMT). In the majority of cases, the infection is restricted to specific dermatomes and responds to oral acyclovir, without visceral dissemination. We report the case of a 40-year-old male who developed dermatomal herpetic infection 8 months post alloBMT. The herpetic rash responded well to treatment with high-dose oral acyclovir. However, within a week of cessation of therapy, the patient re-presented with dermatomal zoster and meningoencephalitis. Although the cutaneous lesions resolved with intravenous acyclovir, clinical features of meningoencephalitis persisted, along with evidence of varicella zoster virus (VZV) DNA in cerebrospinal fluid (CSF). A satisfactory response to treatment was observed only after the addition of intravenous foscarnet to acyclovir. Based on our experience with this patient, we suggest that in a subset of alloBMT recipients, late dermatomal herpes zoster infections may respond only partially to treatment with standard oral acyclovir. The use of oral acyclovir preparations with higher bioavailability (valacyclovir) or intravenous acyclovir early on may prevent the considerable morbidity associated with disseminated zoster infection. Bone Marrow Transplantation (2000) 26, 795-796.

Acyclovir↗
PubMed2000

Use of superficial femoropopliteal vein for suprainguinal arterial reconstruction in the presence of infection.

BACKGROUND: Conventional treatment of mycotic aneurysms or graft infections of the aortoiliac segment by in situ or extra-anatomic prosthetic reconstruction has a high mortality and morbidity rate, with a substantial risk of persistent graft infection. The use of autologous vein may reduce this. METHODS: Eleven patients with suprainguinal arterial infections including two with mycotic aortic aneurysms, four with aortic graft infections, four infected femorofemoral grafts and an infected axillofemoral graft were treated by debridement and in situ reconstruction with autologous superficial femoropopliteal vein. All patients received appropriate antibiotic therapy and were followed by regular postoperative duplex imaging. Preoperative femoral vein duplex imaging was performed in eight of the 11 patients. RESULTS: Ten of the 11 patients survived with a functioning graft and without limb loss or evidence of infection at 4-33 months. One patient died from myocardial infarction after operation. Three patients had minor swelling of one leg. Four patients required subsequent angioplasty of anastomotic stenoses detected by duplex surveillance. CONCLUSION: Superficial femoropopliteal vein is an excellent conduit for suprainguinal reconstruction in the presence of infection. Duplex imaging is useful for confirming the suitability of deep veins for use as a graft and for postoperative surveillance.

Aged↗
PubMed2000

Is regional tonometry a reliable index of tissue oxygenation? A comparative study with conventional global monitoring.

This study was carried out on 30 critically ill patients admitted to the ICU of Farwania Hospital (Kuwait). All patients had clinical evidence of organ dysfunction or impending multiple organ failure. The severity of their pathology on admission was assessed according to the APACHE II score. The study of each patient began after inserting the pulmonary artery catheter. The prospectively defined end-point of the study was the removal of the pulmonary artery catheter (72 hours) or death of the patient with the catheter in situ. The aim of the study was to determine the sensitivity and specificity of the intra-gastric mucosal pH (pHi) and other derived data in assessing the adequacy of tissue oxygenation, guiding therapy and prediction outcome. The results showed that pHi, pHa-Hi and PaCO2-PO2regional (reg) gradients were the most sensitive indices of tissue oxygenation and predictors of outcome. The mortality rate increased when pHi, PaCO2-PCO2reg and pHa-pHi gradients were < 7.3, > 10 mm Hg and < 0.2 respectively. The derived variables obtained by invasive monitoring like base deficit (BD), lactate concentration in mixed venous blood (Lmv) and oxygn uptake index (O2 UI) were valuable adjunct indices of tissue oxygenation. The risk ofmortality increased whten the BD was > -5.5 +/- 1.2 meq.L-1, Lmv was > 4.5 +/- 1.2 mmol.L-1, and O2UI was < 100 +/- 6 ml.min-1.m-2. We recommend the use of gastric tonometry in routine ICU clinical practice.

Adult↗
PubMed1999

Combination of the novel farnesyltransferase inhibitor RPR130401 and the geranylgeranyltransferase-1 inhibitor GGTI-298 disrupts MAP kinase activation and G(1)-S transition in Ki-Ras-overexpressing transformed adrenocortical cells.

To test the Kirsten-Ras (Ki-Ras) alternative prenylation hypothesis in malignant transformation, we used a novel farnesyltransferase inhibitor competitive to farnesyl-pyrophosphate, RPR130401, and a CaaX peptidomimetic geranylgeranyltransferase-1 inhibitor GGTI-298. In Ki-Ras-overexpressing transformed adrenocortical cells, RPR130401 at 1-10 microM inhibited very efficiently the [(3)H]farnesyl but not [(3)H]geranylgeranyl transfer to Ras. However, proliferation of these cells was only slightly sensitive to RPR130401 (IC(50)=30 microM). GGTI-298 inhibited the growth of these cells with an IC(50) of 11 microM but cell lysis was observed at 15 microM. The combination of 10 microM RPR130401 and 10 microM GGTI-298 inhibited efficiently (80%) cell proliferation. These combined inhibitors but not each inhibitor alone blocked the cell cycle in G(0)/G(1) and disrupted MAP kinase activation. Thus, combination of two inhibitors, at non-cytotoxic concentrations, acting on the farnesyl-pyrophosphate binding site of the farnesyltransferase and the CaaX binding site of the geranylgeranyltransferase-1 respectively is an efficient strategy for disrupting Ki-Ras tumorigenic cell proliferation.

Adrenal Glands↗
PubMed1999

Elicitins trap and transfer sterols from micelles, liposomes and plant plasma membranes.

Using elicitins, proteins secreted by some phytopathogenic Oomycetes (Phytophthora) known to be able to transfer sterols between phospholipid vesicles, the transfer of sterols between micelles, liposomes and biological membranes was studied. Firstly, a simple fluorometric method to screen the sterol-carrier capacity of proteins, avoiding the preparation of sterol-containing phospholipidic vesicles, is proposed. The transfer of sterols between DHE micelles (donor) and stigmasterol or cholesterol micelles (acceptor) was directly measured, as the increase in DHE fluorescence signal. The results obtained with this rapid and easy method lead to the same conclusions as those previously reported, using fluorescence polarization of a mixture of donor and acceptor phospholipid vesicles, prepared in the presence of different sterols. Therefore, the micelles method can be useful to screen proteins for their sterol carrier activity. Secondly, elicitins are shown to trap sterols from purified plant plasma membranes and to transfer sterols from micelles to these biological membranes. This property should contribute to understand the molecular mechanism involved in sterol uptake by Phytophthora. It opens new perspectives concerning the role of such proteins in plant-microorganism interactions.

Algal Proteins↗