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1.
Eur J Clin Nutr ; 70(8): 912-7, 2016 08.
Article in English | MEDLINE | ID: mdl-26669570

ABSTRACT

BACKGROUND/OBJECTIVES: The prevalence of gestational diabetes mellitus (GDM) is increasing worldwide. GDM may be prevented by improving the diets of pregnant women. The objective of this study was to evaluate the effect of dietary counselling on the diets of pregnant women at GDM risk. SUBJECTS/METHODS: This study was a secondary analysis of a randomised controlled trial the Finnish gestational diabetes prevention study (RADIEL) in which pre-pregnant and pregnant women with previous GDM or BMI ⩾30 kg/m(2) were allocated into two groups, namely the control and the intervention groups. The control group received standard antenatal dietary counselling according to the Finnish Nutrition Recommendations. The intervention group participated in one individual dietary counselling session and one group dietary counselling session in addition to the standard counselling. This study included women who were recruited during pregnancy. To assess changes in food intake, food-intake questionnaires were collected during the first and the second trimester of pregnancy. Bootstrap type analysis of covariance was used, and 242 participants were included in the final analysis to study changes in food intake. RESULTS: The intakes of low-fat cheese (baseline adjusted mean 0.09 times/day; 95% confidence interval (CI) 0.07, 0.24; P=0.040) and fish (baseline adjusted mean 0.28 times per week; 95% CI 0.08, 0.49; P=0.011) showed a significant increase in the intervention group compared with the control group. CONCLUSIONS: This study showed that dietary counselling in early pregnancy can lead to modest dietary improvements in pregnant women at GDM risk.


Subject(s)
Counseling/methods , Diabetes, Gestational/prevention & control , Diet/psychology , Eating/psychology , Nutrition Therapy/psychology , Adult , Diabetes, Gestational/psychology , Diet Records , Feeding Behavior/psychology , Female , Humans , Nutrition Therapy/methods , Pregnancy , Treatment Outcome
2.
Anal Chim Acta ; 886: 214-20, 2015 Jul 30.
Article in English | MEDLINE | ID: mdl-26320656

ABSTRACT

Byproducts of arachidonic (AA) and docosahexaenoic acid (DHA) oxidation are highly relevant for the study of free radical associated conditions in the perinatal period. Plasma metabolites can provide the clinician with a snapshot of the oxidant status of patients before and after specific clinical interventions (e.g.: supplementation with oxygen). We describe a new andreliable ultra-performance liquid mass spectrometry method to determine F2-isoprostanes and other byproducts (isoprostanes, isofurans, neuroprostanes, neurofurans) in newborn serum samples. Cord blood samples were obtained from severely depressed newborn infants (Apgar score 1 min < 3; arterial cord pH < 7.00), and aliquoted for serum determination and stored at -80 °C. A UHPLC-MS/MS method was employed. It has a series of technical advantages: simple sample treatment; reduced sample volume (100 µL) which is essential for preterm neonates with low circulating blood volume, high throughput of sample analysis (96 samples in less than 24 h) and high selectivity for different isoprostanes isomers. Excellent sensitivity was achieved within limits of detection between 0.06 and 4.2 nmol L(-1), which renders this method suitable to monitoranalyte concentration in newborn samples. The method's precision was satisfactory; with coefficients of variation around 5-12% (intra-day) and 7-17% (inter-day). The reliability of the described method was assessed by analysis of spiked serum samples obtaining recoveries between 70% and 120%. The proposed method has rendered suitable for serum determination for newborn babies at risk of oxygen free radical associated conditions.


Subject(s)
Biomarkers/blood , Chromatography, High Pressure Liquid/methods , Lipid Peroxidation , Lipids/blood , Oxidative Stress , Tandem Mass Spectrometry/methods , Humans , Infant, Newborn/blood , Limit of Detection
3.
J Evol Biol ; 28(7): 1321-34, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26011732

ABSTRACT

Sexual conflicts and their evolutionary outcomes may be influenced by population-specific features such as mating system and ecological context; however, very few studies have investigated the link between sexual conflict and mating system. The self-compatible, mixed-mating hermaphrodite Collinsia heterophylla (Plantaginaceae) is thought to exhibit a sexual conflict over timing of stigma receptivity. This conflict involves (i) delayed stigma receptivity, which intensifies pollen competition, and (ii) early fertilization forced by pollen, which reduces seed set. We investigated the potential for the conflict to occur under field conditions and performed glasshouse crosses within eight populations to assess its consistency across populations. Flowers were visited, and produced seeds after pollination, at all developmental stages, suggesting that the conflict can be of significance under natural conditions. In the glasshouse, early pollination imposed costs in all populations. Overall, the timing of first seed set was most strongly affected by the maternal parent, denoting stronger female than male ability to influence the onset of stigma receptivity. Crosses also revealed a negative relationship between donor- and recipient-related onset of receptivity within individuals, a novel result hinting at trade-offs in sex allocation or a history of antagonistic selection. Neither timing of stigma receptivity, timing of first seed set, nor pollen competitive ability covaried with population outcrossing rate. In conclusion, these results indicate that sexually antagonistic selection may be present in varying degrees in different populations of C. heterophylla, but this variation does not appear to be directly related to mating system variation.


Subject(s)
Flowers/physiology , Plantaginaceae/physiology , Reproduction/physiology , Animals , Bees , California , Crosses, Genetic , Genetics, Population , Plant Nectar/metabolism , Plantaginaceae/genetics , Pollen , Pollination , Seeds/growth & development
4.
Ann Oncol ; 24(7): 1912-1918, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23508823

ABSTRACT

BACKGROUND: The epidemiological evidence on possible relationships between coffee consumption and prostate cancer (PCa) risk by subtype of the disease (localized, advanced) and fatal PCa risk is limited. MATERIALS AND METHODS: A population-based cohort of 44 613 Swedish men aged 45-79 years was followed up from January 1998 through December 2010 for incidence of localized (n = 2368), advanced (n = 918) and fatal (n = 515) PCa. We assessed the associations between coffee consumption and localized, advanced and fatal PCa risk using competing-risk regressions. We examined possible effect modification by body mass index (BMI). RESULTS: For localized PCa, each one cup increase in daily coffee consumption was associated with a 3% reduced risk [sub-hazard ratio (SHR) = 0.97, 95% confidence interval (CI) = 0.95-0.99]. For advanced and fatal PCa, we found a non-significant inverse association; each one cup increase was associated with a 2% reduced risk of advanced [SHR (95% CI) = 0.98 (0.95-1.02)] and fatal PCa [SHR (95% CI) = 0.98 (0.93-1.03)]. We observed evidence of effect modification by BMI for localized PCa (Pinteraction = 0.03); the inverse association was stronger among overweight and obese men (BMI ≥ 25 kg/m(2)) compared with normal-weight men (BMI < 25 kg/m(2)). CONCLUSIONS: We observed a clear inverse association between coffee consumption and risk of localized PCa, especially among overweight and obese men.


Subject(s)
Coffee , Prostatic Neoplasms/epidemiology , Aged , Humans , Male , Middle Aged , Multivariate Analysis , Neoplasm Grading , Proportional Hazards Models , Prospective Studies , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Risk Factors , Surveys and Questionnaires , Sweden/epidemiology
5.
Altern Ther Health Med ; 18(3): 25-32, 2012.
Article in English | MEDLINE | ID: mdl-22875559

ABSTRACT

CONTEXT: Conventional guidelines in Sweden recommend primary care management for back and neck pain, yet these two conditions are the most common ones for which patients use complementary therapies. Despite the recent growth of integrative medicine (IM) in different clinical, academic, and societal contexts, few studies have defined and investigated comprehensive models of integrative care as compared to conventional management, especially using randomized clinical trials. OBJECTIVE: The study explores patients' experiences and perceptions when receiving conventional or integrative care in the management of back and neck pain. DESIGN: The research team conducted this study within a larger interventional study. In that study--a pragmatic randomized clinical pilot trial--the team developed a model for integrative medicine that combines complementary therapies that have an emerging evidence base and conventional treatments for patients with nonspecific back and neck pain. The research team implemented the model and compared the results for integrative care to results for conventional primary care. The current qualitative study included 11 focus-group discussions: conventional care (n= 5) and integrative care (n=6). SETTING: The research team implemented the interventional study in south suburban Stockholm, an area with higher unemployment, lower incomes, and receipt of more welfare support and sickness benefits compared to the average levels in Stockholm. PARTICIPANTS: The participants in the focus-group discussions were volunteers drawn from the larger randomized clinical trial. OUTCOME MEASURES: The research team transcribed all discussions from the focus groups verbatim and used latent content analysis to evaluate the data. RESULTS: Receiving diagnostic support and excluding pathology were strong reasons for participants to seek conventional care. Participants reported that they found conventional management to be reductionistic, with a focus on disease, and a lack of accessibility, time, and guidance. In contrast, participants reported that integrative care was holistic, whole-person management and facilitated increased treatment response, support, empowerment, and self-help strategies. Participants, however, perceived integrative care to be challenging because of additional treatment costs with complementary therapies and collaborative shortcomings between integrative and conventional practitioners generally. CONCLUSION: Integrative care represents a combination of valuable conventional medical diagnosis with empowering self-help strategies for some patients with nonspecific back and neck pain in Swedish primary care. Future studies should also investigate experiences and perceptions in the longer term from the perspective of patients, caregivers, and health systems.


Subject(s)
Back Pain/therapy , Complementary Therapies/methods , Integrative Medicine/methods , Neck Pain/therapy , Patient Satisfaction/statistics & numerical data , Precision Medicine/methods , Adult , Aged , Female , Focus Groups , Holistic Health , Humans , Male , Middle Aged , Pain Measurement , Surveys and Questionnaires , Sweden , Treatment Outcome , Urban Population/statistics & numerical data , Young Adult
6.
Br J Anaesth ; 107(5): 782-9, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21948951

ABSTRACT

BACKGROUND: Postoperative pain after radical retropubic prostatectomy is moderate to severe. The primary aim of this study was to assess whether intra-abdominal local anaesthetics provide similar analgesia compared with thoracic epidural analgesia (TEA). METHODS: Fifty patients, ASA I-II, participated in this prospective, double-blinded study. All patients had TEA. After operation, they were randomized into two groups of 25 patients: Group PCLA (patient-controlled local analgesia): self-administration of 10 ml of ropivacaine 2 mg ml⁻¹ via the intra-abdominal catheter for 48 h. Group TEA: infusion of 10 ml h⁻¹ of ropivacaine 1 mg ml⁻¹, fentanyl 2 µg ml⁻¹, and epinephrine 2 µg ml⁻¹ epidurally for 48 h. The primary endpoint was pain on coughing at 4 h after operation. Rescue medication was morphine i.v. as required. RESULTS: Pain on coughing at 4, 24, and 48 h was significantly lower in Group TEA [0 (0-10)] compared with Group PCLA [4 (0-10)] (P<0.05). Significantly lower pain intensity was also found in Group TEA compared with Group PCLA at the incision site, deep pain, and pain on coughing at 4 and 24 h (P<0.05). Morphine consumption was significantly greater in Group PCLA [12 (0-46)] compared with Group TEA [0 (0-20)] at 0-48 h after operation [median (range)] (P=0.015). Maximum expiratory pressure was higher in Group TEA compared with Group PCLA at 24 h (P<0.01). CONCLUSIONS: TEA provides superior postoperative pain relief with better preservation of expiratory muscle strength compared with PCLA.


Subject(s)
Analgesia, Epidural/methods , Analgesia, Patient-Controlled/methods , Pain, Postoperative/drug therapy , Prostatectomy , Adrenergic alpha-Agonists/therapeutic use , Aged , Amides , Analgesics, Opioid/therapeutic use , Anesthesia, Local , Anesthetics, Local , Double-Blind Method , Epinephrine/therapeutic use , Fentanyl/therapeutic use , Humans , Male , Middle Aged , Morphine/therapeutic use , Pain Measurement , Prospective Studies , Ropivacaine , Time Factors , Treatment Outcome
7.
Osteoporos Int ; 22(3): 883-91, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21153404

ABSTRACT

UNLABELLED: In this prospective study, 87 children were followed up from birth to 14 months with data on maternal vitamin D status during the pregnancy. Postnatal vitamin D supplementation improved vitamin D status but only partly eliminated the differences in bone variables induced by maternal vitamin D status during the fetal period. INTRODUCTION: Intrauterine nutritional deficits may have permanent consequences despite improved nutritional status postnatally. We evaluated the role of prenatal and postnatal vitamin D status on bone parameters in early infancy. METHODS: Eighty-seven children were followed from birth to 14 months. Background data were collected with a questionnaire and a 3-day food record. At 14 months bone variables were measured with peripheral computed tomography (pQCT) from the left tibia. Serum 25-OHD and bone turnover markers were determined. Findings were compared with maternal vitamin D status during pregnancy. RESULTS: The children were divided into two groups based on vitamin D status during pregnancy. Despite discrepant S-25-OHD at baseline (median 36.3 vs. 52.5 nmol/l, p < 0.001), the values at 14 months were similar (63 vs. 66 nmol/l, p = 0.58) in Low D and High D. Serum 25-OHD increased more in Low D (p < 0.001) despite similar total intake of vitamin D (mean 12.3 µg/day). In Low D, tibial bone mineral content (BMC) was lower at birth but BMC gain was greater (multivariate analysis of variance [MANOVA]; p = 0.032) resulting in similar BMC at 14 months in the two groups. In High D, tibial total bone cross-sectional area was higher at baseline; the difference persisted at 14 months (MANOVA; p = 0.068). Bone mineral density (BMD) and ΔBMD were similar in the two groups. CONCLUSIONS: Postnatal vitamin D supplementation improved vitamin D status but only partly eliminated the differences in bone variables induced by maternal vitamin D status during the fetal period. Further attention should be paid to improving vitamin D status during pregnancy.


Subject(s)
Bone Development/drug effects , Prenatal Exposure Delayed Effects , Tibia/growth & development , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamins/therapeutic use , Bone Density , Diet , Dietary Supplements , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Pregnancy , Prospective Studies , Tibia/diagnostic imaging , Tomography, X-Ray Computed , Vitamin D/therapeutic use
8.
Digestion ; 83(1-2): 3-12, 2011.
Article in English | MEDLINE | ID: mdl-20838049

ABSTRACT

AIM: To test temporary percutaneous gastric electrical stimulation (TPGES) in patients with drug-refractory nausea/vomiting and nonestablished indications for GES. METHODS: 27 patients (2-81 years) underwent TPGES with electrodes implanted at gastroscopy and received stimulation for 7-21 days with low current settings (5-7 mA) either as open stimulation (n = 14) or randomized to double-blind crossover stimulation (n = 13; ON for 12-14 days, OFF for 12-14 days). Symptoms were recorded daily. Nonresponders were offered another period (14-21 days) with increased stimulation (8-10 mA). RESULTS: Mean lead implantation time was 14 min. Leads were kept implanted for ≤60 days. 22 of 27 evaluable patients had a favorable symptom reduction, preferentially of nausea/vomiting, irrespective of delayed or normal gastric emptying rate: postsurgical gastroparesis 7/8, chronic intestinal pseudo-obstruction 2/2, idiopathic gastroparesis 1/1, functional dyspepsia 6/9, diabetes mellitus 2/2, postsurgical nausea/vomiting 2/2, malformation syndrome 1/1, intestinal neuropathy 1/1, intestinal interstitial cells of Cajal deficiency 0/1. 6 patients had a clear symptom reduction during the ON period compared with stimulation OFF. Four of 7 patients improved with increased stimulation (8-10 mA). Twenty of the 22 responders received a permanent GES implant, 90% of them still being responders at last follow-up. CONCLUSION: TPGES seems promising to study new indications for GES and to select responders/non-responders.


Subject(s)
Electric Stimulation Therapy/methods , Nausea/therapy , Vomiting/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Chronic Disease , Cross-Over Studies , Double-Blind Method , Electrodes, Implanted , Female , Gastric Emptying , Humans , Male , Middle Aged , Patient Selection , Stomach , Treatment Outcome , Young Adult
9.
Br J Cancer ; 100(1): 170-3, 2009 Jan 13.
Article in English | MEDLINE | ID: mdl-19088721

ABSTRACT

In a national register-based study of incidence trends and mortality of incidental prostate cancer in Sweden, we found that a significant proportion (26.6%) of affected men diagnosed died of their disease, which challenges earlier descriptions of incidental prostate cancer as a non-lethal disease.


Subject(s)
Prostatic Neoplasms/epidemiology , Adult , Aged , Aged, 80 and over , Humans , Incidence , Male , Middle Aged , Prostatic Neoplasms/mortality , Prostatic Neoplasms/surgery , Registries , Sweden/epidemiology , Transurethral Resection of Prostate
10.
Neurogastroenterol Motil ; 18(9): 823-30, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16918761

ABSTRACT

Gastric electrical stimulation (GES) is effective for medically refractory nausea and vomiting in patients with idiopathic or diabetic gastroparesis (DGP). We studied whether GES has similar effects in chronic intestinal pseudoobstruction (CIP). Patients referred for chronic small bowel (SB) motor dysfunction requiring parenteral nutrition and having a weekly vomiting frequency (WVF) >/=7 refractory to prokinetics and antiemetics were included. Patients were implanted for high-frequency GES 12 stimuli min(-1), laparoscopy being the first-line implantation procedure. Results were compared with those obtained in 11 DGP patients. Three patients with familial CIP and one patient with postsurgical CIP fulfilled the criteria. Gastric emptying was delayed in two and was normal in two patients. SB transit time was markedly delayed. Laparoscopy was used in three patients, one patient required laparotomy. During GES, WVF decreased from 24 (mean) before GES to 6.9 at 12 months and 7.5 at last visit. Vomiting reduction was 50-90% at last visit. For the DGP patients, WVF decreased from 23 before GES to 3.5 at 12 months and 3.5 (P < 0.01) at last visit. In patients with CIP and medically refractory vomiting, GES seems to have an anti-vomiting effect comparable to that seen in patients with severe DGP. GES should be considered as a therapeutic option for these patients.


Subject(s)
Electric Stimulation Therapy , Intestinal Pseudo-Obstruction/complications , Stomach/physiology , Vomiting/etiology , Vomiting/therapy , Adult , Aged, 80 and over , Chronic Disease , Diabetes Mellitus , Electrodes, Implanted , Female , Gastric Emptying/physiology , Gastrointestinal Motility/physiology , Gastroparesis/complications , Humans , Infant, Newborn , Laparoscopy , Male , Manometry , Middle Aged , Nausea/etiology , Nausea/therapy
11.
J Hered ; 96(5): 550-6, 2005.
Article in English | MEDLINE | ID: mdl-16135706

ABSTRACT

Nigella degenii ssp. barbro and ssp. jenny differ from related taxa in being dimorphic for pollen color, with some plants having dark pollen and others light pollen. In this study we performed experimental crosses to determine whether the difference in pollen color is governed by few or many loci and whether the two subspecies utilize the same gene to control pollen color. Patterns of segregation in crosses between morphs show that dark pollen is dominant over light pollen and that a single major gene is responsible for most of the variation in pollen color. Consequently it should be relatively easy for pollen color dimorphisms to establish and spread in these subspecies. Aberrant segregation ratios were attributed to genetic factors that reduced the expression of the allele conferring dark pollen or processes that sorted between color morphs during seed development. Crosses between dark pollen plants from different subspecies showed signs of complementation in the F2 generation, but the frequency of the light morph was too low to support a model involving complementary action of recessive alleles at two separate loci. Based on this and other observations, we hypothesize that the pollen color difference is controlled by the same major locus in the two subspecies.


Subject(s)
Genetics, Population , Nigella/genetics , Pigmentation/genetics , Pollen/genetics , Analysis of Variance , Crosses, Genetic , Genetic Complementation Test , Inheritance Patterns/genetics , Models, Genetic , Nigella/physiology , Pigmentation/physiology , Pollen/physiology , Selection, Genetic , Species Specificity
12.
Am J Clin Nutr ; 72(5): 1196-201, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11063449

ABSTRACT

BACKGROUND: Human milk, rich in cytokines, may contain the potent permeability- and angiogenesis-promoting agent vascular endothelial growth factor (VEGF). OBJECTIVE: We wanted to study whether free or bound VEGF is present in human milk and whether it and its receptors (VEGFR-1 and -2) are expressed in lactating breast or newborn intestinal tissue. DESIGN: The study had a longitudinal design with collection of human milk from healthy (n = 32) and diabetic (n = 5) women at 2, 7, and 30 d postpartum. Milk was analyzed for VEGF by enzyme-linked immunosorbent assay along with plasma samples collected 2 d postpartum. Immunohistochemistry was used to localize VEGF and its receptors in lactating breast and newborn intestine. Gel filtration with radiolabeled VEGF was performed to study whether human milk contains VEGF binding proteins. RESULTS: Human milk VEGF concentrations in healthy (76 +/- 19 microg/L, x +/- SD) and diabetic (75 +/- 25 microg/L) women did not differ at 2, 7 (23 +/- 7 and 27 +/- 8 microg/L, respectively), or 30 d (14 +/- 5 and 17 +/- 7 microg/L, respectively) postpartum. VEGF was undetectable in all but 3 plasma samples. Human milk was free of VEGF binding proteins. VEGFR-1 and -2 immunoreactivity was seen in the glandular epithelial cells of the newborn intestine and lactating breast, whereas VEGF was present only in breast glandular epithelium. CONCLUSIONS: The high concentrations of VEGF in human milk, especially colostrum, are not affected by maternal diabetes and may play a role in newborn nutrition.


Subject(s)
Breast/chemistry , Endothelial Growth Factors/analysis , Intestines/chemistry , Lymphokines/analysis , Milk, Human/chemistry , Receptor Protein-Tyrosine Kinases/analysis , Receptors, Growth Factor/analysis , Chromatography, Gel , Colostrum/chemistry , Diabetes Mellitus, Type 1/metabolism , Endothelial Growth Factors/blood , Epithelium/chemistry , Female , Humans , Immunohistochemistry , Infant, Newborn , Lactation , Lymphokines/blood , Pregnancy , Pregnancy in Diabetics/metabolism , Receptors, Vascular Endothelial Growth Factor , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
13.
J Med Chem ; 43(21): 3852-61, 2000 Oct 19.
Article in English | MEDLINE | ID: mdl-11052790

ABSTRACT

The relative binding affinities to human dihydrofolate reductase of four new potential antifolates, containing ester linkages between the two aromatic systems, were estimated by free energy perturbation simulations. The ester analogue, predicted to exhibit the highest binding affinity to human dihydrofolate reductase, and a reference ester (more structurally related to methotrexate) were synthesized. As deduced from the measured IC(50) values, the calculated ranking of the ligands was correct although a greater difference in affinity was indicated by the experimental measurements. Among the new antifolates the most potent inhibitor exhibited a similar pharmacokinetic profile to methotrexate but lacked activity in a complex antiarthritic model in rat in vivo.


Subject(s)
Folic Acid Antagonists/metabolism , Methotrexate/analogs & derivatives , Methotrexate/metabolism , Tetrahydrofolate Dehydrogenase/metabolism , Animals , Antirheumatic Agents/chemical synthesis , Antirheumatic Agents/chemistry , Antirheumatic Agents/pharmacology , Arthritis, Experimental/drug therapy , Biological Availability , Female , Folic Acid Antagonists/chemical synthesis , Folic Acid Antagonists/chemistry , Folic Acid Antagonists/pharmacology , Humans , Male , Methotrexate/chemical synthesis , Methotrexate/chemistry , Models, Biological , Models, Molecular , Protein Binding , Rats , Tetrahydrofolate Dehydrogenase/chemistry , Thermodynamics
14.
Medicine (Baltimore) ; 79(5): 299-309, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11039078

ABSTRACT

Ten male pseudohermaphrodites with 17 beta-hydroxysteroid dehydrogenase 3 (17 beta-HSD3) deficiency were evaluated in 1 clinic with an average follow-up of 10.1 years. The diagnoses were made by demonstrating low to normal serum testosterone levels, high androstenedione levels, and high ratios of serum androstenedione to testosterone in the basal state or after treatment with human chorionic gonadotropin. The molecular features of the underlying mutations were identified in all 7 families. Two additional males in the same families are believed to be affected on the basis of history obtained from family members. All of the 46,XY individuals in these families were registered at birth and raised as females (despite the presence of ambiguous genitalia in all or most), and all virilized after the time of expected puberty due to a rise in serum testosterone to or toward the normal male range. The age at diagnosis varied from 4 to 37 years. Ten individuals were studied by the same psychologist, and change of gender role (social sex) from female to male occurred in 3 subjects and in the 2 presumed affected subjects not studied. The individual with the highest serum testosterone level maintained female sexual identity, and in 2 families some of the affected males changed gender role and others did not. Thus, while androgen action plays a role in the process, additional undefined psychological, social, and/or biologic factors must be determinants of gender identity/role behavior. Management of the 7 individuals who chose to maintain female sex roles included castration, clitoroplasty, vaginal enlargement procedures when appropriate, treatment of hirsutism, cricoid cartilage reduction, and estrogen replacement. Three of the 7 are married (2 twice), 1 is involved in a long-term heterosexual relationship, 1 is engaged to be married, and the other 2 are not married and not believed to be sexually active. The 3 subjects who changed gender role behavior to male underwent hypospadias repair, and 1 was given supplemental testosterone therapy. One of these men is divorced, and the other 2 (aged 29 and 35 years) are unmarried. The diagnosis in 8 of these subjects was made after the time of expected puberty; it is unclear whether the functional and social outcomes would have been different if the diagnosis had been made and therapy begun earlier in life.


Subject(s)
17-Hydroxysteroid Dehydrogenases/deficiency , Disorders of Sex Development/diagnosis , Adolescent , Adult , Androstenedione/blood , Child , Disorders of Sex Development/enzymology , Disorders of Sex Development/psychology , Disorders of Sex Development/therapy , Follicle Stimulating Hormone/blood , Follow-Up Studies , Humans , Luteinizing Hormone/blood , Male , Testosterone/blood
15.
Scand J Urol Nephrol ; 34(1): 21-6, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10757265

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the effects of a long series of electro-acupuncture (EAP) sessions on bedwetting symptoms. MATERIAL AND METHODS: Twenty-five children (age range 7-16 years) with monosymptomatic nocturnal enuresis and treated earlier without success were included in the study. The median number of wet nights per week was 4.7 before treatment. Bedwetting, voided volume, sleep and nocturia were evaluated 3 weeks, 3 months and 6 months after 20 sessions of EAP lasting 8 weeks. RESULTS: All the children, with the exception of one, tolerated EAP treatment well. At the three follow-up sessions it was found that the number of dry nights had increased gradually from a median of 2.3 in the pre-test to 3.0, 4.3 and 5.0 per week, respectively. Compared to pre-treatment findings there were more dry nights in 65% of the children (p < 0.001) and 5 out of 23 children were responders (> 90% reduction of the numbers of wet nights) at the 6 months' follow-up. According to the parents, the sleep arousal threshold had decreased in about 50% of the children.


Subject(s)
Electroacupuncture , Enuresis/therapy , Adolescent , Child , Enuresis/etiology , Female , Follow-Up Studies , Humans , Long-Term Care , Male , Patient Acceptance of Health Care , Urination Disorders/etiology , Urination Disorders/therapy
16.
Scand J Gastroenterol ; 35(2): 190-7, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10720119

ABSTRACT

BACKGROUND: Oxazolone-induced colitis in the rat is an immune-driven model of human colitis. The aim of the present study was to measure the changes in the absorptive and exudative permeabilites, oedema formation, and local blood flow in this model during the development of inflammation. We also assessed the effects of acute (<1 h), topical glucocorticosteroid (GCS) treatment on these factors. METHODS: Colitis was induced by local instillation of oxazolone in previously sensitized animals. Calculating the 40-min plasma-equivalent extravascular volume quantitated the plasma exudation rate. This was determined by using labelled albumin as marker for total tissue content of plasma and Evans blue content as marker for the intravascular volume. Absorptive permeability was simultaneously measured as uptake of rectally administered (51Cr)-labelled ethylenediaminetetraacetic acid (EDTA). In separate experiments regional blood flows were measured by means of the labelled microsphere method. RESULTS: At both 3 and 24 h after challenge marked enhancements of both exudative and absorptive permeabilities were found. At 24 h there was also an increase in local blood flow. GCS treatment abolished all of the hyperaemia and the main part of the exudative response but had no significant effect on the absorptive permeability. CONCLUSIONS: In this model immunologic mechanisms induce permeability and blood flow changes similar to those in the human disease. It seems suitable for the study of GCS and other anti-inflammatory or immune-modulating drugs.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Budesonide/therapeutic use , Colitis/drug therapy , Colon/blood supply , Administration, Topical , Animals , Anti-Inflammatory Agents/administration & dosage , Budesonide/administration & dosage , Colitis/chemically induced , Colitis/pathology , Colitis/physiopathology , Colon/metabolism , Colon/pathology , Disease Models, Animal , Edetic Acid/pharmacokinetics , Endothelium/metabolism , Epithelium/metabolism , Female , Glucocorticoids , Humans , Intestine, Small/blood supply , Oxazolone , Permeability , Rats
17.
Eur J Pharm Sci ; 9(4): 333-43, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10664473

ABSTRACT

The mechanism of action for the anti-arthritic effect of methotrexate (MTX) was investigated in rats with antigen-induced arthritis (AIA). Arthritis intensity was quantified as area under the curve (AUC) for the joint swelling. The response to MTX was in several respects similar to what is seen in the clinic. The drug reduced the AUC in a dose-dependent manner after oral weekly (2-4 mg/kg/week) or daily (0.3 mg/kg/day) dosing. This effect was not affected by supplementation with an equal dose of folate. The model thus seemed suitable for this type of study. Supplementation with folate in excess abolished the effect of MTX. A structurally similar antifolate, aminopterin, also reduced the arthritis. The effect thus seemed to be due to folate antagonism although a complete inhibition of dihydrofolate reductase (DHFR) might not be essential. Hence, it could be that the main target is a process downstream of DHFR. It has been proposed that inhibition of AICAR-transformylase induce the release of adenosine with anti-inflammatory properties. Here the adenosine antagonist R-PIA reduced the arthritis but when MTX was combined with adenosine antagonists no attenuation of the anti-arthritic effect was seen. On the contrary, three adenosine agonists (8-p-sulphophenyltheophyllamine 30 mg/kg i.p. twice daily; 3,7-dimethyl-1-propargylxanthine, p.o. 3 mg/kg/day and 8-cyclopentyl-1,3-dipropylxanthine, 1.5 mg/kg/day p.o.) potentiated MTX. The specific thymidylate synthase inhibitor 5-fluourouracil (0. 3-3.0 mg/kg/day) had no anti-arthritic effect. Neither did our data support the hypotheses that syntheses of polyamines or cytokines were primary targets. It is thus possible that the mechanism of action is inhibition of a process downstream of DHFR but the release of adenosine seems not to be important.


Subject(s)
Adenosine/physiology , Arthritis, Experimental/drug therapy , Methotrexate/pharmacology , Animals , Biogenic Polyamines/biosynthesis , Cells, Cultured , Cytokines/biosynthesis , Enzyme Inhibitors/pharmacology , Female , Folic Acid/pharmacology , Folic Acid Antagonists/pharmacology , Leucovorin/pharmacology , Purinergic P1 Receptor Agonists , Rats , Rats, Inbred Strains , Synovial Membrane/cytology , Synovial Membrane/drug effects , Synovial Membrane/metabolism , Thymidylate Synthase/antagonists & inhibitors
18.
J Rheumatol ; 26(9): 2018-24, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10493685

ABSTRACT

OBJECTIVE: To measure intracellular and tissue pH in periarticular soft tissue during different phases of antigen induced arthritis in the rat. METHODS: pH was calculated using the following values: (1) the distribution of [14C]-dimethyl-oxazolidinedione; (2) the total tissue water and the extracellular space water volume, which was measured as [14C]-sucrose distribution in nephrectomized rats. Experiments were performed during both maximal inflammation (Day 3) and the restorative phase (Day 14). RESULTS: In all animals both tissue (pHt) and intracellular (pHi) pH were lower in arthritic joints than in the contralateral control. Mean pHt in control joints was 7.37+/-0.03. In arthritic rats it was 7.30+/-0.05 on Day 3 after challenge and 7.27+/-0.03 on Day 14. The pHi ranges were 6.86-7.81 for controls, 6.65-7.28 for arthritis Day 3, and 5.66-6.91 for arthritis Day 14. CONCLUSION: In this model there is a reduction in pH in the periarticular tissue of arthritic joints. The magnitude is, however, relatively small and the pannus tissue is not uniquely acidic in comparison with other compartments. There does not seem to be a correlation between pH and changes in metabolic balance, pannus formation, or healing.


Subject(s)
Acidosis/metabolism , Arthritis/metabolism , Hydrogen-Ion Concentration , Knee Joint/metabolism , Animals , Arthritis/immunology , Body Water/metabolism , Cells, Cultured , Culture Techniques , Dimethadione/metabolism , Disease Models, Animal , Female , Inflammation/metabolism , Knee Joint/blood supply , Knee Joint/pathology , Nephrectomy , Rats , Rats, Inbred Strains , Reference Values , Sucrose/metabolism , Time Factors
19.
J Rheumatol ; 25(9): 1778-84, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9733460

ABSTRACT

OBJECTIVE: Based on the hypothesis that blood flow in the inflamed joint is inadequate to maintain aerobic glycolysis, we sought to estimate the correlation between blood flow, glucose metabolism, and cellular proliferation rate in the arthritic joint. METHODS: Experiments were performed on rats with antigen induced arthritis (AIA). Regional blood flows (RBF) were measured with the microsphere technique, glucose metabolism by determination of [14C]2-deoxy-D-glucose (2-DG) uptake, and the proliferative response as the incorporation of [3H]-thymidine. RESULTS: In periarticular soft tissue of the arthritic knee the only significant change in the weight related RBF was an approximate 70% rise on Day 14 after arthritis onset. The RBF was lowest on Day 3 and the time course for the changes was inversely related to intensity of vascular inflammation. Weight related 2-DG uptake was more elevated than the RBF and peaked on Day 3. [3H]-thymidine incorporation in the soft tissue was only markedly enhanced on Day 3. Neither 2-DG nor [3H]-thymidine uptake was affected by treatment with methotrexate or indomethacin. In epiphyseal bone RBF was reduced on the first day of arthritis, but steadily increased thereafter. CONCLUSION: In AIA an intense vascular leakiness negatively affects the synovial blood. There is a marked enhancement of glucose metabolism, but only a minor part of this increase seems to be induced by increased cellular proliferation.


Subject(s)
Arthritis/physiopathology , Glucose/metabolism , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Arthritis/chemically induced , Arthritis/metabolism , Arthritis/pathology , Autoradiography , Blood Flow Velocity/drug effects , Cell Division/drug effects , Deoxyglucose/metabolism , Female , Immunosuppressive Agents/pharmacology , Indomethacin/pharmacology , Joints/blood supply , Joints/drug effects , Joints/pathology , Methotrexate/pharmacology , Rats , Serum Albumin, Bovine
20.
J Orofac Pain ; 12(1): 27-34, 1998.
Article in English | MEDLINE | ID: mdl-9656896

ABSTRACT

This study focuses on the influence of trait anxiety and mood variables on changes in tooth pain threshold following two similar methods of somatic afferent stimulation, one familiar (manual acupuncture) and one unfamiliar (low-frequency transcutaneous electrical nerve stimulation [low-TENS]). Twenty-one acupuncture responders, treated for long-lasting orofacial muscular pain but naive to low-TENS, were selected for the study. In an experimental session, acupuncture and low-TENS were randomly given during two periods separated by a rest interval. Tooth pain thresholds (PT) were measured before and after stimulation with a computerized electrical pulp tester. Trait anxiety and depression were assessed with psychometric forms before the experimental session in all patients, whereas momentary mood was assessed in 10 randomly selected patients with visual analogue scales during and after the two types of stimulation. Following acupuncture, the group average PT increased significantly, whereas no significant change was observed following low-TENS. Higher scores on trait anxiety correlated significantly with a low PT increase following low-TENS, and higher ratings of stress correlated significantly with a low PT increase following acupuncture. This indicates that the magnitude of analgesia induced by these methods may be modified by psychologic factors like anxiety and stress.


Subject(s)
Facial Pain/psychology , Pain Threshold/psychology , Temporomandibular Joint Dysfunction Syndrome/psychology , Acupuncture Therapy , Anxiety/physiopathology , Facial Pain/physiopathology , Humans , Psychometrics , Regression Analysis , Statistics, Nonparametric , Stress, Psychological/physiopathology , Temporomandibular Joint Dysfunction Syndrome/physiopathology , Transcutaneous Electric Nerve Stimulation
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