[Psychological and social support for patients with mastectomies]. / Il supporto psicologico e sociale alle pazienti mastectomizzate.

Cancer patients need general emotional support but doctors and nurses often fail to recognise patients needs. This literature review aims at demonstrating the effect of social and psychosocial support on breast cancer women. All the article published from 1980 were reviewed. Psychotherapeutic counselling and psychosocial interventions were given by a range of people, including nurses, psychologists, psychiatrists and volunteers. Unfortunately the poor quality of the studies, which are often small and poorly controlled, does not allow to make a definitive statement on the impact of psychosocial interventions. The multiplicity of types of intervention and outcomes used make comparisons between studies difficult. However, when considered in conjunction with the evidence that informal social support from partners, friends and relatives is associated with better outcomes, this research highlights the importance of psychosocial factors for breast cancer patients.

Value of buserelin testing in the evaluation of hirsute women.

It has been recently reported that many hirsute women are affected with functional ovarian hyperandrogenism (FOH)-a term that encompasses the heterogeneous polycystic ovary syndrome- and show an abnormal ovarian steroidogenic response to gonadotropin-releasing hormone (Gn-RH) agonists. The aims of the present study were to determine the prevalence of FOH by the assessment of 17-hydroxyprogesterone (17-OHP) response to the Gn-RH agonist buserelin, to correlate these abnormal responses to other parameters suggestive of PCOS, and to assess the possible adrenal origin of hyperandrogenism. Therefore, in 33 consecutive women with hirsutism serum LH, FSH, 17-OHP, dehydroepiandrosterone sulfate (DHEA-S), androstenedione (A), cortisol levels were evaluated in basal conditions and after the administration of buserelin (0.5 mg sc) and ACTH (tetracosactide 0.25 mg iv). Two patients were affected with a non classic congenital adrenal hyperplasia (CAH)-21OH deficiency. In 5 other women ACTH test caused a rate increase 17-OHP (30-0)/30 min > 19 nmol/L/min (0.25 +/- 0.03; mean +/- SE), suggesting the possible existence of heterozygote non classic CAH-21OH. One patient showed a DHEA-S response to ACTH (from 10.3 to 17.2 mumol/L), which was compatible with late-onset 3 beta-Hydroxy-delta 5 steroid dehydrogenase deficiency. Out of the 25 patients with normal responsiveness to ACTH, 11 women (group A) showed higher 17-OHP and A levels, in comparison to normal women, both in basal conditions (17-OHP = 4.18 +/- 0.72 vs 1.74 +/- 0.34 nmol/L, p < 0.005; A = 11.8 +/- 1.2 vs 6.0 +/- 0.7 nmol/L, p < 0.05) and after buserelin (17-OHP = 15.61 +/- 1.31 vs 6.96 +/- 0.9 nmol/L; A = 19.0 +/- 1.9 vs 7.5 +/- 0.8 nmol/L; p < 0.001). In 6 of these 11 patients basal and buserelin-stimulated LH levels were higher than in normals. The remaining 14 patients (group B) showed normal baseline and buserelin-stimulated 17-OHP and A concentrations. In this group only 2 patients had high basal and stimulated LH levels. An augmented LH/FSH ratio was present in 5 and 1 cases of groups A and B, and polycystic ovaries at ultrasonography were observed in 7 and 8 cases of groups A and B, respectively. It is to note that an abnormal 17-OHP response to buserelin was present also in 3 of the 5 patients with abnormal 17-OHP rise after ACTH test, suggesting an adrenal and ovarian cause of hyperandrogenism. In conclusion, an abnormal response to one or both stimulation test was present in 57% of cases: an adrenal origin of hirsutism was detected in 15%, a combined adrenal and ovarian origin was found in 9% and an ovarian cause was present in 33%. Buserelin testing is an useful means to reveal the presence of FOH.

Abnormalities of endocrine function in patients with clinically "silent" adrenal masses.

Because, in recent years, patients with incidentally discovered adrenal masses have been encountered increasingly, their endocrine function was investigated in basal conditions and after dynamic tests. Thirty-two patients (23 women and 9 men, aged 28-74 years) were studied. Lesion diameter, as documented by computed tomography and/or nuclear magnetic resonance imaging, ranged between 5 and 65 mm; the tumors were localized on the right in 22 patients, on the left in 5 and bilaterally in 5 cases. In basal conditions, urinary free cortisol (UFC) excretion, plasma adrenocorticotropin (ACTH) and cortisol levels were normal, except for 4 patients who showed high UFC and ACTH levels in the low-normal range. Ovine corticotropin-releasing hormone (CRH, 1 microgram/kg iv) was given to 18 patients, inducing normal ACTH and cortisol responses in 12, blunted responses in 4 and no response in 2 cases. No reduction in ACTH and cortisol levels after suppression tests was observed in 4 of 29 patients after dexamethasone (1 mg overnight) or in 6 of 29 after loperamide. The 4 patients who were unresponsive to both tests did not show any further inhibition after high-dose dexamethasone administration, had low plasma ACTH levels and showed impaired or absent responses to the CRH test: they were diagnosed as affected with preclinical Cushing's syndrome. An exogenous ACTH test performed in 30 patients caused a normal cortisol rise. Basal mean 17-hydroxy-progesterone (17-OHP) levels were not different from those in normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term thromboxane-synthase inhibition prolongs survival in murine lupus nephritis.

Systemic lupus erythematosus (SLE) is an autoimmune disease, characterized by nephritis, in which mortality is largely influenced by the severity of renal involvement. As there are evidences that thromboxane (TX)A2 plays an important role in the pathogenesis of lupus nephritis, we decided to assess the effects of long-term suppression of TXA2 synthesis on the progression of the disease, by designing a study of TXA2-synthase inhibition having adequate size to detect an effect on mortality as the primary end-point. Thus, we randomized 362 NZBxNZW mice (11-week-old at entry) to one of the following treatments: a TXA2 synthase inhibitor, FCE 22178 (300 mg/kg daily), saline or cyclophosphamide (5 mg/mouse weekly x 4 weeks) used as reference treatment. The TXA2 synthase inhibitor suppressed TXA2 biosynthesis, as reflected by urinary TXB2 and 2,3-dinor-TXB2 excretion (by 78% and 90%, respectively) and significantly reduced mortality (death rate: 34% vs. 61% in controls, at 37 weeks, P < 0.01). A significant reduction in proteinuria (9 +/- 1.6 vs. 17.3 +/- 2.4 mg/24 hr in FCE 22178 vs. saline, P < 0.01) and glomerular lesions was observed up to 30 weeks but not at 37 weeks. In contrast, cyclophosphamide prevented the development of proteinuria and histologic lesions, and reduced mortality to 8% at 37 weeks. Renal plasma flow and glomerular filtration rate were lower (by 29% and 52%, respectively) in 37-week-old as compared to young NZBxNZW mice. These parameters were further depressed by cyclophosphamide (by 48% and 45% vs. age-matched controls, respectively, P < 0.01) but were not altered significantly by FCE 22178.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth abnormalities in cultured mesangial cells from rats with spontaneous glomerulosclerosis.

Age-related glomerulosclerosis (GS) occurs in normotensive rats of the Milan strain (MNS), but not in genetically-matched hypertensive animals (MHS). Altered mesangial cell (MC) proliferation and matrix expansion are common features of the glomerular scarring process. We evaluated proliferation and matrix protein synthesis of cultured MC from MNS and MHS animals aged 1 and 8 months, that is, before and after the occurrence of GS. [3H]-thymidine (TdR) incorporation into DNA of MC from MNS rats stimulated by 10% FBS serum increased with donor aging from 115 +/- 6.0 to 176 +/- 15, P < 0.01 (% cpm/well over quiescent controls +/- SEM). Under the same experimental conditions, cell counts changed from 101 +/- 4.0 to 146 +/- 5.0, P < 0.01 (% cells/well over quiescent controls). Additionally, cytosolic Ca2+ concentration ([Ca2+]i) rised from 115 +/- 19 to 220 +/- 32 nM and from 112 +/- 24 to 734 +/- 136 nM when fura-2-loaded cells from young and old MNS rats, respectively, were stimulated with 1% FBS. The rate of collagen production also increased with donor age, as well as collagen IV and laminin B1 mRNA expression. In contrast, in MC from MHS rats both DNA synthesis and cell replication rate declined as function of donor age. No differences in the [Ca2+]i responses to FBS were observed, nor collagen production changed with MHS rat senescence. We conclude that the age-associated decline of proliferative activity in MC from MHS animals could actually reflect a normal process of cell aging, possibly protecting from the occurrence of GS.(ABSTRACT TRUNCATED AT 250 WORDS)

Agents combining thromboxane receptor antagonism with thromboxane synthase inhibition: [[[2-(1H-imidazol-1-yl)ethylidene]amino]oxy]alkanoic acids.

A new class of compounds combining thromboxane-A2 (TxA2) receptor antagonism and thromboxane synthase inhibition is described. A first series of (E)- and (Z)-[[[2-(1H-imidazol-1-yl)ethylidene]amino]oxy]pentanoic acids showed relevant thromboxane synthase inhibition associated with weak TxA2 receptor antagonism, while a series of (+/-)-(E)-[[[2-(1H-imidazol-1-yl)-3-phenylpropylidene]amino]oxy] pentanoic acids, structurally derived from the former, showed potent and well-balanced dual activity. Structural requirements for significant single and dual activity are discussed. Two close congeners of the latter series, (+/-)-(E)-5-[[[1-cyclohexyl-2-(1H-imidazol-1-yl)-3- phenylpropylidene]amino]oxy]pentanoic acid 23c and its p-fluorophenyl analog 23m, inhibited TxB2 production in vitro, in rat whole blood during clotting, with IC50 of 0.06 and 0.37 microM and antagonized the binding of [3H]SQ 29548 to washed human platelets, with IC50 of 0.08 and 0.02 microM, respectively. These two compounds were selected for further pharmacological evaluation and were shown to antagonize U46619-induced platelet aggregation in human platelet rich plasma with IC50 of 0.30 and 0.44 microM, respectively. They were both orally available, and in particular 23m caused a long lasting ex vivo TxA2 synthase inhibition in the fed rat. The levorotatory enantiomer of 23c, stereospecifically synthesized as a model compound, was found to be more potent than racemic 23c with regard to TxA2 receptor antagonism (IC50 = 0.04 microM) and equivalent to the latter with regard to TxA2 synthase inhibition. A molecular modeling study concerning the levorotatory enantiomer of 23c (S), TxA2, and representative TxA2 antagonists of different classes led to the definition of a putative pharmacophoric model for the TxA2 receptor ligands.

Consequences of acute nitric oxide synthesis inhibition in experimental glomerulonephritis.

To assess the functional relevance of the enhanced glomerular nitric oxide (NO) synthesis during acute nephrotoxic serum (NTS) nephritis, a NO synthesis inhibitor (NOI) NG-monomethyl-L-arginine was administered to normal (N + NOI) and acutely nephritic (NTS + NOI) Munich-Wistar rats, and systemic and glomerular hemodynamic responses were contrasted with those observed in vehicle-treated normal and nephritic (NTS) controls. Urinary protein excretion rates were equal in normal and N + NOI rats but were markedly elevated in NTS animals and further increased in NTS+NOI. NO inhibition in normal animals (normal versus N + NOI) led to reductions in glomerular plasma flow rate and the glomerular capillary ultrafiltration coefficient (Kf) and elevations in afferent and efferent arteriolar resistances and net transcapillary hydraulic pressure difference (delta P), as well as an increase in systemic arterial pressure. The increase in delta P offset the falls in glomerular plasma flow rate and Kf, and GFR was preserved. Directionally similar responses in efferent resistance occurred in NTS + NOI compared with NTS, however, afferent resistance was not further affected by NOI. Additionally, although Kf was severely depressed in the NTS group (approximately 60% versus normal), it was not further depressed by NOI treatment. Polymorphonuclear cell (PMN) infiltration/glomerulus was mildly increased in N + NOI over normal. In contrast, PMN number in NTS + NOI rats was diminished as compared with NTS.(ABSTRACT TRUNCATED AT 250 WORDS)

Value of serum dehydroepiandrosterone sulfate assay in the evaluation of pituitary-adrenal insufficiency after pituitary adenomectomy.

The value of dehydroepiandrosterone sulfate (DHEA-S), a specific marker of adrenal androgen production, in the assessment of clinical states of hypercortisolism and hypocortisolism has been suggested. Since the way to simply test for ACTH reserve in patients (pts) with pituitary tumors after adenomectomy is not standardized, in this study serum DHEA-S concentration was measured in order to establish whether its determination might be a sensitive index of ACTH deficiency. Serum DHEA-S concentration was evaluated in 29 pts with hypothalamic-pituitary tumors (16 females, 13 males, aged 20-70 yr), 14 of whom had GH-secreting adenomas, 13 nonfunctioning adenomas, 1 prolactinoma and 1 craniopharyngioma. Serum DHEA-S and cortisol (F) levels were determined both before and every day for 8 days after pituitary adenomectomy. Before surgery in all pts mean DHEA-S and F basal values were 3.57 +/- 0.42 mumol/L and 391.8 +/- 29.0 nmol/L, respectively. Eight out of 29 pts showed reduced DHEA-S levels (0.85 +/- 0.19 mumol/L), which remained lower than normal in the postsurgical period; on the contrary, F levels were reduced in only 2 and 3 cases before and after surgery, respectively. In 3 other pts DHEA-S levels were normal before surgery and then were low in the postoperative period, while serum cortisol remained normal in all cases. In most of these patients, the finding of impaired responses to hypothalamic-pituitary-adrenal tests, together with a reduced corticosteroid urinary excretion, confirmed the existence of a secondary hypoadrenalism and the necessity for an adequate replacement therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Differences in ouabain-induced natriuresis between isolated kidneys of Milan hypertensive and normotensive rats.

1. Several observations support the hypothesis that in rats of the Milan hypertensive strain elevated levels of a circulating ouabain-like factor might normalize the elevated Na+ reabsorption, but, on the other hand, might contribute to the development of hypertension. 2. As the receptor occupancy of this endogenous factor seems to be reversible, the aim of our study was to test, in vitro, the hypothesis of its presence in isolated kidneys from Milan hypertensive rats by studying the response to exogenous ouabain before and after prolonged washing. 3. The kidneys were isolated from adult Milan hypertensive rats and from age-matched normotensive controls and ouabain was given at two different experimental time intervals: shortly (15 min) after washout or after a further 60 min of washout (75 min in total). Comparative experiments with the diuretic hydrochlorothiazide were performed using the same protocol. 4. Ouabain given after 15 min of perfusion caused an increase in renal vascular resistance, diuresis and natriuresis; these haemodynamic and tubular responses were similar in kidneys from both Milan hypertensive and Milan normotensive rats. If given after the washout period, ouabain caused a comparable increase in renal vascular resistance, but a significantly greater natriuresis in kidneys from Milan hypertensive rats as compared with kidneys from Milan normotensive rats. On the other hand, hydrochlorothiazide caused similar natriuresis in kidneys from both strains after washout. 5. These results support the hypothesis that a factor, capable of interacting with the ouabain receptor on the Na+/K(+)-ATPase of tubular cells, is present in the kidney of adult Milan hypertensive rats and that it can be removed by prolonged washout.

Proarrhythmic activity of intracoronary endothelin in dogs: relation to the site of administration and to changes in regional flow.

The endothelium-derived peptide, endothelin, has been shown to exert powerful constrictor activity in both isolated and in situ coronary arteries. Recent in vitro data on isolated cardiac myocytes suggest that the substance might also possess electrophysiologic properties. We investigated the possibility that endothelin (ET-1) may exert proarrhythmic effects when infused selectively in the coronary circulation of open-chest-anesthetized dogs. Animals were instrumented for the measurement of left anterior descending (LAD) or left circumflex (LCX) coronary artery blood flow, left systolic ventricular pressure (LSVP), dP/dtmax, mean arterial pressure (MAP), and epicardial electrocardiogram (ECG; three leads). Data were recorded during infusion (2 min) of saline (n = 5) or increasing doses of endothelin (5-80 pmol/kg) given selectively in either the LCX (n = 10) or the LAD (n = 10). When infused into the LCX, endothelin produced a dose-dependent decrease in flow (40 +/- 23% at 80 pmol/kg, mean +/- SD, p less than 0.01) with a concomitant increase in coronary resistance and a decrease in dP/dtmax and MAP. ECG changes typical of myocardial ischemia paralleled the decrease in flow and culminated in ventricular fibrillation at the highest dose (80% of dogs). Endothelin caused similar hemodynamic effects when infused in the LAD, but fatal arrhythmias occurred for lower doses and for little or no change in coronary blood flow. Thirty percent of the animals died at 10 and 60% died at 20 pmol/kg, doses that induced only a moderate decrease (8 +/- 7 and 21 +/- 12%, respectively) in LAD total blood flow. Ventricular tachycardia always preceded ventricular fibrillation and death.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of racemic, S- and R-indobufen on cyclooxygenase and lipoxygenase activities in human whole blood.

Racemic indobufen inhibits human platelet aggregation by reducing thromboxane (TX) A2 biosynthesis. In order to ascertain which of the two optical isomers is responsible for its pharmacological activity, we compared the effects of racemic (SR +/-), S(+) enantiomer and R(-) enantiomer indobufen on cyclooxygenase and 5-lipoxygenase activities by assessing the biosynthesis of TXB2, prostaglandin (PG) E2 and leukotriene (LT) B4 in human whole blood stimulated with the Ca2+ ionophore A23187. Racemic indobufen caused a dose-dependent inhibition of TXB2 and PGE2 production (IC50: 0.53 +/- 0.06 and 0.34 +/- 0.02 micrograms/ml, respectively; mean +/- S.D., n = 4). S-Indobufen was approximately 2-fold more potent than the racemate in inhibiting the synthesis of cyclooxygenase products. R-Indobufen affected the same enzyme but only at considerably higher concentrations (IC50: 53 +/- 8 micrograms/ml, n = 3). Serum LTB4 concentrations were significantly reduced only at indobufen concentrations greater than 50 micrograms/ml. In conclusion, indobufen is a selective inhibitor of the cyclooxygenase activity of platelet PGG/H synthase in a concentration range corresponding to the therapeutic plasma levels in man. This inhibitory effect is largely due to the S isomer of the drug.

Role of enhanced glomerular synthesis of thromboxane A2 in progressive kidney disease.

Normotensive rats of the Milan strain (MNS) spontaneously develop focal glomerulosclerosis. In order to explore the contribution of glomerular thromboxane (TX) A2 synthesis to the development of the disease, we have characterized the time course of renal functional and biochemical changes, and their modification by long-term treatment with a TX-synthase inhibitor. Oral administration (150 mg.kg-1 from 1 to 14 months of age) of FCE 22178 suppressed enhanced glomerular TXB2 production at all experimental times (mean inhibition 80%) and proteinuria (varying between 27.1 and 73.0%) while preserving renal blood flow and glomerular filtration rate. These effects of TX-synthase inhibition were seen in the absence of any statistically significant changes in systemic blood pressure. Moreover, FCE 22178 had no antihypertensive effects in hypertensive rats of the Milan strain (MHS) nor in spontaneously hypertensive rats (SHR). Treatment also prevented the age-related hypoalbuminemia and hyperlipidemia observed in control MNS and significantly (P less than 0.01) reduced glomerular histologic damage, as demonstrated by light microscopy studies and measurement of sclerotic area. We conclude that: 1) MNS rats provide an animal model of long-lasting proteinuria characterized by an age-related increase in glomerular TXB2 production paralleled by progressive loss of renal structural integrity and function and by a secondary dyslipidemia; 2) pharmacological inhibition of glomerular TX-synthase attenuates the structural as well as the functional expression of kidney disease, without a primary effect on systemic blood pressure. These data are suggestive of an important modulating role of TXA2 in the progression of MNS renal disease.

Precocious puberty in a boy with a PRL-, LH- and FSH-secreting pituitary tumour: hormonal and immunocytochemical studies.

The case of a 7-year-old boy affected with precocious puberty and a large intra- and suprasellar pituitary tumour is described. He had hyperprolactinemia and elevated serum LH, FSH and testosterone concentrations. Pre-operative dynamic hormonal studies showed a rise of PRL, LH and FSH levels after TRH (200 micrograms iv) and a rise of LH and FSH after GnRH (100 micrograms iv). Dopamine infusion (4 micrograms.kg-1.min-1 for 180 min) did not affect gonadotropins and greatly reduced serum PRL. GnRH analogue (buserelin, 0.5 mg sc t.i.d. for 10 days) administration inhibited both LH and FSH, but did not affect PRL concentration. Serum LH and FSH increased after ethinyl-estradiol (0.5 mg orally) administration, and were not affected by bromocriptine (5-7.5 mg/day for 10 days), which decreased serum PRL levels. The patient underwent transfrontal neurosurgery and a large tumour mass was completely removed. Morphological study of the excised tumour, by electron microscope double label immunotechnique, revealed that a large number of tumour cells (70-85%) were positive for PRL, LH and FSH, co-localized in the same secretory granule. After neurosurgery, serum PRL, LH, FSH and testosterone levels fell to within the normal limits. Two months later the patient was well and signs of precocious puberty had partially regressed; hormone levels were in the normal range and MR imaging control did not demonstrate any residual lesion in the sellar region.

Diuretic effect of bumetanide in isolated perfused kidneys of Milan hypertensive rats.

The Milan hypertensive strain of rats (MHS) is characterized in the prehypertensive phase (4 weeks of age) by a significantly faster bumetanide-sensitive cell membrane Na+,K+,Cl(-)-cotransport as compared to matched normotensive controls (MNS). The isolated kidney preparation, which allows the study of renal function under controlled in vitro conditions, was chosen to compare the natriuretic effect of the loop diuretic, bumetanide, to that of two other diuretics (amiloride and hydrocholorothiazide) acting on different parts of the nephron. Concentrations ranging from 10(-7) to 10(-4) M were tested in 4-week-old MHS and MNS. Our results showed that the natriuretic response to all diuretics was greater in MHS as compared to MNS when evaluated as absolute Na+ excretion (UNA+); this is likely because of the faster basal glomerular filtration rate (GFR) in the hypertensive strain (874 +/- 126 in MHS vs. 556 +/- 33 microliters.min-1.g-1 k wt in MNS, P less than 0.05). However, when calculated either as a difference from basal values (delta UNa+), or per ml of glomerular filtration rate, the response of MHS kidneys to amiloride and hydrochlorothiazide was similar in the two strains: delta UNa+ after amiloride at (10(-4) M was + 2.1 +/- 0.7 in MHS versus + 1.2 +/- 0.2 mumol.g-1.g-1 k wt in MNS; after hydrochlorothiazide 10(-4) M it was + 1.7 +/- 0.9 in MHS versus + 1.1 +/- 0.4 mumol.min-1.g-1 k wt in MNS, values not statistically different.(ABSTRACT TRUNCATED AT 250 WORDS)