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Biomedical subjects

W Scott

Publications and source records attributed to W Scott.

At least 19 recordsLinked to original sources
PubMed1992

A physiologically based kinetic model of rat and mouse gestation: disposition of a weak acid.

A physiologically based toxicokinetic model of gestation in the rat and mouse has been developed. The model is superimposed on the normal growth curve for nonpregnant females. It describes the entire gestation period including the period of organogenesis. The model consists of uterus, mammary tissue, maternal fat, kidney, liver, other well-perfused maternal tissues, and other poorly perfused maternal tissues, embryo/fetal tissues, and yolk sac and chorioallantoic placentas. It takes into account the growth of maternal tissues such as uterus, mammary glands, fat, and liver during pregnancy, as well as growth of the conceptus. The gestation model is based on published values of organ volumes and blood flows for the rat throughout pregnancy. It is scaled to the mouse using conventional scaling procedures. Its descriptive utility has been examined with the test chemical 5,5'-dimethyloxazolidine-2,4-dione (DMO), a weak acid that is not bound measurably in plasma or tissues and is eliminated by excretion in the urine. Concentrations of DMO were monitored in maternal rat and embryo plasma and in homogenates of maternal rat muscle and whole embryo after ip administration at 9:00 AM on Day 13 of gestation. On the basis that distribution of DMO is determined solely by its pK and the pH's of body fluids, pH and excretion rate values were estimated by visual optimization of model predictions to the concentration profile. Successful prediction of concentrations of DMO in the same tissues of pregnant mice after its ip administration at 9:00 AM on Day 10 or 11 of gestation required only adjustment for pH's of mouse body fluids.

Animals↗
PubMed1991

Sequentially administered ethinyl estradiol and medroxyprogesterone acetate in the treatment of refractory epithelial ovarian carcinoma in patients with positive estrogen receptors.

The activity of sequentially administered hormonal therapy was investigated over 25 days in 25 patients with epithelial ovarian carcinoma who had estrogen receptor (ERc)-positive tumors. Patients received ethinyl estradiol (EE) (50 micrograms/d) on days 1 to 7 and medroxyprogesterone acetate (MPA) (400 mg/d) on days 8 to 25. Twenty-three patients completed one or more courses of treatment. There were no complete responses (CR). Four partial responses (PR) with durations of 9, 4, 3, and 1 months were seen. Two incomplete responses with durations of 6 and 4 months were also seen. Six patients had stable disease (SD), and 11 patients had progression. The overall response rate was 17% and may represent a modest improvement in response over those in previously published studies conducted with MPA alone. No significant toxic effects were noticed, and some patients reported an improved sense of well-being. However, two patients experienced depression with this treatment. The mean ERc values in responders, patients with SD, and nonresponders were 70.0, 36.7, and 47.9 fmol/mg cytosolic protein, respectively. Future studies of hormonal therapy in patients with ovarian carcinoma should attempt to identify more reliable indices for determining sensitivity to these agents.

Administration, Oral↗
PubMed1991

legless insertional mutation: morphological, molecular, and genetic characterization.

Limb morphogenesis is an excellent model system to study pattern formation during vertebrate development. The legless (lgl) insertional mutation can serve as a tool to analyze specific events in limb development at the embryologic, genetic, and molecular levels. Hemizygous mice of this transgenic line are phenotypically normal, but homozygous mutants are inviable and exhibit limb, brain, and craniofacial malformations, as well as situs inversus. By morphological analysis of mutant hindlimb buds we show absence of a normal apical ectodermal ridge, a structure required for limb bud outgrowth, and an unusually high degree of mesenchymal and ectodermal cell death. Mutant embryos are extremely sensitive to retinoic acid, a known teratogen with a proposed role in limb development. The hindlimb malformations in legless mutants are less severe when bred into the BALB/c background, suggesting the involvement of other strain-specific genes. Molecular analysis of the disrupted region indicates two tightly linked insertion sites. Sequences flanking the transgene insertions have been cloned and mapped to chromosome 12, near the iv (situs inversus viscerum) locus. Consistent with this, complementation tests confirm allelism of lgl and iv and suggest that the transgene insertion may have disrupted more than one gene. Phylogenetically conserved sequences flanking the transgene insertions were identified and used to isolate candidate lgl and iv cDNAs.

Alleles↗
PubMed1991

The activity of locally applied cytotoxics to breast cancer cells in vitro.

The ability of commonly used operative lavage solutions to destroy breast cancer cells was investigated. The cytotoxicity of solutions of Savlon, noxythiolin, povidone iodine, hydrogen peroxide, bleomycin and water on two human breast cancer cell lines was measured in vitro. Viable cells were determined by ability to exclude trypan blue. Results have been analysed with standard non-parametric tests and demonstrate that all solutions tested significantly (P less than 0.01) reduced the number of viable cells recovered when compared with a control solution of phosphate buffered saline. Solutions of Savlon, 2.5% noxythiolin and povidone iodine were more effective than the other agents in reducing the number of recovered viable cells.

Anti-Infective Agents, Local↗
PubMed1990

Yellow nails, lymphedema and pleural effusion. Treatment of chronic pleural effusion with pleuroperitoneal shunting.

Pleural effusion secondary to lymphedema may be chronic, symptomatic and refractory to treatment, occasionally requiring invasive and painful procedures such as chemical pleurodesis, open pleural abrasion or pleurectomy to achieve control of the effusion and gain symptomatic relief. We report a patient with yellow nail syndrome and chronic pleural effusion successfully treated with pleuroperitoneal shunting.

Aged↗
PubMed1989

Efficacy of computed tomography of the thorax and upper abdomen and whole-body gallium scintigraphy for staging of lung cancer.

To assess the efficacy of performing both computed tomography (CT) of the thorax and upper abdomen and whole-body gallium scintigraphy for staging lung cancer, the results of each test were compared with those obtained by chest radiography and clinical examination in 100 patients. Clinical efficacy was defined in terms of accuracy in staging the tumor based either on surgery, biopsy, or clinical and radiologic follow-up. The CT provided significantly superior accuracy in 27 patients and minor additional staging information in 17 patients compared with the gallium scan. Whole-body gallium scintigraphy provided important additional information in nine patients and minor additional information in a further eight. The diagnostic yield of CT and gallium scanning was considered equivalent in 39 cases. Of the nine cases in which gallium was significantly superior to CT, clinical findings which suggested the presence of metastases had been noted before the scan in four cases. The authors' results confirm the utility of CT for staging lung cancer and indicate that the additional yield from gallium scintigraphy is relatively low provided a thorough history and physical examination have been performed.

Adult↗
PubMed1989

Treatment of advanced endometrial adenocarcinoma with cyclic sequential ethinyl estradiol and medroxyprogesterone acetate.

Fifteen patients with recurrent or progressive endometrial adenocarcinoma of moderate to poor histologic differentiation were entered in a phase II trial of sequentially administered oral ethinyl estradiol and medroxyprogesterone acetate. There were no significant clinical responses in 12 patients evaluated for response and four patients experienced thromboembolic complications. This cyclic treatment regimen is considered ineffective for this patient population at the dosages and schedules used.

Adenocarcinoma↗
PubMed1989

Energy-sparing adaptations in human pregnancy assessed by whole-body calorimetry.

The hypothesis that the energy cost of human pregnancy can be minimized by energy-sparing metabolic adaptations was tested using serial 24 h whole-body calorimetry. Eight healthy, well-nourished women were studied prepregnant and at 6, 12, 18, 24, 30 and 36 weeks gestation. Basal metabolic rate (BMR) showed highly characteristic changes within each subject and large inter-individual differences (F 3.5, P less than 0.01). Some subjects showed a highly significant depression of metabolism up to 24 weeks gestation in support of the initial hypothesis. At 36 weeks BMR ranged from +8.6 to +35.4% relative to the prepregnant baseline. This wide variability was not explained by differences in the amount of lean tissue gained. Women displaying the energy-sparing suppression of BMR tended to be thin, suggesting that changes in metabolism may be responsive to initial energy status (delta BMR v. prepregnant body fat: r 0.84, P less than 0.005). Changes in 24 h energy expenditure closely paralleled changes in BMR (r 0.98, P less than 0.001), since the energy cost of minor voluntary activity and thermogenesis remained very constant within each individual. Pregnancy decreased the net cost of weight-dependent and weight-independent standard exercises when expressed per kg body-weight: stepping -10 (SD 2)%, P less than 0.001 at 18-36 weeks, cycling -26 (SD 7)%, P less than 0.01 at 12-36 weeks. The average integrated maintenance costs of pregnancy matched previous group estimates from well-nourished women, but individual estimates ranged from -16 to +276 MJ (coefficient of variation 93%). This high level of variability has important implications for the prescription of incremental energy intakes during pregnancy. It may also have had evolutionary significance.

Adaptation, Physiological↗
PubMed1989

The use of heart rate monitoring in the estimation of energy expenditure: a validation study using indirect whole-body calorimetry.

1. A modified heart rate (HR) method for predicting total energy expenditure (TEE) was cross-validated against whole-body calorimetry (CAL). Minute-by-minute HR was converted to energy expenditure (EE) using individual calibration curves when HR exceeded a pre-determined 'FLEX' value designed to discriminate periods of activity. ('FLEX' HR was defined as the mean of the highest HR during rest and the lowest HR during the lightest imposed exercise.) Sedentary EE (below FLEX) was calculated as the mean EE during lying down, sitting and standing at rest. Sleeping EE was calculated as basal metabolic rate (BMR) predicted from standard equations. 2. Calibration curves of oxygen consumption v. HR for different postures at rest and during exercise were obtained for twenty healthy subjects (eleven male, nine female); mean r 0.941 (SD 0.04). The mean FLEX HR for men and women were 86 (SD 10) and 96 (SD 6) beats/min respectively. 3. Simultaneous measurements of HR and EE were made during 21 h continuous CAL, which included 4 x 30 min imposed exercise (cycling, rowing, stepping, jogging). HR exceeded FLEX for a mean of 98 (SD 41) min. Mean TEE by CAL (TEE.CAL) was 8063 (SD 1445) kJ. 4. The HR method yielded a mean non-significant underestimate in TEE (TEE.HR) of 1.2 (SD 6.2)% (range -11.4 to +10.6%). Regression of TEE.HR (Y) v. TEE.CAL (X) yielded Y = 0.868 X + 927 kJ, r 0.943, SE of the estimate 458 kJ, n 20. 5. The satisfactory predictive power and low cost of the method makes it suitable for many field and epidemiological applications.

Adolescent↗
PubMed1989

Randomized comparison of viral oncolysate plus radiation and radiation alone in uterine cervix carcinoma.

A randomized, controlled study was performed in patients with high-risk, untreated squamous cell carcinoma of the uterine cervix to evaluate the adjunctive use of viral oncolysate (VO) prepared from the SW756 cell line. Seventy-five patients were stratified by tumor volume and randomized to receive radiation therapy (RT) alone or RT plus intradermal immunization with VO. Fifty-one (68%) patients relapsed with a median survival (MS) of 29.1 months and a median progression-free interval (MPFI) of 18.0 months. No differences in MS or median PFI were observed by treatment arm or site of relapse, although a trend toward improved MS and median PFI in patients with small-volume primary lesions was suggested. Serum surface-binding antibody activity (greater than or equal to 1:8) to the SW756 cell line was detected in 14 of 41 unselected patients prior to therapy. Virus hemagglutination inhibitory activity (greater than or equal to 1:8) was detected in 37 of 41 patients before treatment. four-fold increases in titer were observed to the SW756 cell line in 83% and to influenza in 74% of patients tested after immunization. Preirradiation measurements of phytohemagglutinin-induced blastogenesis by the relative proliferation index (RPI) method in 39 patients revealed RPI values less than 0.58 in nine patients, eight of whom relapsed. At 3-6 months after the initiation of irradiation, 32 of 39 patients had values less than 0.58. Patients in the RT group with values less than 0.58 had significantly more relapses than those who received RT plus VO.

Adult↗
PubMed1988

Community-based health reporting.

A development monitoring service at the local level was established in 1978/79 in several communities in Kerala State (India) to collect socioeconomic and health-related data. These were collected from key community members and by household surveys using paid local staff as interviewers. Selected results for five years from three geographically distinct areas are presented, for three categories of data: health service infrastructure, infant mortality and overall morbidity, and weight and height of children under 10 years old. The three areas were a fishing village (A), a relatively remote highland community (B) and an agricultural area close to the state capital (C). During the five-year period there were rather modest improvements in the delivery of health and other services. Infant mortality rates fluctuated between 14 and 91 per 1,000 live births, reflecting the fact that the sample size (10,000 to around 25,000 for each area) was inadequate for calculating that rate. Morbidity rates also fluctuated markedly, without showing any definite trend. However, morbidity was defined as illness resulting in the inability to carry out normal activities, thus excluding cases of worm infestation and much diarrhoea, for example. A detailed analysis of reported symptoms for one year showed that respiratory tract diseases accounted for about half the cases of illness reported. The percentage of children with abnormally low weight- or height-for-age fell markedly in one area over three successive years (height-for-age from 41.6% to 33.2%, weight-for-age from 58.5% to 44.7%), but were significantly greater in another area with a higher average income, indicating that economic factors alone were not responsible for the improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

The insulin receptor. Structural basis for high affinity ligand binding.

Treatment of the soluble insulin receptor from human placenta with 1.25 mM dithiothreitol and 75 mM Tris at pH 8.5 results in complete reduction of interhalf disulfide bonds (class 1 disulfides) and dissociation of the tetrameric receptor into the dimeric alpha beta form. The alpha beta receptor halves exhibit a reduced affinity for insulin binding (Böni-Schnetzler, M., Rubin, J. B., and Pilch, P. F. (1986) J. Biol. Chem. 261, 15281-15287). Kinetic experiments reveal that reduction of class 1 disulfides is a faster process than the loss of affinity for ligand, indicating that events subsequent to reduction of interhalf disulfides are responsible for the affinity change. We show that a third class of alpha subunit intrachain disulfides is more susceptible to reduction at pH 7.6 than at pH 8.5 and appears to form part of the ligand binding domain. Reduction of the intrachain disulfide bonds in this part of the alpha subunit leads to a loss of insulin binding. Modification of this putative binding domain by dithiothreitol can be minimized if reduction is carried out at pH 8.5. When the insulin receptor in placental membranes is reduced at pH 8.5, the receptor's affinity for insulin is not changed when binding is measured in the membrane. However, the Kd for insulin binding is reduced 10-fold when alpha beta receptor halves are subsequently solubilized. Scatchard analysis of insulin binding to reduced or intact receptors in the membrane and in soluble form together with sucrose density gradient analysis of soluble receptors suggests that alpha beta receptor halves remain associated in the membrane after reduction, but they are dissociated upon solubilization. We interpret these results to mean that the association of two ligand binding domains, 2 alpha beta receptor halves, is required for the formation of an insulin receptor with high affinity for ligand.

Cell Membrane↗
PubMed1986

Benzodiazepine-opiate antagonism--a problem in intensive-care therapy.

A 14-year-old previously fit schoolboy was admitted with staphylococcal pneumonia secondary to influenza A infection. His condition deteriorated as he developed adult respiratory distress syndrome (ARDS); during a stormy recovery exceptionally high doses of benzodiazepines and opiates were given in order to suppress voluntary breathing during a successful period of assisted ventilation. It is possible that benzodiazepine-opiate antagonism developed. Subsequent studies in laboratory mice indicate that the respiratory depressant effects of morphine can be antagonized by prior treatment with lorazepam.

Adolescent↗
PubMed1985

Technical and clinical assessment of oxygen concentrators.

One membrane oxygen enricher (Oxygen Enrichment Company OE-4E) and four molecular sieve (MS) concentrators (Mountain Medical Econo2, De Vilbiss MINI DeVO2, Cryogenic Roomate III, and Mountain Medical Mini O2) have been studied to assess technical and clinical performance. During four weeks of continuous operation at a flow rate of 2 l min-1 (6 l min-1 for OE-4E) consistent oxygen levels were delivered by all machines (mean greater than 93% for MS concentrators, 36.5% for OE-4E). At flow rates of up to 21 mm-1 all four MS machines delivered oxygen concentrations greater than 92%, but at 3 l min-1 (Econo2 89.6%, MINI DeVO2 93.9%, Roomate III 92.0%, Mini O2 85.0%) and at 4 l min-1 (Econo2 78.0%, Mini DeVO2 84.7%, Roomate III 83.3%, Mini O2 69.1%) the two newer machines gave higher oxygen concentrations. In 20 hypoxic patients the mean oxygen saturation levels achieved when they were breathing oxygen from the MS concentrators at a flow rate of 2 l min-1 were similar (Econo2 92.6%, MINI DeVO2 92.5%, Roomate II 92.6%), but the level achieved when they were breathing from the OE-4E, at the equivalent flow rate of 6 l min-1, was lower (91.0%, p less than 0.005). The performance of concentrators in service (Econo2, MINI DeVO2, Mini O2) was satisfactory when judged by patients' oxygen saturation levels and delivered oxygen concentrations. The OE-4E may be indicated for a small number of patients who require oxygen with high humidification. The four MS concentrators studied are all suitable for domiciliary use, but the MINI DeVO2 and Roomate III have advantages in terms of better performance at high flow rates and reduced size and weight.

Aged↗