Maternal antenatal daytime sleepiness and child neuropsychiatric and neurocognitive development.

BACKGROUND: The prevalence of sleep problems among pregnant women is over 50%, and daytime sleepiness is among the most common sleep problems. Previous studies have associated antenatal sleep problems with adverse maternal health and neonatal outcomes, but the consequences of antenatal sleep problems and particularly daytime sleepiness on child psychological development have not been assessed prospectively. METHODS: In this prospective cohort study including 111 mother-child dyads, we examined the associations of maternal daytime sleepiness during pregnancy, assessed at 17 and 28 weeks of gestation using the Epworth Sleepiness Scale, with child neuropsychiatric problems and neuropsychological development, assessed with mother-rated questionnaires and individually administered neuropsychological tests, at child age 2.6-5.7 years (mean = 4.3 years). RESULTS: Independently of sociodemographic and perinatal covariates and maternal depressive and anxiety symptoms during and/or after pregnancy, maternal antenatal daytime sleepiness was associated with increased total [unstandardized regression coefficient (B) = 0.25 standard deviation (s.d.) units; 95% confidence interval (CI) 0.01-0.48] and internalizing (B = 0.25 s.d.s: 95% CI 0.01-0.49) psychiatric problems and ADHD symptoms (B = 0.27 s.d.s: 95% CI 0.04-0.50) in children, and with poorer executive function, particularly in the areas of attention, working memory and inhibitory control (B = -0.39 s.d.s: 95% CI -0.69 to -0.10). CONCLUSIONS: Maternal antenatal daytime sleepiness carries adverse consequences for offspring psychological development. The assessment of sleep problems may be an important addition to standard antenatal care.

Contributions of climate, leaf area index and leaf physiology to variation in gross primary production of six coniferous forests across Europe: a model-based analysis.

Gross primary production (GPP) is the primary source of all carbon fluxes in the ecosystem. Understanding variation in this flux is vital to understanding variation in the carbon sink of forest ecosystems, and this would serve as input to forest production models. Using GPP derived from eddy-covariance (EC) measurements, it is now possible to determine the most important factor to scale GPP across sites. We use long-term EC measurements for six coniferous forest stands in Europe, for a total of 25 site-years, located on a gradient between southern France and northern Finland. Eddy-derived GPP varied threefold across the six sites, peak ecosystem leaf area index (LAI) (all-sided) varied from 4 to 22 m(2) m(-2) and mean annual temperature varied from -1 to 13 degrees C. A process-based model operating at a half-hourly time-step was parameterized with available information for each site, and explained 71-96% in variation between daily totals of GPP within site-years and 62% of annual total GPP across site-years. Using the parameterized model, we performed two simulation experiments: weather datasets were interchanged between sites, so that the model was used to predict GPP at some site using data from either a different year or a different site. The resulting bias in GPP prediction was related to several aggregated weather variables and was found to be closely related to the change in the effective temperature sum or mean annual temperature. High R(2)s resulted even when using weather datasets from unrelated sites, providing a cautionary note on the interpretation of R(2) in model comparisons. A second experiment interchanged stand-structure information between sites, and the resulting bias was strongly related to the difference in LAI, or the difference in integrated absorbed light. Across the six sites, variation in mean annual temperature had more effect on simulated GPP than the variation in LAI, but both were important determinants of GPP. A sensitivity analysis of leaf physiology parameters showed that the quantum yield was the most influential parameter on annual GPP, followed by a parameter controlling the seasonality of photosynthesis and photosynthetic capacity. Overall, the results are promising for the development of a parsimonious model of GPP.

Macrophages in the murine pancreas and their involvement in fetal endocrine development in vitro.

Macrophages are a heterogeneous population of cells that belong to the mononuclear phagocyte system. They play an important role in tissue homeostasis and remodeling and are also potent immune regulators. Pancreatic macrophages are critically involved in the development and pathogenesis of autoimmune diabetes. To elucidate the ontogeny of pancreatic macrophages, we characterized in this study the macrophages present in the adult and developing fetal pancreas of normal mice. We additionally examined the presence of local macrophage precursors and the involvement of macrophages in the growth of endocrine tissue in the fetal pancreas. We identified two phenotypically distinct macrophage subsets in the adult pancreas. The majority of macrophages was CD45(+)ER-MP23(+)MOMA-1(+). Under noninflammatory conditions, only a minority ( approximately 5%) of the pancreatic macrophages additionally expressed the macrophage marker F4/80. In contrast, in the fetal pancreas, phenotypically, mature macrophages were identified exclusively by their expression of F4/80 and lacked detectable staining with ER-MP23 and MOMA-1 antibodies. In fetal pancreas organ cultures, we could show that macrophages develop from pre-existing precursors, which are present in the fetal pancreas at embryonic age 12.5. Moreover, the number of macrophages increased significantly when macrophage-colony stimulating factor was added to these cultures. It is important that this increase of F4/80-positive cells was paralleled by an increase in the number of insulin-producing cells, suggesting that macrophages support the growth of these endocrine cells.

The Drosophila VEGF receptor homolog is expressed in hemocytes.

Several signalling pathways have been defined by studies of genes originally characterised in Drosophila. However, some mammalian signalling systems have so far escaped discovery in the fly. Here, we describe the identification and characterisation of fly homologs for the mammalian vascular endothelial growth factor/platelet derived growth factor (VEGF/PDGF) and the VEGF receptor. The Drosophila factor (DmVEGF-1) gene has two splice variants and is expressed during all stages, the signal distribution during embryogenesis being ubiquitous. The receptor (DmVEGFR) gene has several splice variants; the variations affecting only the extracellular domain. The most prominent form is expressed in cells of the embryonic haematopoietic cell lineage, starting in the mesodermal area of the head around stage 10 of embryogenesis. Expression persists in hemocytes as embryonic development proceeds and the cells migrate posteriorly. In a fly strain carrying a deletion uncovering the DmVEGFR gene, hemocytes are still present, but their migration is hampered and the hemocytes remain mainly in the anterior end close to their origin. These data suggest that the VEGF/PDGF signalling system may regulate the migration of the Drosophila embryonic haemocyte precursor cells.

Post-ERCP pancreatitis: reduction by routine antibiotics.

Cholangitis and pancreatitis are severe complications of endoscopic retrograde cholangiopancreatography (ERCP). Antibiotics have been considered important in preventing cholangitis, especially in those with jaundice. Some have suggested that bacteria may play a role in the induction of post-ERCP pancreatitis. It is not clear, however, whether the incidence of post-ERCP pancreatitis could be reduced by antibiotic prophylaxis, as is the case with septic complications. In this prospective study, a total of 321 consecutive patients were randomized to the following two groups: (1) a prophylaxis group (n = 161) that was given 2 g of cephtazidime intravenously 30 minutes before ERCP, and (2) a control group (n = 160) that received no antibiotics. All patients admitted to the hospital for ERCP who had not taken any antibiotics during the preceding week were included. Patients who were allergic to cephalosporins, patients with immune deficiency or any other condition requiring antibiotic prophylaxis, patients with clinical jaundice, and pregnant patients were excluded. In the final analysis six patients were excluded because of a diagnosis of bile duct obstruction but with unsuccessful biliary drainage that required immediate antibiotic treatment. The diagnosis of cholangitis was based on a rising fever, an increase in the C-reactive protein (CRP) level, and increases in leukocyte count and liver function values, which were associated with bacteremia in some. The diagnosis of acute pancreatitis was based on clinical findings, and increases in the serum amylase level (>900 IU/L), CRP level, and leukocyte count with no increase in liver chemical values. The control group had significantly more patients with post-ERCP pancreatitis (15 of 160 in the prophylaxis group vs. 4 of 155 in the control group; P = 0.009) and cholangitis (7 of 160 vs. 0 of 155; P = 0.009) compared to the prophylaxis group. Nine patients in the prophylaxis group (6%) and 15 patients in the control group (9%) had remarkably increased serum amylase levels (>900 IU/L) after ERCP, but clinical signs of acute pancreatitis with leukocytosis, CRP reaction, and pain developed in four of nine patients in the prophylaxis group compared to 15 of 15 patients with hyperamylasemia in the control group (P = 0.003). In a multivariate analysis, the lack of antibiotic prophylaxis (odds ratio 6.63, P = 0.03) and sphincterotomy (odds ratio 5.60, P = 0.05) were independent risk factors for the development of post-ERCP pancreatitis. We conclude that antibiotic prophylaxis effectively decreases the risk of pancreatitis, in addition to cholangitis after ERCP, and can thus be routinely recommended prior to ERCP. These results suggest that bacteria could play a role in the pathogenesis of post-ERCP pancreatitis

Proton NMR spectroscopy of the phospholipids in human uterine smooth muscle and placenta.

The parameters regulating the fluidity of myometrial and placental phospholipids include double bonds, fatty acid chain lenght and the cholesterol/phospholipid ratio. The transformation of these parameters was studied during pregnancy and labor. Myometrial and placental tissue samples were collected from 24 patients: 6 were nonpregnant, 6 early-pregnant, 6 late-pregnant not in labor and 6 in labor. After butanol extraction, tissue cholesterol and lipid phosphorus were determined. Proton NMR spectroscopy of the phospholipids was performed at 500 MHz. The myometrial cholesterol/phospholipid ratio was slightly elevated in pregnant patients not in labor. The uterine muscle of the nonpregnant patients contained more CH=CH groups in the phospholipids than that of the late-pregnant patients. There were 29 more double bonds in placental than in uterine tissue per 100 fatty acid molecules. The average fatty acid chain length varied from 14.0 to 18.8. The placenta has longer fatty acid chains than the uterine smooth muscle. The myometrial carbon chain was shortened on the average by 1.4 and the placental by 1.0 carbon atoms, when the patient went into clinical labor. These findings suggest fluidity changes in myometrial and placental phospholipids during human pregnancy and labor.

Sinusitis in the common cold.

BACKGROUND: Acute community-acquired sinusitis is considered a bacterial complication of the common cold. Radiologic abnormalities in sinuses occur, however, in most patients with upper respiratory virus infections. OBJECTIVE: Assessment of the occurrence, clinical profile, laboratory findings, and outcome of radiologically confirmed sinusitis was carried out as part of a common cold study in young adults. METHODS: Clinical examinations and radiography of the paranasal sinuses were carried out on days 1, 7, and 21 in 197 patients with the common cold. The symptoms were recorded on diary cards on days 1 to 20. Ten viruses and 5 bacteria were studied as etiologic agents of common cold as reported earlier. Serum C reactive protein concentrations, erythrocyte sedimentation rates, and total white blood cell counts with differentials were determined in 40 randomized subjects on day 7. The effect of 6 days of intranasal fluticasone propionate treatment of the common cold in the prevention of sinusitis was analyzed. RESULTS: On day 7, 39% of patients with the common cold in the placebo group (n = 98) had sinusitis, which we would prefer to call viral sinusitis. The symptoms of patients with sinusitis and those without it were not clinically distinguishable. Viral infection was detected in 81.6% of patients with sinusitis. No significantly increased levels of antibodies to bacteria were detected. Serum C reactive protein concentrations, erythrocyte sedimentation rates, and white blood cell counts were low in patients with sinusitis. All patients made a clinical recovery within 21 days without antibiotic treatment. Fluticasone propionate treatment tended to prevent paranasal sinusitis, especially in rhinovirus-positive subjects. CONCLUSION: Viral sinusitis frequently occurs in the early days of the common cold, but it is a self-limited illness. The sinuses should not be imaged in patients with the common cold if the signs and symptoms of illness gradually become less severe and no specific signs suggestive of bacterial sinusitis occur.

The common cold: effects of intranasal fluticasone propionate treatment.

OBJECTIVE: A double-blind, randomized, placebo-controlled trial was conducted to study the effect of the intranasal corticosteroid, fluticasone propionate (FP), in the naturally occurring common cold. METHODS: One hundred ninety-nine young adults received high-dose FP (200 microg four times daily) or placebo beginning 24 to 48 hours after onset of the common cold for 6 days. All symptoms were recorded on diary cards on days 1 to 20, and clinical examinations were carried out on days 1, 7, and 21. Nasopharyngeal aspirates were collected on days 1 and 7 for detection of rhinoviruses (found in 105 subjects) and Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis (found in 52 subjects) in the nasopharynx. RESULTS: In general, FP treatment had no clinically recognizable effects on the symptoms of the common cold, although it significantly reduced nasal congestion and cough on some study days. After treatment, rhinoviruses were cultured more often in the FP treatment group (37% vs 14%, p < 0.001), but this had no effect on the symptoms of common cold. FP treatment produced no changes in the colonization of pathogenic bacteria in the nasopharynx. Some symptoms of common cold were significantly more severe during days 1 to 10 (p < 0.05) in subjects found to have positive cultures for S. pneumoniae, H. influenzae, or M. catarrhalis in the nasopharynx on day 1 (n = 33). CONCLUSION: FP treatment does not have any marked effects on the symptoms of the common cold. FP treatment induced prolonged shedding of viable rhinoviruses. Some symptoms of the common cold were significantly more severe in subjects with pathogenic bacteria in the nasopharynx.

Tissue phospholipids during human pregnancy by 31P NMR: myometrium, decidua, placenta and fetal membranes.

The biophysical environment formed by phospholipids, rather than the amount of functional proteins, can be rate limiting for factors controlling myometrial contractility and pregnancy maintenance. We therefore studied myometrial, decidual, placental and fetal membrane phospholipids using the 31P NMR spectrum. This enabled us to identify bulk phospholipids over 0.05 mmol/kg. The method was checked for reliability for the reproductive tissues studied. The chemical shift of phospholipid standards was slightly different according to whether a single compound or a mixture was analyzed. The bulk phospholipids found were phosphatidylcholine (PC), phosphatidylethanolamine, sphingomyelin (SM) and phosphatidylinositol. The ratio PC/SM decreased during pregnancy in the decidua, placenta and fetal membranes, but not in the myometrium. Pregnancy did not induce significant changes in the total myometrial phospholipids. Their composition was stable even during clinical labor. The fetal tissues, placenta and fetal membranes contained about twice as much phospholipid as the maternal tissues, myometrium and decidua. There was no sign of lysocompounds, cardiolipin or phosphatidic acid. This supports the view that the extraction and analyzing techniques used earlier probably created artefacts. The increased fluidity of the myometrial and placental phospholipids during pregnancy may depend on factors other than the composition of phospholipids.

Elevated serum group II phospholipase A2 levels are associated with decreased blood flow velocity in the umbilical artery.

Twenty-two hospitalized patients, diagnosed as having hypertensive disorder of pregnancy, were selected from two University Clinics. Maternal serum samples were analyzed for serum group II phospholipase A2 (PLA2-II) by time-resolved fluoroimmunoassay. At the same time, umbilical artery blood flow velocities were measured with color Doppler sonography for orientation and pulsatile Doppler sonography for recording waveforms. Nineteen normotensive third-trimester pregnant patients served as a control group. Maternal serum PLA2-II was elevated in 8 cases with preeclampsia. This elevation was invariably associated with decreased blood flow velocity in the umbilical artery. In 1 case, the clinical condition allowed simultaneous follow-up of serum enzyme and blood flow velocity: a further rise of serum PLA2-II was linked to a further decrease in the blood flow velocity of the umbilical artery. A large spillover of the elevated PLA2-II content from the preeclamptic placenta into the maternal serum is associated with a decrease in blood flow velocity in the umbilical artery. The enzyme might serve as a link between local proximal (placenta) and systemic distal (umbilical arterial blood flow) effectors.

The effect of nimesulide and naproxen on the uterine and ovarian arterial blood flow velocity. A Doppler study.

BACKGROUND: To measure the effect of oral naproxen and nimesulide treatments on the uterine and ovarian arterial blood flow velocity in both eumenorrheic and dysmenorrheic women. METHODS: The double-blind, placebo-controlled, study comprised six eumenorrheic women receiving either placebo or nimesulide (100 mg, single oral dose) during two consecutive cycles. Six women with moderate to severe dysmenorrhea were treated with placebo, nimesulide or naproxen (500 mg, single oral dose) during three consecutive cycles. Uterine impedance (pulsatile index, PI) was measured during the cycle day 1 at four different levels of the uterus and in the ovarian branch of the uterine artery at 0, 30, 60, and 120-140 min, with a color Doppler ultrasonograph for orientation and with pulsatile Doppler for recording waveforms. RESULTS: In the eumenorrheic women no significant changes were found with any treatment. In dysmenorrheic patients, nimesulide relieved symptoms and caused a decrease in uterine artery PI earlier than naproxen. Both treatments reduced the elevated uterine impedance in dysmenorrhea close to the normal level. When analyzing the PIs of the uterine artery at 4 different levels, the most prominent changes were observed in the fundus. The ovarian branch remained unaffected. CONCLUSIONS: Color Doppler ultrasonography and pulsatile Doppler are good methods for investigating disease- or drug-induced changes in uterine and ovarian blood flow velocities. Nimesulide induced a slightly faster and more complete decrease of the elevated uterine vascular resistance in dysmenorrhea, towards normal eumenorrheic levels, than naproxen. The fundal part of the uterus appears to be an important site of the pathogenesis in primary dysmenorrhea.

Oviductal function is critical for very early human life.

For normal fertilization, the ovum must be picked up from the ovarian surface or from the abdominal cavity into the ampulla. The rapid transport of gametes includes a complex reorganization of the oviductal smooth muscle electrical activity that precedes the mechanical activity. The 3-day stay at the ampulla-isthmic junction requires both signals from the ovum to the oviduct and vice versa, supporting the ovum and regulating its to-and-fro movements. Oviductal fluid, a principal factor in tubal function, coats the newly fertilized egg, activates transcription and gives a signal for sperm fertility potential. Early blocks to embryo development in in vitro conditions, as compared to in vivo success, means that critical developments during the first cell cycles of embryonic life in the oviduct are actively regulated by oviductal embryotrophic factors. These have been used clinically in co-culture systems. Lytic factors are weak in human and other primates, predisposing to high incidence of tubal pregnancies, with considerable impact on medical practice. Diverse oviductal factors affect the incidence, infection being the most significant. Optimal oviductal function is necessary to provide a proper environment for early human life.

Myometrial estrogen and progesterone receptor binding in pregnancy: inhibition by the detergent action of phospholipids.

We characterized the phospholipid inhibition of estradiol and progesterone binding to guinea-pig and human myometrial receptors. Of twelve compounds studied, phosphatidylinositol (PI), lysophosphatidic acid and lysophosphatidylcholine (lyso-PC) were the most active inhibitors (50% inhibition at 10(-5) M). Lyso-PC with fatty acid chain length C14:0 inhibited ligand binding both to estrogen receptor (ER) and progesterone receptor (PR), C16:0 only to PR and C18:0 neither to ER nor to PR. The lyso-derivates were more inhibitory than the parent compounds. The ionic detergent (sodium taurocholate) inhibited both ER and PR binding, but the non-ionic detergent (Triton X-100) only PR. Triton X-100 enhanced the PI-induced inhibition of ER binding by a factor of 10. PR was more sensitive to inhibition than ER in all cases. The type of inhibition was non-competitive. At term pregnancy, ligand binding to myometrial ER or PR was low or absent in humans, but moderate in the guinea-pig. Phospholipid extracts of human decidua and fetal membranes contained PI and phosphatidylserine rather than lyso-PC. The extract was a potent inhibitor of ligand binding to PR (50% inhibition at 10(-6) M phospholipid phosphorus), but not to ER. The physicochemical environment, modulated by phospholipids acting as detergents, may regulate sex steroid function also in vivo. This might have special significance for pregnancy maintenance.

Mastitis today: incidence, prevention and treatment.

The study concerned 664 women of South-West Finland, and they were studied 5-12 weeks after delivery. The total frequency of mastitis in this population was much higher than generally reported in literature, 24% as opposed to 3%. The frequency of mastitis was similar among nulli- and multiparous women. The diagnosis was based on the judgement of midwives of physicians. If a multiparous woman has had mastitis during a previous puerperium, the probability of mastitis during a subsequent puerperium is threefold. The type of skin, its reaction of the sun, allergies, rashes, getting cold and oxytocin medication during delivery did nto affect the incidence of mastitis. Mothers under 21 and over 35 years of age had a decreased incidence (P = 0.034) of mastitis. If the women had sore nipples, the frequency increased (P = 0.003). Prophylaxis, by means of physical training, neither decreased nor increased the frequency of puerperal mastitis. The treatment advised by midwives and physicians was primarily conservative, but 38% received antibiotics; some of the antibiotics were not effective against staphylococcal infection.

Vaginal progesterone after tubal pregnancy.

We studied the effect of vaginal progesterone (P) treatment during the luteal phase of patients who had had a tubal pregnancy (TP) and were planning another, in a prospective, randomized, double-blind trial. The outpatient clinics of two University hospitals and three central hospitals had 135 patients treated for tubal pregnancy: 100 with grossly normal fallopian tubes (supposing an accidentally abnormal luteal phase as a possible etiology of their first TP) and 35 with signs of earlier pelvic inflammatory disease (PID etiology). They were treated with vaginal P (25 mg b.i.d.) or placebo during cycle days 16-24, for 10 months. Serum P levels after a single vaginal or oral dose were compared. The rates of conception, delivery, spontaneous abortion and recurrent TP were recorded, and fetal and placental weight measured. Both vaginal and oral formulas of P provoked a physiological (24-43 nmol/l) rise in serum concentrations. P and placebo-treated cycles resulted in a nearly equal number of pregnancies (33/37 resp.). Of the 55 infants born 53 were to mothers without signs of earlier PID (53/100); only 2 (2/35) to mothers in whom signs had been present. Recurrent TP occurred in 9% of all pregnancies. Four out of six recurrent TPs were patients with signs of PID (4/35), but two were without such signs (2/100): one occurred during placebo and one during P-treated cycle. Prophylactic P treatment of patients at risk of recurrent TP does not improve fertility or prevent recurrent TP. This indicates, that the functional etiology of recurrent TP, as compared to infection, is not important.

Group I and group II phospholipase A2 in serum during normal and pathological pregnancy.

Phospholipase A2 groups I (pancreatic) and II (synovial) could be a link between local and systemic changes in pregnancy, reflected in catalytic activity. We studied whether normal pregnancy, preeclampsia, preterm labor and four other diseases have processes involving serum phospholipase A2s. Pancreatic and synovial-type phospholipase A2 were measured in the serum of 59 normal pregnant women and 89 patients with pathological pregnancy by newly developed time-resolved fluoroimmunoassays, and the catalytic activity by a radiochemical method using micellar phosphatidylcholine as substrate. During pregnancy weeks 6-14, synovial-type phospholipase A2 and catalytic activity were elevated 2- to 4-fold, but at 37 weeks values were normal. Pregnancy-induced hypertensive diseases increased by 4- to 10-fold the concentration of synovial-type phospholipase A2, reflected in catalytic activity. In 8 out of 14 cases, the enzyme was increased if the fetus was to be delivered prematurely. The enzymes studied remained within the reference interval in cases of hepatogestosis, fetal asphyxia, diabetes and twin pregnancy. Newly developed specific immunoassays for measuring different types of phospholipase A2 in serum can provide insights for clinical follow-up.

Nimesulide in dysmenorrhoea.

Nimesulide does not affect active intrauterine pressure, as measured using microsensors, or the direction and velocity of the propagation of uterine activity, but nevertheless alleviates pain significantly by 30 minutes after oral administration. In dysmenorrhoeic patients, resting pressure is high only in the fundus. Nimesulide reduces the pressure during the maximal but not during the submaximal pain period, with concomitant alleviation of pain. The drug changes the painful state of uterine contracture to painless cyclic contractions. With a single oral dose of 100mg, nimesulide is evenly distributed in female genital tissues (uterine fundus and cervix, oviduct and ovaries), reaching peak concentrations and peak plasma: tissue ratio (0.5) 3 hours after administration. Tissue concentrations range from 0.3 to 1.8 micrograms/g. Two 100mg oral doses of nimesulide administered to dysmenorrhoeic women in a double-blind placebo-controlled cross-over study reduced prostaglandin F2 alpha levels in menstrual blood from 382 to 94 micrograms/L. Double-blind placebo-controlled studies also confirmed that nimesulide relieves pain in dysmenorrhoeic patients.

Analysis of uterine contractility after administration of the non-steroidal anti-inflammatory drug nimesulide.

To study the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on uterine contractility in different parts of the uterus and on the direction and velocity of propagation of the activity, intra-uterine pressure (IUP) was measured simultaneously in 10 dysmenorrheic and 5 eumenorrheic patients with two microtransducer catheters at two locations (30 mm apart) before and after taking nimesulide, a newly developed NSAID. The uterus developed higher pressure cycles in the fundus than in the isthmus, in both eumenorrheic and dysmenorrheic conditions. Nimesulide did not affect either the active pressure (AP) or the direction and velocity of propagation of the activity, though it alleviated pain significantly. In dysmenorrheic patients, resting pressure (RP) is at a high level only in the fundus. The velocity of propagation ranged from 12 to 19 mm/s. The mathematical probability of procervical activity (1.0 if all procervical; 0.0 if all profundal), and thus the transport, was 0.59 in eumenorrheic and 0.68 in dysmenorrheic patients, the average for the whole series being 0.65. The luminal content (menstrual blood) moves in the cervical direction much more slowly than would be expected on the basis of simple calculations of velocity (velocity vector) of propagation.

Distribution of oral nimesulide in female genital tissues.

Nimesulide is a non-steroidal anti-inflammatory agent which has proved to be effective in reducing menstrual discomfort in dysmenorrhoeaic women. To determine the concentrations of this drug in the uterus (fundus, cervix), oviduct, and ovaries and to correlate these findings with plasma concentrations, a single oral dose of 100 mg nimesulide was administered 1 to 6 h before surgery to 12 women undergoing hysterectomy and salpingo-oophorectomy, mainly for fibroids. Tissue samples were taken, concentration of nimesulide measured by HPLC, and findings compared with plasma concentrations. One patient not undergoing treatment served as control. Nimesulide concentration in the tissues studied was highest 3 h after administration, as expected from the drug's pharmacokinetic profile. The highest tissue/plasma ratio (0.5) was also found at that time. Average tissue concentrations at 1, 2, 3, and 6 h after drug intake ranged from 0.3 to 1.8 micrograms g-1, and plasma concentrations from 2.6 to 4.1 micrograms ml-1. Nimesulide was evenly distributed in the tissues studied.