Applying the case method for teaching within the health professions--teaching the students.

CONTEXT: When using the Case Method in teaching situations, problem-solving is emphasized and taught, in order to acquire the skills and later be able to apply them in new situations. The basis of the learning process is the students' own activity in the situation and is built on critical appraisal and discussion. OBJECTIVES: To explain what the Case Method is, what it is not and to describe when and where to use the Case Method. The objective is also to describe how to write a 'case', how to lead a 'case' discussion and how to deal with problems. Why one should use the Case Method is also highlighted. APPLICATION: The case used should be founded on a real life situation, containing a problem that must be handled. The structure and use of the white board plays a central part. It is important that the setting allows the teacher to interact with all the students. Groups of up to 30 students can be handled with ease, though larger groups are feasible in the right physical setting. Within the health professions, the Case Method can be used at all levels of training and to a certain extent the same case can be used--the depth with which it is addressed depends on the student's prior knowledge. Different professions and specialists can take part. A whole curriculum can be built up around the Case Method, but more often it is used together with other pedagogic methods. CONCLUSION: The Case Method is a well-structured, student-activating way of teaching, well-suited to hone problem-solving skills within health education programmes.

[The case method--a new student-activating method in medical education]. / Casemetodik--ny studentaktiv pedagogik i läkarutbildningen.

The case method is a student-activating method, used together with problem based learning (PBL) and traditional teaching methods in the curriculum for undergraduate medical education at the Faculty of Medicine in Lund/Malmö, Sweden. The case method provides training in the solving of clinical problems and is thus especially useful at the clinical level of medical education, and in an integrated and problem based curriculum. The case method consumes less teaching resources than PBL, and might thus be useful in a situation with increasing numbers of medical students.

Characterization of 5-hydroxytryptamine receptors mediating circular smooth muscle contraction in the human umbilical artery.

The study was performed to characterize pharmacologically the contractile 5-hydroxytryptamine (5-HT) receptors in the circular smooth muscle of the isolated human umbilical artery. Effects of agonists and antagonists for different 5-HT receptor subtypes were studied in intact endothelium vessel segments. All agonists induced concentration-dependent circular smooth muscle contractions. The potency was in declining order 5-HT > alpha-methyl-5-HT > sumatriptan >/= 2-methyl-5-HT. The effects of 5-HT and alpha-methyl-5-HT were antagonized by ketanserin, as well as methiothepin. The contractile effect of sumatriptan was antagonized by methiothepin but not by ketanserin. The 5-HT3 receptor antagonist, MDL 72222, did not affect the contraction by any of the agonists, including 2-methyl-5-HT. It is concluded that the 5-HT-induced contraction in the circular smooth muscle of the human umbilical artery seems to be mediated by a mixed population of 5-HT1-like receptors and 5-HT2 receptors.

Endothelium-derived prostanoids reduce 5-hydroxytryptamine-induced contraction in the human uterine artery.

The contribution of endothelium-linked mechanisms to the contraction induced by 5-hydroxytryptamine (5-HT) was investigated in the isolated human uterine artery. 5-HT contracted the uterine artery concentration-dependently. Removal of the endothelium or treatment with the cyclooxygenase inhibitor indomethacin potentiated the contractile response to 5-HT. The nitric oxide synthase inhibitor L-N(G)-monomethyl-arginine (L-NMMA) did not influence the contraction induced by 5-HT. Indomethacin did not affect the response to 5-HT in endothelium-denuded vessels. The 5-HT1 receptor agonist 5-carboxyamidotryptamine (5-CT) did not relax precontracted arteries. Removal of the endothelium did not change the response to 5-HT in the presence of the 5-HT(1B/D) receptor antagonist GR127935 and the 5-HT1A and 5-HT1B receptor antagonist -pindolol. The 5-HT1B receptor antagonist SB224289 did not affect the contraction induced by 5-HT. The results indicate that the 5-HT-induced contraction in the human uterine artery is accompanied by the release of an endothelium-derived relaxing factor (EDRF). This EDRF seems to be a prostanoid, probably prostacyclin (PGI2). The endothelium-linked mechanism seems to be mediated via a 5-HT1 receptor, but it is not possible to further classify the receptor subtype by the information obtained in this study.

Endothelins--vasoactive peptides and growth factors.

The endothelins (ETs) are regulatory peptides, distributed in many organ systems and with potent physiological effects. ETs represent the most powerful vasoconstrictive substances known today. They also act as growth factors and seem to be involved in fetal development. Much data support a pathophysiological role for ETs, especially in diseases of the vascular system, such as hypertension, preeclampsia, ischemic heart disease, subarachnoidal haemorrhage, and cerebral ischemia. The development of drugs affecting ET-receptors and the biosynthesis of ETs presently attract great interest for the establishment of new treatments of diseases in which ETs are involved. Hopefully, the elaboration of more specific ET-receptor ligands will fulfill some of these expectations.

Atypical receptors mediate the response to endothelin-1 and sarafotoxin S6b in the human umbilical artery.

The receptors mediating smooth muscle response to endothelin-1 and sarafotoxin S6b in the human umbilical artery were investigated in vitro. Both agonists induced contractions that were unaffected by the endothelin ET(B) receptor antagonist BQ 788 (10(-9), 10(-8), 10(-7) M). The non-selective endothelin ET(A/B) receptor antagonist PD 142893 (10(-7) M) decreased the contraction induced by endothelin-1. PD 142893 (10(-9) M) enhanced the contraction induced by sarafotoxin S6b whereas higher concentrations had no effect. Removing the endothelium did not affect the antagonising action of PD 142893 on endothelin-1-induced contractions while the enhancement of the sarafotoxin S6b-induced contraction was abolished. Sarafotoxin S6b induced relaxation in segments precontracted by 5-hydroxytryptamine and exposed to the endothelin ET(A) receptor antagonist BQ 123 (10(-7) M) and PD 142893 (10(-9) M) abolished this relaxation. These endothelial receptors seem neither to be classical endothelin ET(A) nor endothelin ET(B) receptors and they are not activated by endothelin-1.

5-Hydroxytryptamine contracts human uterine artery smooth muscle predominantly via 5-HT2 receptors.

Serotonergic receptors were classified in the isolated human uterine artery with intact endothelium, using agonists and antagonists for 5-hydroxytryptamine (5-HT) receptors. The efficacy for different agonists rated: alpha-methyl-5-HT (5-HT2) = 5-HT (non-selective) = 2-methyl-5-HT (5-HT3) >> sumatriptan (5-HT1), and the potency as: sumatriptan = 5-HT > 5-HT > alpha-methyl-5-HT > 2-methyl-5-HT. The contractile effects of 5-HT and alpha-methyl-5-HT were antagonized by the 5-HT2 receptor antagonist ketanserin and the non-selective antagonist methiothepin. The efficacy of sumatriptan was comparatively low. No interaction was encountered between 2-methyl-5-HT and MDL72222, suggesting an absence of 5-HT3 receptors. The results indicate that the contractile serotonergic receptor population in the human uterine artery mainly comprises 5-HT2 receptors, although a minor contribution of contractile 5-HT1 receptors cannot be excluded.

Treatment of uterine fibroids with GnRH-analogues prior to hysterectomy.

GnRH-analogues have a longer half-life and stronger receptor affinity than native GnRH. They block the secretion of gonadotropins from the anterior pituitary, producing a hypoestrogenic state. Preoperative treatment with GnRH-agonists for 3 months prior to hysterectomy reduces the size of uterine fibroids by about 50%. The hematologic profile is improved and subjective symptoms reduced. Other results are: a smaller peroperative blood loss, a shorter hospitalization time, and a tendency to easier operations. Side effects are predominantly hypoestrogenic. Treatment with GnRH-agonists before hysterectomy is recommended in cases of large fibroids, when technical problems may be anticipated, when preoperative anemia is present, or when it is desirable to postpone surgery.

Oxygen promotes contraction by endothelin-1 in human umbilical artery.

The influence of oxygen on the contractile response to endothelin-1 in the human umbilical artery was investigated in vitro. Segments of human umbilical artery were suspended in organ baths to record the circular motor activity induced by endothelin-1 at a pO2 of 12 kPascal (kPa) or 45 kPa. Endothelin-1 induced a concentration-dependent contraction which was significantly larger at 45 kPa O2 compared with the contractile response at 12 kPa O2.

The place of Zoladex in deferred surgery for uterine fibroids. Zoladex Myoma Study Group.

Two hundred and forty-seven patients with uterine fibroids were randomized to surgery alone or 3 months' Zoladex (Zeneca, Macclesfield, Ches., UK) followed by surgery. Zoladex significantly reduced uterine and fibroid volumes (p = 0.0001). There was a significantly (p = 0.002) greater mean rise in haemoglobin from entry to preoperation in the Zoladex group (1 g/dl) compared with the surgery-alone group (0.3 g/dl) as well as a tendency towards easier surgery, and reduced operative blood loss. Zoladex-treated patients had a significantly (p = 0.016) shorter hospital stay and pelvic pain and abdominal pressure symptoms were significantly (p < 0.0001) reduced in this group. Zoladex was well tolerated.

A one-year multicenter study of efficacy and safety of a continuous, low-dose, estradiol-releasing vaginal ring (Estring) in postmenopausal women with symptoms and signs of urogenital aging.

OBJECTIVE: We studied the efficacy, safety, and acceptability of an estradiol-releasing (6.5 to 9.5 micrograms per 24 hours) silicone vaginal ring (Estring) in postmenopausal women with symptoms and signs of urogenital aging during a treatment period of 1 year. STUDY DESIGN: The study was open with blind analysis of vaginal cytologic testing. In addition to gynecologic examination, subjective symptoms were assessed and vaginal pH and urinary samples (for bacteriuria) were obtained before insertion of Estring. This procedure was repeated every 3 months up to 1 year's treatment, together with requests concerning acceptability and adverse experiences. At inclusion and end of Estring treatment, vaginal smears for evaluation of cytologic results were obtained. RESULTS: Estring induced a high maturation value in the vaginal mucosa and restored vaginal pH to levels normality seen in fertile women (< 5.5). For most variables a 90% responder rate (proportion of cured and improved patients) was found after 3 months and up to 1 year regarding subjective symptoms and objective signs of vaginal mucosal atrophy. Twenty-eight (20%) of 136 women, withdrew from the study, 8 (6%) of them because of adverse events. Three women reported vaginal bleeding, none associated with malignancy or endometrial proliferation. Ten (7%) reported vaginal irritation, and in two cases vaginal ulcers were found. About 90% did not remove the ring during any of the 3-month treatment periods, and 78% used the four consecutive rings continuously up to 1 year. The ring was given a strong preference (p < 0.001) by patients with previous experience of other administration forms. CONCLUSION: Estring represents a safe, highly effective, and very well-accepted administration form for long-term treatment of urogenital disorders caused by estrogen deficiency in postmenopausal women.

Characterization of contractile adrenoceptors in the human umbilical artery.

Adrenoceptors mediating contraction in ring segments of human umbilical arteries from normal term pregnancies were investigated in vitro. Contraction was elicited by (order of potency indicated): noradrenaline = the alpha 2-adrenoceptor agonist oxymetazoline >> the alpha 1-adrenoceptor agonist phenylephrine. The alpha 1-adrenoceptor antagonist prazosin antagonized the contraction elicited by noradrenaline and phenylephrine. The alpha 2-adrenoceptor antagonist rauwolscine antagonized the contraction elicited by noradrenaline and oxymetazoline. Oxymetazoline had an efficacy 5 times higher than that of noradrenaline and the 5-hydroxytryptamine receptor antagonist methysergide antagonized the contraction elicited by oxymetazoline. It is suggested that the contractile adrenoceptors in the human umbilical artery consist of both alpha 1 and alpha 2 subtypes. Furthermore, the contractile effect of oxymetazoline seems to be mediated via both alpha 2-adrenoceptors and 5-hydroxytryptamine receptors.

Effects of head-down tilt on atrial natriuretic peptide and the renin system in pregnancy.

We studied the effects of head-down tilt to 10 degrees for 30 minutes on plasma atrial natriuretic peptide and the renin-aldosterone system in 8 preeclamptic pregnant women, 8 healthy pregnant women, and 11 nonpregnant women of fertile age. Mean arterial blood pressure did not change in the pregnant groups but increased significantly in the nonpregnant control subjects. Heart rate decreased significantly in preeclamptic women but remained unchanged in both control groups. Baseline atrial natriuretic peptide concentration was significantly higher in both preeclamptic (66 +/- 4 pmol/L) and pregnant (54 +/- 6 pmol/L) control subjects compared with nonpregnant subjects (40 +/- 2 pmol/L), but the difference between the pregnant groups was not significant. Head-down tilting induced a significant increase in atrial natriuretic peptide only in healthy pregnant women. Baseline plasma renin activity and aldosterone concentrations were significantly higher in pregnant control subjects compared with both the preeclamptic and nonpregnant groups. The differences between the preeclamptic and nonpregnant control groups were nonsignificant. After head-down tilting, plasma renin activity decreased significantly only in nonpregnant control subjects, whereas aldosterone decreased significantly in preeclamptic and nonpregnant control subjects. In preeclampsia, atrial natriuretic peptide release followed blood pressure and not changes in cardiac output. When all 27 women were studied, a correlation between atrial natriuretic peptide and mean arterial pressure was found in the left lateral supine position. The results suggest that pregnant women developing preeclampsia lose their usual hemodynamic control and show reactions resembling the nonpregnant state when subjected to head-down tilt.

Vasoactive peptides and uterine vessels.

Endothelins and atrial natriuretic peptide (ANP) are vasoactive peptides with effects on the human uterine and umbilical arteries. Endothelin (ET) contracts the vascular smooth muscle. Both ETA- and non-ETA-non-ETB-receptors seem to be involved. Autoradiography reveals binding of ET to vascular smooth muscle. ANP counteracts the contractile effects of angiotensin II in the human uterine artery. Head-down tilt results in elevation of plasma ANP in healthy pregnant women, while the same manoeuvre induces down-regulation of the reninangiotensin-aldosterone system in non-pregnant women and patients suffering from pre-eclampsia.

Reduced contractile effect of endothelin-1 and noradrenalin in human umbilical artery from pregnancies with abnormal umbilical artery flow velocity waveforms.

This study on the human umbilical artery was undertaken in order to elucidate possible correlations between changes in response to vasoactive substances in vitro and abnormal umbilical artery flow velocity waveforms in vivo associated with preeclampsia and intrauterine growth retardation. The vascular reactivity to endothelin-1, noradrenalin, serotonin, the thromboxane A2 analogue U46619, substance P and prostacyclin was determined in umbilical artery segments from 13 normal pregnancies and 29 pregnancies complicated with preeclampsia and/or intrauterine growth retardation with normal or abnormal umbilical flow velocity waveforms. The contractile effect in vitro of endothelin-1 and noradrenalin was reduced in segments from pregnancies complicated by abnormal umbilical flow velocity waveforms in vivo. No differences were detected in the contractile effect of serotonin and U46619, or in the relaxatory effect of substance P and prostacyclin. In conclusion, endothelin-1- and noradrenalin-related mechanisms could be involved in the abnormal umbilical flow velocity waveforms associated with preeclampsia and intrauterine growth retardation.

Atrial natriuretic peptide antagonizes the contractile effect of angiotensin II in the human uterine artery.

The regulatory peptides angiotensin II (Ang II) and atrial natriuretic peptide (ANP) are believed to play important roles in the pathogenesis of pre-eclampsia. The interactions between Ang II, ANP and noradrenaline (NA) were studied in vitro on the human uterine artery. Both Ang II and NA contracted the isolated vessel in a concentration-dependent way. At high doses a decrease in the contractile force induced by Ang II but not NA was encountered. ANP inhibited the smooth muscle activity elicited by Ang II, resulting in a dextroshift of the concentration-response curve, and a decrease in both Emax (the maximum contractile response) and pD2 (the negative logarithm of the agonist concentration inducing 50% of the Emax) for Ang II. The results might indicate a specific antagonism between Ang II and ANP, probably at the post-receptor level. ANP did not induce any significant change in pD2 of the concentration-response curve for NA. Only at the highest dose of ANP (10(-7) M) was Emax depressed. Thus, the results only indicate a weak antagonistic relationship between NA and ANP in the human uterine artery.

A comparative multicenter study of the effects of continuous low-dose estradiol released from a new vaginal ring versus estriol vaginal pessaries in postmenopausal women with symptoms and signs of urogenital atrophy.

OBJECTIVE: Our purpose was to study the efficacy, safety, and acceptability of a new estradiol-releasing (6.5 to 9.5 micrograms per 24 hours) silicone rubber vaginal ring compared with Ovesterin 0.5 mg estriol vaginal pessaries. STUDY DESIGN: Gynecologic clinical status, vaginal pH, cytologic characteristics, and occurrence of bacteriuria were determined before starting and after 3 and 12 weeks of treatment in 146 postmenopausal women. RESULTS: Both treatments alleviated the subjective and objective symptoms of estrogen deficiency excellently, and both were equally effective at restoring the vaginal pH to levels normally seen in fertile women (< 5.5). Vaginal cytologic studies showed a significant difference in maturation value in favor of the estradiol-releasing silicone rubber vaginal ring, as measured by the pathologist's assessment of the proliferation of the vaginal mucosa. A total of 77% of users were classified as responders, compared with 39% in the pessary group. Both treatments were well accepted. The administration of the pessary was associated with a significantly higher (p < 0.001) incidence of discomfort than that of the ring, which was given better (p < 0.001) rating by the patients at the 12-week visit. A strong preference (p < 0.001) for the ring was shown by patients with previous experience with pessaries. CONCLUSION: Treatment of urogenital symptoms in postmenopausal women with an estradiol-releasing vaginal ring is shown to be an effective and safe method, exhibiting advantages over treatment with estriol vaginal pessaries.

Endothelium-dependent relaxation to substance P in human umbilical artery is mediated via prostanoid synthesis.

To investigate the relaxatory effect and mode of action of substance P in the human umbilical artery, ring segments of the artery were suspended in organ baths to record the circular motor activity. Substance P induced a significant relaxation in segments with intact endothelium pre-contracted by potassium or 5-hydroxytryptamine. Segments devoid of their endothelium failed to relax when challenged with substance P. The relaxation induced by substance P was inhibited by the cyclo-oxygenase antagonist indomethacin, while the nitric oxide-synthetase inhibitor L-NG-monomethyl-arginine was without effect. These findings suggest that the relaxatory effect of substance P in the human umbilical artery is dependent on an intact endothelium. In contrast to the case in most other vessels, the relaxation is not mediated via the release of endothelium-derived relaxing factor, but seems to be dependent on prostanoid synthesis.