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Biomedical subjects

N Patel

Publications and source records attributed to N Patel.

At least 235 records · Page 13Linked to original sources
PubMed1994

The influence of tape type and of skin preparation on the force required to dislodge angiocatheters.

The study evaluated the effects of different techniques used to secure intravenous (i.v.) catheters. An angiocatheter attached to standard i.v. tubing was taped to human forearm using a standard taping method. A calibrated piezoelectric force transducer was attached to the i.v. tubing. The force applied along the longitudinal axis to pull out the taped catheter was measured and recorded on paper. Three tape types, Curity, Leukopor and Transpore, were evaluated alone, with benzoin skin pretreatment and with mastisol pretreatment. A randomized 3 x 3 block design with 20 replications per block was utilized, and a total of 180 pullout tests were performed on two adult volunteers. Without pretreatment, the forces required to dislodge catheters were (means +/- SEM) 46 +/- 2, 37 +/- 2 and 38 +/- 2 Newtons for Curity, Leukopor and Transpore tape, respectively. Corresponding values for mastisol pretreatment (64 +/- 1, 64 +/- 3 and 52 +/- 3 Newtons) were greater (P < 0.05) for each tape compared with benzoin (54 +/- 3, 53 +/- 2 and 40 +/- 2 Newtons) and no pretreatment. The most frequent failure mode for Transpore tape was by tape fracture, for Curity tape was by separation from the skin of tape and catheter as a single unit, and for Leukopor tape was by catheter separation while tape remained attached to skin (P < 0.001). The data suggest that the application of mastisol prior to taping i.v. catheters with Curity or Leukopor tape helps to minimize the risk of accidental dislodgement.

Adhesiveness↗
PubMed1994

Lack of effect of interferon alpha 2a upon fluorouracil pharmacokinetics.

The disposition of 5-fluorouracil (FUra) was studied in 19 colorectal cancer patients during treatment with FUra and high-dose leucovorin (LV) with or without interferon alpha 2a (IFN-alpha). All received LV 200 mg m-2 over 2 h, then FUra 400 mg m-2 over 5 min then FUra 400 mg m-2 over 22 h, repeated on day 2, on a 14 day cycle. Nine patients also received IFN-alpha 6 MU every 48 h, starting at least 2 weeks before the study. Series of 14 blood samples were assayed for FUra by reversed-phase high-performance liquid chromatography (HPLC). Minimum Akaike information criterion estimation was used to determine the simplest effective pharmacokinetic model. This consisted of a single compartment with first-order (linear) and Michaelis-Menten (non-linear) components to drug elimination. This model gave r2 > 0.98 in 19/20 data sets. With the Michaelis constant (KM) set at 15 microM, values were derived for the volume of distribution (Vd), the maximum rate of non-linear elimination (Vmax) and the first-order elimination rate constant (K1.e). Mean (+/- s.d.) values in control (no IFN-alpha) patients were: Vd 10.4 (+/- 1.9) l m-2, Vmax 182 (+/- 59) mumol l-1 h-1 and k1.e 4.35 (+/- 0.58) h-1. No significant differences were detected in patients receiving IFN-alpha, in whom the equivalent mean values were Vd 10.0 (+/- 0.9) l m-2, Vmax 141 (+/- 27) mumol l-1 h-1 and k1.e 3.96 (+/- 0.5) h-1. Mean trapezoidal AUC0-22 h was similar in the two groups (control patients 116 microM h, IFN-alpha patients 125 microM h). No significant correlations with renal or hepatic function were detected. These results, while not inconsistent with previous reports of a reduced rate of FUra elimination at higher IFN-alpha doses, suggest that any clinical effect of this moderate dose of IFN-alpha on FUra toxicity or activity is due to modulation at target cells, not to pharmacokinetic interaction.

Adult↗
PubMed1994

Site-directed isotope labelling and FTIR spectroscopy of bacteriorhodopsin.

Insight into integral membrane proteins function is presently limited by the difficulty of producing three-dimensional crystals. In addition, X-ray structures of proteins normally do not provide information about the protonation state and structural changes of individual residues. We report here the first use of site-directed isotope labelling and Fourier transform infrared (FTIR) difference spectroscopy to detect structural changes at the level of single residues in an integral membrane protein. Two site-directed isotope labeled (SDIL) tyrosine analogues of bacteriorhodopsin were produced which exhibit normal activity. FTIR spectroscopy shows that out of 11 tyrosines, only Tyr 185 is structurally active during the early photocycle and may be part of a proton wire.

Bacteriorhodopsins↗
PubMed1994

Effect of beta blockade on the neurohumoral and cardiopulmonary response to dynamic exercise in cardiac transplant recipients.

OBJECTIVE: To determine the effects of a small dose of beta blocker on neurohumoral and cardiopulmonary responses after cardiac transplantation. BACKGROUND: Cardiac transplant recipients have a reduced exercise capacity and abnormal cardiovascular responses to exercise. The sympathoadrenal response to exercise has been shown to be abnormal with high venous noradrenaline. The effect of beta blockade on these neurohumoral mechanisms has not been defined. METHODS: 10 non-rejecting cardiac transplant recipients were studied. Patients carried out graded exercise to a symptom limited maximum. Blood samples were taken during exercise. Concentrations of noradrenaline, adrenaline, and atrial natriuretic peptide and plasma renin activity were measured. The next day, the exercise and sampling procedure were repeated after an oral dose of propranolol (40 mg). RESULTS: Patients tolerated exercise poorly after beta blockade, which was reflected in the maximum workload reached. Heart rate and blood pressure were significantly higher at rest and during exercise before beta blockade. Although there was no significant difference when resting, mean (SEM) noradrenaline concentrations during peak exercise were higher after beta blockade (16.2 (2) v 23.6 (2.9) nmol/l, p = 0.001). Adrenaline concentrations at peak exercise were also greater after beta blockade (0.89 (0.31) v 1.18 (0.38) nmol/l, p = 0.055). Atrial natriuretic peptide concentrations tended to be higher after beta blockade (118.75 (50.2) v 169.79 (39.3) pmol/l, p = 0.36). There was no significant change in plasma renin activity. CONCLUSIONS: A small oral dose of a competitive beta blocker such as propranolol has an adverse effect on exercise tolerance and cardiovascular response to exercise in cardiac transplant recipients. There are also increased concentrations of circulating noradrenaline and therefore, sympathetic activity during exercise. beta blockers should be used with caution in cardiac transplant recipients.

Administration, Oral↗
PubMed1994

Advances in image-directed neurosurgery: preliminary experience with the ISG Viewing Wand compared with the Leksell G frame.

Because of the limited application of frame-based stereotaxy to general neurosurgical procedures, we have carried out a preliminary evaluation of the ISG Viewing Wand, a frameless image-directed surgical system that is based on the rapid reformat and accurate three-dimensional reconstruction capability of parallel processor-based computer technology. We have compared the first 36 cases carried out with the system in the Frenchay Neurosurgery Department with a retrospective analysis of the previous 36 cases carried out using the Leksell G frame. The stereotactic cases were completed over a period of 15 months, representing 2.8% of intracranial procedures. The wand cases were completed in 3 months, 13% of the intracranial practice during that time. The wand was used for 28 supratentorial craniotomies (76%), four infratentorial procedures (11%) and five biopsy procedures (13%). Conventional stereotaxy was not used for posterior fossa or skull base procedures. Supratentorial craniotomy was carried out in nine cases (25%), while the remaining 27 cases involved point source localization within the cranium (75%). The mean preparation time prior to surgery was 65 min for the stereotactic cases and 37 min for the wand cases. We therefore conclude that the indications for frame-based stereotaxy and Viewing Wand use are mutually exclusive. Leksell stereotaxy remains the method of choice for point source localization deep within the cranium. All other procedures requiring an image-directed minimally invasive surgical approach are more appropriately carried out using the Viewing Wand. The system has potential immediate application in supratentorial, skull base and infratentorial tumour surgery, vascular surgery, epilepsy surgery and upper cervical spine surgery.

Brain Mapping↗
PubMed1994

Exact permutational tests for group sequential clinical trials.

An efficient numerical algorithm is developed for computing stopping boundaries for group sequential clinical trials. Patients arrive in sequence, and are randomized to one of two treatments. The data are monitored at interim time points, with a fresh block of patients entering the study from one monitoring point to the next. The stopping boundaries are derived from the exact joint permutational distribution of the linear rank statistics observed across all the monitoring times. Specifically, the algorithm yields the exact boundary generating function, Pr(W1 < b1, W2 < b2, ..., Wi-1 < bi-1, Wi = wi), where Wj is the linear rank statistic at the jth interim time point. The distribution theory is based on assigning ranks after pooling all the patients who have entered the study, and then permuting the patients to the two treatments independently within each block of newly arrived patients. The methods are applicable for an arbitrary number of monitoring times, which need not be specified at the start of the study. The data may be continuous or categorical, and censored or uncensored. The randomization rule for treatment allocation can be adaptive. The algorithm is especially useful during the early stages of a clinical trial, when very little data have been gathered, and stopping boundaries are based on the extreme tails of the relevant boundary generating function. In that case the corresponding large-sample theory is not very reliable. To illustrate the techniques we present a group sequential analysis of a recently completed study by the Eastern Cooperative Oncology Group.

Algorithms↗
PubMed1993

Cell-free synthesis, functional refolding, and spectroscopic characterization of bacteriorhodopsin, an integral membrane protein.

Bacteriorhodopsin (bR) is an integral membrane protein which functions as a light-driven proton pump in Halobacterium halobium (also known as Halobacterium salinarium). The cell-free synthesis of bR in quantities sufficient for FTIR and NMR spectroscopy and the ability to selectively isotope label bR using aminoacylated suppressor tRNAs would provide a powerful approach for studying the role of specific amino acid residues. However, no integral membrane protein has yet been expressed in a cell-free system in quantities sufficient for such biophysical studies. We report the cell-free synthesis of bacterioopsin, its purification, its refolding in polar lipids from H. halobium, and its regeneration with all-trans-retinal to yield bacteriorhodopsin in a form functionally similar to bR in purple membrane. Importantly, the yields obtained from in vitro and in vivo expression are comparable. Functionality of the cell-free expressed bR is established using static and time-resolved absorption spectroscopy and FTIR difference spectroscopy.

Bacteriorhodopsins↗
PubMed1993

Cloning by insertional mutagenesis of a cDNA encoding Caenorhabditis elegans kinesin heavy chain.

An additional genetic locus in Caenorhabditis elegans, unc-116, was identified in a screen for mutations resulting in defective locomotion. unc-116 was cloned by use of a transposon insertion mutant and the physical and genetic map of the genome. The cDNA sequence predicts an 815-amino acid protein. Based upon sequence comparison and secondary structure predictions, unc-116 encodes all three domains of the kinesin heavy chain: the motor, stalk, and tail. While the motor and tail domains have a high degree of identity to the equivalent domains of cloned kinesin heavy chains, the rodII domain of the stalk is significantly shorter than those previously reported and is not predicted to form a coiled-coil alpha-helix. Analysis of mutational defects in two C. elegans genes encoding anterograde motor molecules, unc-116 and unc-104, should provide insight into the in vivo functions of these members of the kinesin heavy chain superfamily.

Amino Acid Sequence↗
PubMed1993

Spawning in the zebra mussel (Dreissena polymorpha): activation by internal or external application of serotonin.

The zebra mussel, Dreissena polymorpha, was recently introduced accidentally into the Great Lakes and, due in part to its prodigious reproductive capacity, is spreading rapidly in temperate fresh waters of North America. The present studies examine some of the mechanisms that regulate spawning in this animal. In August and September 1990 and in May 1991 injection of serotonin (5-hydroxytryptamine, 5-HT) induced ripe male, but not female, zebra mussels to spawn. During mid-summer 1991, 5-HT induced spawning in both males and females, and 5-HT could produce spawning responses by either injection or external application. External pH over a broad range (6.0 to 9.1) had no effect on spawning, neither inhibiting induction of spawning by 5-HT nor significantly eliciting spawning itself. With external application, 10(-3) M and 10(-4) M 5-HT caused spawning, but 10(-5) M and 10(-6) M did not. Cyproheptadine, a 5-HT receptor antagonist, reduced the response of both males and females by more than half. Spawning in response to 5-HT was blocked at 4 degrees C, but not at 12 degrees C, 20 degrees C, or 27 degrees C. For male zebra mussels morphological criteria for judging gonadal maturity were well-correlated with probability of spawning in response to 5-HT. For females, the likelihood of spawning in response to 5-HT was not tightly coupled to morphological maturity of the gonad, with many morphologically ripe females failing to spawn and some apparently immature animals releasing oocytes. Prior spawning reduced subsequent responsiveness and intensity of spawning of animals to 5-HT. These experiments support a role for 5-HT in regulating reproduction in zebra mussels and help define conditions by which zebra mussel spawning may be stimulated or inhibited.

Animals↗
PubMed1993

Cumene hydroperoxide-mediated inactivation of cytochrome P450 2B1. Identification of an active site heme-modified peptide.

Cumene hydroperoxide (CuOOH)-mediated inactivation of cytochromes P450 (P450) results in the degradation of their prosthetic heme to products that alkylate the apoprotein. Indirect approaches suggest that this alkylation occurs at the active site. in order to identify the specific apoprotein site(s) alkylated, purified 3H- or 14C-heme-labeled P450 2B1 was incubated with CuOOH and subjected to lysyl endopeptidase-C digestion. Two major peaks (L1 and L2) containing 3H- or 14C-labeled peptides were detected by reverse-phase high pressure liquid chromatography of the digest. L1 contained the highest specific radioactivity and after Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis yielded 3 peptide bands (M(r) approximately 3,500 (P1), 5,000 (P2), and 7,000 (P3)). Although all 3 bands were found radiolabeled, the yield of P1 was higher than that of P2 or P3. Amino acid sequence analysis of the first 13 N-terminal residues of P1 revealed the sequence RICLGEGIARNEL, corresponding to residues 434-446 of the reported 2B1 sequence. A species with the molecular mass of 3771 +/- 1 Da was detected in preliminary electrospray mass spectrometric analysis of L1. Since the theoretical average mass of the predicted peptide (residues 434-466) is 3721.99 Da, the additional 49 +/- 1 Da are considered to be contributed by the alkylating heme fragment. This alkylated 2B1 sequence contains not only Cys436, the conserved residue that provides the SH ligand for heme, but also other highly conserved residues, and therefore corresponds to the heme-sandwiching helix L of P450cam. To our knowledge, this is the first report to localize CuOOH-induced heme alkylation of 2B1 to its active site.

Amino Acid Sequence↗
PubMed1993

Kinetics of cell proliferation as a function of vascular graft material.

Bioresorbable vascular grafts constructed for polyglactin 910 (PG910) and polydioxanone (PDS) and nonresorbable Dacron were interposed into the infrarenal abdominal aortas of New Zealand White rabbits. The prosthesis/tissue complexes were harvested after 2, 3, 4, 12, and 52 weeks. Seventeen, 9, and 1 h prior to sacrifice, animals received tritiated thymidine (0.5 mCi/kg/dose). All specimens were studied grossly and by light and transmission electron microscopy. Mitotic indices (MI's) were determined by autoradiography for inner capsule myofibroblasts at the proximal, mid, and distal segments of each prosthesis. There were no aortic-related deaths. All grafts were patent with no aneurysmal dilatation. At 4 weeks, PG910 resorption was evidenced by macrophage phagocytosis, less so in PDS while Dacron remained intact. At 12 weeks, the PG910 was completely resorbed while PDS resorption continued. The latter was completely resorbed by 52 weeks. There was no significant difference in MI's between proximal, mid, and distal regions for each graft type. The mitotic index paralleled the rate of prosthetic resorption in both PG910 and PDS groups, as high as 28.34 +/- 23.21 in the former 3 weeks after implantation and significantly higher at 4 weeks (7.58 +/- 2.02 and 7.50 +/- 2.66, respectively) than at 52 weeks (0.72 +/- 0.98 and 1.00 +/- 0.22, respectively) in both groups. The mitotic index in the Dacron group never surpassed 1.22 +/- 0.90. We conclude that higher levels of early cell proliferation in bioresorbable grafts closely parallel the kinetics of prosthetic resorption.

Animals↗
PubMed1993

Percutaneous balloon mitral valvotomy in pregnant patients with tight pliable mitral stenosis.

Percutaneous balloon mitral valvotomy was attempted in severely symptomatic (New York Heart Association class III or IV) pregnant patients (mean age 30 years) with tight mitral stenosis. Nineteen patients were pregnant (mean gestation 30 weeks, range 26 to 34) and one patient was in the immediate postpartum period. All patients had undergone a trial of diuretic therapy and 16 were also taking atenolol. Percutaneous valvotomy was performed with the Inoue catheter (18 patients) or the Schneider-Medintag bifoil (2 x 19 mm) balloon catheter (2 patients). The fluoroscopy time was 9.2 +/- 3.4 minutes. After percutaneous valvotomy the mean mitral gradient decreased from 17.9 +/- 6.2 to 5.9 +/- 2.4 mm Hg (p < 0.001). The mitral valve area (pressure half time) increased from 0.8 +/- 0.2 to 1.7 +/- 0.2 cm2 (p < 0.001). These hemodynamic changes were accompanied by immediate symptomatic improvement by at least one New York Heart Association functional grade in all patients. Moderate (3+) mitral regurgitation developed in one patient. Eighteen patients had normal infants delivered vaginally at term without assistance, and one patient had a normal infant delivered by cesarean section at 35 weeks' gestation. We conclude that percutaneous balloon mitral valvotomy for pliable mitral stenosis in pregnancy is safe for both the mother and fetus. We recommend that it be performed in symptomatic patients with tight mitral stenosis so as to avoid hemodynamic complications in the latter stages of pregnancy.

Adult↗
PubMed1993

Copper-64 metabolism in two patients with non-Wilsonian movement disorders and copper deficiency.

Copper-64 studies are presented of 2 patients with non-Wilsonian movement disorder and with abnormal copper handling. Both patients differed from the usual phenotype of non-Wilsonian low copper movement disorder as they had choreiform movement disorders with an onset in the first decade; one patient lacked significant intellectual impairment. Both patients had reduced serum total copper and marginal free copper and caeruloplasmin levels, and both patients were capable of incorporating 64Cu2+ into caeruloplasmin but the second case did so at markedly reduced level. Both showed slightly increased basal and stimulated urinary copper loss compared to normal controls with the rate in patient 1 being capable of leading to copper depletion. Liver copper content was normal in both cases. These 2 patients add to the reports of cases with copper deficiency and movement disorder in whom copper chelation therapy is unlikely to be beneficial.

Adult↗
PubMed1993

Pharmacokinetics of 5-fluorouracil in colorectal cancer patients receiving interferon.

BACKGROUND: The outlook for patients with advanced colorectal cancer remains poor. Recent reports of the combination of 5-fluorouracil (5-FU) and alpha-interferon in colorectal cancer have suggested better response rates. One possible explanation for interaction between 5-FU and interferon is that interferon alters the pharmacokinetics of 5-FU, increasing plasma 5-FU levels. PATIENTS AND METHODS: To investigate the possibility of interaction between the two agents, steady state 5-FU pharmacokinetics was evaluated in patients with colorectal cancer who received 5-FU by continuous i.v. infusion with and without concurrent administration of subcutaneous alpha-interferon. 5-FU levels were measured by reverse-phase high-performance liquid chromatography. RESULTS: Twenty-six patients were evaluated. There were 4 partial responses (15%). There was no significant difference in steady state 5-FU levels whether or not alpha-interferon was administered concurrently. CONCLUSION: Any synergistic activity that may exist between this combination of 5-FU and alpha-interferon is not simply due to altered 5-FU pharmacokinetics.

Adult↗