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Biomedical subjects

R Lewis

Publications and source records attributed to R Lewis.

At least 109 records · Page 6Linked to original sources

A review of bacteriological culture of removed intrauterine contraceptive devices.

A retrospective review of clinical and microbiological data was made, over an 18 month period, of intrauterine contraceptive devices removed and sent for examination. An association with symptoms at time of removal was found for Streptococcus agalactiae, Streptococcus milleri, enterobacteria and obligate anaerobes. Thirty four per cent of IUDs yielded one or more Actinomycesspecies spp but no correlation with symptoms was found. In the small group of symptomatic patients who were followed up, no difference in outcome was observed between those who were treated with antibiotics and those who were not.

Anti-Bacterial Agents↗

Primary care. Failure to achieve take-off.

The Primary Care Act, passed in April, allowed for experimentation with new forms of service delivery and enabled health authorities to commission GP services directly, suspending the national contract. It encouraged HAs, general practices and trusts to submit proposals for pilot projects to improve primary care. More than 500 proposals have been drawn up and the pilot projects are meant to go live on 1 April 1988. But progress has been sluggish. Many HAs are struggling to sustain enthusiasm for pilot projects, and GPs are divided.

Contract Services↗

Preterm labor and preterm premature rupture of the membranes. Diagnosis and management.

Preterm delivery due to preterm labor and pPROM is responsible for most infant morbidity and mortality in the United States. The patient who presents with suspicious symptoms should undergo a thorough evaluation to confirm the diagnosis of either entity and identify a treatable cause. Determination of gestational age, fetal well-being, and the presence of intrauterine infection is a crucial step in subsequent management. Corticosteroid therapy has been demonstrated to be one of the most effective antenatal interventions to reduce infant morbidity and should be administered to patients with preterm labor, if feasible, when fetal pulmonary maturity is absent or undocumented. We recommend a similar protocol regarding gravidas with pPROM remote from term but recognize the need for further study in this area. Acute tocolytic therapy has been demonstrated to offer short-term benefit to enhance corticosteroid effect. However, all of the available tocolytic agents carry significant risks to the mother and fetus. As such, administration of these agents should be given only when the potential benefits outweigh the risks of administration. Evaluation for fetal pulmonary maturity and intrauterine infection, in concert with evaluation of gestational age-dependent risks of prematurity, may be helpful in determining whether tocolysis should be attempted. Adjunctive antibiotic administration has not been shown to reduce maternal or infant morbidity in the face of preterm labor. However, such treatment offers a reduction of chorioamnionitis, prolongation of latency, and a possible reduction of neonatal infectious and gestational age-dependent morbidity in the setting of pPROM remote from term. Finally, current guidelines recommend the administration of intrapartum GBS prophylaxis when preterm birth or prolonged membrane rupture is anticipated if GBS carrier status is unknown or positive. Intrapartum treatment with intravenous penicillin or ampicillin is appropriate.

Adrenal Cortex Hormones↗

Proteolipid protein is necessary in peripheral as well as central myelin.

Alternative products of the proteolipid protein gene (PLP), proteolipid protein (PLP) and DM20, are major components of compact myelin in the central nervous system, but quantitatively minor constituents of Schwann cells. A family with a null allele of PLP has a less severe CNS phenotype than those with other types of PLP mutations. Moreover, individuals with PLP null mutations have a demyelinating peripheral neuropathy, not seen with other PLP mutations of humans or animals. Direct analysis of normal peripheral nerve demonstrates that PLP is localized to compact myelin. This and the clinical and pathologic observations of the PLP null phenotype indicate that PLP/DM20 is necessary for proper myelin function both in the central and peripheral nervous systems.

Adolescent↗

Assessment of the role of alpha2-adrenoceptor subtypes in the antinociceptive, sedative and hypothermic action of dexmedetomidine in transgenic mice.

1. The role of alpha2-adrenoceptor (AR) subtypes in the modulation of acute nociception, motor behaviour and body temperature, has been investigated by determining the activity of the alpha2AR selective agonist dexmedetomidine (Dex) in mice devoid of individual alpha2AR subtypes through either a point (alpha2A) or null (alpha2B/alpha2C) mutation ('knock-out'). 2. In a rodent model of acute thermal nociception, the mouse tail immersion test, Dex, in wild type (WT) control animals, produced a dose-dependent increase in the threshold for tail withdrawal from a 52 degrees C water bath with mean ED50 values of 99.9+/-14.5 (alpha2A), 94.6+/-17.8 (alpha2B) and 116.0/-17.1 (alpha2C) microg kg(-1), i.p. 3. In comparison to the WT controls, Dex (100-1000 microg kg(-1), i.p.), was completely ineffective as an antinociceptive agent in the tail immersion test in the alpha2A AR D79N mutant animals. Conversely, in the alpha2B AR and alpha2C AR knock-outs, Dex produced a dose-dependent antinociceptive effect that was not significantly different from that observed in WT controls, with ED50 values of 85.9+/-15.0 (P>0.05 vs WT control) and 226.0+/-62.7 (P>0.05 vs WT control) microg kg(-1) i.p., respectively. 4. Dex (10-300 microg kg(-1), i.p.) produced a dose-dependent reduction in spontaneous locomotor activity in the alpha2A, alpha2B and alpha2C AR WT control animals with ED50 values of 30.1+/-9.0, 23.5+/-7.1 and 32.3+/-4.6 microg kg(-1), i.p., respectively. Again, Dex (100-1000 microg kg(-1), i.p.) was ineffective at modulating motor behaviour in the alpha2A AR D79N mutants. In the alpha2B AR and alpha2C AR knock-out mice, Dex produced a dose-dependent reduction in spontaneous locomotor activity with ED50 values of 29.1+/-6.4 (P>0.05 vs WT control) and 57.5+/-11.3 (P>0.05 vs WT control) microg kg(-1), respectively. 5. Dex was also found to produce a dose-dependent reduction in body temperature in the alpha2A, alpha2B and alpha2C AR WT control mice with ED50 values of 60.6+/-11.0, 16.2+/-2.5 and 47.2+/-9.1 microg kg(-1), i.p., respectively. In the alpha2A AR D79N mutants, Dex had no effect on body temperature at a dose (100 microg kg(-1), i.p.) that produced a significant reduction (-6.2+/-0.5 degrees C; P<0.01 vs vehicle) in temperature in WT controls. However, higher doses of Dex (300 and 1000 microg kg(-1), i.p) produced a small, but statistically significant decrease in temperature corresponding to -1.7+/-0.4 degrees C and -2.4+/-0.3 degrees C (both P<0.01 vs vehicle), respectively. In the alpha2B AR and alpha2C AR knock-out mice, Dex produced a dose-dependent reduction in body temperature with ED50 values of 28.4+/-4.8 (P>0.05 vs WT control) and 54.1+/-8.0 (P>0.05 vs WT control) microg kg(-1), respectively. 6. In conclusion, the data are consistent with the alpha2A AR being the predominant subtype involved in the mediation of the antinociceptive, sedative and hypothermic actions of Dex. This profile would appear to indicate that an alpha2A AR subtype selective analgesic will have a narrow therapeutic window, particularly following systemic administration.

Adrenergic alpha-Agonists↗

Medical applications of synchrotron radiation x-rays.

The use of synchrotron radiation is not widespread in the field of medicine and in fact few health-care professionals have even heard of it. It is the purpose of this article to explain what it is and to give some examples of how it can contribute to medical science. X-rays have been used for diagnostic medical imaging for more than 100 years and, whilst new techniques such as computed tomography have been developed, the means of producing x-rays has altered little during that time. Synchrotron radiation sources provide multiple, extremely intense and tuneable beams of photons over a huge range of energies from infrared through to hard x-rays. Their advent has revolutionized many experimental techniques and synchrotron radiation is being applied across many fields from imaging to molecular dynamics. It has spawned several methods for studying live and wet tissue samples, yielding information on both structure and composition on all length scales down to atomic resolution. Such techniques have played a crucial role in the development of molecular biology and the solution of protein structures. The application of synchrotron radiation in the field of radiography is now expanding and it is clear that very substantial improvements in image quality and patient dose can be realized. Following an overview of the production and properties of synchrotron radiation, some of the ways in which this remarkable tool has already been exploited for medical research are reviewed and some potential clinical opportunities highlighted.

Animals↗

Biventricular assist device as a bridge to cardiac transplantation in the treatment of peripartum cardiomyopathy.

Peripartum cardiomyopathy is an unexpected complication of the puerperium with a high mortality rate. Appropriate therapy requires accurate identification of this disease, which is frequently difficult in a patient who has been previously healthy. Medical therapy using alteration of intravascular volume (to optimize ventricular preload), the addition of inotropic agents (to correct ventricular function), and intra-aortic balloon counterpulsation (to improve afterload reduction) is the first line of therapy. Surgical therapy, involving cardiac transplantation, is the ultimate treatment. This therapeutic modality, however, is limited by a lack of available organs for transplant. The development of devices to be used as a "bridge" is gaining acceptance and use as a pretransplantation procedure. This use may be considered particularly fundamental in otherwise healthy young women with peripartum cardiomyopathy. These patients frequently can have almost complete recovery and rehabilitation. We report the case of a young woman with peripartum cardiomyopathy who had a favorable outcome. We performed medical and surgical therapy, insertion of a temporary "bridge" device, and ultimately cardiac transplantation.

Adult↗

The cost of health care for HIV-positive patients.

Utilizing a prospective study of health service activity for HIV/AIDS, 2 estimates of hospital costs of care analysed with reference to gender, risk activity, immunological and clinical staging (1987 definition of AIDS) were undertaken. Utilizing combined costs per life year (based on hospital and hospice activity but not primary and community care) the ratio of costs for CD4 < 200 and CD4 > 200 was for most risk groups between 2-5:1 whilst for AIDS: pre-AIDS it was between 3.6-8.3:1 except for homosexuals where it was 12.6:1. A comparison of the standard hospital costs for infectious diseases with the published accounts for clinical AIDS care in Lothian suggests a 3-4-fold underestimate in the costs of providing a comprehensive health care service.

Acquired Immunodeficiency Syndrome↗

Hospital and hospice resource use of HIV-positive patients in Edinburgh.

A prospective study of health service and hospice resource utilization (average length of stay or ALOS, discharge rate, bed day use, outpatient consultation) analysed with reference to gender, risk activity, immunological and clinical staging (1987 definition of AIDS) for the financial year 1992-93 was undertaken at the Regional Infectious Disease Unit (RIDU), City Hospital, Edinburgh, Scotland where 72% of 513 patients were infected via injection drug use. Not surprising therefore overall, drug users were the heaviest users of the inpatient facilities (74% of the discharges and 65% of the bed days) although homosexuals had the highest discharge rate (114 per 100 person years) and rate of bed day use (1654 days per 100 person years). Immunodeficiency (CD4 count < 200 cells/ul) and a clinical diagnosis of AIDS were both associated with greater inpatient and outpatient resource use compared to those without immunodeficiency (CD4 count > or = 200 CD4 cells/ul) or AIDS. Gender effects were complex; the ALOS for women was increased for all risk groups whatever the CD4 count whilst there was no consistent trend of more resource use for women by risk group. Drug users were the heaviest overall users of the local hospice (84% of all admissions, 83% of the bed days and a discharge rate of 76.4 per 100 person years), more than double the rates experienced by the other risk groups. Thus both clinical and immunological staging (AIDS or a CD4 count < 200 cells/ul) were associated with increased resource use in HIV infection and estimates of resource use for AIDS need to be increased by around one-third to take into account hospice use. Despite the preponderance of drug users in Edinburgh, comparisons with other centres did not reveal increased resource use.

Acquired Immunodeficiency Syndrome↗

The use of a novel monitoring apparatus and modified Belzer hydroxyethyl starch perfusate for analysis of glomerular filtration during hypothermic perfusion preservation.

The present study describes an experimental model for measurement of glomerular filtration during hypothermic perfusion preservation (HPP). To facilitate glomerular filtration during HPP, perfusate oncotic pressure was reduced by lowering the concentration of hydroxyethyl starch. Lewis rats underwent HPP at a mean perfusion pressure of 40-46 mmHg. An isograft model was used to demonstrate that retrieval and preparation for HPP did not impact adversely on renal function. Total cold ischemic time (CIT) consisted of the time from retrieval and preparation for perfusion (2 hr) added to the time of HPP. Tubular function studies demonstrated identical concentrations of Na+ and iohexol in ureteral effluent (UE) compared with circulating perfusate and, as such, established that UE flow represented a direct measure of glomerular filtration. Glomerular filtration rate (GFR) was then monitored during HPP by collecting UE in a beaker housed within a computerized Mettler balance system. GFR evolved in a characteristic, biphasic pattern during HPP, increasing from baseline values to reach a peak level at 4.8+/-0.3 hr of CIT and declining progressively thereafter. At 2.5 hr, time of peak values, 10 hr, 19.5 hr, and 24 hr of CIT, GFR values were 29+/-6 microl/min, 39+/-7 microl/min, 20+/-4 microl/min (n=15; P<0.01), 7+/-2 microl/min (n=14; P<0.001), and 14+/-6 microl/min (n=5), respectively. Intrarenal perfusate flows at the same time intervals were 4180+/-292 microl/min, 4083+/-290 microl/min, 3577+/-294 microl/min (P=NS), 1948+/-393 microl/min (P<0.001), and 2175+/-743 microl/min, respectively. Filtration fraction (FF) initially changed in parallel to glomerular filtration. Thereafter, FF either declined at a disproportionately slow rate compared with GFR (n=8) or increased rapidly (n=7). The data suggest that (1) primary change(s) in glomerular dynamics occur during HPP and (2) declining perfusate flow during the later stages of HPP reflects increasing renal vascular resistance localized at a postglomerular level. The data provide an experimental basis for investigating the clinical utility of monitoring glomerular filtration during HPP.

Animals↗

Renal computed tomography with 3-dimensional angiography and simultaneous measurement of plasma contrast clearance reduce the invasiveness and cost of evaluating living renal donor candidates.

Renal computed tomography (CT), 3-dimensional CT angiography (3D-CTA), and simultaneous measurement of glomerular filtration rate (GFR) by x-ray fluorescence determination of plasma contrast clearance (PCC) are alternatives to intravenous urography (IVU), renal arteriography (RA), and 24-hr urine creatinine clearance (CrCl) for evaluation of renal structure and function in living renal donor (LRD) candidates. To determine if CT, 3D-CTA, and PCC provide data comparable to IVU, RA, and CrCl, both methods were used to evaluate 23 LRD candidates. Costs were also compared. Conventional RA identified 19 accessory arteries and one case of medial fibroplasia. Each of these anomalous vessels was recognized on 3D-CTA. Venous anatomy was more clearly delineated on 3D-CTA than the venous phase of conventional RA. CT demonstrated 3 benign cysts and a single, small intraparenchymal calcification in 3 renal units. GFRs measured by PCC and CrCl were 91 +/- 4 and 132 +/- 7 ml/min/1.73m2, respectively (r = 0.64, P < 0.05). Total cost for CT/3D-CTA/PCC was 46% less than that of IVU/RA/CrCl and 40% less than RA/CrCl. CT/3D-CTA/PCC provided reliable structural and functional data at substantially less cost, discomfort, and inconvenience to the living renal donor candidate. As such, CT/3D-CTA/PCC is superior to conventional methods for evaluation of the living renal donor candidate.

Adult↗

High resolution multicolor fluorescence in situ hybridization using cyanine and fluorescein dyes: rapid chromosome identification by directly fluorescently labeled alphoid DNA probes.

We tested DNA probes directly labeled by fluorescently labeled nucleotides (Cy3-dCTP, Cy5-dCTP, FluorX-dCTP) for high resolution uni- and multicolor detection of human chromosomes and analysis of centromeric DNA organization by in situ hybridization. Alpha-satellite DNA probes specific to chromosomes 1, 2, 3, 4 + 9, 5 + 19, 6, 7, 8, 10, 11, 13 + 21, 14 + 22, 15, 16, 17, 18, 20, 22, X and Y were suitable for the accurate identification of human chromosomes in metaphase and interphase cells. Cy3-labeled probes had several advantages: (1) a high level of fluorescence (5-10 times more compared with fluorescein-labeled probes); (2) a low level of fluorescence in solution, allowing the detection of target chromosomes in situ during hybridization without the washing of slides; and (3) high resistance to photobleaching during prolonged (1-2 h) exposure to strong light, thus allowing the use of a high energy mercury lamp or a long integration time during image acquisition in digital imaging microscopy for the determination of weak signals. For di- and multicolor fluorescence in situ hybridization (FISH), we successfully used different combinations of directly fluorophorated probes with preservation of images by conventional microscopy or by digital imaging microscopy. FluorX and Cy3 dyes allowed the use of cosmid probes for mapping in a one-step hybridization experiment. Cyanine-labeled fluorophorated DNA probes offer additional possibilities for rapid chromosome detection during a simple 15-min FISH procedure, and can be recommended for basic research and clinical studies, utilizing FISH.

Carbocyanines↗

Oral terbutaline after parenteral tocolysis: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Our purpose was to determine whether oral terbutaline, used after successful intravenous tocolysis, will prolong pregnancy and prevent recurrent preterm labor. STUDY DESIGN: After successful intravenous tocolysis, 203 women with preterm labor at 24 weeks' to 34 weeks 6 days' gestation were randomized to terbutaline (5 mg orally, every 4 hours) or placebo until 37 weeks' gestation. Women with recurrent preterm labor were treated with intravenous magnesium sulfate; if tocolysis was successful, they continued with the initial study medication. The primary outcome was the percentage delivered of their infants within 1 week of beginning oral tocolytic therapy. Latency, recurrent preterm labor, and maternal and neonatal outcomes were also assessed. RESULTS: Pregnancy outcome data were available in 200 women. There were no differences seen between the two groups in the incidence of delivery at 1 week (18% vs 24%, 95% confidence interval 0.44 to 1.29). In addition, there were no differences regarding median latency, mean gestational age at delivery, or the incidence of recurrent preterm labor (20% vs 16%, 95% confidence interval 0.64 to 2.71). Post hoc evaluation of 96 women enrolled before 32 weeks' gestation suggested pregnancy prolongation with maintenance oral terbutaline (p < 0.01). CONCLUSIONS: Maintenance oral terbutaline therapy initiated at 24 weeks' to 34 weeks 6 days' gestation after successful parenteral tocolysis is not associated with pregnancy prolongation or a reduction in the incidence of recurrent preterm labor.

Administration, Oral↗

The evaluation of infection and pulmonary maturity in women with premature rupture of the membranes.

Although the etiology of PROM is multifactorial, increasing evidence regarding clinical risk factors, membrane histology, membrane culture, and amniotic fluid microbiology shows a strong association with infection. Recent studies suggest an association between genital tract infection, preterm labor (PTL), and preterm premature rupture of the membranes (pPROM). If correct, this information may be used to target areas for prevention, as well as to develop management protocols. This article reviews both the diagnostic tests for the causes associated with pPROM and the evaluation of intraamniotic infection and pulmonary maturity in patients with pPROM.

Female↗