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Biomedical subjects

N Patel

Publications and source records attributed to N Patel.

At least 217 records · Page 12Linked to original sources

Long-term patient self-management of oral anticoagulation.

BACKGROUND: The management of oral anticoagulation is fraught with difficulties. This study assessed a new model of anticoagulation management regarding the ability, safety, and efficacy of patients to self-monitor and self-adjust the dose of their oral anticoagulants guided by a capillary whole-blood prothrombin time (PT) monitor. METHODS: This investigation is a retrospective cohort study of 20 patients compared with 20 matched control patients receiving oral anticoagulation at a tertiary medical institution. RESULTS: Study patients monitored their PTs 2153 times during a mean interval of 44.7 months compared with 1608 PTs in matched control patients during a mean interval of 42.5 months. Study patients made an average of 11.5 dosage changes per patient, contrasted with 22.7 changes per control patient (P < .001). The PTs in study patients were within the recommended therapeutic range in 88.6% (95% confidence interval, 87.2 to 89.9) of the determinations compared with 68.0% (95% confidence interval, 65.7 to 70.3; P < .001) of the determinations made by the matched control patients. In response to the 2153 PTs, study patients made 67 (3.1%) dosage decisions that were considered incorrect based on physician guidelines. None of these changes led to adverse outcomes. There was no significant difference in complication rates between the two groups. CONCLUSIONS: Results from what is the first long-term study of patient self-monitoring of PTs and self-adjustment of the warfarin sodium dosage for oral anticoagulation suggest that patients can successfully measure their own PTs, adjust their own warfarin dosage, and achieve a degree of therapeutic effectiveness at least as good, if not better than patients managed in an anti-coagulation clinic. Larger, prospective, randomized trials are needed to confirm the efficacy and safety of this new approach to therapy and to assess its cost-effectiveness.

Administration, Oral↗

Maze learning in aged rats is enhanced by phenserine, a novel anticholinesterase.

A new generation of cholinesterase inhibitors is expected to overcome some limitations of the therapeutic use of anticholinesterases. Phenserine is a long-acting and selective inhibitor of acetylcholinesterase with a preferential brain uptake. We have assessed the effects of chronic phenserine tartrate treatment on performance of aged Fischer-344 rats in the 14-unit T-maze. Phenserine (1-3 mg kg-1, i.p.) treatment for 5 days significantly reduced the number of errors made in the Stone maze. Other performance variables were also improved. No side effects were noted across 5 days treatment at doses of 1-2 mg kg-1. Phenserine can therefore improve the performance of aged rats in this complex maze task without producing obvious side effects.

Aging↗

Evaluation of different methods of securing intravenous catheters: measurement of forces during simulated accidental pullout.

The purpose of the study was to compare the relative effectiveness of several combinations of tapes and taping methods with respect to the force required to pull out intravenous catheters. A simulated forearm model consisting of a section of firm PVC pipe was used for the first and second series of experiments. In the third experiment, one method of taping catheters was compared in the PVC model and in volunteers. Pullout forces were measured with a force transducer and recorded on paper. In the first experiment, catheters secured with Curity tape resisted pullout to a greater extent than those with Transpore tape and provided approximately twice the force advantage (P < 0.05). In the second experiment using Curity tape, minimum forces to dislodge the catheters were (means +/- SD) 53 +/- 13, 82 +/- 13, 113 +/- 29, 124 +/- 24, 176 +/- 29 and 141 +/- 46 N, for methods 1-6, respectively. In the third series, the minimum pullout forces were higher for Curity than with Transpore tape for both the human and simulated PVC forearm surfaces (63 +/- 11 and 55 +/- 12 N vs 52 +/- 7 and 44 +/- 12 N, P < 0.01), and the pullout forces were higher for the simulated vs. the human skin surface for both tape types (P < 0.01). Compared with Curity tape, Transpore tape was more likely to fail by tape fracture in both the simulated and human skin surfaces (P < 0.05). The data suggest that there are important differences in pullout forces and mechanisms of dislodgement depending on taping method and tape type.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomechanical Phenomena↗

Comparison of fluid warmer performance during simulated clinical conditions.

The study evaluated the warming ability and flow rates associated with four fluid warming devices during pressure driven infusion and during wide open gravity driven roller clamp infusion. Warmers tested were the Astotherm, Flotem IIe, Level 1 System 250 and a modified cardioplegia heat exchanger. Fluids tested were crystalloid, red cells diluted with 200 ml, 0.9% saline, and undiluted red cells. The volume of fluid and outlet temperatures (point where i.v. tubing would be attached to the patient) were measured for each fluid and compared among warmers for each flow rate condition. For pressure driven infusion of red cells and crystalloid, the System 250, and modified heat exchanger delivered warmer fluids (33-35 degrees C) at higher flow rates (160-740 ml.min-1) than the Astotherm and Flotem (23-31 degrees C, 44-268 ml.min-1, P < 0.05). For gravity driven infusion, the System 250 delivered the warmest fluids (33-36 degrees C, P < 0.05) compared with the modified heat exchanger (29-35 degrees C), Astotherm (26-32 degrees C) and Flotem (26-27 degrees C). In conclusion, the modified heat exchanger and System 250 were moderately effective (outlet temperature > 32 degrees C) in warming crystalloid and red cells at pressure driven flow rates. Only the System 250 warmed red cells > 35 degrees C at gravity driven flow rates. The Flotem and Astotherm were not effective in warming rapidly infused solutions. None of the warmers tested was able to deliver fluids at normothermia (> 36.5 degrees C).

Blood↗

The ISG viewing wand: an application to atlanto-axial cervical surgery using the Le Fort I maxillary osteotomy.

Surgical access to the clivus and upper cervical spine may be facilitated by a number of approaches. The Le Fort I maxillary osteotomy has been described to give improved access to the skull base for removal of tumours and treating vertebrobasilar aneurysms. We describe a case in which the combination of a particularly high translocation of the body of C2 and poor mouth opening had precluded a standard transoral approach by restricting access to the operative field. Anterior decompression of the body of C2 was therefore performed via a maxillary down-fracture with the aid of an interactive image guidance system, the ISG Viewing Wand. The ISG Viewing Wand is a new intra-operative 3 dimensional (3D) image guidance system which has now been used in over three hundred neurosurgical cases at Frenchay Hospital, Bristol. We briefly discuss the principles of the viewing wand and describe its unique application providing anatomical navigation in upper cervical spine surgery.

Aged↗

Prevention of preterm birth.

Preterm labour and delivery remain a major cause of perinatal morbidity, mortality and long-term adverse neurodevelopmental outcome. An effective primary prevention strategy is desirable, but current approaches appear largely ineffective at present. Understanding the aetiology of the onset of preterm labour continues to improve with the recognition of the role played by subclinical infection in a significant proportion of cases. The investigation of hormonal influences in the aetiology of preterm labour is at an early stage, but there appears to be a relationship between raised serum relaxin concentrations and preterm delivery (Petersen et al, 1992). The naturally occurring phospholipase A2-inhibitor gravidin, believed to be important in pregnancy maintenance, is found in a reduced concentration in women delivering preterm (Wilson, 1993). The relationship between hormonal levels, socio-economic influences, subclinical infection and actual preterm labour and delivery remains to be established. Secondary prevention with tocolysis remains unsatisfactory, owing to the low therapeutic index of currently available agents and their varied maternal and neonatal adverse effects. The investigation of newer tocolytic agents remains a worthwhile pursuit, whilst the underlying aetiology of preterm labour and effective prevention remains to be elucidated. The widespread recognition of the benefits of antenatal corticosteroid administration and subsequent adoption into clinical practice has reduced, and will continue to reduce, the morbidity associated with preterm birth while newer methods of accelerating fetal maturation are explored and applied in clinical practice.

Adrenal Cortex Hormones↗

Revisional lumbar microdiscectomy: an analysis of operative findings and clinical outcome.

Forty-one consecutive patients who underwent a revision microlumbar exploration for recurrent or persistent sciatica were reviewed retrospectively to analyse the operative findings and assess the clinical outcome following surgery. Thirty-three (80%) patients were found to have a recurrent intervertebral disc protrusion at the previous site, two patients had a disc herniation at a new site, one had severe perineural scarring, two had lateral recess stenosis, one patient had undergone previous exploration at an incorrect site and in two patients no cause for ongoing symptoms was found. Nineteen of the 33 patients with a re-prolapse presented with persistent or recurrent sciatica within 1 year of their first operation. The other 14 patients presented with a late re-prolapse (after 1 year) and their clinical outcome was better than for those patients with an early re-prolapse (12/14 vs 11/19 satisfactory result, respectively). The result of operating on patients with a late re-prolapse was comparable to the 80-95% satisfactory outcomes following primary lumbar microdiscectomy reported by other authors.

Adult↗

Percutaneous balloon dilatation of the mitral valve in critically ill young patients with intractable heart failure.

OBJECTIVE: To assess the outcome of percutaneous balloon dilatation of the mitral valve in critically ill young patients with intractable heart failure. DESIGN: Retrospective analysis of all such patients presenting over a period of 4 years. PATIENTS: Of 432 consecutive patients undergoing percutaneous balloon dilatation of the mitral valve, 12 (mean age 29 years) with intractable heart failure were identified. Nine had severe pulmonary oedema and three had pulmonary oedema with severe right heart failure and hypotension. Three patients were pregnant and three required mechanical; ventilatory support. PROCEDURE: Percutaneous balloon dilatation of the mitral valve was performed using the Inoue balloon technique. The procedure was shortened by excluding full right study, cardiac output measurement, and left ventriculography. The mitral valve morphology and mitral valve area were determined before and after percutaneous balloon dilatation using cross sectional Doppler echocardiography. RESULTS: The procedure was technically successful in all patients. The mean (SD) echocardiographic value of the mitral valve area increased from 0.7 (0.1) to 1.4 (0.2) cm2 with a concomitant reduction in pulmonary artery systolic pressure (Doppler) from 81 (17) to 50 (7) mm Hg. There was a significant clinical improvement in all patients. The mean (range) fluoroscopy time for the procedure was 6.9 (1.7-14.1) min. During follow up (mean 10 months) nine patients were in New York Heart Association (NYHA) functional class I, one was in class II, one under NYHA elective mitral valve replacement, and one, who refused elective surgery, died suddenly at home. CONCLUSION: Percutaneous balloon dilatation of the mitral valve can be performed as a life saving procedure in critically ill patients with mitral stenosis, as even a modest increase in valve area in these patients produces gratifying clinical improvement.

Adult↗

Respiratory symptoms in children dying from malignant disease.

Shortness of breath and other respiratory symptoms frequently complicate the symptomatic management of terminally ill adults. The extent of the problem in children is not known, but anecdotal evidence from nurses and physicians experienced in paediatric oncology has suggested that respiratory problems are less frequent in children dying from malignant disease than in adults. This is a retrospective review of all children dying from cancer under the care of the symptom care team at the Royal Marsden Hospital between 1982 and 1993. The results show that respiratory symptoms were recorded during the last three months of life in 40% of analysable case histories. The nature of respiratory symptoms in paediatric cancer patients is discussed.

Child↗

Glucose inhibits human placental GH secretion, in vitro.

Human placenta specifically expresses the GH-V gene leading to the production of placental Growth Hormone (PGH). During pregnancy, PGH levels increase progressively in maternal blood, but its regulation remains unknown. In this study the effect of glucose on PGH secretion by human term placenta was tested, in vitro, by means of two different experimental models: organ culture of villous tissue and primary culture of isolated cytotrophoblasts. PGH was assayed in the culture medium by an immunoradiometric assay using a specific PGH monoclonal antibody. The presence of glucose (25 mmol/L) in the culture medium significantly inhibited (p < 0.001) the secretion of PGH by either placental villous explants or by cultured trophoblast cells. This inhibitory effect of glucose on PGH secretion was dose-dependent. More than 50% inhibition being observed with 5.5 mmol/L. In the same conditions, the daily production of hPL and hCG, were unmodified. Furthermore, the glucose-induced inhibition of PGH secretion was more effective when cultured trophoblast cells are differentiated into syncytiotrophoblast. This study demonstrates, for the first time, that among the gestational polypeptide hormones secreted by the human placenta, only PGH secretion is modulated by glucose, suggesting a key metabolic role for this hormone during pregnancy.

Culture Media↗

Involvement of the fourth alpha-helix of mouse granulocyte-macrophage colony-stimulating factor in binding to the alpha-subunit of the receptor complex.

Mouse granulocyte-macrophage colony-stimulating factor (mGM-CSF) proteins with substitutions for residues located within alpha-helix D were examined for biological activity and receptor binding properties. Alanine substitutions of the surface exposed positions indicated that several residues contribute to the ligand-receptor interface. Position K108 and particularly D102 appeared to dominate the binding epitope recognized by mGM-R alpha. Several amino acid substitutions were made for K108 which reduced binding with concommitant losses in bioactivity. Substitutions for D102 resulted in binding affinities less than 0.1% that of the wild-type mGM-CSF and bioactivity decreased to 1.0%. Comparative analysis using high and low affinity binding conditions indicated that mGM-R beta binding was unaffected by these mutations.

Amino Acids↗

Structural studies on bioactive compounds. Part 26. Hydrogen bonding in the crystal structure of the N-methylformamide solvate of the immunomodulatory agent 2-amino-5-bromo-6-phenylpyrimidin-4-one (bropirimine): implications for the design of novel anti-tumour strategies.

The immunomodulatory agent bropirimine crystallizes from N-methylformamide (NMF) as a triply hydrogen-bonded duplex in the manner of a Watson-Crick guanine:cytosine base pair. The stoichiometry of the solvate is bropirimine:NMF (2:1) and all NMF molecules are in the Z-rotomeric form. The intermolecular hydrogen bonding is disrupted when the solvate is dissolved in deuteriated dimethyl sulphoxide at 37 degrees C. Bropirimine and other molecules which possess the 2-aminopyrimidin-4-one fragment are potentially capable of recognizing guanine or cytosine residues in single-stranded RNA or DNA by Watson-Crick bonding or double-stranded DNA by Hoogsteen bonds. The immunomodulatory properties of these compounds might be triggered by these encounters.

Adjuvants, Immunologic↗

Potentiation of osteoclast bone-resorption activity by inhibition of nitric oxide synthase.

We have examined the effects of modulating nitric oxide (NO) levels on osteoclast-mediated bone resorption in vitro and the effects of nitric oxide synthase (NOS) inhibitors on bone mineral density in vivo. Diaphorase-based histochemical staining for NOS activity of bone sections or highly enriched osteoclast cultures suggested that osteoclasts exhibit substantial NOS activity that may account for basal NO production. Chicken osteoclasts were cultured for 36 hr on bovine bone slices in the presence or absence of the NO-generating agent sodium nitroprusside or the NOS inhibitors N-nitro-L-arginine methyl ester and aminoguanidine. Nitroprusside markedly decreased the number of bone pits and the average pit area in comparison with control cultures. On the other hand, NOS inhibition by N-nitro-L-arginine methyl ester or aminoguanidine dramatically increased the number of bone pits and the average resorption area per pit. In a model of osteoporosis, aminoguanidine potentiated the loss of bone mineral density in ovariectomized rats. Aminoguanidine also caused a loss of bone mineral density in the sham-operated rats. Inhibition of NOS activity in vitro and in vivo resulted in an apparent potentiation of osteoclast activity. These findings suggest that endogenous NO production in osteoclast cultures may regulate resorption activity. The modulation of NOS and NO levels by cells within the bone microenvironment may be a sensitive mechanism for local control of osteoclast bone resorption.

Amino Acid Oxidoreductases↗

Viral induction of low frequency interferon-alpha producing cells.

The human peripheral blood mononuclear cells responsible for IFN-alpha production in response to viral stimuli have been most often described as either monocytes (as typified by the response to Sendai virus) or as a light density, HLA-DR+ population which is negative for most cell surface markers characteristic of mature T cells, B cells, monocytes, or natural killer cells (as typified by the response to Herpes simplex virus (HSV)). The frequency of IFN-alpha-producing cells (IPC) responding to Sendai virus is typically 10-fold or more higher than those responding to HSV. In the current study, we have used ELISpot assays to determine the frequency of IPC responding to DNA and RNA viruses including HSV, Sendai, vesicular stomatitis virus, cytomegalovirus, adenovirus, SV40, influenza, measles, mumps, Newcastle disease virus (NDV) and human immunodeficiency virus (HIV). The enveloped viruses but not the nonenveloped viruses (adenovirus and SV40) elicited an IFN-alpha response. The frequency of IPC for each of the other viruses was more similar to the low frequency HSV-responding population than to the higher frequency Sendai virus response. These included several viruses in the same family as Sendai virus, namely the paramyxo viruses measles, mumps, and NDV. IPC were also tested for sensitivity to the lysosomotropic drug chloroquine, which diminishes IFN-alpha produced in response to HSV but not Sendai virus. With the exception of Sendai virus, chloroquine treatment abrogated the majority of IFN-alpha produced and IPC against each of the viruses. We conclude that low frequency, nonmonocytic NIPC account for the majority of IFN-alpha production in response to different viruses.

Cell Line↗