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Biomedical subjects

S Patel

Publications and source records attributed to S Patel.

At least 415 records · Page 23Linked to original sources
PubMed1996

Efficacy and safety of divided dose administration of mivacurium for a 90-second tracheal intubation.

STUDY OBJECTIVE: To compare the safety and effectiveness of 0.25 mg divided doses of mivacurium chloride to succinylcholine for a 90-second tracheal intubation. DESIGN: Randomized, double-blind, multicenter study in two groups. SETTING: Operating rooms at four university medical centers. PATIENTS: 200 healthy ASA status I and II adult patients scheduled for elective surgery with general anesthesia and endotracheal intubation. INTERVENTIONS: Patients were premedicated with 1 to 2 mg midazolam and 2 micrograms/kg fentanyl. Anesthesia was induced with 2 mg/kg propofol. Group A received 0.25 mg/kg mivacurium given as a divided dose (0.15 mg/kg followed in 30 seconds with 0.1 mg/kg). Group B (control) received 1.5 mg/kg succinylcholine (SCh) preceded two minutes earlier by 50 micrograms/kg d-tubocurarine (dtc). MEASUREMENTS AND MAIN RESULTS: Tracheal intubation grading, train-of-four response of the adductor pollicis, heart rate (HR), and mean arterial blood pressure (MAP) were measured and evaluated. Chi-square analysis was performed for comparison between Group A and Group B with respect to the frequency distribution of intubation using the scores excellent, good, and poor and not possible (combined). Group B had a significantly higher excellent score of intubation than Group A, 84% versus 56% (p < 0.0001). No significant difference was found between the two groups when the scores excellent and good were combined (Fisher's Exact test, p = 0.28). The changes in MAP and HR were similar for the two groups. CONCLUSIONS: When Sch is not desirable, mivacurium 0.25 mg/kg given as a divided dose provides good to excellent intubation conditions 90 seconds after the initial dose without significant changes in MAP or HR. It can be an appropriate alternative for short surgical procedures. It must be emphasized that this conclusion does not apply to rapid-sequence induction-intubation.

Adolescent↗
PubMed1996

Feasibility of using a swine portal vein containing a metallic stent for creating a portacaval shunt.

RATIONALE AND OBJECTIVES: We evaluated the feasibility of using a metallic stented portal vein as a conduit for portacaval shunt in pigs. METHODS: A metallic self-expanding stent was placed in the portal vein of five pigs under combined ultrasound and fluoroscopic guidance via a percutaneous transhepatic approach. After 6 weeks, a portacaval shunt was performed using the stented portal vein as a conduit. A single angiogram followed immediately by sacrifice and histologic examination was performed on each pig at a varying time interval postshunt. RESULTS: One pig died 3 days after the shunt procedure because of a presumed surgical technical failure and a consequent thrombosed portal vein. Angiographic patency of the portacaval shunt was confirmed in the four remaining pigs. Postmortem histologic evaluation showed more complete endothelialization and subintimal organization in the more chronic stents. Thrombus occurred only in the stent of the pig that died. There was no significant luminal obstruction in the other four stents. CONCLUSION: Our results suggest that a stented portal vein can be used successfully as a conduit for portacaval shunt in pigs.

Angiography↗
PubMed1996

Fluoride pharmacokinetics and changes in lumbar spine and hip bone mineral density.

Debate about the use of fluoride for the treatment of vertebral osteoporosis has centered not only on whether fluoride treatment decreases vertebral fractures, but also the interindividual vertebral bone mineral density (BMD) response, the potential for nonvertebral fractures, as well as side effects and tolerability. These effects may be dose dependent and, in this study, we examine the pharmacokinetics of sodium monofluorophosphate (MFP) in osteoporotic patients and relate this to changes in BMD. Plasma fluoride absorption curves were measured from 0 to 6 h after ingestion of MFP at baseline and during long-term dosing in 21 patients with vertebral osteoporosis (T scores < or = 2). BMD was measured at baseline and at 12 months at the lumbar spine (LS), femoral neck (FN), trochanter, and Ward's triangle. We found that fluoride elimination was inversely related to creatinine clearance. LS BMD increased from a median of 0.77 g/cm2 (range 0.69 to 0.99) at baseline to 0.88 g/cm2 (0.75 to 1.13) (p < 0.001) after 12 months. This equates to a median increase of 12% (range -1.2 to 37). Median femoral neck BMD decreased from 0.75 g/cm2 (0.62 to 0.94) at baseline to 0.69 g/cm2 (0.62 to 0.92) (p = 0.13) after 12 months. This equates to a decrease of -2% (-19 to 10). BMD at the other hip sites also decreased slightly. Changes in LS and FN BMD were not significantly related (r = 0.28, p = 0.29). The various pharmacokinetic parameters measured were not related to changes in LS BMD; however, there was an inverse relationship between trough fluoride concentration during long-term dosing and change in FN BMD. Further studies are required to see if this relationship can be used to monitor osteoporotic patients treated with fluoride and prevent significant decreases in FN BMD and possibly fractures at this site.

Adult↗
PubMed1996

BRCA2 mutations in primary breast and ovarian cancers.

The second hereditary breast cancer gene, BRCA2, was recently isolated. Germline mutations of this gene predispose carriers to breast cancer, and, to a lesser extent, ovarian cancer. Loss of heterozygosity (LOH) at the BRCA2 locus has been observed in 30-40% of sporadic breast and ovarian tumours, implying that BRCA2 may act as a tumour suppressor gene in a proportion of sporadic cases. To define the role of BRCA2 in sporadic breast and ovarian cancer, we screened the entire gene for mutations using a combination of techniques in 70 primary breast carcinomas and in 55 primary epithelial ovarian carcinomas. Our analysis revealed alterations in 2/70 breast tumours and none of the ovarian carcinomas. One alteration found in the breast cancers was a 2-basepair (bp) deletion (4710delAG) which was subsequently shown to be a germline mutation, the other was a somatic missense mutation (Asp3095Glu) of unknown significance. Our results suggest that BRCA2 is a very infrequent target for somatic inactivation in breast and ovarian carcinomas, similar to the results obtained for BRCA1.

Aged↗
PubMed1996

Ochratoxin A in wheat: a second intercomparison of procedures.

The European Commission, Measurements and Testing Programme (BCR) has undertaken a project to improve methodology and to prepare certified reference materials for ochratoxin A determination. The first phase of this project, an intercomparison of procedures for the determination of ochratoxin A in wheat, at a content of approximately 13 micrograms/kg, has already been reported. The second intercomparison study, described in this paper, involved 26 European laboratories, from 11 countries, which analysed wheat naturally contaminated at a level of approximately 7 micrograms/kg, and a 'blank' wheat sample (ochratoxin A content < 0.2 microgram/kg). The participants used a variety of procedures which involved different extraction solvents and clean-up procedures. All laboratories used HPLC as the determinative step. Some laboratories also used immunoaffinity column clean-up in comparison with their normal method. Recoveries of the normal methods used by laboratories ranged from 58 to 114%; only three laboratories obtained recoveries outside the accepted range of 70 to 110%. Recoveries of the immunoaffinity column methods, using two sources of column, ranged from 58 to 114% for one and from 4 to 86% for the other. The between-laboratory reproducibility coefficient of variation for all results was 34% for the normal methods, and 34 and 42% for the two types of immunoaffinity columns. It was noted that, after the results were corrected for spike recovery, some laboratories became outliers owing to low spike recoveries. Further investigations of the spiking protocols used by each laboratory showed that the time left for evaporation of the spiking solvent was crucial to the recovery obtained.

Chromatography, High Pressure Liquid↗
PubMed1996

Survey of ethnic foods for mycotoxins.

A survey has been carried out in the UK to determine the levels of mycotoxins in a range of ethnic foods. The survey involved analysis of 121 samples of ethnic foods, purchased from specialist shops, for aflatoxins, ochratoxin A and the Fusarium mycotoxins (fumonisins, zearalenone and trichothecenes). The samples were of cereal and cereal product, fats and oils, nuts and nut products, seeds, spices and herbs, pickles, sauces and a variety of canned vegetable and/or pickle products. Low concentrations of mycotoxins were present in many samples analysed. The types and levels of mycotoxins present varied with the type of sample. The most common contaminants were the trichothecenes and ochratoxin A. Trace levels of aflatoxins, ochratoxin A, zearalenone, fumonisins and trichothecenes were detected in samples containing cereal, such as rice, noodles, corn flour and pitta bread. Trace levels of aflatoxins and zearalenone were detected in a sample of chili oil and ochratoxin A in a sample of sesame oil. Only one sample of nut (almond) contained aflatoxin while aflatoxins, ochratoxin A, zearalenone and deoxynivalenol (a trichothecene) were detected in various seeds. Aflatoxins, ochratoxin A and fumonisins were found in chili paste and zearalenone and ochratoxin A in curry pastes. The highest mycotoxin levels and frequency of occurrence were in chili powder, curry powder and ginger.

Chromatography, High Pressure Liquid↗
PubMed1996

The effect of bupivacaine skull block on the hemodynamic response to craniotomy.

The placement of pointed cranial pins into the periosteum is a recognized acute noxious stimulation during intracranial surgery which can result in sudden increases in blood pressure and heart rate, causing increases in intracranial pressure. A skull block (blockade of the nerves that innervate the scalp, including the greater and lesser occipital nerves, the supraorbital and supratrochlear nerves, the auriculotemporal nerves, and the greater auricular nerves) may be effective in reducing hypertension and tachycardia. Twenty-one patients were allocated in a prospective, double-blind fashion to a control group or a bupivacaine group. After a standardized induction and 5 min prior to head pinning, a skull block was performed. Patients in the control group received a skull block of normal saline, while the bupivacaine group received a skull block with 0.5% bupivacaine. Systolic (SAP), diastolic (DAP), mean arterial pressure (MAP), heart rate (HR), and end-tidal isoflurane were recorded at the following times: 5 min after the induction of anesthesia, during performance of the skull block, during head pinning, and 5 min after head pinning. Significant increases in SAP of 40 +/- 6 mm Hg, DAP of 30 +/- 5 mm Hg, MAP of 32 +/- 6 mm Hg, and HR of 22 +/- 5 bpm occurred during head pinning in the control group, while remaining unchanged in the bupivacaine group. These results demonstrate that a skull block using 0.5% bupivacaine successfully blunts the hemodynamic response to head pinning.

Adolescent↗
PubMed1996

Hydration (water binding) of the mammalian corneal stroma ex vivo and vitro: sample mass and error considerations.

The corneal stroma is well-known for its capacity to absorb water from experimental solutions but there are considerable differences in how this is actually assessed and described. Measurements on rabbit, sheep, and cow samples ex vivo are presented along with examples of the progressive changes in the stroma in vitro in saline solutions. These are used as the basis for theoretically assessing the impact of systematic and unintentional errors (related to excesses of water or water vapor on the samples) on the estimates of water content, as are the effects of unintentional loss of water from wet samples. Substantial differences in data can easily arise from such errors and/or differences in sample mass. Standardization of the methods for stromal hydration and swelling is required. As a minimum, sample origin (including species), sample dimensions and mass, and the resolution of the weighing protocols are needed, along with details of dry and wet sample handling. With the likelihood of modest errors for the commonly used samples and procedures, reporting hydration data to more than one decimal place is not justified.

Animals↗
PubMed1996

Tazarotene-induced gene 1 (TIG1), a novel retinoic acid receptor-responsive gene in skin.

Retinoids exert their effect through ligand-dependent transcription factors, retinoic acid receptors (RARalpha, beta, and gamma) and retinoid X receptor (RXRalpha, beta, and gamma), which belong to the superfamily of steroid/thyroid/vitamin D3, nuclear receptors. Using a subtraction hybridization approach, we have identified a cDNA sequence, Tazarotene Induced Gene 1 (TIG1), which is highly upregulated in skin raft cultures by an RARbeta/gamma -selective retinoid AGN 190168 (tazarotene/ethyl 6-[2-(4,4-dimethylthiochroman-6-yl)-ethynyl]nicotinate), which is effective in the treatment of psoriasis. The retinoid-mediated upregulation in the expression of TIG1 was confirmed by Southern and Northern analyses. Upon sequencing, TIG1 was found to be a novel cDNA which encodes a protein of 228 amino acids whose sequence suggests that is a transmembrane protein with a small N-terminal intracellular region, a single membrane-spanning hydrophobic region, and a large C-terminal extracellular region containing a glycosylation signal. We demonstrate that TIG1 is also upregulated by AGN 190168 in skin raft cultures prepared from psoriatic fibroblasts and normal keratinocytes and in primary fibroblast and keratinocyte cultures. We also show that TIG1 is upregulated by retinoic acid receptor but not by retinoid X receptor-specific synthetic retinoids. Finally, we demonstrate that TIG1 is induced by AGN 190168 in psoriatic lesions during the course of clinical treatment of the disease.

Amino Acid Sequence↗
PubMed1996

Antagonism of the effects of (+)-PD 128907 on midbrain dopamine neurones in rat brain slices by a selective D2 receptor antagonist L-741,626.

1. The ability of PD 128907 to activate dopamine receptors in the ventral tegmental area, substantia nigra pars compacta, and striatum was investigated by use of in vitro electrophysiological recording and fast cyclic voltammetry. The affinity of a novel D2 selective antagonist L-741,626 for receptors activated by this agonist was measured to determine if its effects were mediated by D2 or D3 receptors. 2. The active (+) enantiomer of PD 128907 bound with high affinity and selectivity to rat D3 dopamine receptors. The Ki values for (+)-PD 128907 were 620 nM at D2, 1 nM at D3 and 720 nM at D4 receptors. 3. (+)-PD 128907 inhibited cell firing in both the ventral tegmental area and substantia nigra pars compacta with EC50 values of 33 nM (pEC50 = 7.48 +/- 0.10, n = 10) and 38 nM (pEC50 = 7.42 +/- 0.15, n = 5), respectively. No effects of (+)-PD 128907 (100 nM) were observed on glutamate or GABA-mediated synaptic potentials elicited by focal bipolar stimulation. 4. L-741,626 antagonized these effects of (+)-PD 128907 in a concentration-dependent and surmountable manner with an affinity, determined from Schild analysis, of 20 nM (pKB = 7.71 +/- 0.14) in the ventral tegmental area and 11 nM (pKB = 7.95 +/- 0.18) in the substantia nigra pars compacta. 5. (+)-PD 128907 also inhibited dopamine release in the caudate-putamen with an EC50 of 66 nM (n = 5). The affinity of L-741,626 for these nerve terminal autoreceptors (pKB = 7.71 +/- 0.06; = 20 nM) was identical to that observed on midbrain dopamine neurones. 6. These data demonstrate that the D3 receptor ligand (+)-PD 128907 is a potent agonist on rat midbrain dopamine neurones. However, its lack of regional selectivity, and the high affinity of the selective D2 receptor antagonist L-741,626 for receptors activated by (+)-PD 128907, was more consistent with an action on D2 autoreceptors rather than upon a D3 dopamine receptor subtype.

Animals↗
PubMed1996

The purification and characterization of biological 6-sulphatoxymelatonin and comparison with synthetic 6-sulphatoxymelatonin.

We have purified the major metabolite of melatonin, 6-sulphatoxymelatonin, from urine and compared it to its synthetic counterpart. For preparation of the biological material, oral melatonin was administered to human volunteers and their urine extracted onto Amberlite XAD-2 resin to remove urea; the glucuronide metabolites of melatonin were removed by silica chromatography; and 6-sulphatoxymelatonin was separated from N-acetyl serotonin sulphate, the other sulphate metabolite of melatonin, by preparative thin-layer chromatography. Synthetic 6-sulphatoxymelatonin was produced by reacting 6-hydroxymelatonin with chlorosulphonic acid in dimethylformamide; the reaction mixture was purified on Florisil and preparative thin-layer chromatography was used to remove indolic by-products of the reaction. Elemental and X-ray microanalysis of the biological and synthetic products showed that classical methods used for their purification introduced inorganic impurities, such as silicon- and chlorine-containing compounds, which were not detectable by thin-layer chromatography, infrared spectroscopy, nuclear magnetic resonance spectroscopy, or gas chromatography-mass spectrometry. We introduced further purification steps to remove these inorganic impurities, monitoring the process using elemental and X-ray microanalysis. Extensive characterization of the resulting purified products showed that the biological and synthetic compounds were identical.

Chromatography, Gel↗
PubMed1996

Heminested inverse PCR for IS6110 fingerprinting of Mycobacterium tuberculosis strains.

A heminested inverse PCR (HIP) for the amplification of sequences flanking the Mycobacterium tuberculosis insertion sequence IS6110 has been developed. The method depends upon primers that anneal to IS6110 at sites between its 5' end and the closest BsrFI site. The accuracy of HIP was demonstrated by the amplification of sequences within plasmid constructs carrying one or two copies of the insertion sequence IS986 in different orientations. The identities of the amplicons produced from strains carrying a single copy of IS6110 were verified by nucleotide sequencing. Analyses of 204 M. tuberculosis strains including those involved in outbreaks showed that IS6110 HIP is highly discriminatory and reproducible. HIP fingerprinting of these 204 strains generated 136 distinct types, and its discriminatory power was equivalent to that of standard restriction fragment length polymorphism analysis. The method is therefore of value for the rapid fingerprinting of M. tuberculosis strains for epidemiological purposes.

Base Sequence↗
PubMed1996

Current and potential future drug treatments for osteoporosis.

There has been a major interest in the drug treatment of osteoporosis and an increase in the number of drugs available in most countries. The ideal drug (one which increases or restores bone density and trabecular connectivity) is still not available. However, in patients with relatively preserved trabecular connectivity and moderately reduced bone density, several agents have shown substantial clinical benefit. Oestrogens are still the mainstay of drug treatment, but the risks of breast cancer versus the cardiovascular and skeletal benefits with long term use have to be assessed in the individual. Newer tissue specific oestrogens show some promise in this respect. The bisphosphonates and possibly fluoride are likely to be the major alternatives to oestrogens in the medium term. The newer bisphosphonates, alendronate and in the future risedronate, are likely to supersede etidronate. Calcitriol probably has a limited role, confined to those patients in whom HRT or bisphosphonates are not appropriate. Calcium supplementation, or an increase in dietary intake if deficient, irrespective of which agent is used, is also of benefit. In older patients there is considerable support for using a combination of calcium and vitamin D. Whether combination treatment, for example oestrogens, bisphosphonates, and calcium together, will result in greater efficacy remains to be conclusively shown, but may be an attractive option in younger patients with higher bone turnover. Apart from fluoride, bone formation stimulators are unlikely to have a major role until the next century, although it may be possible to use growth factors as part of an ADFR regimen (A = activate remodelling, D = depress resorption, F = free formation, and R = repeat). This is still an important theoretical approach and needs further work with newer agents to see if increased efficacy can be found. In addition sequential treatment may be necessary in view of the limited time periods over which particular agents, such as intermittent fluoride (four years), have been examined, and this will have to be individually tailored. Other approaches include trying to increase peak bone mineral density, although influencing the young to prevent a disease that may not manifest itself for half a century is daunting.

Aged↗
PubMed1996

Gene deletions in spinal muscular atrophy.

Two candidate genes (NAIP and SMN) have recently been reported for childhood onset spinal muscular atrophy (SMA). Although affected subjects show deletions of these genes, these deletions can lead to either a very mild or a severe phenotype. We have analysed a large number of clinically well defined patients, carriers, and normal controls to assess the frequency and extent of deletions encompassing both of these genes. A genotype analysis indicates that more extensive deletions are seen in the severe form of SMA than in the milder forms. In addition, 1 center dot 9% of phenotypically normal carriers are deleted for the NAIP gene; no carriers were deleted for the SMN gene. Our data suggest that deletions in both of these genes, using the currently available assays, are associated with both a severe and very mild phenotype.

Chromosomes, Human, Pair 5↗
PubMed1996

Evolution of photochemically induced focal cerebral ischemia in the rat. Magnetic resonance imaging and histology.

BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) is increasingly used to study the pathophysiological evolution of cerebral ischemia in humans and animals. We have investigated photochemically induced (rose bengal) focal cerebral ischemia, a relatively noninvasive, reproducible model for stroke, and compared the evolution of the ischemic response in vivo and postmortem with MRI and histology, respectively. METHODS: MR images weighted for T2, diffusion, and T2* and parallel histological sections stained with cresyl fast violet (CFV) and for glial fibrillary acid protein were obtained from 34 adult male Hooded Lister rats at seven time points (3.75 to 196 hours) after bilateral ischemia induction. From CFV histology, lesion volumes and cell counts were calculated; from diffusion-weighted and T2-weighted images, apparent diffusion coefficients and lesion volumes were determined. RESULTS: Both MRI and histology revealed a well-defined lesion at 3.75 hours after irradiation and a consistent pattern of temporal evolution; lesion apparent diffusion coefficients decreased significantly by 3.75 hours, increased significantly by day 2, and correlated strikingly with the decline in lesion CFV-positive cell numbers. After day 2, astrocytes and connective tissue cells invaded the infarct. Throughout the time course, lesion volumes determined in vivo and postmortem (after shrinkage correction) agreed well. CONCLUSIONS: MRI changes quantitatively reflect histopathology, revealing reproducible primary and secondary damage characteristics noninvasively. These changes essentially replicate those reported for other animal stroke models and clinically, emphasizing the value both of MRI and the photochemically induced focal cerebral ischemia model in stroke research.

Animals↗
PubMed1996

Favourable outcome of scleroderma renal crisis.

Severe hypertension and rapidly progressive acute renal failure is a well recognized complication of scleroderma, often referred to as the renal crisis, and widely thought to cause irreversible deterioration in renal function. With the advent of angiotensin-converting-enzyme inhibitors (ACE-I) the outlook for patients with this condition has dramatically improved. We report here one such patient.

Acute Kidney Injury↗