bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Seizures Due to a Probable Interaction between Valproic Acid and Meropenem
Authors: Coves-Orts Francisco Javier , Borrás-Blasco Joaquín , Navarro-Ruiz Andrés , Murcia-López Ana , Palacios-Ortega Francisco
Published: February 2005

OBJECTIVE:

To report a probable interaction between meropenem and valproic acid that resulted in the development of epileptic seizures.

CASE SUMMARY:

A 21-year-old woman presented to our emergency department because of a new-onset, generalized tonic—clonic seizure and was admitted to the intensive care unit. Treatment with valproic acid 1000 mg as a continuous intravenous infusion over 24 hours was initiated. On day 6, the serum concentration of valproic acid was 52.5 μg/mL. On day 13, treatment with intravenous meropenem 1 g 3 times daily was started. On day 15, when the patient was afebrile, numerous myoclonic episodes occurred involving her arms and face; the serum concentration of valproic acid at that time was 42 μg/mL. The valproic acid dose was increased to 2880 mg. Two days later, a generalized tonic—clonic seizure occurred despite the increased dosage, and the plasma concentration of valproic acid fell to 7 μg/mL. The valproic acid dose was increased the following day to 3600 mg; however, the serum concentrations remained <10 μg/mL. On day 19, based on the results of a blood culture and the suspicion of an interaction between meropenem and valproic acid, meropenem therapy was suspended. The serum concentration of valproic acid was 52.4 μg/mL on day 27. Three days later, the patient was asymptomatic and was discharged.

DISCUSSION:

Coadministration of valproic acid and other drugs that are metabolized by the hepatic cytochrome P450 isoenzyme system can lead to clinically relevant interactions by induction or inhibition of enzymes in shared metabolic pathways. In view of studies in experimental models, the interaction between carbapenem antibiotics and valproic acid is at least possible. Use of the Naranjo probability scale indicated a probable relationship between acute seizures and a meropenem—valproic acid interaction in this patient.

CONCLUSIONS:

This case report provides strong evidence for an interaction between valproic acid and meropenem. Clinicians should be aware of this potential interaction that may be associated with a serious adverse effect as the result of the decrease of the valproic acid serum concentrations.
Effect of Cotherapy Reduction on Tolerability of Epilepsy Add-On Therapy: A Randomized Controlled Trial
Authors: Naritoku Dean K , Hulihan Joseph F , Schwarzman Lesley Kraut , Kamin Marc , Olson William H
Published: February 2005

BACKGROUND:

Adverse effects are the most common cause for failure of an antiepileptic drug (AED), especially when an AED is added to existing therapy. With the increased drug load, it may not be possible to titrate the newly added AED to effective doses. Reducing the dosage of AED cotherapy as the new drug is introduced may improve tolerability.

OBJECTIVE:

To evaluate reduction of AED cotherapy as a strategy to improve tolerability and patient retention when a new AED is added to existing therapy.

METHODS:

In a 20-week, randomized, open-label study, topiramate was initiated as add-on therapy in adults and adolescents (⩾12 y of age) with inadequately controlled partial-onset seizures. Patients were randomized to receive treatment in which adverse events could be managed by adjustments in AED cotherapy (flex-dose group) or treatment in which AED cotherapy dosages remained fixed (fixed-dose group). Topiramate could be adjusted as needed in both groups. In the flex-dose group, patients exited randomized treatment when topiramate was discontinued. In the fixed-dose group, patients exited when AED cotherapy was reduced due to adverse events or when topiramate was discontinued. The primary study outcome was the percentage of patients exiting randomized treatment due to adverse events.

RESULTS:

The flex-dose group comprised 297 patients; 302 patients were in the fixed-dose group. Significantly fewer patients in the flex-dose group exited the study due to adverse events (16% vs 23% in the fixed-dose group; p = 0.02). In the flex-dose group, 10% (17 of 168) of patients discontinued topiramate due to adverse events after AED cotherapy was reduced versus 22% (29 of 129) when AED cotherapy was not reduced.

CONCLUSIONS:

Reduction of AED cotherapy is a useful strategy to improve tolerability and retention when topiramate is initiated as adjunctive therapy.
Assessment of Risks Related to Medicine Dispensing by Nonprofessionals in Colombia: Clinical Case Simulations
Authors: Vacca Claudia , Orozco José , Figueras Albert , Capellà Dolors
Published: February 2005

BACKGROUND:

Appropriate dispensing is one of the steps for rational drug use, so it is generally advised that the dispenser should have relevant and updated knowledge, skills, and attitudes.

OBJECTIVE:

To assess pharmacies and nonprofessional employees' (NEs) skills and knowledge, as well as their response to several specific case simulations in Bogotá, Colombia.

METHODS:

A descriptive cross-sectional study was performed on a random sample of 371 pharmacies in Bogotá. Information from each pharmacy was obtained using 2 approaches: (1) direct interview to collect data on organizational aspects of the store and characteristics of NEs, and (2) simulation (both by direct interview and by telephone) to assess dispensing responses in 6 simulated clinical cases.

RESULTS:

More than half of the simulated clinical situations resulted in inappropriate dispensing (direct simulations 57%; telephone simulations 55%). The proportion of correct answers to theoretical questions regarding a specific therapeutic problem during interviews was higher than the response when a simulation presented that same case and a dispensing act was expected. The educational background of the NEs included in the study points to a specific problem: two-thirds of the individuals selling medicines had completed only secondary-level education and only 2% of the sample had a pharmacist as technical director. Continuing education courses were either directly organized by drug manufacturers (one-third of the courses attended by pharmacists) or sponsored by them (more than an additional one-third).

CONCLUSIONS:

NEs should be considered part of the therapeutic chain and, if appropriately updated or instructed, could play a very important role in the always difficult promotion of rational drug use. Public health institutions and universities should be more actively involved in the provision of independent, unbiased, and essential information on common therapeutic problems, safety concerns, and new drug prescription restrictions.
Sequential-Context-Dependent Hippocampal Activity Is Not Necessary to Learn Sequences with Repeated Elements
Authors: Bower Mark R. , Euston David R. , McNaughton Bruce L.
Published: February 2005

Learning sequences of events (e.g., a-b-c) is conceptually a simple problem that can be solved using asymmetrically linked cell assemblies [e.g., “phase sequences” (Hebb, 1949)], provided that the elements of the sequence are unique. When elements repeat within the sequence, however (e.g., a-b-c-d-b-e), the same element belongs to two separate “contexts,” and a more complex sequence encoding mechanism is required to differentiate between the two contexts. Some neural structure must form sequential-context-dependent, or “differential,” representations of the two contexts (i.e., b as an element of “a-b-c” as opposed to “d-b-e”) to allow the correct choice to be made after the repeated element. To investigate the possible role of hippocampus in complex sequence encoding, rats were trained to remember repeated-location sequences under three conditions: (1) reward was given at each location; (2) during training, moveable barriers were placed at the entry and exit of the repeated segment to direct the rat and were removed once the sequence was learned; and (3) reward was withheld at the entry and exit of the repeated segment. In the first condition, hippocampal ensemble activity did not differentiate the sequential context of the repeated segment, indicating that complex sequences with repeated segments can be learned without differential encoding within the hippocampus. Differential hippocampal encoding was observed, however, under the latter two conditions, suggesting that long-term memory for discriminative cues present only during training, working memory of the most recently visited reinforcement sites, or anticipation of the subsequent reinforcement site can separate hippocampal activity patterns at the same location.
Influence of Naturally Occurring Variations in Maternal Care on Prepulse Inhibition of Acoustic Startle and the Medial Prefrontal Cortical Dopamine Response to Stress in Adult Rats
Authors: Zhang T. Y. , Chrétien P. , Meaney M. J. , Gratton A.
Published: February 2005

In rats, naturally occurring variations in maternal care contribute to the development of individual differences in the behavioral and neuroendocrine responses to stress during adulthood. The dopamine (DA) projection to the medial prefrontal cortex (mPFC) plays an important role in mediating stress responsivity and is thought to be involved also in regulating sensorimotor gating. In the present study, we compared prepulse inhibition (PPI) of acoustic startle as well as the left and right mPFC DA stress responses in the adult offspring of high- and low-licking/grooming (LG) dams. Our data indicate that the offspring of low-LG animals are impaired on measures of PPI compared with high-LG animals. We also observed in low-LG animals a significant blunting of the mPFC DA stress responses that was lateralized to the right hemisphere, whereas in high-LG animals, the left and right mPFC DA stress responses were equally attenuated. Although mPFC levels of DA transporter did not differ between the two groups of animals, mPFC levels of catechol-O-methyl transferase immunoreactivity of low-LG animals were significantly lower than those of high-LG animals. These data provide evidence that variations in maternal care can lead to lasting changes in mPFC DA responsivity to stress and suggest the possibility that such changes in mesocorticolimbic DA function can also lead to deficits in sensorimotor gating.
Frontal Lobe Inputs to the Digit Representations of the Motor Areas on the Lateral Surface of the Hemisphere
Authors: Dum Richard P. , Strick Peter L.
Published: February 2005

We examined the frontal lobe connections of the digit representations in the primary motor cortex (M1), the dorsal premotor area (PMd), and the ventral premotor area (PMv) of cebus monkeys. All of these digit representations lie on the lateral surface of the hemisphere. We used intracortical stimulation to identify the digit representations physiologically, and then we injected different tracers into two of the three cortical areas. This approach enabled us to compare the inputs to two digit representations in the same animal. We found that the densest inputs from the premotor areas to the digit representation in M1 originate from the PMd and the PMv. Both of these premotor areas contain a distinct digit representation, and the two digit representations are densely interconnected. Surprisingly, the projections from the digit representation in the supplementary motor area (SMA) to the PMd and PMv are stronger than the SMA projections to M1. The projections from other premotor areas to M1, the PMd, and the PMv are more modest. Of the three digit areas on the lateral surface, only the PMv receives dense input from the prefrontal cortex. Based on these results, we believe that M1, the PMd, and the PMv form a densely interconnected network of cortical areas that is concerned with the generation and control of hand movements. Overall, the laminar origins of neurons that interconnect the three cortical areas are typical of “lateral” interactions. Thus, from an anatomical perspective, this cortical network lacks a clear hierarchical organization.
Feeding Cues Alter Clock Gene Oscillations and Photic Responses in the Suprachiasmatic Nuclei of Mice Exposed to a Light/Dark Cycle
Authors: Mendoza Jorge , Graff Caroline , Dardente Hugues , Pevet Paul , Challet Etienne
Published: February 2005

The suprachiasmatic nuclei (SCN) of the hypothalamus contain the master mammalian circadian clock, which is mainly reset by light. Temporal restricted feeding, a potent synchronizer of peripheral oscillators, has only weak influence on light-entrained rhythms via the SCN, unless restricted feeding is coupled with calorie restriction, thereby altering phase angle of photic synchronization. Effects of daytime restricted feeding were investigated on the mouse circadian system. Normocaloric feeding at midday led to a predominantly diurnal (60%) food intake and decreased blood glucose in the afternoon, but it did not affect the phase of locomotor activity rhythm or vasopressin expression in the SCN. In contrast, hypocaloric feeding at midday led to 2-4 h phase advances of three circadian outputs, locomotor activity rhythm, pineal melatonin, and vasopressin mRNA cycle in the SCN, and it decreased daily levels of blood glucose. Furthermore, Per1 and Cry2 oscillations in the SCN were phase advanced by 1 and 3 h, respectively, in hypocalorie- but not in normocalorie-fed mice. The phase of Per2 and Bmal1 expression remained unchanged regardless of feeding condition. Moreover, the shape of behavioral phase-response curve to light and light-induced expression of Per1 in the SCN were markedly modified in hypocalorie-fed mice compared with animals fedad libitum. The present study shows that diurnal hypocaloric feeding affects not only the temporal organization of the SCN clockwork and circadian outputs in mice under light/dark cycle but also photic responses of the circadian system, thus indicating that energy metabolism modulates circadian rhythmicity and gating of photic inputs in mammals.
Variations in Vertical Location of Kootenai River White Sturgeon during the Prespawn and Spawning Periods
Authors: Paragamian Vaughn L. , Duehr Jeremy P.
Published: February 2005

Our objectives were to determine the general water column habitat use of Kootenai River white sturgeon Acipenser transmontanus during the prespawn and spawning periods and to determine the degree of their benthic existence. Depth‐sensitive radio transmitters were attached to five male and four female white sturgeon and were periodically monitored day and night from April through June 2001. A total of 297 radio contacts were made, of which 209 included the depth of the river. One fish was not used for statistical analysis because its behavior was often modified by the presence of our boat. Of the 209 contacts, 75% (156) were made within the bottom one‐third of the water column. Mean depth of the fish during the daytime prespawn and daytime spawning period was different (9.7 and 6.5 m, respectively), and the distribution between these two periods was significantly different. Some of the variation was likely due to the deeper habitat of the daytime prespawn staging reach compared with that of the daytime spawning period location (12.6 and 7.7 m, respectively). White sturgeon used a variety of locations throughout the water column, were closer to the river bottom during the spawning period, and were much more mobile during the spawning period than we previously believed. We were also able to chart some white sturgeon as they gradually cruised the contour of the river bottom several meters from the substrate yet paused momentarily. Although depth‐sensitive transmitters were well suited to further defining some white sturgeon behavioral characteristics, they lacked the precision to achieve instantaneous locations.
Lack of Sex Specificity for Growth Hormone Pseudogene in Fall‐Run Chinook Salmon from the Columbia River
Authors: Chowen Trevor R. , Nagler James J.
Published: February 2005

Two qualitative male‐specific genetic markers are currently known for Chinook salmon Oncorhynchus tshawytscha and have been used to identify sex in this species. Here we compare the relative specificity of these markers—growth hormone pseudogene (GHp) and OtY1—with phenotypic sex in fall‐run Chinook salmon from three different naturally spawning populations and one hatchery population on the Columbia River, Washington. In comparison with OtY1, GHp demonstrated a reduced specificity for the male sex in all populations examined and overall was present in just 81% of males sampled. Conversely, some females from all but the Yakima River population tested positive for the GHp marker. Therefore, GHp is determined to be a relatively poor indicator of phenotypic sex for fall‐run Chinook salmon from the Columbia River due primarily to underrepresentation among males and also to some overrepresentation among females. The potential for GHp to be an accurate genetic marker for phenotypic sex in Chinook salmon appears to be a population‐specific phenomenon.
Cover Picture: Spontaneous Transformation of Stabilizer‐Depleted Binary Semiconductor Nanoparticles into Selenium and Tellurium Nanowires (Adv. Mater. 3/2005)
Authors: Tang Z. , Wang Y. , Sun K. , Kotov N. A.
Published: February 2005

The cover image shows a transmission electron microscopy image of selenium nanowires from the self‐reorganization process of stabilizer‐depleted CdSe nanoparticles in the presence of a complexing agent. On p. 358, Kotov and co‐workers report the preparation of semiconductor nanowires with tightly controlled diameter using stabilizer‐depleted nanoparticles rather than typical molecules as reaction precursors.
Titelbild: Theoretical and Synthetic Studies on [Zn2(η5‐C5Me5)2]: Analysis of the ZnZn Bonding Interaction (Angew. Chem. 8/2005)
Authors: del Río Diego , Galindo Agustín , Resa Irene , Carmona Ernesto
Published: February 2005

Stark verdrilltes permethoxyliertes Hexa‐peri‐hexabenzocoronen bildet Einschlusskomplexe mit Hexafluorbenzol‐ und Fulleren‐Gastmolekülen. Die “doppelt konkave” Oberfläche ermöglicht dabei die Koordination geeigneter Gastmoleküle über beide Seiten, und die flexiblen Methoxygruppen an der Peripherie passen ihre Orientierung an die Größe und Form der Gastmoleküle an. Weitere Einzelheiten finden sich in der Zuschrift von K. Müllen et al. auf S. 1273 ff.
Evaluation of PM3 calculations applied to organotin compounds: crystal structure of [Ph2SnCl2 (1,10‐phenanthroline‐5,6‐dione)]·2Me2CO
Authors: de Alencastro Ricardo Bicca , Bomfim João A. S. , Filgueiras Carlos A. L. , Howie R. Alan , Wardell James L.
Published: February 2005

PM3 calculated geometries of a set of mainly organotin compounds covering different coordination numbers at tin were compared with published experimental results, obtained either by electron or X‐ray diffraction. In addition, data for the previously unreported acetone solvated Ph2SnCl2·1,10‐phenanthroline‐5,6‐dione complex, [Ph2SnCl2(pdon)]·2Me2CO, are included. Copyright © 2004 John Wiley & Sons, Ltd.
Acute‐phase reactants and the risk of relapse/recurrence in polymyalgia rheumatica: A prospective followup study
Authors: Salvarani Carlo , Cantini Fabrizio , Niccoli Laura , Macchioni Pierluigi , Consonni Dario , Bajocchi Gianluigi , Vinceti Marco , Catanoso Maria Grazia , Pulsatelli Lia , Meliconi Riccardo , Boiardi Luigi
Published: February 2005

Objective

To determine laboratory parameters that may be useful in identifying polymyalgia rheumatica (PMR) patients who require long‐term corticosteroid therapy.

Methods

A prospective followup study of 94 consecutive untreated patients with PMR were assessed for relapse/recurrence for a mean of 39 months. This cohort represented all the patients diagnosed over a 4‐year period in 2 Italian secondary referral centers. Patients were monitored for clinical signs and symptoms, erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP), and serum interleukin‐6 (IL‐6). IL‐6 levels were also measured in 43 controls matched to the patients for age and sex.

Results

The ESR was elevated in 91.5% of the patients prior to therapy initiation, as were CRP in 98.9% and serum IL‐6 in 92.6%. Forty‐seven (50.0%) patients had at least 1 relapse/recurrence during the followup period and 24 (25.5%) had at least 2. After 4 weeks of prednisone therapy, ESR was elevated in 13.2% patients, CRP in 41.9%, and serum IL‐6 in 37.2%. IL‐6 levels remained persistently elevated in 9.9% and CRP in 8.7% of patients during the first year of followup, whereas no patient had persistently elevated ESR. Persistently elevated CRP and IL‐6 levels were significantly associated with an increased risk of relapse/recurrence. In particular, patients with persistently elevated levels of IL‐6 during the first year of therapy had the highest relative risk.

Conclusion

Despite the control of clinical symptoms, corticosteroids do not adequately control the inflammatory process in a subset of patients with PMR who have persistently elevated levels of CRP and IL‐6 and who have a higher risk of relapsing.
Cost‐utility and cost‐effectiveness analyses of a long‐term, high‐intensity exercise program compared with conventional physical therapy in patients with rheumatoid arthritis
Authors: van den Hout Wilbert B. , de Jong Zuzana , Munneke Marten , Hazes Johanna M. W. , Breedveld Ferdinand C. , Vliet Vlieland Theodora P. M.
Published: February 2005

Objective

To estimate the cost utility and cost effectiveness of long‐term, high‐intensity exercise classes compared with usual care in rheumatoid arthritis (RA) patients.

Methods

RA patients (n = 300) were randomly assigned to either exercise classes or UC; followup lasted for 2 years. Outcome measures were quality‐adjusted life years (QALYs) according to the EuroQol (EQ‐5D), Short Form 6D (SF‐6D), and a transformed visual analog scale (VAS) rating personal health; functional ability according to the Health Assessment Questionnaire (HAQ) and McMaster Toronto Arthritis Patient Preference Interview (MACTAR); and societal costs.

Results

QALYs in both randomization groups were similar according to the EQ‐5D and SF‐6D, but were in favor of usual care according to the VAS (annual difference 0.037 QALY; 95% confidence interval [95% CI] 0.002, 0.069). Functional ability was similar according to the HAQ, but in favor of the exercise classes according to the MACTAR (annual difference 2.9 QALY; 95% CI 0.9, 4.9). Annual medical costs of the exercise program were estimated at €780 per participating patient (€1 ≈ $1.05). The increase per patient in total medical costs of physical therapy was estimated at €430 (95% CI €318, 577), and the increase in total societal costs at €602 (95% CI €−490, 1,664). For societal willingness‐to‐pay equal to €50,000 per QALY, usual care had better cost utility than exercise classes, and significantly so according to the VAS.

Conclusion

From a societal perspective and without taking possible preventive health effects into account, long‐term, high‐intensity exercise classes provide insufficient improvement in the valuation of health to justify the additional costs.
Effect of cardiovascular comorbidities and concomitant aspirin use on selection of cyclooxygenase inhibitor among rheumatologists
Authors: Greenberg Jeffrey D. , Bingham Clifton O. , Abramson Steven B. , Reed George , Sebaldt Rolf J. , Kremer Joel
Published: February 2005

Objective

To evaluate the effects of cardiovascular comorbidities and aspirin coprescription on cyclooxygenase (COX)‐2 inhibitor (coxib) prescribing patterns among rheumatologists.

Methods

A prospective cohort study was carried out with rheumatoid arthritis and osteoarthritis patients in the Consortium of Rheumatology Researchers of North America registry. Medication and comorbidity data were obtained prospectively from physician and patient questionnaires between March 2002 and September 2003. Multivariate adjusted associations between coxib use and specific cardiovascular variables, including aspirin use, were examined.

Results

A total of 3,522 arthritis patients were included. COX inhibitors, including coxibs, nonselective nonsteroidal antiinflammatory drugs (NSAIDs), and meloxicam, were prescribed to a larger proportion of osteoarthritis patients (68.4%) than rheumatoid arthritis patients (47.1%) in our study (P < 0.001). COX inhibitors were prescribed to the majority of aspirin users (51.5%) and a similar proportion of nonusers (49.8%). In multivariate analyses, independent predictors of coxib use versus nonselective NSAID use included diagnoses of osteoarthritis (odds ratio [OR] 2.52, 95% confidence interval [95% CI] 1.81–3.52) and diabetes (OR 1.63, 95% CI 1.06–2.51). Conversely, aspirin use independently predicted selection of a nonselective NSAID rather than a coxib (OR 0.73, 95% CI 0.55–0.98). Neither a history of myocardial infarction nor stroke predicted utilization of a coxib. Similarly, cardiovascular variables did not predict the use of rofecoxib versus celecoxib.

Conclusion

Our data indicate that COX inhibitor coprescription among aspirin users is frequent. Despite cardiovascular concerns regarding the coxibs, our data suggest that aspirin use, but not cardiovascular comorbidities, predicted the selection of nonselective NSAIDs over coxibs.
Fatigue in patients with ankylosing spondylitis: A comparison with the general population and associations with clinical and self‐reported measures
Authors: Dagfinrud Hanne , Vollestad Nina K. , Loge Jon H. , Kvien Tore K. , Mengshoel Anne Marit
Published: February 2005

Objective

To investigate 1) levels of fatigue in patients with ankylosing spondylitis (AS) compared with the general population; 2) the relationships between fatigue and demographic, self‐reported, and clinical measures; and 3) the performance of both a generic and a disease‐specific measure of fatigue.

Methods

Patients with AS (n = 152) were compared with people from the general population (n = 2,323). Fatigue was assessed by the Short Form 36 (SF‐36) vitality scale and the fatigue item of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Other measures of self‐reported health included BASDAI for disease activity, Bath Ankylosing Spondylitis Functional Index for functional abilities, and the SF‐36 for mental health. Clinical measures comprised Bath Ankylosing Spondylitis Metrology Index for joint mobility and erythrocyte sedimentation rate and C‐reactive protein as inflammatory markers. The explanatory power of demographic, self‐reported, and clinical measures was examined in a block regression model.

Results

The mean ± SD SF‐36 vitality score was 43 ± 24 in the patients and 60 ± 21 in the general population (P < 0.001). The SF‐36 vitality and the BASDAI fatigue scores were consistently associated with measures of mental health and disease activity. Clinical measures did not show explanatory power. A cutoff at 70 mm on the BASDAI fatigue item implied specificity of 0.77 and sensitivity of 0.82.

Conclusion

Self‐reported measures of disease activity and mental health contributed significantly to explain fatigue, whereas clinical measures of inflammation and joint mobility did not. The BASDAI fatigue item reached acceptable sensitivity and specificity with a cutoff at 70 mm when using the low vitality scores of SF‐36 as an external indicator.
Role of radiation therapy in patients with a diagnosis of both systemic lupus erythematosus and cancer
Authors: Benk Véronique , Al‐Herz Adeeba , Gladman Dafna , Urowitz Murray , Fortin Paul R.
Published: February 2005

Objective

To determine whether radiation therapy (RT) is denied to patients with lupus and cancer and whether RT causes unusual toxicity in those receiving it.

Methods

We included patients with lupus followed at the University of Toronto Lupus Clinic between 1972 and 2001 who had developed cancer. Demographic, clinical, and laboratory information were collected prospectively. Pathologic proof of cancer was obtained. Three radiation oncologists blinded for the diagnosis of lupus, the modalities of cancer treatment, and the hypothesis of the study reviewed patient data independently. They assessed the indication for RT and whether it should be curative or symptomatic. Recommendation for RT was considered when at least 2 of the 3 radiation oncologists concurred. A review of the literature was conducted.

Results

Forty cases of cancer in 38 patients were identified. Most frequent cancer sites were breast (8), skin (8), digestive (7), and hematologic (7). Median patient age was 58 years. The radiation oncologists recommended RT in 26 cases, either with a curative (14) or a symptomatic intent (12). Only 4 patients received RT, 3 with a curative intent and 1 with a symptomatic intent. None of these 4 patients developed any unusual toxicity. The literature review did not support the fact that lupus patients do not tolerate RT.

Conclusion

Sixty‐five percent of our lupus patients with cancer could have received curative or symptomatic RT but only 10% received it. No patient developed any toxicity. RT may be inappropriately withheld from lupus patients with cancer.
Development and assessment of indicators of rheumatoid arthritis severity: Results of a Delphi panel
Authors: Cabral Danielle , Katz Jeffrey N. , Weinblatt Michael E. , Ting Gladys , Avorn Jerry , Solomon Daniel H.
Published: February 2005

Objective

To develop a set of indicators for assessing the severity of rheumatoid arthritis (RA) through medical records.

Methods

A list of 47 potential indicators of RA was reviewed by an expert Delphi panel of 6 rheumatologists. The Delphi method is a formal approach for gathering expert opinion. The 47 potential indicators included items from the following 5 categories: radiologic and laboratory findings, clinical and functional status measures, extraarticular manifestations, prior surgical history, and medications. The panelists rated the potential indicators' relationship to RA disease severity. Each panelist rated each indicator on a scale of 0–6, in which 0 indicated no relationship at all with severe RA and 6 indicated a perfect relationship with severe RA. After a baseline set of ratings, a literature review was distributed to the panelists along with the panel's initial mean ratings and the ranges. The panelists then met to discuss the literature and rerate all indicators.

Results

After repeat ratings and review of relevant literature, the panel rated 28 of 47 (60%) potential indicators as having a strong or very strong relationship to severe RA. These 28 indicators were drawn from all 5 categories of potential indicators. There was agreement among the panelists on ratings for 41 of 47 indicators. Agreement was defined as a range of scores among the panelists ≤3.

Conclusion

A Delphi panel of rheumatologists agreed that data generally available in medical records may serve as potential indicators of severe RA.
Stable incidence of primary systemic vasculitides over five years: Results from the German vasculitis register
Authors: Reinhold‐Keller Eva , Herlyn Karen , Wagner‐Bastmeyer Rosemarie , Gross Wolfgang L.
Published: February 2005

Objective

To register all newly diagnosed patients with primary systemic vasculitides (PSV) in a large region in northern Germany.

Methods

Between January 1, 1998 and December 31, 2002 all newly diagnosed cases of PSV were identified in a large mixed rural/urban northern German region consisting of 2,777,275 habitants in a population‐based prospective study. The following sources were used: departments of all hospitals, including their outpatient clinics; all departments of pathology; and the reference immunologic labs serving the catchment area.

Results

During 5 years, 642 PSV patients were identified. The incidence rates for all PSV were between 40 and 54 cases per 1 million and per year. People at age 50 years and older had a 3–5‐fold higher risk of developing PSV compared with those younger than 50 years. The incidence rates of antineutrophil cytoplasmic antibody (ANCA)–associated PSV (Wegener's granulomatosis [WG], microscopic polyangiitis [MPA], Churg‐Strauss syndrome [CSS]) were between 9.5 and 16/million/year. WG occured 2–3 times more frequently than MPA or CSS.

Conclusion

Results of a population‐based vasculitis register over 5 years for the incidence of PSV among 2.78 million habitants in northern Germany revealed a stable incidence for all PSV. Compared with other European studies coming from small regions or referral centers, the incidence rates for ANCA‐associated PSV were the same as in Norway, lower than those in United Kingdom, but higher than those in Spain.
Characteristics of Saccharomyces cerevisiae gal1Δ and gal1Δhxk2Δ mutants expressing recombinant proteins from the GAL promoter
Authors: Ah Kang Hyun , Kyu Kang Woo , Go Su‐Min , Rezaee Abbas , Hari Krishna Sajja , Ki Rhee Sang , Kim Jeong‐Yoon
Published: February 2005

Galactose can be used not only as an inducer of the GAL promoters, but also as a carbon source by Saccharomyces cerevisiae, which makes recombinant fermentation processes that use GAL promoters complicated and expensive. To overcome this problem during the cultivation of the recombinant strain expressing human serum albumin (HSA) from the GAL10 promoter, a gal1Δ mutant strain was constructed and its induction kinetics investigated. As expected, the gal1Δ strain did not use galactose, and showed high levels of HSA expression, even at extremely low galactose concentrations (0.05–0.1 g/L). However, the gal1Δ strain produced much more ethanol, in a complex medium containing glucose, than the GAL1 strain. To improve the physiological properties of the gal1Δ mutant strain as a host for heterologous protein production, a null mutation of either MIG1 or HXK2 was introduced into the gal1Δ mutant strain, generating gal1Δmig1Δ and gal1Δhxk2Δ double strains. The gal1Δhxk2Δ strain showed a decreased rate of ethanol synthesis, with an accelerated rate of ethanol consumption, compared to the gal1Δ strain, whereas the gal1Δmig1Δ strain showed similar patterns to the gal1Δ strain. Furthermore, the gal1Δhxk2Δ strain secreted much more recombinant proteins (HSA and HSA fusion proteins) than the other strains. The results suggest that the gal1Δhxk2Δ strain would be useful for the large‐scale production of heterologous proteins from the GAL10 promoter in S. cerevisiae. © 2005 Wiley Periodicals, Inc.
Impact of membrane solid–liquid separation on design of biological nutrient removal activated sludge systems
Authors: Ramphao M. , Wentzel M. C. , Merritt R. , Ekama G. A. , Young T. , Buckley C. A.
Published: February 2005

Installing membranes for solid–liquid separation into biological nutrient removal (BNR) activated sludge (AS) systems makes a profound difference not only in the design of the BNR system itself, but also in the design approach for the whole wastewater treatment plant (WWTP). In multizone BNR systems with membranes in the aerobic reactor and fixed volumes for the anaerobic, anoxic, and aerobic zones (i.e., fixed volume fractions), the mass fractions can be controlled (within a range) with the interreactor recycle ratios. This zone mass fraction flexibility is a significant advantage in membrane BNR systems over conventional BNR systems with SSTs, because it allows for changing of the mass fractions to optimize biological N and P removal in conformity with influent wastewater characteristics and the effluent N and P concentrations required. For PWWF/ADWF ratios in the upper range (fq ∽ 2.0), aerobic mass fractions in the lower range (fmaer < 0.60), and high (usually raw) wastewater strengths, the indicated mode of operation of MBR BNR systems is as extended aeration WWTPs. Although the volume reduction compared with equivalent conventional BNR systems with secondary settling tanks is not as large (40% to 60%), the cost of the membranes can be offset against sludge thickening and stabilization costs. Moving from a flow‐unbalanced raw wastewater system to a flow‐balanced (fq = 1), low (usually settled) wastewater strength system can double the ADWF capacity of the biological reactor, but the design approach of the WWTP changes from extended aeration to include primary sludge stabilization. The cost of primary sludge treatment then has to be paid from the savings from the increased WWTP capacity. © 2005 Wiley Periodicals, Inc.
Oxygen transfer phenomena in 48‐well microtiter plates: Determination by optical monitoring of sulfite oxidation and verification by real‐time measurement during microbial growth
Authors: Kensy Frank , Zimmermann Hartmut F. , Knabben Ingo , Anderlei Tibor , Trauthwein Harald , Dingerdissen Uwe , Büchs Jochen
Published: February 2005

Oxygen limitation is one of the most frequent problems associated with the application of shaking bioreactors. The gas–liquid oxygen transfer properties of shaken 48‐well microtiter plates (MTPs) were analyzed at different filling volumes, shaking diameters, and shaking frequencies. On the one hand, an optical method based on sulfite oxidation was used as a chemical model system to determine the maximum oxygen transfer capacity (OTRmax). On the other hand, the Respiration Activity Monitoring System (RAMOS) was applied for online measurement of the oxygen transfer rate (OTR) during growth of the methylotropic yeast Hansenula polymorpha. A proportionality constant between the OTRmax of the biological system and the OTRmax of the chemical system were indicated from these data, offering the possibility to transform the whole set of chemical data to biologically relevant conditions. The results exposed “out of phase” shaking conditions at a shaking diameter of 1 mm, which were confirmed by theoretical consideration with the phase number (Ph). At larger shaking diameters (2–50 mm) the oxygen transfer rate in MTPs shaken at high frequencies reached values of up to 0.28 mol/L/h, corresponding to a volumetric mass transfer coefficient (kLa) of 1,600 1/h. The specific mass transfer area (a) increases exponentially with the shaking frequency up to values of 2,400 1/m. On the contrary, the mass transfer coefficient (kL) is constant at a level of about 0.15 m/h over a wide range of shaking frequencies and shaking diameters. However, at high shaking frequencies, when the complete liquid volume forms a thin film on the cylindric wall of the well, the mass transfer coefficient (kL) increases linearly to values of up to 0.76 m/h. Essentially, the present investigation demonstrates that the 48‐well plate outperforms the 96‐well MTP and shake flasks at widely used operating conditions with respect to oxygen supply. The 48‐well plates emerge, therefore, as an excellent alternative for microbial cultivation and expression studies combining the advantages of both the high‐throughput 96‐well MTP and the classical shaken Erlenmeyer flask. © 2005 Wiley Periodicals, Inc.
High‐resolution 8 Tesla imaging of the formalin‐fixed normal human hippocampus
Authors: Chakeres Donald W. , Whitaker Chastity D.S. , Dashner Roger A. , Scharre Douglas W. , Beversdorf David Q. , Raychaudhury Abhik , Schmalbrock Petra
Published: February 2005

The purpose of this study was to evaluate the capacity of high‐resolution magnetic resonance imaging (MRI) to visualize the normal anatomic features of the human hippocampus in vitro, using high field imaging equipment, parameters, and acquisition times appropriate for imaging human subjects in vivo. This research compared high field, high‐resolution MRI of formalin‐fixed normal human hippocampus specimens to histologic sectioning of the same hippocampus samples. Four specimens were evaluated using an 8 Tesla (T), 80 cm bore whole‐body MRI scanner equipped with a 12.7 cm single strut transverse electromagnetic resonator (TEM) coil. Hahn spin echo images were acquired with a repetition time (TR) of 800 msec, echo times (TE) of 20, 50, 90, and 134 msec, and an acquisition time (TA) of 3.25 min. The image quality was superb with demonstration of most of the features of the hippocampus. High field, high‐resolution MRI can be used to depict multiple layers of the formalin‐fixed human hippocampus in vitro using an 8 T whole‐body scanner, a TEM coil, and short acquisition times compatible with human imaging in vivo. Clin. Anat. 18:88–91, 2005. © 2005 Wiley‐Liss, Inc.
Clinical significance of variations in the interconnections between flexor digitorum longus and flexor hallucis longus in the region of the knot of Henry
Authors: O'Sullivan E. , Carare‐Nnadi R. , Greenslade J. , Bowyer G.
Published: February 2005

Tendon transfer of the flexor digitorum longus tendon (FDLT) or the flexor hallucis longus tendon (FHLT) into the tibialis posterior tendon is carried out in patients with tibialis posterior dysfunction. FDLT and FHLT are connected in the region of the knot of Henry. The present study has investigated the anatomical variations of this tendinous interconnection. The results could be used to determine which of the two tendons should be transected proximal to the region of the knot of Henry in the surgical treatment of tibialis posterior dysfunction. In over two‐thirds of cadaver specimens investigated, tension applied solely to FHLT resulted in flexion of all digits and the hallux. On the basis of these results, we propose that identification of the tendon to be transected should be decided at the time of surgery depending on the anatomical pattern. Based on the evidence provided by 16 cadaveric dissections, transection of FDLT proximal to the region of the knot of Henry for the repair of tibialis posterior dysfunction would result in retention of function of the hallux and lesser digits in the majority of cases. Clin. Anat. 18:121–125, 2005. © 2005 Wiley‐Liss, Inc.
Unusual fibrous band on the left aspect of the aortic arch
Authors: Porzionato Andrea , Macchi Veronica , Parenti Anna , DeCaro Raffaele
Published: February 2005

During dissection of a 63‐year‐old female cadaver, a firm ribbon‐like band was found on the left aspect of the aortic arch. Careful dissection showed that the band (6 cm long, 8 mm wide, 2 mm thick) connected the left superior intercostal vein with the accessory hemiazygos vein. Histological examination showed the fibrous structure of the band and showed the presence of a thread‐like vascular lumen. The topography and venous connections of the band indicated its origin from persistence of the embryonic anastomosis between the left superior intercostal and accessory hemiazygos veins. This anastomosis derives from the rostral portion of the supracardinal vein that usually regresses on the left side but forms the terminal arch of the azygos vein on the right side. The severe atherosclerosis present in this patient at the level of the aortic arch may have enhanced the effects of arterial pressure on the adjacent venous anastomotic vessel causing reduction of blood flow and progressive fibrosis. The persistence of this venous anastomosis and its possible age‐related fibrosis may have clinical relevance in central venous catheter placement. Clin. Anat. 18:137–140, 2005. © 2005 Wiley‐Liss, Inc.
Demonstration of the appearance of the paraspinal musculoligamentous structures of the cervical spine using ultrasound
Authors: Leung Y.L. , Roshier A.L. , Johnson S. , Kerslake R. , McNally D.S.
Published: February 2005

The application of ultrasound in the imaging of the neck has primarily focussed on anterior structures (e.g., thyroid gland). Structures located on the posterior aspect of the neck have received little attention. This study illustrates the capability of modern ultrasound equipment in visualising the musculoligamentous structures of the neck, particularly the paraspinal musculature. Ten healthy adult volunteers (6 female; 4 male) underwent ultrasound examination of the cervical spine. A standardised technique for transducer placement was adopted and successive images of the neck of each subject were obtained. Spatial compound (extended field of view) images were obtained in subjects using one of two different ultrasound systems. Images of structures produced by ultrasound were compared to those achieved with magnetic resonance imaging in three subjects. Identification of key landmarks aided orientation and identification of structures. The internal architecture of the musculoligamentous structures of the cervical spine, especially the posterior neck muscles, was demonstrated well using ultrasound. Our study showed that modern ultrasound equipment is capable of producing clear images of the posterior cervical spine musculature and certain bony features. Clin. Anat. 18:96–103, 2005. © 2005 Wiley‐Liss, Inc.
Do sagittal plane anatomical variations (angulation) of the cervical facets and C2 odontoid affect the geometrical configuration of the cervical lordosis?
Authors: Harrison Deed E. , Harrison Donald D. , Haas Jason W. , Janik Tadeucz J. , Holland Burt
Published: February 2005

Anthropometric and statistical evaluation of measurements from digitization of 252 lateral cervical radiographs were used to investigate any correlation between radiographic measurements of cervical lordosis with sagittal plane facet angulation, articular pillar height, and inclination of the C2 odontoid with respect to the body of C2. Some researchers have hypothesized that facet and odontoid architecture variations can cause a reduction in cervical lordosis. To evaluate this hypothesis, the posterior aspect of the C2 dens, vertebral body corners, and superior and inferior facet surfaces of C2–C7 were digitized on 252 lateral cervical X‐rays to calculate global angle, segmental angles, dens angle, facet angles, and facet height. No correlation between facet angle, articular pillar height, and cervical curve was found. Similarly, no correlation between the sagittal angle of the dens and any angle of cervical curvature was identified. There was correlation between the global ARA C2–C7 angle and the Cobb angles at C1–C7 (r = 0.71) and C2–C7 (r = 0.82). There was correlation between the global inclination of the atlas vertebral angle (APL) and the Cobb angle at C1–C7 (r = 0.66), Cobb angle at C2–C7 (r = 0.39), ARA C2–C7 (r = 0.42), and anterior translation of C2 compared to C7 (r = −0.46). Because no correlation between cervical facet and odontoid architecture and any segmental or global angle of cervical lordosis was found, conservative and surgical rehabilitative techniques aimed at the reduction of sagittal cervical deformities do not need to account for a patient's architecture of the cervical facets nor odontoid. Clin. Anat. 18:104–111, 2005. © 2005 Wiley‐Liss, Inc.
Mushroom cloud appearance of hemorrhage into the superficial anterior abdominal wall associated with an underlying rectus sheath hematoma
Authors: Gulamhuseinwala Nadim , Webb Philippa
Published: February 2005

We present a case of rectus sheath hematoma compounded by anterior abdominal wall haemorrhage. Its clinical and anatomical relationship is discussed. Clin. Anat. 18:141–145, 2005. © 2005 Wiley‐Liss, Inc.
Cystic duct and Heister's “valves”
Authors: Dasgupta D. , Stringer M.D.
Published: February 2005

The anatomy and physiology of the cystic duct have been relatively neglected by anatomists and the function of the spiral mucosal folds or “valves” of Heister, first described in 1732, remains obscure. The gross and microscopic anatomy of the cystic duct is reviewed together with results from laboratory investigations into the function of the cystic duct and its spirally arranged folds. The duct and spiral folds contain muscle fibers responsive to pharmacologic, hormonal, and neural stimuli. There is, however, no convincing evidence of a discrete muscular sphincter within the duct. Although the cystic duct is unlikely to play a major role in gallbladder filling and emptying, it appears to function as more than a passive conduit. Coordinated, graded muscular activity in the cystic duct in response to hormonal and neural stimuli may facilitate gallbladder emptying. The principal function of the internal spiral folds that are found in man and other animals may be to preserve patency of this narrow, tortuous tube rather than to regulate bile flow. Clin. Anat. 18:81–87, 2005. © 2005 Wiley‐Liss, Inc.