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Biomedical subjects

J C Scott

Publications and source records attributed to J C Scott.

At least 73 records · Page 4Linked to original sources

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↗

Decreased fentanyl and alfentanil dose requirements with age. A simultaneous pharmacokinetic and pharmacodynamic evaluation.

The effect of increasing age on the dose of fentanyl or alfentanil required to produce the same electroencephalographic (EEG) stage was studied in adult male patients. The pharmacokinetic and pharmacodynamic components of each patient's dose-response relationship were evaluated simultaneously. Frequent arterial blood samples drawn during and after an infusion of fentanyl or alfentanil were assayed by radioimmunoassay and permitted determination of each patient's pharmacokinetic profile. The EEG was analyzed by power spectral analysis and a parameter (spectral edge frequency) chosen to quantitate the narcotic-induced EEG slowing. An inhibitory sigmoid Emax pharmacodynamic model related spectral edge frequency to narcotic serum concentrations. The dose requirement of fentanyl or alfentanil decreased significantly with increasing age (a 50% decrease from age 20 to 89). No age-related changes in the pharmacokinetic parameters were found. Brain sensitivity (as determined by EEG changes) did decrease significantly with age. Thus, the decreased dose requirement in the elderly had a pharmacodynamic explanation, using the EEG as a measure of narcotic drug effect.

Adult↗

EEG quantitation of narcotic effect: the comparative pharmacodynamics of fentanyl and alfentanil.

Fentanyl and alfentanil produce very similar electroencephalographic (EEG) changes in humans. With increasing serum concentrations of either narcotic, progressive slowing in frequency occurs. This narcotic effect on the brain was quantitated using off-line EEG power spectrum analysis. During EEG recording, six unpremedicated patients received a fentanyl infusion (150 micrograms/min), and six received alfentanil (1,500 micrograms/min) until a specific level of EEG depression (delta waves) occurred. Timed arterial blood samples were obtained for measurement of the narcotic serum concentrations. The narcotic-induced EEG changes were found to lag behind (in time) the serum narcotic concentration changes. To accurately relate EEG changes to serum narcotic concentrations, a pharmacodynamic model (inhibitory sigmoid Emax) was combined with a pharmacokinetic model that incorporated an "effect" compartment. (The effect compartment is the separate pharmacokinetic compartment where drug effect is directly proportional to drug concentration. It is the effect site.) The magnitude of the time lag was quantitated by the half-time of equilibration between serum narcotic concentrations and concentrations in the effect compartment. With fentanyl a significantly greater time lag was present (half-time = 6.4 +/- 1.3 min; mean +/- SD) than with alfentanil (half-time = 1.1 +/- 0.3 min). This difference in time lag between blood concentration and effect may be due to the larger brain-blood partition coefficient for fentanyl. The steady-state serum concentration that caused one-half of the maximal EEG slowing was 6.9 +/- 1.5 ng/ml for fentanyl, compared with 520 +/- 163 ng/ml for alfentanil.(ABSTRACT TRUNCATED AT 250 WORDS)

Alfentanil↗

Indication for interstitial brachytherapy in carcinoma of the uterine cervix.

More than 40 patients with gynecological, genitourinary, and gastrointestinal malignancies, both primary and recurrent but confined to the pelvis, were treated with interstitial irradiation over a four-year period. Interstitial irradiation was the choice of treatment for early carcinoma of the prostate, carcinoma of the anal canal less than T2, recurrent carcinoma of the uterine cervix, and carcinoma of the cervical stump. The authors' experience in treating recurrent carcinoma of the uterine cervix with interstitial irradiation is the basis for the indications for selecting the technique of interstitial irradiation presented.

Brachytherapy↗

Endogenous formation of N-nitrosoproline upon cigarette smoke inhalation.

It was the goal of this study to assay the potential of inhaled cigarette smoke for endogenous N-nitrosation of amines in smokers by measuring urinary excretion of N-nitrosoproline (NPRO). Nonsmoking and smoking men were placed on a controlled diet which was low in proline and in ascorbic acid. On days 1-3, the volunteers received the controlled diet alone (Group I); on days 4-6, the diet was supplemented by a single daily dose of 300 mg proline (Group II); on days 7-9, the diet was supplemented by a single daily dose of 1 g ascorbic acid followed by 300 mg proline (Group III); and for the last three days, a single daily dose of 1 g ascorbic acid was given (Group IV). Collections of 24-h urine were made on days 3, 6, 9 and 12 of the study. The urine was analysed for NPRO, creatinine and cotinine. The mean 24-h NPRO excretion for 13 nonsmokers in Group I was 3.6 micrograms, whereas the NPRO excretion in 13 smokers was 5.9 micrograms/24 h, significantly higher than that of the nonsmokers (p less than 0.05). Urinary NPRO in 14 nonsmokers of Group II was significantly lower than that of the 14 smoking volunteers (p less than 0.05). In Group III smokers had reduced urinary levels of NPRO as a consequence of ascorbic acid intake. Differences in NPRO excretion by smokers and nonsmokers in Group IV were insignificant. These findings suggest that the documented endogenous N-nitrosation of proline which occurs as a result of cigarette smoke inhalation may also apply to other N-nitrosatable amines, including nicotine, and thus lead to in-vivo formation of carcinogenic N-nitrosamines. Four nonsmokers exposed to passive smoke for 80 min three times per day did not exhibit elevated NPRO levels in their 24-h urine.

Adult↗

Surgery following initial treatment of ovarian carcinoma: restaging (second-look) and palliative operations.

Of 73 patients treated for ovarian carcinoma at the University of Nebraska Medical Center between 1976 and 1982, 37 underwent a second operative procedure following initial surgery. A total of 14 had a second look following complete clinical response, 11 had intestinal diversion, and 12 underwent other procedures. Second-look surgery proved useful in evaluating patients in clinical remission and directing subsequent management. The majority of patients whose operations were for persistent or recurrent disease had short survival. However, such surgery helps occasional patients and should be considered when circumstances warrant.

Carcinoma↗

A survey of blood pressure in the state of Maryland.

To provide baseline data for a state program to coordinate hypertension resources, a blood pressure (BP) survey was undertaken in Maryland in 1978. A statewide probability sample of households was chosen; each adult member was eligible for interview and measurement of BP. A total of 6,425 adults were interviewed for an overall response rate of 79.5%. Using a definition of diastolic blood pressure (DBP) of 95 mm Hg or higher or use of antihypertensive medication, 15.1% of state residents were estimated to be hypertensive. Of these, 85.8% were estimated to be aware of their condition, 77.6% of them were treated, and 67.6% had their BP controlled to a normal level by medication. Data are also presented using DBP 90 mm Hg or higher. A comparison of data from the Hypertension Detection and Follow-up Program (HDFP) home screen in 1973-1974 and comparable information from this survey showed lower rates of awareness, treatment, and BP control in hypertensives at HDFP home screen. Results of this survey will be compared with those of a second statewide survey conducted four years later to assess changes in rates of hypertension awareness, treatment, and control.

Adult↗

Diagnostic significance and sequelae of cone biopsy.

All cone biopsies from our institution over a 10-year period were reviewed. Two hundred seventy-one patients underwent 274 procedures. Preoperative colposcopic evaluation markedly reduced the proportion of patients with residual cervical epithelial neoplasia (CIN). No patient in our series required conization for diagnosis of frankly invasive carcinoma. Following colposcopy and conization, 8% of patients had disease extending to the surgical margins; eight of 11 such patients (72%) with adequate follow-up had no further CIN. Colposcopy and cytology underestimate the final pathologic diagnosis in many patients with incomplete visibility of the transformation zone, so conization is mandatory in this circumstance. Conization in pregnancy was associated with increased hemorrhage; colposcopy has reduced the need for this operation in gravid patients.

Biopsy↗

N-Nitrosomorpholine and other volatile N-nitrosamines in snuff tobacco.

Ten popular snuff brands from the USA and Sweden were analyzed for volatile N-nitrosamines (VNA). Seven of these samples contained between 20 and 70 p.p.b. of N-nitrosomorpholine (NMOR), a strong animal carcinogen. Some of the snuff containers which were made of waxed cardboard contained morpholine. This observation and a model study with the container waxes plus [14C]morpholine indicate that NMOR possibly can be formed by way of diffusion of the morpholine into the snuff and subsequent N-nitrosation. The VNA including NMOR (60-1150 p.p.b.) together with N-nitrosodiethanolamine (NDELA; 225-3300 p.p.b.) and the four tobacco-specific N-nitrosamines (TSNA; 1300-80,000 p.p.b.) contribute significantly to the carcinogenic potential of snuff. This tobacco product, although a known human carcinogen, is becoming increasingly popular especially among young people in the USA and Sweden. A recently introduced Swedish brand with individual snuff portions wrapped in aluminum foil was free of VNA (less than 2 p.p.b.) and contained relatively low levels of NDELA (290 p.p.b.) and TSNA (4200 p.p.b.). This indicates that practical approaches towards lowering N-nitrosamine levels in these snuff products are available.

Carcinogens↗