A randomized study of the effect of mifepristone alone or in conjunction with ethinyl estradiol on ovarian function in women using the etonogestrel-releasing subdermal implant, Implanon®

BackgroundMifepristone alone or in combination with ethinyl estradiol (EE) can effectively stop an episode of uterine bleeding in women using the etonogestrel-releasing contraceptive implant, Implanon® but could impair contraceptive efficacy.AimTo examine the effects of administration of mifepristone alone or with EE on ovarian function and cervical mucus consistency in women using Implanon.Study DesignWomen using Implanon were randomized to mifepristone 25 mg twice daily on day 1 plus placebo 1 daily for 4 days or plus EE 20 mcg daily for days 2–5. Measurements of serum estradiol (E₂), progesterone (P₄), luteinizing hormone (LH), follicle-stimulating hormone (FSH), cervical mucus examination and maximal follicle size (by vaginal ultrasound) were carried out at various times.ResultsFollowing mifepristone intake, there was a dramatic increase in E₂ levels ranging from 543 to 1183 pmol/L (p=.000), which was not correlated with maximal follicle size or preceded by LH or FSH increase. The increase in E₂ triggered an LH increase resulting in development of a luteinized follicle in four women with no evidence of ovulation. One of these women had estradiol and progesterone levels suggestive of ovulation, but no corpus luteum was seen. Almost all women had very low mucus scores, which did not correlate with E₂ levels.DiscussionDespite a transient increase in E₂ levels after mifepristone, there was no evidence of subsequent ovulation irrespective of whether they also received EE. The mechanism by which mifepristone in the presence of etonogestrel results in a rapid increase in E₂ levels remains unclear and could not be related to any significant changes in FSH, LH, ovarian follicle dynamics or subsequent possible ovulation.ConclusionPregnancy is very unlikely to occur if mifepristone and EE are given during use of Implanon to stop an episode of bleeding.     

Prevalence of hypothyroidism and diabetes mellitus in elderly kibbutz members

The aim of this study was to determine the prevalence of hypothyroidism and diabetes mellitus (DM) in elderly (aged 65–92 years) kibbutz members in Northern Israel. Method: The medical records of 1096 elderly (642 females and 454 males) residing in 11 kibbutzim were reviewed for data regarding thyroid function tests (TSH and FT4) and fasting blood glucose. Fasting blood glucose levels above 7.8 mmol/l was considered diagnostic for diabetes mellitus. Results: The prevalence of hypothyroidism was 14% (9.7% in males and 18.2% in females) and that of DM was 11.5% (12.1% in males and 11.1% in females). In 74% of the diabetics the diagnosis was made after the age of 60 years. Distribution of treatment modalities in diabetics was as follows: diet only 42%, oral hypoglycemic agents 52% and Insulin 6%. Subclinical hypothyroidism (serum TSH levels above 4.5 mU/L with normal FT4 levels) was detected in 38% of all the hypothyroid subjects. Conclusion: The data suggest that diabetes mellitus and primary hypothyroidism are common disorders in elderly subjects. DM in the elderly can usually be handled with diet and oral hypoglycemic drugs. Since the clinical features of hypothyroidism in the elderly are often atypical, we suggest that elderly subjects should be screened for hypothyroidism.     

Heterogeneity of NSD1 alterations in 116 patients with Sotos syndrome

Sotos syndrome is an overgrowth syndrome characterized by distinctive facial features, learning difficulties, and macrocephaly with frequent pre- and postnatal overgrowth with advanced bone age. Here, we report on our experience in the molecular diagnostic of Sotos syndrome on 116 patients. Using direct sequencing and a quantitative multiplex PCR of short fluorescent fragments (QMPSF)-based assay allowing accurate detection of both total and partial NSD1 deletions, we identified NSD1 abnormalities in 104 patients corresponding to 102 Sotos families (90%). NSD1 point mutations were detected in 80% of the index cases, large deletions removing the NSD1 gene entirely in 14%, and intragenic NSD1 rearrangements in 6%. Among the 69 detected distinct point mutations, 48 were novel. The QMPSF assay detected an exonic duplication and a mosaic partial deletion. QMPSF mapping of the 15 large deletions revealed the heterogeneity of the deletions, which vary in size from 1 to 4.5 Mb. Clinical features of NSD1-positive Sotos patients revealed that the phenotype in patients with nontruncating mutations was less severe that in patients with truncating mutations. This study confirms the heterogeneity of NSD1 alterations in Sotos syndrome and therefore the need to complete sequencing analysis by screening for partial deletions and duplications to ensure an accurate molecular diagnosis of this syndrome.     

Variation in sources of clinician-rated and self-rated instrumental activities of daily living disability

BACKGROUND: It is unclear how well self-reports and clinician ratings of performance in the instrumental activities of daily living (IADLs; household maintenance tasks) correspond and why they may differ. METHODS: We assessed clinician-rated IADL performance using an occupational therapy protocol, the Assessment of Motor and Process Skills (AMPS). AMPS and self-rated IADL disability were compared in two groups of nondemented elderly persons without ADL limitation: a group with functional limitation only (self-reported difficulty in some area of upper or lower body function, n = 139) and a group that reported functional limitation plus IADL disability (difficulty in at least one IADL task, n = 49). Occupational therapists were blind to self-reports, and all assessments were conducted in respondent homes. RESULTS: Self-rated IADL disability was significantly associated with the AMPS motor skill score (r = -.34, p <.001), but the motor skill score was only moderately sensitive (61%) and specific (67%) in identifying self-rated disability. In adjusted logistic regression models, clinician-rated performance and self-rated IADL disability shared some physical predictors, but only clinician-rated performance was related to cognitive status. AMPS process skill scores did not relate to self-rated IADL disability or physical or cognitive status. CONCLUSIONS: In this sample of older adults without dementia or ADL disability, clinician ratings of IADL motor skill and self-rated IADL disability were correlated. Physical deficits appear to be more salient in self-ratings than is cognitive ability, because cognitive ability (in particular, verbal fluency) was associated only with clinician-rated IADL performance.     

Two independent de novo mutations as a cause for neurofibromatosis type 1 and Noonan syndrome in a single family

Here we report on a family with two siblings born to unrelated healthy parents, one with neurofibromatosis type 1 (NF1) and the other with Noonan syndrome (NS). Molecular investigations performed on the NF1 and PTPN11 genes showed two independent de novo mutations as a cause for NF1 in the NF1 proband and NS in her affected brother. Both de novo mutations were potentially of paternal origin, given the advanced paternal age at the time of conception. ? 2012 Wiley Periodicals, Inc.     

Predictors of partner relationships during pregnancy and infancy

The partner relationship of 153 women hospitalized for a high-risk pregnancy, 75 of their partners, 218 women who experienced a low-risk pregnancy and 147 of their partners was studied to determine risk-status or gender differences at pregnancy, the postpartal hospitalization, 1, 4, and 8 months following birth. A theoretical causal model predicting partner relationships was tested, followed by model respecification to derive the best explanatory model for each group. No differences were observed between low- and high-risk mothers' partner relationship; however, high-risk fathers scored lower than low-risk fathers. Partner relationships for all groups were significantly higher during pregnancy and at birth than at 4 and 8 months after birth. Respecified models explained from 26% to 63% of the variance in partner relationship during pregnancy, and from 31% to 52% at 8 months after birth. © 1993 John Wiley & Sons, Inc.     

Acute bacterial meningitis at the 'Complexe Pédiatrique' of Bangui, Central African Republic

To precis the aetiologies of children meningitis and the susceptibility to antibiotics of bacteria responsible for meningitis in Bangui, we conducted a prospective study between October 2004 and September 2005, at the 'Complexe Pédiatrique de Bangui', Central African Republic (CAR). Children from 1 day to 16 years with suspected meningitis and who underwent a lumbar puncture were enrolled. Gram staining, culture on chocolate blood medium, cell count, biochemistry (protein level, glucose ratio), capsular antigen detection were performed for each cerebrospinal fluid. MICs were determined by the E-test method. Four hundred and seventeen patients were enrolled during the study period; 130 were proven acute bacterial meningitis and 37 probable bacterial meningitis. Among proven bacterial meningitis, Streptococcus pneumoniae was the most common organism responsible for meningitis (62 cases, 48%) followed by Haemophilus influenzae (46 cases, 35%) and by Neisseria meningitidis and Salmonella sp. (8 cases, 6% each). Ninety-four percent and 96% of S. pneumoniae strains tested remain susceptible to benzylpenicilline and chloramphenicol, respectively. A beta-lactamase was detected in 92% of H. influenzae strains tested. However, MICs 50% and 90% for amoxicillin were found to be 1 and 4 mg/l, respectively and 33% of these strains were resistant to chloramphenicol. The global mortality rate was 35% (59/167). This mortality rate was 47% for S. pneumoniae, 33% for H. influenzae, 62% for Salmonella sp. and 13% for N. meningitidis. The probabilistic treatment with ampicillin and chloramphenicol usually administered for children meningitis in Bangui must be reconsidered particularly in cases of H. influenzae meningitis. It is of importance to reduce the presentation delays of children with suspected meningitis in Bangui. The H. influenzae b immunization would allow a dramatic reduction of meningitis cases and deaths in Central African children.     

The evolving role of nurses in primary care medical settings

The role of nurses in primary care is understudied. The purpose of this study was to describe the current registered nurse (RN) role in three Primary Care Networks (PCNs) in western Canada and to identify opportunities for optimal utilization of RNs in these settings. Case study methodology included interviews and document review. Although the RN role evolved during the study, most RNs focused on chronic disease management. Role ambiguity was evident between nurses and with interprofessional team members. Relationships of RNs to other providers, particularly physicians, impacted the enactment of the nursing role. Other barriers to role enactment included physician fee‐for‐service remuneration, management structures and processes, lack of access to electronic medical records and lack of previous opportunities to apply primary health‐care education in the practice setting. Further work is needed to optimize the RN role in primary care to ensure maximum impact for patients, providers and the health system overall.     

Deodorants: an experimental provocation study with isoeugenol

Axillary dermatitis is common and overrepresented in people with contact allergy to fragrances. Many people suspect their deodorants to be the incriminating products. In order to investigate the significance of isoeugenol in deodorants for the development of axillary dermatitis when used by people with and without contact allergy to isoeugenol, patch tests with deodorants and ethanol solutions with isoeugenol, as well as repeated open application tests (ROAT) with roll-on deodorants with and without isoeugenol at various concentrations, were performed in 35 dermatitis patients, 10 without and 25 with contact allergy to isoeugenol. A positive ROAT was observed only in patients hypersensitive to isoeugenol (P<0.001) and only in the axilla to which the deodorants containing isoeugenol had been applied (P<0.001). Deodorants containing isoeugenol in the concentration range of 0.0063-0.2% used 2 times daily on healthy skin can thus elicit axillary dermatitis within a few weeks in people with contact allergy to isoeugenol.     

Temozolomide in children with progressive low-grade glioma

We conducted a phase II study to assess the efficacy of oral temozolomide (TMZ) in children with progressive low-grade glioma. Thirty eligible patients were enrolled on this study. Median age at enrollment was 10 years (range, 4-18 years). Eligible patients received TMZ (200 mg/m(2) per day) by mouth for five days every four weeks. Patients received a median of nine cycles (range, 2-12 cycles) of treatment. Best responses in the 26 patients (86%) with optic pathway glioma (OPG)/pilocytic astrocytoma (PA) included partial response in 3 patients (11%), minor response in 1 (4%), stable disease in 10 (38%), and progressive disease in 12 (46%). Only one of four patients with fibrillary astrocytoma had stable disease for 29 months after TMZ. The overall disease stabilization rate in patients with OPG/PA was 54%, and disease control was maintained for a median interval of 34 months. Seventeen of 26 patients had progressive disease either on or off therapy, and three have died of disease. The two-year progression-free and overall survivals in patients with OPG/PA were 49% (95% CI, 30%-67%) and 96% (95% CI, 89%-100%), respectively. Worst toxicity related to TMZ in all 30 patients included grade 2-4 thrombocytopenia in seven patients, grade 2-4 neutropenia in seven, grade 2 skin rash in one, and intratumor hemorrhage in one. TMZ given in this schedule was successful in stabilizing disease in a significant proportion of the patients with OPG/PA, with manageable toxicity.