Angiosarcoma of the breast: Report of a case and autopsy findings

We report a case of angiosarcoma of the breast and the autopsy findings. The patient was a 35-year-old premenopausal woman who complained of a tumor in her left breast. We found a tumor measuring 55 mm in diameter in the lower external quadrant. The tumor was elastic and soft, smooth surfaced, well-defined and mobile. Dimpling sign or change of skin color were not observed. Clinically it was diagnosed as phyllodes tumor, but tumorectomy revealed primary angiosarcoma of the breast. Further extended surgery was recommended, but the patient refused additional therapy. Histological findings revealed a free surgical margin and neither lymph node metastasis nor distant metastasis were clinically observed. Seven months later, local recurrence in the same breast was recognized and finally radical mastectomy was carried out. Histological findings showed recurrence of angiosarcoma in the left breast but lymph node metastasis was not detected. Two months after mastectomy, metastases to the cervical and thoracic vertebrae were observed and radiation therapy was performed. Sixteen months from onset, she died due to multi-organ failure as general metastases of angiosarcoma. At autopsy, metastases to many organs including the digestive system were observed. The incidence of primary angiosarcoma of the breast is low but its prognosis is poor. This case emphasized the difficulties in clinical diagnosis and treatment for the angiosarcoma of the breast.     

Prevention by morphine of apomorphine- and oxytocin-induced penile erection and yawning: involvement of nitric oxide

The possible involvement of nitric oxide in the prevention by morphine of apomorphine- and oxytocin-induced penile erection and yawning was investigated by measuring the concentration of NO₂- and NO₃- in the dialysate obtained with a vertical microdialysis probe implanted in the paraventricular nucleus of the hypothalamus of male rats. Either apomorphine (80 μg/kgs.c.) or oxytocin (30 ng i.c.v.) increased significantly basal NO₂- and NO₃- concentration in the paraventricular dialysate, penile erection and yawning. Morphine (1, 5 and 10mg/kg i.p.) prevented dose-dependently either apomorphine or oxytocin responses when given 15min before apomorphine or oxytocin. Prevention by morphine of apomorphine and oxytocin responses was abolished by naloxone (3mg/kg i.p.) given 15min before morphine. Morphine prevented apomorphine and oxytocin responses also when given in the lateral ventricles or directly in the paraventricular nucleus. In contrast, the selective agonist of the kappa opioid receptor subtype U-69,593 was found to be ineffective. The present results confirm previous findings showing that morphine acts through μ receptors in the paraventricular nucleus to prevent apomorphine and oxytocin-induced penile erection and yawning and suggest that this morphine effect is mediated by a decreased activity of nitric oxide in the paraventricular nucleus of the hypothalamus. Received: 30 September 1996 / Accepted: 24 January 1997     

Factors Influencing the Growth in Knowledge of Trainees in General Practice

Objectives: The relation between the content of postgraduate training for general practice and the outcome in terms of the growth in knowledge of trainees was investigated. The training variables included were: (1) the number of patients seen per day, (2) the trainer, (3) the practice and (4) the theoretical curriculum.Methods: Subjects were 58 trainee-trainer pairs. Growth in knowledge was assessed by two written tests administered with eight months interval. Training variables were evaluated by means of questionnaires and logbook-registration. The correlation was explored between each of the training variables and the knowledge tests scores. To correct for interactional effects, a step-wise multiple regression analysis was performed with the second test as dependent variable and the first test as well as the training variables as independent variables.Results: Significant growth in knowledge was demonstrated. Non of all training variables investigated explained the variance in scores on the second test equally good or better than the scores on the entry test.Conclusions: The impact of the separate training-components on the growth in knowledge, remains unclear. We may speculate, that the sort of knowledge assessed with the written literature based true/false test is different from the sort of knowledge transferred during every day training: evidence based knowledge versus experience based knowledge. Equally valid is the conclusion that these findings fit into the theory that in adult learning the outcome is more learner than teacher dependent.This revised version was published online in September 2005 with corrections to the Cover Date.     

Confocal Laser Scanning Microscopic Visualization of the Transport of Dextrans After Nasal Administration to Rats: Effects of Absorption Enhancers

Purpose. To visualize the transport pathway(s) of high molecular weight model compounds across rat nasal epithelium in vivousing confocal laser scanning microscopy. Furthermore, the influence of nasal absorption enhancers (randomly methylated -cyclodextrin and sodium taurodihydrofusidate) on this transport was studied. Methods. Fluorescein isothiocyanate (FITC)-labelled dextrans with a molecular weight of 3,000 or 10,000 Da were administered intranasally to rats. Fifteen minutes after administration the tissue was fixed with Bouin. The nasal septum was surgically removed and stained with Evans Blue protein stain or DiIC18(5) lipid stain prior to visualization with the confocal laser scanning microscope. Results. Transport of FITC-dextran 3,000 across nasal epithelium occurred via the paracellular pathway. Endocytosis of FITC-dextran 3,000 was also shown. In the presence of randomly methylated -cyclodextrin 2% (w/v) similar transport pathways for FITC-dextran 3,000 were observed. With sodium taurodihydrofusidate 1% (w/v) the transport route was also paracellular with endocytosis, but cells were swollen and mucus was extruded into the nasal cavity. For FITC-dextran 10,000 hardly any transport was observed without enhancer, or after co-administration with randomly methylated -cyclodextrin 2% (w/v). Co-administration with sodium taurodihydrofusidate 1% (w/v) resulted in paracellular transport of FITC-dextran 10,000, but morphological changes, i.e. swelling of cells and mucus extrusion, were observed. Conclusions. Confocal laser scanning microscopy is a suitable approach to visualize the transport pathways of high molecular weight hydrophilic compounds across nasal epithelium, and to study the effects of absorption enhancers on drug transport and cell morphology.     

Release of [3H]5-hydroxytryptamine from the intermediate area of rat thoracic spinal cord is modulated by presynaptic autoreceptors

Serotonin (5-HT) nerve terminals innervate sympathetic preganglionic neurons of the intermediolateral cell column (IML); however, neither the depolarization-induced release of 5-HT nor the presence of presynaptic modulatory autoreceptors have been directly studied in this system. We used in vitro superfusion of the microdissected intermediate area (including the intermediolateral cell column, intercalated nucleus, and central autonomic nucleus) of the rat thoracic spinal cord to measure basal and stimulated release of preloaded [³H]5-HT. Elevated K⁺ evoked a concentration- and Ca²⁺ dependent release of [³H]5-HT. Exogenous 5-HT and the 5-HT_1B agonist, CGS-12066B, both decreased the K⁺-stimulated release of [³H]5-HT. A 5-HT_1B antagonist (methiothepin) blocked the 5-HT- and the CGS-12066B-induced inhibition of K⁺-evoked release of [³H]5-HT. A 5-HT_1A antagonist (NAN-190) did not alter the inhibitory actions of exogenous 5-HT. Moreover, a 5-HT_1A agonist (8-OH-DPAT), a 5-HT_2A/2C agonist [(+/-)-DOI hydrochloride], and a 5-HT₃ agonist (2-methyl-5-HT) did not alter the K⁺ evoked release of [³H]5-HT. These data demonstrate that 5-HT is released from the intermediate area of the rat thoracic spinal cord. The 5-HT receptor subtype involved in the inhibition of the evoked release of [³H]5-HT is of the 5-HT_1B subtype. These findings may help clarify the complex role of 5-HT in spinal regulation of the sympathetic nervous system. © 1994 Wiley-Liss, Inc

1 This article is US Government work and, as such, is in the public domain in the United States of America.

     

Management challenges and markets

The scarcity of resources in healthcare systems has general causes and country-specific causes. Common to most healthcare systems is a strong emphasis on management and an increased attention to the role of the market. Management and market are concepts which need clarification: management applies not only to individual institutions but to systems of institutions. Market implies not only the pursuit of individual interests but also the assumption of responsibility. The design or redesign of healthcare systems must take into account the level of management skills which each system and its institutions can rely on. Cost patterns in a healthcare system develop around its institutional design. Different factors produce varying levels of costs in different healthcare systems. The same applies to the effort needed to reach a certain degree of effectiveness in output. An outline of strengths and weaknesses of options for the design of healthcare systems is presented in the final part of the article. These should always be considered together with the specific features of each country.     

Postnatal development of vascular β-adrenoceptor-mediated responses and the increase in the adrenaline content of the adrenal gland have a parallel time course

The present study was undertaken to analyse the relationship between postnatal development of vascular ₂-adrenoceptor-mediated responses and the content of adrenaline in the adrenal gland and its concentration in plasma. Dog saphenous vein tissue from newborn, two-weeks old and adult animals were either preloaded with ³H-noradrenaline (or ³H-adrenaline) to study prejunctional -adrenoceptor-mediated effects or mounted in organ baths to determine isoprenaline-induced relaxation of preparations contracted by phenylephrine to about 65010 of the maximum. The adrenal glands and samples of blood from the same animals were taken for estimation of adrenaline and noradrenaline.At birth, there were no -adrenoceptor-mediated effects pre- or postjunctionally. At two weeks, while the results at the prejunctional level were not significantly different from those obtained in newborns, at the postjunctional level there was a relaxant response to isoprenaline, which antagonised about 35010 of the previous contraction to 1.75 mol·l^–1 phenylephrine. In adults, isoprenaline (50 nmol·l^–1) increased by 24% tritium overflow evoked by electrical stimulation of tissues preloaded with ³H-noradrenaline but not that of tissues preloaded with ³H-adrenaline. On the other hand, propranolol (1 mol·l^–1) reduced by 21% the overflow of tritium evoked by electrical stimulation of tissues preloaded with ³H-adrenaline but not that of tissues preloaded with ³H-noradrenaline; postjunctionally, the maximal response to isoprenaline antagonised 70% of the previous contraction to 1.75 mol·l^–1 phenylephrine.At birth the catecholamine content of the adrenals was relatively low (2.9 ol·g^–1) and the adrenaline/noradrenaline ratio was 0.26; two weeks later, the catecholamine content was 14.5 mol·g-1and the adrenaline/noradrenaline ratio was 0.74; in adults, the catecholamine content was 24.5 mol·g^–1 and the adrenaline/noradrenaline ratio was 2.3. In plasma, the highest concentration of adrenaline was observed at birth (11.8 nmol·l^–1); two weeks later it was 5.5 nmol·l^–1 and in adulthood it fell to 3.1 nmol·l^–1.On the basis of these results, it is concluded that some link between the postnatal increase in adrenaline adrenal content and the development of ₂-adrenoceptor-mediated pre- and postjunctional effects may exist. Additionally it is suggested that circulating adrenaline may trigger the development of ₂-adrenoceptor-mediated responses as well as some hypertensive states occurring as a consequence of an overreactivity of the sympathoadrenal system. Correspondence to: S. Guimarães at the above address     

Molecular genetic studies of early breast cancer evolution

Summary In the past few years there has been an explosion in the number of patients diagnosed with hyperplastic breast disease andin situ breast cancer. Based on epidemiological data, these morphologically defined lesions may be categorized as those with little malignant potential (e.g. typical hyperplasia or proliferative disease without atypia [PDWA]), those with significant malignant potential which may already be initiated (e.g. atypical ductal hyperplasia [ADH]), and early transformed lesions which are malignant but not yet invasive (e.g. ductal carcinomain situ [DCIS]). They may represent sequential evolutionary stages in the ontogeny of invasive breast cancer, with each morphologically defined stage resulting from accumulating genetic changes culminating in a transformed clonal lineage capable of invasion and metastasis. Using loss-of-heterozygosity (LOH) analysis, we are studying the genetic changes associated with these lesions in archival tissue samples. 50% (6/12) of the proliferative lesions (PDWA and ADH) and 80% of the DCIS shared their LOH patterns with more advanced lesions from the same breast, strongly supporting a precursor/product relationship between these lesions and the cancers they accompany.     

Evaluation of regional haemodynamics and alterations of vascular wall of the lower limbs in hypertensive subjects

This study was designed to analyse the relationship betweenarterial hypertension and changes in arterial blood flow andvascular wall damage of the lower limbs in hypertensive patientswith various degrees of hypertension. Six hundred and fifty-four hypertensive patients (421 malesand 233 females) aged 35 to 70 years and 88 healthy subjects(63 males and 25 females) aged 39 to 60 years were studied.Strain-gauge plethysmography of the lower limbs was used tocalculate arterial calf blood flow (RF), arterial calf bloodflow after post-ischaemic hyperaemia (PF), basal and minimalvascular resistances (BVR and MVR), time to reach peak flow(tPF), time until 50% reduction of peak flow (tT) and totalrecovery time (tT). In 108 (67 males and 41 females) of the hypertensive patients,a morphological study by echo-Doppler duplex scanning of thepopliteal artery was performed to measure medial-intimal thickeningand popliteal lumen diameter. Our results indicate that regional haemodynamics of the lowerlimbs worsened in hypertensives in comparison with control subjects.In addition, the change in peripheral haemodynamics was relatedto the degree of hypertension. Moreover, medial-intimal thickeningwas significantly (P<0.05) higher in severe hypertensivesthan mild hypertensives. Popliteal lumen diameter was significantly(P<0.05) lower in severe hypertensives than moderate andmild hypertensives. In all these subjects mean blood pressurewas correlated directly (r=0.31; P<0.001) with medial-intimalthickening and inversely (r= – 0.37; P<0.001) withpopliteal lumen diameter. Multiple regression analysis indicatedthat mean blood pressure, age and serum cholesterol were independentlycorrelated to medial-intimal thickening. This relationship wasnot influenced by the diabetic patients and smokers among thegroups. Our results indicate that hypertension impairs peripheral flowand encourages the development of medial-intimal thickening.