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Biomedical subjects

N J Anderson

Publications and source records attributed to N J Anderson.

At least 19 recordsLinked to original sources

Valacyclovir for the management of herpes viral infections.

The Herpesviridae family (Types 1-8) continues to inflict considerable morbidity and social stigma upon humanity. Once infected with the herpes viruses, especially Types 1-3, they establish permanent residence within our nervous system and reactivate during periods of stress, trauma, and/or other precipitating factors. To date, there is no cure for herpes viral infections but antivirals can attenuate the symptoms and duration of episodic outbreaks. Prophylactic therapy can suppress recurrences. The first antiviral with selective activity against virus-infected cells is considered to be acyclovir. Our article will highlight the clinical indications of the current generation, valacyclovir, which is a prodrug of acyclovir. We consider valacyclovir as a second-generation antiviral, having taken into account the initial selectivity and safety profile of its progenitor, acyclovir.

Acyclovir↗

Assessing population structure and gene flow in Montana wolverines (Gulo gulo) using assignment-based approaches.

In North America, wolverines once occupied a continuous range from Alaska southward to New Mexico. In the lower 48 states, small remnant populations remain only in the northwestern United States. Among these remnant populations, the Montana population has the highest probability of long-term persistence given its size and proximity to healthy populations in Canada. In this study, we evaluate population genetic structure and gene flow among Montana wolverines using 10 polymorphic microsatellite loci. Bayesian and frequency-based assignment tests revealed significant population substructure and provide support for at least three subpopulations in Montana. FST values between subpopulations ranged from 0.08 to 0.10 and provide evidence for male-biased dispersal. The high degree of population substructure and low levels of gene flow contrast results from wolverine population genetic studies in less fragmented landscapes of Alaska and Canada. This study provides additional support for the hypothesis that large carnivore populations of Montana are becoming increasingly fragmented due to human development and disturbance.

Animals↗

Endogenous beta-carbolines as clonidine-displacing substances.

Endogenous beta-carbolines, such as harmane, are known to occur in mammalian species including humans. Radioligand binding studies have revealed that certain beta-carbolines display high affinity for both I(1) and I(2) imidazoline-binding sites (IBS). Functional studies have shown that the beta-carboline harmane elicits many characteristics expected of an endogenous ligand IBS. This article discusses the evidence relating to beta-carbolines as endogenous ligands and presents a case for harmane and related compounds as endogenous ligands for IBS.

Adrenergic alpha-Agonists↗

Characterization of [(3)H]harmane binding to rat whole brain membranes.

This study investigates the binding of [(3)H]harmane to rat whole brain homogenates. Saturation studies revealed [(3)H]harmane labels a single, saturable, high-capacity population with high affinity. All the test compounds displaced [(3)H]harmane completely and in an apparently monophasic manner. The displacement profile of the test ligands indicated labeling of MAO-A. Given the high level of MAO-A binding, it is unlikely that a low-capacity I(2) site would be distinguishable from the total [(3)H]harmane population.

Animals↗

Posthaemorrhagic ventricular dilatation in the premature infant: natural history and predictors of outcome.

OBJECTIVE: To investigate the natural history and predictors of outcome of posthaemorrhagic ventriculomegaly in the very low birthweight (VLBW) infant. METHODS: All VLBW infants admitted between September 1994 and September 1997 to the neonatal intensive care units of Brigham and Women's Hospital (Boston), Children's Hospital (Boston), and Christchurch Women's Hospital (New Zealand) with germinal matrix intraventricular haemorrhage (IVH) were identified. All charts and ultrasound scans were reviewed to define the natural history and perinatal and/or postnatal factors of value in prediction of the course of posthaemorrhagic ventriculomegaly. Progressive ventricular dilatation (PVD) was defined from the results of serial cranial ultrasound scans. RESULTS: A total of 248 VLBW infants had evidence of IVH (22% of all VLBW infants, mean (SD) gestational age 26.8 (2.6) weeks). A quarter of the infants exhibited PVD. Spontaneous arrest of PVD occurred without treatment in 38% of infants with PVD. Of the remaining 62% with persistent PVD, 48% received non-surgical treatment only (pharmacological and/or drainage of cerebrospinal fluid by serial lumbar punctures), 34% received surgical treatment with insertion of a ventriculoperitoneal reservoir and/or shunt, and 18% died. The development of PVD after IVH and adverse short term outcome, such as the requirement for surgery, were predicted most strongly by the severity of IVH. CONCLUSIONS: These data reflect the natural history of PVD in the 1990s and show that, despite a slight reduction in its overall incidence, there appears to be a more aggressive course, with appreciable mortality and morbidity in the extremely premature infant. The major predictor of adverse short term outcome, defined as death or need for surgical intervention, was the severity of IVH. These findings may be valuable for the management of very small premature infants.

Boston↗

Complete characterisation of thermally treated sludges.

As disposal options for sludges become more difficult to find and more expensive to operate, those relying on some form of thermal treatment are becoming more commercially attractive. The incentive, especially for more heavily populated countries, is the production of treated solids suitable for beneficial application to land. It is the level of treatment required to achieve this cost effectively which has been the focus of much of the research in this field. There are now several commercially available plants designed to thermally treat sludges and many have been in full scale operation for a number of years. One of the auxiliary claims often made by proponents of such treatments, is that the resultant sludges are more amenable to dewatering and therefore easier and cheaper to handle. In this work we have used a novel filtration rig to obtain complete sets of filtration data for different sludges. Historically sludge characterisation has been achieved by measurement of an empirical Capillary Suction Time (CST) parameter, however with the new filtration apparatus it is now possible to obtain fundamental sludge characteristics across a wide range of volume fractions in hours not days. We have applied this technology to characterise different sludge samples before and after thermal treatment under different sets of operating conditions (pH, temperature and pressure) to simulate some of the commercially available thermal treatment technologies. We have also examined the effects of various chemical oxidants (hydrogen peroxide and Fenton's reagent) used as pretreatments to the thermal process and attempted to compare their cost efficiencies. The results show that the physical structure of the sludge is irreversibly altered by decreasing the pH or heating to temperatures in excess of 150 degrees C in a way which significantly enhances the dewaterability of the material. The treated sludge not only has a higher permeability but also has a higher final per cent solids (often in the autothermal region). In contrast the amounts of chemical additives used in pretreatment to achieve similar effects are cost prohibitive.

Hydrogen-Ion Concentration↗

Mercury accumulation rates and spatial patterns in lake sediments from west Greenland: a coast to ice margin transect.

The Arctic is recognized as an important focus for long-range transport of contaminants, such as mercury (Hg), from industrial regions at lower latitudes. In addition to large geographic gaps, there are few long-term retrospective time trends in arctic research, besides the Greenland ice record, to assess the onset of atmospheric pollution as well as to establish the rates of change in the terrestrial environment. In a study of sediments from 21 lakes along a 150 km transect from the coast to the ice sheet margin in the Søndre Strømfjord (Kangerlussuaq) region, we present stratigraphic evidence for elevated Hg inputs to this ice-free region on Greenland's west coast. Nineteen study lakes showed Hg concentration enrichments (HgEFconc) in surface compared to deeper sediments, with a mean HgEFconc of 3. Higher HgEFconc are found in lakes closest to the ice margin. The existence of this Hg gradient is supported by pollution Hg inventories in three 210Pb-dated cores. While 210Pb inventories and Pb pollution are higher at the coast, pollution Hg inventories are nearly 3-fold higher at the ice margin (570 micrograms m-2) than at the coast (210 micrograms m-2). These dated cores also indicate an onset of Hg pollution in the region beginning at least by the late 19th century but possibly as early as the 17th century.

Environmental Pollutants↗

Modeling diffuse phosphorus loads from land to freshwater using the sedimentary record.

Diffuse phosphorus (P) loads to a small lake, Friary Lough, in a 1 km2 agricultural subcatchment were quantified over 90 years using a palaeolimnological model. The model assumes that lake total phosphorus (TP) is lost to the sediments and to the lake outflow during periods of steady-state or is also stored within the water column during periods of non-steady-state behavior. Reconstructed TP loads during the 1991-1995 time interval of 2.05-2.53 g m-2 yr-1 are verified by hydrochemical monitoring results from the lake inflow during 1997-1998. This provides evidence for the accuracy of the palaeolomnological model and also that TP loads to the lake can be accounted for from external catchment runoff. An analysis of the TP load data in terms of catchment exports shows that there was a linear rate of increase from ca. 1946 to 1995 of 1.20-1.56 kg km-2 yr-1. The rate of increase is similar to river P load data in the larger 1480 km2 catchment taken over 17 years. The rate of TP increase to the lake is interpreted with regard to current soil P models that propose increasing and threshold soil P concentrations as the cause for increasing diffuse P loss in runoff.

Agriculture↗

Pharmacokinetics of norelgestromin and ethinyl estradiol from two consecutive contraceptive patches.

The primary objective of this open-label study was to determine the pharmacokinetics of norelgestromin (NGMN) and ethinyl estradiol (EE)following two consecutive applications of a contraceptive patch (ORTHO EVRA/EVRA). Twelve healthy women wore the first patch on their abdomen for 7 days and, after removal at 168 hours (day 7), wore a second patch for 10 days (i.e., 3 days beyond the intended 7-day wear period). Blood samples were collected before and at various times up to 456 hours (day 19) after application of the first patch for analysis of NGMN and EE. Mean serum concentrations of NGMN and EE remained within the reference ranges, 0.6 to 1.2 ng/ml and 25 to 75 pg/ml, respectively, during the entire 7-day wear period after application of the first patch and for 10 days after application of the second patch; reference ranges are based on studies with ORTHO-CYCLEN/ Cilest. No patch detached spontaneously. No subject discontinued or experienced a serious adverse event.

Administration, Cutaneous↗

The determination of RWJ-38705 (tramadol N-oxide) and its metabolites in preclinical pharmacokinetic studies using LC-MS/MS.

A rapid and reliable analytical method is described for the simultaneous determination of RWJ-38705 (tramadol N-oxide) and several of its major metabolites in the plasma of Sprague-Dawley rats and Beagle dogs. Sample preparation using solid phase extraction was followed by reversed phase liquid chromatography (LC) coupled with tandem mass spectrometric (MS/MS) detection in the positive ionization mode. The assay was linear for all analytes over concentrations ranging from approximately 6 to 2000 ng/ml. The inter-assay reproducibility was generally less than 15% while accuracy values were within 13% of theoretical. The overall recovery of the analytes ranged from approximately 40 to 64% in rat plasma and 53-75% in dog plasma. This assay has proven to be sensitive, specific and reproducible, and it has been readily implemented in preclinical PK studies. Representative plasma concentration versus time profiles resulting from administration of TNO to rats and dogs are presented in this communication.

Administration, Oral↗

Intracameral anesthesia: in vitro iris and corneal uptake and washout of 1% lidocaine hydrochloride.

OBJECTIVES: To characterize the uptake, washout, and metabolism of lidocaine hydrochloride in the iris/ciliary body and cornea. METHODS: Iris/ciliary body uptake of lidocaine hydrochloride was measured by incubating human and rabbit irides in radiolabeled carbon 14-1% lidocaine hydrochloride for 2 to 60 minutes. Washout was determined by incubating the iris in 14C-1% lidocaine hydrochloride for 5 minutes and transferring the iris to a series of wells. The wells contained a common intraocular irrigating solution of essential ions, glucose, and glutathione buffered with bicarbonate (an enriched balanced salt solution [BSS PLUS]), which is similar to aqueous humor. Corneal uptake was measured by exposing the endothelial surface to 14C-1% lidocaine hydrochloride for 5 or 15 minutes. Corneal washout was performed after 5-minute exposure to 14C-1% lidocaine hydrochloride using a 2-chambered diffusion apparatus. Samples of the iris, cornea, and BSS PLUS washout solution were analyzed by high-performance liquid chromatography and liquid scintillation spectrometry. RESULTS: In vitro iris/ciliary body uptake of 14C-1% lidocaine hydrochloride follows a logarithmic curve, with 50% to 60% of maximum lidocaine hydrochloride uptake present at 5 minutes. There was no difference in uptake between human, albino rabbit, and pigmented rabbit irides. Washout of lidocaine from the iris occurs with a halflife of 8 to 9 minutes. Corneal uptake of lidocaine was greater after incubation for 15 vs. 5 minutes. The washout of lidocaine from the cornea had a half-life of 5 minutes. Results of high-performance liquid chromatography confirmed that there were no metabolites or breakdown products in the iris, cornea, or washout solution. CONCLUSIONS: Lidocaine is taken up quickly by the iris/ ciliary body and cornea and rapidly removed from these tissues after BSS PLUS washout. Irrigation during phacoemulsification seems to limit lidocaine exposure to the ocular tissues, resulting in a short duration of anesthesia. Lidocaine is not metabolized or broken down by the iris or cornea during this short period.

Anesthesia, Local↗

Comparison of preservative-free bupivacaine vs. lidocaine for intracameral anesthesia: a randomized clinical trial and in vitro analysis.

PURPOSE: To determine whether intracameral bupivacaine hydrochloride 0.5% is as effective as lidocaine hydrochloride 1.0% in controlling discomfort of patients during phacoemulsification and posterior chamber intraocular lens implantation. In rabbits, corneal endothelial cell function, ultrastructure, and viability were evaluated after in vitro perfusion of bupivacaine 0.5%. METHODS: In a double-masked, controlled trial, 48 eyes of 48 patients with uncomplicated age-related cataract were randomly assigned to receive bupivacaine 0.5% or lidocaine 1.0% intracamerally before phacoemulsification with a posterior chamber intraocular lens. Outcome measures such as pain, visual acuity, amount of sedation, length of surgery, pupil size, intraocular pressure, corneal clarity, and anterior chamber reaction were compared. In laboratory studies, paired rabbit corneas were evaluated by endothelial cell perfusion with either bupivacaine 0.5%, bupivacaine 0.5% and glutathione bicarbonate Ringer solution in a 1:1 ratio or bupivacaine 0.5% buffered to a pH of 7.0. The paired control corneas were perfused with glutathione bicarbonate Ringer solution and rates of corneal swelling were determined. Cell ultrastructure and viability were also evaluated. RESULTS: In the randomized trial, there was no significant difference in the pain patients had during surgery or in the early or late postoperative period. No statistically significant difference was seen between the two groups in terms of pupil size, intraocular pressure, corneal edema, anterior chamber reaction, or visual acuity immediately after the operation or on postoperative day 1. Paired rabbit corneas perfused with bupivacaine 0.5% and bupivacaine 0.5% buffered to a pH of 7.0 swelled significantly (P<.001, P = .009, respectively), and had corneal endothelial cell damage. Dilution of the bupivacaine 1:1 with glutathione bicarbonate Ringer solution prevented corneal edema and damage to the corneal endothelium. Endothelial cell viability was also decreased after perfusion of bupivacaine 0.5% (P<.001). CONCLUSIONS: Clinically, bupivacaine 0.5% is as effective as lidocaine 1.0% for anesthesia during phacoemulsification and posterior chamber intraocular lens implantation. However, in vitro perfusion of bupivacaine 0.5% damaged the corneal endothelium of rabbits except when the drug was diluted 1:1 with glutathione bicarbonate Ringer solution. Surgeons who use 0.2 to 0.5 ml of intracameral bupivacaine 0.5% should be aware of its potential to cause endothelial cell damage because of its lipid solubility. The bupivacaine 0.5% should be diluted at least 1:1 with balanced salt solution before intracameral injection, followed immediately by phacoemulsification. The surgeon should ensure that the bupivacaine 0.5% is nonpreserved and packaged in single-use vials or flip-top containers.

Aged↗

Toxicity of ocular surgical solutions.

Intraocular medications, solutions, and instruments are an integral component of intraocular surgery. The ionic composition, pH, and osmolality should approximate aqueous humor to prevent damage to the corneal endothelium. Intraocular medications should be evaluated for their intrinsic properties and presence of vehicles or preservatives. Many new cleaning procedures and promising new intraocular drugs are likely to be introduced in the future. The responsibility of ocular surgeons is to protect their patients from drug-, solution-, or instrument-related toxicity.

Eye↗

The experience of cancer.

The illness career of the person with cancer has been characterized as a 'living-dying' experience in which, faced with the intolerable incompatibility of life and death, the individual and his or her family attempt to maintain control and 'normalize' everyday activity. Unfortunately, in their everyday struggles, families in North America appear to face social isolation from existing community services and networks that might assist them. Perhaps because the illness is so heavily medicalized and stigmatized, most persons with cancer and their families do not participate in them. A minority benefit from self-help organizations such as Cancer Society groups and survivor coalitions. The palliative care and hospice/home care movements provide an alternative to dying in the acute-care hospital, again, for a minority. Half of those with cancer survive more than 5 years; for these persons, the ordeal has just begun. Survivors must cope with physical disabilities due to surgery and the side effects of other treatments, the psychological traumas of fear of recurrence and social stigma, and the disappointment of a considerably reduced range of future possibilities for career and development. The fact that their relationships with others are negatively affected is well documented, particularly with intimate relationships. In a sense, a person never really 'gets over' cancer: it is a sword of Damocles that continues to hang over the individual and his or her family for the rest of the person's life.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗

A palaeolimnological assessment of diatom production responses to lake acidification.

To quantify diatom palaeoproduction responses to lake acidification, a whole-basin diatom accumulation rate was calculated for the small acidified lake Gaffeln, in the Gårdsjön catchment in south-west Sweden. Changes in the relative frequency of diatom assemblages to acidification were typical of other lakes in the area, notably a decline in planktonic diatoms after approximately 1900 and increase in acid-tolerant benthic species (e.g. Eunotia spp. and Tabellaria binalis). Single deep-water cores could be used to infer past changes in diatom production because of changed sediment-microfossil deposition patterns, probably due to the development of a benthic algal mat in the littoral zone. The basin mean total diatom accumulation rate (based on eight cores) was approximately constant over the last 150 years, while planktonic diatoms decreased from 0.3 x 10(6) frustules cm(-2) year(-1) prior to 1900 to trace levels in the 1970s. There was, however, a corresponding increase in the accumulation of benthic diatoms over the same period, from 0.5 to 1 x 10(6) frustules cm(-2) year(-1) between 1950 and the present, together with changed community structure. The increase in benthic species probably reflects an expansion of the littoral zone as light transparency increased.

Journal Article↗

Life stress, social support, and anxiety in mid- and late-pregnancy among low income women.

The stability and multivariate effects of life stress, social support, and anxiety from mid to late pregnancy in a sample of low-income women were examined. The sample of 190 was approximately equally divided among black, Hispanic, and white groups. Scores from the two time periods were highly consistent. The multivariate effects of life stress and social support on anxiety were similar at the two time periods, explaining 30% to 34% of the variance in anxiety, over and above the effects of ethnicity or marital status. The prospective test (Time 1 variables predicting Time 2 anxiety), however, explained only 22% of the variance in anxiety. Significant stress-buffering effects from social support were found for both the Time 1 regression and the prospective test. The combination of high life stress and low partner support was associated with the highest anxiety. The findings confirmed that mid-pregnancy measures of these psychosocial variables were valid indicators of their level over the course of the remainder of the pregnancy, allowing for early assessment and intervention to improve perinatal well-being.

Adolescent↗