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Biomedical subjects

N Patel

Publications and source records attributed to N Patel.

At least 253 records · Page 14Linked to original sources

Estimation of the correct length of tracheal tubes in adults.

Estimation of the correct length of a tracheal tube is extremely important and should be tailored to the needs of the individual patient. One hundred and eight patients who required tracheal intubation during anaesthesia were studied. The predicted length was estimated in each patient before induction of anaesthesia. The upper end of the cuff was aligned externally with the cricoid cartilage, while the more proximal part of the tube lay alongside the neck to the angle of the mandible. The tube was then curved forwards towards the upper incisor teeth, and the length at the teeth or gums was noted. The anaesthetist, who was unaware of the predicted length, intubated the trachea after induction of anaesthesia. The length of tube inserted was standardised in relation to the vocal cords, and the actual length of tube inserted was recorded. The estimated length was within 1.0 cm and 1.5 cm of the actual length in 91% and 97% of patients respectively.

Adolescent↗

An audit of the obstetric outcome of 148 consecutive pregnancies from assisted conception: implications for neonatal services.

OBJECTIVE: To assess the outcome of pregnancy following assisted conception. DESIGN: Cohort descriptive study. SETTING: Unit of Reproductive Medicine, Ninewells Hospital and Medical School. SUBJECTS: One hundred and forty-eight consecutive assisted conceptions. MAIN OUTCOME MEASURES: Patient characteristics and outcome of pregnancy. RESULTS: Seventy-nine percent of mothers were aged between 26 and 35 years (mean 31.4). The main causes of infertility were tubal (48%), unexplained (35%), anovulatory (8%) and male factor (8%). Primary infertility accounted for 61% of cases and 82% of pregnancies occurred within 3 treatment cycles. Thirty-five (24%) pregnancies miscarried before 14 weeks and 7 (5%) between 15 and 24 weeks gestation. One hundred and three pregnancies resulted in 136 liveborn infants. There was one neonatal death. Thirty-five babies were admitted to SCBU. Antenatally, 13% of patients were admitted to hospital with hypertension and 8% with APH; 50% of multiple and 13% of singleton pregnancies were delivered prematurely, 68% following preterm labour. There were 28 sets of twins (four miscarried at less than 24 weeks) and four sets of triplets. Multiple pregnancy was not associated with cause of infertility, treatment, age or ovarian hyperstimulation syndrome. Seventy-eight per cent of singletons and 50% of multipara were delivered vaginally. CONCLUSIONS: Our data confirm the high incidence of pregnancy loss and preterm delivery associated with assisted conception once allowing for the high rate of multiple pregnancies. The effect of assisted conception programme on health services is discussed.

Abortion, Spontaneous↗

Comparative effects of lithium on the phosphoinositide cycle in rat cerebral cortex, hippocampus, and striatum.

The effects of lithium on muscarinic cholinoceptor-stimulated phosphoinositide turnover have been investigated in rat hippocampal, striatal, and cerebral cortical slices using [3H]inositol or [3H]cytidine prelabelling and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] mass determination methods. Carbachol addition resulted in maintained increases in Ins(1,4,5)P3 and Ins(1,3,4,5)P4 mass levels in hippocampus and cerebral cortex, whereas in striatal slices these responses declined significantly over a 30-min incubation period. Carbachol-stimulated Ins(1,4,5)P3 and Ins(1,3,4,5)P4 accumulations were inhibited by lithium in all brain regions studied in a time- and concentration-dependent manner. For example, in hippocampal slices significant inhibitory effects of LiCl were observed at times > 10 min after agonist challenge; IC50 values for inhibition of agonist-stimulated Ins(1,4,5)P3 and Ins(1,3,4,5)P4 accumulations by lithium were 0.22 +/- 0.09 and 0.33 +/- 0.13 mM, respectively. [3H]CMP-phosphatidate accumulation increased in all brain regions when slices were stimulated by agonist and lithium. The ability of myo-inositol to reverse these effects, as well as lithium-suppressed Ins(1,4,5)P3 accumulation, implicates myo-inositol depletion in the action of lithium in the hippocampus and cortex at least. The results of this study suggest that although significant differences in the magnitude and time courses of changes in inositol (poly)phosphate metabolites occur in different brain regions, lithium evokes qualitatively similar enhancements of [3H]inositol monophosphate and [3H]-CMP-phosphatidate levels and inhibitions of Ins(1,4,5)P3 and Ins(1,3,4,5)P4 accumulations. However, the inability of striatal slices to sustain carbachol-stimulated inositol polyphosphate accumulation in the absence of lithium and the inability to reverse effects with myo-inositol may indicate differences in phosphoinositide signalling in this brain region.

Animals↗

Effect of aging on retinal macular microcirculation: a blue field simulation study.

PURPOSE: Structural changes in the retina are known to occur with aging. This study was performed to investigate whether aging also affects the retinal macular microcirculation. METHODS: Healthy volunteers with ages ranging from 20 to 78 years (mean +/- SD, 49 +/- 19 years) were included in this study. The retinal macular microcirculation was assessed with the blue field simulation technique, based on the blue field entoptic phenomenon. Subjects were asked to match the velocity and density of computer-simulated particles displayed on a screen with those of their entoptically observed leukocytes. Ten matching trials were performed, and an average leukocyte velocity and density were calculated. RESULTS: Significant negative linear correlations were observed between velocity and age (P = 0.0001) and density and age (P = 0.009). Older subjects (50 to 78 years of age) had a significantly slower velocity (0.61 +/- 0.21 mm/s) and smaller density (90 +/- 43 particles per field of view) than younger subjects (0.92 +/- 0.12 mm/s and 135 +/- 65 particles, respectively; unpaired Student's t-test, P = 0.001 and P = 0.01, respectively). CONCLUSIONS: These results suggest that, in normal subjects, retinal macular blood flow decreases with age. The 20% decrease in average velocity with age is very similar to the age-related decrease in number of cells observed in the human foveal ganglion cell layer.

Adult↗

Fasting hyperglycemia in type I diabetes mellitus.

The differential diagnosis of fasting hyperglycemia in type I diabetes includes the Somogyi effect, the dawn phenomenon, and insufficient insulin administration. To determine the causes of fasting hyperglycemia and their effect on subsequent daytime blood glucose control, the authors retrospectively reviewed blood glucose profiles of 126 patients with type I diabetes. The Somogyi effect accounted for 12.6% of all instances of fasting hyperglycemia, the dawn phenomenon, 24.1%, and poor control, 63.3%. Measurement of 3 AM and 5 AM blood glucose values is the key to making a correct diagnosis. Once a patient's fasting hyperglycemia is placed in one of these groups, appropriate treatment can be started.

Adult↗

Effect of diltiazem on lid tension during light-flash-induced eye blinks in the rabbit.

PURPOSE: The purpose of this study was to examine the effect of the Ca blocker diltiazem in combination with the Ca chelator EGTA (ethyleneglycol-bis-ta-amino-ethyl ether]N,N'-tetraacetic acid) on eyelid tension generated during the light-induced eyeblink reflex in the adult rabbit. The goal is to develop nontoxic, nonsurgical therapies for blepharospasm. METHODS: Blinks were triggered in the alert rabbit, and tension was measured with a strain gauge attached to the eyelid. Strain gauge output was amplified, digitized, and stored on computer for later analysis. Experiments consisted of a set of trials in which identical light stimuli were delivered at 0.1 Hz for 5 min. RESULTS: In control trials, blink tensions decreased dramatically for the first seven to nine blinks and then levelled off, indicating that with respect to muscle tension output, blinks contained both rapidly habituating and nonhabituating components. After diltiazem and EGTA were injected in the lid, blinks were reduced 30% to 90% over those in control trials. Reductions could not be explained by injection trauma or irritation due to fluid volume, because injections of saline alone did not produce such tension depression. CONCLUSIONS: Diltiazem-EGTA produces a transient reduction in blink tension. A clinical application will depend on developing methods for the sustained release of these drugs in the eyelid.

Animals↗

Thermodynamics of interaction of a fluorescent DNA oligomer with the anti-tumour drug netropsin.

Fluorescence spectroscopy was used to study the interaction between the minor-groove-binding drug netropsin and the self-complementary oligonucleotide d(CTGAnPTTCAG)2 containing the fluorescent base analogue 2-aminopurine (nP). The binding of netropsin to this oligonucleotide causes strong quenching of the 2-aminopurine fluorescence, observed by steady-state as well as time-resolved spectroscopy. From fluorescence titrations, binding isotherms were recorded and evaluated. The parameters showed one netropsin binding site/oligonucleotide duplex and an association constant of about 10(5) M-1 at 25 degrees C, 3-4 orders of magnitude weaker than for an exclusive adenine/thymine host sequence. From the temperature dependence of the association constant the thermodynamic parameters were obtained as delta G = -29 kJ/mol, delta H = -12 kJ/mol and delta S = +55 J.mol-1.K-1 at 25 degrees C. These parameters resemble those of the interaction of poly[(dG-dC).(dG-dC)] with netropsin, indicating a mainly entropy-driven reaction. The amino group of 2-aminopurine, like that of guanine, resides in the minor groove of DNA. Therefore the relatively weak binding of netropsin to d(CTGAnPTTCAG)2 is probably related to partial blockage of the tight fit of netropsin into the preferred minor groove of an exclusive adenine/thymine host sequence.

2-Aminopurine↗

Excitotoxin induction of ornithine decarboxylase in cerebral cortex is reduced by phospholipase A2 inhibition.

The enzyme ornithine decarboxylase (ODC) has been shown to be induced by a number of conditions such as cold-injury, kindling, ischaemia and excitotoxin injection. In previous studies we have characterised the cortical response to kainate injection into the nucleus basalis and shown a substantial increase in both ODC mRNA and enzyme activity which reaches a maximum at 8h. This response is completely prevented by treatment with MK-801, indicating the involvement of NMDA receptors in mediating this response. Whilst NMDA receptors are known to gate a cation channel leading to increased calcium entry, an additional effect on the release of arachidonic acid has been reported. The possibility that NMDA receptor mediated activation of phospholipase A2 and release of arachidonic acid might mediate this ODC response was investigated in this study by treatment with the phospholipase inhibitors quinacrine and dexamethasone. Treatment of animals with quinacrine (100 mg/kg) at the time of injection of kainate into the nucleus basalis caused a significant attenuation of the induction of ODC in cerebral cortex of 43%. No further attenuation was seen at higher doses. A similar reduction in ODC induction was seen after treatment with dexamethasone (1 mg/kg) but a greater effect could be obtained (65% attenuation) at higher doses. The possible involvement of arachidonic acid derivatives in mediating ODC induction was further investigated by treatment with the cyclo-oxygenase inhibitor indomethacin and the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA). Indomethacin was able to significantly attenuate the induction of ODC (greater than 60%) whilst NDGA (30 mg/kg) was ineffective. These results indicate the possible role of arachidonic acid derivatives in the regulation of the expression of ODC in cerebral cortex after excitotoxin injection.

Animals↗

Explanation at the opioid receptor level for differing toxicity of morphine and morphine 6-glucuronide.

The radiolabelled opioid receptor binding affinities of morphine and its active metabolite morphine 6-glucuronide at the total mu, mu 1, mu 2 and delta receptors were determined. Morphine 6-glucuronide was found to have a 4-fold lower affinity for the mu 2 receptor (IC50 17 nM and 82 nM for morphine and morphine 6-glucuronide respectively, P = 0.01), the receptor postulated to be responsible for mediating the respiratory depression and gastrointestinal effects after morphine. This provides a possible explanation for the reduced respiratory depression and vomiting seen following morphine 6-glucuronide in man. A similar reduction in affinity of morphine 6-glucuronide was seen at the total mu receptor whilst there was no significant difference seen at the mu 1 or delta receptor. Hence the increased analgesic potency of morphine 6-glucuronide over morphine remains unexplained.

Animals↗

High-resolution bone scintigraphy of the adult wrist.

Bony anatomic landmarks of the wrist (e.g., pisiform, hook of hamate, radioulnar joint, and styloid processes of the radius and ulna) were routinely identified in 28 adult patients examined for wrist pain. With the wrists prone and immobilized, bone scintigrams were obtained for 500,000 counts with an asymmetric (133 to 161 keV) Tc-99m energy window and either a converging (best choice) or straight-bore, high-resolution collimator. High-resolution scintigraphy precisely localized degenerative joint disease (nine patients), scaphoid fractures (five), pisiform fracture (one), lunate avascular necrosis (one), radioulnar arthritis (one), septic or inflammatory arthritis (six), ulnocarpal impingement (two), and reflex sympathetic dystrophy syndrome (two). Images obtained palm down with the wrist in ulnar deviation helped identify increased uptake within the scaphoid. Fracture and significant bone or joint disease were excluded in one patient.

Adult↗

Night-time or morning dosing with H2-receptor antagonists: studies on acid inhibition in normal subjects.

H2-receptor antagonists are conventionally given at night. However, it remains unproven whether this regimen affords superior acid inhibition or healing rates for patients with duodenal ulcers compared to morning dosing. We have therefore examined the acid inhibitory effect of 300 mg ranitidine at night compared to 300 mg ranitidine in the morning in 8 normal male subjects. Intragastric acidity was measured by the radiotelemetry method and acid inhibition calculated from the percentage decrease in the area under the curve for hydrogen ion activity against time. Night-time ranitidine resulted in a significantly better (P less than 0.02) decrease of intragastric acidity than the same dose given in the morning (66.8 (61.8-77.6)% vs. 34 (15.5-49.1)%). This difference was found to be due to the fact that morning ranitidine inhibited gastric acid secretion when the intragastric acidity was already buffered by food. These data support the superiority of nocturnal dosing with H2-antagonists.

Adult↗

The analgesic activity of morphine-6-glucuronide.

1. The pharmacokinetics, cardio-respiratory effects and analgesic effects of intravenous morphine-6-glucuronide were studied in 20 cancer patients with pain. Four different dose levels (0.5, 1, 2, and 4 mg 70 kg-1) were studied. Plasma concentrations of morphine-6-glucuronide were measured for 12 h after dosing. Pulse rate, respiratory rate and blood pressure were monitored, and pain relief was measured using two rating scales and a visual analogue scale. 2. The mean elimination half-life (+/- s.d.) of morphine-6-glucuronide was 3.2 +/- 1.6 h. The mean AUC standardised to a dose of 1 mg 70 kg-1 was 390 +/- 263 nmol l-1 h. Mean morphine-6-glucuronide clearance was 96 +/- 38 ml min-1. There was a direct relationship between morphine-6-glucuronide plasma clearance and calculated creatinine clearance (r = 0.81, P less than 0.001). 38 +/- 22% of the dose of morphine-6-glucuronide was recovered unchanged in the urine in 24 h. No morphine or morphine-3-glucuronide was detected in the plasma or urine of any patient after morphine-6-glucuronide treatment. 3. Morphine-6-glucuronide exerted a useful analgesic effect in 17/19 assessable patients for periods ranging between 2 and 24 h. No correlation was observed between dose or plasma morphine-6-glucuronide concentrations, and duration or degree of analgesia. No clinically significant changes in cardio-respiratory parameters were observed. No patients reported sedation or euphoria. Nausea and vomiting were notably absent in all cases. 4. Morphine-6-glucuronide is an effective and well-tolerated analgesic. It is likely that the majority of the therapeutic benefit of morphine is mediated by morphine-6-glucuronide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Comparative effects of BRL 38227, nitrendipine and isoprenaline on carbachol- and histamine-stimulated phosphoinositide metabolism in airway smooth muscle.

1. The ability of BRL 38227 and nitrendipine to affect muscarinic agonist and histamine-stimulated [3H]-inositol phosphate accumulation in slices of bovine tracheal smooth muscle has been studied and compared with the established inhibitory effects of isoprenaline on this pathway. 2. Pre-addition of BRL 38227 (5 microM), nitrendipine (1 microM) or isoprenaline (10 microM) significantly inhibited the subsequent inositol phosphate response to histamine at all concentrations studied (10- 1000 microM). BRL 38227 and nitrendipine also significantly inhibited the [3H]-inositol phosphate response to low (1 microM), but not high (100 microM) concentrations of carbachol. Isoprenaline had no effect at any concentration of carbachol studied. 3. Nitrendipine (IC50 = 95 nM) and BRL 38227 (IC50 = 322 nM) caused concentration-related inhibitions of the inositol phosphate response to histamine (100 microM). Similar maximal inhibitions were caused by each agent (55-58%). Inhibitory effect of BRL 38227 was reduced in potency (IC50 = 5.5 microM), but not magnitude, in the presence of glibenclamide (0.5 microM). 4. Time-course studies comparing the effects of BRL 38227 addition 15 min before, and 10 min after histamine challenge showed that for pre-addition a distinct (less than 2 min) lag occurred following histamine addition before the inhibitory effect of BRL 38227 was manifest. In contrast, when BRL 38227 was added 10 min after histamine, an inhibitory effect was immediately apparent. 5. Further evidence for an initial, 'protected' phase of inositol phosphate accumulation was provided by the finding that BRL 38227 pre-addition had no effect on the early (0-300 s) time-course of inositol 1,4,5-trisphosphate mass accumulation. 6. The inhibitory effect of BRL 38227, but not that of nitrendipine or isoprenaline, on histaminestimulated [3H]-inositol phosphate accumulation was completely prevented in the presence of an elevated extracellular K+ (65 mM) concentration. 7. The results demonstrate that membrane hyperpolarization, and/or blockade of voltage-operated Ca2"-channels can regulate agonist-stimulated phosphoinositide metabolism in airway smooth muscle. The possible contribution of this regulatory mechanism to the relaxant properties of these agents is discussed.

Animals↗

Morphine 6-glucuronide: a metabolite of morphine with greater emetic potency than morphine in the ferret.

1. The emetic potencies of morphine and its metabolite morphine 6-glucuronide have been determined in the ferret by constructing dose-response curves for mean total retches and vomits for subcutaneous doses of 0.05 mg kg-1 to 5 mg kg-1. Morphine 6-glucuronide induced retching and vomiting at lower doses than morphine and at a maximal dose induced more retching and vomiting than morphine. 2. The emesis induced by both morphine and morphine 6-glucuronide was abolished by the preadministration of naloxone (0.5 mg kg-1 s.c.). 3. The 5-HT3 receptor antagonists granisetron and ondansetron (1 mg kg-1, s.c.) failed to abolish or reduce emesis induced by either compound. 4. At a high-dose (5 mg kg-1), morphine but not morphine 6-glucuronide failed to induce emesis and abolished the emesis induced by the cytotoxic drug, cyclophosphamide (200 mg kg-1, i.p.). 5. Preliminary pharmacokinetic studies of intravenous and subcutaneous morphine and morphine 6-glucuronide revealed that morphine 6-glucuronide accounts for less than 1% of the metabolic product of morphine in the ferret. Peak plasma levels of the two compounds after their subcutaneous administration were obtained within 10 min. The metabolic profile of morphine was not dose-dependent. There was no relationship between plasma level and emetic response for either compound.

Animals↗