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Biomedical subjects

J C Scott

Publications and source records attributed to J C Scott.

At least 19 recordsLinked to original sources

Lantibiotic-mediated anti-lactobacillus activity of a vaginal Staphylococcus aureus isolate.

Staphylococcus aureus strain 26 inhibited the growth of 23 of 26 lactobacilli of endocervical origin, but only two of 17 staphylococci, in deferred antagonism tests. The inhibitory agent, a bacteriocin-like inhibitory substance (BLIS) named staphylococcin Au-26, was obtained from vigorously shaken liquid cultures containing a 0.1% (v/v) supplement of Tween 80 and was purified by chromatographic fractionation on XAD-2, carboxymethyl Sephadex and reversed phase HPLC. The molecular mass of staphylococcin Au-26 was estimated by SDS-PAGE to be approx. 2700. The detection of lanthionine residues in the molecule, the high stability to heating at acidic but not alkaline pH values and inactivation by proteinases indicate that staphylococcin Au-26 is a member of the lantibiotic class of peptide antibiotics--the first reported to be produced by a S. aureus strain. Primary sequence analysis showed that the N-terminus of the molecule is isoleucine, a characteristic also displayed by the lantibiotics nisin, epidermin and gallidermin.

Amino Acids

Caustic ingestion injuries of the upper aerodigestive tract.

Few reports have described in detail the injuries that occur to the oral cavity, pharynx, and larynx following caustic ingestion. The role of dynamic radiographic studies to delineate the extent of damage has been minimized. In-depth radiographic analysis of such cases has not, to our knowledge, been previously reported. In order to examine the injuries and functional abnormalities of these sites following caustic ingestion, the records of The Johns Hopkins Swallowing Center were reviewed. Five patients were identified as having significant upper aerodigestive tract caustic injuries. All patients had dysphagia, epiglottis injuries, and incomplete laryngeal protection with aspiration. Four of five had sustained some degree of esophageal stenosis. Also noted were pharyngeal muscle dysfunction, nasopharyngeal regurgitation, tongue fixation, and hypopharyngeal stenosis. Roentgenographic findings are described and illustrated. The multidisciplinary approach to the management and rehabilitation of these patients is discussed.

Adult

Functional improvement in geriatric trauma patients admitted to a dedicated rehabilitation hospital.

A retrospective study was undertaken of trauma patients over 55 years of age who were admitted to a rehabilitation hospital during an 18-month period. Significant risk factors for poorer in-hospital improvement in functional independent measures were male sex, having an offspring listed as next of kin, pre-injury diabetes mellitus and/or dementia, and number of co-morbidities. Being married was found to be protective.

Activities of Daily Living

Which fractures are associated with low appendicular bone mass in elderly women? The Study of Osteoporotic Fractures Research Group.

OBJECTIVE: To determine which types of fractures have an increased incidence in elderly women with low appendicular bone mass. DESIGN: Prospective cohort study. SETTING: Four clinical centers in the United States (Baltimore, Maryland; Minneapolis, Minnesota; Portland, Oregon; Monangehela Valley, Pennsylvania); and one coordinating center in San Francisco, California. SUBJECTS: Ambulatory, nonblack women (9704) aged 65 years or more who were recruited from population-based listings. MEASUREMENTS: We measured bone mass at the distal and proximal radius and calcaneus using single-photon absorptiometry. Fractures were verified radiographically. Associations were calculated as age-adjusted hazard ratios (with 95% Cls) per standard deviation decrease in bone mass. MAIN RESULTS: During a mean follow-up of 2.23 years, 841 nonspinal fractures occurred in 753 women. The risks for fractures of the wrist, foot, humerus, hip, rib, toe, leg, pelvis, hand, and clavicle were significantly related to reduced bone mass (P less than 0.05). These fractures represented 74% of nonspinal fractures. The overall hazard ratio for the occurrence of one or more of these fractures was 1.65 (Cl, 1.49 to 1.82) at the distal radius. In a subsample of the cohort, vertebral fractures were also related to low bone mass. Fractures of the ankle, elbow, finger, and face, however, were not associated with bone mass at any measurement site; the overall hazard ratio for these fractures was 1.12 (Cl, 0.96 to 1.30) at the distal radius. CONCLUSION: Most types of fractures have an increased incidence in elderly women with low bone mass.

Age Factors

Electroencephalographic quantitation of opioid effect: comparative pharmacodynamics of fentanyl and sufentanil.

The authors compared the pharmacodynamics of sufentanil with those of fentanyl using the electroencephalogram (EEG) as a measure of opioid drug effect. Sixteen patients were given a rapid infusion of sufentanil (18.75 micrograms/min) during EEG recording. To quantitate the opioid-induced slowing of the EEG, the authors analyzed its power spectrum and calculated the spectral edge. An inhibitory sigmoid Emax model of the maximal decrease in spectral edge produced by the opioid related spectral edge values to serum concentrations of sufentanil. The resulting data for the pharmacodynamic parameters of sufentanil were compared with fentanyl parameters that were obtained by reanalysis from an identically conducted, previously published study. The half-time of blood-brain equilibration (T1/2Keo) was not statistically different between sufentanil and fentanyl (6.2 +/- 2.8 vs. 6.6 +/- 1.7 min, mean +/- SD, respectively). The intrinsic potency of sufentanil, as measured by the serum concentration needed to cause half the maximal EEG slowing (IC50), was 12-fold greater (0.68 +/- 0.31 ng/ml) than that of fentanyl (8.1 +/- 2.2 ng/ml). The second part of the study verified the hypothesis that administration of equipotent bolus doses would produce equal onset times. Bolus injections of either 125 micrograms of sufentanil or 1,250 micrograms of fentanyl were given during EEG recording. The time from injection to 50% maximal EEG slowing (T50) was calculated for each patient. The values for T50 for the two groups did not differ. The authors conclude that fentanyl and sufentanil have similar pharmacodynamic profiles, the former being 12 times more potent than the latter.

Adolescent

Nalbuphine after major gynecologic surgery. Comparison of patient-controlled analgesia and intramuscular injections.

A randomized investigation compared the efficacy and safety of nalbuphine administered by two methods, a patient-controlled infuser system and intramuscular (IM) injections, after major gynecologic surgery. Forty-seven patients were randomly assigned to receive nalbuphine by either method. The 22 patients using the infuser were given a 2.0-mg, incremental dose with a 10-minute lock-out interval between doses. A similar group receiving 10-15 mg IM every three hours served as the control. Misprogramming, overdosage, depressed respiration and drug dependence were not encountered. Self-administration provided equally satisfactory sedation and more immediate pain relief without painful injections. Although patients with the infuser had the ability to self-administer more medication, they did not use higher doses of nalbuphine than did the IM group. The additional cost of the infuser system was offset by the satisfaction expressed by the patients and by the improved nursing efficiency. Nalbuphine administered with a patient-controlled infuser provided an effective balance between analgesia and sedation and offered advantages over IM injections.

Adult

Appendicular bone density and age predict hip fracture in women. The Study of Osteoporotic Fractures Research Group.

To determine whether measurement of bone density predicts hip fracture in women, we prospectively studied 9703 nonblack women aged 65 years and older who had measurements of bone mineral density using single-photon absorptiometry in the calcaneus, distal radius, and proximal radius. During an average of 1.6 years of follow-up, 53 hip fractures occurred. The risk of hip fracture was inversely related to bone density at all three measurement sites. After adjusting for age, the relative risk of hip fracture was 1.66 for a decrease of 1 SD in the bone density at the calcaneus (95% confidence interval, 1.22 to 2.26), 1.55 (95% confidence interval, 1.13 to 2.11) at the distal radius, and 1.41 (95% confidence interval, 1.06 to 1.88) at the proximal radius. None of the three measurements was a significantly better predictor of hip fracture than the others. After adjusting for bone mineral density, the risk of hip fracture doubled for each 10-year increase in age (relative risk, 2.09; 95% confidence interval, 1.31 to 3.33). We conclude that decreased bone density in the appendicular skeleton is associated with an increased risk of hip fracture, but this accounts for only part of the age-related increase in risk of hip fracture among older women.

Age Factors

Pharmacokinetics of fentanyl administered by computer-controlled infusion pump.

Fentanyl was administered to 21 patients using a computer-controlled infusion pump (CCIP) based on a pharmacokinetic model. Eleven of the patients were dosed according to the pharmacokinetics described by McClain and Hug, and ten of the patients were dosed according to the pharmacokinetics described by Scott and Stanski. The authors measured the difference between the measured arterial fentanyl concentrations and the concentrations predicted by the CCIP for each pharmacokinetic parameter set. The median absolute performance error (MDAPE) in patients dosed according to McClain and Hug's parameters was 61%, and the MDAPE in patients dosed according to Scott and Stanski's parameters was 33%. The population pharmacokinetics in these 21 patients were analyzed using a pooled data technique. The pharmacokinetics of fentanyl in this population showed a smaller central compartment volume and a more rapid initial distribution half-life than previously estimated for fentanyl. The derived pharmacokinetic parameters described these patients well and also predicted the observed fentanyl concentrations from four previously published fentanyl studies with reasonable accuracy. Comparison of the parameters used by the authors with those of McClain and Hug demonstrated that dosing regimens designed from pharmacokinetic models can be fairly accurate at the times sampled in the original study but may not be accurate at time points not sampled in the original research. The authors concluded that although the pharmacokinetics of fentanyl administered by CCIP are the same as the pharmacokinetics of fentanyl administered by a bolus or constant rate infusion, a pharmacokinetic study using a CCIP may be particularly effective at characterizing the most rapid distribution pharmacokinetic parameters, and thus may provide parameters appropriate for subsequent use in a CCIP.

Adult

Evaluation of a nonisotopic probe for detection of Chlamydia trachomatis in endocervical specimens.

A nonisotopic probe (Gen-Probe PACE; Gen-Probe, Inc., San Diego, Calif.) for detection of Chlamydia trachomatis in endocervical specimens was evaluated in 344 women attending a dysplasia clinic or an obstetrics clinic and 158 women who visited an emergency room. For each patient, the probe, a tissue cell culture, and a direct immunofluorescent-antibody test (DFA; MicroTrak; Syva Co., Palo Alto, Calif.) were used. C. trachomatis was detected in 54 specimens by at least one method. Forty-four, 44, and 37 specimens were positive by culture, probe, and DFA, respectively, and 31 were positive by all three methods. Considering culture-positive plus both probe- and DFA-positive results as the "gold standard," we determined the overall sensitivity, specificity, and positive and negative predictive values of the probe to be 80, 98, 82, and 98%, respectively. These values were 94, 98, 84, and 99%, respectively, in emergency room patients and 71, 98, 80, and 97%, respectively, in clinic patients. The sensitivities, specificities, and negative predictive values of the DFA and probe were comparable. The positive predictive values of the DFA in all patients and in emergency room and clinic patients were 97, 100, and 95%, respectively. Given the number of probe-positive results that were not confirmed by culture, we do not recommend using the Gen-Probe PACE to screen for C. trachomatis in women with a low to moderate risk for infection.

Cervix Uteri

Osteoporosis and hip fractures.

Epidemiologic studies have contributed to our understanding of osteoporosis through identification of groups at high risk of fracture and through discernment of factors associated with increased risk of low bone density and fracture. Many of the questions remaining can be addressed only through the use of epidemiologic methods in human populations. These include longitudinal studies in large cohorts to better delineate factors associated with bone loss and fracture and randomized clinical trials to adequately assess therapies. Particularly needed are studies in adolescents to assess determinants of peak bone mass and the effect of subsequent bone loss with aging.

Hip Fractures

Preanesthetic medication in children: a comparison of oral transmucosal fentanyl citrate versus placebo.

Initial studies have suggested that oral transmucosal fentanyl citrate (OTFC) in a dose of 15-20 micrograms/kg may be a safe and effective preanesthetic medication in children and adults, but this has not been demonstrated in a randomized, double-blind fashion. The purpose of this study was to determine in a randomized, double-blind manner, the efficacy of a lollipop containing fentanyl citrate as a preanesthetic medication before surgery in children. Forty health ASA physical status 1 or 2 children 3-12 yr of age were divided randomly and in double-blind fashion into two groups. Group 1 received the lollipop containing OTFC and group 2 received a placebo lollipop. An appropriate size lollipop was chosen so that if the patient received fentanyl, the total dose would be 15-20 micrograms/kg. Anxiety, sedation, and separation scores were assessed preoperatively and ease of induction was rated. Oxygen saturation and respiratory rate were monitored. Time intervals from preanesthetic to induction and from recovery room (PACU) admission to discharge were noted. Recovery room behavior was assessed upon admission and discharge. Complications and the need for postoperative opioids were noted. OTFC produced significantly more sedation and less anxiety compared with that following placebo. Respiratory rate was significantly decreased in the OTFC group, but oxygen saturation was not significantly different between groups. Anxiety and separation scores and the quality of induction were better in the OTFC group. There was a higher incidence of nausea and pruritus in the fentanyl group. OTFC did not prolong the PACU stay.

Administration, Oral

Studies in REST. I. Reduced Environmental Stimulation Therapy (REST) and reduced alcohol consumption.

Reduced Environmental Stimulation Therapy (REST), formerly known as "sensory deprivation," was used in conjunction with pre-recorded anti-alcohol messages to reduce alcohol consumption. Subjects were college students of both sexes who were "heavy social drinkers," that is, early prodromal alcoholics. There were two studies. In the pilot study experimental subjects had two and a half hours of REST, during which they heard one of two differently worded anti-alcohol messages. After two weeks their alcohol intake dropped significantly from baseline levels (33% and 29%); control subjects showed no significant changes. In a replication and follow-up study experimental subjects had two and a half hours of REST, during which they heard a revised version of the most effective anti-alcohol message used in the pilot study. Two weeks later their alcohol consumption dropped 55% from baseline levels. These reductions in alcohol intake were fully sustained on follow-up three months and six months later. Untreated control subjects showed increased alcohol intake on follow-up.

Adult

Testing computer-controlled infusion pumps by simulation.

The pharmacokinetic behavior of intravenous anesthetic drugs can be described by two- or three-compartment models. Rapid achievement and maintenance of steady plasma concentrations of these drugs requires a complicated delivery scheme, perhaps best controlled by a computer. The authors developed a method of simulating the performance of a computer-controlled infusion pump from the differential equations describing drug transfer between compartments. They also derived a mathematically simple and flexible approximate solution to these equations using Euler's numerical method. They incorporated this approximate solution into a computer-controlled infusion pump for intravenous drugs. They tested their pump by simulating the administration of fentanyl to a hypothetical patient whose fentanyl pharmacokinetics were described by a three-compartment model. The exact analytical solution served as the standard of comparison. The approximation technique, using a 15-s interval between model updates, had a maximum error of 0.35 ng.ml-1, and rapidly converged on the exact solution. The simulations revealed oscillations in the system. The authors suggest that such simulations be used to evaluate computer-controlled infusion pumps prior to clinical trials of these devices.

Anesthetics

Decreased morbidity and increased survival in cervical cancer treatment.

Thirty-seven patients with previously untreated invasive carcinoma of the uterine cervix, International Federation of Gynecology and Obstetrics (FIGO) stages IB to IVA, were treated with 4,000 rad external beam radiotherapy (EXRT) to midplane, followed by two intracavitary endocurietherapy (ECT) applications of 2,500 rad each to point "A" using a Kumar applicator, for a total dose of 9,000 rad. The major complication rate was 2.7 percent, and the local control rate was 85 percent (22/26 patients) for stages IB and II, and 91 percent (10/11 patients) for stages III and IVA. The three-year uncorrected observed actuarial survival was 80.3 percent for stages IB and II, and 81.8 percent for stages III and IVA. The three-year adjusted actuarial survival rate was 95.2 percent for stages IB and II, and 90.5 percent for stages III and IVA.

Brachytherapy

Betamethasone dipropionate in optimized vehicle. Intermittent pulse dosing for extended maintenance treatment of psoriasis.

A study was done of extended maintenance therapy using either betamethasone dipropionate (Diprolene) in optimized vehicle (OV) (ointment) or placebo in patients with psoriasis vulgaris. Of 59 patients originally enrolled in the study, 38 assessable patients achieved clearing of at least 85% improvement from baseline with traditional betamethasone in OV twice a day for two to three weeks before intermittent pulse dosing was attempted. Thereafter, the test medication was used on weekends (three consecutive doses at 12-hour intervals) once a week. Fourteen patients (74%) of the betamethasone in OV group and four patients (21%) of the placebo group maintained a remission status for 12 weeks. Intermittent pulse dosing with betamethasone in OV seems safe and efficacious maintenance therapy in selected psoriatic patients.

Administration, Topical

Improved radioreceptor assay of opiate narcotics in human serum: application to fentanyl and morphine metabolism.

A recently developed radioreceptor assay (RRA) (1) that employs 3H-naloxone and rat brain membrane homogenates was improved two ways. First, the brain membranes were preincubated in the presence of sodium ions, and second, manganase-II ions were added to the sample incubations. These changes enhanced the assay sensitivity and reproducibility with stored membrane preparations and reduced the effects of serum constituents (Na+) on ligand-receptor binding. Patient sera were assayed by radioimmunoassay (RIA) and RRA after fentanyl administration and by high-performance liquid chromatography (HPLC) and RRA after morphine administration. The results with both fentanyl assays were comparable, and no fentanyl metabolites were detectable by RRA after HPLC of serum extracts. In contrast, preliminary results with the HPLC-RRA procedure suggest the presence of an active morphine metabolite of unknown structure in sera obtained from patients on morphine therapy.

Animals

HPLC method for the analysis of cyproterone acetate in tablets.

A reversed-phase high-performance liquid chromatographic (HPLC) method is described for the analysis of cyproterone acetate in tablets. This steroid is extracted and quantitated using a C18 column. This procedure is shown to be rapid, simple, and valid in terms of recovery, linearity, and precision. Application of this method to analyze dilute samples obtained from dissolution testing is demonstrated.

Chromatography, High Pressure Liquid

Assay methods for fentanyl in serum: gas-liquid chromatography versus radioimmunoassay.

In this study, two independent laboratories assessed the validity of the fentanyl radioimmunoassay (RIA) by measuring a series of spiked control serum samples and 429 serum samples from 20 patients receiving fentanyl for their anesthesia. Additionally, a gas-liquid chromatographic (GLC) method specific for the parent drug was also applied to the same serum samples. The RIA measurement of fentanyl by the two laboratories resulted in comparable values for both control samples and samples from patients in a range of 0.5-50 ng/ml. The GLC method agreed with both RIA measurements in the spiked control and patient samples. The authors' results demonstrate the validity of the RIA as a measurement technique for fentanyl in human serum samples.

Calibration