Allopregnanolone involvement in feeding regulation, overeating and obesity.

Obesity is strongly associated with ill health, primarily caused by consumption of excessive calories, and promoted (inter alia) by gamma-amino-butyric-acid (GABA) stimulating food intake by activating GABAA receptors (primarily with α3 and α2 subunits) in the hypothalamic arcuate nucleus and paraventricular nucleus. Allopregnanolone is a potent positive GABAA receptor modulating steroid (GAMS). As reviewed here, elevated allopregnanolone levels are associated with increases in food intake, preferences for energy-rich food, and obesity in humans and other mammals. In women with polycystic ovarian disease, high serum allopregnanolone concentrations are linked to uncontrolled eating, and perturbed sensitivity to allopregnanolone. Increases in weight during pregnancy also correlate with increases in allopregnanolone levels. Moreover, Prader-Willis syndrome is associated with massive overeating, absence of a GABAA receptor (with compensatory >12-, >5- and >1.5-fold increases in α4, γ2, and α1, α3 subunits), and increases in the α4, ßx, δ receptor subtype, which is highly sensitive to allopregnanolone. GABA and positive GABA-A receptor modulating steroids like allopregnanolone stimulates food intake and weight gain.

Abdominal adhesions in gynaecologic surgery after caesarean section: a longitudinal population-based register study.

OBJECTIVE: The aim of the study was to evaluate the association between abdominal adhesions at the time of gynaecologic surgery and a history of caesarean delivery, and to investigate obstetric factors contributing to adhesion formation after caesarean section (CS). DESIGN: Longitudinal population-based register study. SETTING: Sweden. POPULATION: Women undergoing benign hysterectomy and/or adnexal surgery in Sweden, 2000-2014, with a previous delivery during 1973-2013 (n = 15 479). METHODS: Information about abdominal adhesions during gynaecological surgery, prior medical history, pregnancies and deliveries were retrieved from Swedish National Health and Quality registers. MAIN OUTCOME MEASURES: Adhesions. RESULTS: In women with previous CS, adhesions were present in 37%, compared with 10% of women with no previous CS [odds ratio (OR): 5.18, 95% confidence interval (CI): 4.70-5.71]. Adhesions increased with the number of caesarean sections: 32% after one CS; 42% after two CS and 59% after three or more CS (P < 0.001). Regardless of the number of CS, factors at CS such as age ≥35 years (aOR: 1.28, 95% CI: 1.05-1.55), body mass index (BMI) ≥30 [adjusted OR (aOR): 1.91, 95% CI: 1.49-2.45] and postpartum infection (aOR: 1.55, 95% CI: 1.05-2.30) increased the risk of adhesions. CONCLUSIONS: Presence of adhesions in abdominal gynaecological surgery is associated with women's personal history of caesarean delivery. The number of caesarean sections was the important predictor of adhesions; advanced age, obesity and postpartum infection further increased the incidence. TWEETABLE ABSTRACT: Repeat caesarean, age, obesity and infection increased the risk of pelvic adhesions after caesarean section.

Plasma Cytokine Levels in Fibromyalgia and Their Response to 15 Weeks of Progressive Resistance Exercise or Relaxation Therapy.

The aims of this study were to compare circulating cytokines between FM and healthy controls and to investigate the effect on cytokine levels by 15 weeks of progressive resistance exercise or relaxation therapy in FM. Baseline plasma cytokine levels and clinical data were analyzed in 125 women with FM and 130 age-matched healthy women. The FM women were then randomized to progressive resistance exercise (n = 49) or relaxation (n = 43). Baseline IL-2, IL-6, TNF-α, IP-10, and eotaxin were higher in FM than in healthy controls (P < 0.041), whereas IL-1ß was lower (P < 0.001). There were weak correlations between cytokine levels and clinical variables. After both interventions, IL-1ra had increased (P = 0.004), while IL-1ß had increased in the relaxation group (P = 0.002). Changes of IFN-γ, IL-2, IL-4, IL-6, IL-8, and IL-17A were weakly correlated with changes of PPT, but there were no significant correlations between changes of cytokine and changes in other clinical variables. The elevated plasma levels of several cytokines supports the hypothesis that chronic systemic inflammation may underlie the pathophysiology of FM even if the relation to clinical variables was weak. However, 15 weeks of resistance exercise, as performed in this study, did not show any anti-inflammatory effect on neither FM symptoms nor clinical and functional variables. This trial is registered with ClinicalTrials.gov NCT01226784, registered October 21, 2010. The first patient was recruited October 28, 2010.

The genes of all seven CYP3A isoenzymes identified in the equine genome are expressed in the airways of horses.

In the present study, we examined the gene expression of cytochrome P450 3A (CYP3A) isoenzymes in the tracheal and bronchial mucosa and in the lung of equines using TaqMan probes. The results show that all seven CYP3A isoforms identified in the equine genome, that is, CYP3A89, CYP3A93, CYP3A94, CYP3A95, CYP3A96, CYP3A97 and CYP3A129, are expressed in the airways of the investigated horses. Though in previous studies, CYP3A129 was found to be absent in equine intestinal mucosa and liver, this CYP3A isoform is expressed in the airways of horses. The gene expression of the CYP3A isoenzymes varied considerably between the individual horses studied. However, in most of the horses CYP3A89, CYP3A93, CYP3A96, CYP3A97 and CYP3A129 were expressed to a high extent, while CYP3A94 and CYP3A95 were expressed to a low extent in the different parts of the airways. The CYP3A isoenzymes present in the airways may play a role in the metabolic degradation of inhaled xenobiotics. In some instances, the metabolism may, however, result in bioactivation of the xenobiotics and subsequent tissue injury.

Differential gene expression of CYP3A isoforms in equine liver and intestines.

Recently, seven CYP3A isoforms - CYP3A89, CYP3A93, CYP3A94, CYP3A95, CYP3A96, CYP3A97 and CYP129 - have been isolated from the horse genome. In this study, we have examined the hepatic and intestinal gene expression of these CYP3A isoforms using TaqMan probes. We have also studied the enzyme activity using luciferin-isopropyl acetal (LIPA) as a substrate. The results show a differential gene expression of the CYP3A isoforms in the liver and intestines in horses. In the liver, CYP3A89, CYP3A94, CYP3A96 and CYP3A97 were highly expressed, while in the intestine there were only two dominating isoforms, CYP3A93 and CYP3A96. The isoform CYP3A129 was not detected in the liver or the intestine, although this gene consists of a complete set of exons and should therefore code for a functional protein. It is possible that this gene is expressed in tissues other than the liver and intestines. In the intestine, both CYP3A96 and CYP3A93 showed the highest gene expression in the duodenum and the proximal parts of the jejunum. This correlated with a high protein expression in these tissues. Studies of the enzyme activity showed the same K(m) for the LIPA substrate in the liver and the intestine, while the maximum velocity (V(max)) in the liver was higher than in the intestine. Our finding of a differential gene expression of the CYP3A isoforms in the liver and the intestines contributes to a better understanding of drug metabolism in horses.

Parental experience of bedside handover during childbirth: A qualitative interview study.

BACKGROUND: It has been described that bedside reporting can contribute to patient safety and increase patient involvement in healthcare. To our knowledge, however, there is no existing research on bedside handover during labour. AIM: The aim of this study was to examine the patient's experiences of bedside handover during labour. METHOD: A qualitative design was used. Nineteen couples were interviewed after childbirth regarding their experiences of bedside handover during delivery. Twelve of those had experienced bedside handover and were, thereby, included in the study. The interviews were performed in a delivery ward in Stockholm during January 2018. The material was analysed according to content analysis. RESULTS: Four main categories emerged from the data: non-verbal communication, verbal communication, concerns, and birth experience. In general, bedside handover was perceived to be positive, the participants felt they were treated professionally, and that they had been involved during the handover. One advantage with the handover was the possibility for parents to confirm the sharing of information during the handover, which made them feel secure. Moreover, most of the parents reported they received good treatment and had a good labour experience. Parents' experiences of bedside handover and midwives' support were summarised as follows: midwives used common words and avoided using medical terminology, and they kept eye contact with the woman and her partner. CONCLUSION: Bedside handover was experienced by both parents as a way of being positively included in the care of their newborn. The caregivers were described as being attentive, respectful, and were good listeners.

Severe odontogenic infections: focus on more effective early treatment.

Our aim was to investigate delay in the treatment of patients with acute odontogenic infections. A prospective clinical study and a questionnaire survey were designed and implemented in the emergency maxillofacial surgical patients of Helsinki University Hospital, Finland, over a one-year period. Altogether 88 adult patients with odontogenic infections confirmed by hospital examination were included in the analysis. The outcome variable was admission to hospital. Two-thirds of the patients had had previous visits for health care for their current infection. Treatment was started in nearly half the patients before hospital admission, and half of the treatment provided was exclusively antibiotics. The focus of infection was detected in half the patients before admission. Patients who were required further hospitalisation were younger than who were discharged (p=0.021). Less well-educated patients were more likely to be hospitalised than patients in other education groups (p=0.033). Leucocytosis was more prevalent in patients with a mandibular focus (p=0.008), non-identified focus (p=0.010), and infection as a result of elective tooth extraction (p=0.026). The number of previous health care visits for the acute infection was notably high. Early treatment of infection may be overlooked, particularly in younger age groups and less well-educated patients. Challenges in making the correct diagnosis and prescribing effective treatment for such infections cause additional health care visits and unnecessary delay in care. More attention should be paid to the early detection and comprehensive primary treatment of odontogenic infections.

Effect of circadian rhythm, age, training and acute lameness on serum concentrations of cartilage oligomeric matrix protein (COMP) neo-epitope in horses.

BACKGROUND: Molecular serum markers that can identify early reversible osteoarthritis (OA) in horses are lacking. OBJECTIVES: We studied serum concentrations of a novel cartilage oligomeric matrix protein (COMP) neo-epitope in horses subjected to short-term exercise and with acute lameness. The effects of circadian rhythm and age were also evaluated. STUDY DESIGN: Longitudinal studies in healthy horses and cross-sectional comparison of lame and non-lame horses. METHODS: Sera were collected from five horses before and after short-term interval exercise and during full-day box rest. Sera from 32 acutely lame horses were used to evaluate age-related effects. Independent samples from control horses (n = 41) and horses with acute lameness (n = 71) were included. COMP neo-epitope concentrations were analysed using custom-developed inhibition ELISAs validated for equine serum. The presence of COMP neo-epitope was delineated in healthy and osteoarthritic articular cartilage with immunohistochemistry. RESULTS: COMP neo-epitope concentrations decreased after speed training but returned to baseline levels post-exercise. No correlations between age and serum COMP neo-epitope concentrations were found (r = 0.0013). The mean (±s.d.) serum concentration of COMP neo-epitope in independent samples from non-lame horses was 0.84 ± 0.38 µg/mL, and for lame horses was 5.24 ± 1.83 µg/mL (P<0.001). Antibodies against COMP neo-epitope did not stain normal articular cartilage, but intracytoplasmic staining was found in superficial chondrocytes of mild OA cartilage and in the extracellular matrix of moderately osteoarthritic cartilage. MAIN LIMITATIONS: ELISA was based on polyclonal antisera rather than a monoclonal antibody. There is a sex and breed bias within the groups of horses, also it could have been of value to include horses with septic arthritis and tendonitis and investigated joint differences. CONCLUSIONS: This COMP neo-epitope can be measured in sera, and results indicate that it could be a biomarker for pathologic fragmentation of cartilage in connection with acute joint lameness.

Living with painful endometriosis - A struggle for coherence. A qualitative study.

OBJECTIVES: The study sought to examine women's experience of painful endometriosis including long-term aspects, social consequences, impact of treatment and development of own coping strategies. STUDY DESIGN: This qualitative study was based on 16 individual interviews analyzed according to grounded theory. The thirteen women (age 24-48) were recruited at a pain clinic in Stockholm, Sweden. RESULTS: A theory illustrating women's experience of living with painful endometriosis was developed with three categories and one core category. Bidirectional interactions between the categories and with the core category were found. Endometriosis influenced the women's sensations, feelings and reactions, creating a sense of difference from other women (category: Woman with painful endometriosis). The condition led to either helpful or harmful encounters with health care and significant others (category: Dependence). It also had overall physical, social and existential consequences (category: A ruined life). To cope, the women had to struggle for coherence by searching for understanding, coping and meaning (core category: Living with painful endometriosis). CONCLUSIONS: Living with severe painful endometriosis signified a struggle for coherence. The women needed to deal with feelings of difference, dependence and a ruined life and thus struggled for understanding, coping and meaning. Health-care providers should promote the struggle for coherence by explaining the feeling of difference, minimizing dependence and supporting the process of disease-related grief.

The role of long-term physical exercise on performance and brain activation during the Stroop colour word task in fibromyalgia patients.

The Stroop colour word test (SCWT) has been widely used to assess changes in cognitive performance such as processing speed, selective attention and the degree of automaticity. Moreover, the SCWT has proven to be a valuable tool to assess neuronal plasticity that is coupled to improvement in performance in clinical populations. In a previous study, we showed impaired cognitive processing during SCWT along with reduced task-related activations in patients with fibromyalgia. In this study, we used SCWT and functional magnetic resonance imagingFMRI to investigate the effects of a 15-week physical exercise intervention on cognitive performance, task-related cortical activation and distraction-induced analgesia (DIA) in patients with fibromyalgia and healthy controls. The exercise intervention yielded reduced fibromyalgia symptoms, improved cognitive processing and increased task-related activation of amygdala, but no effect on DIA. Our results suggest beneficial effects of physical exercise on cognitive functioning in FM.

Tolerance development to Morris water maze test impairments induced by acute allopregnanolone.

The progesterone metabolite allopregnanolone, like benzodiazepines, reduces learning and impairs memory in rats. Both substances act as GABA agonists at the GABA-A receptor and impair the performance in the Morris water maze test. Women are during the menstrual cycle, pregnancy, and during hormone replacement therapy exposed to allopregnanolone or allopregnanolone-like substances for extended periods. Long-term benzodiazepine treatment can cause tolerance against benzodiazepine-induced learning impairments. In this study we evaluated whether a corresponding allopregnanolone tolerance develops in rats. Adult male Wistar rats were pretreated for 3 days with i.v. allopregnanolone injections (2 mg/kg) one or two times a day, or for 7 days with allopregnanolone injections 20 mg/kg intraperitoneally, twice a day. Thereafter the rats were tested in the Morris water maze for 5 days and compared with relevant controls. Rats pretreated with allopregnanolone twice a day had decreased escape latency, path length and thigmotaxis compared with the acute allopregnanolone group that was pretreated with vehicle. Pretreatment for 7 days resulted in learning of the platform position. However, the memory of the platform position was in these tolerant rats not as strong as in controls only given vehicle. Allopregnanolone treatment was therefore seen to induce a partial tolerance against acute allopregnanolone effects in the Morris water maze.

Substrate and product dependence of force and shortening in fast and slow smooth muscle.

To explore the molecular mechanisms responsible for the variation in smooth muscle contractile kinetics, the influence of MgATP, MgADP, and inorganic phosphate (P(i)) on force and shortening velocity in thiophosphorylated "fast" (taenia coli: maximal shortening velocity Vmax = 0.11 ML/s) and "slow" (aorta: Vmax = 0.015 ML/s) smooth muscle from the guinea pig were compared. P(i) inhibited active force with minor effects on the V(max). In the taenia coli, 20 mM P(i) inhibited force by 25%. In the aorta, the effect was markedly less (< 10%), suggesting differences between fast and slow smooth muscles in the binding of P(i) or in the relative population of P(i) binding states during cycling. Lowering of MgATP reduced force and V(max). The aorta was less sensitive to reduction in MgATP (Km for Vmax: 80 microM) than the taenia coli (Km for Vmax: 350 microM). Thus, velocity is controlled by steps preceding the ATP binding and cross-bridge dissociation, and a weaker binding of ATP is not responsible for the lower V(max) in the slow muscle. MgADP inhibited force and V(max). Saturating concentrations of ADP did not completely inhibit maximal shortening velocity. The effect of ADP on Vmax was observed at lower concentrations in the aorta compared with the taenia coli, suggesting that the ADP binding to phosphorylated and cycling cross-bridges is stronger in slow compared with fast smooth muscle.

Repeated allopregnanolone exposure induces weight gain in schedule fed rats on high fat diet.

Ingestion of energy rich high fat diets is one of the determining factors associated with the obesity epidemic. Therefore, much can be learned from studies of obesity-related substances given to animals fed a high fat diet. The progesterone metabolite allopregnanolone is a potent positive modulator of the gamma-aminobutyric acid (GABA)A-receptor, and both allopregnanolone and GABA have been implicated in evoking hyperphagia. In this study, food intake and body weight gain were investigated during repeated allopregnanolone exposure. Male Wistar rats were studied when fed chow ad libitum, with chow access for 4h per day or with 45% high fat pellets for 4h per day. Rats on the high fat diet were separated into obesity prone and obesity resistant individuals. Subcutaneous injections of allopregnanolone were given once daily over five consecutive days. Repeated exposure to allopregnanolone lead to increased weight gain, significantly so in schedule fed rats on a high fat diet. The increased weight gain was correlated to an increased energy intake. Both obesity resistant and obesity prone rats responded to allopregnanolone with increased weight gain. Obesity resistant rats treated with allopregnanolone increased their energy intake and ate as much as vehicle treated obesity prone rats. Their weight gain was also increased to the level of obesity prone rats injected with just the vehicle carrier oil. Thus, it appears that allopregnanolone may be one of the endogenous factors involved in weight gain, especially when the diet is rich in fat.

Normalization of aberrant resting state functional connectivity in fibromyalgia patients following a three month physical exercise therapy.

Physical exercise is one of the most efficient interventions to mitigate chronic pain symptoms in fibromyalgia (FM). However, little is known about the neurophysiological mechanisms mediating these effects. In this study we investigated resting-state connectivity using functional magnetic resonance imaging (fMRI) before and after a 15 week standardized exercise program supervised by physical therapists. Our aim was to gain an understanding of how physical exercise influences previously shown aberrant patterns of intrinsic brain activity in FM. Fourteen FM patients and eleven healthy controls successfully completed the physical exercise treatment. We investigated post- versus pre-treatment changes of brain connectivity, as well as changes in clinical symptoms in the patient group. FM patients reported improvements in symptom severity. Although several brain regions showed a treatment-related change in connectivity, only the connectivity between the right anterior insula and the left primary sensorimotor area was significantly more affected by the physical exercise among the fibromyalgia patients compared to healthy controls. Our results suggest that previously observed aberrant intrinsic brain connectivity patterns in FM are partly normalized by the physical exercise therapy. However, none of the observed normalizations in intrinsic brain connectivity were significantly correlated with symptom changes. Further studies conducted in larger cohorts are warranted to investigate the precise relationship between improvements in fibromyalgia symptoms and changes in intrinsic brain activity.

The changing pattern of neonatal mortality in a regionalized system of perinatal care: A current update.

OBJECTIVE: Our earlier studies about the changing pattern of neonatal mortality were based on data from 1978-1979 and 1982-1983. In this report, we provide a modern update of the causes of neonatal deaths to help focus prevention measures. STUDY DESIGN: We reviewed neonatal deaths for the years 1995 and 1996 and assigned a clinical cause of death. Deaths were reviewed and analyzed by place of birth and death, according to level of care. We provided an estimate of the change in causes of death between 1982-1983 and 1995-1996 and calculated an idealized neonatal mortality rate for each level of care and for the entire state. RESULTS: The major changes in causes of death occurred in the respiratory distress syndrome (RDS) and extremely low birth weight (ELBW) categories. RDS showed a substantial decline, but ELBW deaths increased by nearly the same amount that RDS declined. The idealized neonatal mortality rate calculations suggest that fewer potentially medically preventable deaths occur now than in 1982-1983. Currently, more neonatal deaths of level I births occur in level III facilities than in 1982-1983. However, at that time, Iowa had only one tertiary facility, and the level II regional hospitals were the site of more deaths. CONCLUSION: We believe that assigning deaths to a clinical category rather than to a catastrophic final event helps focus on sources of preventable death in the medical care system. To reduce neonatal mortality, the incidence of lethal congenital malformations and ELBW infants must be impacted.

Progesterone concentrations in maternal and fetal serum are lower during functional dystocia than in normal labor.

Concentrations of progesterone and estradiol (E2) were measured in parturient serum and in fetal cord serum during normal labor and in women with functional dystocia. In the study group, there were no cases of cephalopelvic disproportion. In oxytocin-resistant dystocia, the course of labor could not be corrected with oxytocin. To ascertain the effect of oxytocin, we included a number of women whose labor had been induced with oxytocin, followed by normal cervical dilatation and descent of the fetus. All the parturients were grouped retrospectively into those with normal labor and those with dystocia, based on previous definitions. The serum concentrations of progesterone in both the fetal cord and maternal vein were found to be significantly lower in the oxytocin-resistant dystocia group than in women in spontaneous normal labor and those with oxytocin-induced labor and normal progression (P less than .05-.005). Oxytocin had no evident effect on the serum concentration of either progesterone or E2, nor did concentrations vary following epidural blockade. Serum E2 concentrations in the maternal vein were similar in all delivery groups. Fetal cord E2 serum concentrations were similar in all vaginal deliveries. Women with the most severe oxytocin-resistant dystocia, delivered by cesarean, had significantly lower serum concentrations of E2 in fetal cord serum compared with the vaginally delivered women (P less than .001).

Unexpected stimulatory effect of progesterone on human myometrial contractile activity in vitro.

OBJECTIVE: To investigate the effects of continuous exposure of progesterone on contractile activity of term human myometrium in vitro. METHODS: Myometrial biopsy specimens were obtained from 14 term pregnant women undergoing elective cesarean. The specimens were immediately immersed in Hepes buffer and buffer containing 0.33, 4.1, and 70 micrograms/mL progesterone. Muscle biopsies were dissected along the bundles of smooth muscle under stereomicroscope. These myometrial strips were mounted in tissue baths and superfused with Hepes buffer and buffer containing different concentrations of progesterone. RESULTS: The progesterone concentration of 0.33 microgram/mL had no significant effect on myometrial contractile activity. The concentrations of 4.1 and 70 micrograms/mL increased the frequency of contractions (P < .01 for each) and tonus (P < .01 for each), decreased the activity area of contractions (P < .01 for each), and delayed the onset of contractions (P < .01 and P < .05, respectively). CONCLUSION: When the myometrium is not deprived of progesterone, this hormone may have excitatory effects on the frequency of contractions and tonus of the lower uterine segment of term human myometrium.

Antitachyphylactic effects of progesterone and oxytocin on term human myometrial contractile activity in vitro.

OBJECTIVE: To determine whether progesterone causes any changes in the action of oxytocin on the contractile activity of term human myometrium in vitro. METHODS: Myometrial biopsies from 13 term pregnant women undergoing cesarean delivery were immediately immersed in Hepes buffer or buffer containing 5 micrograms/mL progesterone. In the laboratory under a stereomicroscope, the specimens were dissected into 1 x 7.5-mm muscle strips. These were mounted into six tissue baths and superfused with Hepes buffer and buffer containing 5 micrograms/mL progesterone, 5 micrograms/mL progesterone plus 10 microU/mL oxytocin, 5 micrograms/mL progesterone plus 100 microU/mL oxytocin, 10 microU/mL oxytocin, and 100 microU/mL oxytocin. Isometric tension was recorded constantly for at least 3 hours. RESULTS: The frequency of myometrial contractions and tonus increased by superfusion with progesterone, progesterone plus oxytocin, and oxytocin alone compared to buffer. In addition, a gradual decrease in frequency was observed after 60 minutes of contractions with oxytocin alone, whereas progesterone plus oxytocin had no such decrease. The activity area of contractions was greater with 10 microU/mL oxytocin and decreased with progesterone, progesterone plus both concentrations of oxytocin, and 100 microU/mL oxytocin alone, compared to buffer. CONCLUSIONS: Progesterone stimulated the frequency of contractions and tonus of strips from the lower uterine segment of term human myometrium. A lasting increase in the frequency of contractions was observed with superfusion of progesterone plus oxytocin, suggesting that progesterone counteracted the reaction of tachyphylaxis to oxytocin.

Early interdisciplinary rehabilitation programme for whiplash associated disorders.

PURPOSE: To assess the clinical outcomes of a multidisciplinary rehabilitation programme for early intervention of chronic whiplash associated disorders (WAD). The primary aim of the programme was to increase levels of activity and independence in patients suffering WAD. METHODS: Ninety subjects with purported chronic symptoms associated with whiplash associated disorder (WAD) were referred to a multi-centre multi-modal 5- and 8-week rehabilitation programme in 1997-1998, during which prospective and retrospective functional and psychological evaluations were conducted, the follow-up was to 6 months. RESULTS: Subjects indicated they were satisfied with the programme. Retrospective evaluation indicated increased ability to cope with and control pain and, to some extent, psychological aspects. The pain intensity in the neck and upper back were significantly decreased at 6 months follow-up. However, for most of the functional and psychological markers, no significant changes were found. CONCLUSIONS: A multi-modal rehabilitation programme for the chronic suffering attributed to WAD had positive effects according to several aspects of the retrospective evaluations, but according to most of the aspects evaluated prospectively the programme does not appear to have significant benefits.

Rock matrix diffusivity determinations by in-situ electrical conductivity measurements.

A fast method to determine rock matrix diffusion properties directly in the bedrock would be valuable in the investigation of a possible site for disposal of nuclear waste. An "effective diffusivity borehole log" would provide important information on the variability of this entity over the area studied. As opposed to traditional matrix diffusion laboratory experiments, electrical conductivity measurements are fast, inexpensive and also easy to carry out in-situ. In this study, electrical resistivity data from borehole logging, as well as from measurements on the actual core, is evaluated with the purpose of extracting matrix diffusivity data. The influence of migration of ions in the electrical double layer, which can be of great importance in low ionic strength pore water, is also considered in evaluating the in-situ data to accurately determine the effective pore diffusivity. The in-situ data compare fairly well to those measured in the rock core.