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Biomedical subjects

S E Jones

Publications and source records attributed to S E Jones.

At least 37 records · Page 2Linked to original sources

Binge drinking among undergraduate college students in the United States: implications for other substance use.

The authors examined the relationship between binge drinking and other substance use among US college students, using nationally representative data from the 1995 National College Health Risk Behavior Survey implemented by the Centers for Disease Control and Prevention. Compared with nonbinge drinkers, current binge drinkers were significantly more likely to report "ever" using and current use of cigarettes, marijuana, cocaine, and other illegal drugs. The researchers also found that the more often students binge drank, the more likely they were to have ever used cigarettes, marijuana, cocaine, and other drugs, and the more likely they were to report current use of cigarettes and marijuana. Those who design programs to prevent binge drinking and use of other substances should take into account the reality that many students use more than one substance and that the more frequently students report binge drinking, the more likely they are to be using other substances as well.

Adolescent↗

Prevalence and correlates of sunscreen use among US high school students.

Sun exposure during childhood and adolescence increases the risk of skin cancer later in life. To determine the prevalence and correlates of sunscreen use among US high school students, researchers assessed data on sunscreen use, demographic characteristics, and health behaviors obtained from the 1999 Youth Risk Behavior Survey (YRBS). This survey used a three-stage cluster sample design to produce a nationally representative sample of students in grades 9-12 (N = 15,349). Overall, 13.3% (95% confidence interval, +/- 1.3) of students used sunscreen always or most of the time (i.e., frequent use). Frequent sunscreen use was lower among males (8.6%, +/- 1.2) than females (18.1%, +/- 1.9) and among Blacks (4.8%, +/- 1.7) and Hispanics (10.8%, +/- 2.8) than Whites (16.5%, +/- 1.9). Frequent sunscreen use decreased with age. Infrequent use of sunscreen was associated with other risky health behaviors, such as driving after drinking or riding in a car with a drinking driver, smoking cigarettes, being sexually active, and being physically inactive. Results indicate a need for health education interventions addressing sunscreen use that target high school students.

Administration, Cutaneous↗

Adenoma in the middle ear: a report of two cases.

Middle-ear adenoma has been reported only in small numbers by surgeons. The few large series reported have been presented by histopathologists. We add two cases of middle-ear adenoma to the published literature, together with pre-, per- and post-operative imaging of one case, as a demonstration of this rare clinical entity. We discuss the pathology of middle-ear adenoma, its diagnosis and treatment, and suggest ways of improving its management.

Adenoma↗

Frontal recess surgery for diving-related frontal pain: case report.

We report the case of a professional scuba diver who was unable to dive because he began experiencing severe frontal pain on descent. Following endoscopic surgery to open the frontal recess, the man was able to resume diving unrestricted by pain. We discuss the causes and treatment of this complaint, and we suggest that this might be considered a new indication for surgery in a limited number of cases.

Adult↗

Modulated expression of secreted frizzled-related proteins in human retinal degeneration.

Inherited retinal degenerations such as retinitis pigmentosa (RP) are characterized by progressive loss of photoreceptors, apparently by apoptosis, and our recent report of increased secreted Frizzled-related protein-2 (SFRP2) in RP retinas suggests altered Wnt signalling may be a component of the degenerative process. The present study shows that levels of SFRPI, SFRP3 and SFRP5 mRNAs are also abnormal in RP, giving rise to idiosyncratic expression patterns. In highly degenerative retinas, the SFRP proteins localize mainly to the inner limiting membrane, but in a well-preserved retina SFRPI and SFRP5 are notably localized to the surviving photoreceptors. Together with increased c-jun mRNA expression in all cases examined, these results support the notion that disruptions of Wnt network signalling are involved retinal neurodegeneration.

Adaptor Proteins, Signal Transducing↗

Use of small fluorescent molecules to monitor channel activity.

The Mechanosensitive channel of Large conductance (MscL) allows bacteria to rapidly adapt to changing environmental conditions such as osmolarity. The MscL channel opens in response to increases in membrane tension, which allows for the efflux of cytoplasmic constituents. Here we describe the cloning and expression of Salmonella typhimurium MscL (St-MscL). The amino acid sequence encoding for this MscL exhibits a high degree of similarity to Escherichia coli MscL (Eco-MscL). Using a fluorescence efflux assay, we demonstrate that efflux through the MscL channel during hypoosmotic shock can be monitored using endogenously produced fluorophores. These fluorophores are synthesized by a cotransformed gene, cobA. In addition, we observe that thermal stimulation, i.e., heat shock, can induce efflux through MscL.

Amino Acid Sequence↗

Low-affinity block of cardiac K(+) currents by nifedipine.

Nifedipine inhibits a variety of K(+) currents with IC(50) between 4 and 40 microM. Among the more sensitive of these are two types (transient outward and ultrarapid hKv1.5) found in the heart. To evaluate the actions of the drug on other prominent cardiac K(+) currents, guinea-pig ventricular myocytes were voltage-clamped for measurement of inwardly rectifying K(+) current (I(K1)), rapidly activating delayed-rectifier K(+) current (I(Kr)), and slowly activating delayed-rectifier K(+) current (I(Ks)). The currents were unaffected by < or =10 microM nifedipine, but inhibited by higher concentrations; IC(50) values were 260 microM for I(K1), 275 microM for I(Kr), and 360 microM for I(Ks). The time- and voltage-dependent properties of I(Ks) were unaffected by the drug, and full block was attained on the first depolarisation after a rest. The results establish that the sensitivity of I(Kr) and I(Ks) to inhibition by nifedipine is approximately 50 times lower than the sensitivity of other cardiac delayed-rectifier K(+) currents.

Animals↗

Three-dimensional mapping of cortical thickness using Laplace's equation.

We present a novel, computerized method of examining cerebral cortical thickness. The normal cortex varies in thickness from 2 to 4 mm, reflecting the morphology of neuronal sublayers. Cortical pathologies often manifest abnormal variations in thickness, with examples of Alzheimer's disease and cortical dysplasia as thin and thick cortex, respectively. Radiologically, images are 2-D slices through a highly convoluted 3-D object. Depending on the relative orientation of the slices with respect to the object, it is impossible to deduce abnormal cortical thickness without additional information from neighboring slices. We approach the problem by applying Laplace's Equation (V2psi = 0) from mathematical physics. The volume of the cortex is represented as the domain for the solution of the differential equation, with separate boundary conditions at the gray-white junction and the gray-CSF junction. Normalized gradients of psi form a vector field, representing tangent vectors along field lines connecting both boundaries. We define the cortical thickness at any point in the cortex to be the pathlength along such lines. Key advantages of this method are that it is fully three-dimensional, and the thickness is uniquely defined for any point in the cortex. We present graphical results that map cortical thickness everywhere in a normal brain. Results show global variations in cortical thickness consistent with known neuroanatomy. The application of this technique to visualization of cortical thickness in brains with known pathology has broad clinical implications.

Algorithms↗

Identification by array screening of altered nm23-M2/PuF mRNA expression in mouse retinal degeneration.

In the rd/rd mouse model of inherited retinal degeneration, the majority of photoreceptors die apoptotically between postnatal age (P)10 and 20 days, during which period the inner retina appears morphologically unaffected. To examine mRNA changes associated with the degeneration, we performed differential screening of 588 arrayed murine cDNAs using probes reverse-transcribed from P8 predegenerative and control mouse retinal RNAs. We detected altered expression of the gene encoding nm23-M2, a member of the family of nucleoside diphosphate kinases implicated in diverse processes including metastasis suppression and transcriptional regulation. Retinal nm23 mRNA levels increased during degeneration while control levels decreased over age-matched time-points. In situ hybridization showed the high level of expression at P20 in rd/rd was concentrated in the retinal ganglion cells. Previous studies have indicated upregulation of the stress-response related gene alphaB-crystallin in the rd/rd inner retina, and increased nm23 levels may be a component of this response to photoreceptor loss and altered retinal architecture.

Animals↗

Exemestane improves survival compared with megoestrol acetate in postmenopausal patients with advanced breast cancer who have failed on tamoxifen. results Of a double-blind randomised phase III trial.

Exemestane is an aromatase inactivator. 769 Postmenopausal women with advanced breast cancer who had failed on tamoxifen were randomised to exemestane or megoestrol acetate in this double-blind trial. Objective response rate was similar between treatments. Median time to progression, time to treatment failure and overall survival was significantly longer with exemestane. Drug-related withdrawals and drug-related deaths were more common with megoestrol acetate.

Androstadienes↗

Discriminating between the effect of shunt and reduced VA/Q on arterial oxygen saturation is particularly useful in clinical practice.

There is an extensive literature on methods for discriminating between an increased shunt and a reduced ratio of ventilation to perfusion. In this review we prefer the terms "VA/Q" and "reduced or low VA/Q" rather than "V/Q inequality" to refer to the effects on arterial oxygenation of reducing V/Q below 0.8 to about 0.1. Almost without exception the conventional methods for measuring shunt and reduced VA/Q are invasive as well as technically complex. For most clinicians who are dealing with a hypoxemic patient the relevance of these entities is not so obvious as to justify the time and difficulty in either understanding or measuring them. However this review shows that, while an increased shunt and a decreased VA/Q both reduce arterial oxygen saturation (SaO2) at a particular inspired oxygen concentration (PIO2), the effect of shunt and reduced VA/Q have important clinical differences on the relationship between PIO2 and SaO2. The review also outlines a simple non-invasive method for measuring shunt and reduced VA/Q which illustrates the value of discriminating between them in clinical practice.

Diagnosis, Differential↗

Delphi-panel analysis of appropriateness of high-dose chemotherapy and blood cell or bone marrow autotransplants in women with breast cancer.

BACKGROUND: There is controversy whether high-dose chemotherapy and a blood cell or bone marrow autotransplant is a better treatment than conventional-dose chemotherapy for women with local/regional or metastatic breast cancer. Subject selection and time-to-treatment biases make definitive comparison impossible. Recent results of randomized trials are contradictory. OBJECTIVE: Determine appropriateness of high-dose chemotherapy and a blood cell or bone marrow autotransplant in women with breast cancer. PANELISTS: Nine breast cancer experts from diverse geographic sites and practice settings. EVIDENCE: Boolean MEDLINE searches of 'breast cancer' and 'chemotherapy' and/or 'blood cell' or 'bone marrow transplants'. PROCESS: We used a modified Delphi-panel group judgement process. Clinical variables were permuted to define 2058 clinical settings. Each panelist rated appropriateness of high-dose therapy and an autotransplant versus conventional therapy on a 9-point ordinal scale (1: most inappropriate, 9: most appropriate). An appropriateness index was developed based on median rating and amount of disagreement. The relationship of appropriateness indices to the permuted clinical variables was considered by analysis of variance and recursive partitioning. CONCLUSIONS: In women with local/regional breast cancer autotransplants were rated: 1) appropriate in those with > or = 10 cancer-involved lymph nodes; 2) uncertain in those with 4-9 cancer-involved nodes; and 3) inappropriate in women with < or = 3 cancer-involved lymph nodes. In women with metastatic breast cancer autotransplants were rated: 1) appropriate in those with metastases to 'favorable' sites (skin, lymph node, pleura) and a complete or partial response to chemotherapy; 2) uncertain in women with metastases to 'unfavorable' sites (lung, liver, or central nervous system) and a complete response to chemotherapy or those with bone metastases and a complete or partial response or stable disease after chemotherapy; and 3) inappropriate in other settings.

Antineoplastic Agents↗

Differences in the effects of urinary incontinence agents S-oxybutynin and terodiline on cardiac K(+) currents and action potentials.

1. The cardiac electrophysiological effects of S-oxybutynin, a single-enantiomer drug under evaluation for the management of urinary incontinence, have been investigated and compared with those of terodiline, an incontinence agent withdrawn following reports of QT lengthening and ventricular tachyarrhythmia. Membrane currents were recorded from whole-cell configured guinea-pig and rabbit ventricular myocytes, and action potentials were recorded from guinea-pig and rabbit papillary muscles. 2. L-type Ca(2+) current (I:(Ca,L)), rapidly-activating K(+) current (I:(Kr)) and slowly-activating K(+) current (I:(Ks)) were unaffected by submicromolar S-oxybutynin and inhibited by higher concentrations; IC(50) values were 17.8 microM for I:(Ca,L), 12 microM for I:(Kr), and 41 microM for I:(Ks). Terodiline IC(50) values were somewhat lower for I:(Ca,L) (15.2 microM) and I:(Ks) (30 microM), but 24 fold lower in the case of I:(Kr) (0.5 microM). 3. The durations of action potentials in guinea-pig and rabbit papillary muscles driven at 1 Hz were unaffected or moderately shortened by 0.1 - 100 microM S-oxybutynin, but lengthened by terodiline. Terodiline (< or =10 microM) also depressed maximal upstroke velocity. 4. The action potential plateau shortened by an average of 23% when control rabbit papillary muscles were driven at 0.4 Hz instead of 1 Hz. Plateau shortening was significantly smaller in the presence of drugs (30 microM S-oxybutynin, 3 and 30 microM terodiline), suggesting that they suppress the transient outward current (I:(to)) involved in rate-dependent shortening. In experiments on rabbit ventricular myocytes, 3 and 30 microM S-oxybutynin inhibited I:(to) by 9+/-2% and 35+/-3%, respectively, whereas 3 and 30 microM terodiline inhibited the current by 31+/-3% and 87+/-3%, respectively. 5. The results indicate that S-oxybutynin has relatively weak non-specific effects on cardiac ion channels, and that clinically relevant submicromolar concentrations are unlikely to have terodiline-like proarrhythmic actions on the myocardium.

Action Potentials↗

Selective phenylalkylamine block of I(Kr) over other K(+) currents in guinea-pig ventricular myocytes.

Previous studies on verapamil and D600 have established that the Ca(2+)-channel blockers also inhibit delayed-rectifier K(+) currents in cardiac tissues and myocytes. However, estimated IC(50) values range over two to three orders of concentration, and it is unclear whether this reflects a high selectivity by one or both of the phenylalkylamines for particular K(+) channels. The purpose of the present study was to determine the concentration-dependent actions of verapamil and D600 on three defined cardiac K(+) currents. Guinea-pig ventricular myocytes in the conventional whole-cell configuration were bathed with normal Tyrode's or K(+)-free solution, and pulsed from -80 mV for measurement of the effects of 0.01 microM to 3 mM verapamil and D600 on the inwardly-rectifying K(+) current (I:(Kl)) and the two delayed-rectifier K(+) currents, rapidly-activating I:(Kr) and slowly-activating I:(Ks). The phenylalkylamines inhibited both inward- and outward-directed I:(Kl). The IC(50) values for outward I:(Kl) were approximately 220 microM. Verapamil and D600 were approximately equipotent inhibitors of the delayed-rectifier K(+) currents. They inhibited I:(Kr) with IC(50) near 3 microM, and I:(Ks) with IC(50) > or =280 microM. These results are discussed in relation to previous findings on K(+) currents and to the clinical actions of the drugs.

Animals↗

Optic chiasmal herniation--an under recognized complication of dopamine agonist therapy for macroprolactinoma.

The initial presentation of macroprolactinoma with visual field impairment, especially in males, is well recognized. Successful treatment with dopamine agonist therapy is characterized by a reduction in hyperprolactinaemia and often rapid and progressive resolution of the visual impairment. A small proportion of patients may subsequently develop a secondary deterioration in both their visual fields and visual acuities despite normalization of prolactin levels and tumour shrinkage. When pituitary apoplexy can be excluded this may result from traction on the optic chiasm which is pulled down into the now partially empty sella. We report a series of seven patients in whom chiasmal traction is believed to be the cause of their secondary deterioration in visual acuity occurring after dopamine agonist therapy for macroprolactinoma. The clinical history of two patients both of whom had rapid resolution of field defect with bromocriptine therapy but subsequently developed a recurrence of their bitemporal hemianopia is detailed. In both patients MRI scanning showed not only tumour involution but also marked optic chiasm herniation into the pituitary fossa. Surgical treatment was considered too risky; but on reduction of bromocriptine dosage the field defect improved in both cases; there was a modest elevation of prolactin and a degree of tumour re-expansion. The latter is believed to have released tethering of the optic chiasm and/or its vascular supply and thus obviated the need for surgery. Regular monitoring of visual fields in patients with macroprolactinoma receiving medical treatment is therefore important. Early recognition of secondary field loss due to chiasmal herniation enables correction of the visual field loss by manipulation of the medical therapy.

Adult↗

Analysis of the electrophysiologic effects of short-term oxybutynin on guinea pig and rabbit ventricular cells.

The objective of this study was to investigate the cardioactive properties of oxybutynin, a drug that is widely prescribed for management of voiding dysfunction. Membrane currents were recorded from whole-cell-configured guinea pig ventricular myocytes, and action potentials were recorded from guinea pig and rabbit papillary muscles. L-type Ca2+ current (I(Ca),L), inward-rectifier K+ current (I(K1)), and delayed-rectifier K+ current (I(K)) were unaffected by < or = 1 microM oxybutynin, and inhibited by higher concentrations. The concentrations that reduced the currents to one-half of predrug control amplitude (K0.5) were as follows: 1(Ca),L, 16.1 microM, I(K1), 18.2 microM, rapidly activating I(K)(I(Kr)), 11.4 microM, and slowly activating I(K)(I(Ks)), 28.7 microM. Action-potential durations at 20 and 90% repolarization (APD20, APD90) were unaffected by oxybutynin < or =3 microM in guinea pig papillary muscles driven at 1 Hz; higher concentrations selectively shortened the APD20 by as much as 25% (100 microM), and caused moderate reductions in maximal upstroke velocity. Changes in the action potentials of rabbit papillary muscles were even smaller than in the guinea pig muscles. Because the peak therapeutic plasma concentration of oxybutynin is in the 0.01-0.1 microM range, the results suggest that the drug is highly unlikely to have adverse effects on cardiac electrical activity.

Action Potentials↗