Quality of life on home parenteral nutrition or after intestinal transplantation.

AIM: We compared the health related quality of life (HRQOL) of stable patients on home parenteral nutrition (HPN) and of patients who underwent successful intestinal transplantation (ITx). METHODS: HRQOL was evaluated by the non-disease-specific Short Form 36 instrument, which examines eight specific domains and scores them on a scale of 0% to 100%. Patient scores were standardized for the sex-matched and age-matched group scores of the healthy population by calculating the Z-score (reduced value: Z-score < -1). RESULTS: Eighteen patients on HPN and 12 patients who underwent ITx were studied. The two groups did not differ for primary intestinal disease, cause of intestinal failure, presence of a stoma, body mass index, and employment and marital status. HPN Z-scores were physical functioning -2.3, physical role -1.5, body pain -1.0, general health -1.2, vitality -0.5, social functioning -0.9, emotional role -0.7, and mental health 0.0. ITx Z-scores were physical functioning -1.7, physical role -0.8, body pain 0.0, general health -0.4, vitality 0.0, social functioning -0.4, emotional role -0.3, and mental health 0.0. Only the body pain Z-scores differed significantly (P = .012). CONCLUSIONS: The value of the physical components of the SF-36 was reduced in all the components in the HPN patients and in the physical functioning component in the ITx patients. The mental health components were normal in both. Successful ITx showed a better subjective physical health feeling than stable HPN.

Italian guidelines for intestinal transplantation: potential candidates among the adult patients managed by a medical referral center for chronic intestinal failure.

In 2002, the Italian guidelines for eligibility of patients for intestinal transplantation (ITx) were defined as: life-threatening complications of home parenteral nutrition (HPN), lack of venous access for HPN, locally invasive tumors of the abdomen, Chronic intestinal failure (CIF) with a high risk of mortality, primary disease-related poor quality of life (QoL) despite optimal HPN. Our aim was to identify potential candidates for ITx according to these national guidelines among patients managed by a medical referral center for CIF. Records of patients who received HPN were reviewed. CIF was considered reversible or irreversible (energy by HPN <50% or >50% basal energy expenditure). Patients with irreversible CIF were considered eligible for ITx in the absence of a contraindication, as are used for solid organs Tx. From 1986 to 2003 among 64 patients who met the entry criteria 23 showed reversible and 41 irreversible, CIF. Twenty-one patients with irreversible CIF had an indication for ITx, but eight had also contraindications; thus 13 were eligible, including intestinal pseudo-obstruction (n = 6), mesenteric ischemia (n = 3), Crohn's (n = 2), radiation enteritis (n = 1), and desmoid (n = 1). Indications for ITx included HPN liver failure (n = 2), lack of venous access (n = 2), CIF with high risk of mortality (n = 3), very poor QoL (n = 6 including 5 with pseudo-obstruction). According to the Italian guidelines for ITx, 31% of patients with irreversible CIF managed by a medical referral center were eligible for ITx. Primary disease-related poor QoL was the indication in half of them. Studies on the QoL after ITx are required to allow patients to make an educated decision.

The SF-36 instrument for the follow-up of health-related quality-of-life assessment of patients undergoing home parenteral nutrition for benign disease.

INTRODUCTION: The non-disease-specific SF-36 instrument was applied to detect changes in quality of life among patients at a single center who were receiving home parenteral nutrition (HPN) for intestinal failure. METHODS: All HPN patients completed the questionnaire during routine visits. The SF-36 examines eight domains (scores: 0% to 100%): physical functioning (PF), role-functioning physical (RP), body pain (BP), general health (GH), vitality (VT), social functioning (SF), as well as role-functioning emotional (RE) and mental health (MH). Patient responses were standardized for the sex- and age-matched group scores of the healthy population by calculating the Z-score: (healthy population mean score - patient raw score)/healthy population standard deviation (reduced value: Z-score < -1). A difference in a domain score was considered significant in the individual patient if it was greater than the 90% confidence interval for healthy subjects and if it produced a change in Z-score category. General, sociodemographic, underlying disease and HPN-related factors were collected. RESULTS: For 31 enrolled adult patients, the baseline mean Z-score was reduced in five domains: PF, RP, BP, GH and SF. Twenty patients underwent a second SF-36 assessment 10 +/- 2 months later: the HRQOL worsened in eight and improved in 10 (no. worsened domains > no. improved or vice versa). The worsened subgroup showed a decrease in body mass index (P =.104), an increase in the number of HPN infusions per week (P =.065), and a greater incidence of intestinal motility disorders (P =.161), of liquid oral diet (P =.027), and of nycturia (P =.028). CONCLUSIONS: The SF-36 instrument reflecting the generic HRQOL assessment may be a suitable tool for patients on HPN.

Safety and efficacy of home parenteral nutrition for chronic intestinal failure: a 16-year experience at a single centre.

BACKGROUND: Comparisons between safety and efficacy of home parenteral nutrition and of intestinal transplantation for treatment of chronic intestinal failure derived from observational studies. AIMS: To present the 16-year experience of home parenteral nutrition by the Chronic Intestinal Failure Centre of Bologna University. PATIENTS: A total of 40 adult patients were enrolled between 1986 and 2001. METHODS: Safety indices: survival and cause of death, catheter-related bloodstream infection, deep vein thrombosis, liver disease. Efficacy indices: nutritional and rehabilitation status, quality of life (SF36 instrument), re-hospitalisation rate. STATISTICS: Kaplan-Maier analysis and Cox model for survival probability and risk factors; logistic regression for catheter-related bloodstream infection risk factors. RESULTS: Survival rates at 1, 3 and 5 years were 97, 82 and 67% respectively. Survival was higher in patients < or = 40 years. One death was home parenteral nutrition-related. Incidence of catheter-related bloodstream infection: 0.30/year home parenteral nutrition, was lower in patients treated by a specialized nursing protocol. Incidence of deep vein thrombosis was 0.05/year home parenteral nutrition. Hepatosteatosis occurred in 55%. Body weight remained stable or increased in 80%. Rehabilitation was total or partial in 74%. Re-hospitalisation rate was 0.70/year home parenteral nutrition. Quality of life scored significantly lower than in healthy populations in six out of eight domains. CONCLUSIONS: Home parenteral nutrition is a safe and efficacious therapy for chronic intestinal failure. Survival compares favourably with survival after intestinal transplantation.

Pulsatile secretion of ACTH and cortisol in premenopausal women: effect of obesity and body fat distribution.

OBJECTIVE: There is emerging evidence that women with visceral obesity may have hyper-responsiveness of the hypothalamic-pituitary-adrenal axis. There are no studies on basal daily secretory pattern of ACTH and cortisol in subjects with different obesity phenotypes. DESIGN AND PATIENTS: In this study we examined daytime pulsatile secretion of ACTH and cortisol in two groups of premenopausal obese women with visceral (V-BFD) (BMI 37.1 +/- 1.7) and subcutaneous (S-BFD) (BMI 38.8 +/- 1.5) body fat distribution (measured by CT scan) and in a group of normal weight healthy controls (BMI 21.1 +/- 0.5). After an overnight fast, blood samples were taken at 15-minute intervals for 12 h (49 samples, from 0800 h until 2000 h). All women avoided breakfast but had a normal lunch and dinner, both containing similar food, energy and nutrient composition. ACTH and cortisol responses to mixed meals at noon and in the evening were also investigated. RESULTS: Mean values of ACTH and cortisol did not differ between the groups. However, ACTH pulse frequency was significantly higher in V-BFD (P < 0.06) and S-BFD (P < 0.02) obese women than in controls, without any significant differences between the two obese subgroups. Mean ACTH pulse amplitude was lower in the V-BFD than in S-BFD obese (P < 0.02) and control (P < 0.05) groups. Cortisol episodic characteristics did not differ between V-BFD and S-BFD obese and controls. All differences in ACTH pulsatile parameters between obese and controls and between the two obese subgroups were evident only in the morning, with no further significant differences during the early and late afternoon. There were no significant differences in cortisol parameters during the three periods of the day between the various groups, apart from late afternoon cortisol pulse frequencies, which were significantly lower in V-BFD than in controls. After lunch, ACTH and cortisol levels significantly increased in all groups, but the cortisol increase tended to be more rapid in V-BFD than in the other two groups. After dinner, ACTH significantly increased in V-BFD and controls but not in the S-BFD group, whereas cortisol rose significantly in all groups, but significantly less in S-BFD than in V-BFD and controls. CortisolAUC (but not ACTHAUC) after lunch was significantly higher than after dinner in all groups. ACTH response after each meal was similar in all groups, but cortisolAUC after dinner was significantly lower in S-BFD than in V-BFD women. CONCLUSION: This study demonstrates that in premenopausal women, obesity, particularly the visceral phenotype, is associated with several abnormalities of ACTH pulsatile secretion, particularly in the morning. On the contrary, no major differences were present in either blood concentrations, diurnal rhythm or secretory pattern of cortisol between obese and controls. The responses to meals seem to indicate a much more rapid cortisol response after lunch in women with visceral obesity and a reduced activation of the hypothalamic-pituitary-adrenal axis after dinner in women with subcutaneous obesity.

[Finasteride: a new drug for the treatment of male hirsutism and androgenetic alopecia?]. / La finasteride: un nuovo farmaco nel trattamento dell'irsutismo e dell'alopecia androgenica maschile?

Finasteride is a drug which inhibits the transformation of testosterone into its active metabolite, dihydrotestosterone, in the target organs, i.e. the skin, the scalp, the liver and the prostate. In the pathogenic mechanism of hirsutism and androgenetic alopecia, and important role is presumably played by alterations of the mechanisms which transform testosterone into dihydrotestosterone. In some conditions an increase in dihydrotestosterone has been demonstrated, due to increased activity of the enzyme 5 alpha-reductase. The effect of finasteride develops above all at the level of type II 5 alpha-reductase. Recent studies have evaluated the effect of finasteride in patients of both sexes with hirsutism and androgenetic alopecia. In women with various forms of hyperandrogenism, the use of the drug at the doses commonly used for the treatment of benign prostatic hyperplasia seems to have induced a significant reduction in the degree of hirsutism. Furthermore, both in animals and men with alopecia, the drug seems to have led to an increase in the number and an improvement in the shape of the follicles in the anagen phase, and a simultaneous decrease of dehydrotestosterone at the level of the scalp. This study represents a review of the main results obtained over the last two years and reports the prospects which the use of finasteride may have in this context.

Hypothalamic-pituitary-adrenal axis activity and its relationship to the autonomic nervous system in women with visceral and subcutaneous obesity: effects of the corticotropin-releasing factor/arginine-vasopressin test and of stress.

In a previous study, we demonstrated that premenopausal women with visceral obesity have hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, characterized by an exaggerated hormone response to corticotropin-releasing factor (CRF) and corticotropin (ACTH) stimulation. The hypothalamic peptide flow that stimulates the pituitary, particularly after a physiological stress challenge, involves not only CRF, but also arginine-vasopressin (AVP), which synergizes the CRF capacity to stimulate pituitary hormone secretion. Previous studies in humans have demonstrated that combining AVP with CRF permits maximal stimulation of the pituitary, providing a more appropriate method of assessing pituitary hormone reserve. We therefore investigated the response of the HPA axis to combined CRF and AVP stimuli in obese women with different obesity phenotypes. Moreover, we examined hormonal and cardiovascular responses to several mental stress tasks, according to previously standardized procedures. Two groups of age-matched premenopausal eumenorrheic obese women with visceral (V-BFD) or subcutaneous (S-BFD) body fat distribution and a group of normal-weight healthy controls were investigated. All women randomly underwent the following protocol: (1) a combined CRF/AVP test (100 micrograms plus 0.3 IU intravenously [IV], respectively); (2) a standardized stress test, which consisted of completing two puzzles and a mental arithmetic test; and (3) a control saline test. Blood samples for ACTH and cortisol determinations were obtained before and during each test, and measurements of arterial blood pressure and pulse rate were made at regular intervals during the stress test. After combined CRF/AVP administration, ACTH and cortisol were significantly higher in V-BFD than in the other two groups. In contrast, no significant hormonal variation was found in either group during stress tasks. During the stress test, pulse rate (but not arterial blood pressure) significantly increased after 8 and 15 minutes in the V-BFD group, whereas no significant variation was found in S-BFD and control women. A significant correlation was present between the pulse rate and change in cortisol level during the stress test at minutes 8 (r=.54, P<.05) and 15 (r=.57, p<.01) in all women considered together. Subjective emotional involvement during stressful tasks was measured by a two-dimensional short verbal scale, which revealed that the stress section had a more significant impact in obese V-BFD than in S-BFD and control women. These data therefore confirm that women with visceral obesity have hyperactivity of the HPA axis, and that the combined CRF/AVP stimulation may offer a good tool for investigating pituitary reserve in this obesity phenotype. Moreover, the results indicate that these women probably have a hyperreactive sympathetic response to acute stress that seems interrelated to that of the HPA axis.

Nitrendipine treatment in women with polycystic ovarian syndrome: evidence for a lack of effects of calcium channel blockers on insulin, androgens, and sex hormone-binding globulin.

It has been shown that in vitro calcium channel blockers may regulate insulin secretion, and in vivo studies have demonstrated that they can reduce the degree of hyperinsulinemia and ameliorate the insulin-resistant state in subjects (particularly men) with obesity and hypertension. It is also commonly accepted that hyperinsulinemia may be an important factor responsible for the development of hyperandrogenism in obese women with polycystic ovarian syndrome (PCOS). We, therefore, investigated whether the administration of nitrendipine, a widely used calcium channel blocker, may improve both insulin levels and hyperandrogenism in a group of seven insulin-resistant hyperinsulinemic women with obesity and PCOS. They were treated for 7-8 days with oral nitrendipine (10 mg, twice daily) or placebo using a double blind, cross-over design. Before and after treatment, blood samples were obtained for androgen and sex hormone-binding globulin determinations, and an oral glucose tolerance test was performed, measuring glucose and insulin. Both nitrendipine and placebo failed to decrease basal and stimulated insulin levels. Moreover, no significant variations in testosterone, dehydroepiandrosterone sulfate, or sex hormone-binding globulin concentrations were observed after either treatment. Therefore, these data fail to support previous suggestions that calcium channel blockers may play a role in the treatment of hyperandrogenism and hyperinsulinemia in obese women with PCOS.