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Biomedical subjects

P E Smith

Publications and source records attributed to P E Smith.

At least 19 recordsLinked to original sources
PubMed1992

Quenched molecular dynamics simulations of tuftsin and proposed cyclic analogues.

We have used high-temperature quenched molecular dynamics calculations to investigate the conformational properties of tuftsin (Thr-Lys-Pro-Arg) in solution. Conformers obtained after quenching of the dynamical structures were sorted into families depending on their relative energies and backbone conformations. By examination of these families, several cyclic analogues of tuftsin were proposed and examined theoretically by further quenched dynamics simulations. Two of the four proposed analogues were found to adopt essentially identical conformations to that of linear tuftsin. It is suggested that these two derivatives (cyclo[Thr-Lys-Pro-Arg-Gly] and cyclo[Thr-Lys-Pro-Arg-Asp]) may be biologically active, and that the introduction of cyclic conformational constraints should help to reduce the entropic penalty to peptide binding.

Amino Acid Sequence↗
PubMed1992

Amino acid side-chain populations in aqueous and saline solution: bis-penicillamine enkephalin.

The potentials of mean force (pmfs) for rotation around the chi 1 aromatic side-chain dihedrals of the zwitterionic bis-penicillamine enkephalin pentapeptide have been determined in both aqueous and saline solution. These side chains are known to be associated with the pharmacophore and their conformational populations are thought to be critical for activity. It is found that the association between chloride ions and the peptide in saline solution simulations has profound effects on the relative energies of the g-, g+, and t conformations, and also the barriers between them. Using the pmfs we have also calculated the respective Boltzmann-weighted 3J alpha beta vicinal coupling constants. The agreement between the calculated and experimentally determined coupling constants is poor for the pmf in pure water, but substantially improved for the pmf determined in saline solution. Reasons for these differences appear to be related to the experimental conditions.

Amino Acid Sequence↗
PubMed1992

Familial breast and ovarian cancers.

Breast and ovarian cancer develop independently of each other but share some genetic commonality. Definition and identification of hereditary breast cancer are very complex. Ovarian cancer can be inherited in an autosomal dominant pattern with variable gene penetrance, a site specific hereditary pattern, or a pattern of tumor combinations. Medical management of high risk individuals, follow-up, screening, and counseling needs are important issues to the woman and other family members.

Breast Neoplasms↗
PubMed1992

A portable mouth pressure meter.

The design and function of a device for bedside measurement of maximum static respiratory pressures is reported. The ability to measure maximum inspiratory and expiratory pressures allows a simple means of monitoring respiratory muscle weakness in both acute and chronic conditions.

Equipment Design↗
PubMed1992

Reimbursement for clinical nutrition services: a 10-year experience.

Charges for nutrition products and services grew more than 800% between 1980 and 1990 at Children's Memorial Medical Center, Chicago, Ill. Three factors contributed to the growth in charges: distinguishing special services from those included in the bed charge, requiring rigorous documentation of services ordered and provided, and building administrative support for the program. Of the charges, 91% were related to nutrition support. The hospital converted 99% of the charges to private payers into actual revenue. The charge program provides the structure, discipline, and data to demonstrate the value of nutrition services for improving patient outcomes and may help sustain financial support even if the health care industry continues to move away from direct payment for services. Charging for nutrition products and services is a useful way for dietitians to document and be compensated for the value of their services in a hospital setting.

Documentation↗
PubMed1991

Conformational analysis. Part 16. Conformational free energies in substituted piperidines and piperidinium salts.

The conformational free energies (-delta G degree) of a number of 4-substituted piperdines and piperidinium salts have been determined by the J-value method. For the 4-substituted piperdines (R = Me, Phenyl, CO2Et, Br, OH, F) the relative conformer energies are almost identical to those of the analogous cyclohexanes. The methyl and phenyl compounds showed no change in the couplings on protonation, implying no change in the conformer energies. In contrast, in the remaining compounds with polar 4-substituents an almost constant stabilisation of the axial conformer of ca. 0.7 -0.8 kcal mol-1 was observed on protonation. In three cases (R = F, OH and Br) the conformational preference is reversed on protonation and the axial form is favored. The conformer energies of both the free bases and the piperidinium salts can be quantitatively predicted by molecular mechanics calculations using the COSMIC force-field, in which the electrostatic interactions are calculated by a simple Coulombic model with the partial atomic charges in the molecules given by the CHARGE2 routine, and an effective dielectric constant of five. The precise agreement obtained demonstrates conclusively that the electrostatic interactions between the substituents and the protonated nitrogen are the cause of the conformational changes on protonation, and that these can be modelled successfully using existing force-fields.

Magnetic Resonance Spectroscopy↗
PubMed1991

Charge calculations in molecular mechanics. Part 8. Partial atomic charges from classical calculations.

The CHARGE2 programme, which involves the classical calculation of both the inductive and resonance contributions to the partial atomic charges in molecules is described, and the charges and electrostatic potentials obtained presented for some illustrative examples. In substituted methanes (CH3X, CF3X, CCl3X) the effects of varying the electronegativity of the substituents and the alpha- and beta-substituent contributions are clearly illustrated for a variety of substituent groups X. The problems involved in the inclusion of silicon into this scheme are detailed, together with the methods of overcoming them. The partial atomic charges (sigma and pi contributions) and electrostatic potentials for some silicon oxygen compounds are presented and discussed. The partial atomic charges from CHARGE2 for all the natural amino acids as their N-acetyl, N'-methylamides are given and compared with those obtained from the AMBER and ECEPP/2 force fields. Considerable differences in these figures are observed, with the AMBER charges consistently much larger than those from the other two methods. The CHARGE2 partial atomic charges and electrostatic potentials for the four common nucleic acids, adenine, cytosine, guanine and thymine, are given and compared with those derived from other calculations. Again there is general similarity but also there are considerable differences, with those from the AMBER force field somewhat larger than the other methods.

Amino Acids↗
PubMed1991

Domiciliary investigation of sleep-related hypoxaemia in Duchenne muscular dystrophy.

In Duchenne muscular dystrophy (DMD) nocturnal oxygen desaturation occurs during rapid eye movement (REM) sleep. Polysomnography, which requires hospital admission, will detect sleep-related breathing abnormalities. In order to avoid the inconvenience of hospital admission for the disabled patient, we investigated overnight oxygenation in ten boys with DMD by domiciliary oximetry. In four boys the results of oximetry were compared with those of a polysomnographic recording. The "repeatability" of domiciliary oximetry was assessed in six boys by performing oximetry on two non-consecutive nights. Older boys with DMD may develop a cardiomyopathy. In order to assess cardiac rhythm and ST segment changes we performed simultaneous Holter monitoring and oximetry in seven boys with overnight hypoxaemia. Six of the initial ten boys studied demonstrated episodic nocturnal hypoxaemia and there was a strong correlation between minimum oxygen saturation overnight and daytime arterial oxygen and carbon dioxide tensions (PaO2 r = 0.89; PaCO2 r = -0.87). Despite adequate REM time during polysomnography, greater oxygen desaturation was found during domiciliary oximetry. No difference was found in the severity of desaturation recorded in the boys who were studied on two separate occasions. Five boys demonstrated marked heart rate variation during hypoxaemic episodes and more serious arrhythmias occurred overnight in the three most hypoxaemic boys. Domiciliary oximetry is a simple, repeatable method of assessing overnight oxygenation and compares well with polysomnography. In boys with advanced DMD and severe nocturnal hypoxaemia, 24 h electrocardiographic monitoring may detect potentially life-threatening arrhythmias.

Adolescent↗
PubMed1989

Charge calculations in molecular mechanics 7: application to polar pi systems incorporating nitro, cyano, amino, C=S and thio substituents.

A previously described method for calculating partial atomic charges in molecules has been applied to a variety of different functional groups with pi electrons. The pi charges have been determined by varying the relevant Hükel coulombic and resonance integrals so as to reproduce the experimental dipole moments of known compounds. These include nitro, cyano, mercapto and thiocarbonyl compounds, anilines and a series of heterocyclic ring compounds involving nitrogen, oxygen and sulphur atoms. The calculated dipole moments are in good agreement with experimental values and are a considerable improvement on other calculated values, while requiring only a fraction of the computational time necessary for more rigorous methods. The resulting pi densities compare favourably with other theoretical (CNDO, MNDO and STO-3G) methods.

Amines↗
PubMed1989

Deterring bone loss by exercise intervention in premenopausal and postmenopausal women.

This study investigated the efficacy of 4 years of exercise intervention in deterring bone loss in middle-aged women, and is a correction and extension of previously published data. Sixty-two control subjects (mean age 50.8) and 80 exercise subjects (mean age 50.1) completed a 4-year study. Subjects exercised three times a week, 45 minutes per session. Bilateral radius, ulna, and humerus bone mineral content (BMC) and width (W) were measured on each subject 11 times over the 4-year period. The two groups did not differ initially in age, height, or weight, but the control group had a greater maximum VO2 (ml/kg/min) than the exercise group. Slopes and intercepts of the bone variables vs. time were determined for each subject, and these values were used for between-group comparisons of loss. The control group BMC and BMC/W declined significantly in all three bones in both arms. The exercise group rate of decline was significantly less than that of the control group for 12 of the 18 bone variables. The greatest effect of the exercise intervention was on the ulna and radius. Exercise subjects lost significantly less than control subjects in left and right ulna and radius BMC and BMC/W, and left ulna and radius W. Lesser differences between groups were observed in the humerus. BMC and W loss rates of the left humerus were reduced in the exercise group, with no difference between exercise and control subjects in the other humerus variables. To determine if menopausal status influenced the response to exercise, we analyzed the difference between groups for premenopausal and postmenopausal subjects separately. Regardless of menopausal status, exercise subjects had lower bone loss rates than control subjects. In both premenopausal and postmenopausal subjects, exercise reduced bone loss significantly for 10 of the 18 bone variables. It can be concluded that physical activity significantly reduces bone loss in the arms of middle-aged women.

Adult↗
PubMed1989

Profiles of instant heart rate during partial seizures.

Instant heart rate (R-R intervals) can be readily studied during spontaneous seizures recorded with ambulatory cassette AEEG/AECG techniques. Ninety-three seizures were recorded in 32 patients with complex partial epilepsy. Instant R-R interval plots showed that 74% of seizures were associated with a dominant tachycardia, the most characteristic features of which were the initial steep acceleration phase at seizure onset and the wide fluctuations in heart rate ('exaggerated sinus arrhythmia') which occurred during and immediately after the seizure. Five percent of seizures were associated with a dominant but transient phase of heart rate slowing during or towards the end of the seizure. Nineteen percent of seizures showed equivocal or negative ictal effects on the heart rate and rhythm despite unequivocal AEEG seizure discharges. Conversely, other patients had characteristic heart rate changes despite equivocal AEEG abnormality. The heart rate profiles showed striking seizure-to-seizure similarities when multiple fits were recorded in the same patient. Ratemeter profiles may be clinically useful to locate epileptic seizures in long duration records; they can help to locate seizures which are either inaccurately timed or poorly identified by the event marker, or not clearly associated with definite AEEG changes. The secondary cardiac effects of epilepsy may be misdiagnosed if their primary cerebral origin is not suspected.

Adult↗
PubMed1989

Calcium supplementation and bone loss in middle-aged women.

This 4-y study investigated the effects of a calcium carbonate supplement on bone loss in 169 women aged 35-65 y, randomly assigned to placebo and treatment (1500 mg Ca/d) groups in a double-blind design. Bone mineral content (BMC) and width (W) were measured bilaterally on the radius, ulna, and humerus. BMC and BMC/W loss rates were consistently lower in treatment than in control subjects. Loss was significantly reduced in the left and right humerus and the right radius. In premenopausal subjects, only left humerus BMC loss was significantly reduced by Ca supplementation. In postmenopausal treatment subjects, BMC and BMC/W bone loss was reduced in all 12 (bilateral radius, ulna, and humerus) of the bone variables measured, 5 at p less than 0.01 and 2 at p less than 0.05. Ca supplementation counteracted a large portion of the additional bone loss attributable to menopause in this population.

Absorptiometry, Photon↗
PubMed1989

Protriptyline treatment of sleep hypoxaemia in Duchenne muscular dystrophy.

Protriptyline 20 mg daily reduced the total time spent in rapid eye movement sleep in an open study in four subjects with Duchenne muscular dystrophy. Sleep related hypoxaemia and episodes of desaturation were reduced. Anticholinergic side effects were prominent, however, in these patients, precluding its use for regular treatment.

Adolescent↗
PubMed1989

Oxygen treatment of sleep hypoxaemia in Duchenne muscular dystrophy.

Patients with Duchenne muscular dystrophy develop progressive ventilatory muscle weakness and often die of respiratory complications. Recurrent, often profound, hypoxaemia has been shown in a previous study by this group to occur during rapid eye movement (REM) sleep in these patients before they develop sleep symptoms. In this study the efficacy and physiological effects of nocturnal oxygen in such patients have been assessed. Seven patients with Duchenne muscular dystrophy (age range 16-22 years; mean vital capacity 1.37 litres) with normal arterial blood gas tensions when awake were investigated by standard overnight polysomnography on an acclimatization night followed by two successive nights on which they received room air and nasal oxygen (2 litres/min) respectively in random order. Total sleep time, proportion of REM and non-REM sleep, and frequency and duration of arousals were similar on the two nights. When breathing air six of the seven subjects developed oxygen desaturation of more than 5% during REM sleep. With oxygen only one subject showed any oxygen desaturation exceeding 2.5%. Oxygen desaturation was associated with periods of hypopnoea or cessation of respiratory effort. The mean duration of episodes of hypopnoea and apnoea was prolonged during oxygen breathing by 19% and the mean duration of episodes during REM sleep by 33% (the proportion of REM sleep associated with hypopnoea and apnoea increased in all subjects). Heart rate in non-REM sleep fell by 9.3%; heart rate variation in REM and non-REM sleep was unchanged. These acute studies show that oxygen reduces the sleep hypoxaemia associated with respiratory muscle weakness; whether long term treatment will be possible or desirable is not clear as oxygen potentiates the underlying ventilatory disturbance.

Adolescent↗