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Biomedical subjects

S Shaikh

Publications and source records attributed to S Shaikh.

At least 37 records · Page 2Linked to original sources
PubMed2001

Growth inhibition and differentiation of C6 glioma cells on treatment with hmba.

HMBA, a differentiation inducer belonging to the class of hybrid polar compounds, is known to induce terminal differentiation of a number of leukemic and solid tumour cell lines. In this report we have shown that HMBA markedly inhibits growth of C6 glioma cells at non-cytotoxic concentrations ranging from 2.5 m m to 10 m m in a dose-dependent manner. The growth inhibitory effect can be detected as early as 18--24 h. By the sixth day the growth inhibition decreases at all the concentrations tested. Treatment with HMBA results in an accumulation of C6 cells in G0/G1 phase along with a decrease in the number of cells in S phase. HMBA induces morphological differentiation of C6 cells and increases expression of glial fibriliary acidic protein (GFAP), a marker for mature astrocytes. HMBA induces c-fos and represses cycloheximide-induced c-jun and fra-1 expression. HMBA-induced growth inhibition of C6 cells is accompanied by a decrease in Cdk4 protein levels. However, HMBA fails to sustain low Cdk4 levels, which may be responsible for HMBA's failure to sustain the growth inhibitory effect.

Acetamides↗
PubMed2001

Leber hereditary optic neuropathy associated with antiretroviral therapy for human immunodeficiency virus infection.

PURPOSE: Antiretroviral therapy has reduced the morbidity and mortality associated with human immunodeficiency virus (HIV) infection. However, side effects are increasingly recognized, including a commonly reported toxic mitochondrial myopathy. We report such a case of Leber hereditary optic neuropathy in a patient with antiretroviral therapy for HIV infection and speculate on a possible toxic etiologic role in the development of Leber hereditary optic neuropathy by a shared mitochondrial mechanism. METHODS: Case Report. Bilateral optic disk abnormalities observed in a 38-year-old HIV positive man with a family history of Leber hereditary optic neuropathy were documented with fundus photography, color vision testing, and visual field testing. Mitochondrial DNA testing was used to confirm the genetic predisposition to Leber hereditary optic neuropathy. RESULTS: Progressive bilateral optic nerve pallor temporally associated with the administration of antiretroviral medication was observed. Diagnostic testing revealed progressive visual field and color vision loss as well as a mitochondrial DNA mutation consistent with Leber hereditary optic neuropathy. CONCLUSION: Antiretroviral therapy may be associated with the onset of Leber hereditary optic neuropathy in genetically predisposed patients.

Adult↗
PubMed2001

Fluorescein angiographic findings in ocular siderosis.

PURPOSE: To report a case of siderosis from a retained intraocular iron foreign body manifesting localized retinal capillary nonperfusion documented by fluorescein angiography. METHODS: Case Report. In a 35-year-old man with decreased vision in the left eye, studies included fundus photography, fluorescein angiography, visual field testing, and electrophysiology. Surgical foreign body extraction and histopathologic examination were performed. RESULTS: Preoperatively, in the left eye, humphrey visual fields and electrophysiology testing revealed marked depression. Fluorescein angiography demonstrated nasal capillary nonperfusion with occlusion of the second- and third-order arterioles extending along a gradient from the foreign body. Microscopic examination of the lens capsule confirmed the diagnosis of siderosis secondary to a retained iron foreign body. CONCLUSION: Extensive capillary nonperfusion may be associated with a retained iron intraocular foreign body, as documented by fluorescein angiography.

Adult↗
PubMed2001

Comparative efficacy and safety of remifentanil and fentanyl in 'fast track' coronary artery bypass graft surgery: a randomized, double-blind study.

This multi-centre, parallel group, randomized, double-blind study compared the efficacy and safety of high-dose remifentanil administered by continuous infusion with an intermittent bolus fentanyl regimen, when given in combination with propofol for general anaesthesia in 321 patients undergoing elective coronary artery bypass graft surgery. A significantly lower proportion of the patients who received remifentanil had responses to maximal sternal spread (the primary efficacy endpoint) compared with those who received fentanyl (11% vs 52%; P<0.001). More patients who received remifentanil responded to tracheal intubation compared with those who received fentanyl (24% vs 9%; P<0.001). However, fewer patients who received remifentanil responded to sternal skin incision (11% vs 36%; P<0.001) and sternotomy (14% vs 60%; P <0.001). Median time to extubation was longer in the subjects who received remifentanil than for those who received fentanyl (5.1 vs 4.2 h; P=0.006). There were no statistically significant differences between the two groups in the times for transfer from intensive care unit or hospital discharge but time to extubation was significantly longer in the remifentanil group. Overall, the incidence of adverse events was similar but greater in the remifentanil group with respect to shivering (P<0.049) and hypertension (P<0.001). Significantly more drug-related adverse events were reported in the remifentanil group (P=0.016). There were no drug-related adverse cardiac outcomes and no deaths from cardiac causes before hospital discharge in either treatment group.

Adult↗
PubMed2001

Diffuse unilateral hemorrhagic retinopathy associated with accidental perinatal strangulation. A clinicopathologic report.

OBJECTIVE: To report an unusual case of diffuse retinal hemorrhage associated with strangulation in a neonate with a tightly wrapped nuchal cord around his neck at birth who was noted to have eyelid and subconjunctival petechial hemorrhages upon delivery. METHODS: Clinical diagnostic examination as well as postmortem gross and histopathologic examination of ocular and central nervous system structures was performed. RESULTS: Funduscopic and gross pathologic examination of the eyes revealed extensive unilateral retinal hemorrhage of the right eye only. This was corroborated by histopathologic studies, which revealed unilateral diffuse hemorrhage throughout all nuclear layers of the retina with a particularly dense nerve fiber layer and sub-internal limiting membrane hemorrhage in the macula along with extraocular muscle and episcleral hemorrhage. Clinical, gross, and microscopic examination also revealed multiple areas of hemorrhage involving the right side of the brain and throughout the cerebellum. CONCLUSION: Although retinal findings in nonaccidental trauma are common, accidental strangulation retinopathy in neonates is a rare occurrence. To the authors' knowledge, this case is the only documented histopathologic study of hemorrhagic retinopathy associated with strangulation in the literature.

Airway Obstruction↗
PubMed2001

Clinical effectiveness of mandibular implant-retained overdentures.

INTRODUCTION: The literature reports that the treatment of fully edentulous mandibles with implant-retained overdentures has become a recognised form of therapy: however long-term data on the success are limited. The aim of the present study was to describe the clinical effectiveness of mandibular implant-supported/retained overdentures in the management of a group of edentulous patients. MATERIALS AND METHODS: The study group consisted of 59 consecutive edentulous patients attending the clinic of prosthetic dentistry at Cardiff Dental Hospital, who had been provided with implants in the mandible for complete overdenture retention. Several clinical parameters were examined in each patient: mobility of each implant, probing pocket depth, the presence or absence of plaque and calculus on each implant, bleeding index, marginal bone loss, jaw bone quality and quantity, complications that had occurred with the implants and patients opinions of the treatment. DISCUSSION: Of implants placed, 97% remained in function. Three fixtures had been lost. There was a high frequency of bleeding on probing. Complications associated with treatment included damage or looseness of abutment screws, fracture of the bar, entrapment of food beneath the overdenture and looseness of the opposing non-implant-retained complete denture. CONCLUSION: In general a very high degree of patient satisfaction with the implant-retained overdentures was recorded.

Adult↗
PubMed2000

Trabeculectomy with intraoperative mitomycin C versus 5-fluorouracil. Prospective randomized clinical trial.

OBJECTIVE: To evaluate the relative efficacy and safety of 5-fluorouracil (5-FU) and mitomycin C (MMC) when used as adjuncts with primary trabeculectomy in eyes not at high risk for failure. DESIGN: Prospective multicenter, randomized clinical trial. PARTICIPANTS: One hundred thirteen patients with primary open-angle, pseudoexfoliative, pigmentary, or angle-closure glaucoma undergoing primary trabeculectomy were recruited. METHODS: One eye of each patient was randomized to receive either 5-FU (50 mg/ml for 5 minutes) or MMC (0.4 mg/ml for 2 minutes). MAIN OUTCOME MEASURES: Intraocular pressure (IOP), visual acuity, complications, and interventions were documented at fixed intervals after surgery. The study also examined progression of visual field loss, long-term complications, and bleb appearance 3 years after surgery. RESULTS: Of the 108 patients with complete perioperative information, 54 eyes received 5-FU and 54 received MMC. The proportion of patients reaching different predefined target IOPs after surgery was slightly higher in the MMC group than in the 5-FU group. This difference was less than 25%, which would have been necessary to achieve statistical significance with a power of 0.8 and the sample size used. Likewise, there was no statistically significant difference between the groups with regard to mean preoperative IOP, complications, or interventions. Mean postoperative follow-up was 309 and 330 days in the 5-FU and MMC groups, respectively (P = 0.593). CONCLUSIONS: 5-Fluorouracil and MMC were found to be equally safe and effective adjuncts to primary trabeculectomy in the short- and medium-term postoperative periods.

Aged↗
PubMed2000

Association study of dopamine receptor gene polymorphisms with drug-induced hallucinations in patients with idiopathic Parkinson's disease.

Some patients with idiopathic Parkinson's disease experience hallucinations as a result of treatment with levodopa and dopamine agonists. There is evidence for some heterogeneity in these hallucinating patients based on duration of Parkinson's disease at onset of hallucinations. We compared the frequency of polymorphisms in the dopamine D2 and D3 receptor genes between patients with drug-induced hallucinations and non-hallucinating patients. Two polymorphisms close to DRD2 and one in DRD3 were studied. No association was found with the whole group of hallucinating patients and their controls. However, an association was found with late-onset hallucinations and the C allele of the TaqIA polymorphism, 10.5 kb 3' to DRD2. This polymorphism may be in linkage disequilibrium with a mutation in DRD2 or a nearby gene that predisposes to drug-induced hallucinations which occur later in the course of idiopathic Parkinson's disease.

Alleles↗
PubMed1999

Nup153 is an M9-containing mobile nucleoporin with a novel Ran-binding domain.

We employed a phage display system to search for proteins that interact with transportin 1 (TRN1), the import receptor for shuttling hnRNP proteins with an M9 nuclear localization sequence (NLS), and identified a short region within the N-terminus of the nucleoporin Nup153 which binds TRN1. Nup153 is located at the nucleoplasmic face of the nuclear pore complex (NPC), in the distal basket structure, and functions in mRNA export. We show that this Nup153 TRN1-interacting region is an M9 NLS. We found that both import and export receptors interact with several regions of Nup153, in a RanGTP-regulated fashion. RanGTP dissociates Nup153-import receptor complexes, but is required for Nup153-export receptor interactions. We also show that Nup153 is a RanGDP-binding protein, and that the interaction is mediated by the zinc finger region of Nup153. This represents a novel Ran-binding domain, which we term the zinc finger Ran-binding motif. We provide evidence that Nup153 shuttles between the nuclear and cytoplasmic faces of the NPC. The presence of an M9 shuttling domain in Nup153, together with its ability to move within the NPC and to interact with export receptors, suggests that this nucleoporin is a mobile component of the pore which carries export cargos towards the cytoplasm.

Amino Acid Sequence↗
PubMed1999

The safety and effectiveness of remifentanil as an adjunct sedative for regional anesthesia.

UNLABELLED: We assessed the sedative potential of continuous infusions of remifentanil with a validated composite alertness scale in 160 patients (ASA physical status I or II) undergoing hip replacement surgery with spinal block (n = 61) or hand surgery using brachial plexus block (n = 93). They were randomized to receive one of the following initial dose regimens in double-blinded fashion: placebo or 0.04, 0.07, or 0.1 microg x kg(-1) x min(-1) remifentanil subsequently titrated to effect. Additional midazolam IV was allowed for adequate sedation as required. The combined analysis of both surgery groups revealed a dose-related increase in achievement of sedation level > or =2 within 15 min of the start of the study drug infusion; all remifentanil dose comparisons with placebo reached significance (P < 0.001). The remifentanil 50% effective dose for a composite sedation level > or =2 within 15 min of the start of drug infusion was estimated as 0.043 microg x kg(-1) x min(-1) (95% confidence interval 0.01, 0.059). The requirement for midazolam decreased with increasing remifentanil dose compared with placebo (P < 0.001). The median time to return to alertness after the end of infusion was 10-12 min in the remifentanil groups and 5 min in the placebo group. Significant incidences of nausea, pruritus, sweating, and respiratory depression were reported during remifentanil infusions compared with placebo. The data suggest that remifentanil may be useful for supplementation of regional anesthesia, provided that ventilation is carefully monitored. IMPLICATIONS: In this dose-finding, placebo-controlled study, remifentanil infusions were used to provide sedation during spinal and brachial plexus regional anesthesia. The 50% effective dose for achievement of sedation was 0.043 microg x kg(-1) x min(-1). Return to alertness occurred after 10-12 min (median time). Remifentanil infusions can be used to supplement regional anesthesia, but this requires careful monitoring of ventilation.

Adjuvants, Anesthesia↗
PubMed1999

Sequential recruitment of NPC proteins to the nuclear periphery at the end of mitosis.

Nuclear pore complexes (NPCs) are extremely elaborate structures that mediate the bidirectional movement of macromolecules between the nucleus and cytoplasm. With a mass of about 125 MDa, NPCs are thought to be composed of 50 or more distinct protein subunits, each present in multiple copies. During mitosis in higher cells the nuclear envelope is disassembled and its components, including NPC subunits, are dispersed throughout the mitotic cytoplasm. At the end of mitosis, all of these components are reutilized. Using both conventional and digital confocal immunofluorescence microscopy we have been able to define a time course of post-mitotic assembly for a group of NPC components (CAN/Nup214, Nup153, POM121, p62 and Tpr) relative to the integral nuclear membrane protein LAP2 and the NPC membrane glycoprotein gp210. Nup153, a component of the nuclear basket, associates with chromatin towards the end of anaphase, in parallel with the inner nuclear membrane protein, LAP2. However, immunogold labeling suggests that the initial Nup153 chromatin association is membrane-independent. Assembly of the remaining proteins follows that of the nuclear membranes and occurs in the sequence POM121, p62, CAN/Nup214 and gp210/Tpr. Since p62 remains as a complex with three other NPC proteins (p58, 54, 45) during mitosis and CAN/Nup214 maintains a similar interaction with its partner, Nup84, the relative timing of assembly of these additional four proteins may also be inferred. These observations suggest that there is a sequential association of NPC proteins with chromosomes during nuclear envelope reformation and the recruitment of at least eight of these precedes that of gp210. These findings support a model in which it is POM121 rather than gp210 that defines initial membrane-associated NPC assembly intermediates.

Animals↗
PubMed1999

Function and assembly of nuclear pore complex proteins.

Nuclear pore complexes (NPCs) are extremely elaborate structures that mediate the bidirectional movement of macromolecules between the nucleus and cytoplasm. The current view of NPC organization features a massive symmetrical framework that is embedded in the double membranes of the nuclear envelope. It embraces a central channel of as yet ill-defined structure but which may accommodate particles with diameters up to 26 nm provided that they bear specific import/export signals. Attached to both faces of the central framework are peripheral structures, short cytoplasmic filaments, and a nuclear basket assembly, which interact with molecules transiting the NPC. The mechanisms of assembly and the nature of NPC structural intermediates are still poorly understood. However, mutagenesis and expression studies have revealed discrete sequences within certain NPC proteins that are necessary and sufficient for their appropriate targeting. In addition, some details are emerging from observations on cells undergoing mitosis where the nuclear envelope is disassembled and its components, including NPC subunits, are dispersed throughout the mitotic cytoplasm. At the end of mitosis, all of these components are reutilized to form nuclear envelopes in the two daughter cells. To date, it has been possible to define a time course of postmitotic assembly for a group of NPC components (CAN/Nup214, Nup153, POM121, p62 and Tpr) relative to the integral inner nuclear membrane protein LAP2 and the NPC membrane glycoprotein gp210. Nup153, a dynamic component of the nuclear basket, associates with chromatin towards the end of anaphase coincident with, although independent of, the inner nuclear membrane protein, LAP2. Assembly of the remaining proteins follows that of the nuclear membranes and occurs in the sequence POM121, p62, CAN/Nup214 and gp210/Tpr. Since p62 remains as a complex with three other NPC proteins (p58, p54, p45) during mitosis, and CAN/Nup214 maintains a similar interaction with its partner, Nup84, the relative timing of assembly of these additional four proteins may also be inferred. These observations suggest that there is a sequential association of NPC proteins with chromosomes during nuclear envelope reformation and the recruitment of at least eight of these precedes that of gp210. These findings support a model in which it is POM121 rather than gp210 that defines initial membrane-associated NPC assembly intermediates and which may therefore represent an essential component of the central framework of the NPC.

Animals↗
PubMed1998

The effect of silicone ocular surgical devices on serum IgG binding to silicones.

PURPOSE: To determine whether silicone materials used in retinal detachment repair and cataract surgery increase serum IgG binding to silicone and identify correlations with complications of ocular surgery. METHODS: Serum from 49 patients who had ocular surgery using silicone materials was examined. Patient groups included scleral buckling (n = 25), silicone oil tamponade (n = 3), scleral buckling and silicone oil tamponade (n = 9), and silicone lens implants after cataract extraction (n = 12). Convalescent samples for all patients and preoperative samples from 19 patients (18 scleral buckling and one silicone oil tamponade) were examined. Postoperative complications were monitored for up to 108 months (mean, 10.7 months; mode, 1.5 months; range, 1 to 108 months). Samples were evaluated for the extent of IgG binding to silicones using a micromodification of a previously described enzyme-linked immunosorbent assay method. RESULTS: In 19 patients, IgG binding levels in preoperative samples were 21 arbitrary units (AU) or less. Of the 25 buckling patients, one developed complications; however, in all patients the postoperative levels of IgG binding to silicone were low (2.2 to 20.0 AU). Although four silicone lens patients developed mild complications, none displayed postoperative IgG binding levels of greater than 20 AU. Three patients who underwent both scleral buckling and silicone oil tamponade developed complications; one of these patients, who was also noted to have systemic connective tissue disease, had a significant elevation in postoperative serum IgG binding to silicone. CONCLUSIONS: Statistically significant elevations of serum IgG binding to silicone were noted postoperatively in only one patient who had a systemic connective tissue disease. The complication rate and frequency of enhanced serum IgG binding to silicone was low, making correlations to surgical complications difficult. Examination of matched samples suggested that if ocular exposure to silicone implants enhances the level of serum IgG binding to silicones, it must be a rare event that should not alter the clinical use of these important devices.

Adult↗
PubMed1998

Remifentanil in combination with propofol for spontaneous ventilation anaesthesia.

We have investigated the effect of four doses of remifentanil on the incidence of respiratory depression and somatic response at incision. Remifentanil was administered as a loading dose of 0.125, 0.25, 0.375 or 0.5 microgram kg-1 and at a maintenance infusion rate of 0.025, 0.05, 0.075 or 0.1 microgram kg-1 min-1, respectively, with an infusion of propofol 6 mg kg-1 h-1. Responses occurred in 88% of patients with remifentanil 0.025 microgram kg-1 min-1 compared with 30-40% in the other groups. Respiratory depression after incision increased from 6% with remifentanil 0.025 microgram kg-1 min-1 to 73% with 0.1 microgram kg-1 min-1. Increases in propofol infusion rate to 7.2-8.4 mg kg-1 h-1 produced adequate maintenance of anaesthesia. Reductions in remifentanil doses to 0.025-0.05 microgram kg-1 min-1 resulted in adequate respiration at the end of surgery in 88% of patients. Maintenance infusions of the two drugs for spontaneous ventilation are likely to be in these ranges. However, the ideal loading doses and infusion rates for induction remain to be established.

Adolescent↗