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.

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.

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.

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.

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.

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.

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.

Perinatal changes in expression of aquaporin-4 and other water and ion transporters in rat lung.

1. At birth, rapid removal of lung liquid from potential airspaces is required to establish pulmonary gas exchange. To investigate the role for water channels, aquaporins (AQP) and ion transporters in this process, the mRNA expression of AQP, Na+,K(+)-ATPase and the amiloride-sensitive Na+ channel (ENaC) were studied in the fetal and postnatal rat lung. 2. The mRNA expression of all transporters studied increased postnatally. 3. The following water channels were expressed in the lung, AQP1, 4 and 5. The most specific perinatal induction pattern was observed for AQP4. A sharp and transient increase of AQP4 mRNA occurred just after birth coinciding with the time course for clearance of lung liquid. This transient induction of AQP4 mRNA at birth was lung-tissue specific. Around birth there was a moderate increase in AQP1 mRNA, which was not transient. AQP5 increased continuously until adulthood. 4. Fetal lung AQP4 mRNA was induced by both beta-adrenergic agonists and glucocorticoid hormone, which are factors that have been suggested to accelerate the clearance of lung liquid. 5. Immunocytochemistry revealed that AQP4 was located in the basolateral membranes of bronchial epithelia in newborn rats, consistent with the view that this is the major site for perinatal lung liquid absorption. 6. The Na+,K(+)-ATPase alpha 1 subunit and ENaC alpha-subunit mRNA also increased around birth, suggesting that they co-operatively facilitate lung liquid clearance at birth. 7. These data indicate that removal of lung liquid at birth is associated with pronounced and well-synchronized changes in the expression of AQP and the ion transporters studied. The transient perinatal induction of AQP4, which could be prenatally induced by beta-adrenergic agonists, and the localization of this water channel strongly suggest that it plays a critical role for removal of lung liquid at the time of birth.

High progesterone is related to effective human labor. Study of serum progesterone and 5alpha-pregnane-3,20-dione in normal and abnormal deliveries.

BACKGROUND: The role of progesterone levels during human labor is unclear. OBJECTIVE: To investigate serum concentrations of progesterone and 5alpha-pregnane-3,20-dione in normal and abnormal deliveries. METHODS: Venous and umbilical cord serum samples were collected from 108 parturient women. In a further 49 deliveries, arterial and venous umbilical cord sera were collected separately. The concentrations of progesterone and 5alpha-pregnane-3,20-dione were determined by radioimmunoassay. The delivery modes studied were: elective cesarean section; oxytocin-resistant dystocia; normal but induced delivery, and normal spontaneous delivery. RESULTS: Progesterone concentrations in maternal and umbilical serum were higher following normal labor than after dystocia (p<0.005) and elective cesarean section (p<0.005). The maternal and umbilical progesterone concentrations in dystocia and elective cesarean section were between 77-43% of those in normal labor. The concentrations did not vary between gestational weeks 37 and 42, within the different modes of delivery. The 5alpha-pregnane-3,20-dione serum concentration in the fetal compartment was twice that in the maternal compartment (p<0.001); its concentration in venous umbilical serum was higher than in corresponding arterial samples (p<0.001). No distinct differences in the 5alpha-pregnane-3,20-dione serum concentration were found with regard to parity or mode of delivery. CONCLUSION: High progesterone concentrations during parturition appear to be related to effective labor. The findings support results from in vitro experiments on human term myometrium.

Continuous progesterone exposure associated with high contraction frequency in human term myometrial strips.

It has been shown that progesterone slightly reduced the work of human term myometrial strips. In vitro, 5 alpha-pregnane-3,20-dione and 3 alpha-hydroxy-5 alpha-pregnan-20-one, two major extra-hepatic metabolites of progesterone, had only minor effects or none at all. The myometrial strips were stored and superfused in a progestin-free buffer until the onset of contractions when progestin superfusion was commenced. In vivo, the human myometrium is never deprived of the influence of these steroids, either prior to or during labor. In the present investigation we studied whether progesterone and the two named progesterone metabolites would have a different effect when the myometrial strips were not deprived of steroid. Muscle biopsy samples from the lower uterine segment were immediately placed and stored in buffer containing progesterone, 5 alpha-pregnane-3,20-dione, or 3 alpha-hydroxy-5 alpha-pregnan-20-one. The strips were then bisected; one half was superfused with progestin buffer, and the other half with plain buffer to serve for control purposes. In strips continuously exposed to progesterone, the onset of contractions was delayed, compared with their progesterone-depleted controls. This was as expected, according to current opinion regarding progesterone and parturition. Once muscular contractions were established, the contraction frequency was significantly higher, due to a shorter muscular relaxation time, in the progesterone-superfused strips than in the controls and strips treated with progesterone metabolite superfusion. This was unexpected and can be interpreted as if continuous presence of progesterone facilitates human myometrial contraction frequency once contractions have started. Conversely, the 5 alpha-progesterone metabolites showed no effect or minor effects.

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.

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.

Testing of quantitative parameters in the 32P-postlabelling method.

The 32P-postlabelling technique involves many steps that need to be carefully controlled in order to obtain a reliable quantitative determination of DNA adducts. We have studied several of the parameters involved in the DNA digestion procedures as well as those concerned in the phosphorylation reaction. Since adducts behave in very different ways in the labelling reaction, an individual protocol has to be worked out for each particular type of adduct. Quantitation is usually possible only if a synthesized standard of the adduct under investigation is run in parallel to the DNA samples throughout the whole procedure.

Some quantitative considerations about DNA adduct enrichment procedures for 32P-postlabelling.

The concentrations of 2'-deoxyribonucleoside-3'-monophosphates remaining in calf-thymus DNA digests after nuclease P1 digestion or extraction into 1-butanol, the most commonly used adduct enrichment procedures prior to the application of the 32P-postlabelling assay, were measured using HPLC and 32P-postlabelling methods. When 10 micrograms of DNA digested to mononucleotides was used, the total amount of nucleotides remaining in the samples were approximately 4 and approximately 14 pmol after nuclease P1 treatment or 1-butanol extraction respectively. The influence of various concentrations of normal nucleotides on the labelling efficiency of a 2'-deoxyguanosine-3'-monophosphate adduct of benzo[a]pyrene diol-epoxide was also studied and found to depend upon the ratio of normal nucleotides/adducted nucleotides present in the sample. Also, the ATP/normal nucleotides ratio in the phosphorylation reaction may affect the quantitation of the adducts and thus deserves due consideration.

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).

Effects in vitro of progesterone and two 5 alpha-reduced progestins, 5 alpha-pregnane-3,20-dione and 5 alpha-pregnane-3 alpha-ol-20-one, on contracting human myometrium at term.

Progesterone is known to prevent labour at term in domestic animals, but its effect in primates is uncertain. 5 alpha-reduced progesterone metabolites are more potent central nervous system depressants than progesterone is itself. Progesterone and its 5 alpha-reduced metabolites also relax pregnant rat myometrium in vitro. The serum concentration of the initial 5 alpha-reduced metabolite, 5 alpha-pregnane-3,20-dione, is high during pregnancy, but decreases significantly prior to parturition. The next metabolite, 5 alpha-pregnane-3 alpha-ol-20-one, has anaesthetic properties in human beings. The purpose of this study was to ascertain whether these progesterone metabolites also suppress contracting human uterine muscle at term. An in vitro model was devised. Strips of human myometrial muscle were mounted in organ chambers and after regular contractions had become established, the strips were superfused with progestin solutions. The progestins were dissolved in the buffer using an ultrasound bath. Progesterone, used as reference substance, slightly reduced the measured amount of muscular work performed per contraction, recordable after 18 min of exposure (p less than 0.05). Similar results have been reported previously in the literature; 5 alpha-pregnane-3 alpha-ol-20-one showed the same tendency though not significant at the 5% level. 5 alpha-pregnane-3,20-dione evidently reduced the contraction frequency after 10 min of exposure (p less than 0.05). None of the substances affected the duration of the contraction. These 5 alpha-reduced progesterone metabolites are thus not potent inhibitors of contracting human term myometrium in vitro.

Relation between lightscanning and the histologic and mammographic appearance of malignant breast tumors.

The relation between real-time transillumination (lightscanning) and the histologic appearance of 243 breast carcinomas was evaluated. Lightscanning mainly failed in identifying ductal and lobular carcinomas in situ. The result of lightscanning was also poor regarding small, invasive carcinomas. The absorption patterns in elastosis and scar tissue associated with carcinoma played no important role in the ability of lightscanning to identify a cancer. The relation between the lightscanning and mammographic appearance of 85 breast cancers from the same material was also evaluated. Lightscanning performed poorly in identifying tumors characterized by classifications as compared to tumors with other mammographic appearances. However, the difference was not significant.

Stereotactic fine-needle aspiration for cytologic diagnosis of nonpalpable breast lesions.

Fine-needle aspiration for cytologic diagnosis was performed on 219 nonpalpable breast lesions by using a stereotactic localization technique. Cytologic results were correlated with mammographic findings, and therapeutic decisions were based on the results of both procedures. Representative cytologic material was obtained in 74% of the lesions. Strict criteria of representativeness were observed. If only cases with representative cytologic yield are considered, the sensitivity was 93% and the specificity was 97%. The predictive values were high except for the predictive value of a negative cytologic finding in a spiculated lesion (50%). Sampling errors caused by abundant fibrosis, needle deviation, and difficulty in defining the lesion on the stereoscopic views are discussed. Another source of sampling error may be the mixed nature of some lesions consisting of benign and malignant components. Fine-needle aspiration of 219 nonpalpable breast lesions by using a stereotactic localization device yielded representative cytologic samples in 74% of the lesions.

Serum concentrations of progesterone and 5 alpha-pregnane-3,20-dione during labor and early post partum.

Serum 5 alpha-pregnane-3,20-dione (5 alpha DHP) and progesterone (P) concentrations were studied in 11 women with uncomplicated pregnancies and deliveries during spontaneous labor and immediately after delivery. Blood samples were drawn 3-6 times during labor, as soon as possible post partum and 1, 3, 6 and 12 h post partum. P and 5 alpha DHP were analysed using RIA methods. There were no significant changes during labor in serum concentration of P and 5 alpha DHP, the values being 366 nmol/l +/- 25 SE and 128 nmol/l +/- 16 SE respectively. Whereas an earlier study has shown a significant decrease in 5 alpha DHP serum concentration between late pregnancy and spontaneous labor, this study showed no decrease during labor, indicating that the decrease occurred before the onset of labor. After parturition, the elimination of P from serum was faster and proportionally greater than for 5 alpha DHP, with a half-life of 38 min for P and 58 min for 5 alpha DHP. About 2-3 h post partum the serum concentrations stabilized just above luteal phase values. 12 h post partum, P and 5 alpha DHP were 12% and 23% respectively of pre-partum values.