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Biomedical subjects

P Svensson

Publications and source records attributed to P Svensson.

At least 19 recordsLinked to original sources

Changes in jaw muscle EMG activity and pain after third molar surgery.

Limited jaw-opening capacity is frequently encountered following third molar surgery and may impair function. The aim of this study was to investigate the electromyographic (EMG) activity in jaw muscles after third molar surgery to obtain more insight into the mechanisms of restrictions in jaw opening. Twenty subjects were examined before, 24 h and 1 week after surgery. Ten healthy controls were subjected to the same examination at two different occasions for intersession variability. The EMG activity of the masseter and anterior digastricus muscles was recorded at different jaw positions and during maximum voluntary clenching. Pain intensity was assessed at rest and during movements. The EMG activity in the jaw muscles increased with opening level (P < 0.01), but did not change after surgery. In contrast, the EMG activity during clenching was decreased in all muscles after surgery (P < 0.05). The pain intensity after surgery increased with jaw opening level (P < 0.001), but was in general not correlated to EMG level. Pain intensity during clenching was increased after surgery (P < 0.001), but not correlated to EMG level. The EMG activity did not change between visits in the control group. In conclusion, the results indicate that third molar surgery does not influence the EMG activity in the masseter and anterior digastricus muscles during various levels of static jaw opening, but decreases the EMG activity during clenching. However, these changes are not influenced by pain intensity. The results have implications for the understanding of the phenomenon of trismus.

Adult↗

Somatosensory function following painful repetitive electrical stimulation of the human temporomandibular joint and skin.

Temporomandibular disorders (TMD) are common pain problems in the population with uncertain pathophysiology and mechanisms. The aim of this experimental study was to: (1) Establish an experimental pain model using electrical stimuli to describe characteristics of nociception from the human temporomandibular joint (TMJ) and overlying skin. (2) Test the hypothesis that there would be sex-related differences in TMJ sensitivity. Forty-three healthy subjects (24 men and 19 women) participated. Using two unipolar needle electrodes into the skin (above the TMJ) in one session or into the TMJ in the other session, sensory detection threshold (SDT), pain detection threshold (PDT), and summation threshold (SumT) were measured, before and after repetitive electrical stimulation. Painful repetitive electrical stimulation was applied for 20 min with individually adjustment of the intensity of the stimuli to keep the pain rating around five on a 0-10 cm visual analogue scale (VAS). Sensitivity to tactile and pin-prick stimuli were assessed at 11 sites around the TMJ using two von Frey nylon filaments (5.16 and 84.96 g), as well as pressure pain threshold (PPT) and pressure pain tolerance (PPTOL) before the stimulation, after 20 min of stimulation and finally 15 min after the end of stimulation. Numerical rating scale (NRS) from 0 to 100 was used to rate the intensity of applied von Frey filaments. SDT, PDT, and SumT were higher in the TMJ than in the skin. These three measures increased after painful repetitive stimulation for 20 min (de-sensitization). In contrast to this effect, a hypersensitivity to pin-prick stimuli was detected around the TMJ area on the stimulated side after 20 min of electrical stimulation in the TMJ, but not in the skin. A bilateral hyposensitivity to tactile stimuli was detected after skin and TMJ stimulation. PPT and PPTOL did not show a significant change over time. Except for lower TMJ PPTOLs in women than men there were no significant sex-related differences in mechanical or electrical measures. The present findings indicate differences in the elicitation of hypersensitivity following repetitive electrical stimulation of skin and deep tissues. The mechanisms underlying these findings are not clear but differences in the induction of long-term potentiation and depression is a possibility. From a clinical point of view, the lack of sex differences in most of the used measures indicates that the higher prevalence of women than men amongst patients with persistent TMJ pain problems not entirely can be ascribed to a higher sensitivity of the TMJ. Further studies will examine the somatosensory sensitivity of patients with TMJ pain problems.

Adult↗

Experimental skin pain and muscle pain induce distinct changes in human trigeminal motoneuronal excitability.

Seeking information on the physiological properties of the trigeminal motoneuronal pool we investigated changes in the excitability of trigeminal motor system induced by two types of experimental pain (muscle and skin). In one session, we studied the effect of muscle pain induced by hypertonic saline infusion into the masseter muscle on the recovery cycle of the heteronymous H-reflex in the temporalis muscle and the homonymous silent period (SP) in the masseter muscle, both elicited by stimulation of the masseteric nerve in ten-healthy subjects. In another session, we studied the effect of laser stimuli applied to the perioral region, at conditioning intervals from 20 to 160 ms, on the temporalis H-reflex and masseter SP in nine healthy subjects. Whereas laser-induced skin pain significantly inhibited the temporalis H-reflex and facilitated the masseter SP (P < 0.01), muscle pain left the time course of the temporalis H-reflex and masseter SP unchanged (P > 0.05). The timing of temporalis H-reflex suppression and masseter-SP enhancement induced by laser stimuli indicates that facial skin nociceptors inhibit trigeminal motoneurones via multysynaptic reflex pathways. Hypertonic saline, a stimulus that predominantly activates group III and IV afferents, left both variables reflecting trigeminal motoneuron excitability unchanged. Due to the differences between the two experimental models, we cannot conclude that such inhibitory reflex pathway does not exist from muscle nociceptors to trigeminal motoneurones.

Adult↗

Sensitivity of rat temporalis muscle afferent fibers to peripheral N-methyl-D-aspartate receptor activation.

The temporalis muscle is a common source of pain in headache and chronic craniofacial pain conditions such as temporomandibular disorders, which have an increased prevalence in women. The characteristics of slowly conducting temporalis afferent fibers have not been investigated. Therefore, the aim of the present study was to examine the characteristics of slowly conducting temporalis muscle afferent fibers and to determine whether these fibers are excited by activation of peripheral N-methyl-D-aspartate receptors. The response properties of a total of 117 temporalis afferent fibers were assessed in male and female rats. A majority of these fibers had high mechanical thresholds and slow conduction velocities (<10 m/s). The mechanical threshold of the temporalis afferent fibers was inversely correlated with afferent conduction velocity, however, no sex-related differences in mechanical threshold were identified. There were also no sex-related differences in N-methyl-D-aspartate-evoked afferent discharge. Indeed, injection of a high concentration (1600 mM) of N-methyl-D-aspartate into the temporalis muscle was necessary to evoke significant afferent discharge. Thirty minutes after the initial injection of N-methyl-D-aspartate into the temporalis muscle, a second injection of N-methyl-D-aspartate produced a response only about 50% as large as the initial injection. Co-injection of ketamine (20 mM) with the second injection of N-methyl-D-aspartate significantly decreased N-methyl-D-aspartate-evoked afferent discharge in both sexes. This concentration of ketamine is greater than that needed to attenuate afferent discharge evoked by injection of glutamate into the masseter muscle. These results suggest that unlike masseter afferent fibers, temporalis afferent fibers are relatively insensitive to peripheral N-methyl-D-aspartate receptor activation.

Afferent Pathways↗

One hour of tongue-task training is associated with plasticity in corticomotor control of the human tongue musculature.

Corticomotor control of the human tongue has been reported to undergo neuroplastic changes following several days of training in a tongue-protrusion task. The aims of the present study were to determine if a 1 h tongue-task training is sufficient to induce signs of neuroplastic changes in the corticomotor pathways, and to obtain preliminary information on the time course of such changes. Corticomotor excitability was assessed by changes in electromyographic activity evoked by transcortical magnetic stimulation (TMS) in 11 healthy subjects. Motor evoked potentials (MEPs) recorded in the tongue musculature and the first dorsal interosseous (FDI) muscle were assessed at four sessions: at baseline before training, 30 min after training, and 1 and 7 days after training. All subjects performed successfully the task (success rate: 38+/-4%). Thresholds for evoking MEPs by TMS in the tongue were decreased at 30 min, 1 and 7 days after training compared with baseline (ANOVA: P<0.001). Tongue MEP amplitudes were significantly increased at 1 day follow-up and had returned to baseline values at 7 days follow-up (ANOVA: P<0.001). No significant effect of tongue-task training on FDI MEPs was observed (ANOVA: P=0.160). Corticomotor topographic maps revealed increases (ANOVA: P<0.001) in area at the 1 day follow-up. The success rate was significantly correlated to the net increases in tongue MEPs at 1 day follow-up (Spearman: 0.615; P=0.0039). The present findings confirm that tongue task training is associated with plasticity of corticomotor excitability specifically related to the tongue musculature and further document that plasticity is evident within 30 min post-training and may last up to at least 7 days.

Adult↗

Reproducibility of the masseteric exteroceptive suppression period using stimulus-response curves.

The present study evaluated the reproducibility of the late exteroceptive suppression period (ES2) and of pain perception. The surface electro-myogram (EMG) was recorded from the left masseter muscle in 12 males and 12 females (22-31 year). Thirteen fixed stimulus intensities from 5 to 25 mA with 2.5 mA intervals were applied at random to the left mental area, and stimulus-response (S-R) curves were built for each subject. The first stimulation intensity at which the ES2 appeared was defined the reflex threshold, while the lowest stimulus intensity the subjects scored as painful, was called the pain threshold. Using the S-R curves, the other reflex parameters (appearance level, saturation level, slope from appearance to saturation, maximum duration of ES2, and maximum suppression degree) were also determined. Two measurement sessions were scheduled. Both the reflex and the pain sensation appeared at significantly lower stimulus intensity in females than males (P < 0.05). The reflex threshold, the reflex appearance and saturation level showed a significant decrease from the first to second session (P < 0.05), while the pain threshold was significantly higher during the second session (P < 0.01). By contrast, a good reproducibility was found for the maximum duration and suppression degree of ES2. Consequently, if S-R curves would be used to study the relation between the ES2 parameters and stimulus intensity in normal subjects for their applicability in clinical conditions, maximum duration and maximum suppression degree should be focused upon, in order to avoid session and gender effects as confounding factors.

Adult↗

Patterns of experimentally induced pain in pericranial muscles.

Nociceptive mechanisms in the craniofacial muscle tissue are poorly understood. The pain pattern in individual pericranial muscles has not been described before. Experimental muscle pain was induced by standardized infusions of 0.2 ml 1 m hypertonic saline into six craniofacial muscles (masseter, anterior temporalis, posterior temporalis, trapezius, splenius capitis and sternocleidomastoid) in 20 healthy subjects. The pressure pain thresholds (PPTs) were determined before and after infusions. The subjects continuously reported intensity of saline-induced pain on an electronic visual analogue scale (VAS) and the perceived area of pain was drawn on anatomical maps. The pain areas were measured and the localization determined by a new centre-of-gravity method. The PPTs were lowest on the sternocleidomastoid muscle (anova: P<0.001), but the saline-evoked VAS pain scored highest following injection into the masseter muscle (anova: P<0.05). The centre-of-gravity measures demonstrated significantly different localization of the pain areas (anova: P<0.001). The trigeminally vs. the cervically innervated muscles had significantly different patterns of spread and referral of pain according to trigeminally vs. cervically innervated dermatomes (P<0.005). In conclusion, there appear to be characteristic pain patterns and pain sensitivity in different craniofacial muscles in healthy volunteers, which may be of importance for further research on different craniofacial pain conditions.

Face↗

Activated protein C resistance -- in the absence of factor V Leiden -- and pregnancy.

BACKGROUND: Activated protein C (APC) resistance with or without factor V Leiden (FVL) is a major risk factor for venous thromboembolism. Many previous pregnancy studies have been focused on APC resistance caused by FVL. Very few have investigated APC resistance in the absence of FVL (APCR(FVL-)). MATERIAL AND METHODS: In a prospective study of 2480 unselected gravidae, blood was drawn in early pregnancy (mean = 12 weeks of gestation). APC resistance was analyzed by an APTT-based method (Coatest) APC-resistance) and the presence of FVL was determined by PCR. The APCR(FVL-) group had similar mean APC resistance ratio as the heterozygous carriers of FVL. The analyses were carried out no earlier than 3 months after delivery when all data were recorded. Small-for-gestational age (SGA) was used as a proxy for intrauterine growth restriction. RESULTS: When compared with the control group, women with APCR(FVL-) had no increased risk of SGA, pre-eclampsia, first trimester fetal loss or venous thromboembolism. However, they had an increased risk of second trimester fetal loss (7.3% vs. 2.7%, P = 0.01), and a tendency of being overweight (17.3% vs. 12.6%, P = 0.19) and of delivering extremely preterm (2.8% vs. 1.0%, P = 0.11). CONCLUSION: Women with APC resistance not caused by FVL were not at increased risk for SGA, pre-eclampsia, first trimester fetal loss, or abnormal blood loss. However, they showed an increased prevalence of second trimester fetal loss.

Activated Protein C Resistance↗

Influence of sensory deprivation and perturbation of trigeminal afferent fibers on corticomotor control of human tongue musculature.

Several recent studies with transcranial magnetic stimulation (TMS) have demonstrated changes in motor evoked potentials (MEPs) in human limb muscles following modulation of sensory afferent inputs, but little is known about the regulation of the human tongue motor control. To test the effect of local anesthesia (LA) of the lingual nerve and topical application of capsaicin stimulation on tongue MEPs. Fourteen volunteers participated (21-30 years) in two randomized sessions; before, during a nerve block of the lingual nerve or topical capsaicin application (30 microl 5%) on the tongue, and after anesthesia or pain had subsided. EMG electrodes were placed on the tongue and the first dorsal interosseous (FDI) muscle (control). EMG signals were amplified, filtered (20 Hz-1 kHz), and sampled at 4 kHz (Nicolet, USA). TMS were delivered with a figure-of-eight coil (Magstim 200, UK). Scalp sites at which EMG responses were evoked in the relaxed tongue or FDI at the lowest stimulus strength were determined, i.e., motor threshold (T). MEPs were assessed using stimulus-response curves in steps of 10% T. Eight stimuli were presented at each stimulus level. The proximal hypoglossal nerve was activated by TMS delivered over the parieto-occipital skull distal to the right ear. Eight stimuli were delivered at 50% of maximum stimulator output. ANOVAs were used to analyze latency and peak-to-peak amplitudes. Capsaicin evoked mild pain (2.8+/-0.5), and a strong burning sensation (6.2+/-0.4) on 0-10 visual analogue scales. MEP amplitudes in tongue and FDI were not influenced by capsaicin (P>0.44) but by stimulus strength (P<0.001). MEP latencies in tongue (8.9+/-0.2 ms) and FDI (22.4+/-0.4 ms) were not affected by capsaicin (P>0.19). Hypoglossal nerve stimulation evoked a short-latency (3.6+/-0.9 ms) response (mean amplitude 65+/-9 microV); but was unaffected by capsaicin (P>0.54). LA did not have any effect on FDI MEPs but was associated with a significant facilitation of tongue MEPs at T+50% and T+60% about 50 min after the nerve block in the recovery phase. Also in this condition, the direct motor responses evoked by hypoglossal nerve stimulation remained constant. No direct effect of a strong burning sensation could be shown on peripheral or central corticomotor pathways to the relaxed tongue musculature, however, LA of the lingual nerve (cranial nerve V) seems able to induce a delayed change in corticomotor control of tongue musculature (cranial nerve XII) possibly related to unmasking effects at the cortical level but not completely excluding excitability changes at the brain stem level.

Adult↗

Cerebellar inhibition of inferior olivary transmission in the decerebrate ferret.

Stimulation around the superior cerebellar peduncle or within the deep cerebellar nuclei is known to inhibit the inferior olive with a very long latency. It has been suggested that this inhibition is mediated by the GABA-ergic nucleo-olivary pathway, but alternative explanations such as activation of an indirect excitatory pathway or a pathway via the red nucleus are possible. A long-latency inhibition via the nucleo-olivary pathway would have profound implications for cerebellar function and the present study was performed to test alternative explanations and to characterize the nucleo-olivary inhibition. Climbing fibre responses (CFRs), evoked by periorbital stimulation and recorded from the cerebellar cortex, could be inhibited by stimulation of two distinct mesencephalic areas. One was located within the superior cerebellar peduncle and the other about 1 mm further ventrally. Inhibition evoked from either area occurred in the inferior olive and was independent of a red nucleus relay. Single Purkinje cell recordings revealed that inhibition from the ventral area was not secondary to olivary activation. It is concluded that stimulation of the ventral area activated nucleo-olivary fibres. The inhibition elicited by stimulation within the peduncle probably resulted from indirect activation on the nucleo-olivary fibres via antidromic activation of the interpositus nucleus. The time courses of the inhibition from the two areas were indistinguishable. The duration of the strongest inhibition was short and had a sharp peak at about 30 ms. It is suggested that the time course of the inhibition is important for temporal regulation of learned responses.

Animals↗

Effects of masticatory muscle fatigue without and with experimental pain on jaw-stretch reflexes in healthy men and women.

OBJECTIVE: To examine the effects of experimentally evoked masticatory muscle fatigue, without and with experimental muscle pain, on the short-latency jaw-stretch reflex, using a randomised crossover design. METHODS: Reflexes were evoked in both the masseter and temporalis muscles in 15 men and 13 women. The study was performed in two blocks, both containing 3 experimental conditions (before, directly after, and 15 min after provocation). Provocation consisted of a fatiguing chewing test, followed by an intramuscular injection of either isotonic saline (IS; non-painful) or hypertonic saline (HS; painful). RESULTS: No significant effects of the experimental condition 'fatigue+IS' were found for any of the reflex outcome variables. For each muscle, the 'fatigue+HS' condition yielded significantly higher normalized reflex amplitudes than the other conditions. Several muscles displayed gender differences regarding both onset latency and normalized reflex amplitude. CONCLUSIONS: Experimentally evoked mild-to-moderate muscle fatigue does not modulate the human jaw-stretch reflex. On the other hand, experimental muscle pain, evoked after the performance of a fatiguing chewing test, does yield a facilitation of this reflex. The gender differences found in both onset latency and peak-to-peak amplitude stress the need to take gender into consideration in future jaw reflex studies. SIGNIFICANCE: The sensitivity of the human jaw-stretch reflex can be modulated by HS-induced muscle pain; not by muscle fatigue that is provoked by intense chewing.

Adult↗

Risk of a first venous thrombotic event in carriers of a familial thrombophilic defect. The European Prospective Cohort on Thrombophilia (EPCOT).

BACKGROUND: Reliable risk estimates for venous thrombosis in families with inherited thrombophilia are scarce but necessary for determining optimal screening and treatment policies. OBJECTIVES: In the present analysis, we determined the risk of a first venous thrombotic event in carriers of a thrombophilic defect (i.e. antithrombin-, protein C- or protein S deficiency, or factor V Leiden). PATIENTS AND METHODS: The asymptomatic carriers had been tested prior to this study in nine European thrombosis centers because of a symptomatic carrier in the family, and were followed prospectively for 5.7 years on average between March 1994 and January 2001. Annually, data were recorded on the occurrence of risk situations for venous thrombosis and events (e.g. venous thrombosis, death). RESULTS: Twenty-six of the 575 asymptomatic carriers (4.5%) and seven of the 1118 controls (0.6%) experienced a first deep venous thrombosis or pulmonary embolism during follow-up. Of these events, 58% occurred spontaneously in the carriers compared with 43% in the controls. The incidence of first events was 0.8% per year (95% CI 0.5-1.2) in the carriers compared with 0.1% per year (95% CI 0.0-0.2) in the controls. The highest incidence was associated with antithrombin deficiency or combined defects, and the lowest incidence with factor V Leiden. CONCLUSIONS: The incidence of venous events in asymptomatic individuals from thrombophilic families does not exceed the risk of bleeding associated with long-term anticoagulant treatment in the literature (1-3%).

Adolescent↗

Glutamate evoked neck and jaw muscle pain facilitate the human jaw stretch reflex.

OBJECTIVE: Although pain and neuromuscular function are clearly linked in several clinical conditions manifested in the craniofacial and cervical regions, it is unclear if pain in these regions influences reflexly evoked activity in the jaw or neck muscles in humans. The aim of the present study was to test the effects of glutamate-evoked jaw or neck muscle pain on the jaw stretch reflex recorded in both jaw and neck muscles. METHODS: Nineteen healthy men participated in the study. Electromyographic (EMG) recordings were made from the left masseter (MAL) and right masseter (MAR) muscles and the right sternocleidomastoid (SCM) and splenius (SP) muscles. Glutamate (1 M) or isotonic saline was injected into the MAR or right SP in random order and then the other solution was injected 1-3 weeks later. Pain intensity was scored on a 10 cm visual analogue scale. Stretch reflexes were evoked by standardized jaw stretches before, during and 15 min after the end of the experimental muscle pain. Twenty trials were averaged in each condition. RESULTS: Pain evoked by MAR or SP glutamate injections was associated with a significant increase in the stretch reflex amplitude recorded in both MAR and SCM. The onset and offset times and duration of the stretch reflex did not change in any muscle during the various pain conditions. Injection of isotonic saline into the MAR or SP did not produce any significant change in the reflex parameters in any of the muscles. CONCLUSIONS: The results indicate the close interplay between the craniofacial and cervical regions in the neuromuscular changes that may result from musculoskeletal pain in either region. SIGNIFICANCE: The changes in neuromuscular activity documented in this study may be involved in the clinical occurrence of altered muscle activity in the orofacial and cervical regions as a result of deep tissue trauma and pain.

Adult↗

Effects of experimental muscle pain on mechanical properties of single motor units in human masseter.

OBJECTIVE: Muscle pain is known to influence muscle activity but the details of its effects on the mechanical properties of single motor units (SMU) have not been described. We have recently reported a decreased firing rate of SMU in the human masseter muscle during painful contractions with a constant force output. Force output can be modulated by the SMU discharge rate in relation to the contractile properties of SMU. Therefore, the objective of the present study was to measure the mechanical properties of SMU in the masseter to clarify the mechanism which underlies the decrease in SMU firing rate during jaw-muscle pain. METHODS: A spike-triggered averaging (STA) technique was used to determine the mechanical properties of low-threshold SMU in the masseter muscle recorded with fine wire electrodes during a voluntary isometric contraction. The twitch amplitude, contraction time, and half-relaxation time were determined from the averaged force records before and during experimental jaw-muscle pain induced by injection of 0.2 ml (100 microg/ml) capsaicin in 8 healthy subjects. Injections of 0.2 ml isotonic saline served as a non-painful control in 11 healthy subjects. RESULTS: The twitch amplitude was significantly increased during capsaicin-evoked muscle pain (P<0.001) without significant changes of half-relaxation time and contraction time. No significant changes in SMU twitch properties were observed during the control injections. CONCLUSIONS: Potentiation of twitch force could be a possible compensatory mechanism to maintain a constant force output during painful isometric contractions when SMU firing decreases. This finding therefore provides new information on the adaptation of motor function by muscle pain.

Adult↗

Office blood pressure underestimates ambulatory blood pressure in peripheral arterial disease in comparison to healthy controls.

Patients with peripheral arterial disease (PAD) constitute a subgroup of high-risk hypertensives, but controlled studies on 24-h blood pressure (BP) and diurnal variation of BP are lacking. This study was performed in order to test the hypothesis that office BP (OBP) may underestimate 24-h BP in PAD patients in comparison to a matched control group. In all, 98 male patients (mean age 68 years) with a history of intermittent claudication and an ankle/brachial index less than 0.9, and 94 controls matched for age but without PAD or ischaemic heart disease performed 24-h recordings of ambulatory BP. A total of 59 patients had a history of hypertension and 69 were on treatment with BP-lowering drugs as compared to 17 and 23 of the control subjects, respectively. Office as well as 24-h systolic BP (SBP) were higher in patients as compared to controls (151 +/- 22 vs 140 +/- 20 mmHg, P < 0.001 and 142 +/- 14 vs 133 +/- 15 mmHg, P < 0.001, respectively), but did not differ with regard to diastolic BP. In an analysis of covariance with the continuous factors age, office SBP and the categorical factor antihypertensive treatment, 24-h SBP was higher in PAD patients compared to controls (P < 0.05). The difference between office and night SBP was lower in PAD patients with antihypertensive treatment compared to controls (P = 0.01). In conclusion, Male patients with PAD had higher systolic but not diastolic BP than age-matched control subjects. In PAD patients, 24-h SBP was higher than expected from OBP compared to controls. Night SBP was higher only in patients with antihypertensive treatment. In PAD patients, especially when on antihypertensive treatment, the severity of hypertension may be underestimated when based on OBP only.

Aged↗

Feedback control of Purkinje cell activity by the cerebello-olivary pathway.

The pathway from the deep cerebellar nuclei to the inferior olive, the source of the climbing fibre input to the cerebellum, inhibits olivary transmission. As climbing fibre activity can depress the background firing of the Purkinje cells, it was suggested that nucleo-olivary (N-O) inhibition is a negative feedback mechanism for regulating Purkinje cell excitability. This suggestion was investigated, in a set-up with decerebrate ferrets, both by blocking and by stimulating cerebellar output while recording Purkinje cell activity. Blocking the N-O pathway was followed by an increased climbing fibre activity and a dramatic reduction in simple spike firing. Stimulation of the N-O fibres depressed climbing fibre responses and caused an increase in simple spike firing. These results are taken as support for the feedback hypothesis.

Action Potentials↗

Hereditary thrombophilia and fetal loss: a prospective follow-up study.

BACKGROUND: As the placental vessels are dependent on the normal balance of procoagulant and anticoagulant mechanisms, inherited thrombophilia may be associated with fetal loss. OBJECTIVES: We performed a prospective study to investigate the relation between inherited thrombophilia and fetal loss, and the influence of thromboprophylaxis on pregnancy outcome. PATIENTS AND METHODS: Women were enrolled in the European Prospective Cohort on Thrombophilia (EPCOT). These included women with factor (F)V Leiden or a deficiency of antithrombin, protein C or protein S. Controls were partners or acquaintances of thrombophilic individuals. A total of 191 women (131 with thrombophilia, 60 controls) had a pregnancy outcome during prospective follow-up. Risk of fetal loss and effect of thromboprophylaxis were estimated by frequency calculation and Cox regression modelling. RESULTS: The risk of fetal loss appeared slightly increased in women with thrombophilia without a previous history of fetal loss who did not use any anticoagulants during pregnancy (7/39 vs. 7/51; relative risk 1.4; 95% confidence interval 0.4, 4.7). Per type of defect the relative risk varied only minimally from 1.4 for FV Leiden to 1.6 for antithrombin deficiency compared with control women. Prophylactic anticoagulant treatment during pregnancy in 83 women with thrombophilia differed greatly in type, dose and duration, precluding solid conclusions on the effect of thromboprophylaxis on fetal loss. No clear benefit of anticoagulant prophylaxis was apparent. CONCLUSIONS: Women with thrombophilia appear to have an increased risk of fetal loss, although the likelihood of a positive outcome is high in both women with thrombophilia and in controls.

Adolescent↗