Search PubMed⌕ Search

Biomedical subjects

S Duncan

Publications and source records attributed to S Duncan.

At least 37 records · Page 2Linked to original sources
PubMed1995

Intrapulmonary pharmacokinetics of clarithromycin and of erythromycin.

The intrapulmonary pharmacokinetics of orally administered clarithromycin (500 mg every 12 h for five doses) or erythromycin (250 mg every 6 h for nine doses) were studied in 32 healthy adult volunteers. Four of the subjects, two in the clarithromycin group and two in the erythromycin group, were smokers. Bronchoscopy, bronchoalveolar lavage, and venipuncture were performed at 4, 8, 12, 24, and 48 h after administration of the last dose of clarithromycin and at 4, 8, and 12 h after administration of the last dose of erythromycin. Clarithromycin was measured by high-performance liquid chromatography, and erythromycin was measured by a microbiological assay. No systemic sedation was used. There were no major adverse events. The concentrations of antibiotics in epithelial lining fluid (ELF) were calculated by the urea dilution method. The volumes (mean +/- standard deviation) of ELF were 1.9 +/- 2.0 ml and 1.5 +/- 0.7 ml in the clarithromycin and erythromycin groups, respectively (P > 0.05). There was no effect of smoking on the amount of bronchoalveolar lavage fluid recovered, the volume of ELF, or the number of erythrocytes present in the lavage fluid (P > 0.05 for all comparisons). The total number of alveolar cells, however, was almost threefold greater in the smokers versus that in the nonsmokers (P < 0.05). Clarithromycin was concentrated in ELF (range, 72.1 +/- 73.0 micrograms/ml at 8 h to 11.9 +/- 3.6 micrograms/ml at 24 h) and alveolar cells (range, 505.8 +/- 293.1 micrograms/ml at 4 h to 17.0 +/- 34.0 micrograms/ml at 48 h). 14-(R)-Hydroxyclarithromycin was also present in these compartments, but at lower concentrations than the parent compound. The concentrations of erythromycin in ELF and alveolar cells were low at 4, 8, and 12 h following the last dose of drug (range, 0 to 0.8 +/- microgram/ml in ELF and 0 to 0.8 +/- 1.3 microgram/ml in alveolar cells). The clinical significance of any antibiotic concentrations in these compartments in unclear. The data suggest, and we conclude, that clarithromycin may be a useful drug in the treatment of pulmonary infections, particularly those caused by intracellular organisms.

Adult↗
PubMed1994

Interactions of intestinal mediators in the mode of action of cholera toxin.

Cholera toxin (CT) and prostaglandin E2 (PGE2) increased the synthesis of 3',5'-cyclic adenosine monophosphate (cAMP) in rabbit intestinal mucosa, which appeared to be responsible for inducing the release of 5-hydroxytryptamine (5-HT) from enterochromaffin cells into the intestinal lumen. With isolated intestinal cells, CT induced the synthesis of PGE2 more efficiently from epithelial cells than from lamina propria cells; however, the basal amount of this eicosanoid produced by lamina propria cells was approximately six-fold more than that formed by the epithelial cells. The CT-induced stimulation of arachidonate metabolism appeared to be generalised in nature, as PGF2 alpha and leukotrienes were synthesised in addition to PGE2. Injection of dibutyryl cAMP into the intestinal lumen in vivo markedly reduced both basal levels of PGE2, as well as CT-induced levels of PGE2, released into the luminal fluid. Similarly, when biopsy samples of tissue from rabbit intestinal loops, challenged in vivo with dibutyryl cAMP, were washed and incubated in vitro, the amount of PGE2 synthesis remained below basal levels. In contrast, when biopsy samples of normal small intestinal tissue were exposed in vitro to dibutyryl cAMP, PGE2 synthesis increased. Thus, cAMP appeared to down-regulate the levels of intestinal eicosanoids in vivo, despite its innate capacity to evoke PGE2 synthesis from mucosal tissue in vitro. Thus, the data indicate that CT-induced mediators exhibit interactive effects that alter their cellular concentrations, that in turn could affect the biological responses.

Animals↗
PubMed1994

Luminescence-based detection of activity of starved and viable but nonculturable bacteria.

A naturally luminescent bacterium, Vibrio harveyi, and two bacteria, Escherichia coli and Pseudomonas fluorescens, which had been genetically marked with luminescence were starved in liquid medium at 4 and 30 degrees C for 54 days. Total cell concentrations and concentrations of culturable and viable cells were determined by acridine orange staining, dilution plate counting, and direct viable counting, respectively, and population activity was measured by luminometry. V. harveyi became nonculturable but maintained viability during starvation at 4 degrees C and maintained both culturability and viability at 30 degrees C. In contrast, E. coli became viable but nonculturable during starvation at 30 degrees C but not at 4 degrees C. Luminescence of nonculturable cells of both strains, and culturable cells of V. harveyi, decreased to background levels during starvation. Luminescence of starved culturable cells of E. coli also fell below background levels but occasionally increased to detectable values. Viable, nonculturable forms of P. fluorescens were not detected at either temperature, and cells starved at 4 degrees C showed no decrease in luminescence measured during incubation of samples at 25 degrees C. Following incubation of late-log-phase cells with yeast extract and nalidixic acid, changes in light output directly paralleled changes in cell length, as observed during direct viable counting. Quantification of changes in luminescence following incubation of starved cells with yeast extract enabled measurement of the activity of both culturable and viable but nonculturable cells. Measurement of luminescence was significantly more sensitive, rapid, and convenient in quantifying activity following nutrient amendment than measurement of changes in cell length.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteria↗
PubMed1994

Kindergarten predictors of first-grade reading achievement: a regular classroom sample.

Routinely collected measures for 38 children in the kindergarten program in a middle-class school in a small midwestern city were analyzed as predictors of first-grade reading achievement on the Iowa Tests of Basic Skills and of first-grade performance on the Cognitive Abilities Test. Correlations among all variables are given. Stepwise multiple regression analyses predicting the first-grade variables showed that consonant-sound-identification was the best predictor of first-grade reading achievement and that the Peabody Picture Vocabulary Test--Revised was the best predictor of cognitive ability. A second multiple regression analysis examined the contribution of each kindergarten variable to first-grade reading and cognitive scores. Analysis indicated that these children entered kindergarten with highly developed early reading skills which facilitated success with systematic reading instruction.

Achievement↗
PubMed1993

Lack of effect of concomitant clobazam on interictal 123I-iomazenil SPECT.

Single photon emission computed tomography (SPECT) is being increasingly used as an adjunctive technique in the localisation of epileptogenic foci prior to surgery. Fourteen patients (five male, nine female; mean age 31 years) with refractory complex partial seizures, all of whom had abnormal 99Tc HM-PAO SPECT scans, were imaged again using the benzodiazepine receptor ligand 123I-iomazenil. Eleven of these patients displayed the same abnormality on both scans. The magnitude of the deficit, however, was slightly greater (P < 0.05) on the iomazenil scan compared with the HM-PAO study. These 11 patients were then randomised into two groups. Group 1 (n = 7) received clobazam 20 mg/day for a minimum of 7 days before a second iomazenil study was performed. Patients in group 2 (n = 4) underwent a second iomazenil scan at the same time interval as those in group 1, but without the additional clobazam. The resultant scans were reported blind to treatment. There were no qualitative or quantitative differences between the first and second iomazenil studies in either group. Patients can be imaged using 123I-iomazenil without withdrawing clobazam therapy. From this preliminary study, there seems little advantage in using iomazenil in place of HM-PAO to delineate the extent of the zone of epileptogenesis. Whether iomazenil SPECT will prove to be more sensitive in identifying the site of the epileptic focus remains to be determined.

Adult↗
PubMed1993

Molecular mediators formed in the small intestine in response to cholera toxin.

The molecular mechanism of experimental cholera, leading to increased water and electrolyte secretion, was evaluated with the rabbit intestinal loop model. The levels of cyclic adenosine monophosphate (cAMP), prostaglandin E2 (PGE2), and 5-hydroxytryptamine (5-HT) were measured in mucosal tissue or luminal fluids from intestinal segments exposed to cholera toxin (CT). Each mediator increased in a dose-dependent manner coinciding with the amount of fluid accumulating in the CT-treated loops within the 16 h observation period. Interestingly, a substantial amount of the cAMP in the CT loops was released into the intestinal lumen, along with the fluid. Fluid accumulation was evoked by instillation of PGE2 and CT into the intestinal segments, but not by 5-HT. Large doses of dibutyryl cAMP at 50 mg/ml, but not at 25 mg/ml, also evoked fluid accumulation when injected into the intestine. Further, CT evoked the release of 5-HT from the mucosa, although the high doses of cAMP caused a massive release of 5-HT. PGE2 injection was without effect on 5-HT release. Although CT increased the amount of PGE2 into the luminal fluid, no effect on PGE2 levels was observed by injecting any dose of dibutyryl cAMP or 5-HT into the intestinal lumen. Our interpretation of these data is that CT stimulates the independent synthesis and release of both cAMP and PGE2. The cAMP appears to cause the release of 5-HT from the enterochromaffin cells. Since dibutyryl cAMP did not evoke a PGE2 response, it was concluded that cAMP could elicit secretion of fluid without the participation of PGE2; however, the cAMP doses were not physiological.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Acute rejection of lung allografts with various immunosuppressive protocols.

Between February 1990 and December 1991, 69 patients who survived for a minimum of 5 days after single-lung (27), double-lung (32), or heart-lung transplantation (10) were studied to learn the incidence and severity of acute rejection and the possible effects of various immunosuppressive protocols on this rejection. Acute rejection was less common (2.1 versus 3.1 episodes/patient) after transplantation in those 30 candidates who received rabbit antithymocyte globulin for the first 5 postoperative days versus the 28 who were maintained on cyclosporine, azathioprine, and prednisone alone (p < 0.05), but no patient escaped at least one episode. Patients given cyclosporine received more 3-day courses of methylprednisolone (p < 0.02) than those given rabbit antithymocyte globulin (2.5 versus 1.7 courses). Although no disadvantage in terms of infectious morbidity was noted in the rabbit antithymocyte globulin group, no obvious intermediate advantage was noted in survival (85% at 12 months) or grade of rejection or airway flows. The most common histopathologic grades were mild (A2) and moderate (A3); the average grade was A2.3. FK 506 was tested in 11 patients, and early results are promising relative to low early and likely fewer late episodes of rejection. No differences were noted in the likelihood of rejection for any procedures.

Acute Disease↗
PubMed1992

Interictal HM-PAO SPECT: a routine investigation in patients with medically intractable complex partial seizures?

Single photon emission computed tomography (SPECT) is increasingly being used as an adjunctive technique in the localisation of epileptogenic foci prior to surgery. As yet, few studies have been undertaken to establish the clinical associations of areas of reduced cerebral perfusion. Sixty-three consecutive patients (15 male, 48 female; median age 30 years, range 14-57 years) with medically intractable complex partial seizures (median/month 8, range 1-36) were investigated as outpatients. All had normal high resolution computerised X-ray tomography (CT) of brain. Twenty-seven (47%) exhibited significant perfusion defects on SPECT scanning with a rotating gamma camera system using Tc-99 HM-PAO. There were no significant differences between patients with normal and abnormal scans in terms of age at scanning or at onset of epilepsy or number of seizures. Patients with perfusion defects did, however, have longer median histories of epilepsy than those with normal scans (normal: 10 years, abnormal: 22 years; P = 0.01). Patients with abnormal scans were no more likely to have suffered febrile convulsions in early childhood. The correlation of abnormal SPECT scans with routine surface EEG recordings was poor with only 41% of cases showing clear agreement between the site of hypoperfusion and focal epileptic activity. It is not yet possible to predict clinically those patients who will exhibit perfusion defects on interictal TC-99 HM-PAO SPECT scanning.

Adolescent↗
PubMed1992

Proliferation of cytomegalovirus-primed lymphocytes in bronchoalveolar lavages from lung transplant patients.

Previous reports have described an association between cytomegalovirus infection and increased donor-specific alloreactivity of bronchoalveolar lavage (BAL) lymphocytes in transplanted lungs and a higher risk of bronchiolitis obliterans due to chronic rejection. We have postulated that during infection, intragraft CMV-specific lymphocytes are activated and release lymphokines that augment cellular rejection. This study deals with an analysis of CMV antigen induced proliferation of 28 BAL lymphocyte and 27 peripheral blood lymphocytes samples from 17 lung transplant patients with or without CMV infection. Kinetic studies of lymphocyte proliferation have shown that CMV infection of the lung allograft is associated with an accelerated response of BAL lymphocytes but not PBL, following in vitro exposure to CMV antigen. These findings indicate an accumulation of primed CMV-specific lymphocytes within the lung allograft during CMV infection. Evidence has also been obtained that primed CMV-specific lymphocytes may persist for months in BAL. We conclude that the CMV antigen induced proliferation assay is useful for studies of CMV infection in transplant patients.

Antigens, Viral↗
PubMed1992

A survey of prescription label preferences among community pharmacy patrons.

Fifty-five randomly selected community pharmacy patrons were surveyed regarding their preferences between four different prescription labels. The variables displayed on the four labels were: (i) laser printed, (ii) dot-matrix printed, (iii) glossy surface, and (iv) matt surface. The study population was stratified by age and gender. Statistical analysis of the results indicated a clear preference by all groups for the laser printed labels (P less than 0.001), and the only other statistically significant finding was the preference for the matt surface (P less than 0.05) of females between the ages of 16 and 39. The implications for these differences on label readability are discussed, and recommendations are offered for the use of improved laser technology for computer-generated prescription labels.

Adolescent↗
PubMed1991

Categories and particulars: prototype effects in estimating spatial location.

A model of category effects on reports from memory is presented. The model holds that stimuli are represented at 2 levels of detail: a fine-grain value and a category. When memory is inexact but people must report an exact value, they use estimation processes that combine the remembered stimulus value with category information. The proposed estimation processes include truncation at category boundaries and weighting with a central (prototypic) category value. These processes introduce bias in reporting even when memory is unbiased, but nevertheless may improve overall accuracy (by decreasing the variability of reports). Four experiments are presented in which people report the location of a dot in a circle. Subjects spontaneously impose horizontal and vertical boundaries that divide the circle into quadrants. They misplace dots toward a central (prototypic) location in each quadrant, as predicted by the model. The proposed model has broad implications; notably, it has the potential to explain biases of the sort described in psychophysics (contraction bias and the bias captured by Weber's law) as well as symmetries in similarity judgments, without positing distorted representations of physical scales.

Adolescent↗
PubMed1991

Tracheomalacia and bronchopulmonary dysplasia.

Wheezing in the infant with bronchopulmonary dysplasia results from various pathophysiologic mechanisms, including upper or central airway obstruction. We report an infant with bronchopulmonary dysplasia who presented with episodic wheezing associated with hypoxia and bradycardia without evidence of stridor. Bronchoscopy revealed the presence of tracheomalacia. Upper or central airway obstruction, if undiagnosed, may be life-threatening. We suggest that wheezing with hypoxia and bradycardia in neonates should alert the physician to the possibility of tracheomalacia, even in the absence of audible stridor. Infants presenting with these symptoms should undergo bronchoscopy to confirm the diagnosis.

Adult↗
PubMed1991

Snoring (I). Daytime sleepiness in regular heavy snorers.

Fifteen men, mean (means) age 44 years, were investigated. Their means body mass index was 21.9 kg/m2, and all of them had a respiratory disturbance index below 5 and had good nocturnal oxygen saturation. The subjects were monitored several nights both with and without the following devices: a tight-fitting facial mask, a pneumotachometer, and an esophageal balloon. They were also monitored with and without nasal continuous positive airway pressure. The Multiple Sleep Latency Test was administered after three of the experimental nights (after the baseline nights and after the second nasal CPAP night). Determination of short EEG arousals during nocturnal sleep, which lasted 2 to 10 s, was performed. The relationship between short EEG arousals, the esophageal pressure nadir, and airflow decrease was investigated. We also determined the relationship between clinical reporting of decrease in daytime alertness and MSLT results, and the relationship between MSLT results and the frequency of EEG arousals. The monitoring indicated that heavy snorers may present significant increase in Pes nadir with abrupt decrease in flow leading to EEG arousals. The frequency at which EEG arousals occur has an impact on MSLT scores. Nasal CPAP improves MSLT scores and eliminates these respiration-related EEG arousals. Some heavy snorers without obstructive sleep apnea syndrome may be at risk of having a decrease in daytime alertness.

Adult↗
PubMed1991

Endogenous N-nitrosation and cancer of the biliary tract.

Evidence is presented that N-nitroso compounds occur in bile from patients who have undergone surgery for gallstones or had gastrectomy and from unoperated persons. It is unlikely, therefore, that local formation of nitrosamines can account for the excess risk for gallbladder cancer in the first two groups. Gastric formation remains the likeliest hypothesis.

Bile↗
PubMed1991

The "natural history" of the transplanted lung: rates of pulmonary functional change in long-term survivors of heart-lung transplantation.

Long-term pulmonary function in HLT is well preserved with no evidence of functional decline as a result of transplant "aging," providing the allografts remain free of complications. Long-term survivors with OB appear to be able to maintain adequate oxygenation despite the marked alterations of pulmonary function. The ability to preserve gas exchange at reasonable levels of oxygenation may be the factors permitting extended survival with OB for mean periods of 36.0 months or greater. Preliminary studies suggest that a declining FEF50/FVC, at a time when pulmonary function is normal, may be an index of impending airway disease. Physiologically, from a long-term point of view, HLT remains a viable option for selected patients with end-stage cardiopulmonary disease.

Bronchiolitis Obliterans↗