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Biomedical subjects

S Saeed

Publications and source records attributed to S Saeed.

At least 19 recordsLinked to original sources
PubMed2006

Interinstitutional and intrainstitutional transmission of a strain of Acinetobacter baumannii detected by molecular analysis: comparison of pulsed-field gel electrophoresis and repetitive sequence-based polymerase chain reaction.

Pulsed-field gel electrophoresis and repetitive sequence-based polymerase chain reaction provided comparable strain discrimination with minor discordance in typing Acinetobacter baumannii clinical isolates from patients at our hospital and affiliated institutions. Typing revealed a cluster strain with intrainstitutional and interinstitutional spread during the study period. A long-term acute care facility may have been the reservoir.

Acinetobacter Infections↗
PubMed2006

Impact of initial antibiotic choice and delayed appropriate treatment on the outcome of Staphylococcus aureus bacteremia.

The study presented here investigated the impact of initial antibiotic choice (beta-lactams vs vancomycin) on the outcome of 342 patients with Staphylococcus aureus bacteremia (50.9% with methicillin-resistant isolates) encountered between 1 January 2002 and 30 June 2003. Initial antibiotics were inappropriate (beta-lactams) in 60 (34.5%) methicillin-resistant cases and suboptimal (vancomycin) in 62 (36.9%) methicillin-susceptible cases. Time to effective antibiotic therapy was longer in methicillin-resistant cases (25.5+/-28.6 vs 9.6+/-16.6 h; p<0.0005). All-cause in-hospital mortality was higher with inappropriate therapy (35.0 vs 20.9%; p=0.02). Initial vancomycin treatment was associated with a higher incidence of delayed clearance (>or=3 days) of methicillin-susceptible bacteremia (56.3 vs 37.0%; p=0.03). The results indicate inappropriate initial therapy is associated with higher in-hospital mortality and initial vancomycin may delay clearance.

Adult↗
PubMed2005

Microporosity enhances bioactivity of synthetic bone graft substitutes.

This paper describes an investigation into the influence of microporosity on early osseointegration and final bone volume within porous hydroxyapatite (HA) bone graft substitutes (BGS). Four paired grades of BGS were studied, two (HA70-1 and HA70-2) with a nominal total porosity of 70% and two (HA80-1 and HA80-2) with a total-porosity of 80%. Within each of the total-porosity paired grades the nominal volume fraction of microporosity within the HA struts was varied such that the strut porosity of HA70-1 and HA80-1 was 10% while the strut-porosity of HA70-2 and HA80-2 was 20%. Cylindrical specimens, 4.5 mm diameter x 6.5 mm length, were implanted in the femoral condyle of 6 month New Zealand White rabbits and retrieved for histological, histomorphometric, and mechanical analysis at 1, 3, 12 and 24 weeks. Histological observations demonstrated variation in the degree of capillary penetration at 1 week and bone morphology within scaffolds 3-24 weeks. Moreover, histomorphometry demonstrated a significant increase in bone volume within 20% strut-porosity scaffolds at 3 weeks and that the mineral apposition rate within these scaffolds over the 1-2 week period was significantly higher. However, an elevated level of bone volume was only maintained at 24 weeks in HA80-2 and there was no significant difference in bone volume at either 12 or 24 weeks for 70% total-porosity scaffolds. The results of mechanical testing suggested that this disparity in behaviour between 70 and 80% total-porosity scaffolds may have reflected variations in scaffold mechanics and the degree of reinforcement conferred to the bone-BGS composite once fully integrated. Together these results indicate that manipulation of the levels of microporosity within a BGS can be used to accelerate osseointegration and elevate the equilibrium volume of bone.

Animals↗
PubMed2005

Management of the patient and family with neurofibromatosis 2: a consensus conference statement.

A consensus conference on neurofibromatosis 2 (NF2) was held in 2002 at the request of the United Kingdom (UK) Neurofibromatosis Association, with particular emphasis on vestibular schwannoma (VS) surgery. NF2 patients should be managed at specialty treatment centres, whose staff has extensive experience with the disease. All NF2 patients and their families should have access to genetic testing because presymptomatic diagnosis improves the clinical management of the disease. Some clinical manifestations of NF2, such as ocular abnormalities, can be detected in infancy; therefore, clinical screening for at-risk members of NF2 families can start at birth, with the first magnetic resonance (MRI) scan at 10-12 years of age. Minimal interference, maintenance of quality of life, and conservation of function or auditory rehabilitation are the cornerstones of NF2 management, and the decision points to achieve these goals for patients with different clinical presentations are discussed.

Adult↗
PubMed2005

Incidence of vestibular schwannoma and neurofibromatosis 2 in the North West of England over a 10-year period: higher incidence than previously thought.

OBJECTIVE: To determine the incidence of vestibular schwannoma (VS) in sporadic, neurofibromatosis type 2 (NF2) germ-line and mosaic form in a 10-year period. STUDY DESIGN: Review of all incident cases of VS presenting to the four main neurosurgical centers for a population of 4.1 million from 1990 to 1999 and cross-referencing with the regional cancer registry. SETTING: Population based. PATIENTS: All patients presenting with VS detected on magnetic resonance imaging scan. RESULTS: A total of 419 sporadic and 64 NF2-related VS were identified over the study period. This represented an incidence of 10.4 per million per year for sporadic VS and 11.8 per million per year including NF2-related tumors. The incidence rose to 14 per million per year in the latter 5 years. The NF2 patient diagnoses represent an estimated birth incidence of 1 in 25,000, and 7% of the patients with VS had NF2, which is higher than previous estimates. CONCLUSIONS: The incidence of VS is rising almost certainly due to increasing diagnosis in the magnetic resonance imaging era. At current rates, 1 per 1,000 individuals will be diagnosed with VS in their lifetime. More VS than previously thought are due to NF2, which may be because of recognition of mosaic forms of the disease.

Adolescent↗
PubMed2003

Institution based tumor registry from Punjab: five year data based analysis.

INTRODUCTION: There are no population based cancer registries in Pakistan except for Karachi Cancer Registry (KCR). No data from Punjab is available in the last decade. We decided to conduct a data base analysis to see the frequencies of different cancers in Punjab. PATIENTS AND METHODS: A retrospective analysis of 5100 patients presenting to Jinnah Hospital between January 1997 to December 2001 with histological diagnosis of cancer was performed. A tumor registry performa on all patients was filled which included demographic data as age, sex, duration of symptoms and disease stage at presentation. All cancers were coded according to international classification of Disease-oncology (ICD-10) classification. RESULTS: Male cancers accounted for 47.7% and female cancers 52.2% of the total cases. In males the three most frequent cancers were leukemias, non-Hodgkins lymphoma and lung cancer. In females breast cancer was the most common cancer accounting for 38.5% female followed by ovarian cancer 13.6%. CONCLUSIONS: Our institution based cancer registry indicates hematological malignancies are the most common cancers in males in Punjab followed by lung and colorectal cancer. In females breast cancer is the commonest cancer followed by ovarian cancer. Gall bladder cancer is relatively more frequent in women while cervical cancer is less commonly observed in our patient population. Despite biases until population based incidences are available, studies like ours may prove beneficial for future health planning and research.

Demography↗
PubMed2002

Expression of the leptin receptor in rat and human nodose ganglion neurones.

There is evidence for interactions between leptin and cholecystokinin in controlling food intake. Since cholecystokinin acts on vagal afferent neurones, we asked whether the leptin receptor was also expressed by these neurones. Primers for different forms of the leptin receptor were used in reverse transcriptase-polymerase chain reaction (RT-PCR) of rat and human nodose ganglia. RT-PCR yielded products corresponding to the long (functional) form as well as short forms of the rat leptin receptor. Moreover, RT-PCR revealed the long form of the leptin receptor in a human nodose ganglion. The identities of RT-PCR products were confirmed by sequencing. Primers corresponding to leptin itself did not give RT-PCR products in nodose ganglia. Immunocytochemical studies revealed leptin-receptor immunoreactivity in neuronal cell bodies. Many neurones co-expressed the leptin and cholecystokinin type A receptors, or leptin receptor and cocaine- and amphetamine-related transcript. We conclude that vagal afferent neurones that express the cholecystokinin type A receptor and cocaine- and amphetamine-related transcript, may also express the long form of the leptin receptor providing a neurochemical basis for observations of interactions between cholecystokinin and leptin.

Animals↗
PubMed2001

Inhibition of tyrosine kinase activity induces caspase-dependent apoptosis in anaplastic large cell lymphoma with NPM-ALK (p80) fusion protein.

OBJECTIVE: The t(2;5)(p23;q35) translocation creates a fusion gene NPM-ALK (p80) that encodes a product with tyrosine kinase activity believed to play an important role in development of anaplastic large cell lymphoma (ALCL). Our study was aimed to analyze tyrosine kinase activity and phosphotyrosine in ALCLs. We were also interested in determining the effect of tyrosine kinase inhibitors on survival of ALCL. METHODS: Eleven cases of ALCL and three ALCL cell lines with t(2;5)(Karpas-299, SUPM2, SU-DHL-1) and 10 Hodgkin's disease (HD) samples were stained with anti-phosphotyrosine antibody. The tyrosine kinase activity, p80 phosphorylation, and the apoptotic effects of two tyrosine kinase inhibitors, herbimycin A and STI-571, were determined on ALCL cell lines. RESULTS: Herbimycin A had showed both a time- and dose-dependent apoptotic effect on all three cell lines, while STI-571 demonstrated a minimal effect. Following herbimycin A treatment, a decrease in tyrosine kinase activity in the ALCL cell lines and inhibition in NPM-ALK (p80) autophosphorylation was demonstrated by immunoprecipitation and Western blotting. Herbimycin A-induced apoptosis was accompanied by caspase-3 activation. Furthermore, apoptosis induced by herbimycin A was blocked by both z-VAD-FMK and z-DEVD-FMK, suggesting a critical role of caspases. CONCLUSIONS: These findings indicate that tyrosine kinase activity is a common characteristic of ALCLs and necessary for ALCL cell survival. These findings further suggest that therapies targeting tyrosine kinases, including p80, may have clinical utility.

Anaplastic Lymphoma Kinase↗
PubMed2001

Analysis of expression of nuclear factor kappa B (NF-kappa B) in multiple myeloma: downregulation of NF-kappa B induces apoptosis.

Nuclear factor-kappa B (NF-kappa B) is an important transcription factor that regulates survival in many cells. Activated NF-kappa B has been shown to protect some haematopoietic neoplastic cells from apoptosis. In the present study, we analysed NF-kappa B status in 13 primary samples from patients with multiple myeloma (MM) and in four myeloma cell lines including U266, RPMI 8226, HS-Sultan and K620. Constitutive activation of NF-kappa B was evaluated by either immunohistochemistry or immunofluorescence using a monoclonal mouse anti-human p65 (Rel A) antibody, which recognizes the unbound, active form of p65 (Rel A). Constitutively active NF-kappa B was present in all MM patient samples as well as in all four myeloma cell lines. Inhibition of constitutively active NF-kappa B, by either proteasome inhibitors (MG132, gliotoxin) or inhibitors of I kappa B phosphorylation (Bay117082, and Bay117085), induced apoptosis as demonstrated by both flow cytometric analysis and light microscopic morphological evaluation. This chemically induced apoptosis was associated with decreased DNA binding of nuclear NF-kappa B as determined by the electrophoretic mobility shift assay. In addition, adenovirus vector with dominant negative I kappa B alpha (Ad5I kappa B) was used for inhibition of NF-kappa B in the U266 cell line. Compared with wild-type, super-repressor-treated cells showed an increased level of apoptosis. These results suggest that constitutive expression of NF-kappa B plays an important role in plasma cell survival in MM.

Adenoviridae↗
PubMed2001

Histone deacetylase inhibitors induce caspase-dependent apoptosis and downregulation of daxx in acute promyelocytic leukaemia with t(15;17).

Histone deacetylase (HDAC) appears to play an important role in the pathogenesis of acute promyelocytic leukaemia (APL) as it is recruited by both PML-RARalpha and PLZF/RAR alpha in leukaemic cells with t(15;17) and t(11;17) respectively. Recent studies have demonstrated that HDAC inhibitors can be therapeutically used in various neoplastic disorders including APL. Cell differentiation was considered the major mechanism of the anti-leukaemic effects of HDAC inhibitors in APL. However, most of these studies either evaluated the effect of HDAC inhibitors in combination with all-trans retinoic acid (ATRA) or focused on the less common form of APL with t(11;17). To investigate the cellular effects of HDAC inhibitors, including sodium butyrate, trichostatin A, and suberoylanilide hydroxamic acid (SAHA), we used two APL cell lines, NB4 and the ATRA-resistant derivative NB4.306. Moreover, primary cells from five patients with cytogenetic evidence for t(15;17) were also studied. Our results demonstrated that HDAC inhibitors induce distinct caspase-dependent apoptosis in APL, which showed both concentration-and time-dependence. In addition, changes in the apoptosis-regulatory proteins, daxx, bcl-2 and bax were analysed. HDAC inhibitors induced downregulation of daxx, but no significant changes were detected in bcl-2 or bax. In conclusion, apoptosis induced by HDAC inhibitors in APL could provide an effective strategy for treatment of patients with t(15;17).

Adaptor Proteins, Signal Transducing↗
PubMed2001

Production and distribution of interleukin 15 and its receptors (IL-15Ralpha and IL-R2beta) in the implant interface tissues obtained during revision of failed total joint replacement.

Failure of total joint replacement (TJR) is a major problem and it is estimated that 15-20% of TJR will fail within 5-10 years after implantation. Most TJR is attributed to aseptic loosening of the implants in association with resorption of related bone due to the release of bone-associated cytokines. IL-15 is a cytokine that activates T cells and natural killer (NK) cells. IL-15 protein is ubiquitous and is expressed in many tissues and cell types. Using immunohistochemical techniques, we demonstrated the expression of IL-15 and its receptors IL-15Ralpha and IL-2Rbeta in the interface tissues obtained from revision surgery. Both IL-15 protein and IL-15Ralpha were observed in macrophages, multinucleated giant cells and endothelial cells around blood vessels. Both the SDS-PAGE and western blot revealed multiple bands and after stages of glycosylation, this resulted in a band at 13 KDa which corresponds to the IL-15 protein. Again RT-PCR results demonstrated a band of 420 bp corresponding to the IL-15 protein. In addition, using U937 cells, the expression of both IL-15 protein and IL-15Ralpha were considerably up-regulated when challenged with retrieved metal particles. Our results illustrated the IL-15 to be an intact protein and that it is stored in the cytoplasm. A dye exclusion cell viability test displayed an increase in toxicity with an increase in the amount of metal particles added. There was a discrepancy between abundant IL-15 mRNA, intracellularly detectable IL-15 protein and apparently inefficient secretion. This suggests that IL-15 protein production is predominantly regulated post-transcriptionally and this is indicated by its strict regulation, especially at cell trafficking. Finally, unlike IL-2, IL-15 plays a certain role in bone resorption that leads to failed joint prostheses. It is apparent that this cytokine is an important T cell mediated immune response which needs further research.

Aged↗
PubMed2001

Skull base involvement by a nasopharyngeal carcinoma shown by Tc-99m MDP SPECT but not by computed tomography.

PURPOSE: Plain radiographs, computed tomography (CT), and more recently magnetic resonance imaging (MRI) are used routinely to stage carcinoma of the nasopharynx. Tc-99m methylene diphosphonate (MDP) SPECT is seldom used for local staging of the disease. MATERIALS AND METHODS: Plain radiographs and CT were used to stage squamous carcinoma of the nasopharynx in a 50-year-old man with a left XII nerve palsy. RESULTS: Findings of the plain radiographs were normal, whereas the CT scan revealed a nonhomogenous hyperdense mass in the nasopharynx but intact underlying bone. Given the symptoms, a Tc-99m MDP planar scan was ordered and showed no enhanced uptake, but SPECT images obtained at the same time revealed markedly increased focal radiotracer uptake in the region of the tumor, indicating osseous involvement. CONCLUSION: Possible bony invasion with a nasopharyngeal carcinoma may be better shown with MDP SPECT than with planar isotope bone scans, plain radiographs, or CT.

Adult↗
PubMed2001

Enhanced 99Tc(m)-MIBI SPECT detection of hibernating myocardium following the use of sub-lingual nitroglycerine.

The purpose of this study was to assess the feasibility of detecting hibernating myocardium using 99Tc(m)-MIBI SPECT imaging following the use of sublingual glyceryl trinitrate (GTN). Thirty-eight subjects were studied, five asymptomatic and 33 with a history of myocardial ischaemia or myocardial infarction (MI). The study was conducted on two separate days, both at rest, one under controlled basal conditions and the other 20 min following the sublingual administration of GTN. A total of 190 cardiac segments were qualitatively analysed and 72 segments with fixed defects were compared to the study following the use of GTN for evidence of improved radionuclide uptake. Following GTN, 73.6% of fixed segment defects showed no change in uptake, 5.5% showed probable improvement whilst in 20.8% a definite enhanced uptake was demonstrated. In 3.7% of segments, worsening of radionuclide uptake was observed.

Administration, Sublingual↗
PubMed2000

Constitutive expression of NF-kappa B is a characteristic feature of mycosis fungoides: implications for apoptosis resistance and pathogenesis.

The NF-kappa B family of transcription factors is an important regulator of genes expressed during inflammatory responses, immunoglobulin (Ig) class switching, cellular differentiation, and apoptosis. Recently, members of the NF-kappaB family, including p65(Rel A), have been implicated in promoting survival of various hematopoeitic neoplasms, including T cell malignancies such as adult T cell leukemia-lymphoma. We investigated the expression of active NF-kappa B p65(Rel A) in cases of mycosis fungoides (MF) and the effect of chemical inhibitors of NF-kappa B on apoptosis in cutaneous T cell lymphoma (CTCL) cell lines. Paraffin-embedded tissues from 23 cutaneous lesions and a single lymph node biopsy from patients diagnosed with MF were evaluated for p65(Rel A) expression by using a monoclonal mouse antibody that detects the activated form of p65(Rel A). Apoptosis after treatment with the NF-kappa B inhibitors gliotoxin, MG132, BAY 11-7082, and BAY 11-7085 was quantitatively measured in the CTCL cell lines HuT-78 and HH by propidium iodide (PI)/cell cycle analysis for detection of a hypodiploid (sub-G(0)) population and by determination of increased Annexin V/7-amino-actinomycin D (7-AAD) expression. Nuclear extracts from CTCL cells before and after chemical inhibition were analyzed for NF-kappa B nuclear DNA-binding activity by electrophoretic mobility shift assay (EMSA) with quantitative densitometry. Nuclear expression of p65(Rel A) before and after treatment with the various inhibitory compounds was measured by immunofluorescence staining in each CTCL cell line. Neoplastic T lymphocytes from 22 of 24 cases of MF showed strong nuclear and cytoplasmic expression of active p65(Rel A). Compared with untreated control cells, a marked increase in apoptosis, a significant decrease in NF-kappa B DNA-binding activity, and a marked decrease in nuclear p65(Rel A) expression were seen in cells from both CTCL cell lines after chemical NF-kappa B inhibition. These data show that the active form of NF-kappa B p65(Rel A) is commonly expressed in neoplastic T lymphocytes in patients with MF. In CTCL cell lines, the significant decrease in nuclear NF-kappa B expression and the marked increase in spontaneous apoptosis caused by chemical NF-kappa B inhibition suggest a critical role for NF-kappa B in the pathogenesis and tumor cell maintenance of CTCLs. HUM PATHOL 31:1482-1490.

Anti-Infective Agents↗
PubMed2000

Imaging tumors in humans with Tc-99m-VIP.

Vasoactive intestinal peptide (VIP) was modified at the C terminus with a spacer and four amino acids to serve as a chelating moiety. The modified peptide, TP 3654, was labeled with Tc-99m and evaluated in normal volunteers, as well as in patients with a history of cancer. Renal clearance (67%) was the primary route of excretion, with approximately 20% of the radioactivity clearing through the hepatobiliary system. No adverse reaction was noted in any of the subjects and all, except one small, of the known lesions as seen by CT, MRI, Tc-99m-MIBI, or mammography were correctly identified within a few minutes of an i.v. injection of approximately 10 mCi of Tc-99m-TP 3654 (specific activity 11.3 x 10(3) Ci/m mol). The scans were in concordance in nine patients. In the remaining two, one with a visible mass in the neck from high grade spindle cell sarcoma and the other with a palpable mass in a breast from ductal epithelial hyperplasia, were localized only with Tc-99m-TP 3654, but not with Tc-99m-MIBI. Both malignancies are known to express VIP receptors. The VIP analog promises to be a nontoxic and reliable agent for imaging cancers in humans that express VIP receptors.

Adenocarcinoma↗
PubMed2000

99mTc-labeled vasoactive intestinal peptide analog for rapid localization of tumors in humans.

In recent years, imaging tumors with receptor-specific biomolecules has been the focus of increasing interest. Vasoactive intestinal peptide (VIP) has a high affinity for specific receptors that are expressed in high density on a large number of malignant tumors. VIP was modified (TP 3654) without compromising its biologic activity and labeled with 99mTc. Pharmacokinetics and feasibility studies were performed in 3 healthy volunteers and 11 patients with a history of cancer. Imaging was performed for up to 2 h after injection. Within 24 h after injection of 99mTc-TP 3654 (370-555 MBq/5 microg), approximately 70% of the tracer cleared through the kidneys and 20% through the liver. Blood clearance was rapid. No adverse reaction was noted in any subject. All known tumors were clearly delineated within 20 min. Findings were compared with the results of 99mTc-methoxyisobutyl isonitrile, CT, MRI, or histology. There was concordance in 9 patients. In the other 2 patients, only the VIP scan was positive for tumors known to express VIP receptors. The early results of imaging tumors with 99mTc-VIP are promising and warrant further study.

Adult↗
PubMed1999

Hepatitis B awareness and attitudes amongst dental health care workers in Riyadh, Saudi Arabia.

This study was done to investigate the current awareness and uptake of the hepatitis-B vaccination, as well as any changes in patterns over the years. A questionnaire was distributed among all dental staff, including dental specialists, general dentists, hygienists and dental surgery assistants at the dental department of the Military Hospital, Riyadh. Out of 126 DHCW, 112 (88.2%) responded. Ninety-six (85.7%) completed full course of vaccination, 4 (3.6%) did not intend to, be vaccinated and 10 (8.9%) were naturally immune. Of the 96 vaccinate, 42 (43.8%) did not confirm the vaccine efficacy by serological tests. And 54 vaccinate who had post-vaccination serology test, 26 (48.2%) did not check the results of the test. It is concluded from the study that in spite of greater acceptability of the HB vaccine by the DHCW, still a large proportion of them need further advise on the importance of post-vaccination serological tests.

Attitude of Health Personnel↗