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Objective: To characterize dropouts from type-2 diabetes (T2D) care in communal primary health care., Design: An observational study., Setting: In a Finnish city, patients with T2D who had not contacted the public primary health care system during the past 12 months were identified with a computer based search and contacted by a trained diabetes nurse., Subjects: Dropouts from T2D treatment., Main Outcome Measures: Demographic factors, laboratory parameters, examinations, medications, and comorbidities., Results: Of the patients with T2D, 10% (n = 356) were dropouts and 60% of them were men. Median HbA1c was 6.5 (QR for 25% and 75%: 6.0, 7.7) %, (45 [42,61] mmol/mol). Of the dropouts, 14% had HbA1c ≥ 9.0% (75 mmol/mol), and these patients were younger than the other dropouts (mean age 54.4 [SD 10.8] years vs. 60.6 [9.4] years, p < 0.001). Median low-density lipoprotein (LDL) cholesterol level was 2.8 (QR 2.1, 3.4) mmol/l. Median systolic blood pressure (BP) was 142 (QR 130, 160) mm Hg. Median diastolic BP was 86 (78, 94) mm Hg. Of the dropouts, 83% had comorbidities and 62% were prescribed metformin as a treatment., Conclusions: Ten percent of T2D patients were dropouts of whom those with a poor glycaemic control were younger than the other dropouts. BP and LDL cholesterol concentrations were non-optimal among the majority of the dropouts. Metformin was prescribed less frequently to the dropouts than is usual for T2D patients. The comorbidities were equally common among the dropouts as among the other T2D patients. KEY POINTS   Which kinds of patients are dropouts from type-2 diabetes care is not known. • One-tenth of the patients with T2D were dropouts and they generally had good glycaemic control. • Blood pressure and LDL cholesterol concentrations were non-optimal among the majority of the dropouts. • Fourteen percent of these dropouts had HbA1c > 9% (75 mmol/mol) and they were more often younger than the other dropouts.

Background: Alcohol use among emergency patients has been studied earlier, but the data regarding alcohol use especially among critically ill and injured patients treated in the prehospital setting is scarce. The aim of this study was to evaluate the incidence of alcohol use and the characteristics of cases attended by a physician staffed mobile intensive care unit (MICU)., Findings: During a 2 month period, exhaled air alcohol concentration-measured as a part of routine patient examination in all adolescent and adult patients treated by the MICU-was recorded. The MICU encountered 258 patients, of which 82 could be tested for alcohol use. Of the tested patients 43 % gave a positive breath test result. Proportion of male patients providing a positive result in the breath test did not differ significantly those of women. The primary reason for not to test the patient was a decreased level of consciousness in one-fifth of the initial 258 patients., Conclusions: A significant proportion (47 %) of the encountered patients could not be tested due to their critical condition. Alcohol use was observed in 43 % of those capable of providing a breath test sample. The rate of positive tests seemed to be higher than those reported from emergency departments. Novel diagnostic methods to detect alcohol consumption in non-cooperative patients are warranted.

Background: To reduce physicians' inappropriate laboratory requests for their patients, administrators have used methods such as modifying a laboratory request order form with an agreed requesting protocol for the most common diagnoses in primary health care., Objective: To study the effects of removing the erythrocyte sedimentation rate (ESR) and aspartate transaminase (AST) which are considered of limited clinical value for primary care clinical decision-making from a computerized laboratory test order form. These tests were removed to another new view from the electronic laboratory menu where the physicians, instead of just ticking the desired test from the list, had to do 4-8s extra work by writing down the abbreviation to order the test., Methods: An observational controlled prospective study based on a before-after design was performed by removing AST and ES from the laboratory test order form of the computerized laboratory system for all primary care in the city of Helsinki, Finland. The numbers of annual and monthly use of AST and ESR and their controls, alanine transaminase (ALT) and C-reactive protein (CRP) ordered by General practitioners (GPs) was recorded over an eight-year period: four years before and a four years after the removal of AST and ES., Results: Removing AST and ESR from the computerized laboratory test order form decreased their use by up to 90%, whereas the use of the control tests increased throughout the follow-up period. The variation in use of these removed tests also decreased., Conclusion: Removing a laboratory test from a computerized laboratory test order form may significantly reduce GPs' use of the laboratory test. Further studies are needed, however, to ensure the safety of this type of intervention., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: In primary care, financial incentives have usually been directed to physicians because they are thought to make the key decisions in order to change the functions of a medical organization. There are no studies regarding the impact that directing these incentives to all disciplines of the care team (e.g. group bonuses for both nurses and doctors) may have, despite the low frequency with which diagnoses were being recorded for primary care visits to doctors. This study tested the effect of offering group bonuses to the care teams., Methods: This was a retrospective quasi-experimental study with before-and-after settings and two control groups. In the intervention group, the mean percentage of visits to a doctor for which a diagnosis was recorded by each individual care team (mean team-based percentage of monthly visits to a doctor with recorded diagnoses) and simultaneously the same data was gathered from two different primary care settings where no team bonuses were applied. To study the sustainability of changes obtained with the group bonuses the respective data were derived from the electronic health record system for 2 years after the cessation of the intervention. The differences in the rate of marking diagnoses was analyzed with ANOVA and RM-ANOVA with appropriate post hoc tests, and the differences in the rate of change in marking diagnoses was analyzed with linear regression followed by t-test., Results: The proportion of doctor visits having recorded diagnoses in the teams was about 55 % before starting to use group bonuses and 90 % after this intervention. There was no such increase in control units. The effect of the intervention weakened slightly after cessation of the group bonuses., Conclusion: Group bonuses may provide a method to alter clinical practices in primary care. However, sustainability of these interventions may diminish after ceasing this type of financial incentive.

Objective: To study the effects of applying an emergency department (ED) triage system, combined with extensive publicity in local media about the "right" use of emergency services, on the division of work between ED nurses and general practitioners (GPs)., Design: An observational and quasi-experimental study based on before-after comparisons., Setting: Implementation of the ABCDE triage system in a Finnish combined ED where secondary care is adjacent, and in a traditional primary care ED where secondary care is located elsewhere., Subjects: GPs and nurses from two different primary care EDs., Main Outcome Measures: Numbers of monthly visits to different professional groups before and after intervention in the studied primary care EDs and numbers of monthly visits to doctors in the local secondary care ED., Results: The beginning of the triage process increased temporarily the number of independent consultations and patient record entries by ED nurses in both types of studied primary care EDs and reduced the number of patient visits to a doctor compared with previous years but had no effect on doctor visits in the adjacent secondary care ED. No further decrease in the number of nurse or GP visits was observed by inhibiting the entrance of non-urgent patients., Conclusion: The ABCDE triage system combined with public guidance may reduce non-urgent patient visits to doctors in different kinds of primary care EDs without increasing visits in the secondary care ED. However, the additional work to implement the ABCDE system is mainly directed to nurses, which may pose a challenge for staffing.

Patients' limited literacy and language fluency of different kinds cause them problems in navigating the medical interview. However, it is not known how physicians' native language skills affect the reported intensity of pain among Finnish emergency patients. Data were collected with two consecutive questionnaires in 16 healthcare centres and outpatient departments along the Finnish coast. Swedish and Finnish speaking 18-65-year-old emergency patients were eligible for this study. Our patients were predominantly Finnish speakers. Patient-rated poor language skills in Finnish among the physicians in ED setting increased statistically significantly pain reported by the Finnish speaking patients and their dissatisfaction with the health service. These patients were also less motivated to adhere to the instructions given by their physician. Patients speaking various languages reported less degree of pain. Foreign physicians' poor language proficiency in Finnish was expected to explain only some of the patients' pain experience. Physicians' good native language skills may help to reduce pain experience. Despite concordant language communication, other unknown barriers in the interaction might reduce the magnitude of pain reported.

Specific language impairment is associated with enduring problems in language-related functions. We followed the spatiotemporal course of cortical activation in SLI using magnetoencephalography. In the experiment, children with normal and impaired language development heard spoken real words and pseudowords presented only once or two times in a row. In typically developing children, the activation in the bilateral superior temporal cortices was attenuated to the second presentation of the same word. In SLI children, this repetition effect was nearly nonexistent in the left hemisphere. Furthermore, the activation was equally strong to words and pseudowords in SLI children whereas in the typically developing children the left hemisphere activation persisted longer for pseudowords than words. Our results indicate that the short-term maintenance of linguistic activation that underlies spoken word recognition is defective in SLI particularly in the left language-dominant hemisphere. The unusually rapid decay of speech-evoked activation can contribute to impaired vocabulary growth., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To evaluate the ability of language tests to identify children with specific language impairment (SLI) in primary health care. All the language tests presently in clinical use in Finland were applied., Method: All the children with SLI living in one city in Finland constituted the cohort. Test scores were collected from 83 subjects drawn from a birth cohort of 4,553 children. Finally 31 case-control pairs were studied. All SLI diagnoses were set in secondary health care. Test scores of 14 language tests were examined that, together with subtests, included 39 different tasks., Results: Out of 39 performed tests, the difference in test scores between children with SLI and their matched controls was statistically significant in 26 tests. A group of six tests had good sensitivity and moderate specificity for SLI diagnosis and they correctly classified children with SLI to either F80.1 or F80.2 diagnosis category., Conclusion: The results suggest that most of the language tests in Finnish identify children with SLI and, furthermore, that these tests identify language deficits that are consistent with those found in other studies. More studies with larger age-matched populations are needed., (Copyright © 2013 S. Karger AG, Basel.)

Objectives: To investigate the effect of dog and cat contacts on the frequency of respiratory symptoms and infections during the first year of life., Methods: In this birth cohort study, 397 children were followed up from pregnancy onward, and the frequency of respiratory symptoms and infections together with information about dog and cat contacts during the first year of life were reported by using weekly diaries and a questionnaire at the age of 1 year. All the children were born in eastern or middle Finland between September 2002 and May 2005., Results: In multivariate analysis, children having dogs at home were healthier (ie, had fewer respiratory tract symptoms or infections) than children with no dog contacts (adjusted odds ratio, [aOR]: 1.31; 95% confidence interval [CI]: 1.13-1.52). Furthermore, children having dog contacts at home had less frequent otitis (aOR: 0.56; 95% CI: 0.38-0.81) and tended to need fewer courses of antibiotics (aOR: 0.71; 95% CI: 0.52-0.96) than children without such contacts. In univariate analysis, both the weekly amount of contact with dogs and cats and the average yearly amount of contact were associated with decreased respiratory infectious disease morbidity., Conclusions: These results suggest that dog contacts may have a protective effect on respiratory tract infections during the first year of life. Our findings support the theory that during the first year of life, animal contacts are important, possibly leading to better resistance to infectious respiratory illnesses during childhood.

Background: We studied whether it is possible to predict severity of pain during medical abortion. We also studied how well medical staff recognizes the pain perceived by these women., Study Design: Fifty-four women (mean age 26 years, range 18-42 years) undergoing medical abortion before the 64th day of gestation (mean 47 days, range 32-63 days) were asked to estimate their menstrual pain and the pain perceived during medical abortion by visual analogue scale (VAS). Both the intensity and unpleasantness of pain were evaluated separately. The nurses observing the women undergoing medical abortion at the outpatient clinic were asked to estimate by VAS scores their perception of the intensity of pain of the women., Results: Higher age (magnitude r = -0.30; unpleasantness r = -0.28), increasing number of previous pregnancies (r = -0.34; r = -0.36) and deliveries (r = -0.57; r = -0.60) correlated negatively and advanced gestational length (r = 0.31; r = 0.32) positively with magnitude and unpleasantness of pain evoked by abortion. Twenty-eight (51.8%) of the women were nulliparous. Pain during medical abortion correlates positively (magnitude r = 0.34; unpleasantness r = .0.41) with pain during menstruation. There was no difference between either the intensity or unpleasantness of pain during menstruation and pain during medical abortion. Medical staff accurately assessed the pain women experienced during medication abortion (magnitude r = 0.83; unpleasantness r = 0.79)., Conclusion: Pain during medical abortion correlates with the pain during menstruation. This finding makes counseling of women choosing medical abortion easier and helps in planning the pain relief needed., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background and aims Medical abortion is often performed at outpatient clinics or gynaecological wards. Yet, some women may stay at home during medical abortion. Pain has been reported to be one of the main side effects of the procedure. Methods We studied whether perceived abortion pain was related to the subjectively evaluated ability to stay at home during medical abortion. The size of the study group was 29 women. We also studied how well these women remembered the intensity and unpleasantness of the abortion pain in a control visit performed 3-6 weeks after abortion. Results Especially, the unpleasantness associated with the pain during abortion was an important predictor when women evaluated their ability to stay at home during medical abortion. In those women who might have been able to stay at home in their own view, midwives looking after these women at the outpatient clinic estimated the pain intensity and unpleasantness also about 50% lower than in those who were not able to stay home in their own view. There were no significant differences in intensity, unpleasantness in hindsight of menstruation pain, or the area of this pain in the pain drawings in those women who considered that they might have stayed at home during medical abortion when compared with those who did not. No difference was found in age, gestational age, magnitude of previous pregnancies, miscarriages, vaginal deliveries, induced abortions, Beck's Depression Index (BDI), Beck's Anxiety Index (BAI) or AUDIT scores between those who could have stayed at home or those who would not have been able to stay at home during abortion. Components of abortion pain decreased significantly during the second post-abortion day. The more deliveries the subject had experienced the less pain she had during abortion. Multiparous women reported less than a fourth of the pain magnitude of the nulliparous women during abortion. Parity explained both intensity and unpleasantness of abortion pain better than the expected ability to stay at home. The remembrance of the intensity or unpleasantness of abortion pain correlated with actual pain reported at the time of abortion. However, this remembrance did not correlate with the ability to stay at home during the medical abortion. Conclusions The unpleasantness of pain during and immediately after abortion was recalled, not as a measure of the pain itself, but as a deciding factor in their judgement of whether or not they would be able to undergo medical abortion at home. Abortion pain is an important factor in enhancing home-based management of medical abortions. Medical staff may be able to detect those women who do not cope at home during the process by observing the intensity of pain. Therefore, proper treatment of pain might reduce the need for hospital-based medical abortions. Implications These patients need better care and guidelines for the care of women undergoing medical abortions should include clear recommendations for analgesic treatments, at the least adequate doses of nonopioid analgesics such as paracetamol in combination with NSAIDs like ibuprofen or diclofenac.

Background: The volume of emails is rising rapidly everywhere. However, there is no data available concerning how primary healthcare physicians feel about the use of email communication between themselves, with their managers and with other people contacting them., Objective: The objective of this study was to find out what the attitudes of primary care physicians are towards email at work., Methods: The use of email was studied among a convenience sample of primary healthcare physicians., Results: Physicians thought that email was a good instrument for delivering information but not as an instrument for leadership. Physicians in lead positions thought more often than ordinary general practitioners (GPs) that email is good for information. The leaders used email more actively than other GPs. The contents of the emails received by the GPs differed depending on the site of work. The total number of emails was higher in urban areas than in rural areas. Emails relating to administration, educational information and meeting materials were more often sent in rural than in urban primary healthcare settings. Information about daily work arrangements and about social events were more frequently emailed in urban than in rural surroundings. Email was considered important for information inside the system but a somewhat difficult tool for discussing complicated subjects. Generally, it was agreed that there was some unimportant information filtering through this medium to the target GPs. GPs were uncertain whether important data reached everybody who needed it or not. Still, almost everybody used the email system regularly and the use of it was considered relatively easy. GPs were generally prone to adopt advice and instructions given via email and implemented those in their working routines. The use of the email system was related to technical ability to use the system. The easier the GP thought that the email system was the more he used it. Rural GPs were more critical in applying advice shared via email than their counterparts in urban areas. In general, physicians thought that email was a good method for reaching many people at the same time. However, the main points of the messages may be missed and the whole email may sometimes not be read., Conclusion: Especially during periods of change in the workplace, it is very important that management is conducted personally. Care must be taken so that disinformation does not spoil the informative value of email in the administration of primary health care. The needed technical assistance should be given to everyone in order to get the best advantage from the use of the email system.

Desorption atmospheric pressure photoionization (DAPPI) is an ambient ionization technique for mass spectrometry (MS) that can be used to ionize polar as well as neutral and completely non-polar analytes. In this study polydimethylsiloxane (PDMS) was used as a solid phase extraction sorbent for DAPPI-MS analysis. Pieces of PDMS polymer were soaked in an aqueous sample, where the analytes were sorbed from the sample solution to PDMS. After this, the extracted analytes were desorbed directly from the polymer by the hot DAPPI spray solvent plume, without an elution step. Swelling and extracting the PDMS with a cleaning solvent prior to extraction diminished the high background in the DAPPI mass spectrum caused by PDMS oligomers. Acetone, hexane, pentane, toluene, diisopropylamine and triethylamine were tested for this purpose. The amines were most efficient in reducing the PDMS background, but they also suppressed the signals of low proton affinity analytes. Toluene was chosen as the optimum cleaning solvent, since it reduced the PDMS background efficiently and gave intensive signals of most of the studied analytes. The effects of DAPPI spray solvents toluene, acetone and anisole on the PDMS background and the ionization of analytes were also compared and extraction conditions were optimized. Anisole gave a low background for native PDMS, but toluene ionized the widest range of analytes. Analysis of verapamil, testosterone and anthracene from purified, spiked wastewater was performed to demonstrate that the method is suited for in-situ analysis of water streams. In addition, urine spiked with several analytes was analyzed by the PDMS method and compared to the conventional DAPPI procedure, where sample droplets are applied on PMMA surface. With the PDMS method the background ion signals caused by the urine matrix were lower, the S/N ratios of analytes were 2-10 times higher, and testosterone, anthracene and benzo[a]pyrene that were not detected from PMMA in urine, were observed in the MS spectrum., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background and aims Social factors and social environment shape the pain behavior of patients. Social workers support pain treatment in a multidisciplinary pain clinic by altering the social environment of a patient. Even though a social worker in a multi-professional care team contributes to the care of select, severely pain-afflicted patients extensively, neither the patient socio-demographic status nor interventions by social workers have been systematically documented. Only individual case histories have been published. Developing social work activities, which have potential financial consequences, for example, requires charting the current situation prior to systematic research into the efficacy of individual social work interventions. Methods This study systematically details the performance and work volume of the social worker, as well as the socio-demographics of patients during a 16-month period in a multidisciplinary pain clinic of a university hospital. Results Fifty-five patients were included. Twenty-nine were women and 26 men. They were about 10% of all patients seen at the pain clinic during the same time. Most of the patients were at their middle age. The largest group of subjects worked in public or other services. The second largest group consisted of those working in stores, hotels and restaurants. Over half of the subjects worked in the service industry. Since the subjects had scant vocational education, they worked mainly in manual labor. Most of the patients had problems with making a living, signifying that a major number of the patients visited the social worker because of financial problems. About half of the patients were indebt and three were undergoing debt counseling. Of homeowners, 21% were indebt, while the portion of those living rented accommodation was almost two thirds. All patients seen by the social worker received some form of public assistance. Over half of the patients had participated in rehabilitation assessment. The social worker saw 39 patients once, one patient twice and 15 patients three or more times. The duration of a visit was typically 1-2 h. The issues of a patient are addressed by contacting authorities and negotiating with other health care staff. According to the used 'SOSU' classification data, the social situation was charted for 49 patients, while the benefits and assistance provided by the Social Insurance Institution of Finland was discussed with half of the patients. The social worker discussed employment based pension with about a third of the patients. Social assistance, the last-resort economic assistance under social welfare, was considered with one fifth of the patients. Psychosocial work was recorded for 19 patients, comprising longer-term, supportive discussion. Conclusions The majority of the patients is of active working age but their working capacity is often decreased. However, they have difficulties in getting compensation for reduced ability to making a living. Hence, they have economic difficulties of various types and need counselling and support. The main duty of the social worker appeared to be advising the patient in using the social welfare system, as the clients turned out to constitute a marginalized group.

Background and aims As far as we know, the range of issues particular to social work, when working with clients at a pain clinic has not been previously researched. Methods A retrospective study of referrals at the multidisciplinary Pain Clinic of Helsinki University Central Hospital was conducted based on medical records, focusing on pain conditions, treatments and patient flow. Variables used were age, gender, pain conditions, treatment interventions, pain duration and intensity, disruption in everyday life due to pain, psychiatric co-morbidities, referrals, outside care providers, post-treatment care and health habits. Referrals were made mainly by other HUCH units or municipal health centers. Results The median age of patients (n = 55) was 44 years. The majority of patients were referred to the pain clinic by municipal health centers. Almost similar number of patients was referred by other HUCH clinics. The largest disease group was musculoskeletal diseases, afflicting 25 patients. Almost the same number of patients (22) suffered from neurological and sensory nervous system diseases. Three patients suffered from persistent somatoform pain disorder and five patients did not fall into any of these categories. Pharmacotherapy was the most prevalent treatment method at the pain clinic, and it was prescribed to all patients. The post-treatment care of the patients was mainly provided by primary health care services. Duration of pain was more than 3 years in more than 60% of the patients. There was a considerable lack of information about pain intensity in the patient files. For the majority of patients, pain caused difficulty in movement, housework, recreation, and sleeping. Patients referred to the pain clinic's social worker had not benefited greatly from previous interventions. More than half of the patients had received psychiatric consultation either at the pain clinic or in some other setting. Most often the patients had been diagnosed to suffer from depression by a psychiatrist. Over a third of the patients had reported suicidal intents to the hospital staff. Conclusions The pain situation of patients was severe, in terms of intensity and disability. Treatment was primarily based on drug therapy, and patients generally continued treatment in outpatient services. Depression and substance abuse were common; a third had experienced suicidal intent. By searching for symptoms, the social worker pays attention to signs of depression at the clinic. Co-operation with social workers in outpatient services is also critical for social after-care. This requires that the social worker of a pain center has an excellent and practical knowledge of the social welfare and service systems.

Background: Many Finnish emergency departments (ED) serve both primary and secondary health care patients and are therefore referred to as combined emergency departments. Primary care specialists are responsible for the initial assessment and treatment. They, thereby, also regulate referral and access to tertiary care. Primary health care EDs are easy for the public to access, leading to non-acute patient visits to the emergency department. This has caused increased queues and unnecessary difficulties in providing immediate treatment for those patients who need it the most., Methods: A face-to-face triage system based on the letters A (patient directly to secondary care), B (to be examined within 10 min), C (to be examined within 1 h), D (to be examined within 2 h) and E (no need for immediate treatment) for assessing the urgency of patients' treatment needs was applied in the main ED in the City of Vantaa, Finland (Peijas Hospital) as an attempt to provide immediate treatment for the most acute patients. The first step was an initial patient assessment by a health care professional (triage nurse). If the patient was not considered to be in need of immediate care (i.e. A-D) he was allocated to group E and examined after the more urgent patients were treated. The introduction of this triage system was combined with information to the public on the "correct" use of emergency services. The primary aim of this study was to assess whether the flow of patients was changed by implementing the ABCDE-triage system in the combined ED. To study the effect of the intervention on patient flow, numbers monthly visits to doctors were recorded before and after intervention in Peijas ED and, simultaneously, in control EDs (Myyrmäki in Vantaa, Jorvi and Puolarmetsä in Espoo). To study does the implementation of the triage system redirect patients to other health services, numbers of monthly visits to doctors were also scored in the private health care and public office hour services of Vantaa primary care., Results: The number of patient visits to a primary care doctor in 2004 decreased by up to eight percent (340 visits/month) as compared to the previous year in the Peijas ED after implementation of the ABCDE-triage system. Simultaneously, doctor visits in tertiary health care ED increased by ten percent (125 visits/month). ABCDE-triage was not associated with a subsequent increase in the number of patient visits in the private health care or office hour services. The number of ED visits in the City of Espoo, used as a control where no triage was applied, remained unchanged., Conclusions: The present ABCDE-triage system combined with public guidance may reduce patient visits to primary health care EDs but not to the tertiary health care EDs.

Management of patients presenting with chronic pain is a common problem in primary care. Essentially, the classification of chronic pain falls into 3 broad categories: (1) pain owing to tissue disease or damage (nociceptive pain), (2) pain caused by somatosensory system disease or damage (neuropathic pain), and (3) pain without a known somatic background. Key challenges in developing a targeted holistic approach to treatment include appropriate diagnosis of the cause or causes of pain; identifying the type of pain and assessing the relative importance of its various components; and determining appropriate treatment. In clinical examination, sensory abnormalities are the crucial findings leading to a diagnosis of neuropathic pain, for which pharmacotherapy with antidepressants and anticonvulsants represents the cornerstone of medical treatment. Chronic neuropathic pain is underrecognized and undertreated, yet primary care physicians are uniquely placed on the frontlines of patient management, where they can play a pivotal role in treatment and prevention through diagnosis, therapy, follow-up, and referral. This review provides guidance in understanding and identifying the neuropathic contribution to pain presenting in primary care; assessing its severity through patient history, physical examination, and appropriate diagnostic tests; and establishing a rational treatment plan.

Background: The increasing prevalence of specific language impairment (SLI) is a matter of current debate., Aims: Speech and language therapists and other authorities in Finland have discussed the prevalence of SLI since the 1990s. This discussion has been based on international studies because of the lack of national studies. This paper presents the first Finnish prevalence study of SLI in primary healthcare and, thus, participates in the international discussion on the prevalence of SLI. Furthermore, two samples of delayed language development (DLD) were studied., Methods & Procedures: This is a retrospective study from 1989-1999. It was conducted on the population of one of the biggest towns in Finland, and was collected from the statistical records of speech and language therapists., Outcomes & Results: The prevalence of SLI increased, and this increase was statistically significant. The prevalence of SLI was less than 1% in age group 0-6 years and, thus, presents a much lower prevalence than international discussion has suggested. SLI seems to be present particularly in boys though it was also increasing in girls. Furthermore, children with SLI seem to be more affected by receptive difficulties over the period studied. Particularly important is the observation that the prevalence of DLD was also increasing, and together with SLI they suggest a prevalence rate of 2.5% in Finland., Conclusions: The low prevalence of SLI in this study might be a consequence of the path of intervention that effectively separates SLI from delayed language development. Furthermore, the questions of language specific features needs to be emphasized. The findings of this study suggest that the prevalence of SLI increased as did the prevalence of DLD. The range of prevalence estimates of SLI in different studies raises the need for national and international epidemiological studies of SLI with equal criteria of assessment in each language.

Background and Objectives: Chronic pain, dementia, and depression may reduce activities of daily life in elderly people. We evaluated the correlation between pain intensity and daily activities, cognitive state, and depression, as well as their interrelationships in home-dwelling elderly people with chronic pain., Methods: Forty-one elderly home-dwelling people who suffered from long-lasting pain, and who participated in a rehabilitation program, were enrolled. Severity of pain at rest and after pain-provoked motion was assessed on a visual analog scale (VAS, 0 to 100) and a 5-point verbal rating scale (VRS). Cognitive status was assessed with the mini-mental state examination (MMSE, 0 to 30), depression on the geriatric depression scale (GDS, 0 to 15), and functional ability in daily life was assessed with the Barthel Index (0 to 100)., Results: VAS and VRS scores correlated positively with each other. Rating pain at rest on the VRS (mean 1.0, median 1) correlated with severity of depression (GDS mean 5.4) (r = 0.3997, P < 0.01), while scores on the VAS did not. Pain ratings at rest did not correlate with the Barthel Index (mean 87.7), but the latter correlated positively with motion-evoked VRS pain scores (mean 2.8, median 3) (r = 0.42829, P < 0.01). The MMSE (mean 25.3) did not correlate with any pain parameter, but it correlated positively with the Barthel Index (r = 0.3660, P < 0.05). The Barthel Index correlated negatively with the GDS (r = -0.39969, P < 0.01)., Conclusion: In home-dwelling elderly people, chronic pain states do not seem to reduce daily activities as much as cognitive dysfunction and depression. The seemingly controversial finding of a positive correlation between daily activities and pain in motion, and lack of correlation with pain at rest, may be explained by a relatively low intensity of pain in our study people.

Implementation of the EU Water Framework Directive will call for new lake monitoring and management strategies. Therefore, different methods need to be tested in order to achieve reliable assessment of lake background conditions and water quality. Sediment-based techniques provide one such tool for lake management. In this work, 10 lakes, presumed to be naturally eutrophic, were investigated with a paleolimnological short core study. The aim of the study was to examine the composition of the diatom assemblages in their natural state, estimate their change over time and assess the background nutrient levels. One sediment profile from each lake was divided into six sub-samples that were analyzed for diatoms (60 samples). Diatom-based inference models were applied to reconstruct the past total phosphorus concentration and assess the eutrophication. The results indicated that all the lakes studied had already been nutrient-rich before the impact of modern agriculture. However, diatom assemblages have changed remarkably over time and total phosphorus concentrations have generally increased, so at present only two of the study lakes are close to their natural status. This suggests that naturally eutrophic lakes will probably require management actions to fulfill the new directive requirements in the future.

Antidromic activation of nociceptive nerve fibres innervating the skin produces an axon reflex that involves extravasation and vasodilation of cutaneous blood vessels. We determined whether the axon reflex of the hindlimb skin is influenced by an experimental model of neuropathy induced by unilateral ligation of spinal nerves L(5) and L(6) in the rat. Ligation of spinal nerves induced symptoms mimicking tactile allodynia, as indicated by a marked decrease of the hindlimb withdrawal threshold to mechanical stimulation. The axon reflex induced by antidromic electrical stimulation of nociceptive fibres innervating the plantar skin ipsilateral to the ligation was attenuated according to determination of extravasation response and blood flow response. Lidocaine block or transection of the sciatic nerve of the neuropathic limb did not induce any change in basal blood flow of the plantar skin. The results indicate that ligation of spinal nerves induces an attenuation of the axon reflex. This attenuation reflects a decrease in the efferent function of primary afferent nociceptors innervating the hypersensitive skin of the hindpaw. The attenuation of antidromically-induced vascular responses was not caused by overriding sympathetic activity, as indicated by lack of blood flow effects by lidocaine blocks or a transection of the sciatic nerve., (Copyright 2002 Elsevier Science Inc.)

We investigated the spatial and temporal expression of basement-membrane-forming and neurite-outgrowth-supporting matrix proteins after a unilateral dorsal root injury combined with a collagen I/laminin-1 graft and a stab wound lesion to the dorsal horn of the adult rat spinal cord. Ten days after injury, the gamma1 laminin was induced in the reactive glia. At this early stage, the glial cells failed to express type IV collagen and the alpha1 laminin. One month after injury, reactive astrocytes in the dorsal horn of the lesioned side expressed gamma1 laminin, type IV collagen, and the alpha1 laminin whereas astrocytes of the normal spinal cord or the uninjured contralateral dorsal horn were negative. Both astrocytes and neurons of the ipsilateral ventral horn were induced to express laminin-1 and gamma1 laminin. Astrocytes of the ipsilateral ventral horn also expressed type IV collagen. Simultaneously with the changes in expression of the extracellular matrix proteins, the expression pattern of basic fibroblast growth factor (FGF-2) was markedly altered after spinal cord injury. In normal and contralateral spinal cord, FGF-2 was expressed in nerve fibers, but its expression changed from neuronal into glial in the ipsilateral spinal cord within 1 month after injury. Four months after injury, expression of both type IV collagen and the alpha1 laminin had declined, but the astrocytes at the injury site continued expressing the gamma1 laminin. Cultured astrocytes were negative for type IV collagen, but several cytokines, including IL-1beta and TGFbeta1, induced expression of type IV collagen in the astrocytes. These factors also increased deposition of type IV collagen matrix in the glial cultures. These results indicate that type IV collagen and the alpha1 laminin are induced in reactive astrocytes after spinal cord injury in vivo. Induction of type IV collagen in astrocytes in vitro by cytokines indicates that blood-borne or local factors at the injury site may induce the spinal cord glial expression of type IV collagen in vivo. Simultaneous expression of laminin-1 and alpha1 laminin with type IV collagen is known to lead to production of basement membranes. This may hamper the neurite-outgrowth-promoting potential of the gamma1 laminin by initiating formation of the glial scar., ((c) 2002 Elsevier Science.)

Recent work has shown that a significant portion of the total loss of phosphorus (P) from agricultural soils may occur via subsurface drainflow. The aim of this study was to compare the concentrations of different P forms in surface and subsurface runoff, and to assess the potential algal availability of particulate phosphorus (PP) in runoff waters. The material consisted of 91 water-sample pairs (surface runoff vs. subsurface drainage waters) from two artificially drained clayey soils (a Typic Cryaquept and an Aeric Cryaquept) and was analyzed for total suspended solids (TSS), total phosphorus (TP), dissolved molybdate-reactive phosphorus (DRP), and anion exchange resin-extractable phosphorus (AER-P). On the basis of these determinations, we calculated the concentrations of PP, desorbable particulate phosphorus (PPi), and particulate unavailable (nondesorbable) phosphorus (PUP). Some water samples and the soils were also analyzed for 137Cs activity and particle-size distribution. The major P fraction in the waters studied was PP and, on average, only 7% of it was desorbable by AER. However, a mean of 47% of potentially bioavailable P (AER-P) consisted of PPi. The suspended soil material carried by drainflow contained as much PPi (47-79 mg kg-1) as did the surface runoff sediment (45-82 mg kg-1). The runoff sediments were enriched in clay-sized particles and 137Cs by a factor of about two relative to the surface soils. Our results show that desorbable PP derived from topsoil may be as important a contributor to potentially algal-available P as DRP in both surface and subsurface runoff from clayey soils.

Lesion of presumably ischemic origin of the rat sciatic nerve was induced photochemically by laser irradiation combined with systemic administration of a photosensitizing organic dye, erythrosin B. We have studied the pathologic features of the nerve after the photochemical insult with light- and electronmicroscopy and related them to behavioral signs of neuropathic pain. At the irradiated nerve site, occlusion of blood vessels was seen and the vessels were packed with aggregated thrombocytes, fibrins and deformed erythrocytes, supporting the notion that photochemical reaction caused intraneural ischemia. The degree of the nerve injury at the center of irradiation was related to the duration of the laser exposure. Brief irradiation (30 seconds) only caused identifiable injury to myelinated fibers, whereas longer irradiation (2 minutes) caused greater injury to myelinated and unmyelinated fibers, characterized by extensive axonal degeneration and demyelination. The rats irradiated for 2 minutes, but not 30 seconds, exhibited neuropathic pain-like behaviors, expressed as mechanical and cold allodynia. The nerve injury was most severe 7 days after ischemia and regeneration of both myelinated and unmyelinated fibers was observed 3 months later. The nerve caudal to the irradiation exhibited Wallerian degeneration 7 days after the insult, whereas at 10 mm proximal to the irradiation the nerve was largely normal. It is thus concluded that photochemically induced intraneural ischemia caused injury to both myelinated and unmyelinated fibers, with myelinated fibers being more susceptible. However, the development of neuropathic pain-like behaviors may require injury to the unmyelinated fibers.

A laser and erythrosin-B-induced sciatic nerve injury decreases thresholds of a mechanically induced paw withdrawal reflex and enhances cold-induced withdrawal behavior of the affected limb. Exposure of the affected paw to a normally innocuous cold stimulus results in a transient decrease in the threshold of the mechanically evoked paw withdrawal reflex in neuropathic but not in intact rats. The present data suggest that in an experimental neuropathic state a normally innocuous cold stimulus may further sensitize spinally mediated withdrawal reflexes to stimuli of another stimulus modality, in this case, to innocuous tactile stimuli. Therefore, testing mechanical allodynia in neuropathic rats immediately after testing cold allodynia may produce artifactual results., (Copyright 2000 Academic Press.)

Neuropathic pain responds poorly to opioids. We now report that combination of systemic morphine (2 mg/kg) and dextromethorphan (45 mg/kg), a clinically available antitussive with NMDA-antagonist properties, markedly alleviated mechanical and cold allodynia-like behavior in a rat model of peripheral mononeuropathy. Neither drug produced a significant effect on its own at these doses. The anti-allodynic effect of morphine plus dextromethorphan was reversed by naloxone. The present results suggest that a combination of NMDA-antagonist and opiates might be effective in treating neuropathic pain. Furthermore, the effect of this drug combination is mainly mediated via opioid receptors.

Carrageenan was used to study inflammation-induced changes in spinal nociception and its brain stem modulation in the pentobarbitone-anesthetized rat. Carrageenan was administered intraplantarly into one hindpaw 2 h before the start of electrophysiological single unit recordings of wide-dynamic range (WDR) neurons of the spinal dorsal horn. Carrageenan produced a significant leftward shift in the stimulus-response function for mechanical stimuli, whereas that for noxious heat stimuli was short of statistical significance. Conditioning electrical stimulation in the rostroventromedial medulla (RVM) significantly attenuated noxious heat-evoked, but not mechanically evoked, responses to spinal dorsal horn WDR neurons in the control (contralateral) side. However, in the carrageenan-treated side RVM stimulation had no significant effect on mechanically or noxious heat-evoked responses. Following direct spinal administration of neuropeptide FF (NPFF), noxious heat-evoked responses, but not mechanically evoked responses, were attenuated by RVM-stimulation also in the carrageenan-treated side. This selective NPFF-induced enhancement of brain stem-spinal inhibition was not reversed by naloxone. The results indicate that carrageenan-induced inflammation significantly changes the response properties of spinal nociceptive neurons and their brain stem-spinal modulation. During inflammation, NPFF in the spinal cord produces a submodality-selective potentiation of the antinociceptive effect induced by brain stem-spinal pathways, independent of naloxone-sensitive opioid receptors.

Reinnervation of the muscles and skin in the rat hindpaw was studied after transection and attempted repair of the sciatic nerve. Reconnecting the transected nerve with lens cleaning paper was at least as effective in rejoining the transected nerves as traditional microsurgical neurorraphy. Paper induced a slightly bigger fibrous scar around the site of transection than neurorraphy, but this scar did not cause impairment of functional recovery or excessive signs of neuropathic pain. We conclude that a paper graft can be used in restorative surgery of severed peripheral nerves.

We have developed a noninvasive method for studying quantitatively the magnitude of hindlimb withdrawal reflexes induced by noxious heat in lightly anesthetized rats. The amplitude, latency, and duration of the hindlimb withdrawal was determined by a very small piezoceramic device placed on the hamstring muscle while the glabrous skin of the hindpaw was stimulated using a feedback-controlled contact thermostimulator. An increase in the amplitude and duration of the withdrawal response, concomitant with a decrease in the response latency, was found with increasing stimulus temperature. The sensitivity of the method was verified using morphine, which produced a dose-related (3.5-7.0 mg/kg) attenuation of all these response components. The use of a piezoceramic device for measuring the withdrawal response provides a quantitative, noninvasive method for evaluating the magnitude of various components of the nocifensive withdrawal reflexes induced by noxious stimuli in lightly anesthetized rats.

We compared the effect of skin temperature on the critical threshold temperature eliciting heat pain with the effect of skin temperature on the response latency to the first heat pain sensation in healthy human subjects. Also, we determined the effect of the duration of a heat stimulus ramp on pain threshold. Furthermore, we determined the effect of skin temperature on mechanically induced pain. We found that the latency to the first pain sensation induced by a radiant heat stimulus was significantly decreased with an increase in the skin temperature (25-35 degrees C). However, independent of the rate of the stimulus rise (3-10 degrees C/s) and independent of the stimulus location (hairy vs glabrous skin), the threshold temperature for eliciting the heat pain sensation, determined with a contact thermostimulator, was not changed by a change in the skin temperature in the same subjects. With a fast rate of stimulus rise, a higher pain threshold was obtained than with a slow rise of stimulus temperature. However, this difference was found only with subject-controlled ascending stimuli (method of limits) but not with experimenter-controlled, predetermined stimulus ramps (method of levels). The heat pain threshold was higher in the glabrous skin of the hand than in the hairy skin of the forearm. With increasing stimulus duration (2.5-10 s), the threshold temperature eliciting the heat pain sensation was significantly decreased. The mechanically induced pain threshold was not influenced by the skin temperature. The results indicate that the critical temperature for eliciting heat pain is independent of the skin temperature in humans. However, a change in skin temperature is an important source of an artefactual change in heat pain sensitivity when the radiant heat method (latency or energy) is used as an index of pain sensitivity. With a method dependent on reaction time (the method of limits), the heat pain threshold was artefactually increased, with fast rates of stimulus rise due to the long delay of slowly conducting heat pain signals in reaching the brain. With an increase in the duration of the heat stimulus, the critical temperature for eliciting pain sensation was significantly decreased, which may be explained by central neuronal mechanisms (temporal summation).

Effects of the selective alpha 2-adrenoceptor agonist, medetomidine, on a compound volley of a tibial nerve stimulation-evoked spinal reflex, pain-induced phrenic motor responses and on postoperative neuropathic pain behavior were studied in rats. Medetomidine (0.3 mg/kg) decreased the amplitude of the compound volley recorded from peroneal nerve in response to tibial stimulation in pentobarbital (40 mg/kg) anesthetized rats. Atipamezole, an alpha 2-adrenoceptor antagonist (1.5 mg/kg) fully restored the response when given 60 min after the medetomidine administration. Pain-evoked phrenic motor responses were completely inhibited upon combination anesthesia by pentobarbital (40 mg/kg) and medetomidine (0.3 mg/kg) (PB+M) but not upon plain pentobarbital anesthesia (50 or 60 mg/kg) (PB50,PB60). To study the effect of medetomidine on postoperative neuropathic pain behavior (autotomy), transection of sciatic nerve was done under PB+M, PB50 or PB60 anesthesia. No differences between the groups were found in the postoperative pain behavior during eight-week follow up. The results show that activation of alpha 2-adrenergic receptors by medetomidine under pentobarbital anesthesia mitigates trauma-induced afferent barrage, whereas it does not reduce the subsequent autotomy.

Effects of different kinds of nerve lesions on denervation-induced self-mutilation (autotomy) was studied in the rat. Four different types of lesion were used: nerve transection, nerve transection combined with ligation and extirpation of the distal part of the transected nerve, nerve resuturation with a microsurgical technique, and lidocaine treatment after transection but before and during nerve resuturation. To determine the degree of nerve regeneration, the extensor muscles of the ankle joint were prepared and weighed after the follow-up period. If the transected nerves were resutured the incidence and severity of autotomy decreased significantly when compared to the transection+ligation-treated rats. The pretreatment with lidocaine did not further decrease the autotomy behavior of the rats whose nerves were resutured. In those rats who performed autotomy the early onset of self-mutilation correlated positively with a moderate, but not high or low, degree of restoration of the muscle weight. The present results suggest that autotomy can be decreased with good surgical techniques after nerve resuturation.

We investigated the role of laminin in functional recovery of a peripheral nerve injury using electrophysiological and behavioral approaches on the rat sciatic nerve in vivo. These studies were complemented by neurofilament protein immunocytochemistry on the sciatic nerve 20 days after an operation, in which an 8-mm piece of the nerve was removed and replaced by a graft of laminin, its neurite outgrowth-promoting peptide, a control peptide, collagen, or by resuturing of the removed piece of the nerve. Electrophysiological measurements of muscle strength 4 months after the sciatic nerve transection showed that a laminin graft was as effective as neurorrhaphy in supporting functional recovery of an injured peripheral nerve. A laminin graft also significantly reduced autotomy in the operated animals. Immunocytochemistry confirmed that both a laminin graft and resuturing supported growth of the 200-kDa neurofilament-positive axons into the distal stump of the nerve within 20 days of operation. A graft with a neurite outgrowth-promoting peptide of the B2 chain of laminin supported similar axon growth, whereas another peptide graft also derived from laminin or a collagen graft did not support axon growth. All grafts allowed Schwann cell growth into the distal stumps of the nerves, but neurites accompanied them only in the regeneration-supporting grafts and in the resutured nerves. The Schwann cells of the regenerating nerves expressed high levels of the neurite outgrowth-promoting domain of the B2 chain of laminin, whereas the Schwann cells of the degenerating nerves failed to express this domain in the distal stumps of the degenerating nerves. These results provide the first in vivo evidence for the functional role of laminin in peripheral nerve regeneration. As the neurite outgrowth-promoting domain of the B2 chain of laminin is as efficient as laminin or resuturing in supporting a short-term recovery of an injured sciatic nerve, this area may be a regeneration-promoting domain of this glycoprotein. More importantly, as grafting significantly reduces post-traumatic pain behavior in the operated animals, the laminin graft surgery may provide a useful method for clinical restoration of the injured peripheral nerves.

Background: The effects of selective alpha-agonist medetomidine and alpha 2-antagonist atipamezole on gastrointestinal motility were studied., Methods: The passage of intragastrically administered Evans blue in the small bowel of unanesthetized rats was followed, and the stomachs were weighted after killing the rats., Results: Subcutaneous medetomidine, 0.01-0.1 mg/kg, was found to delay small intestinal transit but not gastric emptying, with a maximal effect seen at 0.03 mg/kg. Atipamezole fully reversed the effect of 0.1 mg/kg of medetomidine with a dose of 2.5 mg/kg. Atipamezole alone did not affect small intestinal transit. Subcutaneous morphine, 6 mg/kg, delayed gastric emptying and small intestinal transit, whereas intraperitoneal morphine only delayed gastric emptying. Subcutaneous atipamezole, 0.06 mg/kg, was partially able to reverse the delayed intestinal transit but did not inhibit morphine-induced gastric retention. Subcutaneous atipamezole, 0.06 mg/kg, reversed laparotomy-induced ileus completely., Conclusions: Atipamezole may provide a useful treatment for postlaparotomy ileus.

We studied the effects of atipamezole, an alpha 2-adrenoceptor antagonist, on hypnosis induced by medetomidine, an alpha 2-adrenoceptor agonist (1 mg/kg IP), and pentobarbital (40 mg/kg IP) by testing the righting reflex in the rat. The duration of antinociception was assessed with repeated pinch tests. Medetomidine-induced hypnosis and antinociception were inhibited by atipamezole at doses greater than 0.1 mg/kg. Atipamezole restored the righting reflex at a dose ratio that was 1:10 or more to that of medetomidine used to induce hypnosis. Subcutaneous atipamezole (1.5 mg/kg) increased the duration of hypnosis induced by pentobarbital (40 mg/kg) and pentobarbital + medetomidine (0.3 mg/kg). Hypnosis induced by methohexital (60 mg/kg IP) was also prolonged by atipamezole. The capacity of atipamezole to reverse the effects of medetomidine is also reduced in the presence of barbiturates. Thus, atipamezole should be used only at low doses to reverse a combination anesthesia induced by barbiturates and medetomidine.

Effect of cocaine on morphine-induced analgesia and the accompanying respiratory depression, bradycardia and hypolocomotion/sedation was studied in rats. Cardiovascular and respiratory effects were studied under pentobarbitone-induced anaesthesia. Cocaine enhanced morphine-induced analgesia in the formalin test, hot plate test and heat-induced tail withdrawal test in intact rats. However, in spinal rats a similar combination of cocaine with morphine did not produce increased latencies in the tail withdrawal test. Of the three analgesic tests used, the formalin test was the most sensitive to the enhancement, as well as to the effects of morphine or cocaine alone. Morphine at the dose of 6 mg/kg produced complete analgesia in the formalin test, significant hypolocomotion/sedation, significant bradycardia and significant decrease in the respiratory rate. At an equianalgesic dose (complete analgesia in the formalin test) of morphine (3 mg/kg)-cocaine (5 mg/kg)-combination no significant changes in heart rate, respiratory rate or locomotion(/alertness) were observed. Changes in skin blood flow determined by the laser Doppler flow method were not significant in any of the experimental conditions. The results indicate that cocaine enhances morphine-induced analgesia, mainly due to supraspinal mechanisms. In contrast, the morphine-induced bradypnoea, bradycardia and hypolocomotion/sedation are attenuated by cocaine.

Spermine, a polyamine, is known to enhance motor functional recovery after a sciatic nerve lesion in the rat. The effect of spermine on the sensory axonal elongation after a sciatic crush was studied with the pinch-test from the sural nerve in the rat. The effect of spermidine, another polyamine, on the motor functional recovery after a trauma was studied by using the toe-spreading ability as an indicator of motor recovery after a sciatic crush in the rat. Spermine enhanced the rate of regeneration of the sensory axons by 16%. Spermidine enhanced the rate of the motor recovery by 30%. These results suggest that not only spermine but also spermidine enhance regeneration of peripheral somatic nerves.

The behavioral effects of atipamezole (0.5-4.5 mg/kg), a new and highly selective alpha 2-adrenoceptor antagonist, were studied in four behavioral models: open-field, elevated plus-maze, two compartment exploratory test and forced swimming test. Atipamezole (1.5 and 4.5 mg/kg) produced a dose-dependent suppression of locomotor activity in the open field test. In the two compartment exploratory test, the same doses of atipamezole decreased locomotor activity in a 5 min test but not in a 10 min test. The numbers of transitions between the compartments were not significantly affected by atipamezole. Doses of 0.5-4.5 mg/kg did not significantly change the time spent in the open arms or the total number of arm entries in the plus-maze, and doses of 1.5 and 4.5 mg/kg decreased defecation marginally. Vocalization during the forced swimming test was increased by atipamezole (1.5 mg/kg) but the duration of immobility was not increased over the dose range (0.5-1.5 mg/kg) of atipamezole used. Our results suggest that, in the rat, atipamezole decreases motor activity in the early phase of the exploration of new surroundings. In the doses used, atipamezole may suppress defecation and increase vocalization in rats.

In the pentobarbitone-anesthetized cat, the threshold of the tooth pulp-elicited jaw-opening reflex was elevated in a dose-dependent way (30-100 micrograms/kg, IP) following the administration of medetomidine, an alpha-2-adrenoceptor agonist. This elevation was significantly reduced by atipamezole (1 mg/kg, IP), an alpha-2-adrenoceptor antagonist. The inhibitory interaction between two successive dental stimuli applied to the same tooth (in-field inhibition) was suppressed by a lower dose of medetomidine (30 micrograms/kg) than the threshold elevation to single electrical pulses (55 micrograms/kg). Only the highest dose of medetomidine used (100 micrograms/kg) significantly influenced the temporally facilitated (in-field facilitation) response. In comparison, cocaine, a nonspecific monoaminergic agent, did not produce a significant threshold elevation of the tooth pulp-elicited jaw-opening reflex (1-25 mg/kg, IP). It is concluded that medetomidine, through an action on alpha-2-adrenoceptors, can suppress a predominantly nociceptive trigeminal reflex in anesthetized cats. The threshold evoked by single electric pulses, in-field inhibition, and in-field facilitation display differential sensitivities to medetomidine effects.

Analgesia produced by systemic cocaine (20 mg/kg intraperitoneally) was not attenuated by dexamethasone (0.25-2.5 mg/kg) in the formalin or tail pinch test in rats. The result suggests that the activation of the corticotropin releasing factor-adrenocorticotropin/beta-endorphin axis does not explain cocaine-induced analgesia.

We studied the effects of different sensory and behavioral manipulations on autotomy (self-mutilation). Lidocaine and bupivacaine pretreatments of the transected nerves delayed the onset of autotomy. Short prelesional stimulation (crush) of the transected nerve did not enhance autotomy significantly. Daily handling decreased autotomy behavior strongly and a visual cue placed on the denervated skin increased autotomy slightly. The delayed onset of the autotomy behavior after locally administered anesthetics suggests that the lesion-induced afferent barrage modified self-mutilation. The decreased self-mutilation after daily handling could be a consequence of handling stress. The increase of autotomy after the visual cue might have resulted from the attention-induced increase of the activity in ascending nociceptive tracts.

The effect of systemic (intravenous) medetomidine, an alpha-2 adrenoceptor agonist, on pain thresholds was studied in healthy human subjects (n = 6). Medetomidine produced a dose-dependent (cumulative doses: 25 and 50 micrograms) sedative effect evaluated by visual analog scale. Also, a dose-dependent decrease of blood pressure but not of heart rate was seen after administration of medetomidine. Pain threshold to electric stimulation of the tooth pulp and cutaneous heat pain threshold were uninfluenced by medetomidine. An index of cutaneous thermal sensitivity to innocuous stimuli, the width of the thermoneutral zone, also was uninfluenced by medetomidine. Medetomidine produced a significant attenuation of the affective-motivational component (unpleasantness) of tourniquet-induced ischemic pain, whereas the sensory-discriminative component (pain magnitude estimate) of the ischemic pain was not attenuated. The results suggest that systemic medetomidine alone at subanesthetic but sedative and hypotensive doses does not significantly influence the intensity and thresholds of experimental pain, whereas the affective-motivational component of pain can be attenuated.

The effect of systemically administered medetomidine, a selective alpha-2-adrenoceptor agonist, was studied by electrophysiological recordings of the peripherally evoked responses of three different types of sensory neuronal populations in the rat: medial thalamic neurons exclusively responding to mechanical cutaneous stimuli at noxious intensities, spinothalamic tract neurons of the spinal cord responding exclusively or differentially to mechanical cutaneous stimuli at noxious intensities, and low-threshold mechanoreceptive spinal dorsal horn neurons with ascending projections. The neuronal effects were compared with the behavioral data obtained in mechanically and thermally induced nociceptive tail reflex tests in intact and spinal rats. A reversal of the antinociceptive effects was attempted by systemically (1.5 mg/kg, i.p.) or intrathecally (25 micrograms) administered atipamezole, a selective alpha-2-adrenoceptor antagonist. Systemically administered medetomidine produced an atipamezole-reversible, dose-dependent suppressive effect on the evoked responses of nociceptive medial thalamic and spinothalamic tract neurons. A lower dose of medetomidine was needed to suppress significantly (half-maximally) evoked responses of the nociceptive medial thalamic neurons (100 micrograms/kg) than those of the nociceptive spinothalamic tract neurons (300 micrograms/kg). The decrease of evoked responses of the nociceptive spinothalamic tract neurons was accompanied by a decrease in spontaneous activity. The responses of the low-threshold mechanoreceptive projection neurons of the spinal cord were not influenced by medetomidine (30-300 micrograms/kg). The reflex studies with a (anesthetic) medetomidine dose of 300 micrograms/kg indicated that in intact and otherwise drug-free rats, medetomidine produced a significant prolongation of the nociceptive reflex response latency to a tail-pinch and heat; these antinociceptive effects of systemic medetomidine were reversed by systemically and intrathecally applied atipamezole. In spinal rats systemically applied medetomidine (300 micrograms/kg) also produced a significant prolongation of the tail-flick latency, which was reversed by systemically applied atipamezole. The results suggest that a high anesthetic dose of systemically applied medetomidine (300 micrograms/kg) can suppress nociceptive sensory neuronal and reflex responses due to spinal segmental mechanisms through an action on alpha-2-adrenoceptors. This spinal effect is selective to responses of nociceptive neurons, and at least partly postsynaptic as indicated by the concomitant decrease in spontaneous activity. At a lower, subanesthetic (but sedative) dose (100 micrograms/kg) the antinociceptive effect of systemically applied medetomidine can be explained by supraspinal alpha-2-adrenergic mechanisms.

Medetomidine, a new alpha 2-adrenoceptor agonist produced dose-dependent (30-100 micrograms/kg i.p.) analgesia in the formalin test in rats, and this effect was reversed by atipamezole (1 mg/kg), a new alpha 2-adrenoceptor antagonist. However, medetomidine at the dose of 100 micrograms/kg did not influence tail flick latencies or latencies of the biting response to mechanical pinch stimuli. Moreover, medetomidine produced sedation and a decrease in locomotor activity. In comparison, the non-sedative monoaminergic agent, cocaine (25 mg/kg), produced highly significant analgesic effects in the formalin and mechanical pain tests. The cocaine effect in the formalin test was not reversed by atipamezole (1 mg/kg). It is concluded that the analgesic effect of medetomidine in the formalin test is due to supraspinal mechanisms related to sedation and is mediated by alpha 2-adrenoceptors. The alpha 2-adrenoceptors are not involved in cocaine-induced anagesia.

The effects of inhibition of polyamine synthesis on the motor and sensory functional neural recovery after a sciatic crush lesion was studied by measuring sensory and motor function of a crushed sciatic nerve after daily exposure to alpha-difluoromethylornithine (DFMO). DFMO increased the time needed for functional motor recovery by 13% in the toe-spread test when the lesion was about 20 mm proximal to the target muscle. DFMO reduced the rate of sensory axonal elongation by 24% in the pinch-test.

The motor functional recovery after sciatic nerve crush was measured in rats treated with daily injections of (a) thyrotropin-releasing hormone (2.0 mg/kg, (b) alpha-melanocyte-stimulating hormone (0.07 mg/kg/48 h), or (c) testosterone propionate (4.4 mg/kg). The recovery of the motor function of the sciatic nerve was indicated by using the return of the toe-spreading response. None of the treatments differed significantly from saline controls in the time needed for recovery. The same procedure (without injections) was carried out with castrated and noncastrated male rats in order to test the effect of the lack of testosterone on recovery time after sciatic crush. The groups did not differ significantly as to their recovery times. The same method was used to study the effect of spermine (10.0 mg/kg/day) on the recovery of motor function. Spermine seemed to reduce the time needed for recovery from a mean value of 15.7 to 11.0 days (P less than 0.01). We also studied the effect of daily injections of spermine (13.0 mg/kg) on the sensory division of the peripheral nerve using the foot-flick test. The time needed for recovery after crush in the sciatic notch was reduced from 13.7 to 7.7 days (P less than 0.005). These results do not support the hypothesis that alpha-melantocyte-stimulating hormone, thyrotropin-releasing hormone, or testosterone enhance functional recovery of severed motor axons. Our results confirm a previous observation that spermine reduces the time needed for recovery after trauma in peripheral motor neurons. The result of the foot-flick test suggests that spermine enhances both motor and sensory recovery.

The sciatic nerve was transected unilaterally 7-10 weeks before electrophysiological single unit recordings were made from somatically activated neurons in the midline bulboreticular formation of the rat. Their responses to high-intensity electrical stimulation of the saphenous nerve area were significantly stronger on the lesioned side. In control rats no such side difference was found. The result indicates that sciatic nerve transection unmasks polysynaptic somatic input to the midline bulboreticular formation.