bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Study with EMG, Pressure Algometry and Manual Palpation in Tension-Type Headache and Migraine
Authors: Sandrini G , Antonaci F , Pucci E , Bono G , Nappi G
Published: March 2003

According to International Headache Society classification criteria, the presence of pericranial muscle disorder in tension-type headache should be evaluated using one of the following methods: EMG, pressure algometry or manual palpation. The purpose of this study was to compare the results of these three methods in 15 patients with episodic tension-type headache, 29 with chronic tension-type headache and 22 presenting migraine without aura compared to those obtained in healthy individuals. Algometric and EMG recordings at the frontalis muscle during mental arithmetic were more impaired in episodic and chronic tension headache patients than in controls and migraine patients. Chronic tension headache patients were significantly impaired at the trapezius muscle in all three tests compared to controls. Our data indicate that when two or three tests were carried out the diagnostic capacity was significantly improved in comparison to only one test. Moreover, since a different pattern could be seen with pain and without pain, the existence of headache at the time of testing should be taken into consideration.
A Study of Adaptive Responses in Cell Signaling in Migraine and Cluster Headache: Correlations Between Headache Type and Changes in Gene Expression
Authors: Gardiner IM , Ahmed F , Steiner TJ , McBain A , Kennard C , de Belleroche J
Published: March 2003

The project was an investigation into whether changes in the expression of G-proteins underlie altered cell signaling in migraine and cluster headache. The basis for this assumption is that altered physiological responses are seen in migraineurs and that differences in cell signaling are detected biochemically in various cell types isolated from peripheral blood. Levels of three G-protein mRNAs—Gsα, Giα, and Gα, were quantified in lymphocytes from clinically well-defined migraine and cluster headache patients and correlated with headache type and influence of drug treatment. Giα mRNA was reduced by 50% in all migraine patients compared with control subjects; similarly in patients with or without aura, in patients with a migraine headache at the time of sampling, and patients in a quiescent state. No reduction in the levels of Gsα or Gα mRNA were seen in migraine patients. A smaller reduction was seen in cluster headache patients, most marked in those without medication. Levels of Gsα mRNA were significantly reduced in cluster headache patients compared with migraine patients. The marked down-regulation of Giα mRNA in migraine, whether quiescent or acute, indicates either an adaptive response to headache in this group of patients or that low levels of Giα mRNA make individuals more susceptible to migraine.
Headache in Children in Dutch General Practice
Authors: van der Wouden JC , van der Pas P , Bruijnzeels MA , Brienen JA , van Suijlekom-Smit LWA
Published: March 2003

Aim: To describe the occurrence of headache in general practice, the diagnoses made in general practice, and the management.

Method: Data from the Dutch national survey of morbidity and interventions in general practice were used. The practice population (103 practices) comprised 63753 children aged 0-14 years.

Results: In 634 episodes, headache was a reason for encounter. The incidence of headache presented to the general practitioner was 40.2 per 1000 person years. More than half of the episodes were related to an infectious disease, among which upper respiratory tract infections predominated. The incidence rate of the diagnosis idiopathic headache was 7.3 episodes per 1000 person years. The incidence increased with age and was higher in girls than in boys. In only 12% of cases of idiopathic headache were special investigations carried out, mostly blood examinations. Medication was prescribed in 27% of all episodes of idiopathic headache. In the absence of an infectious disease, many headache episodes were associated with psychosocial problems. Family problems and school problems were mentioned most often.

Conclusion: Headache in children as reason for encounter is a common problem in general practice, often associated with an infectious disease. When confronted with a child with idiopathic headache, the general practitioner should be aware of a possible psychosocial component.
Psychiatric Comorbidity and Psychosocial Stress in Patients with Tension-Type Headache From Headache Centers in Italy
Authors: Puca F , Genco S , Prudenzano MP , Savarese M , Bussone G , D'Amico D , Cerbo R , Gala C , Coppola MT , Gallai V , Firenze C , Sarchielli P , Guazzelli M , Guidetti V , Manzoni G , Granella F , Muratorio A , Bonuccelli U , Nuti A , Nappi G , Sandrini G , Verri AP , Sicuteri F , Marabini S
Published: March 2003

A multicenter study was carried out in 10 Italian Headache Centers to investigate the prevalence of psychosocial stress and psychiatric disorders listed by the IHS classification as the “most likely causative factors” of tension-type headache (TTH). Two hundred and seventeen TTH adult outpatients consecutively recruited underwent a structured psychiatric interview (CIDI-c). The assessment of psychosocial stress events was carried out using an ad hoc questionnaire. The psychiatric disorders that we included in the three psychiatric items of the fourth digit of the IHS classification were depressive disorders for the item depression, anxiety disorders for the item anxiety, and somatoform disorders for the item headache as a delusion or an idea. Diagnoses were made according to DSM-III-R criteria. At least one psychosocial stress event or a psychiatric disorder was detected in 84.8% of the patients. Prevalence of psychiatric comorbidity was 52.5% for anxiety, 36.4% for depression, and 21.7% for headache as a delusion or an idea. Psychosocial stress was found in 29.5% of the patients and did not differ between patients with and without psychiatric comorbidity. Generalized anxiety disorder (83.3%) and dysthymia (45.6%) were the most frequent disorders within their respective psychiatric group. The high prevalence of psychiatric disorders observed in this wide sample of patients emphasizes the need for a systematic investigation of psychiatric comorbidity aimed at a more comprehensive and appropriate clinical management of TTH patients.
Influence of Intense Light Stimulation on Trigeminal and Cervical Pain Perception Thresholds
Authors: Kowacs PA , Piovesan EJ , Werneck LC , Tatsui CE , Lange MC , Ribas LC , da Silva HP
Published: March 2003

Thirty-three migraineurs and 23 healthy controls were submitted to pressure algometry before and after light-induced discomfort was elicited by progressive light stimulation in a monoblind fashion. Pressure algometries were performed on the emergence of the supraorbital, infraorbital, mental and greater occipital nerves, and over the temporal muscles, always throughout the same sequence and from right to left. Measurements were carried out before and immediately after light stimulation and after 10 min of the second algometry. The final result for each site measured at each time-point was the mean of the three measurements. Light stimulation was carried out progressively until light-induced discomfort was reported, to a maximum of 20 000 lux. A heat-blocking glass protected patients' eyes. Migraineurs presented significant and persistent drops in pain perception thresholds after light stimulation, at all sites tested ( P = 0.002 to < 0.0001). These drops were not seen in controls, in whom, conversely, a less significant increase was seen on right infraorbital and left temporal muscle sites. Our results indicate that in migraineurs, light may have a relevant role in trigeminal and cervical pain perception thresholds.
CACNA1A Gene Polymorphisms in Cluster Headache
Authors: Sjöstrand C , Giedratis V , Ekbom K , Waldenlind E , Hillert J
Published: March 2003

Cluster headache (CH) is a primary headache disorder where the aetiological and pathophysiological mechanisms still are largely unknown. An increased risk of CH in first- and second-degree relatives suggests the importance of genetic factors. Mutations of the P/Q type calcium channel alpha 1 subunit (CACNA1A) gene on chromosome 19p13 have been shown to cause several neurological disorders with a wide clinical spectrum, mainly episodic diseases. Missence mutations of the gene cause familial hemiplegic migraine (FHM) and it is also likely to be involved in the more common forms of migraine. The CACNA1A gene is thus a promising candidate gene for CH. In this study we performed an association analysis of an intragenic polymorphic (CA)n-repeat with marker D19S1150 and a (CAG)n-repeat in the 3′UTR region, in 75 patients with CH according to IHS criteria and 108 matched controls. Genotypes and allele frequencies were similarly distributed in patients and controls. Linkage disequilibrium between the two markers was similar in patients and controls. We conclude that an importance of the CACNA1A gene in sporadic CH is unlikely.
Cervicogenic Headache (Ceh) After Whiplash Injury
Authors: Drottning M , Staff PH , Sjaastad O
Published: March 2003

The main objective of the present investigation was to search for cervicogenic headache (CEH) after whiplash injury. Whiplash patients ( n = 587), were followed for a year after their emergency service consultation. A total of 222 patients with headache after 1 month went through interview and examinations at 6 weeks, 6 months and 1 year. All included persons received a questionnaire after 1 year. De novo CEH seemed to be present in 8% at 6 weeks and in 3% at 1 year. Previous car accidents, pre-existing headache and neck pain were more frequent in chronic CEH individuals than in those in the cohort without CEH. Range of motion in the neck was reduced in 65% of chronic CEH individuals hours after the accident, compared with 41% in the cohort. Cybex inclinometer, at 6 weeks and 1 year, demonstrated reduced extension in the neck. CEH seems to be present after whiplash injury, particularly in the early phase. It seems similar to, but probably not identical to, non-whiplash CEH.
Age at Onset and Sex Ratio in Cluster Headache: Observations Over Three Decades
Authors: Ekbom K , Svensson DA , Träff H , Waldenlind E
Published: March 2003

Five hundred and fifty-four patients with episodic cluster headache (ECH) and chronic cluster headache (CCH) were examined between 1963 and 1997. Mean age at onset was significantly higher in women with CCH compared with women with ECH and in men with ECH or CCH. In women with CCH age at onset was evenly distributed from 10 to 69 years, whereas in men with CCH and in both sexes with ECH, there was a peak when they were in their 20s. In women with ECH a second peak of onset occurred in their 50s. Although not statistically significant, primary CCH started later in women (mean 50.8 years) than secondary CCH (mean 35.5 years). There was a significant variation in the male : female ratio with respect to age at onset, being largest between 30 and 49 years of age (ECH 7.2 : 1; CCH 11.0 : 1) and lowest after 50 (ECH 2.3 : 1; CCH 0.6 : 1). During the observation period of more than 30 years there was a trend towards a decreasing male preponderance; the male: female ratio was significantly higher among patients with onset before rather than after 1970. The proportion of episodic vs. chronic CH did not change during the study period. The nature of the sex- and age-related pattern of cluster headache onset remains to be elucidated but mechanisms associated with sex hormone regulation, perhaps of hypothalamic origin, may be involved, as well as environmental factors related to lifestyle.
Orthostatic Headache Syndrome with Csf Leak Secondary To Bony Pathology of the Cervical Spine
Authors: Eross EJ , Dodick DW , Nelson KD
Published: March 2003

The syndrome of orthostatic (low pressure) headaches is well described and most commonly occurs following deliberate violation of the dura (e.g. lumbar puncture). This syndrome can also occur spontaneously and results from the leakage of CSF. We describe three patients who suffered from spontaneous CSF leaks secondary to bony pathology of the cervical spine, and propose that this may be a more common aetiology than originally thought. Often these patients are difficult to manage medically, and surgery may be necessary for symptomatic relief.
The trouble with kids: an account of problems experienced with local children by people with learning disabilities
Authors: Whittell Bridget , Ramcharan Paul
Published: March 2003

Recent research carried out in North Wales, which has been funded by the Wales Office for Research and Development, has focused attention on the everyday lives of a small number of people with learning disabilities living in the community. Although many positive stories and experiences have emerged, negative incidents of abuse and victimization have also been experienced by the majority of participants. The present article concentrates on incidents of abuse and victimization which have involved children as the perpetrators, drawing upon the experiences of a married couple who participated in this research. Their experiences are not uncommon and highlight this as an issue which requires attention by looking at more positive and proactive ways of preventing and tackling problems involving children – and also adults – in the community.
Emergence of participatory methodology in learning difficulty research: understanding the context
Authors: Chappell Anne Louise
Published: March 2003

The past few years have seen the development of an important debate over methodology in disability research. The rise of emancipatory and participatory methodologies has meant that disabled people are making increasing demands to be included in the research process. The present paper will examine this debate and its implications for learning difficulty research. The article will discuss the reasons why participatory methodology is gaining greater acceptance than emancipatory methodology among learning difficulty researchers by examining the position of participatory research in the methodological traditions of social research into learning difficulty.
‘He will finish up caring for me’: people with learning disabilities and mutual care
Authors: Williams Val , Robinson Carol
Published: March 2003

Until recently, the carer's perspective has dominated research on families who include someone with a learning disability and recent legislation has underlined the carer's rights. Previous research has found that some more able people with learning disabilities were very aware of their parents' growing needs, and were taking on responsibilities within the family to help and support their carer/parents. However, recent legislation still dichotomizes family members into carers and cared‐for people. The present paper is based on a research study of the impact of the UK Carers Act 1995 on families with someone with a learning disability. It involved canvassing the views of people with learning disabilities about their experience of assessments and their relationships within the family. The present authors found that many people with learning disabilities expressed empathy for their carer's point of view and that several people (including some who had high support needs themselves) were performing care tasks for their elderly parents. However, no one appeared to recognize the situation as one of mutual care, and parents generally carried on defining themselves as carers since they took responsibility and exercised control. The present authors conclude that mutual caring is far more common than is recognized and includes people with severe learning disabilities. A more holistic approach to assessment of needs is required that can take into account the complex web of interdependence within a family. Rather than categorizing people into ‘carers’ and ‘cared‐for’, the present authors suggest a model that recognizes mutually supportive partnerships within the family.
Feeding problems, gastrostomy and families: a qualitative pilot study
Authors: Rouse Lindsey , Herrington Peter , Assey Joanna , Baker Roger , Golden Shirley
Published: March 2003

Feeding problems are often found in children with severe and profound learning disabilities. It is increasingly common for these children to receive a gastrostomy button so that they can maintain an adequate nutritional intake. The psychological implications of this operation for families and carers have received little attention, with most studies focusing on medical and nutritional outcomes. The present paper describes the qualitative findings of interviews carried out with professionals and parents as part of a pilot study. The themes which emerged included the need for early multidisciplinary support and information for parents, improved communication between professionals, and problems relating to funding. Suggestions for improved service delivery are proposed.
Experimental study of aqueous fluid infiltration into quartzite: implications for the kinetics of fluid redistribution and grain growth driven by interfacial energy reduction
Authors: Nakamura M. , Watson E. B.
Published: March 2003

To investigate the kinetics of interfacial energy‐driven fluid infiltration, experiments were carried out in a quartzite–water system at 621–925°C and 0.8 GPa. Infiltration couples were made by juxtaposing presynthesized dry quartzite cylinders and fluid reservoirs. The infiltration process was confirmed by the presence of pores at the quartzite grain edges. As predicted from theoretical considerations and previous experiments, wetting fluids such as pure water and NaCl aqueous solution infiltrated into quartzite, whereas nonwetting CO2‐rich fluids did not. Newly precipitated quartz layers at the surfaces of the infiltrated sample proved that infiltration took place by a dissolution–precipitation mechanism.

The enhancement of grain growth by fluid infiltration was observed over the entire range of experimental temperatures. The fluid fraction, gauged by the porosity of the run products, increases at the infiltration front and then decreases towards the fluid reservoir to form a high‐porosity zone with a maximum porosity of 2.3–2.9%. As infiltration proceeds, the high‐porosity zone advances like a travelling wave. This porosity wave is probably caused by a grain curvature gradient resulting from preferential grain growth in the infiltrated part of the quartzite, perhaps combined with other factors. The infiltration kinetics were modelled with a steady‐state diffusion model over the high‐porosity zone. The solubility difference between dissolving and precipitating grains was deduced to be 2 × 10−2−3 × 10−1 wt %. The experimentally obtained infiltration rate of aqueous fluid in the steady‐state diffusion regime (2 ± 0.5 × 10−8 m sec−1 at 823°C) is much faster than the estimated metamorphic fluid flux rates, so that interfacial energy‐driven fluid redistribution in quartz‐rich layers could significantly contribute to the fluid flux in high‐grade metamorphism, at least over a short distance.

Cathodoluminescence observations of the run products revealed that the grain growth of quartzite in the presence of fluid proceeds extensively, which would promote the chemical equilibration between fluid and rock more effectively than would volume diffusion in quartz crystals.
An exhumed palaeo‐hydrocarbon migration fairway in a faulted carrier system, Entrada Sandstone of SE Utah, USA
Authors: Garden I. R. , Guscott S. C. , Burley S. D. , Foxford K. A. , Walsh J. J. , Marshall J.
Published: March 2003

The Moab Anticline, east‐central Utah, is an exhumed hydrocarbon palaeo‐reservoir which was supplied by hydrocarbons that migrated from the Moab Fault up‐dip towards the crest of the structure beneath the regional seal of the Tidwell mudstone. Iron oxide reduction in porous, high permeability aeolian sandstones records the secondary migration of hydrocarbons, filling of traps against small sealing faults and spill pathways through the Middle Jurassic Entrada Sandstone. Hydrocarbons entered the Entrada Sandstone carrier system from bends and other leak points on the Moab Fault producing discrete zones of reduction that extend for up to 400 m from these leak points. They then migrated in focused stringers, 2–5 m in height, to produce accumulations on the crest of the anticline. Normal faults on the anticline were transient permeability barriers to hydrocarbon migration producing a series of small compartmentalized accumulations. Exsolution of CO2 as local fault seals were breached resulted in calcite cementation on the up‐dip side of faults.

Field observations on the distribution of iron oxide reduction and calcite cements within the anticline indicate that the advancing reduction fronts were affected neither by individual slip bands in damage zones around faults nor by small faults with sand: sand juxtapositions. Faults with larger throws produced either sand: mudstone juxtapositions or sand: sand contacts and fault zones with shale smears. Shale‐smeared fault zones provided seals to the reducing fluid which filled the structural traps to spill points.
Criteria of food quality in different contexts
Authors: Meiselman Herbert L.
Published: March 2003

Food quality is considered from three perspectives: the product, the consumer, and the food service environment. These are examined in the chronological order in which they developed in the food field. Product quality is still the most common usage of the term quality and originated in quality assurance/quality control with its focus on defect avoidance and conformance to specifications. Consumer perceptions of quality are a newer view of quality, although some writers argue that all judgments of quality are consumer‐based in the end. The consumer view of quality underscores that quality is relative and situational. Service quality is the newest dimension of quality to be considered. It is argued that food quality in the food service environment should consider both food quality and service quality. A number of conclusions for consideration of food quality are presented.
National‐scale conservation assessments at an appropriate resolution
Authors: Hopkinson Paul , Evans Julianne , Gregory Richard D.
Published: March 2003

Abstract.  Most national‐scale conservation assessments are carried out at a resolution that is different from the actual size of protected areas in the study region. Coincidence between nature reserves and both hotspots (areas of high species richness) and complementary areas (sets of sites within which all species are represented) have been reported. However, the resolution (size of grid cells) of the species’ distribution data upon which many of these studies are based is often close to an order of magnitude larger than the size of the reserves. Presumably, only a proportion of the species recorded in the coarse grid cells will actually be present on reserves. We use fine (2 × 2‐km square grid cells) and coarse (10 × 10‐km square grid cells) resolution data of national distributions for breeding birds throughout Great Britain, and presence data for avian species on Royal Society for the Protection of Birds (RSPB) nature reserves, to investigate the proportion of species in the local area (100 km2) that are actually present on reserves. RSPB reserves contain between 50% and 70% of species from the local area. These proportions are significantly higher than for randomly selected, non‐reserve areas, indicating that RSPB reserves contain higher concentrations of bird species than the wider countryside. Furthermore, on RSPB reserves these proportions of threatened and non‐threatened species are equal, whereas in non‐reserve areas the proportions of non‐threatened species are significantly higher than threatened species. Thus, reserves hold a higher proportion of threatened species than occurs in the wider countryside.
Heterogeneity, speciation/extinction history and climate: explaining regional plant diversity patterns in the Cape Floristic Region
Authors: Cowling R. M. , Lombard A. T.
Published: March 2003

This paper investigates the role of heterogeneity and speciation/extinction history in explaining variation in regional scale (c. 0.1–3000 km2) plant diversity in the Cape Floristic Region of south‐western Africa, a species‐ and endemic‐rich biogeographical region. We used species‐area analysis and analysis of covariance to investigate geographical (east vs. west) and topographic (lowland vs. montane) patterns of diversity. We used community diversity as a surrogate for biological heterogeneity, and the diversity of naturally rare species in quarter degree squares as an indicator of differences in speciation/extinction histories across the study region. We then used standard statistical methods to analyse geographical and topographic patterns of these two measures. There was a clear geographical diversity pattern (richer in the west), while a topographic pattern (richer in mountains) was evident only in the west. The geographical boundary coincided with a transition from the reliable winter‐rainfall zone (west) to the less reliable non‐seasonal rainfall zone (east). Community diversity, or biological heterogeneity, showed no significant variation in relation to geography and topography. Diversity patterns of rare species mirrored the diversity pattern for all species. We hypothesize that regional diversity patterns are the product of different speciation and extinction histories, leading to different steady‐state diversities. Greater Pleistocene climatic stability in the west would have resulted in higher rates of speciation and lower rates of extinction than in the east, where for the most, Pleistocene climates would not have favoured Cape lineages. A more parsimonious hypothesis is that the more predictable seasonal rainfall of the west would have favoured non‐sprouting plants and that this, in turn, resulted in higher speciation and lower extinction rates. Both hypotheses are consistent with the higher incidence of rare species in the west, and higher levels of beta and gamma diversity there, associated with the turnover of species along environmental and geographical gradients, respectively. These rare species do not contribute to community patterns; hence, biological heterogeneity is uniform across the region. The weak topography pattern of diversity in the west arises from higher speciation rates and lower extinction rates in the topographically complex mountains, rather than from the influence of environmental heterogeneity on diversity.
Biotransformation in vitro of the 22R and 22S epimers of budesonide by human liver, bronchus, colonic mucosa and skin
Authors: Cortijo Julio , Urbieta Elena , Bort Roque , V.castell Jose , Ruiz‐Bravo Carlos , Martinez Jorge , Palacios‐Pelaez Ricardo , Lledó Salvador , Morcillo Esteban J.
Published: March 2003

The pharmacological effects of glucocorticoids are greatly influenced by their pharmacokinetic properties. In the present report, the in vitro biotransformation of the 22R and 22S epimers of the topical steroid budesonide was studied in the S‐9 fraction of human liver, bronchus, skin and colonic mucosa.

The disappearance of unchanged epimers of budesonide was measured during 90 min of incubation by high performance liquid chromatography. The rate of disappearance was high in human liver while little biotransformation occurred in bronchial tissue and colonic mucosa, and none was detected in the skin. A marked decay of the initial concentration of unchanged budesonide epimers was noticed after 2 h incubation in cultured human hepatocytes, while only a small decrease was observed after 24 h incubation in cultured human airway smooth muscle cells and BEAS‐2B cells. The 22R epimer of budesonide suffered greater in vitro biotransformation than the 22S epimer in human hepatic, bronchial and colonic tissues.

These findings extend those of other studies, and confirm that the high therapeutic ratio of budesonide is due to negligible local biotransformation combined with high level of liver metabolism for locally absorbed budesonide.
Cardiac cellular actions of hydrochlorothiazide
Authors: Galán Loipa , Ferrer Tania , Artiles Adriana , Talavera Karel , Salinas Eduardo , Orta Gerardo , García‐Barreto David , Alvarez Julio L.
Published: March 2003

In long term treatment, thiazide diuretics such as hydrochlorothiazide (HCTZ) lower blood pressure by decreasing peripheral resistance rather than by their diuretic effect. This action has been attributed to the opening of Ca2+‐activated K+ channels in vascular smooth muscle cells. However, little is known about their cardiac cellular actions. Here we investigated the possible actions of HCTZ on action potential and contraction of rat ventricular muscle strips and on the ionic currents of isolated rat ventricular cardiomyocytes. HCTZ depressed ventricular contraction with an IC30 of 1.85 μM (60% decrease at 100 μM). Action potential duration at −60 mV and maximal rate of depolarization were, however, only slightly decreased by 12% and 22%, respectively, at 100 μM. At the single cell level, HCTZ (100 μM) depressed the fast Na+ current (INa) and the L‐type Ca2+ current (ICaL) by 30% and 20%, respectively. The effects on ICaL were not voltage‐or frequency‐dependent. In cells intracellularly perfused with 50 μM cyclic adenosine, monophosphate HCTZ reduced ICaL by 33%. The transient (Ito), the delayed rectifier and the inward rectifier potassium currents were decreased by 20% at 100 μM HCTZ. The effects on Ito were voltage‐dependent. In conclusion, HCTZ at high concentrations possesses a negative inotropic action that could be in part due to its blocking action on INa and ICaL. The actions of HCTZ on multiple cardiac ionic currents could explain its weak effect on action potential duration.
Inhibition of rat parotid and submandibular gland functions by ofloxacin, a fluoroquinolone antibiotic
Authors: Abdollahi Mohammad , Isazadeh Zahra
Published: March 2003

While fluoroquinolones are widely used in the treatment of various infectious disease, not enough attention has been paid to their adverse effects on salivary glands functions. In the present study, the effects of ofloxacin, a fluoroquinolone antibiotic, on rat parotid and submandibular gland functions, were examined in an acute experiment. Ofloxacin (OFLX) was administered intraperitoneally at various doses (20, 40, and 80 mg/kg). Pure parotid and submandibular saliva were collected intraorally by microployethylene tubes under anaesthesia using a dissecting microscope. Flow rate, amylase activity, total protein, and calcium concentrations were reduced by all doses of OFLX (20, 40, 80 mg/kg, P < 0.01) in parotid saliva. In parotid saliva, sodium and potassium were increased by doses of 20 and 40 mg/kg (P < 0.01) and 20, 40, 80 mg/kg (P < 0.01) respectively. In submandibular saliva, flow rate, total protein and calcium concentrations were significantly reduced by all doses (20, 40, 80 mg/kg, P < 0.01). Sodium and potassium concentrations were also increased by a dose of 80 mg/kg, (P < 0.05) in submandibular saliva.

It is concluded that ofloxacin inhibits rat salivary gland functions, which might be observed as a side‐effect in humans. Properties of fluoroquinolones to alter intracellular cAMP and calcium levels and their ability to suppress DNA, RNA and protein synthesis of acinar cells might be possible reasons for the observed changes.
Wine polyphenols modulate calcium handling in rat aorta: involvement of nitric oxide pathway
Authors: Diebolt Myriam , Andriantsitohaina Ramaroson
Published: March 2003

The effects of short‐term oral administration of red wine polyphenolic compounds (RWPCs) on blood pressure and vascular reactivity were investigated in rats. The consequence of RWPCs treatment on agonist‐induced contractility of rat aorta with respect to Ca2+ handling was assessed, by examining both intracellular Ca2+ store and extracellular Ca2+ influx components of the response.

Rats were treated daily for 7 days by intragastric administration of either 5% glucose, or RWPCs (20 mg/kg) [from two different sources, i.e. Provinols (SFD, Vallont Pont d'Arc, France) and RWPC1 (INRA, Montpellier, France)]. Administration of these compounds produced a decrease in systolic blood pressure. The consequence of RWPCs treatment on vascular smooth muscle was investigated in rat aorta without endothelium exposed to noradrenaline. In Ca2+‐free medium, RWPC1 but not Provinols treatment induced an increase in noradrenaline‐induced contraction. After depletion of intracellular Ca2+ stores by noradrenaline in Ca2+‐free medium, addition of CaCl2 in the continuous presence of agonist induced an increase in contraction, which was not significantly different between control, Provinols‐ and RWPC‐treated rats. The presence of an inhibitor of sarcoplasmic reticulum Ca2+‐ATPase, thapsigargin, significantly reduced noradrenaline‐induced contraction in Ca2+‐free medium in RWPCs‐treated aorta, as compared to that of control. Interestingly, the inhibitory effect of thapsigargin on the response linked to the release of Ca2+ from internal stores in RWPCs‐treated vessels was completely prevented in the presence of NO‐synthase inhibitor, L‐nitro arginine methyl ester, the inhibitor of guanylyl cyclase, oxadiazoloquinoxaline or the protein kinase G inhibitor, 8‐Bromoguanosine‐3′‐5‐cyclic monophosphorothioate, Rp isomer.

These results suggest that short‐term administration of RWPCs in rats induced subtle alteration of thapsigargin‐sensitive component of agonist‐induced contraction in rat aorta linked to Ca2+ release from intracellular store. Calcium release from intracellular stores sensitive to thapsigargin was implicated in this mechanism. The prevention of the inhibitory effect of thapsigargin by the inhibitors of NO/cyclic guanosine monophosphate pathway after RWPCs treatment highlights the role of NO in this phenomenon.
Drug‐induced prolongation of the QT interval: why the regulatory concern?
Authors: Shah Rashmi R.
Published: March 2003

The views expressed in this paper are those of the author and do not necessarily represent the views or the opinions of Medicines Control Agency, other regulatory authorities or any of their advisory committees.
Safety pharmacology – a progressive approach
Authors: Redfern William S. , Wakefield Ian D. , Prior Helen , Pollard Christopher E. , Hammond Timothy G. , Valentin Jean‐Pierre
Published: March 2003

Although deaths and life‐threatening adverse drug reactions (ADRs) in Phase I clinical trials are extremely rare, less severe ADRs occur with an incidence of over 13%. Of the candidate drugs (CDs) that fail prior to marketing, it is generally acknowledged that about 1 in 5 do so because of ADRs in the clinic. Once new chemical entities (NCEs) are on the market, ADRs are estimated to be the fourth leading cause of death in the USA. These various statistics indicate that there is room for improvement in preclinical safety assessment, and a smarter approach to safety pharmacology (SP) can contribute to this. Rather than `bundling' the SP studies together just prior to Phase I trials, a step‐wise, streamlined approach can be adopted throughout the drug discovery process. In this way, the SP information can contribute to making informed judgements at each milestone throughout the preclinical drug discovery process: (i) to assist in series and compound selection; (ii) to assess potential risk of failure in the clinic due to ADRs; (iii) to predict potential ADRs that the clinical pharmacologists can focus on; (iv) to define a therapeutic window for acute dosing in humans. To achieve these objectives, the SP tests need to be carefully selected, adequately validated in‐house, and be robust and reliable. To achieve (ii) above, outcome criteria have to be set which, for each test (in vitro and in vivo), take into account acceptable safety margins for the particular therapeutic target. Thus, highly sensitive and predictive SP tests positioned strategically and as early as possible should contribute to reducing attrition during clinical development and ultimately to marketing safer medicines more rapidly.
The internal jugular vein valve may have a significant role in the prevention of venous reflux: evidence from live and cadaveric human subjects
Authors: Silva M. A. , Deen K. I. , Fernando D. J. S. , Sheriffdeen A. H.
Published: March 2003

Introduction: The internal jugular vein valve (IJVV), which is situated just above the termination of the internal jugular vein, is the only valve between the heart and the brain. This means that it plays a role in the prevention of cephalad flow of venous blood. If the IJVV is damaged or becomes incompetent, increase in intrapleural pressure could result in raised intracranial pressure. Additionally, the jugular venous pulse (JVP) is used clinically to estimate right atrial pressure, a functional IJVV may prevent accurate estimation of the JVP.

Objectives: To describe the presence and the competence of the IJVV in post‐mortem and live human subjects.

Design – setting and methods: The anatomical appearance of the IJVV from 30 cadavers was studied. Competence was checked by measuring maximum hydrostatic pressure before reflux occurred through the valve. The function of the valve was evaluated in 25 live subjects using colour duplex scanning.

Results: The IJVV was present in all cadavers just before its termination (60 IJVVs from 30 subjects). The valve was bicuspid in most cases (93%). The competence of 41 IJVVs was checked of which only three (7%) were found to be incompetent. All IJVVs in live subjects were found to be competent.

Conclusion: This study confirms that a functional IJVV is present just above the termination of the internal jugular vein. The IJVV may therefore prevent reflux of venous blood from the right atrium into the internal jugular vein.
Influence of work rate on the determinants of oxygen deficit during short‐term submaximal exercise: implications for clinical research*
Authors: Reybrouck Tony , Defoor Johan , Bijnens Bart , Mertens Luc , Gewillig Marc
Published: March 2003

Objective: The effect of increasing work rate was studied on the determinants of the oxygen deficit.

Methods: Exercise testing was performed on a treadmill and gas exchange was measured on a breath‐by‐breath basis. Eleven healthy subjects, aged 18–25 years, performed three square wave exercise tests of different intensity. Before exercise, gas exchange was measured at rest in the standing position for 3 min, followed by a 6‐min square wave exercise test, randomly assigned at 4, 8 or 12% inclination. Immediately after exercise the recovery gas exchange was determined for 3 min. To calculate oxygen deficit, the oxygen uptake (O2) values at onset of exercise were subtracted from the steady‐state value, the differences were cumulated and expressed as a percentage of the total oxygen cost for the 6‐min exercise.

Results: The oxygen deficit increased significantly (P<0·001) with increasing work rate (6·1 ± 1·4% for 4%, 8·4 ± 2·1% for 8% and 9·4 ± 1·7% at 12% inclination). This resulted from a somewhat slower increase of O2 at the onset of exercise at the highest work rate, reflected by a significantly higher time constant for O2 at 8 and 12% (24·6 ± 7·3 s at 8% and 24·1 ± 6·3 s at 12% versus 20·2 ± 8·1 s at 4%). More importantly a significantly higher steady‐state value for O2 was found at the highest exercise level, compared with the other exercise intensities.

Conclusion: The higher oxygen deficit at the highest level of exercise is determined by a slower time constant and a higher asymptote value for O2.
World‐Wide Species Richness Patterns of Tiger Beetles (Coleoptera: Cicindelidae): Indicator Taxon for Biodiversity and Conservation Studies
Authors: Pearson David L. , Cassola Fabio
Published: March 2003

The family of tiger beetles (Cicindelidae) is an appropriate indicator taxon for determining regional patterns of biodiversity because (1) its taxonomy is stabilized; (2) its biology and general life history are well understood, (3) individuals are readily observed and manipulated in the field, (4) the family occurs world‐wide and in a broad range of habitat types; (5) each species tends to be specialized within a narrow habitat; (6) patterns of species richness are highly correlated with those of other vertebrate and invertebrate taxa; and (7) the taxon includes species of potential economic importance. Logistical advantages provide some of the strongest arguments for selecting tiger beetles as an appropriate indicator taxon. Species numbers of tiger beetles are relatively well known for 129 countries. Eight countries alone account for more than half the world total of 2028 known species. Species numbers are also indicated for eleven biogeographical zones of the world. For gridded squares across North America, the Indian subcontinent, and Australia, species richness of tiger beetles, birds, and butterflies shows significant positive correlations. However, tiger beetle species numbers can be reliably determined within fifty hours on a single site, compared to months or years for birds or butterflies, and the advantage of using tiger beetles in conservation biology is evident
Recent Invasions of the Gulf of Maine: Three Contrasting Ecological Histories
Authors: Berman Jody , Harris Larry , Lambert Walter , Buttrick Melanie , Dufresne Michael
Published: March 2003

Introduced species are common members of estuarine communities where their role as competitors and predators is of concern, This paper examines the invasion of Gulf of Maine benthic habitats by the ecologically similar alien invertebrates Styela clava, Botrylloides diegensis, and Membranipora membranacea.

Styela clava increased slowly in abundance at study sites in Beverly, Massachusetts and Portsmouth, New Hampshire. We found no evidence of competitive dominance by S. clava, even though it is the competitive dominant in similar habitats elsewhere. Botrylloides diegensis rapidly became a dominant species after its arrival in the Great Bay Estuary, but this dominance was short‐lived. B. diegensis persists in the estuary as an early colonist of primary space and as an epibiont on secondary substrates in established communities. Membranipora membranacea became the dominant epiphyte on laminarian kelps within two years. Although M. membranacea overgrew the native epiphytes Obelia geniculata and Electra pilosa in the overwhelming majority of encounters these native species are more common on other algal hosts. Therefore, competitive dominance is not likely a factor in the successful invasion of the Gulf of Maine by M. membranacea.

These species provide evidence for opposing views of the role of competition in mediating community invasion. We show that ecological similarity among species is not an accurate criterion to predict either the mechanism of invasion or the means of persistence. In addition, these data indicate that biological invasions must be examined on broad spatial and temporal scales; short‐term or narrowly focused studies can lead to incorrect conclusions.
The Species Problem and Conservation: What are We Protecting?
Authors: ROJAS MARTHA
Published: March 2003

Abstract: Although conservation biologists base most of their activities on species taxa, they have participated little in the debate of systematists and evolutionary biologists about the recognition and nature of species. It is clear from this debate that there is no agreement on what species are, how they should be delimited, or what they represent. But in conservation science, and particularly in the selection, design and management of protected areas, species are either treated as types or as evolutionary units. A typological view of species may lead to a failure to protect the real diversity of life in the long term, if conservation priorities are set on the basis of species numbers or on circumscriptions of endangered, threatened, or endemic species taxa that result from the use of different species concepts. Considering species as typological entities may also lead workers to disregard geographic variation and to neglect the problem of deciding which level of variability to protect. It may even affect the goal of maintaining the evolutionary potential of organisms, if the focus is placed on the preservation of a sample of the existing types in populations that will persist as little changed as possible. When species are considered as evolutionary units, attention is shifted from the level of species to that of populations and metapopulations. Problems may still arise if these populations are considered in the context of species taxa, particularly if their composition is managed or if indicator species are used. A closer interaction between systematists and conservation biologists is suggested. Although the pressures of time and the difficulties faced by conservation biologists cannot be denied, considering the species problem more critically may result in recognizing the limitations of the taxonomic information used; it may also contribute to the refinement of the concepts and methods involved in their activities, making them more congruent with the nature of biological diversity.
Alien Flora in Grasslands Adjacent to Road and Trail Corridors in Glacier National Park, Montana (U.S.A.)
Authors: TYSER ROBIN W. , WORLEY CHRISTOPHER A.
Published: March 2003

Abstract: Alien plant species have rapidly invaded and successfully displaced native species in many grasslands of western North America. Thus, the status of alien species in the nature reserve grasslands of this region warrants special attention. This study describes alien flora in nine fescue grassland study sites adjacent to three types of transportation corridors—primary roads, secondary roads, and backcountry trails—in Glacier National Park, Montana (U.S.A.). Parallel transects, placed at varying distances from the adjacent road or trail, were used to determine alien species richness and frequency at individual study sites. Fifteen alien species were recorded, two Eurasian grasses, Phleum pratense and Poa pratensis, being particularly common in most of the study sites. In sites adjacent to primary and secondary roads, alien species richness declined out to the most distant transect, suggesting that alien species are successfully invading grasslands from the roadside area. In study sites adjacent to backcountry trails, absence of a comparable decline and unexpectedly high levels of alien species richness 100 m from the trailside suggest that alien species have been introduced in off‐trail areas. The results of this study imply that in spite of low levels of livestock grazing and other anthropogenic disturbances, fescue grasslands in nature reserves of this region are vulnerable to invasion by alien flora. Given the prominent role that roadsides play in the establishment and dispersal of alien flora, road construction should be viewed from a biological, rather than an engineering, perspective. Nature reserve man agers should establish effective roadside vegetation management programs that include monitoring, quickly treating keystone alien species upon their initial occurrence in nature reserves, and creating buffer zones on roadside leading to nature reserves.