Geometrical restoration during total hip arthroplasty is related to change in gait pattern - a study based on computed tomography and three-dimensional gait analysis.

BACKGROUND: The effect of change in hip anatomy on change in gait pattern is not well described in current literature. Therefore, our primary aim was to describe and quantify changes in hip geometry and gait pattern 1 year after total hip arthroplasty (THA) in individuals with hip osteoarthritis. Our secondary aim was to explore the effect of postoperative change in femoral neck anteversion (FNA) and femoral offset and acetabular offset (FO/AO) quota on postoperative change in hip rotation and hip adduction moment during gait, respectively, 1 year after THA". METHODS: Sixty-five individuals with primary hip osteoarthritis, scheduled for THA, were analyzed in this prospective intervention study. Participants were evaluated pre- and 1 year postoperatively with computed tomography-scans, three-dimensional gait analysis, and patient-reported outcome measures. Multiple linear regressions were performed to evaluate the association between change in joint anatomy and change in gait pattern after THA. RESULTS: One year postoperatively, global offset was symmetrical between sides as a result of decreased acetabular offset and increased femoral offset on the operated side. Quality of overall gait pattern improved, and participants walked faster and with less trunk lean over the affected side. FNA and hip rotations during walking changed equally in external and internal directions after THA and change in hip rotation during walking was associated with change in FNA in the same direction. An increase in external hip adduction moments was, on the other hand, not associated with change in FO/AO quota but with a more upright walking position and increased walking speed. CONCLUSIONS: The findings of this study suggest that geometrical restoration during THA impacts postoperative gait pattern and, in addition to known factors such as FO, height of hip rotation center, and leg length discrepancy, the FNA must also be taken into consideration. TRIAL REGISTRATION: Trial registration: Clinicaltrial.gov , NCT01512550 , Registered 19 January 2012 - Retrospectively registered.

Sensitization to minor cat allergen components is associated with type-2 biomarkers in young asthmatics.

BACKGROUND: Cat allergy is a major trigger of asthma world-wide. Molecular patterns of cat sensitization vary between individuals, but their relationship to inflammation in asthmatics has not been extensively studied. OBJECTIVE: To investigate the prevalence and levels of IgE antibodies against different cat allergen components and their relationship to type-2 inflammation and total IgE among young asthmatic subjects sensitized to furry animals. METHODS: Patients with asthma (age 10-35 years; n = 266) and IgE sensitization to cat, dog or horse extract (ImmunoCAP), were analysed for IgE to the cat allergen components Fel d 1 (secretoglobin), Fel d 2 (serum albumin), Fel d 4 and Fel d 7 (lipocalins). Independent associations between IgE-antibody concentrations, and fraction of exhaled nitric oxide (FeNO), blood eosinophil (B-Eos) count, and total IgE were analysed by multiple linear regression after adjustment for possible confounders. RESULTS: The level of IgE against Fel d 2 was independently related to FeNO (P = .012) and total IgE (P < .001), and IgE against Fel d 4 associated with Β-Eos count (P = .009) and total IgE (P < .001). IgE antibodies against Fel d 1 or cat extract did not independently relate to these inflammatory markers (P = .23-.51). CONCLUSIONS: Levels of IgE to lipocalin (Fel d 4) and serum albumin (Fel d 2), but not to secretoglobin (Fel d 1) or cat extract, were independently associated with type-2 biomarkers and total IgE in young asthmatics. CLINICAL RELEVANCE: We suggest that measurement of IgE to minor cat allergen components may be useful when investigating asthma morbidity in cat allergic subjects.

Component-resolved diagnosis of dog allergy

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Human memory CD4+ T cell response to the major dog allergen Can f 5, prostatic kallikrein.

BACKGROUND: Human CD4+ T cell responses to important animal allergens are still insufficiently understood. OBJECTIVE: To comprehensively characterize in vitro and ex vivo the peripheral blood memory CD4+ T cell responses of subjects with and without allergy to the major dog allergen Can f 5, the only known animal allergen in the kallikrein family of proteins. METHODS: Can f 5-specific memory CD4+ T cell lines (TCLs) were established from the peripheral blood of 12 subjects with and 12 subjects without allergy to Can f 5 and characterized for their functional and phenotypic properties. The results were evaluated with those obtained ex vivo with a novel CD154 enrichment method. The epitopes recognized by the Can f 5-specific TCLs were determined with 72 overlapping 16-mer peptides covering the sequence of the allergen. RESULTS: Can f 5-specific TCLs were obtained at about tenfold higher frequency from allergic than from non-allergic subjects. Functionally, the TCLs of allergic subjects displayed a Th2-biased cytokine phenotype and increased T cell receptor avidity, whereas the TCLs of non-allergic subjects displayed a Th1-/Th0-biased cytokine phenotype and lower TCR avidity. The higher frequency and the Th2 phenotype of Can f 5-specific memory CD4+ T cells in allergic subjects were confirmed by the CD154 enrichment method ex vivo. Six distinct T cell epitope regions of Can f 5 were predominantly recognized by the TCLs from allergic subjects. CONCLUSIONS AND CLINICAL RELEVANCE: Can f 5-specific memory CD4+ T cell responses differ considerably between subjects with and without allergy, as assessed by both in vitro and ex vivo approaches. Peptides containing the dominant T cell epitopes of Can f 5 can be employed for developing peptide-based immunotherapy for dog allergy.

Ultra-low-dose estradiol and norethisterone acetate: bleeding patterns and other outcomes over 52 weeks of therapy.

BACKGROUND: Continuous combined hormone replacement therapy (HRT) with 0.5 mg 17ß-estradiol (E2) + 0.1 mg norethisterone acetate (NETA) received marketing approval based on 24-week results. The current study collected data up to 52 weeks, including consideration of bleeding, a major reason for stopping HRT. METHODS: This 52-week (13 lunar-month), non-interventional, prospective study involved 169 women from Norway and Sweden receiving daily oral 0.5 mg E2 + 0.1 mg NETA to treat menopausal symptoms. Incidences and cumulative rates of amenorrhea (no bleeding or spotting) and no bleeding (women could have spotting) were evaluated, together with hot flushes and quality of life. RESULTS: Overall, > 78% and > 90% of subjects were amenorrheic or had no bleeding, respectively, in each of the first 3 lunar months, while > 88% and > 96% were amenorrheic or had no bleeding, respectively, in each of lunar months 10, 11 and 12. Cumulative rates of amenorrhea and no bleeding were 67% and 83%, respectively, in lunar months 1-3, and 84% and 94%, respectively, in lunar months 10-12. The number of hot flushes declined during treatment (means at weeks 1, 12 and 52, respectively: 15.5, 5.0 and 4.1 [mild]; 19.0, 3.0 and 2.3 [moderate]; 10.8, 1.1 and 0.9 [severe]). Improvement in all four domains of the Menopause-Specific Quality of Life-Intervention questionnaire (vasomotor, psychosocial, physical and sexual) was evident by week 26. CONCLUSION: For women receiving 0.5 mg E2 + 0.1 mg NETA, lack of bleeding-related side-effects, together with beneficial effects on hot flush symptoms and quality of life, may promote treatment continuance.

Peanut allergy is common among hazelnut-sensitized subjects but is not primarily the result of IgE cross-reactivity.

BACKGROUND: Hazelnut and peanut are botanically unrelated foods, but patients are often sensitized and allergic to both, for reasons that are not well understood. METHODS: To investigate molecular cosensitization and cross-reactivity to peanut in hazelnut-sensitized individuals, children (n = 81) and adults (n = 80) were retrospectively selected based on sensitization to hazelnut. IgE to hazelnut extract, Cor a 1, 8, 9 and 14, to peanut extract, Ara h 1, 2, 3, 8 and 9, and to Bet v 1 was determined by ImmunoCAP. Allergy to hazelnut and peanut was established by DBPCFC and/or detailed clinical history. Patients were either tolerant or displayed subjective or objective symptoms to either food. IgE cross-reactivity between hazelnut and peanut storage proteins was assessed by reciprocal ImmunoCAP inhibition experiments. RESULTS: Of the 161 hazelnut-sensitized subjects, 109 (68%) were also sensitized to peanut, and 73 (45%) had clinical expression of allergy to peanut that was not associated with the presence or severity of hazelnut allergy. Instead, it was associated with IgE reactivity to peanut storage proteins, in particular Ara h 2. No cross-reactivity could be detected between Ara h 2 and Cor a 14, and 2 of 13 subjects displayed extensive cross-reactivity between 11S globulins; in plasma of both individuals, Ara h 3 almost completely inhibited IgE binding to Cor a 9. CONCLUSIONS: Peanut allergy is not primarily the result of IgE cross-reactivity to hazelnut storage proteins. IgE to Cor a 14 and Ara h 2 may serve as useful markers of primary sensitization to hazelnut and peanut, respectively.

A case of dog-related human seminal plasma allergy.

Allergy to human seminal plasma (HSP) is rare. It presents with a variety of symptoms, ranging from localized changes to generalized reactions or even anaphylactic shock. Symptoms typically start within minutes to one hour after exposure. Diagnosis is based on history, evidence of specific IgE antibodies and skin prick testing (SPT). A 25-year-old Caucasian woman presented with eyelid swelling, generalized urticaria and dyspnea immediately after unprotected coitus with her partner. No symptoms occurred when barrier contraception was used. SPTand IgE testing (ImmunoCAP) demonstrated sensitization to HSP and dog dander. The patient's self-designed desensitization protocol, consisting of H1 blocker premedication followed by unprotected sexual intercourse, ameliorated her systemic reactions gradually and reduced the frequency of emergency hospital visits. She had a known allergy to male but not female dogs, and was highly sensitized to dog allergen Can f 5, a protein homologous to human prostate-specific antigen (PSA), suggesting a possible link to her HSP allergy.

A comparison of active management and expectant management of the third stage of labour: a Swedish randomised controlled trial.

OBJECTIVE: to compare blood loss in women actively and expectantly managed in the third stage of labour. DESIGN: randomised controlled trial (RCT). SETTING: two delivery units at a Swedish university hospital. POPULATION: healthy women with normal pregnancies, at gestational age 34-43 weeks, with singleton cephalic presentation and expected vaginal delivery. METHODS: the women were randomly allocated to either active (n = 903) or expectant (n = 899) management of the third stage of labour. MAIN OUTCOME MEASURES: the primary outcome was blood loss > 1000 ml, and secondary outcomes were mean blood loss, duration of third stage, retained placenta, haemoglobin level and blood transfusion. RESULTS: blood loss > 1000 ml occurred in 10% of the actively managed group and 16.8% of the expectantly managed group (P < 0.001). Mean blood loss was 535 ml in the actively managed group and 680 ml in the expectantly managed group (P < 0.001). A prolonged duration of the third stage was associated with increased blood loss. Increased placenta weight was associated with increased blood loss. The haemoglobin level was 118 g/dl in actively managed women and 115/dl in expectantly managed women (P < 0.001) the day after childbirth. The occurrence of retained placenta and the number of blood transfusions did not differ between the groups. CONCLUSIONS: active management of the third stage of labour was associated with less blood loss compared with expectant management. It is reasonable to advocate this regime, especially in primiparous women.

Molecular and immunological characterization of Can f 4: a dog dander allergen cross-reactive with a 23 kDa odorant-binding protein in cow dander.

BACKGROUND: Dog dander is an important cause of respiratory allergy but its content of allergenic components is still incompletely known. While Can f 1, 2, 3 and 5 have been studied in detail, only fragmentary information is available on the lipocalin Can f 4. OBJECTIVE: To purify, clone and characterize dog dander allergen Can f 4. METHODS: Can f 4 was purified from dog dander extract by size exclusion, ion exchange and reverse phase chromatography. A cDNA encoding Can f 4 was cloned and used to produce recombinant Can f 4 in Escherichia coli. A 23 kDa protein from cow dander, displaying cross-reactivity with Can f 4, was purified and identified by amino acid sequencing and mass spectrometry. IgE antibody binding to dog and cow dander extract and to individual dog allergens among 37 dog allergic subjects and 44 pollen allergic controls was studied using ImmunoCAP. RESULTS: A dog genome segment containing the Can f 4 gene was bioinformatically identified and enabled the cloning of Can f 4 cDNA. Recombinant Can f 4 displayed close immunological and biochemical similarity to purified natural Can f 4 and bound IgE antibodies from 13/37 (35%) sera of dog allergic subjects. Can f 4 reactive sera showed IgE binding to a 23 kDa protein present in cow dander extract, related to a family of odorant-binding proteins. The dog and cow proteins shared 37% sequence identity and their cross-reactivity was demonstrated by IgE inhibition experiments. CONCLUSION: Recombinant Can f 4 brings the panel of available dog allergens closer to completion and will be important in component-resolved diagnostics in allergy to animal epithelial allergens.

Contribution of variant alleles of ABCB11 to susceptibility to intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) has a complex aetiology with a significant genetic component. ABCB11 encodes the bile salt export pump (BSEP); mutations cause a spectrum of cholestatic disease, and are implicated in the aetiology of ICP. METHODS: ABCB11 variation in ICP was investigated by screening for five mutant alleles (E297G, D482G, N591S, D676Y and G855R) and the V444A polymorphism (c.1331T>C, rs2287622) in two ICP cohorts (n = 333 UK, n = 158 continental Europe), and controls (n = 261) for V444A. PCR primers were used to amplify and sequence patient and control DNA. The molecular basis for the observed phenotypes was investigated in silico by analysing the equivalent residues in the structure of the homologous bacterial transporter Sav1866. RESULTS: E297G was observed four times and D482G once. N591S was present in two patients; D676Y and G855R were not observed. The V444A polymorphism was associated with ICP (allelic analysis for C vs T: OR 1.7 (95% CI 1.4 to 2.1, p<0.001)). In addition, CC homozygotes were more likely to have ICP than TT homozygotes: OR 2.8 (95% CI 1.7 to 4.4 p<0.0001). Structural analyses suggest that E297G and D482G destabilize the protein fold of BSEP. The molecular basis of V444A and N591S was not apparent from the Sav1866 structure. CONCLUSIONS: Heterozygosity for the common ABCB11 mutations accounts for 1% of European ICP cases; these two mutants probably reduce the folding efficiency of BSEP. N591S is a recurrent mutation; however, the mechanism may be independent of protein stability or function. The V444A polymorphism is a significant risk factor for ICP in this population.

Lower-than-standard dose peg-IFN alfa-2a for chronic hepatitis C caused by genotype 2 and 3 is sufficient when given in combination with weight-based ribavirin.

Mono-therapy with pegylated interferon (peg-IFN) has shown that a lower-than-standard dose yields the same sustained viral response (SVR) rates as standard doses for chronic hepatitis C virus (HCV) infection caused by genotypes 2 or 3. Our aim was to see if a fixed, lower-than-standard dose of peg-IFN alfa-2a (135 microg weekly) in combination with ribavirin 11 mg/kg daily for 24 weeks yields sufficient SVR rates for genotypes 2 or 3. Hundred consecutive patients with a mean age of 44 years (range 20-69 years), 59 with genotype 3 and 41 with genotype 2, were studied. Rapid viral response (RVR) with HCV-RNA <15 IU/mL at treatment week 4 and SVR were calculated. RVR was achieved by 28/40 (70%) patients with genotype 2 and 41/58 (71%) with genotype 3. Significantly more genotype 2 patients with RVR achieved SVR 27/28 (96%) than genotype 2 patients who failed to achieve RVR, 8/12 (66%), P = 0.009. The corresponding figures for genotype 3 patients were 39/41 (95%) vs 11/17 (65%), respectively, P = 0.002. In total, SVR was achieved by 35/41 (85%) patients with genotype 2 and 51/59 (86%) patients with genotype 3, respectively. We found that 135 microg peg-IFN alfa-2a weekly was sufficient for treatment of genotype 2 and 3 chronic hepatitis C when combined with RBV dosed daily according to body weight. This combination yielded high SVR rates (85-86%) and may be cost-saving.

Leadership, governance and management in dental education - new societal challenges.

Dental schools around the world face new challenges that raise issues with regard to how they are governed, led and managed. With rapid societal changes, including globalization and consumerism, the roles of universities and their funding have become intensely debated topics. When financial burdens on universities increase, so does the pressure on dental schools. This is exacerbated by the relative expense of running dental schools and also by the limited understanding of both university managers and the public of the nature and scope of dentistry as a profession. In these circumstances, it is essential for dental schools to have good systems of leadership and management in place so that they can not only survive in difficult times, but flourish in the longer term. This paper discusses the concept of governance and how it relates to leadership, management and administration in dental schools and hospitals. Various approaches to governance and management in dental schools on different continents and regions are summarized and contrasted. A number of general governance and leadership issues are addressed. For example, a basic principle supported by the Working Group is that an effective governance structure must link authority and responsibility to performance and review, i.e. accountability, and that the mechanism for achieving this should be transparent. The paper also addresses issues specific to governing, leading and managing dental schools. Being a dean of a modern dental school is a very demanding role and some issues relating to this role are raised, including: dilemmas facing deans, preparing to be dean and succession planning. The importance of establishing a shared vision and mission, and creating the right culture and climate within a dental school, are emphasized. The Working Group advocates establishing a culture of scholarship in dental schools for both teaching and research. The paper addresses the need for effective staff management, motivation and development, and highlights the salience of good communication. The Working Group suggests establishing an advisory board to the dean and school, including lay persons and other external stakeholders, as one way of separating governance and management to some extent and providing some checks and balances within a dental school. Several other suggestions and recommendations are made about governance, management and leadership issues, including the need for schools to promote an awareness of their roles by good communication and thereby influence perceptions of others about their roles and values.

Efficacy and tolerability of continuous combined hormone replacement therapy in early postmenopausal women.

OBJECTIVE: Continuous combined hormone replacement therapy (ccHRT) based on estradiol valerate (E2V) and medroxyprogesterone acetate (MPA) is effective for relief of menopausal symptoms three years or more after the menopause. This study was undertaken to examine the efficacy and tolerability of ccHRT in early postmenopausal women (last menstrual period 1.3 years before study entry). STUDY DESIGN: This was a 52-week, randomized, double-blind, multinational study of ccHRT comprising three different dose combinations of E2V/MPA in 459 early postmenopausal non-hysterectomized women experiencing 30 or more moderate to severe hot flushes a week and/or vasomotor symptoms requiring treatment. MAIN OUTCOMES MEASURES: The primary endpoint was change in frequency and severity of moderate to severe hot flushes at 12 weeks. Secondary outcome measures included number of bleeding days and evaluation of tolerability. RESULTS: The frequency of hot flushes was reduced by >or=70% after one month (P<0.001 for all doses at week 2 onwards), with little evidence of statistically different dose effects. Severity of flushing was also attenuated by ccHRT. Mean number of bleeding days fell to <1 per 28-day cycle at 52 weeks. Rates of amenorrhoea approached 80-90% at the end of the study, but were significantly lower at several time points with the highest-dose regimen (2 mg E2V + 5 mg MPA) than with the lower-dose options (1 mg E2V + 2.5 mg MPA and 1 mg E2V + 5 mg MPA; P<0.05). Adverse events declined in frequency over time with all regimens but throughout the study were more numerous with the highest-dose regimen than with lower doses (P= 0.0002). CONCLUSIONS: Continuous combined HRT was effective for the relief of climacteric symptoms in early postmenopausal women and was well tolerated.

Intrahepatic cholestasis of pregnancy: the severe form is associated with common variants of the hepatobiliary phospholipid transporter ABCB4 gene.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is characterised by troublesome maternal pruritus, raised serum bile acid levels and increased fetal risk. Mutations of the ABCB4 gene encoding the hepatobiliary phospholipid transporter have been identified in a small proportion of patients with cholestasis of pregnancy. In a recent prospective study on 693 patients with cholestasis of pregnancy, a cut-off level for serum bile acid (> or =40 micromol/l) was determined for increased risk of fetal complications. OBJECTIVES: To investigate whether common combinations of polymorphic alleles (haplotypes) of the genes encoding the hepatobiliary ATP-binding cassette (ABC) transporters for phospholipids (ABCB4) and bile acids (ABCB11) were associated with this severe form of cholestasis of pregnancy. METHODS: For genetic analysis, 52 women with bile acid levels > or =40 micromol/l (called cases) and 52 unaffected women (called controls) matched for age, parity and geographical residence were studied. Gene variants tagging common ABCB4 and ABCB11 haplotypes were genotyped and haplotype distributions were compared between cases and controls by permutation testing. RESULTS: In contrast with ABCB11 haplotypes, ABCB4 haplotypes differed between the two groups (p = 0.019), showing that the severe form of cholestasis of pregnancy is associated with the ABCB4 gene variants. Specifically, haplotype ABCB4_5 occurred more often in cases, whereas haplotypes ABCB4_3 and ABCB4_7 were more common in controls. These associations were reflected by different frequencies of at-risk alleles of the two tagging polymorphisms (c.711A: odds ratio (OR) 2.27, p = 0.04; deletion intron 5: OR 14.68, p = 0.012). CONCLUSION: Variants of ABCB4 represent genetic risk factors for the severe form of ICP in Sweden.

Knee kinematics and kinetics during gait, step and hop in males with a 16 years old ACL injury compared with matched controls.

The objective of this study was to compare subjects who sustained an ACL injury during soccer 16 years ago with a control group with regard to knee kinematics and kinetics of gait, step activity and cross over hop. Secondly, in the injured subjects, the purpose was to study the impact on kinematics and kinetics of characteristics such as operative status, meniscal resection, being symptomatic, having knee extensor weakness and of having radiographic knee OA. Data from a 3-dimensional gait analysis system (VICON) were used to calculate kinetics and kinematics during gait, step activity and cross over hop of 12 male subjects who had an anterior cruciate ligament injury 16 years earlier. Twelve uninjured subjects matched for age, sex, BMI and activity level served as controls. No significant differences in knee kinematics and kinetics between the ACL group and the control group were found. The variability of some parameters of step and all parameters of hop activity was generally larger in the ACL injured subjects compared with the controls. The ACL injured subjects had a significantly worse clinical status compared with the controls. Reduced knee extension strength was associated with joint moment reductions especially during step activity and cross over hop. Despite a significantly worse clinical status, as determined by self-report and isokinetic strength testing, no significant differences were seen in knee joint kinetics and kinematics in an ACL injured group 16 years after injury compared with a matched control group. The variation was larger among the ACL injured subjects indicating the need for larger study groups in gait and movement analysis in long-term follow-up of ACL injury.

A low-dose start in hormone replacement therapy provides a beneficial bleeding profile and few side-effects: randomized comparison with a conventional-dose regimen.

OBJECTIVE: To compare bleeding control, efficacy and safety of two dose-ranging continuous combined hormone replacement therapy (HRT) regimens with those of a conventional continuous combined HRT. METHODS: An open, 2-year, multicenter study was conducted in 393 postmenopausal women recruited from 16 study sites. The women were randomized to three continuous combined HRT regimens. One group (n = 131) started with 1 mg of estradiol valerate (E2V) plus 2.5 mg of medroxyprogesterone acetate (MPA), the second group (n = 130) received 1 mg E2V + 5 mg MPA and the third (n = 132) 2 mg estradiol (E2) and 1 mg norethisterone acetate (NETA). In the two E2V/MPA groups the initial E2V dose of 1 mg was increased to 2 mg after six cycles (one cycle = 28 days) to evaluate the effect of dose increase on bleeding control. RESULTS: The E2V/MPA regimens with a lower estrogen dose induced less bleeding and other adverse effects during the first six cycles than did the E2/NETA regimen. Bleeding disturbances and breast tenderness resulted in significantly more discontinuations in the E2/NETA group. After the estrogen dose increase in the E2V/MPA regimens, all groups showed comparable bleeding patterns and adverse effect profiles. The lower E2V dose was as effective as standard-dose E2 in relieving climacteric symptoms. All regimens provided excellent endometrial safety. No hyperplasias were reported. CONCLUSIONS: Continuous combined HRT should be started, and continued, with the lowest effective doses. An increase of the estrogen dose is recommended only if the initial dose is not sufficient for symptom control.

A longitudinal population study of climacteric symptoms and their treatment in a random sample of Swedish women.

OBJECTIVES: To assess, first, the prevalence and severity of symptoms associated with the climacteric period and their treatment and, second, the prevalence of exercise, smoking and body weight in a population-based sample of Swedish women. MATERIAL AND METHODS: Prospective, longitudinal cohort study, initiated in 1992, in women aged 46, 50, 54, 58 and 62 years with a follow-up 6 years later. Information was obtained from the same women (n=3816) on both occasions using a postal questionnaire regarding sociodemographic variables, general and reproductive health, the occurrence of climacteric symptoms and their severity, and the use of hormone replacement therapy (HRT). RESULTS: The prevalences of climacteric symptoms were as follows (1992/1998): vasomotor symptoms, 52%/62%; depression/irritability, 57%/65%; sleeping disturbances, 51%/69%; muscle/joint pain, 55%/70%; and loss of libido, 38%/57%. HRT with medium-potency estrogens was currently being used by 34% (1992: 14%), and 12% (1992: 8%) were using low-potency estrogens. The maximum prevalence of HRT (medium-potency estrogens) use was found in the 56-year-old group, at 46% (1992: 25% in the 54-year-old group). Body mass for the whole group had increased from 66.3 to 68.9 kg. Exercise was more frequent in all age groups in 1998 compared to 1992. There was a decrease in current smokers from 32 to 26% between the two periods. Compared with 1992, the women in all five birth cohorts considered themselves to be less healthy and quality of life had decreased for the whole group. CONCLUSIONS: The prevalence of symptoms associated with the climacteric period and the use of HRT had increased markedly in this longitudinal study of the same women followed between 1992 and 1998. During the same period, smoking decreased, while body weight and exercise frequency increased.

Low dose hormone replacement therapy: clinical efficacy.

The frequency of hormone replacement therapy (HRT) users has increased during the last 2 decades. A majority of women taking HRT prefer to use formulations that will not induce bleeding disturbances. Accordingly many women prefer continuous combined HRT to obtain amenorrhoea. Previously comparatively high doses of estrogens and progestogens were prescribed to women in the climacteric period. Low doses of estrogens such as estradiol 1 mg and conjugated equine estrogens 0.3 mg orally per day or transdermally applied estradiol 25 mug per 24 hours have been shown to be effective for the treatment of vasomotor symptoms and for prevention of bone loss. With low dose HRT in a continuous combined regimen amenorrhoea will be obtained in a majority of women after a few months of treatment. Low doses of progestogen especially if given on a continuous basis have been shown to protect the endometrium from hyperplasia. Favourable effects in lipid- and lipoprotein patterns have been reported. In addition, fewer side effects such as mastalgia have been found during treatment with low dose regimen compared to high doses. For women requesting HRT it might be a rational alternative to begin with low dose formulations since these doses are sufficient for the majority of women.

Antigen inhibition of collagen-induced arthritis is associated with up-regulation of IL-4 mRNA and induction of Ox40 on T cells in draining lymph nodes.

The addition of a foreign antigen to an inoculum completely inhibits the development of collagen-induced arthritis (CIA). However, the mechanism of this phenomenon, antigen -inhibition, is incompletely understood. Previous studies have demonstrated that the inhibition of arthritis is not mediated through suppression of the antibody response to cartilage antigens. In this paper we investigated cytokine mRNA levels in lymph nodes cells recovered 3, 7 or 16 days from animals immunized with either collagen II in IFA or OVA + collagen II in IFA. At day 7, but not at other time-points, IL-4 mRNA was up-regulated in the lymph nodes of OVA-inhibited non-arthritic animals compared to control animals which all developed arthritis. No significant differences between the two groups could be detected when expression of IFN-gamma, IL-2, TNF-alpha, IL-1beta or IL-10 mRNA was analysed. Flow cytometry analysis of draining lymph node cells demonstrated that the T cell marker Ox40 was up-regulated in the OVA-inhibited group. Our results indicate that the complete inhibition of CIA caused by addition of OVA to the collagen II inoculum is due to the presence of a TH2 environment resulting from an increased production of IL-4 mRNA and a parallel increase in Ox40+ T cells.