bluuebunny/crossref_metadata_2025 huggingface dataset:
NANOSTRUCTURE OF THE DIATOM FRUSTULE AS REVEALED BY ATOMIC FORCE AND SCANNING ELECTRON MICROSCOPY
Authors: Crawford Simon A. , Higgins Michael J. , Mulvaney Paul , Wetherbee Richard
Published: March 2003

The cell wall (frustule) of the freshwater diatom Pinnularia viridis (Nitzsch) Ehrenberg is composed of an assembly of highly silicified components and associated organic layers. We used atomic force microscopy (AFM) to investigate the nanostructure and relationship between the outermost surface organics and the siliceous frustule components of live diatoms under natural hydrated conditions. Contact mode AFM imaging revealed that the walls were coated in a thick mucilaginous material that was interrupted only in the vicinity of the raphe fissure. Analysis of this mucilage by force mode AFM demonstrated it to be a nonadhesive, soft, and compressible material. Application of greater force to the sample during repeated scanning enabled the mucilage to be swept from the hard underlying siliceous components and piled into columns on either side of the scan area by the scanning action of the tip. The mucilage columns remained intact for several hours without dissolving or settling back onto the cleaned valve surface, thereby revealing a cohesiveness that suggested a degree of cross‐linking. The hard silicified surfaces of the diatom frustule appeared to be relatively smooth when living cells were imaged by AFM or when field‐emission SEM was used to image chemically cleaned walls. AFM analysis of P. viridis frustules cleaved in cross‐section revealed the nanostructure of the valve silica to be composed of a conglomerate of packed silica spheres that were 44.8 ± 0.7 nm in diameter. The silica spheres that comprised the girdle band biosilica were 40.3 ± 0.8 nm in diameter. Analysis of another heavily silicified diatom, Hantzschia amphioxys (Ehrenberg) Grunow, showed that the valve biosilica was composed of packed silica spheres that were 37.1 ± 1.4 nm and that silica particles from the girdle bands were 38.1 ± 0.5 nm. These results showed little variation in the size range of the silica particles within a particular frustule component (valve or girdle band), but there may be differences in particle size between these components within a diatom frustule and significant differences are found between species.
ROLE OF ULTRAVIOLET RADIATION IN MAINTAINING THE THREE‐DIMENSIONAL STRUCTURE OF A CYANOBACTERIAL MAT COMMUNITY AND FACILITATING NITROGEN FIXATION
Authors: Sheridan Richard P.
Published: March 2003

Cyanobacterial mat communities were collected in the mangrove forest bordering the Grand Cul de Sac Marin, Guadeloupe, French West Indies, which supports a community of nitrogen fixing cyanobacterial mats established on the trunk and branches of black mangrove (Avicennia germinans L.). This study presents results that are focused on the mat community and the physiological and morphological adaptations to UV radiation. The dominant surface species of the mat, Nostoc cf commune Vaucher and Scytonema sp., possessed the UV‐shielding pigment scytonemin. Mats grown on medium D agar without nitrogen under photosynthetically active radiation (PAR) only, rapidly became disorganized compared with those exposed to PAR + UV‐A (320– 400 nm) + UV‐B (280–320 nm) irradiation. Concurrent with disorganization, acetylene reduction activity (ARA = one third of N2 reduction) was severely reduced, whereas mats irradiated with PAR + UV‐A + UV‐B maintained high ARA activity. Mats incubated for 27 days under PAR + UV‐A + UV‐B then exposed to PAR only exhibited a 68% stimulation of ARA, whereas ARA values were 33% inhibited in mats incubated with PAR only and then exposed to PAR + UV‐A + UV‐B. This favorable equilibrium was facilitated by the mats' three‐dimensional structure in which the most UV‐resistant species, N. commune, covers the surface with UV‐sensitive species below this protective covering. The UV stressor was essential for the maintenance of mat structure and ARA.
NITROGEN STRESS RESPONSE OF PROCHLOROCOCCUS STRAIN PCC 9511 (OXYPHOTOBACTERIA) INVOLVES CONTRASTING REGULATION OF ntcA AND amt11
Authors: Lindell Debbie , Erdner Deana , Marie Dominique , Prášil Ondřej , žek Michal Koblí , Le Gall Florence , Rippka Rosmarie , Partensky Frédéric , Scanlan David J. , Post Anton F.
Published: March 2003

The ntcA and amt1 genes (encoding a transcriptional activator of genes involved in nitrogen metabolism and a high affinity ammonium transporter respectively) from the axenic Prochlorococcus strain PCC 9511 were amplified, cloned, and sequenced. Cultures of this strain were exposed to nitrogen deprivation, and the expression of ntcA and amt1 was monitored along with cell density, photochemical quantum yield (as determined from Fv/Fm measurements), and cellular C:N ratios. Nitrogen deprivation led to arrested cell growth, reduced photochemical quantum yields, and increased cellular C:N ratios. Surprisingly, transcript accumulation patterns of ntcA and amt1 were not correlated. High levels of amt1 transcript were observed in both nitrogen‐replete and ‐deplete conditions. Expression of amt1 declined under severe deprivation of either phosphorus or nitrogen and showed a positive correlation with photochemical quantum yield. In contrast, ntcA expression was specifically enhanced in the absence of ammonium. High ntcA transcript levels were maintained over time and did not decline with low Fv/Fm values under severe N deprivation. Although ntcA transcript levels correlated somewhat with cellular C:N ratios, at the onset of nitrogen deprivation increases in ntcA mRNA levels occurred before increases in cellular C:N ratios. Constitutively high ammonium transporter expression together with low cellular ammonium requirements are likely to have important implications for the success of Prochlorococcus in the nitrogen‐poor oligotrophic waters where they are most abundant. The function of NtcA in Prochlorococcus strain PCC 9511 remains unclear.
DIEL VARIATIONS IN OPTICAL PROPERTIES OF MICROMONAS PUSILLA (PRASINOPHYCEAE)1
Authors: DuRand Michele D. , Green Rebecca E. , Sosik Heidi M. , Olson Robert J.
Published: March 2003

Micromonas pusilla (Butcher) Manton et Parke, a marine prasinophyte, was used to investigate how cell growth and division affect optical properties of phytoplankton over the light:dark cycle. Measurements were made of cell size and concentration, attenuation and absorption coefficients, flow cytometric forward and side light scattering and chl fluorescence, and chl and carbon content. The refractive index was derived from observations and Mie scattering theory. Diel variations occurred, with cells increasing in size, light scattering, and carbon content during daytime photosynthesis and decreasing during nighttime division. Cells averaged 1.6 μm in diameter and exhibited phased division, with 1.3 divisions per day. Scattering changes resulted primarily from changes in cell size and not refractive index; absorption changes were consistent with a negligible package effect. Measurements over the diel cycle suggest that in M. pusilla carbon‐specific attenuation varies with cell size, and this relationship appears to extend to other phytoplankton species. Because M. pusilla is one of the smallest eukaryotic phytoplankton and belongs to a common marine genus, these results will be useful for interpreting in situ light scattering variation. The relationship between forward light scattering (FLS) and volume over the diel cycle for M. pusilla was similar to that determined for a variety of phytoplankton species over a large size range. We propose a method to estimate cellular carbon content directly from FLS, which will improve our estimates of the contribution of different phytoplankton groups to productivity and total carbon content in the oceans.
DEVELOPMENT OF HIGH THROUGHPUT SINGLE NUCLEOTIDE POLYMORPHISM GENOTYPING FOR THE ANALYSIS OF NODULARIA (CYANOBACTERIA) POPULATION GENETICS1
Authors: Batley Jacqueline , Hayes Paul K.
Published: March 2003

Any investigation of the genetic structure of populations involves the analysis of a large number of samples and therefore benefits from the use of rapid, inexpensive, and automated methods to assign individuals to a particular genotype. We developed a high throughput SNuPE (single nucleotide primer extension) assay to assess polymorphic base variations at three loci (PC‐IGS, rDNA‐ITS, and gvpA‐IGS) in the genome of the cyanobacterium Nodularia spumigena. Using a 96‐capilliary sequencer, analysis of thirteen 96‐well plates can be performed in the same electrophoretic run, allowing the throughput of 1248 samples in 75 min. The SNuPE method can be broken down into two stages. The first stage comprises amplification of a DNA fragment containing the polymorphic sequence and its purification from un‐incorporated PCR reagents. The second stage involves the annealing and extension of a third primer, the SNuPE primer, the 3′ end of which immediately precedes the variable site in the template. This primer is extended with a single fluorescently labeled dideoxy nucleotide by DNA polymerase, followed by characterization of the extended primers on a DNA sequencing instrument. The length of the extended primer is used to define the locus, and the incorporated fluorescent dideoxy nucleotide gives the identity of the nucleotide at each polymorphic site. Details of this technique and its application to study the genetic structure of Nodularia populations are described.
Phylogenetic Relationships Among Pediastrum sPP. and Hydrodictyon sPP.
Authors: McManus H. A. , Lewis L. A.
Published: March 2003

Within the class Chlorophyceae, the family Hydrodictyaceae (order Sphaeropleales) consists of taxa that form flat or net‐like coenobia and reproduce asexually by way of biflagellated zoospores. Two taxa within this family, Pediastrum and Hydrodictyon, share many features during development, especially the manner of daughter colony formation. The colonies of Pediastrum differ from Hydrodictyon in that growth is planar resulting in two‐dimensional colonies, while three‐dimensional nets are formed in Hydrodictyon. Studies of the Chlorophyceae using morphological and ultrastructural data, as well as molecular sequence data, have supported the close relationship of Pediastrum and Hydrodictyon and they have remained in the family Hydrodictyaceae throughout major classification revisions. However, in these studies only single species of Pediastrum (P. duplex) and Hydrodictyon (H. reticulatum) were included, therefore the exact relationship of these two taxa could not be explored. Preliminary molecular data from a second species of Pediastrum, P. boryanum, indicate that Hydrodictyon may be derived from Pediastrum. In this analysis, H. reticulatum resolves as sister taxon to P. duplex with P. boryanum the ancestral taxon. Further molecular studies of the family Hydrodictyaceae allow exploration of the relationships between Pediastrum spp. and Hydrodictyon spp., and assist in determining whether they are monophyletic. Preliminary analyses include H. reticulatum and H. africanum and several species of Pediastrum, P. duplex, P. boryanum, P. tetras, P. biradiatum and P. simplex. An understanding of the phylogenetic relationships among the species of Pediastrum and Hydrodictyon will allow a more complete comparison of colony formation.
Moderate Physical Activity is Associated with Higher Bone Mineral Density in Postmenopausal Women
Authors: Hagberg James M. , Zmuda Joseph M. , McCole Steve D. , Rodgers Kathleen S. , Ferrell Robert E. , Wilund Kenneth R. , Moore Geoffrey E.
Published: March 2003

OBJECTIVES: To determine the associations between different levels of habitual physical activity, hormone replacement therapy (HRT), and bone mineral density (BMD) in postmenopausal women.

DESIGN: Cross‐sectional.

SETTING: Academic medical center.

PARTICIPANTS: Twenty sedentary women, 20 active nonathletic women, and 23 endurance‐trained athletes, all of whom were postmenopausal, with half of each group on and half not on HRT.

MEASUREMENTS: BMD and body composition determined by dual energy x‐ray absorptiometry, maximal oxygen consumption (VO2max), dietary history by questionnaire, and vitamin D receptor (VDR) genotyping on deoxyribonucleic acid.

RESULTS: Body weight was higher in the active nonathletic than in the sedentary and athletic women. Body fat was lower and VO2max higher in the athletic women than in the sedentary and the active nonathletic women. Physical activity level was significantly associated with BMD in three of the five measurements taken (L1–L4 lumbar spine, trochanter, total body; all P < .05). These differences were also generally significant after adjusting for body weight. The association between physical activity status and BMD at the neck of the femur and Ward's triangle bordered on significance (P = .07–.09). At most sites, the active nonathletic women had higher BMD than did the sedentary and athletic women. HRT was significantly associated only with total body BMD (P < .05). The groups were similar in terms of dietary habits (protein, calcium, sodium, phosphorus intake); VDR genotypes; and family, smoking, and nutritional histories.

CONCLUSION: Given the similarity of the groups with respect to other factors that affect BMD, it appears that prolonged low‐to‐moderate‐intensity physical activity, but not the same number of years of higher‐intensity training for competitive events, was independently associated with higher BMD.
Muscle Power of the Ankle Flexors Predicts Functional Performance in Community‐Dwelling Older Women
Authors: Suzuki Toshimi , Bean Jonathan F. , Fielding Roger A.
Published: March 2003

OBJECTIVES: To test the hypothesis that peak power of the ankle flexors is related to physical functioning in older women with functional limitations.

DESIGN: A cross‐sectional study.

SETTING: University‐based human physiology laboratory.

PARTICIPANTS: Thirty‐four older women (75.4 ± 5.1 years, 67.8 ± 11.3 kg, body mass index 27.4 ± 4.5) with self‐reported functional limitations.

MEASUREMENTS: Plantarflexion (PF) and dorsiflexion (DF) peak power and isometric strength with physical performance (stair climb time, repeated chair rise time, maximal and habitual gait velocity) were determined. An isokinetic dynamometer was used to measure isometric strength, isokinetic peak torque and power of PF and DF at five angular velocities (30°, 60°, 90°, 120°, and 180°·sec−1), and isometric strength.

RESULTS: Peak torque for both PF and DF declined with increasing velocity of movement (PF: P < .0001; DF: P < .0001), whereas peak power increased with increasing velocity up to 120°·sec−1. The strongest univariate associations were found between chair rise time and DF peak power (r = 0.50; P < .002), stair climb time and DF peak power (r = 0.49; P < .003), habitual gait velocity and PF isometric strength (r = 0.53; P < .001), and maximal gait and PF isometric strength (r = 0.47; P < .005). Multivariate regression analysis revealed that DF and PF peak power along with the physical functioning and general health scores from the Medical Outcomes Study Short Form were independent predictors of chair and stair climb performance.

CONCLUSION: These data suggest that ankle muscle power together with self‐reported measures of health and physical functioning are essential components of functional mobility in older women with functional limitations.
Seasonal Variations in Serum Levels of 25‐Hydroxyvitamin D and Parathyroid Hormone but no Detectable Change in Femoral Neck Bone Density in an Older Population with Regular Outdoor Exposure
Authors: Melin Annalisa , Wilske Jan , Ringertz Hans , Sääf Maric
Published: March 2003

OBJECTIVES: To investigate the influence of season and outdoor daylight exposure on serum levels of 25‐hydroxyvitamin D (25OHD), intact parathyroid hormone (PTH), ionized calcium, and femoral neck bone mineral density (BMD).

DESIGN: A 12‐month, longitudinal, prospective study on a consecutively selected sample of healthy independent older people.

SETTING: Men and women living in their own homes in the inner city of Stockholm (latitude 59.2°N).

PARTICIPANTS: Sixty‐four healthy men (n = 13) and women (n = 51), age 79 to 96 (mean age 83.7) were requested to spend at least 3 hours per week outdoors during April through September. Fifteen of these, who failed to comply with the required time outdoors, constituted a separate group. Subjects with serious diseases and subjects with medication that could interfere with vitamin D metabolism or bone mineralization were excluded from the study.

MEASUREMENTS: Daily dietary intakes of calcium and vitamin D were recorded on the basis of the subjects' recall. The participants kept a diary recording the time spent in sunlight and the area of skin exposed. Fasting blood samples were collected and analyzed on four occasions for 25OHD, intact PTH, and ionized calcium. BMD was determined at 6‐month intervals in the femoral neck, using dual energy x‐ray absorptiometry.

RESULTS: At study start in the spring, 6% of the subjects had 25OHD levels below 10 ng/ml and 78% had levels below 31 ng/ml. Forty‐seven percent had intact PTH levels above the upper limit of the reference range (8–51 ng/L). Seasonal variations in the serum levels of 25OHD (P < .001), intact PTH (P < .001) and ionized calcium (P < .001) were observed only in the group with ≥3 hours of weekly outdoor daylight exposure. The 25OHD levels in autumn were positively correlated with the number of hours spent outdoors during the preceding summer (r = 0.63, P < .001). In the whole group and in the group with weekly outdoor exposure of ≥3 hours, there were no significant changes detectable in mean values of femoral neck BMD during the study year. Femoral neck BMD, expressed as Z‐score, was significantly and positively correlated with serum 25OHD (r = 0.38, P = .003 after summer; r = 0.37, P = .003 after winter).

CONCLUSION: The seasonal changes in serum levels of 25OHD, PTH, and ionized calcium and the positive correlation between femoral neck BMD and 25OHD indicate that regular outdoor daylight exposure during the summer could enhance calcium homeostasis and possibly bone health, even among very old people living at northerly latitudes.
Drug Benefit Plans Under Managed Care: To What Extent Do Older Subscribers Selecting Less Drug Coverage Put Themselves at Increased Financial Risk?
Authors: Andrade Susan E. , Gurwitz Jerry H.
Published: March 2003

Many health maintenance organizations (HMOs) have implemented programs that limit drug benefit coverage for Medicare beneficiaries. A retrospective study was conducted among Medicare beneficiaries enrolled in the Fallon Community Health Plan to evaluate the implications of the implementation of an HMO program that allowed Medicare beneficiaries to choose between three drug benefit plans: full drug coverage, a drug benefit plan with a maximum of $1,000 in coverage, or no drug benefit. The mean costs of prescription drugs and other healthcare services were calculated and compared for 14,762 patients enrolled in the three pharmacy benefit plans during the 6‐month period before and the 12‐month period after January 1, 1994, the date of benefit selection. Prescription drug utilization and associated costs were greatest among those members selecting full drug coverage, followed by those with a $1,000 maximum coverage benefit, followed by those selecting no drug coverage (P < .001). The proportion of patients that reached or exceeded $2,000 in prescription drug costs during the 12‐month period was determined to evaluate the frequency of patients incurring potentially catastrophic drug expenditures if they were not enrolled in a full drug‐coverage plan. Only 21 members (0.5%) with the $1,000 maximum drug benefit reached or exceeded this $2,000 threshold; only one member in the no drug coverage group exceeded this level. A relatively small percentage of patients had drug expenditures that exceeded what was allowed under the drug benefit plan selected. The vast majority of older people choosing less‐comprehensive drug benefit plans appeared to make appropriate choices of plans based upon past utilization of prescription and other medical services.
Reproducibility of Blood Pressure Variation in Older Ambulatory and Bedridden Subjects
Authors: Tsuchihashi Takuya , Kawakami Yasunobu , Imamura Tsuyoshi , Abe Isao
Published: March 2003

OBJECTIVES: We investigated the influence of ambulation on the reproducibility of circadian blood pressure variation in older nursing home residents.

DESIGN: Ambulatory blood pressure monitoring was performed twice in 37 older nursing home residents.

SETTING: Nursing home in Japan.

PARTICIPANTS: Subjects included 18 ambulatory nursing home residents who had no limitation on physical activity and 19 bedridden residents who did not participate in physical activity.

MEASUREMENTS: Twenty‐four–hour, daytime, and nighttime blood pressure levels and their variability.

RESULTS: The 24‐hour and daytime variability of systolic blood pressure (SBP) was significantly greater in ambulatory than in bedridden subjects, whereas nighttime variability was similar. Significant correlations in SBP averaged for the whole day, daytime, and nighttime were observed between the two examinations in ambulatory (r = .80–.83) and bedridden (r = .83–.91) subjects, but the variabilities of SBP for the whole day and during the daytime of the first measurement were correlated with those of the second measurement in bedridden (r = .67 and r = .47, respectively) but not in ambulatory (r = .39 and r = .28, respectively) subjects. Significant correlations were found between the nocturnal SBP changes at two occasions in both ambulatory (r = .50) and bedridden (r = .51) subjects, but the dipper versus nondipper profiles, defined as reduction in SBP of greater than 10% versus not, showed low reproducibility in ambulatory subjects; five ambulatory (28%) and one bedridden (5%) subjects showed divergent profiles between the two examinations.

CONCLUSIONS: The reproducibility of blood pressure variation in nursing home residents is influenced by ambulation.
Diurnal, Week‐to‐Week, and Long‐Term Variation in Urine Deoxypyridinoline Cross‐Link Excretion in Healthy Older Women
Authors: Allain Theresa J. , Abraha Hagosa D. , Ouldred Emma L. , Ajmal Raheela , Buxton‐Thomas Muriel S. , Gray Beverley C. , Dnm  , Jackson Stephen H. D. , Blackburn Ann M. , Moniz Caje F.
Published: March 2003

OBJECTIVES: To establish a reference range for morning and afternoon excretion of urinary deoxypyridinoline (DPD) in apparently healthy older women selected from a volunteer database. To assess the extent of diurnal variation and short and long‐term within‐subject longitudinal variation.

DESIGN: Prospective, observational, cohort study.

SETTING: Clinical Age Research Unit, King's College School of Medicine, London, United Kingdom.

PARTICIPANTS: Forty‐two women aged 68 to 89 (median age 75) selected from a volunteer database.

METHODS: Subjects completed an osteoporosis risk factor questionnaire and a physical examination and had a measurement of the broadband ultrasound attenuation and speed of sound of their right heel. Subjects provided six urine samples: morning and afternoon at baseline and 1 week and 60 weeks later for measurement of DPD.

RESULTS: The mean baseline values for DPD of morning and afternoon samples were 7.2 nM/mM and 6.0 nM/mM creatinine, respectively. The majority of subjects showed diurnal variation, with mean afternoon values 15% lower than morning values (P < .0001 for afternoon vs morning values). The mean difference in DPD after 60 weeks was 1.67 nM/mM for morning and 1.34 nM/mM for afternoon creatinine. This difference was not significant. Some individuals displayed marked changes in DPD excretion with no change in health status or treatment. DPD excretion in a nonfasting afternoon sample showed similar characteristics to morning void samples in terms of scatter, week‐to‐week variation, and long‐term reproducibility.

CONCLUSIONS: The study was set up to provide background data to assist the development of a clinical osteoporosis service for older women. Further studies are needed to determine whether these measurements predict fracture risk and respond to treatment changes in this age group.
Neural mechanisms of cutaneous nociceptive pain. (Department of Neurology, University of Würzburg, Germany) Clin J Pain 2000;16:S131–S138.
Authors: Koltzenburg: Martin
Published: March 2003

Acute mechanical, thermal, and chemically induced pains in the skin are signaled by a set of specific nociceptive afferents, which encode the magnitude of the perceived pain by their discharge intensity. After tissue injury or inflammation, a number of changes in their properties of the primary afferent occur parallel to profound changes in the central nervous system. Primary hyperalgesia (within the area of tissue injury) is best explained by changes of the properties of primary nociceptive afferents, whereas secondary hyperalgesia (increased pain sensitivity outside the area of tissue injury) critically requires functional changes in the central nervous system. Collectively, these changes are the basis for many forms of hyperalgesia that can present clinically as incident pain. Knowledge of the various types of hyperalgesia and their underlying mechanisms is required for better treatment of this challenging aspect of chronic pain.
Memantine (a N‐methyl‐d‐aspartate receptor antagonist) in the treatment of neuropathic pain after amputation or surgery: a randomized, double‐blinded, cross‐over study. (Danish Pain Research Center, University of Aarhus, Aarhus, Denmark) Anesth Analg 2000;91:960–966.
Authors: Nikolajsen Lone , Gottrup Hanne , Kristensen Anders G. D. , Jensen: Troels S.
Published: March 2003

Evidence has accumulated that the N‐methyl‐d‐aspartate receptor system plays a role in continuous and stimulus‐evoked pain after nerve injury. The analgesic effect of memantine on a group of patients with chronic pain after surgery was examined in this randomized, double‐blinded, study. Nineteen patients randomly received either memantine or placebo in the first 5‐week treatment period. A washout period of 4 weeks was followed by another 5‐week treatment period of the opposite drug. The dosage of drug was increased from 5 to 20 mg/d. Pain was recorded daily, with the use of a 0‐10 numeric rating scale. Before and at the end of each treatment, pain and sensitivity were also assessed by using the McGill Pain Questionnaire, allodynia to touch, brush, and cold, wind‐up‐like pain, and thresholds to mechanical stimuli (pressure and von Frey hair). A total of 15 patients completed the study. There was no difference between memantine and placebo on any of the outcome measures. Conclude that memantine at a dosage of 20 mg/d does not reduce spontaneous or evoked pain in patients with nerve injury pain.

Comment by Tat‐Leang Lee, M.D. The treatment of patients suffering from chronic neuropathic pain remains a clinical challenge, particularly in cases where opioid therapy fails to provide sufficient pain relief. Experimental data concerning the role of NMDA‐mediated processes in central sensitization and the effects of NMDA receptor antagonists in different models of neuropathic pain have been well established. Currently, clinically available NMDA antagonists have narrow therapeutic windows and are limited by psychomimetic and other side effects. There exists a need to improve on this therapeutic ratio. Potential methods include the use of more selective NMDA antagonists that modulate binding sites within the NMDA complex, using novel routes including central axis delivery, or in combination with drugs. Combinations of opioids and NMDA antagonists may hold the most promise. Recently, a 1:1 mixture of morphine with dexmethorphan hydrobromide allowed satisfactory pain relief in chronic pain patients at a significantly lower morphine dose.1 In this study, there were 3 patients who had morphine as part of their conventional treatment. Although specific data is not available, it would be interesting to know if memantine proved to be more effective in these patients.
The evolving role of antiepileptic drugs in treating neuropathic pain. (Brigham and Women's Hospital, Harvard Medical School, Boston, MA) Neurology 2000;55(Suppl 1): S41–S46.
Authors: Ross: Edgar L.
Published: March 2003

For many years, tricyclic antidepressants (TCAs) were used as initial therapy for the pharmacologic management of neuropathic pain. First‐generation antiepileptic drugs (AEDs) are also used for the treatment neuralgia and migraine headache, respectively. Although TCAs are associated with side effects that limit their usefulness, particularly in the elderly or in patients with multiple problems, comparative meta‐analyses show their tolerability to be greater than that of the first‐generation AEDs. Recently, newer AEDs with more favorable side‐effect profiles have been tested in placebo‐controlled clinical trails for the treatment of neuropathic pain, including painful diabetic neuropathy and postherpetic neuralgia. The results of these trials, together with advances in understanding the pathophysiology of neuropathic pain, provide the basis for reevaluating some of the commonly accepted paradigms that guide approaches to treatment.
Lidocaine disrupts axonal membrane of rat sciatic nerve in vitro. (Miyazaki Medical College, Miyazaki, Japan) Anesth Analg 2000;91:944–948.
Authors: Kanai Yuko , Katsuki Hiroshi , Takasaki: Mayumi
Published: March 2003

To confirm lidocaine‐induced membrane disruption in mammalian nerve, this study measured a lactate dehydrogenase (LDH) leakage from rat sciatic nerve in vitro. Before applying lidocaine, the desheathed nerve was incubated for 60 min in Krebs‐Ringer solution at 37°C to examine basal LDH activity. It was then incubated in 80 mM lidocaine solution at pH 7.3 for 15, 30, 60, or 120 min. Other nerves were immersed in 800 mM choline solution for 120 min. Total LDH activity per wet weight of nerve tissue was assayed using spectrophotometry. It was also determined using nerves cut into 10 segments and incubated in distilled water for 60 min. The LDH activity in the lidocaine group showed a time‐dependent increase. After 60‐min and 120‐min incubation with lidocaine, the amount of LDH activity was significantly increased compared with choline group and was similar to that of the group incubated in distilled water. Conclude that 80 mM lidocaine may be sufficient to cause membrane damage and facilitate the leakage of enzymes from cytoplasm.
The effects of KRN5500, a spicamycin derivative, on neuropathic and nociceptive pain models in rats. (Massachusetts General Hospital, Charlestown, MA) Anesth Analg 2000;91:955–959.
Authors: Abdi Salahadin , Vilassova Natalia , Decosterd Isabelle , Feroz Nusrat , Borsook: David
Published: March 2003

This study investigated the effects of a spicamycin derivative, KRN5500, on two models of neuropathic pain (Chung and Bennett models) and a nociceptive pain model by using Complete Freund's adjuvant. After the establishment of mechanical models, a single intraperitoneal injection of KRN5500 produced significant attenuation of mechanical allodynia in both neuropathic pain models. However, this effect was not observed in rats that had a nociceptive injury. Furthermore, this experimental drug did not alter the mechanical pain threshold on normal, uninjured rats. Conclude that the KRN5500 may have value in the treatment of neuropathic pain.
Spinal effect of the cholecystokinin‐B receptor antagonist CI‐988 on hyperalgesia, allodynia, and morphine‐induced analgesia in diabetic and mononeuropathic rats. (Laboratoire de Physiologie, Clermont‐Ferrand Cedex 1, France) Pain 2000;88:15–22.
Authors: Coudoré Marie‐Ange , Courteix Christine , Fialip Joseph , Boucher Michel , Eschalier: Alain
Published: March 2003

This study examined the effect of intrathecal CI‐99, an antagonist of the CCK‐B receptors, on mechanical hyperalgesia and allodynia in normal, mononeuropathic and diabetic rats. The effect of the combination of CI‐988 and IV morphine on mechanical hyperalgesia in diabetic and mononeuropathic rats was evaluated using isobolographic analysis. Although ineffective in normal rats, CI‐988 induced antinociceptive effects in diabetic and mononeuropathic rats, suggesting an involvement of the CCKergic system in neurogenic pain conditions. The combination of CI‐988 and morphine showed a superadditive interaction in the diabetic rats only. In addition, CI‐988 exhibited a weak antiallodynic effect in mononeuropathic rats, and no antiallodynic effect in diabetic rats. These results show the CCK‐B receptor blockade‐mediated antinociceptive effects and reveal the antinociceptive action of morphine in diabetic rats after CCKergic system inhibition.
A Review of Sympathetically Maintained Pain Syndromes in the Cancer Pain Population:
Authors: Wilsey Barth , Teicheira David , Caneris Onassis A. , Fishman Scott M.
Published: March 2003

Abstract: Accepted wisdom contends that sympathetically maintained pain is rare in cancer pain syndromes. But this may be more of an artifact of how we diagnose this condition than a reflection of its true prevalence. One area in which one might suspect this to be true is in postsurgical states. While there are case reports of sympathetically maintained pain occurring after radical neck dissection, orbital and maxillary exenteration, it has not been reported in the more common areas of postsurgical pain. For instance, although one should suspect that the nerve damage that accompanies post‐thoracotomy and postmastectomy pain syndromes would bring into being a certain incidence of sympathetically maintained pain, it is difficult to find collaborative reports. This may have more to do with the difficulty inherent in diagnosing sympathetically maintained pain than its actual contribution to these persistent cancer pain syndromes. The reason that it is more commonly reported in limb amputation is less comprehensible since blocking the sympathetic fibers that travel to an extremity is easier than those going to the thoracic cavity. In addition to surgically induced sympathetically maintained pain, medical patients with lymphoma and leukemia may have an element of sympathetically maintained pain when they develop postherpetic neuralgia. While the contribution of sympathetically maintained pain in these cases is not totally ignored, its involvement, as in the surgical patients mentioned above, is worthy of another analysis. This paper will discuss the topics introduced above and suggest diagnostic and therapeutic options available for this condition.
Orexin‐A, an hypothalamic peptide with analgesic properties. (SmithKline Beecham Pharmaceuticals, Harlow, Essex, United Kingdom) Pain. 2001;92:81–90.
Authors: Bingham S. , Davey P. T. , Babbds A. J. , Irving E. A. , Sammons M. J. , Wyles M. , Jeffrey P. , Cutler L. , Riba I. , Johns A. , Porter R. A. , Upton N. , Hunter A. J. , Parsons A. A.
Published: March 2003

The hypothalamic peptide orexin‐A and the orexin‐1 receptor are localized in areas of the brain and spinal cord associated with nociceptive processing. In the present study, localization was conformed in the spinal cord and demonstrated in the dorsal root ganglion for both orexin‐A and the orexin‐1 receptor. The efficacy of orexin‐A was similar to that of morphine in the 50°C hotplate test and the carrageenan‐induced thermal hyperalgesia test. However, involvement of the opiate system in these effects was ruled out as they were blocked by the orexin‐1 receptor antagonist SB‐334867, but not naloxone. Orexin‐1 receptor antagonists had no effect in acute nociceptive tests, but under particular inflammatory conditions were prohyperalgesic, suggesting a tonic inhibitory orexin drive in these circumstances. Conclude that the orexinergic system has a potential role in the modulation of nociceptive transmission.
The density of remaining nerve endings in human skin with and without postherpetic neuralgia after shingles. (Massachusetts General Hospital, Harvard Medical School, Boston, MA) Pain. 2001;92:139–145.
Authors: Oaklander Anne Louise
Published: March 2003

Postherpetic neuralgia (PHN), which occurs in some patients after shingles, was used to investigate the neural determinants of chronic pain. Skin biopsies were obtained from 38 adults with or without PHN at least 3 months after healing of shingles on the torso. Vertical sections were immunolabeled against PGP9.5, a pan‐axonal marker, to measure the density of the remaining nerve endings in skin previously affected by shingles. Of 19 subjects without PHN, 17 had more than 670 neurites/mm2 skin surface area, and 18 of 19 subjects with PHN had 640 or fewer neurites/mm2. PHN may be a “phantom‐skin” pain associated with loss of nociceptors. The study implies that the absence of pain after shingles may require the preservation of a minimum density of primary nociceptive neurons, and that the density of epidermal innervation may provide an objective correlate for the presence or absence of PHN pain.

Comment by Miles Day, M.D. This is a good article addressing one of the most difficult chronic pain syndromes to treat. As you know postherpetic neuralgia can be devastating to the patients secondary to the ongoing and sometimes incapacitating pain. This study does not attempt to explain the cause of postherpetic neuralgia. Instead it establishes objective criteria that implies the absence of pain after shingles may require preservation of a minimum density of primary nociceptor neurons and that this density may provide an objective correlate for the presence or absence of postherpetic neuralgia pain. If the implication made by the study is true, it raises a question as to whether or not skin biopsy should be preformed on all patients who have just experienced a case of herpes zoster to determine whether or not they are at risk for developing postherpetic neuralgia. Another question that may arise is whether or not we should empirically treat certain patients for potential postherpetic neuralgia if there neurite density falls below a certain established level. While the information from this study should not be used as a sole factor in determining whether or not a patient with a previous herpes zoster infection will develop postherpetic neuralgia it does add objective data to our armamentarium that can be used to try to prevent or treat the devastating pain caused by postherpetic neuralgia.
Botulinum toxin A and chronic back pain: a randomized, double‐blinded study. (Walter Reed Army Medical Center, Washington, DC) Neurology. 2001;56:1290–1293.
Authors: Foster Leslie , Clapp Larry , Erickson Marleigh , Jabbari Bahman
Published: March 2003

This study investigated the efficacy of botulinum toxin A in chronic low back pain and associated disabilities. Thirty‐one consecutive patients with chronic low back pain who met the inclusion criteria were studied. Each patient's baseline level of pain and degree of disability was documented using the visual analogue scale (VAS) and the Oswestry Low Back Pain Ques‐ tionnaire (OLBPQ). The authors reevaluated the patients at 3 and 8 weeks (VAS) and 8 weeks (OLBPQ). At 3 weeks, 11 of the 15 patients who received botulinum toxin (73.3%) had> 50% pain relief versus 4 of 16 in the saline group. At weeks, 9 of 15 in the botulinum toxin group and 2 of 16 in the saline group had relief. Repeat OLPBPQ at 8 weeks showed improvement in 10 of 15 in the botulinum toxin group versus 3 of 16 in the saline group. No patient experienced side effects. Conclude that paravertebral administration of botulinum toxin A in patients with chronic low back pain relieved pain and improved function at 3 and 8 weeks after treatment.

Comment by Miles Day, M.D. This study evaluates the use of botulinum toxin A in the treatment of myofascial pain in patients with chronic low back pain. It's conclusion is “Paravertebral administration of botulinum toxin A in patients with chronic low back pain relieved pain and impoved function at 3 and 8 weeks after treatment”. While the results of this study are promising I agree with the authors that the conclusion should be regarded with caution because the sample size of patients studied was small. My main criticism is in the selection criteria the authors use in this criteria. As stated in the study six of the patients had a history of disc disease and three had had discectomies five to eighteen years prior to the study. As we in the pain field know, continuing pain after previous surgery can be secondary to multiple causes including disc disease, epidural scaring, myofascial pain, and facet disease. These patients sometime have a hard time delineating the amount of pain that is being generated from each one of these potential causes of ongoing pain. The results of this study may have been better if the inclusion criteria eliminated patients with multiple pain generators and only included patients with myofacial pain.
Clinical and physiologic evaluation of stellate ganglion blockade for complex regional pain syndrome type I. (Ludwig‐Maximilians‐University, Munich, Germany) Clin J Pain. 2001;17:94–100.
Authors: Schürmann Matthias , Gradl Georg , Wizgal Ingrid , Tutic Michaela , Moser Christian , Azad Shanaz , Beyer Antje
Published: March 2003

Stellate ganglion blockade with local anesthetics was carried out via an anterior paratracheal approach in 33 patients suffering from complex regional pain syndrome type I. Twenty‐three (70%) of the 33 patients developed an increased in temperature difference between the treated hand and the contralateral hand of more than 1.5°C after the procedure, which is a clinical sign of sympathicolysis. In 48% of these patients, the sympathetic function test showed an undisturbed sympathetic nervous function. In 10 patients, no significant increase in temperature difference was observed. Only 7 patients with pain relief revealed both clinical sympathicolysis and extinguished sympathetic nerve function and qualified for sympathetically maintained pain. Conclude that clinical investigation is not reliable in the assessment of stellate ganglion blockade. Proof of sympathetically maintained pain based on pain relief after stellate ganglion blockade is not conclusive.
Treatment of idiopathic trigeminal neuralgia: comparison of long‐term outcome after radiofrequency rhizotomy and microvascular decompression. (Heidelberg College of Medicine, Heidelberg, Germany) Neurosurgery. 2001;48:1261–1267.
Authors: Tronnier Volker M. , Rasche Dirk , Hamer Jürgen , Kienle Anna‐Lena , Kunze Stefan
Published: March 2003

The purpose of this study was to evaluate the long‐term outcome of patients after either percutaneous trigeminal rhizotomy or microvascular decompression (MVD) for idiopathic trigeminal neuralgia at a single institution. Overall, the results of the study showed that there was a 50% risk of recurrence of pain 2 years after percutaneous radiofrequency rhizotomy. Conversely, 64% of the patients who underwent MVD remained completely pain free 20 years postoperatively. Patients without sensory impairment after MVD were pain free significantly longer than patients who experienced postoperatively hypesthesia or partial rhizotomy. Conclude that because it is curative and nondestructive, MVD is considered the treatment of choice for trigeminal neuralgia in otherwise healthy people. In this study, it was proved to be a more effective and long‐lasting procedure for patients with typical trigeminal neuralgia than radiofrequency rhizotomy. Patients without postoperative sensory deficit remained pain free significantly longer, which is a strong argument against the “trauma” hypothesis of this procedure.

Comment by Ron Pawl, M.D. This paper is noteworthy in that comparing the follow‐up on 225 of 378 patients who underwent microvascular decompression (MVD) with 206 of 316 who underwent radiofrequency thermocoagulation (RFT), the RFT group stood a 50% risk of recurrent pain by 2 years after the procedure, whereas 64% of those undergoing MVD were pain‐free after 20 years. Furthermore, after MVD, those patients with no postoperative sensory deficit, measured with von Frey hairs, remained pain‐free longer than those with a sensory deficit. This latter finding flies in the face of the concept that to be effective, surgery for trigeminal neuralgia must damage the nerve. The whole concept of RF lesioning of the nerve is to damage it enough to deaden the trigger zone of the affected nerve branch. However, in this study it is noted that postoperative hypesthesia was only temporary after RF lesioning, which might well explain the high rate of pain recurrence in this series. Although the long‐term pain relief in the MVD group is excellent, it must be weighed against the complications. In the MVD group, there were 3 mortalities, diminished hearing in 5%, loss of hearing in 2.6%, facial paralysis in 4 patients, and tinnitus in 4 patients, none of which occurred in the RF group.
Transesophageal monitoring of aortic blood flow during nonemergent canine surgeries
Authors: Wall Piper L. , DVM PhD, DACVECC  , Rudison Maisha M. , Lazic Tatjana , DVM  , Reidesel Dean H. , DVM PhD
Published: March 2003

Objective: To establish baseline values for descending thoracic aortic blood flow parameters as determined with a transesophageal combined M‐mode and pulsed Doppler ultrasound‐based monitoring method.

Design: Preliminary observational study.

Setting: University small animal teaching hospital.

Animals: The study population consisted of anesthetized canine patients undergoing nonemergent surgeries. Prospectively set criteria for inclusion were adequate body size for placement of the esophageal probe and a nonemergent reason for surgery. The criterion for exclusion was recent trauma.

Interventions: Placement of the transesophageal probe.

Measurements and main results: Data was collected during 15 surgeries. Data from three dogs was excluded from data analysis (two recently hit by motor vehicles, one recently having undergone a total hip replacement). Each parameter was stable across time within each individual dog. The ranges of the descending thoracic aortic parameters across the 12 nonemergent cases were as follows: blood flow, 0.038–0.085 L min−1 kg−1; blood flow per beat, 0.31–0.84 mL kg−1; blood acceleration, 6–29 m s2−1; blood peak velocity, 38–105 m s−1; left ventricular ejection time interval 331–492 ms; and diameter, 0.30–0.93 mm kg−1.

Conclusions: The range of descending thoracic aortic blood flow parameters encountered in this small group of dogs during nonemergent surgeries was broad; however, each parameter was quite stable across time with little change occurring in any dog during monitoring.
p phenotype in an Ecuadorian family
Authors: SWEENEY J. D. , WENZ B.
Published: March 2003

The red cell phenotype ‘p’ is reported in an Ecuadorian family of Spanish descent. There are no previous confirmed reports of Ecuadorian individuals with this rare allele. The proband was not the product of a consanguineous marriage. This factor together with certain geographical and historical considerations support speculation that there may be a small cohort of homozygous ‘p’ individuals in the region.
An enzyme‐linked immunosorbent assay for the quantification of serum platelet‐bindable IgG
Authors: Howe SE , Lynch DM , Lynch JM
Published: March 2003

An enzyme‐linked immunosorbent assay (ELISA) using F(ab')2 peroxidase‐ labeled antihuman immunoglobulin and o‐phenylenediamine dihydrochloride (OPD) as a substrate was developed to measure serum platelet bindable IgG (S‐PBIgG). The assay was made quantitative by standardizing the number of normal “target” platelets bound to microtiter plate wells, and by incorporating quantitated IgG standards with each microtiter plate tested to prepare a standard calibration curve. By this method, S‐ PBIgG for normal individuals was 3.4 +/− 1.6 fg per platelet (mean +/− 1 SD; n = 40). Increased S‐PBIgG levels were detected in 36 of 40 patients with clinical autoimmune thrombocytopenia (ATP), ranging from 7.0 to 85 fg per platelet. Normal S‐PBIgG levels were found in 34 of 40 patients with nonimmune thrombocytopenia. This method showed a sensitivity of 90 percent, specificity of 85 percent, and in the sample population studied, a positive predictive value of 0.86 and a negative predictive value of 0.90. This assay is highly reproducible (coefficient of variation was 6.8%) and appears useful in the evaluation of patients with suspected immune‐mediated thrombocytopenia.