Search PubMed⌕ Search

Biomedical subjects

L Lewis

Publications and source records attributed to L Lewis.

At least 55 records · Page 3Linked to original sources

Effects of probenecid on brain-cerebrospinal fluid-blood distribution kinetics of E-Delta 2-valproic acid in rabbits.

E-Delta 2-valproic acid (E-Delta 2-VPA), a major active metabolite of VPA, has been proposed as an alternative to VPA because it is less hepatotoxic and is nonteratogenic. In rodents, VPA and E-Delta 2-VPA have a brain tissue/free plasma concentration ratio less than unity, which suggests rapid removal of the alkanoate anticonvulsants from the central nervous system. This study in rabbits employed a simultaneous iv infusion-ventriculocisternal (VC) perfusion technique to investigate the steady-state kinetics of E-Delta 2-VPA transport at the blood-brain barrier, the blood-cerebrospinal fluid (CSF) barrier, and the neural cell membrane. Probenecid (PBD) was coadministered to probe the mediation of transport by organic anion transporter(s). Rabbits in the control group (N = 6) received an iv infusion of E-Delta 2-VPA to achieve a steady-state plasma concentration of 50 to 60 microg/ml. Blood and cisternal outflow of mock CSF perfusate were continuously sampled. Midway through the experiment, the VC perfusate was switched to one containing [3H]E-Delta 2-VPA. At 225 min, the rabbits were sacrificed, and each brain was removed and dissected into ten regions. Rabbits in the PBD group (N = 9) received an iv infusion and VC perfusion as in the control group as well as concomitant iv infusion of the inhibitor. The mean steady-state VC extraction ratio for [3H]E-Delta 2-VPA did not differ between the control and PBD groups (63.7 +/- 8.3% vs. 60. 6 +/- 9.6%), indicating the lack of a significant PBD-sensitive transport at the choroidal epithelium. Coadministration of PBD elevated brain concentration of cold E-Delta 2-VPA in the absence of a significant change in total or free steady-state plasma concentration. Mean E-Delta 2-VPA brain tissue/free plasma concentration ratios in the various brain regions were 3.5- to 5.2-fold higher in PBD-treated animals than in the controls. Significant increases (3.0- to 4.5-fold) in the mean brain tissue/cisternal perfusate concentration ratios were also observed. Compartmental modeling of the steady-state distribution data suggested that clearance of E-Delta 2-VPA from the brain parenchyma is governed jointly by efflux transporters at the neural cell membrane and brain capillary endothelium. Moreover, PBD-induced elevation of E-Delta 2-VPA tissue concentrations is attributed primarily to inhibition of E-Delta 2-VPA efflux transport at the neural cell membrane, resulting in both intracellular trapping and greater tissue retention of E-Delta 2-VPA.

Animals↗

Adrenomedullin.

Explore the source record for details and available documents.

Adrenomedullin↗

Teleconsulting: a practical account of pitfalls, problems and promise. Experience from the TEAM project group.

In Wales the Tele Education and Medicine (TEAM) project has given clinicians, in both the primary- and secondary-care sectors, practical experience in teleconsulting. From this project we have been able to identify the potential pitfalls and problems in developing and using this new technology. These problems include: using teleconsulting simply because it is fashionable; the failure to base it on the needs of the patients and the primary-care physicians; the failure to validate accuracy, acceptability and cost; the failure to adapt to new technical improvements; and the failure to scale up from a pilot project to a wider teleconsulting service. In our experience technical support is essential and is best facilitated by multisite cooperation, rather than small free-standing projects.

Dermatology↗

Evaluation of a supplementary retention program for African-American baccalaureate nursing students.

This study evaluated the Minority Academic Advising Program (MAAP), a supplementary retention program established for African-American students enrolled in a southern state health sciences university's baccalaureate nursing program. The evaluation method merged a quasi-experimental with a time-series design. A group of 114 black students were included in the study. A comparison group consisting of 608 nursing student cohorts who were predominantly white was incorporated for control purposes. Although the students who were MAAP participants had significantly lower SAT scores, reduced Pre-Admission GPAs, and included a contingent of 11 students at high risk of failing, the following enhancements were identified: their retention-to-graduation rate increased 5.3 percentage points to 97.1%, their nursing program GPA increased nearly one-quarter letter grade, their time-persisted-in-program increased 0.7 months, and their nursing board examination pass rate increased 15 percentage points.

Black or African American↗

Resistance to (-)-2',3'-dideoxy-3'-thiacytidine (3TC) in HIV-1 isolated from paediatric patients.

We conducted detailed virological evaluations of 16 HIV-1-infected paediatric patients treated with 3TC (lamivudine) monotherapy. High-level phenotypic resistance against this compound (up to 2,500-fold) was seen in virtually all cases, usually within 8-12 weeks of initiation of therapy. This was concomitant with the appearance of the M184V mutation in viral reverse transcriptase, previously shown to be responsiblefor such resistance. Viral burden fell in virtually all cases after commencement of therapy, and remained below baseline in each instance studied, despite a rebound effect and the appearance of drug resistance. Viral isolates from some patients underwent a switch from a non-syncytium-inducing (NSI) to a syncytium-inducing (SI) phenotype during the course of the study, although no relationship was apparent between dose of drug employed, time to development of drug resistance or time of appearance of SI phenotype.

Anti-HIV Agents↗

Daily gastrointestinal symptoms in women with and without a diagnosis of IBS.

This study compared daily gastrointestinal symptoms and stool characteristics across two menstrual cycles, and recalled bowel symptoms and psychological distress in women with irritable bowel syndrome (IBS, N = 22), IBS nonpatients (IBS-NP, N = 22), and controls (N = 25). Daily reports of abdominal pain, bloating, intestinal gas, constipation, and diarrhea did not differ significantly between the IBS and IBS-NP groups but both groups reported significantly higher symptoms than the control group. Stool consistencies was significantly looser in the IBS group relative to the control group. Menstrual cycle effects on symptoms were noted in all the groups. There were no significant differences in psychological distress between women with IBS and IBS-NP, but both groups reported significantly higher global distress than the control group. The lack of difference between the IBS and IBS-NP groups in contrast to the results of others, can be understood in terms of differences in recruitment strategies.

Abdominal Pain↗

The use of continuous quality improvement to achieve proper isolation of patients with suspected tuberculosis.

The infection control staff worked on their first project that used the methods of continuous quality improvement from January through July 1993. The purpose of this initial project was to achieve proper isolation of patients with suspected tuberculosis. Flowcharting revealed that appropriate clinical performance by the charge nurses was crucial, and cause and effect diagraming demonstrated the importance of good policies and procedures. The team hypothesized that the charge nurses' current knowledge of tuberculosis and isolation procedures was low and that fewer exposures would occur if a concerted effort were made to educate this particular group. A self-administered examination to test their knowledge base was completed by 87% of approximately 75 charge nurses. The average score was 48 of a possible score of 100. Eight education programs were given to the charge nurses; these included information about tuberculosis and revised policies and procedures. After the intervention, the test was readministered to a group of 20 charge nurses. Scores of this group improved by 49%. Mistakes were made and lessons were learned in this first continuous quality improvement endeavor. Despite the flaws in this project, its ultimate goal of reducing exposures to tuberculosis was achieved.

Algorithms↗

Short- and long-term repeatability of fatty acid composition of human plasma phospholipids and cholesterol esters. The Atherosclerosis Risk in Communities (ARIC) Study Investigators.

We examined short-term and long-term repeatability (reliability) of the fatty acid (FA) composition of plasma phospholipids and cholesterol esters (CEs). For short-term reliability, fasting blood samples of 34 subjects were collected three times, 2 wk apart, and in 24 subjects duplicate samples were collected during each visit. For long-term reliability, two fasting samples were collected in 50 subjects approximately 3 y apart. In both phospholipids and CEs, short-term and long-term reliability coefficients were > 0.65 for the major plasma FAs (16:0, 18:0, 18:2n-6, and 20:4n-6), with the exception of 18:1n-9, but were generally lower for FAs that compose < 1% of total FAs. Reliability tended to be better for CEs than for phospholipids. Method variability was small (< 5% of total variability for most FAs), indicating that biological and dietary variability contribute most to total variability. Plasma FA measurement warrants consideration as a biochemical marker of diet in epidemiologic studies.

Cholesterol Esters↗

Role of bradykinin B2 receptors in the developmental changes of renal hemodynamics in the neonatal rat.

The present study was performed to evaluate the role of bradykinin, acting via B2 receptors, in the developmental rise in renal blood flow (RBF) and glomerular filtration rate (GFR) in the rat. Newborn rats were chronically treated from birth with the kinin B2 receptor antagonist HOE-140 (600 micrograms/kg sc, every 12 h, n = 9) or 0.9% saline (n = 7). Weanling rats (mean age 23 days) were anesthetized with pentobarbital sodium (50 mg/kg ip) for measurements of mean arterial pressure (MAP), GFR, and renal plasma flow estimated from p-aminohippurate (PAH) clearance (ERPF). Outer cortical RBF (OCBF) was measured by laser-Doppler flowmetry. Baseline MAP was similar in HOE-140- and saline-treated rats (96 +/- 4 vs. 97 +/- 4 mmHg). Also, baseline GFR (0.65 +/- 0.05 vs. 0.52 +/- 0.08 ml.min-1.g-1) and ERPF (1.6 +/- 0.2 vs. 1.3 +/- 0.1 ml.min-1.g-1) were not different in HOE-140- and saline-treated rats, respectively. Intravenous infusion of 200 ng bradykinin did not change MAP or OCBF in HOE-140 rats but decreased MAP (-29 +/- 3%, P < 0.05) and OCBF (-20 +/- 2%, P < 0.05) in controls. Intravenous infusion of 25 ng angiotensin II increased MAP equally in both groups (-32 +/- 4%) and caused a similar reduction in OCBF (-37 +/- 14 vs. -46 +/- 5%). The angiotensin type 1 (AT1) receptor antagonist losartan (10 mg/kg iv) decreased MAP equally in both groups (-22 +/- 2%). However, AT1 blockade increased ERPF to 3.1 +/- 0.8 ml.min-1.g-1 (P < 0.05 vs. baseline) in saline but not in HOE-140 rats (1.9 +/- 0.4 ml.min-1.g-1). Kidney renin mRNA and angiotensin II contents were not different in HOE-140 vs. saline groups. The present findings indicate that bradykinin is not a primary mediator of the maturational rise in RBF or GFR in the rat. However, the data suggest that under control conditions, angiotensin II, acting via AT1 receptors, counteracts the renal vasodilatory effects of endogenous bradykinin in the developing kidney.

Angiotensin II↗

Serotonin syndrome.

We describe a patient treated with trazodone, isocarboxazid, and methylphenidate hydrochloride who developed confusion, agitation, poor concentration, rigidity, myoclonus, involuntary movements, orthostatic hypotension, and hyperreflexia. CK was normal, and the syndrome resolved spontaneously over 12 hours. The serotonin syndrome occurs following the use of serotomimetic agents (serotonin reuptake inhibitors, tricyclic and tetracyclic antidepressants, tryptophan, 3,4-methylenedioxy-methamphetamine, dextromethorphan, meperidine, S-adenosylmethionine) alone or in combination with monoamine oxidase inhibitors. It is characterized by various combinations of myoclonus, rigidity, hyperreflexia, shivering, confusion, agitation, restlessness, coma, autonomic instability, low-grade fever, nausea, diarrhea, diaphoresis, flushing, and rarely, rhabdomyolysis and death.

Depressive Disorder↗

Caring for the carers.

The author reports a small-scale study of stress in the labour ward. 25 labour ward staff were asked about stress at work. 80% felt stressed at work, citing overwork as the main cause, and talking to others as the main way of coping. Existing counselling facilities were found to be underused Stress did not appear to spread over into private lives. Only half of those questioned felt adequately supported at work. Participants were offered a 20-minute massage, and all felt this helped reduce stress. The average pulse rate of participants dropped by 12 beats per minute during massage.

Burnout, Professional↗

NASA's Space Life Sciences Training Program.

The Space Life Sciences Training Program (SLSTP) is an intensive, six-week training program held every summer since 1985 at the Kennedy Space Center (KSC). A major goal of the SLSTP is to develop a cadre of qualified scientists and engineers to support future space life sciences and engineering challenges. Hand-picked, undergraduate college students participate in lectures, laboratory sessions, facility tours, and special projects: including work on actual Space Shuttle flight experiments and baseline data collection. At NASA Headquarters (HQ), the SLSTP is jointly sponsored by the Life Sciences Division and the Office of Equal Opportunity Programs: it has been very successful in attracting minority students and women to the fields of space science and engineering. In honor of the International Space Year (ISY), 17 international students participated in this summer's program. An SLSTP Symposium was held in Washington D.C., just prior to the World Space Congress. The Symposium attracted over 150 SLSTP graduates for a day of scientific discussions and briefings concerning educational and employment opportunities within NASA and the aerospace community. Future plans for the SLSTP include expansion to the Johnson Space Center in 1995.

Biological Science Disciplines↗

Symbolization in psychotherapy with patients who are disabled.

Symbols created during the process of psychotherapy serve psychological functions of giving form and substance to previously murky experiences, making what is private something shared, and forging meaningful linkages among thoughts, emotions, and perceptions. Symbols can also enable therapist and patient together to gain insight into transference themes, transformations in identity, and feelings about life changes, as well as serve as guides to articulating treatment goals. Clinical vignettes are used to illustrate the process.

Adult↗

Tubular fluid concentrations and kidney contents of angiotensins I and II in anesthetized rats.

Previous micropuncture studies have reported nanomolar concentrations of angiotensin II in proximal tubular fluid and have indicated that angiotensin II or a precursor may be secreted into the tubular lumen. Further experiments were performed to determine if proximal tubular fluid angiotensin I concentrations are also greater than plasma and kidney levels and to estimate the degree of intrarenal compartmentalization of the angiotensin peptides. Free-flow proximal tubular fluid samples were collected in micropipets and were pooled for each animal. At the end of each experiment, a blood sample was collected and the micropunctured left kidney was harvested and homogenized in methanol. The angiotensin I concentration in proximal tubular fluid samples averaged 6.1 +/- 1.2 pmol/mL, whereas the angiotensin II concentration averaged 8.1 +/- 1.6 pmol/mL (N = 13). HPLC analysis of a separate sample pooled from collections in five rats indicated that the immunoreactive angiotensin I and angiotensin II primarily represented authentic angiotensin I and II. Plasma concentrations of angiotensin I and angiotensin II averaged 0.39 +/- 0.09 and 0.15 +/- 0.03 pmol/mL, respectively. The kidney contents of angiotensin I and angiotensin II were 1.28 +/- 0.24 and 0.97 +/- 0.17 pmol/g of kidney, respectively. These findings indicate that proximal tubular fluid contains nanomolar concentrations of angiotensin I as well as angiotensin II. These high tubular fluid concentrations, which greatly exceed the plasma and kidney levels, likely reflect net secretion of the angiotensin peptides by proximal tubule cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗

Pharmaceutical industry.

Manufacturers are under continuing pressure to reduce prices. To improve profitability, some have entered joint ventures with other manufacturers or with distributors.

Biotechnology↗