bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sinus headache or migraine? Considerations in making a differential diagnosis.
Authors: Cady RK , Schreiber CP 
Published: December 2004

Neurology. 2002 May 14;58(9 Suppl 6):S10‐S14Sinus headache is commonly diagnosed, and patients with headache often cite sinus pain and pressure as a cause of their headaches. A high frequency of diagnosis of sinus headache, which specialists consider to be relatively rare, among patients meeting International Headache Society (IHS) diagnostic criteria for migraine raises the possibility that migraine and perhaps other headache types are sometimes mistaken for sinus headache. This article considers clinical, epidemiologic, and pathophysiologic relationships between sinus headache and migraine and discusses the implications for clinical management of headache. Both historic and new data show that nasal symptoms frequently accompany migraine, although these symptoms are not part of the IHS diagnostic criteria for migraine. Parasympathetic activation, as well as the hypothesized mechanism of neurogenic or immunogenic switching (i.e., crossover interactions of neurogenic and immunogenic inflammation), may account for both the frequent occurrence of nasal symptoms in migraine and the possibility that sinus inflammation can sometimes act as a migraine trigger. Considered in aggregate, the data show that the occurrence of nasal symptoms associated with a headache should neither trigger a diagnosis of sinus disease nor exclude a diagnosis of migraine. It should, in fact, prompt diagnostic consideration of both conditions.Comment: This article summarizes a small pilot study performed in the United States, in which patients with self‐diagnosed “sinus headache” were evaluated as to International Headache Society (IHS) diagnosis. Ninety‐six percent met IHS criteria for migraine or migrainous headache, suggesting that this entity, at least in the United States, is most frequently migraine with accompanying cranial parasympathetic activation. The article is worth tracking down and reading in its entirety, as the section of the article on pathophysiology is quite original and thought provoking. SJT
Cluster headache: the challenge of clinical trials.
Authors: Moore K 
Published: December 2004

Curr Pain Headache. Rep 2002 Feb;6(1):52‐56The design and execution of clinical trials poses special problems for cluster headache. Although there is less inter‐individual and intra‐individual variability of attacks than seen with migraine, the brevity of attacks, spontaneous remissions unrelated to treatment, and the relative rarity of cluster headaches challenge investigators. The International Headache Society has developed guidelines that represent a compromise between scientific rigor and practicality. Only injectable sumatriptan for acute attacks and verapamil for prophylaxis have demonstrated a robust therapeutic effect in controlled clinical trials.Comment: Kenneth Moore raises important methodological considerations. It is possible to undertake crossover trials comparing different active treatments? He is correct in his assertion that few agents show robust efficacy. A major issue relates to the proportion of patients with episodic versus chronic cluster headache where efficacy of active treatments can vary. For example, oral zolmitriptan was effective against placebo only in those patients with episodic disease (Bahra A, Gawel MJ, Hardebo JE, Millson DS, Breen SA, Goadsby PJ. Oral zolmitriptan is effective in the acute treatment of cluster headache. Neurology. 2000;54:1832‐1839). And a set of small studies on melatonin and cluster demonstrate the problems Dr. Moore describes. In one study (Leone M, D'Amico D, Moschiano F, Fraschini F, Busonne G. Metalonin versus placebo in the prophylaxis of cluster headache: a double‐blind pilot study with parallel groups. Cephalalgia. 1996;16:494‐496), the melatonin worked only in episodic, not chronic cluster patients. In the second study (Prinsheim T, Magnoux E, Dobson CF, Hamel E, Aube M. Melatonin as adjuctive therapy in the prophylaxis of cluster headache: a pilot study. Headache. 2002;42:787‐792), melatonin did not work better than placebo in either episodic or chronic cluster patients. Furthermore, the paper abstracted above by Torelli and Manzoni suggests that episodic cluster may progress to chronic cluster as a result of extrinsic factors such as smoking. Finally, there are ethical issues in placebo‐controlled cluster studies, given the severity of the pain and the availability of effective acute and chronic treatments. As noted above, Dr. Peter Goadsby points out the need to persevere with these studies to find nonvasoactive treatments for patients with cluster headache. DSM and SJT
In vivo evidence of altered skeletal muscle blood flow in chronic tension‐type headache.
Authors: Ashina M , Stallknecht B , Bendtsen L , Pedersen JF , Galbo H , Dalgaard P , Olesen J 
Published: December 2004

Brain. 2002 Feb;125(Pt 2):320‐326Painful impulses from tender pericranial muscles may play a major role in the pathophysiology of chronic tension‐type headache. Firm evidence for peripheral muscle pathology as a cause of muscle pain and chronic headache is still lacking. Using a microdialysis technique, we aimed to estimate in vivo blood flow and interstitial lactate concentrations in the trapezius muscle at rest and during static exercise in patients with chronic tension‐type headache and in healthy subjects. We recruited 16 patients with chronic tension‐type headache and 17 healthy control subjects. Two microdialysis catheters were inserted into the trapezius muscle (on the non‐dominant side) of subjects, and dialysates were collected at rest, 15 and 30 min after the start of static exercise (10% of maximal force) and 15 and 30 min after the exercise was completed. All samples were coded and analysed blind. The primary endpoints were to detect a difference between patients and controls in changes of muscle blood flow and the interstitial lactate concentration from baseline to exercise and post‐exercise periods. The increase in muscle blood flow from baseline to exercise and post‐exercise periods was significantly lower in patients than controls (P  =  0.03). There was no difference in resting blood flow between patients and controls (P  =  0.43). Resting interstitial concentration of lactate did not differ between patients (2.51  ± *T0.18 mM; mean ± standard error of the mean) and controls (2.35  ±  0.23 mM, P  =  0.57). There was no difference in change in interstitial lactate from baseline to exercise and post‐exercise periods between patients and controls (P  =  0.38). The present study provides in vivo evidence of decreased blood flow in response to static exercise in a tender muscle in patients with chronic tension‐type headache. We suggest that, because of increased excitability of neurones in the CNS, the central interpretation and response to normal sensory input are altered in patients with chronic tension‐type headache. This may lead to enhanced sympathetically mediated vasoconstriction and thereby a decreased blood flow in response to static exercise.Comment: An important study which links decreased blood flow in statically exercised trapezius muscle in patients with chronic tension‐type headache (CTTH) with muscle tenderness. A better understanding of the pathophysiology of CTTH may provide a clue to novel therapeutic maneuvers. DSM
Cost savings in migraine associated with less chest pain on new triptan therapy.
Authors: Wang JT , Barr CE , Torigoe Y , Wang E , Rowland CR , Goldfarb SD 
Published: December 2004

Am J Manag Care. 2002 Feb;8(3 Suppl):S102‐S107Objectives: This article constructs an economic model to estimate cost of chest‐pain‐related care in migraine patients receiving almotriptan 12.5 mg compared with those receiving sumatriptan 50 mg. Study Design: This population‐based, retrospective cohort study used data from the MEDSTAT Marketscan database (Ann Arbor, Michigan) to quantify incidence and costs of chest‐pain‐related diagnoses and procedures. After a 6‐month exclusion period, the study used a pre‐post design, with baseline and treatment periods defined, respectively, as 5 months before and after receiving sumatriptan therapy. An economic model was constructed to estimate annual cost savings per 1,000 patients receiving almotriptan instead of sumatriptan as a function of differing rates of chest pain. Annual direct medical cost avoided was calculated for a hypothetical health plan covering 1 million lives.Results: Among a cohort of 1,390 patients, the incidence of chest‐pain‐related diagnoses increased significantly (43.6%) with sumatriptan, from 110 during the baseline period to 158 during the treatment period (P  =  .003). Aggregate costs for chest‐pain‐related diagnoses and procedures increased 33.1%, from $22,713 to $30,234. Payments for inpatient hospital services rose 10‐fold; costs for primary care visits and outpatient hospital visits rose 53.1% and 14.4%, respectively. Payments for angiography increased from $0 to $462, and costs for chest radiographs and electrocardiograms increased 58.7% and 31.2%, respectively. Sumatriptan treatment was associated with a 3‐fold increase in payments for services for painful respiration and other chest pain. The model predicted $11,215 in direct medical cost savings annually per 1000 patients treated with almotriptan instead of sumatriptan. Annual direct medical costs avoided for the health plan totaled $195,913.Conclusion: Using almotriptan instead of sumatriptan will likely reduce the cost of chest‐pain‐related care for patients with migraine headaches.Comment: In my view, this study takes conjecture a step too far. The lower reported chest adverse events (AEs) reported in clinical trials where all AEs are scrutinized will not necessarily lead to lower reporting in the clinic. This hypothesis remains to be proven in a well‐designed post‐marketing surveillance program, untarnished by commercial sponsorship. Until such an independent prospective study is carried out, the extrapolations described here and in similar papers are pure conjecture and should be classed as the lowest grade of evidence on a par with uncorroborated clinical opinion. DSM
Mutation analysis of the CACNA1A calcium channel subunit gene in 27 patients with sporadic hemiplegic migraine.
Authors: Terwindt G , Kors E , Haan J , Vermeulen F , Van den Maagdenberg A  , Frants R , Ferrari M 
Published: December 2004

Arch Neurol. 2002 Jun;59(6):1016‐1018Background: Familial hemiplegic migraine is a rare autosomal dominant subtype of migraine with aura that in half of the families is caused by mutations in the CACNA1A gene on chromosome 19p13. In sporadic hemiplegic migraine (SHM), that is, hemiplegic migraine without affected family members, the contribution of the CACNA1A gene is unknown.Objective: To investigate the involvement of the CACNA1A calcium channel subunit gene in SHM.Methods: We screened 27 patients with SHM for mutations in the CACNA1A gene by a combination of single‐strand conformational polymorphism analysis and sequence analysis.Results: One patient with SHM also had ataxia, nystagmus, and cerebellar atrophy on computed tomography and carried a T666M mutation. Another patient with SHM who had no cerebellar signs carried an R583Q mutation. No mutations or interictal neurological abnormalities were found in the remaining 25 patients with SHM.Conclusions: Most patients with SHM do not have a CACNA1A mutation. The results of this study, combined with the findings reported in the literature, show that the presence of cerebellar symptoms in addition to the hemiplegic attacks increases the chance of finding a CACNA1A mutation. In addition, to our knowledge, we have found a first patient with SHM without cerebellar signs with a mutation.Comment: The story on calcium channelopathies and neurologic disorders becomes ever more complex, as multiple neurologic disorders appear linked to varying forms of calcium‐channel mutations. Professor Ferrari has described links to cerebellar disorders, to a peculiar and severe response to head trauma, and to epilepsy, as well as to familial hemiplegic migraine. Now his group finds that the most frequently found calcium channelopathy mutations are not found in most patients with spontaneous hemiplegic migraine. Does this just mean that other mutations, not yet described, cause a common phenotypic expression? Or are there multiple causes for the hemiplegic migraine syndrome, and not all of them due to calcium channelopathies? SJT
A Role of Arabidopsis Inositol Polyphosphate Kinase, AtIPK2α, in Pollen Germination and Root Growth
Authors: Xu Jun , Brearley Charles A. , Lin Wen-Hui , Wang Yuan , Ye Rui , Mueller-Roeber Bernd , Xu Zhi-Hong , Xue Hong-Wei 
Published: December 2004

Abstract
Inositol polyphosphates, such as inositol trisphosphate, are pivotal intracellular signaling molecules in eukaryotic cells. In higher plants the mechanism for the regulation of the type and the level of these signaling molecules is poorly understood. In this study we investigate the physiological function of an Arabidopsis (Arabidopsis thaliana) gene encoding inositol polyphosphate kinase (AtIPK2α), which phosphorylates inositol 1,4,5-trisphosphate successively at the D-6 and D-3 positions, and inositol 1,3,4,5-tetrakisphosphate at D-6, resulting in the generation of inositol 1,3,4,5,6-pentakisphosphate. Semiquantitative reverse transcription-PCR and promoter-β-glucuronidase reporter gene analyses showed that AtIPK2α is expressed in various tissues, including roots and root hairs, stem, leaf, pollen grains, pollen tubes, the flower stigma, and siliques. Transgenic Arabidopsis plants expressing the AtIPK2α antisense gene under its own promoter were generated. Analysis of several independent transformants exhibiting strong reduction in AtIPK2α transcript levels showed that both pollen germination and pollen tube growth were enhanced in the antisense lines compared to wild-type plants, especially in the presence of nonoptimal low Ca2+ concentrations in the culture medium. Furthermore, root growth and root hair development were also stimulated in the antisense lines, in the presence of elevated external Ca2+ concentration or upon the addition of EGTA. In addition, seed germination and early seedling growth was stimulated in the antisense lines. These observations suggest a general and important role of AtIPK2α, and hence inositol polyphosphate metabolism, in the regulation of plant growth most likely through the regulation of calcium signaling, consistent with the well-known function of inositol trisphosphate in the mobilization of intracellular calcium stores.
Complementation of sugary-1 Phenotype in Rice Endosperm with the Wheat Isoamylase1 Gene Supports a Direct Role for Isoamylase1 in Amylopectin Biosynthesis
Authors: Kubo Akiko , Rahman Sadequr , Utsumi Yoshinori , Li Zhongyi , Mukai Yasuhiko , Yamamoto Maki , Ugaki Masashi , Harada Kyuya , Satoh Hikaru , Konik-Rose Christine , Morell Matthew , Nakamura Yasunori 
Published: December 2004

Abstract
To examine the role of isoamylase1 (ISA1) in amylopectin biosynthesis in plants, a genomic DNA fragment from Aegilops tauschii was introduced into the ISA1-deficient rice (Oryza sativa) sugary-1 mutant line EM914, in which endosperm starch is completely replaced by phytoglycogen. A. tauschii is the D genome donor of wheat (Triticum aestivum), and the introduced fragment effectively included the gene for ISA1 for wheat (TaISA1) that was encoded on the D genome. In TaISA1-expressing rice endosperm, phytoglycogen synthesis was substantially replaced by starch synthesis, leaving only residual levels of phytoglycogen. The levels of residual phytoglycogen present were inversely proportional to the expression level of the TaISA1 protein, although the level of pullulanase that had been reduced in EM914 was restored to the same level as that in the wild type. Small but significant differences were found in the amylopectin chain-length distribution, gelatinization temperatures, and A-type x-ray diffraction patterns of the starches from lines expressing TaISA1 when compared with wild-type rice starch, although in the first two parameters, the effect was proportional to the expression level of TaISA. The impact of expression levels of ISA1 on starch structure and properties provides support for the view that ISA1 is directly involved in the synthesis of amylopectin.
The Sources of Carbon and Nitrogen Supplying Leaf Growth. Assessment of the Role of Stores with Compartmental Models
Authors: Lattanzi Fernando Alfredo , Schnyder Hans , Thornton Barry 
Published: December 2004

Abstract
Patterns of synthesis and breakdown of carbon (C) and nitrogen (N) stores are relatively well known. But the role of mobilized stores as substrates for growth remains less clear. In this article, a novel approach to estimate C and N import into leaf growth zones was coupled with steady-state labeling of photosynthesis (13CO2/12CO2) and N uptake (15NO3 −/14NO3 −) and compartmental modeling of tracer fluxes. The contributions of current C assimilation/N uptake and mobilization from stores to the substrate pool supplying leaf growth were then quantified in plants of a C3 (Lolium perenne) and C4 grass (Paspalum dilatatum Poir.) manipulated thus to have contrasting C assimilation and N uptake rates. In all cases, leaf growth relied largely on photoassimilates delivered either directly after fixation or short-term storage (turnover rate = 1.6–3.3 d−1). Long-term C stores (turnover rate &lt; 0.09 d−1) were generally of limited relevance. Hence, no link was found between the role of stores and C acquisition rate. Short-term (turnover rate = 0.29–0.90 d−1) and long-term (turnover rate &lt; 0.04 d−1) stores supplied most N used in leaf growth. Compared to dominant (well-lit) plants, subordinate (shaded) plants relied more on mobilization from long-term N stores to support leaf growth. These differences correlated well with the C-to-N ratio of growth substrates and were associated with responses in N uptake. Based on this, we argue that internal regulation of N uptake acts as a main determinant of the importance of mobilized long-term stores as a source of N for leaf growth.
Gene Expression Programs during Brassica oleracea Seed Maturation, Osmopriming, and Germination Are Indicators of Progression of the Germination Process and the Stress Tolerance Level
Authors: Soeda Yasutaka , Konings Maurice C.J.M. , Vorst Oscar , van Houwelingen Adele M.M.L. , Stoopen Geert M. , Maliepaard Chris A. , Kodde Jan , Bino Raoul J. , Groot Steven P.C. , van der Geest Apolonia H.M. 
Published: December 2004

Abstract
During seed maturation and germination, major changes in physiological status, gene expression, and metabolic events take place. Using chlorophyll sorting, osmopriming, and different drying regimes, Brassica oleracea seed lots of different maturity, stress tolerance, and germination behavior were created. Through careful physiological analysis of these seed lots combined with gene expression analysis using a dedicated cDNA microarray, gene expression could be correlated to physiological processes that occurred within the seeds. In addition, gene expression was studied during early stages of seed germination, prior to radicle emergence, since very little detailed information of gene expression during this process is available. During seed maturation expression of many known seed maturation genes, such as late-embryogenesis abundant or storage-compound genes, was high. Notably, a small but distinct subgroup of the maturation genes was found to correlate to seed stress tolerance in osmoprimed and dried seeds. Expression of these genes rapidly declined during priming and/or germination in water. The majority of the genes on the microarray were up-regulated during osmopriming and during germination on water, confirming the hypothesis that during osmopriming, germination-related processes are initiated. Finally, a large group of genes was up-regulated during germination on water, but not during osmopriming. These represent genes that are specific to germination in water. Germination-related gene expression was found to be partially reversible by physiological treatments such as slow drying of osmoprimed seeds. This correlated to the ability of seeds to withstand stress.
Manipulation of the Blue Light Photoreceptor Cryptochrome 2 in Tomato Affects Vegetative Development, Flowering Time, and Fruit Antioxidant Content
Authors: Giliberto Leonardo , Perrotta Gaetano , Pallara Patrizia , Weller James L. , Fraser Paul D. , Bramley Peter M. , Fiore Alessia , Tavazza Mario , Giuliano Giovanni 
Published: December 2004

Abstract
Cryptochromes are blue light photoreceptors found in plants, bacteria, and animals. In Arabidopsis, cryptochrome 2 (cry2) is involved primarily in the control of flowering time and in photomorphogenesis under low-fluence light. No data on the function of cry2 are available in plants, apart from Arabidopsis (Arabidopsis thaliana). Expression of the tomato (Solanum lycopersicum) CRY2 gene was altered through a combination of transgenic overexpression and virus-induced gene silencing. Tomato CRY2 overexpressors show phenotypes similar to but distinct from their Arabidopsis counterparts (hypocotyl and internode shortening under both low- and high-fluence blue light), but also several novel ones, including a high-pigment phenotype, resulting in overproduction of anthocyanins and chlorophyll in leaves and of flavonoids and lycopene in fruits. The accumulation of lycopene in fruits is accompanied by the decreased expression of lycopene β-cyclase genes. CRY2 overexpression causes an unexpected delay in flowering, observed under both short- and long-day conditions, and an increased outgrowth of axillary branches. Virus-induced gene silencing of CRY2 results in a reversion of leaf anthocyanin accumulation, of internode shortening, and of late flowering in CRY2-overexpressing plants, whereas in wild-type plants it causes a minor internode elongation.
Annotations and Functional Analyses of the RiceWRKYGene Superfamily Reveal Positive and Negative Regulators of Abscisic Acid Signaling in Aleurone Cells
Authors: Xie Zhen , Zhang Zhong-Lin , Zou Xiaolu , Huang Jie , Ruas Paul , Thompson Daniel , Shen Qingxi J. 
Published: December 2004

AbstractThe WRKY proteins are a superfamily of regulators that control diverse developmental and physiological processes. This family was believed to be plant specific until the recent identification of WRKY genes in nonphotosynthetic eukaryotes. We have undertaken a comprehensive computational analysis of the rice (Oryza sativa) genomic sequences and predicted the structures of 81 OsWRKY genes, 48 of which are supported by full-length cDNA sequences. Eleven OsWRKY proteins contain two conserved WRKY domains, while the rest have only one. Phylogenetic analyses of the WRKY domain sequences provide support for the hypothesis that gene duplication of single- and two-domain WRKY genes, and loss of the WRKY domain, occurred in the evolutionary history of this gene family in rice. The phylogeny deduced from the WRKY domain peptide sequences is further supported by the position and phase of the intron in the regions encoding the WRKY domains. Analyses for chromosomal distributions reveal that 26% of the predicted OsWRKY genes are located on chromosome 1. Among the dozen genes tested, OsWRKY24, -51, -71, and -72 are induced by abscisic acid (ABA) in aleurone cells. Using a transient expression system, we have demonstrated that OsWRKY24 and -45 repress ABA induction of the HVA22 promoter-β-glucuronidase construct, while OsWRKY72 and -77 synergistically interact with ABA to activate this reporter construct. This study provides a solid base for functional genomics studies of this important superfamily of regulatory genes in monocotyledonous plants and reveals a novel function for WRKY genes, i.e. mediating plant responses to ABA.