Biomedical subjects

Z Hassan

Publications and source records attributed to Z Hassan.

At least 19 recordsLinked to original sources

PubMed2006

Evaluation of a commercial dengue NS1 antigen-capture ELISA for laboratory diagnosis of acute dengue virus infection.

A commercial dengue NS1 antigen-capture ELISA was evaluated to demonstrate its potential application for early laboratory diagnosis of acute dengue virus infection. Dengue virus NS1 antigen was detected in 199 of 213 acute serum samples from patients with laboratory confirmation of acute dengue virus infection but none of the 354 healthy blood donors' serum specimens. The dengue NS1 antigen-capture ELISA gave an overall sensitivity of 93.4% (199/213) and a specificity of 100% (354/354). The sensitivity was significantly higher in acute primary dengue (97.3%) than in acute secondary dengue (70.0%). The positive predictive value of the dengue NS1 antigen-capture ELISA was 100% and negative predictive value was 97.3%. Comparatively, virus isolation gave an overall positive isolation rate of 68.1% with a positive isolation rate of 73.9 and 31.0% for acute primary dengue and acute secondary dengue, respectively. Molecular detection of dengue RNA by RT-PCR gave an overall positive detection rate of 66.7% with a detection rate of 65.2 and 75.9% for acute primary dengue and acute secondary dengue, respectively. The results indicate that the commercial dengue NS1 antigen-capture ELISA may be superior to virus isolation and RT-PCR for the laboratory diagnosis of acute dengue infection based on a single serum sample.

Acute Disease↗

PubMed2006

Prevalence of IgG antibody against measles, mumps and rubella in bangladeshi children: a pilot study to evaluate the need for integrated vaccination strategy.

The present study was carried out to determine the seroprevalence of IgG antibodies in Bangladeshi children against measles (irrespective of vaccination status), mumps and rubella (MMR) to assess strategic need of combined vaccination for these diseases. A total of 456 children of 1 month to 15 years, were studied. Serum IgG antibodies against MMR were measured by enzyme-linked immunosorbent assay (ELISA). By 3 months, protective IgG antibody level (>40 AU for measles and mumps and >15 IU/ml for rubella) for the diseases found to be between 50% and 80% among the studied children. Protective measles antibody (IgG) was not detected in all the children of 3-9 months and significant number of children between 9 months and 5 years were unprotected (87-65%; P < 0.001). Moreover, children of 3-15 months had no protective antibody level against mumps and significant number of children between 15 months and 5 years were unprotected (92-71%; P < 0.001). Between 5 and 15 years of age, significant number of children became protective (63-85%, P < 0.001). Although, a majority of children between 3 months and 5 years had shown to have no protective antibody against rubella (89-71%; P < 0.01-0.001) between >10 and 15 years 71% children had protective level of antibodies (P < 0.001). No significant difference was observed in antibody prevalence regarding socioeconomic classes, nutritional status and parental education. The data showed that: (i) a significant number of children remain unprotected against MMR in childhood and (ii) an extensive nationwide survey is required to suggest an integrated vaccination strategy in order to implement appropriate control measures of the three infectious diseases.

Adolescent↗

PubMed2005

[Clinicopathological characteristic of keratoglobus].

BACKGROUND: This study describes the clinical, topographical, pachymetrical, and histological features of a unique corneal disorder: keratoglobus. CASE REPORT: Ultrasound pachymetry proved that the structure of the cornea was evenly thinning towards the periphery. Histological examinations disclosed the absence of Bowman's membrane and the thinning of the stromal lamellae. CONCLUSION: On account of the thickness of the recipient's periphery, penetrating keratoplasty proved to be a reasonable surgical procedure in this case.

Child↗

PubMed2005

Scald injury from the Guthrie test: should the heel be warmed?

A 6 day old boy sustained scalds to his right foot from application of a "warm nappy" to increase blood flow to facilitate heel pricking for a routine Guthrie test. It is proposed that active warming of the heel in isolation is not necessary in heel blood sampling.

Ankle Injuries↗

PubMed2005

Head injuries: a study evaluating the impact of the NICE head injury guidelines.

BACKGROUND: The NICE head injury guidelines recommend a different approach in the management of head injury patients. It suggests that CT head scan should replace skull x ray (SXR) and observation/admission as the first investigation. We wished to determine the impact of NICE on SXR, CT scan, and admission on all patients with head injury presenting to the ED setting and estimate the cost effectiveness of these guidelines, which has not been quantified to date. DESIGN: Study of head injury patients presenting to two EDs before and after implementation of NICE guidelines METHODS: The rate of SXR, CT scan, and admission were determined six months before and one month after NICE implementation in both centres. The before study also looked at predicted rates had NICE been applied. This enabled predicted and actual cost effectiveness to be determined. RESULT: 1130 patients with head injury were studied in four 1 month periods (two in each centre). At the teaching hospital, the CT head scan rate more than doubled (3% to 7%), the SXR declined (37% to 4%), while the admission rate more than halved (9% to 4%). This represented a saving of 3381 pounds sterling per 100 head injury PATIENTS: greater than predicted with no adverse events. At the District General Hospital, the CT head scan rate more than quadrupled (1.4% to 9%), the SXR dropped (19 to 0.57%), while the admission rate declined (7% to 5%). This represented a saving of 290 pounds sterling per 100 head injury patients: less than predicted. CONCLUSION: The implementation of the NICE guidelines led to a two to fivefold increase in the CT head scan rate depending on the cases and baseline departmental practice. However, the reduction in SXR and admission appears to more than offset these costs without compromising patient outcomes.

Adolescent↗

PubMed2004

Diabetes mellitus in Tropical Chronic Pancreatitis Is Not Just a Secondary Type of Diabetes.

AIMS: In chronic calcific pancreatitis of the tropics, etiology and relationship to developing diabetes mellitus are unknown. Some consider these cases a straightforward secondary type of diabetes, while others suggest selective beta-cell impairment. Testing pancreatic function, we investigated whether selective beta-cell impairment triggers diabetes associated with tropical pancreatitis. METHODS: At a Bangladeshi research institute, 8 chronic tropical pancreatitis and no diabetes mellitus subjects, 14 fibrocalculous pancreatic diabetics and 27 matched healthy controls underwent arginine (endocrine pancreatic function) and secretin (exocrine pancreatic function assessment) stimulation tests. RESULTS: All patients with clinically-diagnosed, chronic pancreatitis demonstrated pronounced exocrine pancreatic dysfunction with beta-cell functioning differing significantly between the two groups. Compared to controls, patients having tropical pancreatitis and no diabetes showed normal plasma C-peptide values at baseline and after arginine stimulation, while fibrocalculous pancreatic diabetics demonstrated a typical diabetic pattern for plasma C-peptide levels. In contrast, pancreatic alpha-cell functioning (glucagon response to arginine) was preserved in both pancreatitis groups. CONCLUSION: A preserved pancreatic alpha-cell function in diabetics with advanced chronic pancreatitis of the tropics supports the concept of two different pathogenic mechanisms, one eliciting chronic pancreatitis and the other selective pancreatic beta-cell impairment and subsequent diabetes mellitus.

Adult↗

PubMed2004

The EIF2AK3 gene region and type I diabetes in subjects from South India.

Mutations in the EIF2AK3 gene underlie susceptibility to the Wolcott-Rallison syndrome, which is a monogenic disease associated with insulin-deficient neonatal diabetes. Furthermore, suggestive evidence of linkage between type 1 diabetes (T1DM) and the EIF2KA3 chromosomal region has been reported in Scandinavian families. We have investigated the hypothesis that polymorphic variants in and around the EIF2AK3 gene might partially account for susceptibility to T1DM in South Indian subjects. Excess transmission of the common alleles of two polymorphic markers (D2S1786 and 15INDEL, located within the gene) downstream of EIF2AK3, either singly (D2S1786, P = 0.01) and 15INDEL (P = 0.02) or as a combination (P < 0.001), were found in 234 families with a T1DM proband. There was also a clear paternal effect for the 15INDEL marker (P = 0.005) on disease susceptibility. The presence of the common allele of both markers was found in decreased frequency in the subjects with normal glucose tolerance compared to probands with T1DM (both P <or= 0.0001). Major common mutations of the EIF2AK3 gene in T1DM were excluded. In conclusion, this pilot study demonstrates an association between the region around the EIF2AK3 locus and T1DM susceptibility.

Adolescent↗

PubMed2003

Adverse events in plastic surgery.

Adverse events are a serious source of harm to patients and a large drain on the resources of healthcare providers. Retrospective studies have previously been carried out in the USA, Australia and the UK. In this study a prospective approach was employed, using similar methods to previous studies to detect the levels of adverse events over a period of one month. We also recorded the categories, causes and preventabilities of adverse events. We measured the degree of disability and the length of additional bed stay. Of the 537 patients treated in our department, 15 (2.8%) had adverse events; these patients were older than those who did not have adverse events, and were mainly emergency admissions. Most of the adverse events were operative and led to temporary disability. Overall, 139 extra bed stays were attributed to these adverse events. This report confirms the feasibility of conducting a prospective study of adverse events and of making preliminary estimates of their incidence and costs.

Adult↗

PubMed2003

N-acetyl-L-cysteine does not affect the pharmacokinetics or myelosuppressive effect of busulfan during conditioning prior to allogeneic stem cell transplantation.

Busulfan is currently used as a main component in the conditioning regimen prior to allogeneic stem cell transplantation (SCT). Several studies have shown a correlation between exposure to busulfan and transplantation-related liver toxicity, such as venoocclusive disease (VOD) in patients undergoing SCT. Busulfan is metabolized mainly through glutathione (GSH). During high-dose therapy, busulfan may deplete hepatocellular levels of GSH. As part of the conditioning therapy, busulfan is usually followed by high doses of cyclophosphamide. The activation of cyclophosphamide yields a cytotoxic metabolite, 4-hydroxy cyclophosphamide, which is highly reactive and detoxified through GSH. According to recent studies using cell lines and animal models N-acetyl-L-cysteine (NAC), a GSH precursor, does not hamper the myeloablative effect of busulfan during conditioning. In the present study, we administered NAC during conditioning to 10 patients at risk of VOD due to pretransplant liver disorders or elevated liver enzymes. No side effects related to the NAC infusions were observed and busulfan concentrations were not affected. All patients became pancytopenic and engrafted with 100% donor cells. None of the patients developed VOD or liver failure. Increased liver enzymes during conditioning decreased or normalized in all patients. We suggest that NAC therapy is safe and does not impair the myeloablative effect of busulfan during conditioning prior to SCT.

Acetylcysteine↗

PubMed2002

The effect of modulation of glutathione cellular content on busulphan-induced cytotoxicity on hematopoietic cells in vitro and in vivo.

Busulphan is used in conditioning regimens prior to SCT. A relationship between exposure to busulphan, expressed as an area under the plasma concentration time curve (AUC), and effect and/or adverse effects, such as veno-occlusive disease (VOD), was reported. Exhaustion of glutathione (GSH) contributes to VOD and modulation of intracellular levels of GSH influences bulsulphan-induced toxicity in hepatocytes. Thus, increase of GSH might serve as prophylaxis against VOD. However, it should not interfere with the myeloablative effects of busulphan. We investigated the relationship between exposure to busulphan, and its in vitro toxicity to CD34(+) hematopoietic progenitors from volunteers using clonogenic assays. Busulphan inhibited colony formation by CD34(+) cells in an AUC-dependent manner. Myeloid progenitors were more sensitive than erythroid progenitors, expressed as 100% inhibition of colony formation (68.7 +/- 7.5 microg.h/ml and 140.3 +/- 35.7, respectively). The observed exposure corresponds to the total AUC obtained in patients treated with busulphan (1 mg/kg/day) for 4 days. Secondly, we studied the effect of modulation of GSH cellular levels on busulphan-induced toxicity in vitro in CD34(+) cells from volunteers, and in vivo in bone marrow cells from Balb/c mice. The intracellular concentration of GSH was increased or decreased by treatment with N-acetylcysteine or buthionine sulfoximine, respectively. Neither in vitro nor in vivo treatment with GSH modulators affected the hematological toxicity of busulphan. Thus, N-acetylcysteine would not interfere with the myeloablative effect of busulphan and therefore it is a potential candidate for VOD prophylaxis during busulphan-based conditioning regimens.

Acetylcysteine↗

PubMed2002

A phase II trial of liposomal busulphan as an intravenous myeloablative agent prior to stem cell transplantation: 500 mg/m(2) as a optimal total dose for conditioning.

We conducted a phase I/II trial, to evaluate the efficacy and safety of an intravenous liposomal formulation of busulphan (LBu) as a myeloablative agent for stem cell transplantation (SCT). The liposomal busulphan was administered as a 3 h infusion twice daily over 4 consecutive days. Six adults received 1.6-2 mg/kg/dose and 18 children received 1.8-3 mg/kg/dose. Pharmacokinetic parameters were studied after the first and the last dose of busulphan. No significant difference in clearance, AUC, elimination half-lives or distribution volume between the first and the last dose was found in either groups. A significantly (P < 0.005) higher clearance was observed in children after the first and the last dose (3.61 and 3.79 ml/min/kg, respectively) compared to adults (2.40 and 2.33 ml/min/kg, respectively). The elimination half-lives after the first and the last dose were significantly (P < 0.005) shorter in children (2.59 and 2.72 h, respectively) compared to adults (3.35 and 3.61 h, respectively). Clearance correlated significantly with age. However, no significant correlation with age was observed when clearance was adjusted to the body surface area. Two cases of VOD following a total dose of 24 mg/kg were observed. Six patients experienced mucositis. No other organ toxicity was observed. We conclude that intravenous liposomal busulphan pharmacokinetics is age dependent. A dosage schedule based on body surface area should be used especially in young children to reduce the age-dependent difference in kinetics. An intravenous liposomal dose of busulphan of 500 mg/m(2) is suggested to reach a similar systemic exposure and myeloablative effect in both children and adults. Moreover, the novel liposomal form of busulphan showed a favorable toxicity profile and seems safe as a part of the high-dose therapy prior to SCT.

Adult↗

PubMed2002

Genetic susceptibility to fibrocalculous pancreatic diabetes in Bangladeshi subjects: a family study.

Fibrocalculous pancreatic diabetes (FCPD) is an uncommon cause of diabetes, seen mainly in developing countries. A family-based study was carried out in 67 Bangladeshi families, consisting of a proband with FCPD and both parents, to determine whether an association exists between FCPD susceptibility and either the major histocompatiblity complex (MHC) or insulin gene (INS) loci. HLA-DQB1 typing was done using allele-specific primers, and INS was typed using the restriction enzyme HphI. Three microsatellites (TNFa, TNFc and TNFd), from within and flanking the TNF-LT locus, were used for MHC Class IV typing and a PCR-RFLP assay was used to define the -308G/A TNF promoter polymorphism. The extended transmission disequilibrium test (ETDT) was used for statistical analysis. An overall association was observed between FCPD and HLA-DQB1 (P = 0.003), that was largely due to a positive association with HLA-DQB1*0302 and a negative association with HLA-DQB1*0202. Although no association was found between FCPD and TNF-LT microsatellite markers a trend was observed for TNFc (P = 0.037, Pc = 0.15). No association was found between FCPD and INS (P = 0.26). This study confirms an association between FCPD and the MHC using a family-based study design and the stringent ETDT analysis; a novel protective association was found with HLA-DQB1*0202 in Bangladeshi FCPD subjects. The genetic susceptibility to FCPD has features both similar and dissimilar to T1DM.

Bangladesh↗

PubMed2001

Pharmacokinetics of liposomal busulphan in man.

High doses of busulphan are used in conditioning regimens before stem cell transplantation. Great inter-patient variations in pharmacokinetics and a correlation between toxicity and high systemic exposure of busulphan have been shown in several studies. Some authors have suggested therapeutic drug monitoring and intravenous busulphan aiming to reduce the conditioning-related toxicity. Liposomal busulphan (LBu) might be an alternative to intravenous administration of high-dose busulphan in conditioning. In the present study, we investigated the pharmacokinetics of LBu in man. Seventeen consecutive patients were enrolled in the study. LBu as a single low dose (2 to 8 mg) was given to 12 patients (six adults and six children). Five patients received two high doses of LBu which replaced the first and the last doses of the conditioning regimen. The high dose of LBu was raised from 0.4 to 0.9 mg/kg. A significant linear correlation (r2 = 0.928) was found between the dose of LBu and the area under the plasma concentration-time curve (AUC) (P < 0.001). AUC corrected for 1 mg/kg was 5491 +/- 912 ng.h/ml and 5955 +/- 627 ng.h/ml (low dose of LBu in children and adults, respectively) and 6167 +/- 1385 ng.h/ml and 6933 +/- 656 ng.h/ml (ie the first and the last high doses of LBu, respectively). No significant correlation was found between clearance and age or apparent volume of distribution and age (r2 = 0.146 and r2 = 0.046, respectively). No toxicity related to the liposomal formulation of busulphan was observed. We conclude that LBu is suitable for conditioning before stem cell transplantation.

Adolescent↗

PubMed2001

Population pharmacokinetic analysis resulting in a tool for dose individualization of busulphan in bone marrow transplantation recipients.

The aims of the present study were (1) to investigate and quantify the pharmacokinetics, including inter-occasion variability and covariate relationships, of busulphan in BMT patients and (2) to develop a user-friendly initial dosing and therapeutic drug monitoring (TDM) strategy for the treatment of those patients with busulphan. The pharmacokinetics of busulphan was studied in 64 adults and 12 children who received busulphan (1 mg/kg) four times daily for 4 days. A one-compartment model with first order absorption and a lag time was sufficient in describing the concentration-time profile. Oral clearance (CL/F) was found to be correlated to weight (+1.2%/kg), ALT (-13%/microcat/l) and concomitant phenytoin treatment (+21%). CL/F and the volume of distribution (V/F) were estimated to 9.23 l/h and 39.3 l, respectively, in a typical individual. Inter-occasion variability (9.4%) in CL/F was estimated to be less than inter-individual variability (28%), a prerequisite for the value of TDM. Bayesian CL/F estimates based on three samples were in good accordance with those based on all samples. The final population model was implemented into the program Excel. The resulting flexible and easy to use dosing program might be used for both initial and, requiring only three plasma samples, maintenance dose individualization of busulphan therapy.

Administration, Oral↗

PubMed2001

The pharmacodynamic effect of busulfan in the P39 myeloid cell line in vitro.

Busulfan is an alkylating agent currently used in the myeloablative conditioning regimen before stem cell transplantation. Its mechanism of action is not fully understood, nor the reason for its narrow therapeutic window. We studied the pharmacodynamics of busulfan in an in vitro cell line model, allowing us to evaluate the effects of various doses and exposure times on clonogeneic capacity, proliferation and apoptosis. Cells were incubated with busulfan in concentrations ranging from 10 to 100 microg/ml for 2, 4 or 8 h, then washed and cultured in busulfan-free medium for 72 h. Area under the concentration-time curve (AUC) was estimated by using the trapezoidal rule from different concentrations and times of incubation. In all assays busulfan affected the cells in an AUC-dependent manner. Induced changes in the biological parameters studied appeared at different time points after exposure to busulfan stopped. Thus, the decrease in proliferation and clonogenic capacity preceded cell cycle arrest in G2 phase and development of apoptosis, implying that apoptosis is a secondary event to interruption of vital metabolic processes. Biochemically, apoptotic changes were typical for chemotherapy-induced apoptosis with caspase activation, cleavage of Bcl-2 and PARP proteins, while cleavage of actin was not observed. Cells were rescued from apoptosis with a general caspase inhibitor ZVAD-fmk, but not with granulocyte colony-stimulating factor (G-CSF). Our results add new information about busulfan pharmacodynamics and mechanisms underlying the cytotoxic effect of the drug.

Antineoplastic Agents, Alkylating↗

PubMed2001

Molecular characterization of Salmonella weltevreden isolated from poultry: evidence of conjugal transfer of plasmid and antibiotic resistance.

Ten strains of Salmonella weltevreden isolated from poultry sources were examined and found to contain plasmid DNA ranging in size from 1.8 to 68.5 MD. All isolates were susceptible to carbenicillin, cephalothin, ceftriazone, gentamicin, kanamycin and nalidixic acid, but resistance to bacitracin (100%), penicillin G (100%), rifampicin (100%), sulphamethoxazole (100%), cefuroxime (80%) and tetracycline (60%) was recorded. The 55 MD plasmid of strain SW5 determined resistance to penicillin G and tetracycline, which was transmissible to the E. coli K12 recipient at a frequency of 3.52 x 10(-5) transconjugants per input donor cell. The results of arbitrarily primed polymerase chain reaction (AP-PCR), using two 10-mer oligonucleotides and PCR-ribotyping to differentiate between the ten strains of S. weltevreden were compared. The strains were separated into ten different genome types by AP-PCR but were indistinguishable by PCR-ribotyping. These results suggest that poultry may constitute a reservoir for disseminating antibiotic resistance and that AP-PCR may be a valuable tool for epidemiological studies.

Animals↗

PubMed2001

Prevalence of Listeria spp and Listeria monocytogenes in meat and fermented fish in Malaysia.

Fermented fish and meat samples were purchased from supermarket and wet market for microbiological analysis of Listeria species and Listeria monocytogenes contamination. Listeria species were isolated from 17 (73.9%) of 23 samples of imported frozen beef, 10 (43.5%) of the 23 samples of local beef and 14 (56%) of the 25 samples of fermented fish from wet market. Listeria monocytogenes occurred in 15 (75%) of the frozen beef samples, 6 (30.4%) of the 23 samples of local meat and 3 (12%) of the 25 samples from fermented fish. Listeria species was not isolated from any of the 23 samples of imported frozen beef from supermarket and from the 5 samples of buffalo meat examined. This highlights the possibility of Listeria spp or L. monocytogenes to persist in meat and fermented fish in wet market and raises the problem of illness due to the handling and consumption of Listeria-contaminated meat or fermented fish are likely as evidence by the high contamination rates of samples sold at the wet market.

Fish Products↗

PubMed2000

Improvement in raw sago starch degrading enzyme production from Acremonium sp. endophytic fungus using carbon and nitrogen sources.

Attempts were made to improve the growth of endophytic fungus Acremonium sp. and its raw sago starch degrading enzyme (RSSDE) production using different nitrogen and carbon sources at varying pH values and temperatures. It was observed that growth and enzyme activity levels were highest with peptone and sodium nitrate as the nitrogen sources and raw sago starch as the carbon source of which the optimum concentrations were 0.5 g/l, 3 g/l, and 20 g/l, respectively. Cell growth and RSSDE production reached their optimum at pH 5.0 and incubation temperature of 30 degrees C. Under these conditions, the enzyme production was significantly increased by 19- to 22-folds compared to the activity obtained in the original basal medium.

Journal Article↗