The effect of medical education and counselling on treatment adherence and disease severity in patients with acne vulgaris: a non-randomised interventional study.

INTRODUCTION: Acne vulgaris (AV) is a common inflammatory skin disease affecting adolescents and young adults. It affects one's self-esteem and social relationship. In addition, poor adherence to treatment can cause poor treatment response and disease recurrence. This study aims to determine the effectiveness of medical education and counselling on treatment adherence and disease severity. METHODS: This is a non-randomised interventional study with age- and treatment- matched control conducted in a tertiary dermatology clinic from July 2021 to June 2022. Patients in the intervention group received a 10 min video presentation on acne, followed by treatment counselling. The adherence rate was determined objectively (pill counting and tube weighing) and subjectively (ECOB questionnaire). The disease severity was assessed using the Comprehensive Acne Severity Scale (CASS) and Global Acne Grading System (GAGS). RESULTS: A total of 100 patients completed the 12-week study. With intervention, patients have better adherence to topical medication (5% benzoyl peroxide gel: 71% vs 57.9%, p= 0.031; 0.05% tretinoin cream: 58.7% vs 45.4%, p= 0.044) at week 12. However, the intervention program did not improve adherence to oral medication. Overall, with intervention, a significantly higher percentage of improvement in disease severity was noted (47.3% vs. 39.1%, p=0.044). Nonadherence to treatment was attributed mostly to forgetfulness in 54% of the patients, followed by a busy lifestyle (41%) and little knowledge of acne (26%). CONCLUSION: Patients have significantly better adherence to topical medication with education and counselling. Better adherence to treatment leads to more remarkable disease improvement.

Neuromedin U neurones in the rat nucleus of the tractus solitarius are catecholaminergic and respond to peripheral cholecystokinin.

Centrally administered neuromedin U (NMU) has profound effects on food intake and energy expenditure. In the rat, central expression of NMU mRNA is confined to the brainstem and the hypothalamus/pituitary, while mRNA for the receptor NMU2R is expressed in the hypothalamus and hippocampus, as well as in the lining of the ventricular system, but not in the brainstem. We demonstrate that a subpopulation of catecholaminergic neurones in the brainstem nucleus of the tractus solitarius contain NMU and are activated by the gut-derived peptide, cholecystokinin. This is consistent with NMU neurones having an anorectic action, probably via their interaction with other neurones in the paraventricular hypothalamus.

Serum gonadotropin and ovarian steroid levels in women during administration of a norethindrone-ethinylestradiol triphasic oral contraceptive.

We studied the inhibitory effect of a triphasic oral contraceptive (OC) regimen on the pituitary and ovarian function in 29 normal, healthy women. ORTHO* 7/7/7 Tablets contain a constant low dose of ethinylestradiol (EE) and a step-wise increasing level of norethindrone (NE). The pills for the first, middle and last weeks of the 21-day regimen contained, respectively, 0.5, 0.75, and 1.00 mg NE, and all contained 0.035 mg EE. The subjects were divided into 3 groups on the basis of their histories of OC use. Ten had not taken an OC in the previous 2 months, 10 were switched to this study from a fixed-dosage combination OC containing 0.050 mg estrogen, and 9 had been taking ORTHO 7/7/7 Tablets for 5 or more cycles. Serum levels of FSH, LH, estradiol and progesterone were measured and statistically compared with those from 5 normal, untreated women. The results from all study cycles showed that the four hormone profiles were significantly suppressed as compared to the normal patterns. Thus, one mode of action of this new triphasic OC is to inhibit ovulation by suppression of pituitary-ovarian function. This OC treatment appeared to be equally effective among women with varying prior histories of OC therapy.

Stimulation of estradiol production from estrone-3-sulfate by 5 alpha-dihydrotestosterone in cultured human placental explants.

The effect of androgens on the conversion of estradiol (E2) and estrone (E1) from estrone-3-sulfate (E1-S) was studied in explants of normal human term placentas. Explants incubated in medium supplemented with 2.0 microM E1-S showed that 50 microM dihydrotestosterone (DHT) stimulated E2 production 15-fold above control values after 0.5h, but neither 50 microM methyltestosterone (MT) nor 50 microM diethylstilbestrol (DES) had any effect. HCG (5.0 i.u./ml), alone or in combination with one of the androgens, did not influence the E2 production. When the explants were incubated in medium with 0.25 microM E1-S (the average concentration reported for late pregnancy plasma), DHT (0.5-50 microM) caused a dose- and time-dependent increase in E2 production, while E1 production and the combined accumulation of E2 and E1 were slightly inhibited by all doses of DHT during the 0.5-4h incubation. When E1 (0.1 microM) was used as substrate, DHT caused a dramatic dose- and time-dependent shift in the E1-E2 equilibrium towards E2. The results indicate that during late pregnancy, a particular class of androgens may increase the production of the more bioactive E2 from the circulating E1-S; the mode of action may be an enhanced conversion of E1 to E2.

Clinical and echocardiographic evidence suggesting afterload reduction as a mechanism of action of tolazoline in neonatal hypoxemia.

The effect of tolazoline was assessed in 29 hypoxic neonates. Tolazoline was given in a bolus starting at 1 mg/kg and repeated or infused for 5-134 hours. A "good clinical response," defined as a rise in PaO2 of more than 20 mm Hg, was obtained in 23 (79%), 20 of this group were weaned from the respirator, and three died. Six infants did not respond initially and four died. Failure to respond to tolazoline or to be weaned from the ventilator was usually associated with severe additional pathology. Urine output (greater than 1 ml/kg/h) was adequate in most neonates during therapy. In those with preexisting oliguria (less than 1 ml/kg/h), output improved during therapy. Blood pressure monitoring showed a fall in blood pressure in 19 patients during tolazoline administration, but true hypotension only occurred in four; in seven there was no fall and in three there was a rise in blood pressure. Echocardiography was performed prior to therapy in 19 patients and repeated in 12 patients after 24 h. Additional "tracking" was performed at 10 min, 1 h, and 4 h in seven patients. Prior to therapy, right ventricular dysfunction was demonstrated by abnormal right ventricular systolic time intervals (RVSTIs) in 17 of the patients tested. A rapid improvement was evident during therapy especially with "tracking." Left ventricular dysfunction, assessed by left ventricular systolic time intervals (LVSTIs), ejection fraction (EF), shortening fraction (SF), and velocity of circumferential fiber shortening (VCF), was also evident prior to therapy and improved, though more gradually than the RVSTIs.(ABSTRACT TRUNCATED AT 250 WORDS)

Mode of action of dl-norgestrel and ethinylestradiol combination in postcoital contraception. III. Effect of preovulatory administration following the luteinizing hormone surge on ovarian steroidogenesis.

A combination of 1.0 mg dl-norgestrel and 0.1 mg ethinylestradiol was administered orally at 18 hours after the detection of luteinizing hormone rise and again at 30 hours in five healthy volunteers with normal menstrual cycles. The effects on ovarian function were studied by comparing the daily serum levels of progesterone (P), 17 alpha-hydroxyprogesterone, and estradiol (E2) measured in a control (placebo) cycle with those in two consecutive treatment cycles. Treatment did not alter the steroid levels in one subject. P was suppressed in one or both treatment cycles of four subjects. E2 was suppressed in both treatment cycles of one subject and produced widely fluctuating patterns in another. The hormonal patterns in the two consecutive treatment cycles of the same individual were similar in all but one instance, where only the P level in the second treatment cycle was diminished. These results showed that this treatment can elicit steroidogenic responses of varying degrees and duration. The contraceptive action may lie in the altered P and/or E2 level at certain points in the menstrual cycle.

PIP: A combination of 1.0 mg dl-norgestrel and 0.1 mg ethinyl estradiol was administered orally at 18 hours after detection of luteinizing hormone and again at 30 hours in 5 healthy volunteers with normal menstrual cycles. The effects on ovarian function were studied by comparing the daily serum levels of progesterone (P), 17alpha-hydroxyprogesterone, and estradiol (E2) measured in a control (placebo) cycle with those in 2 consecutive treatment cycles. Treatment did not alter the steroid levels in 1 subject. P was suppressed in 1 or both treatment cycles of 4 subjects. E2 was suppressed in both treatment cycles of 1 subject and produced widely fluctuating patterns in another. The hormonal patterns in the 2 consecutive treatment cycles of the same individual were similar in all but 1 instance, where only the P level in the 2nd treatment cycle was diminished. These results showed that this treatment can elicit steroidogenic responses of varying degrees and duration. The contraceptive action may lie in the altered P and/or E2 level at certain points in the menstrual cycle.

Androgens stimulate estradiol production in cultured human placental explants from term pregnancy.

Estradiol production was significantly stimulated in explants of normal human term placenta cultured in the presence of 0.01 mM methyltestosterone. Estradiol levels in the media rose significantly during the first 24 h incubation and increased more markedly over the next two successive 24 h incubations. Dexamethasone and d-norgestrel did not affect estradiol production. Neither progesterone nor hCG levels were altered by any of the three synthetic steroids. The non-aromatizable androgen, 5 alpha-dihydrotesterone (DHT), also significantly stimulated estradiol production in a dose-dependent fashion, with the maximum levels being measured in the media from the first 24 h incubation. In experiments where the explants were cultured for periods between 0.5 to 24 h, DHT elicited both a dose- and time-dependent increase in estradiol production: At all dosages of DHT, the maximum stimulation occurred at the end of 3 h incubation. Again progesterone and hCG productions were not affected. This appears to be the first report of androgens stimulating estradiol production in the human term placenta in vitro.

Mode of action of dl-norgestrel and ethinylestradiol combination in postcoital contraception. II. Effect of postovulatory administration on ovarian function and endometrium.

A combination of 1.0 mg dl-norgestrel and 0.1 mg ethinylestradiol (EE) was administered orally at 36 hours after the detection of the luteinizing hormone peak and again at 48 hours in 12 healthy volunteers with normal menstrual cycles. The effects on ovarian function were studied by comparing the daily serum levels of progesterone (P), 17 alpha-hydroxyprogesterone, and estradiol (E2) in control (placebo) and treatment cycles. Five subjects showed no significant change in the levels of these steroids but had a shortened luteal phase. The treatment significantly decreased both P and E2 levels in three subjects, while two subjects showed diminished E2 levels only. The remaining two subjects had lower P levels and fluctuating E2 patterns. Endometrial biopsies from both study cycles indicated asynchronous development of the epithelial and stromal components in the treatment cycle. These findings (abnormal luteal phase steroid levels and duration and outphased endometrial development) indicate that corpus luteum function was variously affected by the action of norgestrel-EE treatment.

PIP: A combination of 1.0 mg dl-norgestrel and 0.1 mg ethinyl estradiol (EE) was administered orally at 36 hours after detection of the luteinizing hormone peak and again at 48 hours in 12 healthy volunteers with normal menstrual cycles. The effects on ovarian functions were studied by comparing the daily serum levels of progesterone (P), 17alpha-hydroxyprogesterone, and estradiol (E2) in control (placebo) and treatment cycles. 5 subjects showed no significant changes in the levels of these steroids but had a shortened luteal phase. The treatment significantly decreased both P and E2 levels in 3 subjects, while 2 subjects showed diminished E2 levels only. The remaining 2 subjects had lower P levels and fluctuating E2 patterns. Endometrial biopsies from both study cycles indicated asynchronous development of the epithelial and stromal components in the treatment cycle. These findings (abnormal luteal phase steroid levels and duration and outphased endometrial development) indicate that corpus luteum function was variously affected by the action of norgestrel-EE treatment.

Profiles of selected hormones during menstrual cycles of teenage athletes.

Concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone (P), 17 alpha-hydroxyprogesterone (17 alpha OHP), 17 beta-estradiol (E2), and prolactin (HPr) were monitored for one complete menstrual cycle in teenage swimmers, a gynecologically age-matched control group, and a group of fertile adult women. The swimmers experienced anovulatory menstrual cycles. The time from the LH surge to the onset of menses ("luteal" phase) was very short in the swimmers (4.5 +/- 0.6 days) in comparison with the lengths of these phases in the adults (13.4 +/- 1.7 days; P less than 0.05) and in the control group (7.8 +/- 3.0 days; P less than 0.05). In the follicular phase the swimmers' LH concentration was elevated and their FSH concentration was depressed in comparison with each of the other groups (P less than 0.05). Luteal phase FHS, P, E2, and 17 alpha OHP were also lower in the swimmers (P less than 0.05), as was HPr (0.05 greater than P less than 0.10). Gonadotropin concentrations and luteal phase P concentrations were not different (P greater than 0.05) in the adults and the control group. The present findings indicate that the corpora lutea in the swimmers were not functioning properly. It is likely that the swimmers' strenuous daily 2-4 h training regimen is implicated.

Correlation of cyclic AMP and cyclic GMP accumulation and steroidogenesis during stimulation of bovine luteal cells with luteinizing hormone.

The relationship between LH-induced steroidogenesis and the production of cyclic AMP and cyclic GMP was studied as a function of LH dose and time in isolated luteal cells from pregnant cows. Submaximal steroidogenic concentrations of LH caused a transient but significant rise in cyclic AMP that peaked after incubation for 5 min. A consequent rise in progesterone occurred at 30 min even though cyclic AMP had returned to the basal level at that time. Higher steroidogenic doses of LH elicited a maximum increase of cyclic AMP at 5 min and this was sustained for up to 1 h; the related progesterone production was significantly raised at 15 min and reached a maximum plateau at 30 min. The corresponding levels of cyclic GMP did not appear to be altered by any of the LH concentrations used. The present study has provided direct evidence that even at very low doses of LH, cyclic AMP plays an intermediary role in the stimulation of steroidogenesis in a mixed population of cells isolated from the bovine corpus luteum. Cyclic GMP, on the other hand, did not appear to play a role in the action of LH on the same population of luteal cells.

Effects of exercise on the serum concentrations of FSH, LH, progesterone, and estradiol.

The effects of 30 min of exercise (74.1 +/- 3.0% (VO2), on the responses of progesterone (P), estradiol (E2), follicle stimulating hormone (FSH), and luteinizing hormone (LH) were investigated in 10 women. With such exercise significant increments occurred in P (37.6 +/- 9.5%) and E2 (13.5 +/- 7.5%) (P less than 0.05), whereas no changes were observed in FSH and LH (p greater than 0.05). Exercise in the luteal phase and during menses provoked similar changes in P, but E2 concentrations remained unchanged when exercise occurred during menses (p greater than 0.05). With 8-11 weeks of training the menstrual cycles were quite irregular and retesting of subjects in the same phase of the cycle was not possible. Yet, when subjects were retested after training, no changes occurred in P, E2 or LH (p greater than 0.05) but a decrement did occur in FSH (p less than 0.10). Thus, heavy exercise in untrained subjects provokes significant increments in ovarian hormones, whereas no such increments are observed in trained subjects exercising at the same absolute workload.

Mode of action of DL-norgestrel and ethinylestradiol combination in postcoital contraception.

Possible mechanisms of action of a combination of ethinylestradiol (EE) and dl-norgestrel as a postcoital contraceptive agent were studied in 12 healthy female volunteers. An oral dose of 0.1 mg of EE and 1.0 mg of dl-norgestrel was given at the predicted time of ovulation and again 12 hours later. Serum luteinizing hormone, prolactin, progesterone, 17 alpha-hydroxyprogesterone, and estradiol were measured by specific radioimmunoassays in blood samples obtained daily from the 8th day of the menstrual cycle to the 1st day of menses. Hormone profiles suggested that the medication elicited a range of individual variations in pituitary and/or ovarian responses. Histologic examination of the endometrium consistently showed significant alteration in endometrial development with a dissociation in maturation of glandular and stomal components. This postcoital contraceptive acts either by (1) suppressing ovulation or (2) disrupting luteal function by acting directly on the corpus luteum or by interfering with appropriate endometrial responses to ovarian steroids.

Reevaluation of the role of cyclic adenosine 3',5'-monophosphate and protein kinase in the stimulation of steroidogenesis by luteinizing hormone in bovine corpus luteum slices.

Incubation of bovine corpus luteum slices at 37 C with luteinizing hormone showed that 10.0 microng LH/ml caused a maximum rise in tissue cyclic AMP content within 15 min. Slices incubated with 1.0 or 0.1 microng LH/ml showed a much more gradual accumulation of this nucleotide. In the absence of added LH, a marked decline in the amount of cyclic AMP was observed during the first 60 min. The possible role of cyclic AMP in the action of LH was reexamined by studying the dose-response effect of LH on the stimulation of progesterone synthesis, cyclic AMP-dependent protein kinase activation, and cyclic AMP accumulation. After a 2-h incubatin, the results showed that the dose required to elicit a minimal significant stimulation of steroidogenesis was 0.01 microng/ml LH. At this and higher concentrations of LH, a concomitant stimulation of protein kinase activity and progesterone synthesis was also consistently observed. However, significant accumulation of cyclic AMP became consistently detectable only at 0.1 microng/ml LH. This report is the first to show a positive correlation between the activation of cyclic AMP-dependent protein kinase and the stimulation of steroidogenesis in the corpus luteum at the same minimal effective level of LH. These results indicate that cyclic AMP and the cyclic AMP-dependent protein kinase probably play important intermediary roles in the stimulation of steroidogenesis by LH in the bovine corpus luteum.

Adenosine-3',5'-monophosphate in the plasma from human pregnancy.

Adenosine-3',5'-monophosphate (cyclic AMP) concentration was measured in plasma from nonpregnant women; women in the 7-41 weeks of normal pregnancy; during labor; and 5-7 h postpartum. The cyclic AMP levels in the course of normal pregnancy showed an initial peak volume at 14 weeks. After falling to nonpregnant level at 18 weeks, it began to rise steadily and reached a second peak at 34 weeks. A gradual decline was then followed until labor. The postpartum plasma concentration was significantly lower than the nonpregnant level. A similar pattern was found in serial studies in 4 women of normal pregnancy. Sequential cyclic AMP measurement in 5 hypertensive pregnancies showed a markedly elevated level during 16-26 weeks, but became comparable to normal pregnancy values thereafter. In the only preeclamptic patient studied, cyclic AMP was elevated in the 16-27th weeks although no clinical symptom was found until the 31st week. The study showed that the plasma cyclic AMP level in normal pregnancy becomes elevated above nonpregnant level at the end of the first and during the third trimesters. However, this profile appeared to be altered in pregnancies complicated by hypertension.

Dynamics of adenosine-3', 5'- monophosphate transfer among mother, fetus, and amniotic fluid in the rhesus monkey.

Cyclic AMP exchange among the mother, amniotic fluid, and fetus was studied in normal rhesus monkeys at term pregnancy. Following a pulse intravenous administration of 3H-cyclic AMP into the mother, a small fraction of the dose appeared in less than 1 minute in fetal blood. It appeared in the amniotic fluid after 5 minutes and reached maximum level in 20 minutes. The accumulation of 3H-cyclic AMP in the amniotic fluid in 1 hour was 0.03 per cent of the injected dose. The amount and time course of 3H-cyclic AMP accumulation in the fluid were not altered by tying the umbilical vessels. The transfer of 3H-cyclic AMP injected in utero into the fetal femoral artery resembled that in the mother; in 1 hour the amniotic fluid contained 0.22 per cent of the injected dose. When injected directly into the amniotic sac, more than 65 per cent of the injected dose remained unchanged after 1 hour, with minimal transfer into the maternal and fetal compartments. This study showed rapid bidirectional exchange of cyclic AMP between the mother and the fetus. Both of these compartments can contribute cyclic AMP to the amniotic fluid, independently or in concert. It remained fairly stable in the fluid and was not readily metabolized or transported out.

PIP: The exchange of labeled cAMP among maternal and fetal circulation and amniotic fluid in term pregnant rhesus monkeys was monitored. First 6 monkeys received an iv injection of tritiated cAMP. Most Most of the nucleotide disappeared from maternal blood in 1 hour, in a nonlinear manner; it peaked in blood of 1 fetus in 5 minutes, was more concentrated in fetal than maternal blood in 10 minutes and reached low levels in 1 hour. cAMP appeared in amniotic fluid in 5 minutes and reached a plateau in 20 minutes. .03% of the dose was found in amniotic fluid in 1 hour, or .04% in 2 fetuses killed by tying the cord. When cAMP was injected intraarterially into 3 fetuses, complex disappearance curves and rapid transfer to maternal blood were recorded, similar to those seen in the 1st series. .22% of the dose accumulated an amniotic fluid within 1 hour, remaining constant from 30 to 60 minutes. 65% of the cAMP injected into the amniotic fluid of 2 monkeys remained after 1 hour.