On generating functions in additive number theory, II: lower-order terms and applications to PDEs.

We obtain asymptotics for sums of the form ∑ n = 1 P e α k n k + α 1 n , involving lower order main terms. As an application, we show that for almost all α 2 ∈ [ 0 , 1 ) one has sup α 1 ∈ [ 0 , 1 ) | ∑ 1 ≤ n ≤ P e α 1 n 3 + n + α 2 n 3 | ≪ P 3 / 4 + ε , and that in a suitable sense this is best possible. This allows us to improve bounds for the fractal dimension of solutions to the Schrödinger and Airy equations.

Fatty degeneration of the deltoid muscle associated with displaced proximal humerus fractures.

INTRODUCTION: The use of reverse shoulder arthroplasty (RSA) has increased dramatically over the last two decades, with many surgeons now indicating RSA for the acute management of displaced proximal humerus fractures (PHF) in the elderly. RSA relies on adequate deltoid muscle function to obtain a good outcome, yet no literature to date exists which discusses preoperative assessment of deltoid structure prior to RSA. The purpose of this study was to assess for preoperative fatty deltoid-degeneration in patients with displaced PHF. MATERIALS AND METHODS: We reviewed the axial CT scans of 100 consecutive patients with a displaced PHF. Fatty degeneration within each of the three deltoid-heads was graded at three levels, according to Goutallier and colleagues. Fractures were classified according to Neer. RESULTS: Seventy-nine percent of the patients were female, 75% showed 3 or 4 parts fractures. The average cross-sectional area of the posterior deltoid was greatest-representing 37%, 40% and 42% of total area at each level, respectively. Severe fatty degeneration (Stages 3 and 4) was observed in the posterior deltoid only (26%). Absence of fatty degeneration (Stage 0) was observed in < 25% of cases. The Inter-Observer-Reliability for the continuous variables proved to be high. CONCLUSION: Preoperative deltoid fatty degeneration is common in displaced PHF in the elderly. Because CT is commonly obtained to assess fracture morphology and for preoperative planning purposes, it is an ideal tool to assess the deltoid additionally. Future studies are warranted to determine whether preoperative fatty infiltration of the deltoid correlates with mid and long term functional outcomes when RSA is used acutely to manage a PHF. LEVEL OF EVIDENCE: Level IV-consecutive case series.

Shifting microbial communities sustain multiyear iron reduction and methanogenesis in ferruginous sediment incubations.

Reactive Fe(III) minerals can influence methane (CH4 ) emissions by inhibiting microbial methanogenesis or by stimulating anaerobic CH4 oxidation. The balance between Fe(III) reduction, methanogenesis, and CH4 oxidation in ferruginous Archean and Paleoproterozoic oceans would have controlled CH4 fluxes to the atmosphere, thereby regulating the capacity for CH4 to warm the early Earth under the Faint Young Sun. We studied CH4 and Fe cycling in anoxic incubations of ferruginous sediment from the ancient ocean analogue Lake Matano, Indonesia, over three successive transfers (500 days in total). Iron reduction, methanogenesis, CH4 oxidation, and microbial taxonomy were monitored in treatments amended with ferrihydrite or goethite. After three dilutions, Fe(III) reduction persisted only in bottles with ferrihydrite. Enhanced CH4 production was observed in the presence of goethite, highlighting the potential for reactive Fe(III) oxides to inhibit methanogenesis. Supplementing the media with hydrogen, nickel and selenium did not stimulate methanogenesis. There was limited evidence for Fe(III)-dependent CH4 oxidation, although some incubations displayed CH4 -stimulated Fe(III) reduction. 16S rRNA profiles continuously changed over the course of enrichment, with ultimate dominance of unclassified members of the order Desulfuromonadales in all treatments. Microbial diversity decreased markedly over the course of incubation, with subtle differences between ferrihydrite and goethite amendments. These results suggest that Fe(III) oxide mineralogy and availability of electron donors could have led to spatial separation of Fe(III)-reducing and methanogenic microbial communities in ferruginous marine sediments, potentially explaining the persistence of CH4 as a greenhouse gas throughout the first half of Earth history.

Effect of intraoperative weight-bearing simulation on the mechanical axis in total knee arthroplasty.

PURPOSE: Successful outcome after total knee arthroplasty (TKA) requires precise realignment of the mechanical axis. The intraoperative assessment of the mechanical axis is difficult. Intraoperatively, the effect of weight bearing on the lower limb mechanical axis is ignored. We developed a custom-made mechanical loading device to simulate weight-bearing conditions intraoperatively and analysed its effect on the mechanical axis during TKA. METHODS: Measurements of the mechanical axis were obtained during 30 consecutive primary TKAs in osteoarthritic patients using image-free knee navigation system. Half body weight was applied intraoperatively using our device to quantify the effect of intraoperative load application on the mechanical axis, thus receiving indirect information about soft tissue balancing. Furthermore, the intraobserver and interobserver reliability of navigated mechanical axis measurement with and without load was determined. RESULTS: Before TKA, mean mechanical axis was 4.0° ± 4.9° without load. Under loading conditions, the mean change of the mechanical axis was 2.1° ± 2.8°. Repetitive measurements of the senior surgeon and junior surgeon revealed a high intraobserver (ICC 0.997) and interobserver reliability (ICC 0.998). The registration of the mechanical axis without and with application of intraoperative loading demonstrated no significant differences during insertion of the trial components (SD 0.29 ± 0.29) and after the definitive component cementation (SD 0.63 ± 0.44). CONCLUSIONS: Intraoperative quantification and analysis of the mechanical lower limb axis applying defined axial loading by our custom-made loading apparatus is reliable. Ligament stability was unbalanced before TKA and balanced after TKA. For TKA, intraoperative simulation of weight bearing may be helpful to quantify, control and correct knee stability and its influence of mechanical axis.

Bacterial abundance and composition in marine sediments beneath the Ross Ice Shelf, Antarctica.

Marine sediments of the Ross Sea, Antarctica, harbor microbial communities that play a significant role in the decomposition, mineralization, and recycling of organic carbon (OC). In this study, the cell densities within a 153-cm sediment core from the Ross Sea were estimated based on microbial phospholipid fatty acid (PLFA) concentrations and acridine orange direct cell counts. The resulting densities were as high as 1.7 × 107 cells mL⁻¹ in the top ten centimeters of sediments. These densities are lower than those calculated for most near-shore sites but consistent with deep-sea locations with comparable sedimentation rates. The δ¹³C measurements of PLFAs and sedimentary and dissolved carbon sources, in combination with ribosomal RNA (SSU rRNA) gene pyrosequencing, were used to infer microbial metabolic pathways. The δ¹³C values of dissolved inorganic carbon (DIC) in porewaters ranged downcore from -2.5‰ to -3.7‰, while δ¹³C values for the corresponding sedimentary particulate OC (POC) varied from -26.2‰ to -23.1‰. The δ¹³C values of PLFAs ranged between -29‰ and -35‰ throughout the sediment core, consistent with a microbial community dominated by heterotrophs. The SSU rRNA gene pyrosequencing revealed that members of this microbial community were dominated by ß-, δ-, and γ-Proteobacteria, Actinobacteria, Chloroflexi and Bacteroidetes. Among the sequenced organisms, many appear to be related to known heterotrophs that utilize OC sources such as amino acids, oligosaccharides, and lactose, consistent with our interpretation from δ¹³CPLFA analysis. Integrating phospholipids analyses with porewater chemistry, δ¹³CDIC and δ¹³CPOC values and SSU rRNA gene sequences provides a more comprehensive understanding of microbial communities and carbon cycling in marine sediments, including those of this unique ice shelf environment.

Acute treatment of migraine.

Acute treatment of migraine has benefited first from major advances in pharmacological science followed in short order, sometimes preceded, by an improved understanding of pathogenesis, especially of headache. This chapter reviews the mechanisms of migraine that provide an understanding of the pharmacology and therapeutic targets for acute migraine medications. General clinical approaches to acute therapy are reviewed, and indices of acceptable acute therapeutic outcomes are discussed. Currently the serotonin (5-HT) 1B/1D agonist group of drugs, triptans, forms the mainstay of acute therapeutic regimens. Other approaches to acute treatment such as simple analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), ergots, and combination medications are reviewed. Finally, the newest acute treatments that are currently exploratory or under clinical investigation are discussed.

Short-term frovatriptan for the prevention of difficult-to-treat menstrual migraine attacks.

The efficacy of a 6-day regimen of frovatriptan for menstrual migraine (MM; attacks starting on day -2 to +3 of menses) prevention in women with difficult-to-treat MM was assessed. Women with a documented inadequate response to triptans for acute MM treatment were included in this placebo-controlled, parallel-group trial. Women were randomized to double-blind treatment for three perimenstrual periods (PMPs) with either frovatriptan 2.5 mg (q.d. or b.i.d.) or placebo initiated 2 days before anticipated MM. The efficacy analysis included 410 women with 85% completing three double-blind PMPs. The mean number of headache-free PMPs was 0.92 with frovatriptan b.i.d., 0.69 with frovatriptan q.d. and 0.42 with placebo [P < 0.001 (b.i.d.) and P < 0.02 (q.d.) vs. placebo]. When migraine occurred, severity was reduced with frovatriptan q.d. (P < 0.001) and b.i.d. (P < 0.001) vs. placebo. Both frovatriptan regimens were well tolerated. In women with difficult-to-treat MM, a 6-day regimen of frovatriptan significantly reduced MM incidence and severity.

History of childhood maltreatment is associated with comorbid depression in women with migraine.

BACKGROUND: A bidirectional relationship between migraine and depression suggests a neurobiological link. Adverse experiences, particularly childhood maltreatment, may alter neurobiological systems, and predispose to a multiplicity of adult chronic disorders. Our objective is to determine, within a headache clinic population of women, if depression moderates the abuse-migraine relationship. METHODS: At six headache specialty clinics, women with migraine were diagnosed using ICHD-II criteria, and frequency was recorded. A questionnaire regarding maltreatment history, headache characteristics, current depression, and somatic symptoms was completed. RESULTS: A total of 949 women with migraine completed the survey: 40% had chronic headache (> or =15 headache days/month) and 72% had "very severe" headache-related disability. Major depression was recorded in 18%. Physical or sexual abuse was reported in 38%, and 12% reported both physical and sexual abuse in the past. Migraineurs with current major depression reported physical (p < 0.001) and sexual (p < 0.001) abuse in higher frequencies compared to those without depression. Women with major depression were more likely to report sexual abuse occurring before age 12 years (OR = 2.30, 95% CI: 1.14 to 4.77), and the relationship was stronger when abuse occurred both before and after age 12 years (OR = 5.08, 95% CI: 2.15 to 11.99). Women with major depression were also twice as likely to report multiple types of maltreatment (OR = 2.07, 95% CI: 1.27 to 3.35) compared to those without depression. CONCLUSIONS: Childhood maltreatment was more common in women with migraine and concomitant major depression than in those with migraine alone. The association of childhood sexual abuse with migraine and depression is amplified if abuse also occurs at a later age.

Optimal primer design using the novel primer design program: MSPprimer provides accurate methylation analysis of the ATM promoter.

Methylation-specific polymerase chain reaction (PCR) (MSP) is frequently used to study gene silencing by promoter hypermethylation. However, non-specific primer design can lead to false-positive detection of methylation. We present a novel, web-based algorithm for the design of primers for bisulfite-PCRs (MSP, sequencing, COBRA and multiplex-MSP), allowing the determination of a specificity score, which is based on the thermodynamic characteristics of the primer 3'-end. PCR amplification with primers not reaching a high specificity score can result in false-positive findings. We used MSPprimer to design MSP primers for analysis of the ATM promoter. In 37 non-small cell lung cancer (NSCLC) samples and 43 breast cancer samples no promoter methylation was detected. Conversely, published MSP primers not reaching the required specificity score led to non-specific amplification of DNA not converted by bisulfite. The result was a false-positive incidence of ATM promoter methylation of 24% in NSCLC and 48% in breast cancers, similar to published studies. This highlights the critical need for specific primer design for MSP. MSPprimer is a convenient tool to achieve this goal, which is available free of charge to the scientific community.

High prevalence of somatic symptoms and depression in women with disabling chronic headache.

OBJECTIVE: To better define, in women with headache, the relationship of depression and somatic symptoms to headache, characterized by diagnoses, frequency, and disability. METHODS: At six headache specialty clinics, women with headache were classified using ICHD-II criteria, and frequency was recorded. A questionnaire addressing demographics, age at onset of headache, headache-related disability, somatic symptom, and depression severity was completed. Logistic regression was performed to measure the associations of headache frequency and headache-related disability with somatic symptom and depression severity. RESULTS: A total of 1,032 women with headache completed the survey, 593 with episodic (96% with migraine) and 439 with chronic headache (87% with migraine). Low education and household income was more common in chronic headache sufferers and in persons with severe headache disability. Somatic symptom prevalence and severity was greater in persons with chronic headache and with severe headache-related disability. Significant correlation was observed between PHQ-9 and PHQ-15 scores (r = 0.62). Chronic headache, severe disability, and high somatic symptom severity were associated with major depressive disorder (OR = 25.1, 95% CI: 10.9 to 57.9), and this relationship was stronger in the subgroup with a diagnosis of migraine (OR = 31.8, 95% CI: 12.9 to 78.5). CONCLUSIONS: High somatic symptom severity is prevalent in women with chronic and severely disabling headaches. Synergistic relationship to major depression exists for high somatic symptom severity, chronic headache, and disabling headache, suggesting a psychobiological underpinning of these associations.

Mismatch in how oestrogen modulates molecular and neuronal function may explain menstrual migraine.

This paper is designed to provide concepts and stimulate directions for further investigation of menstrual migraine. On the basis of experimental studies and literature review, we propose that abnormalities in how estrogen modulates neuronal function in migraine are due to a mismatch between its gene-regulation and membrane effects. In the interictal phase when estrogen levels peak, increased neuronal excitability is balanced by homeostatic gene regulation in brain cortex, and nociceptive systems. When levels fall at menses, mismatch in homeostatic gene regulation by estrogen unmasks non-nuclear mitogen-activated hyperexcitability of cell membranes, sensitizing neurons to triggers that activate migraine attacks. At the trough of estrogen levels, the down-regulating effect on inflammatory genes is lost and peptide modulated central sensitization is increased as is pain and disability of the migraine attack.

Eletriptan in the early treatment of acute migraine: influence of pain intensity and time of dosing.

This double-blind, placebo-controlled study was designed to evaluate the efficacy and tolerability of early treatment of a single migraine attack, when headache pain was mild, with two doses (20 mg and 40 mg) of eletriptan. Patients (N = 613; female 79%; mean age 39 years) meeting International Headache Society criteria for migraine were encouraged, but not required, to utilize early treatment, thus providing an opportunity to assess the relative contribution to efficacy of pain severity and timing of dose. For the total patient sample (mild-to-severe headaches), 2-h pain-free rates were significantly higher than placebo (22%) on both eletriptan 20 mg (35%; P < 0.01) and eletriptan 40 mg (47%; P < 0.0001). For the cohort of patients who treated their headache when the pain intensity was mild, the 2-h pain-free rate on eletriptan 40 mg was 68% compared with 25% on placebo (P < 0.0001). Pain intensity at the time of taking eletriptan appeared to influence outcome more than the timing of the dose relative to headache onset. Eletriptan was well-tolerated, with adverse event rates similar to placebo when mild headaches were treated.

Impact of migraine on patients and their families: the Migraine And Zolmitriptan Evaluation (MAZE) survey--Phase III.

OBJECTIVE: To investigate the impact of migraine on migraineurs and their families and evaluate migraineurs' preference for different treatment formulations. This study also assessed the prevalence and impact of migraine with menstruation. METHODS: Participants (n = 1028) from around the world (USA [39%], Canada [20%], Europe [37%] and other countries [4%]) completed an online questionnaire. Of these, 866 were migraineurs and 162 were non-migraineurs living with/related to migraineurs. Migraineurs were identified based on responses to a modified Kiel questionnaire and/or diagnosis of migraine by a doctor. Disability was quantified using the Migraine Disability Assessment Scale (MIDAS). RESULTS: Migraineurs missed more days from family/leisure activities than from work/school (mean 4.2 vs 2.4 days) in the previous 3 months. On an additional 6.2 days within the 3-month period, productivity at work/school was reduced by at least half. Inability and reduced ability (by at least half) to perform household work were reported on 6.0 and 6.5 days, respectively. Of the women surveyed, 51% identified menstruation as a trigger for attacks and 6% reported attacks solely with menstruation (i. e. attacks occurred during menstruation on at least 9 out of 10 occasions), the latter associated with a higher pain score than other attacks. Living with or being related to a migraineur decreased nonmigraineurs' ability to participate in home/family life (moderate/great impact 49%) and social/leisure activities (moderate/great impact 47%). In a tradeoff analysis, 60% of treatment choice was driven by formulation type and 40% was driven by speed of onset. As migraine disability increased, speed of onset became more important. CONCLUSIONS: This study confirms the significant burden of migraine on patients and families/cohabitants, highlighting not only reduced productivity and absences from work/school, but also time missed from family/social occasions. Many women identify menstruation to be associated with more painful attacks. Overall, in terms of treatment choice, formulation type was a more important driver than speed of onset; however, as migrainerelated disability escalates, speed of onset becomes more important. To optimise migraine management, treatment choice should be based on individual patients' needs and preferences.

Randomized, placebo-controlled trial of rofecoxib in the acute treatment of migraine.

OBJECTIVE: To investigate the clinical profile of rofecoxib, a long-acting (approximately 17-hour half-life) selective cyclo-oxygenase-2 inhibitor, for the acute treatment of migraine. METHODS: A randomized, double-blind, placebo-controlled, parallel-group study was conducted. Patients age > or =18 treated a moderate or severe migraine headache with placebo (n = 182), rofecoxib 25 mg (n = 183), or rofecoxib 50 mg (n = 192). The primary efficacy measure was headache relief (mild or no pain) 2 hours after dose. RESULTS: The proportions of patients with migraine headache relief at 2 hours after dose were 34.3% for placebo, 54.0% for rofecoxib 25 mg (p < 0.001 vs placebo), and 56.7% for rofecoxib 50 mg (p < 0.001 vs placebo). Rofecoxib 25 and 50 mg were superior to placebo in providing pain freedom at 2 hours, 24-hour sustained headache relief, and 24-hour sustained pain freedom; in reducing photophobia, phonophobia, nausea (50 mg only), and functional disability at 2 hours after dose; and in improving some quality-of-life scores over 24 hours. More patients on rofecoxib 50 mg reported adverse events (39.6%) than patients on rofecoxib 25 mg (26.8%) or placebo (23.6%) regardless of drug relatedness; however, the incidences of drug-related adverse events were similar between treatment groups. These adverse events were generally mild or moderate in severity. The most commonly reported adverse events were dry mouth, dizziness, somnolence, nausea, dyspepsia, paresthesia, and asthenia, with similar incidences between treatment groups. CONCLUSION: Rofecoxib 25 and 50 mg were effective and generally well tolerated for the acute treatment of migraine attacks.

Low dose balsalazide (1.5 g twice daily) and mesalazine (0.5 g three times daily) maintained remission of ulcerative colitis but high dose balsalazide (3.0 g twice daily) was superior in preventing relapses.

BACKGROUND: Balsalazide is a new 5-aminosalicylic acid (5-ASA) containing prodrug. Its efficacy in comparison with standard mesalazine therapy and the optimum dose for maintaining remission of ulcerative colitis are still unclear. AIMS: To compare the relapse preventing effect and safety profile of two doses of balsalazide and a standard dose of Eudragit coated mesalazine. METHODS: A total of 133 patients with ulcerative colitis in remission were recruited to participate in a double blind, multicentre, randomised trial: 49 patients received balsalazide 1.5 g twice daily, 40 received balsalazide 3.0 g twice daily, and 44 received mesalazine 0.5 g three times daily. Efficacy assessments were clinical activity index (CAI) and endoscopic score according to Rachmilewitz, and a histological score. In addition, laboratory tests were performed and urinary excretion of 5-ASA and its metabolite N-Ac-5-ASA was analysed. The study lasted for 26 weeks. RESULTS: Balsalazide 3.0 g twice daily resulted in a significantly higher clinical remission rate (77.5%) than balsalazide 1.5 g twice daily (43.8%) and mesalazine 0.5 g three times daily (56.8%) (p=0.006). The respective times to relapse were 161 days, 131 days (p=0.003), and 144 days (NS). Accordingly, pairwise contrasts of the final endoscopic score demonstrated a significant difference (p=0.005) between the two balsalazide treatment groups while differences between either of these two groups and mesalazine were not statistically significant. Patients treated with balsalazide excreted less 5-ASA and N-Ac-5-ASA than patients receiving mesalazine but these differences were not statistically significant. Discontinuation of the trial because of adverse effects occurred in nine patients: three in the balsalazide 1.5 g twice daily group, two in the balsalazide 3.0 g twice daily group, and four in the mesalazine 0.5 g three times daily group. No clinically important new drug safety related findings were identified in this study. CONCLUSIONS: High dose balsalazide (3.0 g twice daily) was superior in maintaining remission in patients with ulcerative colitis compared with a low dose (1.5 g twice daily) or a standard dose of mesalazine (0.5 g three times daily). All three treatments were safe and well tolerated.

Preference comparison of rizatriptan ODT 10-mg and sumatriptan 50-mg tablet in migraine.

OBJECTIVE: To compare the proportion of patients who prefer rizatriptan orally disintegrating tablet (ODT) 10-mg to sumatriptan 50-mg tablet. BACKGROUND: Migraineurs express treatment preference based on a variety of attributes including the speed of pain relief and medication formulation. Rizatriptan ODT is an orally disintegrating formulation of rizatriptan, a selective 5-HT1B/1D receptor agonist. This study was conducted to determine patient preference between rizatriptan ODT 10-mg and sumatriptan 50-mg tablet for the acute treatment of migraine. METHODS: This was a multicenter, randomized, open-label, two-period crossover study conducted in the United States with 524 enrolled patients. Patients treated a single moderate or severe headache in each treatment period. Patients treated one migraine with either rizatriptan ODT 10-mg or sumatriptan 50-mg tablet, then treated a second migraine with the alternate therapy. Patients completed diary assessments at baseline, and 30, 45, 60, 90, and 120 minutes postdose and rated headache severity on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). At the final study visit following treatment of their second migraine, patients expressed preference for one of the two study medications by completing an interviewer-administered Global Preference Question and then responded to a self-administered series of questions to capture their most important reason for preferring one study medication over the other. Safety measurements were recorded through standard adverse experience reporting. RESULTS: Three hundred eighty-six patients treated two migraine attacks. For those patients who expressed a preference for either rizatriptan ODT or sumatriptan (n = 374), the percentage of patients who preferred rizatriptan ODT 10-mg (57%, n = 213) was significantly greater than those who preferred sumatriptan 50-mg tablet (43%, n = 161) (P<.01). For those patients who treated two migraine attacks and had drug severity measures for both attacks (n = 384), a significantly greater percentage of patients reported pain relief after taking rizatriptan ODT than sumatriptan at the 45- and 60-minute time points (38% versus 29% and 58% versus 49%, respectively) (P<.01). In addition, a significantly greater percentage of patients taking rizatriptan ODT reported a pain-free status at the 60- and 120-minute time points (23% versus 17% [P<.05] and 60% versus 52% [P<.01], respectively). Both rizatriptan ODT and sumatriptan were well tolerated. CONCLUSIONS: A significantly greater proportion of patients preferred rizatriptan ODT 10-mg to sumatriptan 50-mg tablet for the acute treatment of migraine. Efficacy and safety data are consistent with the preference findings.

Potential of the Migraine Disability Assessment (MIDAS) Questionnaire as a public health initiative and in clinical practice.

Migraine is not always well managed in clinical practice, often being under-diagnosed and under-treated. As a result, many sufferers never consult a physician or lapse from care after physician contact. Although most migraine care is provided by general practitioners, others, including specialists, emergency room physicians, pharmacists, and alternative practitioners, may also be involved. A method of standardizing clinical information about migraine is essential for coordinated, logical, and systematic care. The impact of migraine on the patient is an important clinical parameter but one that is seldom inquired about, perhaps because it exhibits such marked variability among and within individuals. Headache-related disability can be an objective and measurable index of this impact. The Migraine Disability Assessment (MIDAS) Questionnaire is a simple and validated instrument with potential for use in clinical practice, research, and public health. It can improve communication between patients and health-care professionals regarding the impact of migraine which, in turn, allows tailoring of the intensity of treatment to the severity of the illness. Changes in the MIDAS score may serve as an end point in assessing treatment efficacy. In populations, MIDAS scores may indicate the burden of migraine in the community and spark public health initiatives to improve management.

Comparison of postoperative headache after retrosigmoid approach: vestibular nerve section versus vestibular schwannoma resection.

OBJECTIVE: To evaluate intradural drilling as a mechanism for the development of postoperative headache after retrosigmoid craniectomy. STUDY DESIGN: A retrospective review of charts was performed on 565 retrosigmoid approaches to the cerebellopontine angle performed between January 1980 and January 1998. Patients treated with retrosigmoid vestibular nerve section without intradural drilling were compared with patients who underwent retrosigmoid removal of vestibular schwannomas in which intradural drilling was performed for exposure of the internal auditory canal. SETTING: Private practice tertiary referral center. PATIENTS: Consecutive patients undergoing retrosigmoid approach between January 1980 and January 1998 were reviewed. MAIN OUTCOME MEASURES: The presence of headache, duration of headache, and severity of headache were noted. RESULTS: In this large series, 54% of patients experienced headaches after vestibular schwannoma removal, and 5% of patients experienced headaches after vestibular nerve section (p < 0.01, chi-square). CONCLUSIONS: Postoperative headache is not a characteristic of retrosigmoid craniectomy in the absence of intradural drilling. Intradural drilling is a probable cause of headache after the retrosigmoid approach. Cranioplasty is not necessary to prevent a high incidence of postoperative headache after retrosigmoid approach.

Oxythiamine and dehydroepiandrosterone induce a G1 phase cycle arrest in Ehrlich's tumor cells through inhibition of the pentose cycle.

Transketolase (TK) reactions play a crucial role in tumor cell nucleic acid ribose synthesis utilizing glucose carbons, yet, current cancer treatments do not target this central pathway. Experimentally, a dramatic decrease in tumor cell proliferation after the administration of the TK inhibitor oxythiamine (OT) was observed in several in vitro and in vivo tumor models. Here, we demonstrate that pentose cycle (PC) inhibitors, OT and dehydroepiandrosterone (DHEA), efficiently regulate the cell cycle and tumor proliferation processes. Increasing doses of OT or DHEA were administered by daily intraperitoneal injections to Ehrlich's ascites tumor hosting mice for 4 days. The tumor cell number and their cycle phase distribution profile were determined by DNA flow histograms. Tumors showed a dose dependent increase in their G0-G1 cell populations after both OT and DHEA treatment and a simultaneous decrease in cells advancing to the S and G2-M cell cycle phases. This effect of PC inhibitors was significant, OT was more effective than DHEA, both drugs acted synergistically in combination and no signs of direct cell or host toxicity were observed. Direct inhibition of PC reactions causes a G1 cell cycle arrest similar to that of 2-deoxyglucose treatment. However, no interference with cell energy production and cell toxicity is observed. PC inhibitors, specifically ones targeting TK, introduce a new target site for the development of future cancer therapies to inhibit glucose utilizing pathways selectively for nucleic acid production.

Modulation of CD28 expression: distinct regulatory pathways during activation and replicative senescence.

The costimulatory molecule CD28 has a restricted tissue distribution and is expressed on T cells and some plasmacytoma cells. Although CD28 is constitutively expressed, its expression is transiently down-regulated following T cell activation and declines progressively with in vitro senescence. In vivo, CD8+ T cells and, less frequently, CD4+ T cells may completely lose CD28 surface expression during chronic infections and with aging. This correlates with changes of nuclear protein-binding activities to two motifs, site alpha and beta, within the CD28 minimal promoter. Both alpha- and beta-bound complexes are found only in lymphoid tissues, in CD28+ T cells, and in some transformed B cells. These complexes are coordinately expressed except during replicative senescence, which is characterized by the down-modulation of site beta- but not site alpha-binding activities. In contrast, T cell activation induces a parallel decline in both site alpha- and beta-binding activities. CD4+ and CD8+ T cells differ in their beta-binding profiles, which may explain the more pronounced down-regulation of CD28 in senescent CD8+ T cells. In vivo expanded CD4+CD28null and CD8+CD28null T cells uniformly lack alpha- and beta-bound complexes, resembling the pattern seen in chronically activated cells and not of senescent cells.