UV-B and temperature enhancement affect spring and autumn phenology in Populus tremula.

Perennial plants growing at high latitudes synchronize growth and dormancy to appropriate seasons by sensing environmental cues. Autumnal growth cessation, bud set and dormancy induction are commonly driven by the length of photoperiod and light quality, and the responses are modified by temperature. However, although ultraviolet (UV)-B radiation is well known to affect plant growth and development, information on the effects on bud phenology is scarce. We examined the separate and combined effects of enhanced temperature and UV-B on autumnal bud set and spring bud break in female and male clones of Populus tremula in an outdoor experiment in Joensuu, Eastern Finland. Enhancements of UV-B and temperature were modulated to +30% and +2 °C, respectively, from June to October 2012. Enhanced UV-B accelerated bud set, while increased temperature delayed it. For both UV-B and temperature, we found sex-related differences in responsiveness. Temperature increase had a stronger delaying effect on bud maturation in male compared with female clones. Also, male clones were more responsive to UV-B increase than female clones. Increasing autumnal temperature enhanced bud break in spring for both sexes, while UV-B enhanced bud break in male clones. In conclusion, we found that UV-B affected phenological shifts in P. tremula, and that temperature and UV-B affected genders differently.

A Case Report of Caudal Migration of a Lumbar Epidural Catheter Confirmed by Doppler Ultrasound: Ultrasound to the Rescue!

Combined spinal-epidural anaesthesia is an excellent technique for providing intraoperative and postoperative analgesia in patients undergoing total knee arthroplasty. Epidural catheters threaded through a Tuohy needle with a cephalad needle bevel orientation follow a winding pattern within the epidural space. Caudal or downward migration of an epidural catheter may lead to unsatisfactory anaesthesia and epidural failure. Colour flow Doppler sonography is emerging as an effective technique to determine the epidural catheter tip position. We report an interesting case of caudal migration of a lumbar epidural catheter confirmed by colour flow Doppler ultrasound.

Dynamical links of convective storms associated with tropospheric biennial oscillation in the Indian monsoon regime.

Tropospheric Biennial Oscillation (TBO) is characterized by a tendency for a relatively stronger monsoon to be followed by a relatively weaker one (positive) or vice-versa (negative). This study examines the distribution of different convective systems occurring during TBO phases over the Indian monsoon region. During negative TBO phase, convection is preferential over the Arabian Sea (AS), whereas during positive TBO phase, it is favoured over the land areas and Bay of Bengal (BoB). The isolated shallow convection (ISC) is dominated over the AS and Indian west coast during negative TBO years. A relatively stable environment (statically) capped with drier mid-troposphere results in abundant ISC over the AS. Broad stratiform rain (BSR) dominates over the central and east coast of India, BoB and Myanmar coast during positive TBO years and wide convective core (WCC) are present along the orographic regions, i.e., Myanmar coast and Western Ghats during negative TBO phase. The anomalous easterlies induced by the upper-ocean temperature gradient interact with the mean monsoon winds during positive TBO to provide pathways for developing BSR echoes. The deep-wide convection (DWC) are higher along the Himalayan foothills during positive TBO years. The moist low-level flow from the AS is trapped by dry mid-level flow from high latitudes, resulting in orographic lifting along the Himalayan foothills and form DWC.

Physical processes controlling the diurnal cycle of convective storms in the Western Ghats.

Diurnal variation of convective storms (CSs) during monsoon season and associated physical mechanisms are significantly important for accurate forecast of short-time and extreme precipitation. The diurnal cycle of CSs is investigated using ground-based X-band radar, Tropical Rainfall Measuring Mission Precipitation Radar, and reanalysis data during the summer monsoon (June-September of 2014) over complex mountain terrain of Western Ghats, India. Diurnally, CSs show a bimodal distribution in the coastal areas, but this bimodality became weak along the upslope regions and on the mountain top. The first occurrence mode of CSs is in the afternoon-evening hours, while the second peak is in the early-morning hours. The diurnal cycle's intensity varies with location, such that it reaches maximum in the afternoon-evening hours and early morning on the mountain top and coastal areas, respectively. Two possible mechanisms are proposed for the observed diurnal variation in CSs (a) the radiative cooling effect and (b) the surface wind convergence induced by the interaction between land-sea breeze, local topography and large-scale monsoon winds. It is also observed that the CSs developed on the mountain top during afternoon-evening hours are deeper than those along the coast. The higher moisture in the lower- and mid-troposphere, higher instability and strong upward motion facilitate deeper CSs during afternoon-evening hours.

Abfraction: Etiopathogenesis, clinical aspect, and diagnostic-treatment modalities: A review.

BACKGROUND: Abfraction is a loss of tooth structure along the gingival margin and manifests with different clinical appearances. It has multifactorial etiology and may occur due to normal and abnormal tooth function and may also be accompanied by pathological wear, such as abrasion and erosion. The theory behind the abfraction is that the tooth flexure in the cervical area is caused due to occlusal compressive forces and tensile stresses. This results in the fractures in the hydroxyapatite (HA) crystals. It is also caused by the low packing density of the Hunter-Schreger band (HSB) at the cervical area. Unfortunately, there is a lack of evidence regarding the outcome of abfraction with or without intervention. The aim of this review is to collect clinical information from the literature and discuss the etiology, pathogenesis, clinical representation, and management. Also, search databases for clinical studies that describe the role of sclerotic dentine in non-carious cervical lesions (NCCLs) are becoming a clinical challenge. METHODS: The literature was searched that described the etiology, pathogenesis, clinical representation, and management of the abfraction lesions. Also, a specific question regarding the formation of sclerotic dentin in the NCCL lesion was described and searched for evidence that challenges etching, bonding, and successfully restoring NCCLs. The databases PUBMED, SCOPUS, MEDLINE, WEB of SCIENCE, and EMBASE were searched using the key terms. The inclusion criteria were the randomized controlled clinical trial, cohort studies, and cross-sectional studies that aimed at determining the role of sclerotic dentine in NCCLs and its effect on etching, bonding. RESULTS: One clinical study was retrieved according to the PRISMA flowchart and PICO format. The longer etching time, total-etch adhesive system, and EDTA pre-treatment of the sclerotic dentin of cervical wedge-shaped defects could improve the bonding strength in lesions like NCCL's. CONCLUSION: In conclusion, clinical challenges that occur due to NCCLs are better managed by a proper understanding of factors like etiopathogenesis, ultra-structure of enamel, and dentine and their effect on the bonding of restorations of the tooth.

Role of substrates and products of PI 3-kinase in regulating activation of Rac-related guanosine triphosphatases by Vav.

Mitogen stimulation of cytoskeletal changes and c-jun amino-terminal kinases is mediated by Rac small guanine nucleotide-binding proteins. Vav, a guanosine diphosphate (GDP)-guanosine triphosphate (GTP) exchange factor for Rac that stimulates the exchange of bound GDP for GTP, bound to and was directly controlled by substrates and products of phosphoinositide (PI) 3-kinase. The PI 3-kinase substrate phosphatidylinositol-4,5-bisphosphate inhibited activation of Vav by the tyrosine kinase Lck, whereas the product phosphatidylinositol-3,4,5-trisphosphate enhanced phosphorylation and activation of Vav by Lck. Control of Vav in response to mitogens by the products of PI 3-kinase suggests a mechanism for Ras-dependent activation of Rac.

Maxillofacial Injuries in Motorcyclists Following the Implementation of Helmet.

BACKGROUND: It has been reported that 20%-60% of all people injured in road traffic accidents (RTAs) tend to have some form of maxillofacial injury. Mangalore city, Karnataka State, India, traffic police has enforced the law to wear helmets to tackle the problem. The outcome of the initiative till date was not measured. Therefore, the objective of the study was to assess the prevalence of maxillofacial injuries among the victims of motorized two-wheeler RTAs, following the passing of the helmet law. MATERIALS AND METHODS: The study was conducted at the Accident and Emergency Department of K.S. Hegde Medical College and Hospital and at the Department of Oral and Maxillofacial Surgery, A.B. Shetty Memorial Institute of Dental Sciences, Nitte (Deemed to be University), Mangalore, Karnataka, India. The inclusion criteria were the patients who had two-wheeler accidents during the time period of 2016-2017 was collected. The data related to age, gender, helmet wearing, diagnosis, and type of orthopedic injuries was included. A descriptive statistics was calculated along with 95% confidence interval; correlation coefficient and odds ratio using STATA software. RESULTS: A total of N = 347 individuals were included in the study. The mean age of the individuals was 33.7 (2-85) years, and the median age was 32 years. 81.55% (N = 283) were male and 18.44% (N = 64) were female. Among the individuals, 51.5% (N = 179) were not wearing helmets and 44.38% (N = 154) of them were males. A total of 25.07 (N = 87) individuals had orthopedic injuries and 16.42% (N = 57) individuals had orthopedic injuries who were not wearing helmets. CONCLUSION: Under the limitations of the study, we conclude that majority of the two-wheelers are not wearing helmets. This study has demonstrated that the impact of wearing helmet on occurrence of craniofacial and orthopedic injuries is less.

Synthesis of 1,3- and 1,2-diphosphatidylglycerol.

A novel phosphonium salt methodology was utilized for the first time to synthesize 1,3-, and 1,2-diphosphatidylglycerol. Optically active 1,2-di-O-acyl-sn-glyceryl phosphate was coupled with unprotected glycerol in the presence of pyridiniumbromide perbromide and triethylamine to yield, after final removal of phosphate protecting group, the title compounds. The 1,2-diphosphatidylglycerol (1,2-isomer of cardiolipin) may be a member of a new class of phospholipids for industrial applications similar to other phosphocholines.

14,15-Epoxyeicosa-5(Z)-enoic acid: a selective epoxyeicosatrienoic acid antagonist that inhibits endothelium-dependent hyperpolarization and relaxation in coronary arteries.

Endothelium-dependent hyperpolarization and relaxation of vascular smooth muscle are mediated by endothelium-derived hyperpolarizing factors (EDHFs). EDHF candidates include cytochrome P-450 metabolites of arachidonic acid, K(+), hydrogen peroxide, or electrical coupling through gap junctions. In bovine coronary arteries, epoxyeicosatrienoic acids (EETs) appear to function as EDHFs. A 14,15-EET analogue, 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE) was synthesized and identified as an EET-specific antagonist. In bovine coronary arterial rings preconstricted with U46619, 14,15-EET, 11,12-EET, 8,9-EET, and 5,6-EET induced concentration-related relaxations. Preincubation of the arterial rings with 14,15-EEZE (10 micromol/L) inhibited the relaxations to 14,15-EET, 11,12-EET, 8,9-EET, and 5,6-EET but was most effective in inhibiting 14,15-EET-induced relaxations. 14,15-EEZE also inhibited indomethacin-resistant relaxations to methacholine and arachidonic acid and indomethacin-resistant and L-nitroarginine-resistant relaxations to bradykinin. It did not alter relaxation responses to sodium nitroprusside, iloprost, or the K(+) channel activators (NS1619 and bimakalim). Additionally, in small bovine coronary arteries pretreated with indomethacin and L-nitroarginine and preconstricted with U46619, 14,15-EEZE (3 micromol/L) inhibited bradykinin (10 nmol/L)-induced smooth muscle hyperpolarizations and relaxations. In rat renal microsomes, 14,15-EEZE (10 micromol/L) did not decrease EET synthesis and did not alter 20-hydroxyeicosatetraenoic acid synthesis. This analogue acts as an EET antagonist by inhibiting the following: (1) EET-induced relaxations, (2) the EDHF component of methacholine-induced, bradykinin-induced, and arachidonic acid-induced relaxations, and (3) the smooth muscle hyperpolarization response to bradykinin. Thus, a distinct molecular structure is required for EET activity, and alteration of this structure modifies agonist and antagonist activity. These findings support a role of EETs as EDHFs.

Helicobacter pylori strain-specific genotypes and modulation of the gastric epithelial cell cycle.

Helicobacter pylori cag+ strains enhance gastric epithelial cell proliferation and attenuate apoptosis in vivo, which may partially explain the increased risk of gastric cancer associated with these strains. The goals of this study were to identify specific H. pylori genes that regulate epithelial cell cycle events and determine whether these effects were dependent upon p53-mediated pathways. AGS gastric epithelial cells were cultured alone or in the presence of 21 clinical H. pylori isolates, H. pylori reference strain 60190, or its isogenic cagA-, picB-, vacA-, or picB-/vacA- derivatives. Coculture of H. pylori with AGS cells significantly decreased cell viability, an effect most prominent with cag+ strains (P < 0.001 versus cag-strains). cag+ strains significantly increased progression of AGS cells from G1 into G2-M at 6 h and enhanced apoptosis by 72 h. Compared with the parental 60190 strain, the picB- mutant attenuated cell cycle progression at 6 h (P < or = 0.05), and decreased apoptosis with enhanced AGS cell viability at 24 h (P < or = 0.04). The vacA- mutant decreased apoptosis and enhanced viability at later (48-72 h) time points (P < or = 0.05). Compared with the wild-type strain, the picB-/vacA- double mutant markedly attenuated apoptosis and increased cell viability at all time points (P < or = 0.05). Furthermore, cocolonization with H. pylori had no significant effect on expression of p53, p21, and MDM2. The diminished AGS cell viability, progression to G2-M, and apoptosis associated with cag+ H. pylori strains were dependent upon expression of vacA and genes within the cag pathogenicity island. These results may explain heterogeneity in levels of gastric epithelial cell proliferation and apoptosis found within H. pyloricolonized mucosa.

Pathogenic Helicobacter pylori strains translocate DNA and activate TLR9 via the cancer-associated cag type IV secretion system.

Helicobacter pylori (H. pylori) is the strongest identified risk factor for gastric cancer, the third most common cause of cancer-related death worldwide. An H. pylori constituent that augments cancer risk is the strain-specific cag pathogenicity island, which encodes a type IV secretion system (T4SS) that translocates a pro-inflammatory and oncogenic protein, CagA, into epithelial cells. However, the majority of persons colonized with CagA+ H. pylori strains do not develop cancer, suggesting that other microbial effectors also have a role in carcinogenesis. Toll-like receptor 9 (TLR9) is an endosome bound, innate immune receptor that detects and responds to hypo-methylated CpG DNA motifs that are most commonly found in microbial genomes. High-expression tlr9 polymorphisms have been linked to the development of premalignant lesions in the stomach. We now demonstrate that levels of H. pylori-mediated TLR9 activation and expression are directly related to gastric cancer risk in human populations. Mechanistically, we show for the first time that the H. pylori cancer-associated cag T4SS is required for TLR9 activation and that H. pylori DNA is actively translocated by the cag T4SS to engage this host receptor. Activation of TLR9 occurs through a contact-dependent mechanism between pathogen and host, and involves transfer of microbial DNA that is both protected as well as exposed during transport. These results indicate that TLR9 activation via the cag island may modify the risk for malignancy within the context of H. pylori infection and provide an important framework for future studies investigating the microbial-epithelial interface in gastric carcinogenesis.

5E, 8Z, 11Z, 14Z-eicosatetraenoic acid, a novel trans isomer of arachidonic acid, causes G1 phase arrest and induces apoptosis of HL-60 cells.

Trans arachidonic acid isomers (trans-AA) constitute a new group of trans fatty acids (trans-FA) generated in vivo via endogenous cis-trans isomerization stimulated by the NO2 radical. Because both NO2 and trans-FA have been implicated as causative factors in cancer, we studied the effect of the trans-AA isomers on proliferation and viability of human promyelocytic (HL-60) cells. The four trans arachidonic (trans-AA) acid isomers synthesized by us have been presently tested with respect to their competence to affect the proliferation and viability of human promyeolocytic HL-60 cells in culture. The data demonstrate that one of the isomers, 5,6-trans-AA, showed distinct activity by targeting cell progression through the cell cycle and inducing apoptosis. The effects were time- and concentration-dependent: the cytostatic effect of 5E-AA was observed at 10 microM following 72 h of treatment. This effect was manifested as a perturbation of cell progression through G1 phase, indicating the 'on' activation of the G1 checkpoint as evidenced by the flow- and laser scanning-cytometry techniques. Apoptotic cells were identified by comparison of their morphology, DNA fragmentation, caspase activation and collapse of mitochondrial potential with control cells. These observations suggested that 5E-AA induced a mitochondrial pathway of apoptosis. There was no evidence of cell-cycle phase specificity in induction of apoptosis by 5E-AA, as the cells showing highly fragmented DNA or caspase-3 activation were distributed in all phases of the cycle. The data suggest that 5E-AA may have at least two targets: one that is cell-cycle specific and associated with the observed arrest in the G1 phase and another, unrelated to the cell cycle, which is responsible for triggering apoptosis indiscriminately, regardless of cycle phase I.

Randomized comparison of different prostaglandin analogues and laminaria tent for preoperative cervical dilatation. World Health Organization Special Programme of Research, Development and Research Training in Human Reproduction: Task Force on Prostaglandins for Fertility Regulation.

In an eleven-centre study, 627 nulliparous subjects in the 8th to 12th week of gestation admitted for termination of pregnancy were allocated to one of five treatments to induce pre-operative cervical dilatation. The treatments were: 0.5 mg PGE2 methyl sulphonylamide; 1.0 mg PGE1 methyl ester; 30 mg 9-methylene PGE2 free acid, 0.5 mg 15-methyl PGF2 alpha; a single medium-sized laminaria tent. The results indicate that the three PGE analogues are at least equally effective as one medium sized laminaria tent and more effective than 0.5 mg 15-methyl PGF2 alpha in producing adequate pre-operative cervical dilatation prior to vacuum aspiration. It is concluded that both pre-treatment with prostaglandin analogues and laminaria tent are effective methods for preoperative cervical dilatation and both types of treatment are associated with a low incidence of side effects. Prostaglandin analogue treatment can be administered by paramedical personnel but laminaria tent insertion has to be performed by medical staff.

A study of interaction of low-dose combination oral contraceptive with Ampicillin and Metronidazole.

Plasma levels of norethisterone (NET), ethinyl estradiol (EE), Ampicillin or Metronidazole were estimated in 16 women, who were taking low-dose oral combination contraceptive pills (containing norethisterone acetate 1 mg and ethinyl estradiol 30 microgram) and in whom concurrently, either Ampicillin (6 women) or Metronidazole therapy (10 women) was given. Neither Ampicillin nor Metronidazole therapy altered the 'peak' or 24-hour plasma levels and area under the curve, for NET and EE. Furthermore, oral contraceptive treatment did not alter the 'peak' levels of Ampicillin or Metronidazole. Progesterone (P) levels were in the anovulatory range in all Ampicillin treated cycles. However, in Metronidazole treated group, two out of 10 women showed a P rise of more than 4 ng/ml. The study was expanded to include another group of 15 women treated with Metronidazole, where only one women showed a P rise of more than 4 ng/ml. The occurrence of 'escape ovulation' as suggested by P rise of more than 4 ng/ml in three out of 25 Metronidazole treated women is either a chance incidence due to a different pharmacological response in them, or most probably due to the default in the regular intake of pills in these women. This is supported by the observation that one out of three women showing a P rise (greater than 4 ng/ml( during concurrent Metronidazole therapy, also showed ovulatory P values in oral contraceptive-only treated cycles. Furthermore, in the control group also, one out of 10 women had ovulatory P levels (greater than 4 ng/ml) in oral contraceptive-only treated cycles.

PIP: Plasma levels of (NET) norethisterone, (EE) ethinyl estradiol, Ampicillin, or Metronidazole were estimated in 16 women who were taking low-dose (OC) oral contraceptives (containing norethisterone acetate, 1 mg, and ethinyl estradiol, 30 mcg) and in whom concurrently, either Ampicillin (6 women) or Metronidazole therapy (10 women) was given. Neither drug altered the peak or 24-hour plasma levels and area under the curve for NET and EE. Furthermore, OC treatment did not alter the peak levels of either Ampicillin or Metronidazole. (P) Progresterone levels were in the anovulatory range in all Ampicillin-treated cycles. However, in Metronidazole-treated group, 2 of 10 women showed a P rise of more than 4 ng/ml. The study was expanded to include another group of 15 women treated with Metronidazole and only 1 woman showed a P rise of more than 4 ng/ml. The occurrence of 'escape ovulation' as suggested by a P rise of more than 4 ng/ml in 3 of 25 Metronidazole-treated women is either a chance incidence due to a different pharmacological response in them, or most probably due to the default in the regular intake of pills in these women. This is supported by the observation that 1 out of 3 women showing a P rise ( 4 ng/ml) during concurrent Metronidazole therapy also showed ovulatory P values in OC-only treated cycles. Furthermore, in the control group, 1 out of 10 women had ovulatory P levels ( 4 ng/ml) in OC-only treated cycles.

Analysis of menstrual records of women immunized with anti-hCG vaccines inducing antibodies partially cross-reactive with hLH.

Menstrual data of 13 control subjects and 88 subjects immunized with three beta-hCG-based vaccine formulations were analysed. Immunization did not change the menstrual regularity; bleeding days were normal (3-7 days) and 89% of the menstrual cycles were within the normal range of 22-35 days. Irregular (short or long) cycles were observed in both immunized and control groups. These were, however, unrelated to prevailing anti-hCG antibody titres or to cross-reactivity of antibodies with hLH.

Phase I clinical trials with three formulations of anti-human chorionic gonadotropin vaccine.

Comparative phase I clinical trials were carried out in 5 centres with three formulations of beta-hCG-based vaccines inducing antibodies against human chorionic gonadotropin. The objectives of these trials were to determine their relative immunogenicity, duration, reversibility and safety. A total of 116 tubal ligated women volunteers were enrolled in the study and 101 subjects were followed-up for one year or more until the antibody titres declined to near zero levels. Every woman receiving the vaccine produced anti-hCG and anti-tetanus antibodies. Clinical examination carried out at intervals of 4-6 weeks revealed no abnormality. No serious side effects or adverse reactions were reported with any of the formulations during primary immunization with three monthly injections of the vaccine. Eleven women, however, demonstrated hypersensitivity to test dose at the time of the booster injection. The reaction was to tetanus toxoid; gonadotropin subunits conjugated to another carrier did not evoke any such reaction. Progesterone in bleeds taken at midluteal phase, as well as complete progesterone and estradiol done in two immunized women, indicated normal ovulatory cycles. Immunization with these formulations had no significant effect on haematological, clinical chemistry and other metabolic parameters. In summary, the results indicate that none of the three beta-hCG-based contraceptive vaccines had any adverse effects clinically, on endocrine status and metabolic parameters. Formulations A and B induced comparatively higher anti-hCG titres than M. Thus, further work can be undertaken to study the efficacy of these vaccines in humans for preventing pregnancy.

Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. I. Contraceptive efficacy and side effects. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation.

A multicentre clinical trial, including 19 centres in 13 countries, assessed the contraceptive efficacy and clinical acceptability of a Silastic 382 vaginal ring releasing 20 micrograms of levonorgestrel for at least 90 days. A total of 1005 women entered the study and 8176.74 woman-months of experience was gathered. The rate of intrauterine pregnancy at one year of use was 3.6 per 100 women (95% confidence interval 2.2-5.0), and of ectopic pregnancy, 0.2% (one case). The principal reasons for discontinuation were menstrual disturbances (17.2% at one year), vaginal symptoms (6.0%) and repeated expulsion of the ring (7.1%). The pregnancy rate with this 20 micrograms levonorgestrel-releasing vaginal ring compares favourably with that of a low estrogen combination oral contraceptive tested by WHO and is less than half that of a progestogen-only oral contraceptive in a WHO randomized study. It is concluded that the WHO intravaginal ring releasing an average of 20 micrograms of levonorgestrel per 24 hours is an effective method of contraception for at least one year of use.

Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. II. Expulsions and removals. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation.

This paper investigates the relationship between expulsions and removals, and demographic characteristics of 1005 women from 19 centres using a vaginal ring releasing 20 micrograms levonorgestrel per 24 hours. Emphasis is placed on discontinuations of method use due to expulsions, on the number and rate of expulsions, and the time at which the first expulsion occurred. The overall life-table discontinuation rate due to expulsion was 7.1% at one year. Life-table discontinuation rates increased with parity and were highest in Asian and lowest in European women. In respect to the number of expulsions experienced by women (expulsions did not necessarily lead to discontinuation), the women of high parity and those from Asia and Europe have the highest rates. The life-table first expulsion rate is 29% at one year. Such rates are highest in Chinese and Asian women. Following a first expulsion, the second expulsion rate is 45% by the end of the subsequent six months. The majority of first expulsions occur at defaecation (134 or 57% of 234 women), urination (12%) and during menstruation (17%). Rings were removed by 121 (12%) women on 201 occasions and for a variety of reasons. The main medical reasons were vaginal discharge and irritation, bleeding pain and dyspareunia. Others removed the ring during defaecation, intercourse or because the ring came out of place. Women also removed rings for curiosity, to show their husbands and to clean.

Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. III. The relationship between pregnancy rate and body weight. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation.

This paper investigates the relationship between pregnancy rates and body weight of 1005 women using a vaginal ring releasing 20 micrograms levonorgestrel per 24 hours. While the overall pregnancy rate at one year was 3.7%, it was found that women have an increasing risk of pregnancy with increasing body weight. For example, a woman of 40 kg has an estimated pregnancy rate of 1.7% in contrast to 9.8% for a woman of 80 kg weight.

Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. IV. Bleeding patterns. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation.

A multicentred clinical trial was conducted in 12 countries to assess the contraceptive efficacy and side effects of a low-dose levonorgestrel-releasing vaginal ring. Contraceptive efficacy and side effects, expulsions and removals, and the relation between pregnancy rate and admission body weight of the women have been reported previously. The effect of ring use on vaginal bleeding patterns as observed from daily menstrual diaries kept by the women is the object of this paper. A total of 1005 women were fitted with the ring and 702 of them provided a menstrual diary suitable for analysis. The description of the bleeding patterns is made using a 90-day reference period approach and following the guidelines published by WHO. In addition the longest bleeding/spotting episode and longest bleeding/spotting-free interval are calculated over the entire diary length. Half of the ring users have vaginal bleeding patterns similar to normal untreated patterns. A quarter experience irregular bleeding, 10% have prolonged cycles and 10% have shortened cycles. Over one year of continuous use, there appears to be no significant trend in these patterns. Users with the worst bleeding patterns tend to discontinue first during the clinical trial and are influenced by their more recent experience of vaginal bleeding irregularities. Life-table analysis of discontinuation rates gives an underestimation of the true incidence of bleeding irregularities. Some comments are made on the limitations of the methods of analysis of menstrual diaries.