Biomedical subjects
R Jensen
Publications and source records attributed to R Jensen.
Standardisation of the single-breath determination of carbon monoxide uptake in the lung.
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Standardisation of the measurement of lung volumes.
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Interpretative strategies for lung function tests.
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A high-fat diet during rat pregnancy or suckling induces cardiovascular dysfunction in adult offspring.
Epidemiological and animal studies suggest that diet-induced epigenetic modifications in early life can contribute to development of the metabolic syndrome in adulthood. We previously reported features of the metabolic syndrome in adult offspring of rats fed a diet rich in animal fat during pregnancy and suckling. We now report a study to compare the relative effects of high-fat feeding during 1) pregnancy and 2) the suckling period in the development of these disorders. As observed previously, 6-mo-old female offspring of fat-fed dams suckled by the same fat-fed dams (OHF) demonstrated raised blood pressure, despite being fed a balanced diet from weaning. Female offspring of fat-fed dams "cross fostered" to dams consuming a control diet during suckling (OHF/C) demonstrated raised blood pressure compared with controls (OC) [systolic blood pressure (SBP; mmHg) means +/- SE: OHF/C, 132.5 +/- 3.0, n = 6 vs. OC, 119.0 +/- 3.8, n = 7, P < 0.05]. Female offspring of controls cross fostered to dams consuming the fat diet (OC/HF) were also hypertensive [SBP (mmHg) 131.0 +/- 2.5 mmHg, n = 6 vs. OC, P < 0.05]. Endothelium-dependent relaxation (EDR) of male and female OHF and OHF/C mesenteric small arteries was similar and blunted compared with OC (P < 0.001). OC/HF arteries showed profoundly impaired EDR (OC/HF vs. OHF, P < 0.001). OHF/C and OC/HF demonstrated hyperinsulinemia and increased adiposity. Features of the metabolic syndrome in adult offspring of fat-fed rats can be acquired both antenatally and during suckling. However, exposure during pregnancy confers adaptive protection against endothelial dysfunction induced by maternal fat feeding during suckling.
Is obstructive sleep apnea syndrome associated with headache?
OBJECTIVE: Obstructive sleep apnea syndrome (OSA) is a common disorder in the general population. Although the mechanisms remain obscure, an association with headache has been reported. We aimed to assess the frequency of OSA in a population of headache patients based on a stratified sampling technique using questionnaire and polysomnography (PSG). METHODS: The survey was provided to new outpatients examined by a neurologist for headache over a 2-year period of time. The patients completed a headache diary during 30 days and those at risk of OSA went through a PSG examination. RESULTS: Of 903 headache patients, 75 reported heavy snoring and episodes of interrupted nocturnal breathing (8%). Among 43 patients examined with PSG, 14 (1.5% of the total study population) had an apnea/hypopnea index of 5 or higher. Eleven of the patients reported morning headache. CONCLUSION: The frequency of OSA in a patients referred to specialist for headache problems is not higher than what is reported for the general population. The relatively low rate of OSA in this selected group of patients with headache referred to neurology for second opinion does not support the notion that OSA brings about headache.
Neurophysiological tests and neuroimaging procedures in non-acute headache: guidelines and recommendations.
The use of instrumental examinations in headache patients varies widely. In order to evaluate their usefulness, the most common instrumental procedures were evaluated, on the basis of evidence from the literature, by an EFNS Task Force (TF) on neurophysiological tests and imaging procedures in non-acute headache patients. The conclusions of the TF regarding each technique are expressed in the following guidelines for clinical use. 1 Interictal electroencephalography (EEG) is not routinely indicated in the diagnostic evaluation of headache patients. Interictal EEG is, however, indicated if the clinical history suggests a possible diagnosis of epilepsy (differential diagnosis). Ictal EEG could be useful in certain patients suffering from hemiplegic and basilar migraine. 2 Recording of evoked potentials is not recommended for the diagnosis of headache disorders. 3 There is no evidence to justify the recommendation of autonomic tests for the routine clinical examination of headache patients. 4 Manual palpation of pericranial muscles, with standardized palpation pressure, can be recommended for subdividing patient groups but not for diagnosis. Pressure algometry and electromyography (EMG) cannot be recommended as clinical diagnostic tests. 5 In adult and paediatric patients with migraine, with no recent change in attack pattern, no history of seizures, and no other focal neurological signs or symptoms, the routine use of neuroimaging is not warranted. In patients with atypical headache patterns, a history of seizures and/or focal neurological signs or symptoms, magnetic resonance imaging (MRI) may be indicated. 6 If attacks can be fully accounted for by the standard headache classification [International Headache Society (IHS)], a positron emission tomography (PET) or single-photon emission computerized tomography (SPECT) and scan will generally be of no further diagnostic value. 7 Nuclear medicine examinations of the cerebral circulation and metabolism can be carried out in subgroups of headache patients for diagnosis and evaluation of complications, when patients experience unusually severe attacks, or when the quality or severity of attacks has changed. 8 Transcranial Doppler examination is not helpful in headache diagnosis. Although many of the examinations described are of little or no value in the clinical setting, most of the tools have a vast potential for further exploring the pathophysiology of headaches and the effects of pharmacological treatment.
Physiotherapy for tension-type headache: a controlled study.
The role of non-pharmacological therapies in the preventive treatment of tension-type headache (TTH) is still an object of debate. The primary aim of this study was therefore to investigate the therapeutic effect of physiotherapy in properly classified patients with TTH in a controlled trial. Fifty patients with TTH, 26 with episodic, frequent (ETTH) and 24 with chronic TTH (CTTH) fulfilling the International Headache Society classification criteria were included in the study. After a 4-week run-in period, they were randomized to either an 8-week period of standardized physiotherapy (group 1) or to an 8-week observation period followed by an identical course of physiotherapy (group 2); after the physiotherapy all patients were followed for a 12-week follow-up period. We then evaluated the number of days with headache, severity and duration of the headache attacks, and drug consumption for symptomatic treatment before and after the course of physiotherapy. Forty-eight patients completed the study. The average number of days with headache per 4-week period was reduced from 16.3 days at baseline to 12.3 days in the last 4 weeks of treatment [from 14.5 days to 10.5 days (P < 0.001) in group 1 and from 18.1 days to 14.1 days (P < 0.001) in group 2]. Severity and duration of headache as well as drug consumption were unchanged throughout the study. Analysing the response to treatment separately in the various subgroups, we found that the number of responders was significantly higher among patients with CTTH vs. patients with ETTH (P < 0.002) and in females vs. males (P < 0.02). No differences were found between patients with and without disorder of pericranial muscles. We conclude that a standardized physiotherapy programme has a good therapeutic effect, albeit on a restricted group of patients.
Possible mechanisms of pain perception in patients with episodic tension-type headache. A new experimental model of myofascial pain.
A new experimental human model of myofascial pain using intramuscular infusion of a combination of bradykinin, serotonin (5-hydroxytryptamine), histamine, and prostaglandin E2 was applied to patients with episodic tension-type headache (ETTH) in order to examine pain perception. Fifteen patients with ETTH and 15 healthy controls completed the randomized, balanced, double-blinded, placebo-controlled study. Pain intensity, punctate hyperalgesia and allodynia, and pain quality were recorded. The combination induced a moderate and prolonged pain in both patients (median 51 min) (P = 0.001) and controls (median 22 min) (P = 0.001). Patients reported more pain than controls both after the combination (P = 0.045) and after placebo (P < 0.001). The McGill pain score [PRI(R)] was significantly higher in patients (P = 0.002) and in controls (P = 0.001), whereas pain quality and hyperalgesia were similar after the combination compared with placebo in the two groups. Due to side-effects nine subjects did not complete the study. The increased pain response, but similar qualitative pain perception, in ETTH patients may be explained by sensitization of peripheral nociceptors even though central mechanisms may also be involved.
Glyceryl trinitrate may trigger endogenous nitric oxide production in patients with chronic tension-type headache.
Experimental studies in humans have shown that nitric oxide (NO) may play an important role in initiation of primary headaches. It has been proposed that activation of L-arginine-NO pathway and increased endogenous production of NO may be responsible for NO induced headache. NO is synthesized from L-arginine and that reaction also yields citrulline. In the present study we aimed to investigate plasma levels of citrulline and arginine as markers of NO production after infusion of the NO donor, glyceryl trinitrate (GTN). We recruited 16 patients with chronic tension-type headache and 16 healthy controls. The subjects were randomly allocated to receive 0.5 microg/kg/min GTN or placebo over 20 min. Patients were examined on headache free days. Blood samples were collected at baseline and 60 min after start of infusion. Both patients and controls developed stronger immediate headache on the GTN day than on the placebo day (P = 0.008). The headache was more pronounced in patients than in controls (P = 0.02). Plasma levels of citrulline increased significantly 60 min after start of GTN infusion compared to placebo infusion in patients (P = 0.01) but not in controls (P = 0.50). Plasma levels of arginine were unchanged in both patients (P = 0.12) and controls (P = 0.18). We suggest that GTN administration may trigger endogenous production of NO in patients with chronic tension-type headache resulting in activation of perivascular sensory afferents.
Induction of prolonged tenderness in patients with tension-type headache by means of a new experimental model of myofascial pain.
Tenderness is the most prominent abnormal finding in patients with tension-type headache (TTH). Recently we developed a model of myofascial tenderness using intramuscular infusion of a combination of bradykinin, serotonin, histamine and prostaglandin E2. We aimed to examine tenderness after this combination in patients with episodic TTH (ETTH). Fifteen patients and 15 healthy controls completed the study. Participants received the combination into the non-dominant trapezius muscle in a randomized, double-blinded and placebo-controlled design. Local tenderness and stimulus-response functions, mechanical pain thresholds (PPDT) in the temporal region and on the finger, and total tenderness score (TTS) were recorded. A local, prolonged, and mild to moderate tenderness was reported both in patients (P = 0.001) and in controls (P = 0.001) after the combination compared with the placebo. The response to the combination tended to be increased in patients. The stimulus-response function was leftward shifted after the combination, compared with baseline in both groups. No changes in PPDT or TTS were found after the infusions, whereas baseline PPDTs were decreased in ETTH compared with controls (PPDTfinger: P = 0.033; PPDTtemporal: P = 0.015). Intramuscular infusion of a combination of endogenous substances induced prolonged tenderness in both patients with episodic TTH and healthy subjects. The present results suggest an increased excitability of peripheral muscle afferents in TTH.
Pain sensitivity in pericranial and extracranial regions.
Chronic myofascial pain is very common in the general population. The pain is most frequently located in the shoulder and neck regions, and nociceptive input from these regions may play an important role for tension-type headache. The mechanisms leading to the frequent occurrence of muscle pain in the shoulder and neck regions are largely unknown. It is possible that the pain is caused by increased sensitivity of muscle nociceptors or by central sensitization induced by nociceptive input from muscle. The primary aim of the present study was to compare muscle pain sensitivity in the trapezius and anterior tibial muscles. The secondary aim was to investigate whether temporal summation, a clinical correlate of wind-up, is more pronounced in muscle than in skin and, if so, whether such a difference is more pronounced in the trapezius than in the anterior tibial region. Sixteen healthy subjects were included. Pressure-pain thresholds and electrical cutaneous and intramuscular pain thresholds were measured at standard anatomical points in the trapezius and anterior tibial regions. Temporal summation was assessed by repetitive electrical stimulation. Pressure-pain thresholds (P = 0.005) and intramuscular electrical pain thresholds (P = 0.006) were significantly lower in trapezius than in anterior tibial muscle. Temporal summation was present in skin and muscle of both regions (P < 0.001). The degree of temporal summation was significantly higher in muscle than in skin in the trapezius region (P = 0.02), but not in the anterior tibial region (P = 0.47). In conclusion, we found that muscle pain sensitivity was higher in the trapezius than in the anterior tibial muscle. We also demonstrated that temporal summation could be induced in both muscle and skin and, importantly, that temporal summation was significantly more pronounced in muscle than in skin in the trapezius but not in the anterior tibial region. These data may help to explain why chronic muscle pain most frequently is located in the shoulder and neck regions.
Peripheral and central mechanisms in tension-type headache: an update.
Despite the tremendous socioeconomic impact of tension-type headache surprisingly little is known about the underlying pathophysiology and treatment. Existing evidence and theories about the relation between central and peripheral mechanisms are discussed. Central sensitization is probably the most important key to understand this widespread disorder. An effective prevention or reversal of this central sensitization will probably be of major importance in future treatment strategies.
ATM-dependent expression of the insulin-like growth factor-I receptor in a pathway regulating radiation response.
The ATM gene is mutated in the syndrome of ataxia telangiectasia (AT), associated with neurologic dysfunction, growth abnormalities, and extreme radiosensitivity. Insulin-like growth factor-I receptor (IGF-IR) is a cell surface receptor with tyrosine kinase activity that can mediate mitogenesis, cell transformation, and inhibition of apoptosis. We report here that AT cells express low levels of IGF-IR and show decreased IGF-IR promoter activity compared with wild-type cells. Complementation of AT cells with the ATM cDNA results in increased IGF-IR promoter activity and elevated IGF-IR levels, whereas expression in wild-type cells of a dominant negative fragment of ATM specifically reduces IGF-IR expression, results consistent with a role for ATM in regulating IGF-IR expression at the level of transcription. When expression of IGF-IR cDNA is forced in AT cells via a heterologous viral promoter, near normal radioresistance is conferred on the cells. Conversely, in ATM cells complemented with the ATM cDNA, specific inhibition of the IGF-IR pathway prevents correction of the radiosensitivity. Taken together, these results establish a fundamental link between ATM function and IGF-IR expression and suggest that reduced expression of IGF-IR contributes to the radiosensitivity of AT cells. In addition, because IGF-I plays a major role in human growth and metabolism and serves as a survival and differentiation factor for developing neuronal tissue, these results may provide a basis for understanding other aspects of the AT syndrome, including the growth abnormalities, insulin resistance, and neurodegeneration.
Physiological aspects of human milk lipids.
Human milk from healthy and well-nourished mothers is the preferred form of feeding for all healthy newborn infants. The nutrient supply with human milk supports normal growth and development of the infant. Here the general characteristics of human milk lipids and recent knowledge on lactational physiology, composition and functional aspects of human milk lipids are discussed. Lipids in human milk represent the main source of energy for the breastfed baby and supply essential nutrients such as fat-soluble vitamins and polyunsaturated fatty acids (PUFA). The essential fatty acids linoleic and alpha-linolenic acids (LA and ALA) are precursors of long-chain polyunsaturated fatty acids (LC-PUFA), including arachidonic (20:4n-6) and docosahexaenoic (22:6n-3) acids (AA and DHA). LC-PUFA serve as indispensable structural components of cellular membranes and are deposited to a considerable extent in the growing brain and the retina during perinatal development. The supply of preformed LC-PUFA with human milk lipids has been related to functional outcomes of the recipient infants such as visual acuity and development of cognitive functions during the first year of life. Recent stable isotope studies indicate that the major portion of milk PUFA is not derived directly from the maternal diet, but stems from endogenous body stores. Thus, not only the woman's current but also her long-term dietary intake is of marked relevance for milk fat composition.
Mechanisms of tension-type headache.
Despite tension-type headache represents one of the most frequent and costly diseases in modern society only very little research on this disease has actually been carried out. In contrast to former belief tension-type headache is a separate entity that can and should be separated from migraine. No specific biochemical abnormalities have yet been identified but a reliable human model of tension-type headache has been developed by means of infusion of a NO-donor, glyceryl trinitrate. Myofascial factors and peripheral sensitization of nociceptors play an important role in the episodic form, and central sensitization has been demonstrated in the chronic form. As chronic tension-type headache usually evolves from the episodic form, prevention and reversal of this central sensitization may be an important target for future pathophysiological studies and drug development.
Calcitonin gene-related peptide levels during nitric oxide-induced headache in patients with chronic tension-type headache.
It has been proposed that nitric oxide (NO) induced headache in primary headaches may be associated with release of calcitonin gene-related peptide (CGRP). In the present study we aimed to investigate plasma levels of CGRP during headache induced by the NO donor glyceryl trinitrate (GTN) in 16 patients with chronic tension-type headache and 16 healthy controls. The subjects were randomly allocated to receive 0.5 microg/kg/min GTN or placebo over 20 min on two headache-free days. Blood samples were collected at baseline, 10, 20 and 60 min after start of infusion. Both patients and controls developed significantly stronger immediate headache on the GTN day than on the placebo day and the headache was significantly more pronounced in patients than in controls. There was no difference between the area under the CGRP curve (AUCCGRP) on GTN vs. placebo day in either patients (P=0.65) or controls (P=0.48). The AUCCGRP recorded on the GTN day did not differ between patients and controls (P=0.36). Both in patients and controls, CGRP levels changed significantly over time, on both the GTN and placebo days (P < 0.05). The present study indicates that NO-induced immediate headache is not associated with release of CGRP.
Cardiac risk stratification of patients with symptomatic spinal stenosis.
The leading cause of death in the perioperative period after noncardiac surgery is a cardiac event. As the number of lumbar surgeries performed in patients older than 65 years of age continues to increase, this patient population with neurogenic claudications is an at risk group for a cardiac event because of their age and associated cardiac risk factors. The authors attempted to document by means of cardiac chemical stress testing, the prevalence of silent ischemic cardiac disease in patients with neurogenic claudication who were candidates for elective lumbar surgery. Eleven of 140 patients (8%) had induced cardiac wall abnormalities on stress testing, indicating myocardial ischemia. The only risk factors associated with cardiac ischemia were smoking and history of heart disease. It is recommended that dobutamine stress echocardiography be performed in patients undergoing elective spinal surgery for symptomatic spinal stenosis if they have a history of previous heart disease, smoking, or both.