Pharmacokinetic and pharmacodynamic effects of vaginal rings releasing levonorgestrel at a rate of 27 micrograms/24 hours: a pilot study

The pharmacokinetic and pharmacodynamic effects of vaginal rings releasing levonorgestrel (L-NOG) at an initial rate of 27 micrograms/24 h were studied in a group of 12 normally menstruating women during 90 days of continuous use (i.e., during three 30-day treatment segments). Blood samples were drawn immediately before insertion, 15 and 30 min, as well as 1, 2, 4, 8, 12 and 24 h after insertion of the rings, and thereafter three times weekly throughout the study for the analysis of L-NOG, estradiol, progesterone and sex hormone-binding globulin (SHBG). Endometrial biopsies were obtained for a morphometric analysis in a pre-treatment (control) cycle and in the 6th and 10th weeks of treatment. The peak of average L-NOG levels was reached within two hours after the insertion of rings. Until 24 h after insertion, the levels did not change significantly. Thereafter, a decrease at a rate of 0.2% per day was initiated. The L-NOG and SHBG levels were highly correlated. This was seen for both the pre-treatment SHBG vs L-NOG (r = 0.96) and the treatment SHBG vs L-NOG levels (r = 0.92). There was a significant (p < 0.001) decrease of SHBG levels due to treatment. During the total of 36 treatment segments, a normal ovarian function was seen in 47% of the segments. The women were anovulatory and had an inadequate lutal function in 28% and 25% of segments, respectively. No correlation between the L-NOG levels and ovarian reaction to treatment was found. The use of L-NOG induced significant changes in the endometrium; the number of glands/mm2 decreased after 6 (p < 0.02) and 10 weeks of use (p < 0.01). Also, the diameter of glands and the occurrence of vacuolated cells decreased significantly (p < 0.02 and p < 0.005, respectively). None of the endometrial parameters or dating was correlated with the ovarian reaction to treatment, indicating independent endometrial effects of L-NOG.     

Insulin-like growth factor I activates the invasion suppressor function of E-cadherin in MCF-7 human mammary carcinoma cells in vitro

The calcium-dependent cell-cell adhesion molecule E-cadherin has been shown to counteract invasion of epithelial neoplastic cells. Using three monoclonal antibodies, we have demonstrated the presence of E-cadherin at the surface of human MCF-7/6 mammary carcinoma cells by indirect immunofluorescence coupled to flow cytometry and by immunocytochemistry. Nevertheless, MCF-7/6 cells failed to aggregate in a medium containing 1.25 mM CaCl2, and they were invasive after confrontation with embryonic chick heart fragments in organ culture. Treatment of MCF-7/6 cells with 0.5 microgram ml-1 insulin-like growth factor I (IGF-I) led to homotypic aggregation within 5 to 10 min and inhibited invasion in vitro during at least 8 days. The effect of IGF-I on cellular aggregation was insensitive to cycloheximide. However, monoclonal antibodies that interfered with the function of either the IGF-I receptor (alpha IR3) or E-cadherin (HECD-1, MB2) blocked the effect of IGF-I on aggregation. The effects of IGF-I on aggregation and on invasion could be mimicked by 1 microgram ml-1 insulin, but not by 0.5 microgram ml-1 IGF-II. The insulin effects were presumably not mediated by the IGF-I receptor, since they could not be blocked by an antibody against this receptor (alpha IR3). Our results indicate that IGF-I activates the invasion suppressor role of E-cadherin in MCF-7/6 cells.     

Hindshaker, a novel myelin mutant showing hypomyelination preferentially affecting the spinal cord

Animals with spontaneous mutations affecting myelin formation have provided useful information about the genetic and cellular mechanisms regulating normal and abnormal myelination. In this paper we describe a novel murine mutation termed hindshaker (hsh), which is inherited in an autosomal recessive manner. Affected mice are characterised by a variable tremor of the hind end which commences at about 2 weeks of age and largely disappears in animals older than 6 weeks. There is hypomyelination affecting predominantly the spinal cord, although the optic nerves and brain are involved to a much lesser degree. The defect of thinly myelinated and naked axons is maximal at 20 days of age and largely resolves with time so that in the adult most axons are myelinated. The myelin structure appears normal and immunostains for the major proteins. Although the distribution of oligodendrocytes in the spinal cord is similar to normal during the period of hypomyelination, there are fewer mature cells. The hsh mutation appears to delay the maturation of oligodendrocytes, particularly in the spinal cord. Additionally, there is a considerable variation in phenotypic expression and in penetrance when the mutation is expressed on different genetic backgrounds, suggesting the hsh locus is subject to the influence of modifying gene(s). Identification of the hsh gene should identify a factor important in the development of oligodendrocytes, particularly those in the spinal cord.     

Electronic thermography for the assessment of acute temporomandibular joint pain

Electronic thermography (ET) has the potential to be a nonionizing, noninvasive, low-cost diagnostic alternative for evaluating temporomandibular joint (TMJ) disorders. This study was designed to evaluate the use of ET as a diagnostic aid in the assessment of patients with acute TMJ pain. Computer measurements made using facial thermography were able to distinguish normal patient populations from symptomatic patients with acute TMJ pain. Additional studies are needed before thermographic diagnosis of TMJ disorders will be clinically accepted.     

Keratin 17 gene expression during the murine hair cycle

Treatment of rats with phenytoin (DPH), an anti-epileptic drug, results in lower tissue thyroid hormone (TH) levels and interferes with the metabolic pathway of TH. To test the hypothesis that DPH affects the enterohepatic cycle of TH and, thus, the kinetics of TH turnover, we performed a kinetic experiment (three-compartment analysis) and a steady-state, double-isotope equilibrium experiment in rats treated for 3 weeks with DPH (50 mg/kg body weight per day) and in untreated controls. This included measurements of TH and TH metabolite levels, as well as the activities of enzymes involved in the TH metabolic pathway. DPH treatment resulted in a decrease in the production of thyroxine (T4) (by 25%) and tri-iodothyronine (T3) (by 37%), a decrease in the T3 concentration in all three pools, and a redistribution of T4 from the fast to the slow pool. The amount of T4 increased in intestinal contents and feces by 66% and 71% respectively. Expressed as a fraction of daily TH disposal, fecal loss of T4 was enhanced from 10 to 23% and that of T3 from 16 to 21%. An increase in T4 and T3 UDP-glucuronyltransferase activities was observed, suggesting that the increased fecal loss of T4 and T3 is secondary to an increased biliary output of their glucuronides. The reduced secretion of TH and increased fecal clearance during DPH treatment can lead in the long run to depletion of TH stores.     

A comparative study of color measurement lntstrumentation

A multiplant Quality Improvement Team [QIT] was firmed to develop and implement an evaluation program for various color measurement .systems as potential replacements for the then-current aging systems. The emphasis qf this article is the analytical methodology utilized to evaluate the various color systems. The evaluation program consisted cf two phases. Phase I was a general overview/review of several systems, while Phase II was an extensive internal comparative evaluation measurement systems. These were Milton-Roy's ColorMate HDS, HunterLab's Ultrascan, Datacolor's CS-5, and BYK-Gardner's The Color Sphere [TCS]. The main comparison criteria were interinstrument agreement [agreement between two instruments ofthe same system], user-friendly software and computer interface capability, vendor amenability to a long-term logistical and maintenance relationship, and price. All systems were evaluated by duplicate measurements on various color tiles, yarns, and polymer flakes-over 1600 measurements on each system. The systems were compared with an instrument matrix, a decision matrix, and a product matrix. The instrument matrix was a comparison qfinstrument parameters, software/math treatments, and economics. The decision matrix was a forced ranking of each system by each criteria category [1–4 scale, with 1 representing the best and 4 representing the worst]. The product matrix accentuated the relative importance ofone criterion category over another by multiplying the forced ranking by the criticality of the category. The criticality of a given category wus determined by consensus within the QIT. Thr combination qf the three matrices allowed the evaluator[.s] t o select the color rneasuremmt system that best satixfied the color measurement needs and requirements of their facility and their products. For this evaluation, all ofthe evaluated systems were superior to the then-current agingsystems. As a result of this methodology, one instrument emerged as clearly superior. © 1994 John Wrley & Sons, Inc.     

Weighing the risks and benefits of an oral cancer screening

The study into the causes underlying nonspecific lymphadenitis (NSL) and adenophlegmons of the maxillofacial region and the neck (AF) revealed a great variety of etiological factors and primary infectious foci in these diseases. Of 204 children admitted to hospital of the city of Derbent, odontogenic genesis of the disease was determined in 27.45% of cases; dermatogenic, stomatogenic in 23.04 and 12.74% of cases, respectively. ENT and systemic diseases were responsible for NSL and AF in 13.23 and 3.43% of cases. The cause remained unclear in 20.09% of patients. NSL and AF occurred most frequently in the coldest (January, February) and the hottest (July, August) months of the year.     

A 6-year clinical assessment of electronic facial thermography

The authors briefly report their experience regarding the opportunities offered by the use of current ultrasound methods in carotid surgery. They describe: a system for the quantification of athcromasic plaque used to monitor non-operated patients over time; ultrasound methods used to analyse the carotid wall to establish whether it can be utilised as an index of vascular aggression in hypertension, diabetes and atherosclerosis; the use of transcranial Doppler; criteria for the definition of high risk plaque; the applications of eco-color Doppler. The paper also illustrates a new pathology identified by the authors, defined as primary intimal fibrous hyperplasia, and the evolution of the carotid wall after endarterectomy. The structural characteristics of primary hyperplasia can only be shown using ultrasound given that arteriography cannot distinguish it from atheromatic stenosis. After endarterectomy the carotid wall is subject to hematic and hemodynamic stimuli which determine the type of evolution of the wall itself. The authors therefore examine the myointimal reaction, myointimal hyperplasia, early restenosis and late restenosis as different facets of the same phenomenon.     

Visual, cognitive, and neurodevelopmental outcome at 51/2 years in children with perinatal haemorrhagic-ischaemic brain lesions

To determine predictive values of early visual and neurocognitive assessment in children with perinatally acquired haemorrhagic or ischaemic brain lesions selected on the basis of ultrasound, 63 children (37 boys, 26 girls), who had been followed and examined until the age of 18 months, were reexamined at 5 1/2 years. Good correlations between visual and neurodevelopmental assessments at 18 months and at 5 1/2 years were found. When ultrasound abnormalities were combined with early visual and neurocognitive assessment data, good predictive values, especially for the group of children who had grade 2 to 4 leukomalacia, were found for visual acuity and neurodevelopment.