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Biomedical subjects

R Miller

Publications and source records attributed to R Miller.

At least 433 records · Page 24Linked to original sources
PubMed1993

On the application of the minimal principle to solve unknown structures.

The Shake-and-Bake method of structure determination is a new direct methods phasing algorithm based on a minimum-variance, phase invariant residual, which is referred to as the minimal principle. Previously, the algorithm had been applied only to known structures. This algorithm has now been applied to two previously unknown structures that contain 105 and 110 non-hydrogen atoms, respectively. This report focuses on (i) algorithmic and parametric optimizations of Shake-and-Bake and (ii) the determination of two previously unknown structures. Traditional tangent formula phasing techniques were unable to unravel these two new structures.

Algorithms↗
PubMed1993

Application of the minimal principle to peptide structures.

A new direct-methods procedure has been devised which consists of phase refinement via the minimal function, R(phi), alternated with Fourier summation and real space filtering. All phases are initially assigned values by computing structure factors for a randomly positioned set of atoms. These phases are then refined by using a parameter shift method to minimize R(phi). The refined phases are Fourier transformed, and a specified number of the largest peaks in the electron-density function are found and used as a new trial structure. The probability of a trial structure converging to a solution appears to depend on structural complexity and a number of refinement parameters. This procedure shows potential for providing fully automatic routine solutions for structures in the 200-400 atom range.

Journal Article↗
PubMed1993

Effects of tropomyosin deficiency in flight muscle of Drosophila melanogaster.

We have studied the structure and function of muscle fibers in which tropomyosin stoichiometry has been reduced by genetic mutation. We used a Drosophila melanogaster flightless mutant Ifm(3)3 and a genetic cross of this mutant with wild type flies to achieve a gradation of tropomyosin gene dosage. We measured the flight ability and wingbeat frequency of the live insects and the ultrastructure and mechanochemistry of isolated single flight muscle fibers. Flight ability is impaired when tropomyosin gene dosage is reduced. Wingbeat frequency also depends upon gene dosage as well as the severity of myofilament lattice disruption and the number of myofilaments in the organized core of the myofibrils. A reduction in number of myofilaments appears to result in a reduction in active muscle stiffness without resulting in an appreciable change in kinetics of force production. Ifm(3)3 is trapped in a relaxed state and cannot generate active force. However, tight-binding rigor cross-bridges are able to form; in the absence of ATP, Ifm(3)3 muscle fibers have high stiffness and force.

Actin Cytoskeleton↗
PubMed1993

Carbamazepine and its metabolites in neuralgias: concentration-effect relations.

The aim of this study was to investigate the use of carbamazepine in the treatment of neuralgic pain and to determine a therapeutic plasma concentration range for carbamazepine in neuralgias. The relation between plasma concentration and the response to treatment (reduction in pain) was examined by logistic regression analysis of carbamazepine and its metabolites, the epoxide, the diol, and 2-hydroxycarbamazepine. The plasma concentrations of carbamazepine, the epoxide, and the diol were significantly related to the probability of a 25% reduction in pain. Only carbamazepine was significantly related to the probability of 50% and 75% pain reduction. However, multiple regression analysis with backward elimination of the data showed a significant correlation between both carbamazepine and the epoxide with regard to the probability of 50% and 75% reductions in pain. This confirms the previous finding that the epoxide has antineuralgic properties [Tomson and Bertilsson 1984]. The therapeutic plasma concentration range for carbamazepine in neuralgias, defined as the range of concentrations that would be expected to provide a 25-75% reduction in pain in 50% of patients, was 2-7 micrograms.ml-1 (HPLC) or 5-17 micrograms.ml-1 (EMIT).

Adult↗
PubMed1993

Bioavailability of controlled release carbamazepine estimated by mixed effect modelling.

The absorption properties of a conventional tablet of carbamazepine (T) and a controlled release form of carbamazepine (TCR) have been compared using a nonlinear mixed effect model (NONMEM). Plasma carbamazepine concentration data were obtained from an open, steady-state, crossover bioavailability study in which 494 measurements were obtained from 13 patients, with an equal number of samples per patient for each dosage form. The pharmacokinetic model used as a one-compartment open model with first-order absorption and elimination. The objective function was used as a measure of the goodness of fit of the model to the data. Body weight was an important determinant of carbamazepine clearance (CL) but not volume of distribution (V). Accounting for the interindividual variability in volume of distribution did not significantly influence the objective function. Including different rates of absorption (ka) for the two dosage forms resulted in a significant improvement in the objective function, as well as reducing the interindividual variability in the rate of absorption. Adding a parameter for relative bioavailability (f) of TCR improved the objective function statistically, but an unrealistic value for V was obtained, and the absorption and elimination rates appeared to be transposed in the classical "flip-flop" manner. Fixing V to the value obtained before introducing f did not change the objective function and permitted estimation of f without the confounding influence of excessive parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1993

Determination of theophylline clearance in South African children.

Theophylline clearance values in South African children were determined using 400 serum theophylline concentration measurements gathered from 109 compliant outpatients during their normal routine care. Population pharmacokinetic analysis was done using the Non-Linear Mixed Effects Model (Nonmem) to analyse the data. Nonmem was also used to estimate the influence of fixed effects (weight, age, race, gender etc) on clearance and its interindividual variability. Gender, age, and weight raised to an iterated exponent were found to be the most important demographic fixed effect parameters influencing clearance. Race was not found to be important. The weight-adjusted values of theophylline clearance decreased with increasing age. The actual values expressed in l.h-1.kg-1 were 0.0949 for children aged 1-5 y; 0.0813 for children aged 5-9 y, and 0.0660 for children of 9-16 y. The values are similar to those reported in other studies.

Adolescent↗
PubMed1993

The prevalence of paranasal sinus disease in HIV infection and AIDS on cranial MR imaging.

Sinusitis poses a difficult clinical challenge in the management of patients with AIDS because of high rates of relapse and the association with unusual pathogens. To determine the prevalence and severity of sinus disease in this group we prospectively analysed the condition of the paranasal sinuses shown on cranial MR scans of 156 patients referred for the investigation of suspected intracranial pathologies. These included 104 HIV seropositive patients, including 93 with an AIDS-defining diagnosis (CDC IV). Forty-two scans were performed on age-matched controls. The scans were timed to control for seasonal variations in sinus disease and were interpreted by two radiologists who were blinded to the clinical and serological status of the patients. Severe mucosal disease (more than one sinus showing > 75% obliteration) or moderate mucosal disease (only one sinus showing > 75% obliteration) was seen in 15.1% (14/93) patients with AIDS and none of the 42 controls (chi 2 = 6.73, P < 0.01). The mean maximum mucosal thickness in patients with AIDS was significantly greater than the control group (P < 0.001) and also significantly greater than in seropositive patients who had not had an AIDS-defining diagnosis (CDC II/III) (P = 0.006). Paranasal sinus mucosal abnormalities seen on MRI are greater in prevalence and severity in patients with AIDS and about one in seven would be expected to have at least one sinus largely obliterated.

Acquired Immunodeficiency Syndrome↗
PubMed1993

A family with HIV and haemophilia.

An Indian Sikh family affected with both HIV and haemophilia is described. The use of interpreters; the regular follow-up in the Concorde trial; family therapy and help with practical problems have been approaches used to help the family despite language and cultural differences.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Molecular structures of two crystalline forms of the cyclic heptapeptide antibiotic ternatin, cyclo[-beta-OH-D-Leu-D-Ile-(NMe)Ala-(NMe)Leu-Leu-(NMe)Ala-D-(NMe)Ala-].

The crystal structures of two solvated forms of ternatin, cyclo[-beta-OH-D-Leu-D-Ile-(NMe)Ala-(NMe)Leu-Leu-(NMe)Ala-D-(NMe)Ala-] are reported. The first crystallizes with two molecules of peptide and one of dioxane in the asymmetric unit: P2(1)2(1)2(1), a = 11.563(1), b = 21.863(2), c = 36.330(4) A. The second crystallizes with two molecules of peptide and one of water in the asymmetric unit: P2(1)2(1)2(1), a = 14.067(2), b = 16.695(1), c = 36.824(6) A. N-Methylation of four of the seven residues of ternatin appears to reduce the number of low-energy conformations the molecule can assume. The same H-bonded macrocyclic ring conformation is adopted by the backbone of each of the four molecules observed here. All the amino-acid side chains, with the exception of D-Ile2, have similar orientations in each of the four conformers. The heptapeptide macrocycle is characterized by: (i) a cis peptide between (NMe)Ala3 and (NMe)Leu4, (ii) a type II beta-bend, involving residues Leu5-(NMe)Ala6-D-(NMe)Ala7-beta-OH-D-Leu1, stabilized by two H-bonds, N1-->O5 and N5-->O1, between Leu5 and beta-OH-D-Leu1 residues, (iii) a third intramolecular H-bond, observed in each of the four molecules, between the hydroxyl group of beta-OH-D-Leu1 and the carbonyl oxygen of D-Ile2.

Amino Acid Sequence↗
PubMed1993

Recurrent patella dislocation treated by closed lateral retinacular release.

This study describes the results of treating selected patients suffering from recurrent dislocation of the patella, with closed lateral retinacular release. Thirty-nine patients were reviewed after a mean follow-up time of 28 months. Thirty patients were substantially improved by the procedure, two patients had sustained a further dislocation. The major complication--haemarthrosis--occurred in four patients. These results compare favourably with those achieved by major realignment procedures. So lateral retinacular release is an effective treatment for selected patients with recurrent patella dislocation, and it offers distinct advantages over other procedures.

Adolescent↗
PubMed1993

Continuous flow resectoscopes. Are the theory and design wrong?

The optical design of rod-lens telescopes has now reached a zenith. The only way of improving the resectoscope is to investigate the ergonomics and flow dynamics. We present a comparative analysis of the flow mechanics of continuous flow resectoscopes. The morphology, flow characteristics and irrigating potential (washout gradient) of several instruments were examined. It was found that when used with balanced continuous flow (inflow and outflow balanced), all of the endoscopes had poor visibility compared with unbalanced continuous flow (inflow > outflow). Possible changes in the design of the instruments are discussed.

Endoscopes↗
PubMed1993

Children of HIV positive haemophilic men.

All 14 children who were conceived at the time their 12 haemophilic fathers were anti-HIV positive were shown to be HIV negative and to be healthy physically and mentally. Eleven of the 12 female partners have remained anti-HIV negative and one has seroconverted. Despite counselling it is likely that children will continue to be conceived by anti-HIV positive haemophiliacs.

Adult↗