Changes of the endometrium during oral hormonal contraception with ethinyl estradiol sulfonate and norethisterone acetate or d-noregestrel

48 fertile women took in three weeks 1 mg ethinylestradiolsulfonate weekly and in the 4th week 10 mg norethisterone acetate, respectively d-norgestrel in different dosages (0,5 mgs, 1,0 mgs, 1,5 mgs or 3,0 mgs). On this 48 women 69 abrasiones were made between the first and 37th treatment cycles in order to estimate the endometrium. Ethinylestradiolsulfonate caused for the most part a proliferation of endometrium, which reached to a glandulare cystic hyperplastic endometrium. We did not observe a reduction of the endometrial respond to this depot-estrogen in dependence on the time of taking. Norethisterone acetate and d-norgestrel effected on a different proliferated endometrium a secretory transfer mation always.     

Pulmonary and cardiac late effects of ionizing radiations alone or combined with chemotherapy

High doses of ionizing radiation (> 40 Gy) cause severe lung fibrosis in approximately 5% of the cases. There is a twofold increase when chemotherapy is added to ionizing radiation. Lung fibrosis is due to the destruction of lung tissue by ionizing radiation but also to various cytokine effects (PDGF-beta, TGF-beta). Only a minority of patients (approximately 10%) with abnormal X-rays will experience clinical symptoms. The most important radiobiological parameters which accounts for pulmonary tolerance is the fraction size. Irradiation of the heart begets multifarious late sequelae which are often left unrecognized. Chronic pericarditis affects approximately 5% of the patients when the irradiation dose exceeds 40 Gy. Coronary artery disease can be diagnosed in 5 to 10% of the patients. This late complication is more likely to occur if the patient was young at the time of the irradiation or if other risk factors are associated. Valvular defects can be found in 15 to 30% of the patients. However, the mortality rate is very low (0.5%). Finally, conduction defects can also be seen in approximately 5% of the patients. It is very likely that the radiation dose given to the heart should not exceed 30 Gy if late sequelae are to be avoided.     

Short-term effects of norethisterone oenanthate and medroxyprogesterone acetate on glucose, insulin, growth hormone, and lipids

The synthesis of (+/-)-1-ethylenedioxy-trans-2-(beta-R,S-hydroxypropyl)-3-(beta-acetoxyethyl)cyclopentane (IV), starting from (+/-)-1-ethylenedioxy-trans-2-propargyl-3-(beta-hydroxyethyl)cyclopentane (I) by indirect hydration with mercuric acetate and hydrogen sulphide, is reported.     

Idiosyncratic ocular symptoms associated with the estradiol transdermal estrogen replacement patch system

BACKGROUND: The medical review officer is a position established by federal statute in 1988. The role of the medical review officer is to interpret positive urine drug tests in view of the donor's medical history. With more than 4 million workers affected by the Department of Transportation guidelines for workplace drug testing, and many private employers having urine drug screening programs, there is a need for medical review officers. METHODS: Materials for this report were collected while the first author was pursuing certification from the Medical Review Officer Certification Council. Much of the data was published in the Federal Register from 1988 through 1993. RESULTS AND CONCLUSIONS: Urine drug testing is divided into three stages: collection, laboratory analysis,and medical review of results. Because the workplace urine drug test is a forensic test, the urine is collected under strict chain of custody. Analysis of specimens is conducted by laboratories that have met stringent technical criteria and are approved by the Substance Abuse and Mental Health Services Administration (formerly the National Institute on Drug Abuse). Family physicians are in a unique position to become medical review officers because of their training and professional roles. Educational programs are available for physicians interested in becoming a medical review officer.     

Estradiol inhibits LDL oxidation: do the progestins medroxyprogesterone acetate and norethisterone acetate influence this effect?

Estrogen replacement therapy in postmenopausal women must be combined with progestin to avoid endometrial cancer. However, progestin addition could antagonize cardioprotective effects of estradiol. Therefore we investigated the effect of the two most commonly used progestins--medroxyprogesterone acetate (progesterone-derivative) and norethisterone acetate (nortestosterone-derivate)--alone and in combination with 17 beta-estradiol on copper-mediated oxidation of low density lipoprotein (LDL). Whereas 17 beta-estradiol alone inhibited the onset of LDL oxidation at the concentrations 0.5, 1.0, 5 and 10 microM, the progestins alone did not demonstrate any significant effect. In the estrogen-progestin combinations of 0.5 microM 17 beta-estradiol with 0.5, 1.0, 5 and 10 microM progestin, respectively, the estradiol effect was not changed. These results suggest that medroxyprogesterone acetate as well as norethisterone acetate do not counteract the beneficial effect of 17 beta-estradiol on LDL oxidation when used in hormone replacement therapy.     

Comparison of transdermal versus oral estradiol on endometrial receptivity

OBJECTIVE: To compare the effects of oral micronized E2 with transdermal E2 on endometrial receptivity in women undergoing oocyte donation. DESIGN: Prospective, randomized, crossover trial. Serum E2 and P concentrations were measured on cycle days 14 and 22 (luteal day +8). Endometrial biopsies were obtained on day 22 and read in a blinded fashion for histology and beta-3-integrin expression. SETTING: University-based donor oocyte program. PATIENTS: Twenty-seven patients presenting for donor oocytes. MAIN OUTCOME MEASURES: Endometrial histology and beta-3-integrin expression. RESULTS: The endometrial glandular histology in women given oral micronized E2 was delayed by a mean of 1.6 days in comparison to that of women given transdermal E2. Seventy percent of women given oral E2 displayed a lag > or = 4 days whereas 29.6% given transdermal E2 displayed a similar lag. Serum E2 levels were 1,194 +/- 108.8 pg/mL (mean +/- SEM; conversion factor to SI unit, 3.671) in women on oral micronized E2 and 117.4 +/- 14.0 pg/mL in those on transdermal E2. CONCLUSION: The supraphysiologic serum E2 levels associated with oral micronized E2 may have a deleterious impact on endometrial receptivity. The development of more physiologic hormone replacement protocols may enhance endometrial receptivity and lead to improved clinical pregnancy rates.     

The influence of norethisterone acetate on urinary urodilatin excretion in postmenopausal women

Malignant hyperthermia developed in two Landrace x Large White pigs, 75 and 105 minutes after the induction of anaesthesia with halothane. Rapid treatment and discontinuation of halothane anaesthesia were unable to reverse the condition in the first case but were successful in the second. The delayed onset of malignant hyperthermia after delivery of halothane is unusual and for successful treatment careful monitoring and rapid and aggressive therapy are needed.     

Gabapentin does not interact with a contraceptive regimen of norethindrone acetate and ethinyl estradiol

Anticonvulsants that induce hepatic metabolism increase clearance of oral contraceptive hormones and thereby cause contraceptive failure. Gabapentin is not metabolized in humans and has little liability for causing metabolic-based drug-drug interactions. In healthy women receiving 2.5 mg norethindrone acetate and 50 microg ethinyl estradiol daily for three consecutive menstrual cycles, concurrent gabapentin administration did not alter the steady-state pharmacokinetics of either hormone. Thus, gabapentin is unlikely to cause contraceptive failure.     

Hemodynamic effects of arbutamine

This study examined the hemodynamic effects of arbutamine, a synthetic catecholamine, in 12 patients with and 7 patients without coronary artery disease. Arbutamine produced a balanced positive inotropic (increase in left ventricular dp/dt) and chronotropic effect (increase in heart rate).     

Bioavailability of estradiol from a new matrix and a conventional reservoir-type transdermal therapeutic system

OBJECTIVE: Bioavailability of estradiol delivered from a newly developed matrix-type transdermal therapeutic system (MTTS) was compared with that of the conventional reservoir-type system (RTTS). Both formulations have a nominal delivery rate of 50 micrograms per day of 17 beta-estradiol (E2). Plasma concentrations of E2 and estrone (E1) were determined at steady state during a 96-h application of each formulation to 34 postmenopausal volunteers, using a two-stage randomized two-period crossover design. RESULTS: The MTTS proved to be equivalent to the RTTS with respect to the extent of E2 absorption. Due to differences in patch design and composition, the rate of absorption was different between the two systems, with less fluctuating E2 plasma levels during application of the matrix system. Local tolerability and adhesion of MTTS appeared to be better than those of the reservoir system.     

Clinical study on chlormadinone acetate alone followed by combination with LH-RH analogue for prostatic cancer: effects on lipid metabolism

Twenty-four previously untreated patients with a diagnosis of prostatic cancer were treated with chlormadinone acetate (CMA) alone (100 mg/day) for 4 weeks, and luteinizing hormone-releasing hormone analogue (LH-RHa) was added for the next 24 weeks. Marked decreases in blood LH, testosterone (T), prostate specific antigen (PSA), gamma-seminoprotein (gamma-Sm), and prostatic acid phosphatase (PAP) were observed after a single dose of CMA. T levels were significantly increased 3 days after the initial dose of LH-RHa, and did not return to the pretreatment level. There were no significant increases in any of the markers, nor were there any flare-up cases. Triglyceride levels, which were slightly elevated before the start of treatment, were significantly decreased 24 weeks after the completion of combined therapy. PSA was evaluated as partial response (PR) or better in 86.7% of the patients. Overall evaluation showed PR or better in 75.0% of the patients. These findings suggest that prior administration of CMA followed by combined administration with LH-RHa is useful in the treatment of prostatic cancer. No negative effects on lipid metabolism were observed at any time during the treatment period.     

Hemodynamic and ventilatory effects associated with increasing inverse inspiratory-expiratory ventilation

Rational modification of an existing cationic alpha-helical antimicrobial peptide (ESF1) for improved activity by increasing amphipathicity was undertaken. ESF1 and two variants (GR7 and SA3) were synthesized and tested for activity range, minimum inhibitory concentration, and hemolytic activity. Biological activity was related to structure as determined by circular dichroism. The substitution of arginine for glycine in position seven was found to increase antimicrobial activity without effecting hemolysis. Increased activity was related to stronger alpha-helix formation in buffer. Increased beta-sheet formation in micellar SDS was observed and speculated to be due to a stronger ability of the variants to form multimolecule complexes, a feature consistent with existing models of cationic peptide activity.     

Effect of a combined trenbolone acetate and estradiol implant on steady-state IGF-I mRNA concentrations in the liver of wethers and the longissimus muscle of steers

Endochondral ossification in growth plates proceeds through several consecutive steps of late cartilage differentiation leading to chondrocyte hypertrophy, vascular invasion, and, eventually, to replacement of the tissue by bone. It is well established that the subchondral vascular system is pivotal in the regulation of this process. Cells of subchondral blood vessels act as a source of vascular invasion and, in addition, release factors influencing growth and differentiation of chondrocytes in the avascular growth plate. To elucidate the paracrine contribution of endothelial cells we studied the hypertrophic development of resting chondrocytes from the caudal third of chick embryo sterna in co-culture with endothelial cells. The design of the experiments prevented cell-to-cell contact but allowed paracrine communication between endothelial cells and chondrocytes. Under these conditions, chondrocytes rapidly became hypertrophied in vitro and expressed the stage-specific markers collagen X and alkaline phosphatase. This development also required signaling by thyroid hormone in synergy. Conditioned media could replace the endothelial cells, indicating that diffusible factors mediated this process. By contrast, smooth muscle cells, fibroblasts, or hypertrophic chondrocytes did not secrete this activity, suggesting that the factors were specific for endothelial cells. We conclude that endochondral ossification is under the control of a mutual communication between chondrocytes and endothelial cells. A finely tuned balance between chondrocyte-derived signals repressing cartilage maturation and endothelial signals promoting late differentiation of chondrocytes is essential for normal endochondral ossification during development, growth, and repair of bone. A dysregulation of this balance in permanent joint cartilage also may be responsible for the initiation of pathological cartilage degeneration in joint diseases.     

Hemodynamic and autonomic effects of intravenous saterinone in patients with chronic heart failure

In this study, the hemodynamic and neurohumoral/autonomic effects of intravenous saterinone (a selective phosphodiesterase type III inhibitor, with additional alpha 1-blocking properties) were evaluated. In a double-blind, placebo-controlled design, 36 patients with moderate to severe heart failure were studied (saterinone, n = 24; placebo, n = 12). Invasive hemodynamic measurements, by using right-heart catheterization, were performed, as well as measurement of plasma neurohormones and analysis of heart rate variability (HRV), to study drug influences on neurohumoral activation and autonomic tone. Systemic vascular resistance significantly decreased during saterinone infusion, accompanied by a decrease in systemic blood pressure (both p values < 0.05) and an increase in heart rate (p = 0.05). Filling pressures also decreased during saterinone, but this was statistically significant only for pulmonary capillary wedge pressure, whereas the cardiac index remained unaffected. Plasma neurohormones (norepinephrine, epinephrine, and renin activity) were not significantly influenced by saterinone. HRV analysis revealed no significant effect of saterinone on autonomic tone. These results suggest that intravenous saterinone has a significant vasodilating effect in patients with moderate to severe chronic heart failure (CHF), without exerting an adverse effect on the autonomic nervous system, as demonstrated by assessment of plasma neurohormones and HRV analysis.     

Plasma estradiol concentrations and pharmacokinetics following transdermal application of Menorest 50 or Systen (Evorel) 50

In order to evaluate the applicability of anthelminthic treatment of wild foxes (Vulpes vulpes) to limit their infection with Echinococcus multilocularis, bait pellets, each containing 50 mg praziquantel, were repeatedly distributed in an area of 566 km2 where many foxes are infected, in southern Germany. After six baiting campaigns (15-20 baits/km2) over a period of 14 months, the prevalence of the cestode in foxes, initially 32%, had fallen to 4%. The effect was most pronounced in the central part of the treated area, where no positive fox was found in the 2 months before the end of the trial. The study was controlled for other factors that could influence the parasite's prevalence, such as the availability of intermediate hosts. While the potential of this baiting method to remove E. multilocularis from wild hosts has been demonstrated, the question of its long-term efficacy and other unresolved problems have to be addressed by consecutive studies before routine application can be recommended.     

Subjective effects of transdermal nicotine among nonsmokers.

The subjective experience of nicotine, which may be influenced by personality traits as well as environmental factors, may be important for understanding the factors associated with the initiation and maintenance of nicotine dependence. The present study examined the effects of 7 mg transdermal nicotine among a relatively large sample (n = 91; 44 women) of college-aged nonsmokers. Using a placebo controlled, double-blind, within-subjects design, nicotine’s effects were examined at rest and again after participants completed a sustained attention task. Sex and personality factors (Behavioral Inhibition and Behavioral Approach; BIS/BAS Scales; Carver & White, 1994) were examined as potential moderators. Overall, the effects of nicotine were generally modest and unpleasant. In the context of the cognitive task, nicotine increased nausea and negative affect but reduced fatigue, relative to placebo. In contrast, effects of nicotine during the initial 4 hr of patch administration, in which participants were in their natural environments, were moderated by individual differences in behavioral approach. Neither behavioral inhibition nor gender reliably moderated any subjective effects of nicotine. The present work suggests transdermal nicotine exerts only modest, mostly negative effects among nonsmokers. Future work should examine both contextual and personality moderators in large samples of participants who are exposed to nicotine through multiple routes of administration. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Faster remission of chronic depression with combined psychotherapy and medication than with each therapy alone.

The main aim of the present novel reanalysis of archival data was to compare the time to remission during 12 weeks of treatment of chronic depression following antidepressant medication (n = 218), psychotherapy (n = 216), and their combination (n = 222). Cox regression survival analyses revealed that the combination of medication and psychotherapy produced full remission from chronic depression more rapidly than either of the single modality treatments, which did not differ from each other. Receiver operating characteristic curve analysis was used to explore predictors (treatment group, demographic, clinical, and psychosocial) of remission. For those receiving the combination treatment, the most likely to succeed were those with low baseline depression (24-item Hamilton Rating Scale for Depression [HRSD; M. Hamilton, 1967] score     

Phase I evaluation of mitoxantrone alone and combined with whole body hyperthermia in dogs with lymphoma

The maximum tolerated dose of mitoxantrone (MX) administered alone or combined with whole body hyperthermia (WBH) was determined in this nonrandomized, prospective study in dogs with lymphoma. MX was administered to 53 dogs every three weeks for a total of six treatments unless progressive disease or persistent, severe toxicity developed. Fifty dogs were evaluable (MX alone n = 30, MX/WBH n = 20). MX was administered as a 1 h infusion at the onset of the plateau phase of WBH in dogs treated with combined therapy. Dogs were evaluated weekly between treatments for the first four treatments with physical examination and complete blood counts to define acute and cumulative toxicity. Dogs were evaluated every three weeks for tumour response until relapse. The maximum tolerated dose (MTD) was defined as that dose in each group that resulted in a 50% incidence of moderate or severe toxicity as estimated from logistic regression analysis of the toxicity data. Myelosuppression was the only toxicity observed. Neutropenia was equal in frequency and severity between treatment groups. Thrombocytopenia was not observed in any dog receiving MX/WBH but occurred in 13% of dogs treated with MX alone. The MTD for MX +/- WBH was 6.1 +/- 0.6 and 6.5 +/- 0.8mg/M2 respectively. A steeper dose response relationship was observed in dogs receiving combined therapy compared to dogs treated with MX alone suggesting WBH may improve the uniformity of patient response to chemotherapy. We concluded that MX may be administered without dose reduction to dogs undergoing WBH and that MX should be evaluated more thoroughly in future thermochemotherapy studies.     

A comparative multicenter study of two transdermal estradiol replacement therapies in the treatment of postmenopausal symptoms

OBJECTIVE: Comparison of the effects of treatment of two transdermal therapeutic systems for estrogen replacement therapy with regard to efficacy, tolerability, and acceptance. DESIGN: Open randomized. SETTING: Multicenter. PATIENTS AND INTERVENTIONS: A study population of 104 postmenopausal women was randomized on a 1:1 basis to treatment with one of two estradiol patches, System (Cilag) and Estraderm (Ciba-Geigy). OUTCOME MEASURES: Systolic and diastolic BP, hot flushes, night sweating, fatigue, insomnia, depression, nervousness, headache, vaginal discomfort (efficacy variables); bleeding, dermatological symptoms, comfort and adhesiveness of patch, and other possible causes of discontinuation (tolerability); general evaluation by patient (acceptance). RESULTS: Considering all efficacy variables, 53% of Systen and 46% of Estraderm patients found the therapy satisfactory. Tolerability was somewhat higher in the Systen group. Adhesiveness of the patch was significantly better for Systen. Overall, 79% of Systen patients and 62% of Estraderm patients evaluated treatment as "good" or "very good." The majority of patients in both groups found the patch very comfortable or only slightly obtrusive.