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Biomedical subjects

S Goel

Publications and source records attributed to S Goel.

At least 19 recordsLinked to original sources
PubMed2006

Peripheral blood mononuclear and tumor cell pharmacodynamics of the novel epothilone B analogue, ixabepilone.

BACKGROUND: We previously demonstrated that peak microtubule bundle formation (MBF) in peripheral blood mononuclear cells (PBMCs) occurs at the end of drug infusion and correlates with drug pharmacokinetics (PK). In the current study, a new expanded evaluation of drug target effect was undertaken. PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with ixabepilone 40 mg/m2 administered as a 1-h i.v. infusion every 3 weeks. Blood, plasma, and tumor tissue sampling was carried out to characterize pharmacodynamics and PK. RESULTS: Forty-seven patients were treated with 141 cycles of ixabepilone. In both PBMCs (n=27) and tumor cells (n=9), peak MBF occurred at the end of infusion; however, at 24-72 h after drug infusion, the number of cells with MBF was significantly greater in tumor cells, relative to PBMCs. A Hill model (EC50=109.65 ng/ml; r2=0.94) was fitted, which demonstrated a relationship between percentage of PBMCs with MBF and plasma ixabepilone concentration. The percentage of PBMCs with MBF at the end of infusion also correlated with severity of neutropenia (P=0.050). CONCLUSIONS: Plasma ixabepilone concentration and severity of neutropenia correlate with the level of MBF in PBMCs. Therefore, this technically straightforward assay should be considered as a complement to the clinical development of novel microtubule-binding agents.

Adult↗
PubMed2006

Neuroblastoma with orbital metastasis: ophthalmic presentation and role of ophthalmologists.

INTRODUCTION: Neuroblastoma is predominantly a tumour of early childhood, which metastasises to the orbits. In such cases, ophthalmologists are involved in the multidisciplinary management. This unique series from a tertiary referral centre is used to elaborate the ophthalmic associations and the ophthalmologist's role in this rare condition. METHODS: A review of case notes was performed on six patients who presented to the paediatric ophthalmology - oncology liaison service at the Leeds teaching hospitals between 1998 and 2003. The ophthalmic outcome and role of the ophthalmologist were assessed. RESULTS: Average age of presentation was 29.8 months (range 15-69 months). Average duration of follow-up was 19.5 months (range 2-58 months). One child died during treatment. Two have completed treatment and are under follow-up. Presenting features of the six children were proptosis in four, periorbital ecchymosis in two, ocular motility restriction in two, and subconjunctival haemorrhage in one. Only one case developed blindness. CONCLUSIONS: The role of the ophthalmologist in patients with metastatic orbital neuroblastoma can vary from a supportive role to one of active intervention and management of ophthalmic complications. The ophthalmologist is involved in diagnosis and staging as well as monitoring response to treatment of both the primary disease and secondary ophthalmic complications.

Child↗
PubMed2006

"Cryoanalgesic preparation" before local anaesthetic injection for lid surgery.

INTRODUCTION: Lid surgery under local anaesthetic is commonplace in ophthalmic practise. The most distressing part of the surgery for the patient is often the injection of local anaesthetic into the sensitive lid skin. Various methods like pre-injection warming of the anaesthetic agent, buffering pH levels, varying agents used, and using thinner gauge needles have been tried to reduce pain levels. Cooling of tissue is known to have anaesthetic properties and has been proposed as a substitute to injection of local anaesthetic in certain surgical procedures. In this study we use the anaesthetic property of cooling, as a pre local anaesthetic injection procedure ("Cryo-preparation"). The anaesthetic injection induced discomfort with and without "cryo-preparation" was then assessed. METHODS: Thirty-nine patients aged 13-85 years (mean = 50, s.d. = 19) were randomly allocated and assessed. Twenty-two patients underwent local lid anaesthetic infiltration with "cryo-preparation," and 17 without. Pain monitoring was performed subjectively and objectively by scoring systems. Results were analysed using unpaired two tailed t-test on Microsoft Excel. RESULTS: Significant reduction in injection pain with cryo-preparation (24.6% reduction in score) was achieved (statistically significant p = 0.039). Surgical anaesthesia was complete in all cases. CONCLUSION: The study shows that "cryopreparation" by local ice application immediately prior to local anaesthetic injection reduces the sensitivity to the injection by a significant 24.6%. Thus while all the advantages of good analgesia are obtained from the injection, the distressing discomfort is reduced. This study serves as a pilot, in demonstrating a novel method of pain control for lid surgery.

Adolescent↗
PubMed2005

The prevalence of pressure ulcers in hospitalised patients in a university hospital in India.

OBJECTIVE: To estimate the prevalence of pressure ulcers in hospitalised patients and any underlying or predisposing factors to ulceration. METHOD: This cross-sectional study took place in a university hospital in Varanasi, India. A total of 445 patients hospitalised in medical and surgical wards were examined in a single day for the number, site and grade of pressure ulcers. Haemoglobin, serum albumin and blood sugar levels of patients with pressure ulcers were recorded. RESULTS: The prevalence of pressure ulcers was high (4.94%). Anaemia, malnutrition and diabetes were important risk factors, while morbidity due to pressure ulcers in long-stay wards, such as neurology, was exceptionally high (40.9%). CONCLUSION: Pressure ulcers remain one of the most neglected aspects of health-care provision in India and identifying their associated risk factors at an early stage may go a long way in preventing their occurrence.

Adult↗
PubMed2004

Primary lumbosacral Wilms tumor associated with diastematomyelia and occult spinal dysraphism. A report of a rare case and a short review of literature.

BACKGROUND: The occurrence of an extrarenal Wilms tumor in the lumbosacral region is an extremely uncommon condition. CASE REPORT: We report a case of Wilms tumor in the lumbosacral region that was associated with diastematomyelia and occult spina bifida. An 18-month-old girl presented with a swelling over the lower back with a tuft of hair on it, which she had had since birth. Imaging of the spine revealed spina bifida, bony diastematomyelia, and tethered cord. Excision of the bony spur and detethering of the cord was done. After a year, she had recurrence of swelling at the same site, weakness of both lower limbs, and incontinence of bladder and bowel. Excision of the mass and bony spur and detethering of the spinal cord were done. Histopathological examination showed features of a Wilms tumor.

Female↗
PubMed2004

Comparison between standard Goldmann applanation prism and disposable applanation prism in tonometry.

BACKGROUND: Disposable devices are increasingly becoming the preferred choice where possible in contact medical equipment. AIM: To evaluate the accuracy of the disposable applanation tonometer head as a potential substitute to the standard Goldmann applanation head. METHODS: The study was prospective. The intraocular pressure recordings in 80 eyes of 42 patients were compared using the disposable and standard Goldmann applanator heads. The Bland and Altman method of assessing agreement between two methods of clinical measurement was used in the analysis. RESULTS: The difference in the readings between the two types of tonometer heads was highly variable (mean difference=0.78 mm Hg, range=-1 to 11 mm Hg). This was because of the distortions on the applanating surface of the disposable device. When the readings associated with the defective heads were excluded, very strong agreement was obtained (mean=0.07 mm Hg, range=-1 to 2 mm Hg). CONCLUSION: Good agreement with standard Goldmann applanation is achieved with the disposable heads except where surface distortions induce significant errors. Careful inspection to ensure well-structured disposable units is imperative in disposable applanation tonometry.

Adult↗
PubMed2004

Laser vs ultrasound biometry--a study of intra- and interobserver variability.

BACKGROUND: Accurate biometry is of vital importance in achieving predictable postoperative refraction following cataract surgery. AIM: To evaluate the accuracy and consistency in biometry, achieved by the new generation laser biometric system in comparison with the ultrasound biometric system. METHODS: The study was randomized and prospective. Biometry was performed in 68 eyes of 39 patients by three groups of biometrists (expert, intermediate user, novice). Expert and intermediate users are compared as group A, and expert and novice are compared in group B. Axial length, anterior chamber depth (ACD), and keratometry results are compared by t-test analysis. RESULTS: Axial length measurement variation between expert and non experts was 10 times less using laser than ultrasound (P<0.001). ACD measurement variation was also significantly less when using laser compared to ultrasound (P=0.003). Need for some level of user training is indicated in ACD measurement since group A achieved more consistent readings than group B. Keratometry measurements on the laser system were unreliable due to high range of results. Biometric failure was seen in 12% of eyes undergoing laser and 1% undergoing ultrasound biometry. CONCLUSION: Axial length determination by laser biometry is more accurate and consistent at all levels of biometrist expertise, compared to ultrasound biometry. ACD and keratometry measurements on the laser systems need some degree of user training in order to produce consistent results.

Adult↗
PubMed2003

Intrathecal fentanyl added to intrathecal bupivacaine for day case surgery: a randomized study.

BACKGROUND AND OBJECTIVE: The implication of intrathecal lidocaine in neurological toxicity has made intrathecal bupivacaine the commonly used drug for local anaesthesia in ambulatory surgery. However, in high doses intrathecal bupivacaine may produce a high level of sensory and motor block, and arterial hypotension; discharge from hospital may be delayed. Intrathecal opioids added to low-dose local anaesthetics produce a synergistic effect without increasing the sympathetic block or delaying discharge. The aim of our study was to identify the minimum effective dose of intrathecal fentanyl that in combination with low-dose intrathecal bupivacaine would provide adequate surgical conditions without prolonging recovery. METHODS: A prospective, single, blind, randomized study was conducted in 45 adult males scheduled for minor urological procedures using intrathecal anaesthesia on a day care basis. Patients were randomly assigned to one of three groups (n = 15 each). They received bupivacaine 0.17% 5 mg--with either fentanyl 7.5 microg (fenta-7.5), 10 microg (fenta-10) or 12.5 microg (fenta-12.5) intrathecally in a total volume of 3 mL. The quality of anaesthesia, haemodynamic stability, time to two-segment and S2 regression, time to micturition, and time to discharge were assessed. RESULTS: The time to two-segment regression and S2 regression with fenta-12.5 was significantly longer than with fenta-7.5 and fenta-10 (P < 0.01). Fenta-7.5 had a significantly higher number of failed blocks (four patients) compared with fenta-12.5 (P < 0.05). The time out of bed, time to micturition and time to discharge were significantly longer with fenta-10 and fenta-12.5 compared with fenta-7.5, and also with fenta-12.5 compared with fenta-10 (P < 0.01). Haemodynamic stability did not differ for all the drug combinations. CONCLUSIONS: Fentanyl 12.5 microg added to low-dose bupivacaine (5 mg) intrathecally provides better surgical anaesthesia and increased reliability of block than intrathecal fentanyl 7.5 or 10 microg. Haemodynamic stability was the same for all dose combinations used.

Adjuvants, Anesthesia↗
PubMed2003

Driving ability after pupillary dilatation.

BACKGROUND: The Royal College of Ophthalmologists' guidelines and Driver and Vehicle Licensing Agency (DVLA) recommend that a patient should not drive with dilated pupils based on the rationale that vision may be compromised in acuity and ability to tolerate glare. Arguments exist against these recommendations suggesting that pupillary dilatation does not have any real bearings on driving ability. Aim To determine the effects of pupillary dilatation on the ability to drive. METHODS: The study was randomised and prospective. A total of 28 patients had their visual parameters (distance vision, near vision, licence plate reading at 20 m or shorter, and glare) measured and analysed pre- and post-tropicamide 1% dilatation. Paired two-tailed Student's t-test and chi(2)-test were used in the analysis. RESULTS: At 20 min, following instillation of one drop of tropicamide 1% there is a significant reduction in visual acuity (VA), for distance Snellen and near. There is a significant reduction in the number of people who could read the licence plate at 20 m. Subjective glare assessment changed from 'none' (average score) in the undilated state to 'mild' in the dilated states. The overall patient feedback indicated that a significant 14% believed they would find it difficult to drive postdilatation. CONCLUSION: This study demonstrates the rationale behind disallowing driving following pupillary dilatation. The risks to safe driving are proved significant as a result of significant reduction in visual quality and quantity after dilatation.

Adult↗
PubMed2003

Phase I clinical study of infusional 5-fluorouracil with oxaliplatin and gemcitabine (FOG regimen) in patients with solid tumors.

BACKGROUND: The aim of this study was to determine the maximum tolerated dose, recommended phase II dose (RPTD) and toxicities of the FOG regimen (infusional 5-fluorouracil, oxaliplatin, gemcitabine). PATIENTS AND METHODS: Patients with advanced solid tumors were treated in an accelerated titration scheme. 5-Fluorouracil was administered intravenously at 200 mg/m(2)/day for 14 days and repeated every 21 days (one cycle). Gemcitabine was administered on days 1 and 8 over 30 min at 450-650 mg/m(2). Oxaliplatin was administered on day 1 over 2 h at 85-130 mg/m(2). For cycles 1, 3 and beyond, gemcitabine followed oxaliplatin; for cycle 2, gemcitabine preceded oxaliplatin. RESULTS: Forty-five and 39 patients were assessable for toxicity and response, respectively. Cycle 1 dose-limiting toxicities (DLT) included neutropenia, thrombocytopenia and diarrhea. No DLT was observed in cycle 1 at the first four dose levels (DL). At DL-5, two of four (50%) patients experienced DLT in cycle 1. Expanding DL-4, nine of 26 (35%) patients experienced DLT in cycle 1. Because recurrent grade 3 toxicities were observed in three of six (50%) patients at DL-3, DL-2 was considered the RPTD. At the RPTD, three patients had a partial response (response rate 23%). CONCLUSIONS: The RPTD for the 5-fluorouracil-oxaliplatin-gemcitabine combination is 200/100/450 mg/m(2). This novel regimen has demonstrated activity in advanced solid tumors and merits further investigation.

Adult↗
PubMed2003

Clinical studies in patients with solid tumors using a second-generation antisense oligonucleotide (GEM 231) targeted against protein kinase A type I.

GEM 231 is a second-generation antisense oligonucleotide targeted against the RIalpha regulatory subunit of cAMP-dependent protein kinase type I (PKA-I). Excessive expression of PKA-I is associated with cell proliferation and transformation, and increased levels of secreted extracellular PKA (ECPKA) are found in the serum of cancer patients. Preclinical studies have demonstrated single-agent antitumor activity of GEM 231 in a variety of human cancer xenograft models, and additive or synergistic antitumor activity has been observed with taxane and/or camptothecin-based combinations. Based on prior safety (MTD) data demonstrating dose-dependent, reversible, and cumulative transaminitis, and high peak plasma concentration (Cmax)-dependent changes in activated partial thromboplastin time (aPTT) with GEM 231 2-h twice-weekly infusions, an alternative schedule of GEM 231 given as a single agent was evaluated in patients with advanced solid tumors. Fourteen patients (median age approximately 60 yrs) with advanced solid malignancies received a total of 78 weeks of therapy. GEM 231 was infused via a CADD pump at 80 mg/m2/day (d) for 3 d/wk (n = 1), then for 5 d/wk at 80 (n = 3), 120 (n = 8), and 180 mg/m2/d (n = 2). One cycle was defined as 4 weeks of therapy. Apparent dose dependency for the occurrence of transaminitis was readily reversible. At 180 mg/m2/d, 2 of 2 patients had cycle 1 dose-limiting toxicity (DLT) transaminitis. One patient treated at 120 mg/m2/d experienced grade 3 transaminase elevations after 8 weeks of therapy, but when serum transaminase values rapidly improved he resumed treatment at 80 mg/m2/d for 6 weeks until tumor progression was documented. Another patient at 120 mg/m2/d developed grade 3 esophagitis after 3 weeks, limiting further dosing. One patient (lung cancer) demonstrated stable disease for 9 weeks. Overall, plasma aPTT was minimally prolonged and changes were transient, peaked at the end of each infusion, and were not associated with spontaneous bleeding. A constitutive symptom (e.g., low-grade fatigue) was common, cumulative, and reversible following discontinuation of therapy. Serum ECPKA was measured by enzymatic assay and Western blotting from blood drawn at the beginning and end of each infusion. Serum ECPKA levels demonstrated a trend to decline with the treatment. In addition to single agent schedules, combination trials were undertaken to assess safety and possible interaction of GEM 231 with taxanes (paclitaxel, docetaxel), given once every 3 weeks (one cycle). While trials using the 2-h twice-weekly GEM 231 infusions are ongoing, preliminary results from both studies show that it is safe to combine paclitaxel or docetaxel with GEM 231. Overall, it is also feasible to administer GEM 231 in combination with taxane or nontaxane chemotherapy (e.g., camptothecins). Phase I combination studies are currently underway to further explore the clinical, pharmacokinetic, and biologic profile of GEM 231 with chemotherapy.

Antineoplastic Agents↗
PubMed2002

Molecular evolution and phylogenetic implications of internal transcribed spacer sequences of nuclear ribosomal DNA in the Phaseolus-Vigna complex.

Molecular phylogeny based on internal transcribed spacer (ITS) sequences was studied to resolve the taxonomic contradiction in Vigna and its relation to Phaseolus. The ITS region of the 18S-26S nuclear ribosomal DNA repeat was sequenced for 29 Vigna species, selected from five of the nine subgenera, and 9 species of Phaseolus. The length of ITS-1 ranged from 187 to 243 bp and 217 to 290 bp, and that of ITS-2 from 187 to 219 bp and 225 to 243 bp, within Vigna and Phaseolus species, respectively. Phylogenies derived from ITS sequences based on maximum-parsimony and neighbor-joining methods gave trees essentially of similar topology. The ITS phylogeny was generally congruent with recent classifications based largely on morphological, biochemical, cytogenetical, and palynological features, except that subgenus Plectotropis of Neotropical origin was revealed to be closely related to subgenus Vigna instead of forming a link between African (subgenus Vigna) and Asiatic (subgenus Ceratotropis) vignas, and subgenus Sigmoidotropis, featuring morphological characters of both Vigna and Phaseolus, was placed as the sister group to the Phaseolus taxa. The ITS sequences were shown to be useful for identifying wild progenitors of V. mungo, V. radiata, V. umbellata, and V. unguiculata and for clarifying taxonomy-related problems in many previously controversial cases. This study also affirms that V. umbellata and V. angularis are the diploid progenitors of the only tetraploid species (V. glabrescens) known in the genus.

Base Composition↗
PubMed2001

Acetoxy-4-methylcoumarins confer differential protection from aflatoxin B(1)-induced micronuclei and apoptosis in lung and bone marrow cells.

The ability of various acetoxy derivatives of 4-methylcoumarins to inhibit the genotoxic changes due to aflatoxin B(1) (AFB(1)) is reported here. Several 4-methylcoumarins (test compounds), such as 7,8-diacetoxy-4-methylcoumarin (DAMC), monoacetoxy-4-methylcoumarin (MAC), 5-N-acetyl-6-acetoxy-4-methylcoumarin (NAMC) and 7,8-dihydroxy-4-methylcoumarin (DHMC) were separately administered intraperitoneally (i.p.) to male wistar rats followed by AFB(1) administration i.p. or intratracheally (i.t.) (2-8 mg/kg b.wt.) and another dose of the test compound. The animals were sacrificed 26h after AFB(1) administration. From animals receiving AFB(1) i.p., bone marrow (BM) cells were isolated and stained with Mayer's haematoxylin and eosin. Micronuclei (MN) in BM were scored by light microscopy. From animals receiving AFB(1) i.t., bronchoalveolar lavage (BAL) was obtained, lung cells (LG) were isolated and stained with fluorochrome 6-diamidino-2-phenylindole (DAPI) for the analysis of MN, apoptotic bodies (AP) and cell cycle variations. Rats were separately treated with the vehicle DMSO to serve as the proper control. AFB(1) caused significant dose-dependent induction of MN in BM as well as LG. AP were observed in LG of rats receiving AFB(1) and was found to correlate with MN induction. DAMC injection caused significant decrease in AP due to AFB(1) in LG and MN in both BM and LG. The effectiveness of MAC was approximately half that of DAMC, thereby indicating that number of acetoxy groups on the coumarin molecule determine the efficacy. The fact that NAMC had no effect either on MN or AP indicate that neither acetoxy group at C-6 nor the N-acetyl group at C-5 facilitate the transfer of acetyl group to P-450 required for inhibition of AFB(1)-epoxidation. DHMC, the deacetylated product of DAMC had no normalizing effect on the induction of MN and AP. These findings confirm our earlier hypothesis that DAMC-mediated acetylation of microsomal P-450 (catalysing epoxidation of AFB(1)) through the action of microsomal transacetylase is responsible for the protective action of DAMC. The relative number and position of acetoxy groups on the coumarin nucleus determine the specificity to the transacetylase necessary for the chemopreventive action.

Acetylation↗
PubMed2001

Painless destruction of the shoulder joint: a case report.

A case of painless destruction of the shoulder joint is reported for its rarity and unusual presentation as a neuroarthropathic joint with no evidence of neurological disease. A differential diagntosis of Gorham-Stout syndrome and avascular necrosis was discussed.

Adult↗
PubMed2001

Hydatiform mole with coexisting live fetus in dichorionic twin gestation.

A case of dichorionic twin pregnancy was diagnosed in a 29-year-old, on routine ultrasound at 12 weeks. Subsequent ultrasounds for persistent vaginal bleeding at 16 weeks revealed molar placenta with viable fetus in both gestational sacs. The patient declined any invasive prenatal testing to confirm the karyotype of the fetus. The pregnancy was managed expectantly until 21 weeks, when she had a spontaneous abortion of twin fetuses and separate placentae with attached molar tissue. A final karyotype on cord blood samples confirmed 46XY and 46XX for both fetuses. Histopathology of molar tissue reported complete mole, with diploid chromosomal pattern on subsequent DNA flow cytometry. The clinical, ultrasound and chromosomal examination suggest that there has been a quadruplet pregnancy where two embryos developed into normal fetuses and other two degenerated to complete moles.

Abortion, Spontaneous↗
PubMed2001

Mechanism of biochemical action of substituted benzopyran-2-ones. Part 8: Acetoxycoumarin: protein transacetylase specificity for aromatic nuclear acetoxy groups in proximity to the oxygen heteroatom.

Our earlier work established a convenient assay procedure for acetoxycoumarin (AC): protein transacetylase (TA) by indirectly quantifying the activity of glutathione (GSH)-S-transferase (GST), the extent of inhibition of GST under the conditions of the assay represented TA activity. In this communication, we have probed the specificity for TA with respect to the number and position of acetoxy groups on the benzenoid as well as the pyranone rings of the coumarin system governing the efficient transfer of acetyl groups to the protein(s). For this purpose, coumarins bearing one acetoxy group, separately at C-3 or C-4 position and 4-methylcoumarins bearing single acetoxy group, separately at C-5, C-6 or C-7 position were synthesized and specificities to rat liver microsomal TA were examined. Negligible TA activity was discernible with 3-AC as the substrate, while the substrate efficiency of other AC were in the order 7-acetoxy-4-methylcoumarin (7 AMC)>6 AMC>5 AMC=5 ADMC=4 AC. To achieve a comparable level of GST inhibition which was proportional to the enzymatic transfer of acetyl groups to the protein (GST), the concentrations of 7-AMC, 6-AMC, 5-AMC and 4-AC were in the order 1:2:4:4, respectively. One diacetoxycoumarin, i.e., 7,8-diacetoxy-4-methylcoumarin (DAMC) was also examined and it was found to elicit maximum level of GST inhibition, nearly twice that observed with 7-AMC. These observations lead to the logical conclusion that a high degree of acetyl group transfer capability is conferred when the acetoxy group on the benzenoid ring of the coumarin system is in closer proximity to the oxygen heteroatom, i.e., when the acetoxy groups are at the C-7 and C-8 positions.

Aflatoxin B1↗