The Apparent Asymmetrical Relationship Between Small Bowel Bacterial Overgrowth, Endotoxemia, and Liver Steatosis and Fibrosis in Cirrhotic and Non-Cirrhotic Patients: A Single-Center Pilot Study.

Introduction: Gut microbiota are a complex ecosystem harboring our intestine. They maintain human body equilibrium, while their derangement, namely, "dysbiosis", has been associated with several gastrointestinal diseases, such as liver steatosis (NAFLD) and liver cirrhosis. Small intestinal bacterial overgrowth (SIBO) is an example of dysbiosis of the upper gastrointestinal (GI) tract. Aim: The aim of this study is to evaluate the relationship between SIBO and levels of endotoxemia and grade of liver steatosis (LS) and liver fibrosis (LF) in hepatologic patients. Materials and Methods: Consecutive outpatients referred to our hepatology clinic were tested for SIBO by the lactulose breath test (LBT) and peripheral blood levels of endotoxemia; LS grading and LF were assessed by abdominal ultrasound and transient elastography, respectively. Results: Fifty-two consecutive patients (17 with alcohol abuse (4.5 ± 0.8 alcohol units per day), 4 with HCV and 2 with HBV infection, 24 of metabolic origin, 2 of autoimmune origin, and 3 with cholangiopathies; mean age 54.7 ± 8.3 years, 31 F, BMI 24.1 ± 1.1 Kg/m2) and 14 healthy volunteers (HV) (mean age 50.1 ± 4.3 years, 9 F, BMI 23.3 ± 1.1 Kg/m2) were enrolled. SIBO prevalence was significantly higher in cirrhotic (LC) vs. non-cirrhotic (LNC) patients and vs. HV (all, p < 0.05), with a significant positive trend according to Child-Pugh status (all, p < 0.05). SIBO prevalence was not correlated with LS stages (all, p = NS). Consensually, endotoxin levels were significantly higher in LC vs. LNC and vs. HV (all, p < 0.05) and significantly correlated with LF in patients with LC, according to Child-Pugh status (all, p < 0.05). Conclusion: This study shows that SIBO prevalence and relative endotoxin blood levels seem to be significantly associated with the grade of LF vs. LS in LC. SIBO is also present under pre-cirrhotic conditions, but its prevalence seems to correlate with liver disease irreversible derangement.

Effects of enteral nutrition on patients with pressure lesions: a single center, pilot study.

OBJECTIVE: Protein-energetic malnutrition (PEM) affects prognosis and mortality in elderly patients as an inadequate nutritional status is a risk factor for the development and worsening of pressure sores (PS). We aimed to evaluate the incidence of PEM in outpatients with PS and to study the impact of nutritional support on the stage of PS. PATIENTS AND METHODS: PS patients, divided in a group treated with artificial nutrition (group A) and those fed orally (group B) at home, were consecutively enrolled in the Integrated Home Care program of Ascoli Piceno between June and September 2015. At T0 the patients underwent medical history, nutritional, anthropometric/biochemical parameters assessment, and the staging of the PS. The same assessments and staging of the pressure lesions were performed three months later (T1). RESULTS: Group A (n=25) started from a better nutritional status vs. group B (n=25) at T0, according to MNA assessment. Group A showed a significant improvement of nutritional status correlating with detailed control of nutrients intake and improvement of PS stage (T0 vs. T1, p<0.05). On the other hand, group B showed a significant difference between nutrients intake and nutritional needs that correlated with both malnutrition state increase and worsening of the PS staging (T0 vs. T1, p<0.05). CONCLUSIONS: The present study shows that PEM has a significant prevalence in the elder, in general, and in older people with PS, in particular. A targeted nutritional intake can prevent and help the healing of PS.

Impact of patients nutritional status on major surgery outcome.

OBJECTIVE: Surgery is a major stress factor that activates several inflammatory and catabolic pathways in man. An appropriate nutritional status allows the body to react properly to this stressor and recover in a faster and more efficient manner. On the other hand, malnutrition is related to a worse surgery outcome and to a higher prevalence of comorbidities and mortality. The aims of this study were to evaluate the nutritional status of patients undergoing major surgery and investigate the potential correlation between malnutrition and surgical outcomes. PATIENTS AND METHODS: Mini Nutritional Assessment (MNA) and global clinical examination (including biochemical parameters and comorbidities existence) were undertaken in 50 consecutive patients undergoing major surgery. Patients' clinical conditions were re-evaluated at 3 and 6 days after surgery, recording biochemical parameters and systemic and/or wound-related complications. RESULTS: A compromised nutritional status was present in more than half (54%) of patients (malnutrition in 10% and risk of malnutrition in 44% of patients, respectively). Females were slightly more at risk of malnutrition (48% vs. 41%, p=NS, females vs. males) and clearly malnourished (14% vs. 7%, p<0.05, females vs. males). Age was an independent risk factor for malnutrition and within the elders' group (> 80 years old) 16.70% of patients was diagnosed with malnutrition and 58.3% was at risk of malnutrition. Systemic complications were registered in all patients both at 3 and 6 days after surgery. However, well-nourished and at-risk of malnutrition patients had earlier complications that only partially resolved within six days after the operation. Malnourished patients showed fewer complications at the 3rd post-surgery follow-up day but had a worse outcome six days after surgery. CONCLUSIONS: Older age and but not female sex are independent risk factors for malnutrition development in patients undergoing major surgery. More interestingly, more than half of patients with an impaired nutritional status presented a less appropriated stress response to surgery. These data suggest that nutritional status assessment may be important to recognize patients at potential risk of surgical complications and that early nutritional interventions must be promptly arranged.

[Autologous peripheral stem cell transplantation in a patient with diffuse systemic sclerosis: our experience]. / Trapianto autologo di cellule staminali periferiche in un paziente con sclerosi sistemica diffusa: nostra esperienza.

The diffuse form of systemic sclerosis (SSc) can often lead to a rapidly progressive course with the involvement of the visceral organs which causes a severe prognosis. The 5-years cumulative mortality is between 30 and 60%, depending on the clinic form at the onset. Until now, no drug treatment has been proved to be efficacious against the progression of the disease or the regression of the fibrosis. Recently autologous peripheral blood stem cell (PBSC) transplantation has been found to be promising. We introduce the case of a patient, male, 56 years old, who came under our observation on February 2001, suffering from a SSc with a severe multisystem involvement of lungs, skin, heart and gastrointestinal tract, and a positive antibodies anti-Scl-70. The 8 months therapy, at first with iloprost and cyclophosphamide, then with bolus of cyclophosphamide, was ineffective, with a rapid worsening of the cutaneous and pulmonary involvement. Under the patient agreement we decided to carry out an autologous PBSC transplantation. On December 2001, we obtained the PBSC mobilization after the administration of cyclophosphamide and lenograstim and the PBSC recovery with two leucoaferesis procedures. On February 2002, we gave the conditioning therapy with: thiotepa, cyclophosphamide, fludarabine, rabbit antilymphocytic globulin; then we made the infusion of PBSC. The bone marrow recovery (GN >500 and PLT >20.000) arrived at the day + 10. For three months after the transplantation we made an antibacterial, antiviral and antifungin prophylaxis with valacocyclovir, co-trimoxazole and fluconazole. The one-year follow-up has shown an essentially good response with the improving of the skin involvement and of the subjective indicators of the disease, while the pulmonary involvement don't seen modified from the high dose therapy.

[Graves-Basedow disease associated with unusual variation of thyroid papillary carcinoma: a clinical case]. / Morbo di Graves-Basedow associato a rara variante di carcinoma papillare della tiroide: caso clinico.

The authors describe a case of papillary carcinoma of the thyroid in a young patient with Graves-Basedow disease, diagnosed 10 years ago and now in long-term remission. Remission was achieved after many cycles of methimazole treatment for recurrent hyperthyroid disease. Clinical symptoms, characterized by pain and nodular swelling in the region of the left thyroid, did not improve after glucocorticoid treatment. Fine needle aspiration cytology disclosed papillary neoplasm of the left thyroid nodule: the decisive histological features, seen after total thyroidectomy, unexpectedly documented a diffuse sclerosing variety of papillary thyroid carcinoma. The patient underwent ablative radioiodine therapy with 131-I and is now in remission, confirmed by total body scintigraphy. The case merits attention because of: the uncommon association of Graves-Basedow disease and differentiated thyroid cancer; the type of tumor, i.e., a diffuse sclerosing variety of papillary thyroid carcinoma which is rarely found and is characterized by specific histological and clinical features.

[The pulmonary cavitary lesion: a clinical case]. / Lesione cavitaria polmonare: caso clinico.

The authors describe a case of hydatid cystic disease presenting as a pulmonary excavation lesion. The peculiarity of this case consisted in the absence of the typical clinical symptoms caused by echinococcal cyst rupture into the bronchial cavity, e.g., hydatid vomica or allergic reaction to parasite antigens. The patient's work history and birthplace (he was a shepherd from Sicily), exclusion of the most frequent diseases causing lung excavation, i.e., tuberculosis, abscess, neoplasm, and his response to specific serological tests (indirect hemagglutination and immunoprecipitation) enabled proper diagnosis and successful surgical treatment. The importance of considering hydatid cystic disease in the differential diagnosis of pulmonary cavitary lesions, even in non-endemic areas and when clinical symptoms are atypical, is stressed. New diagnostic approaches and modern treatment options for hydatidosis are also discussed.

[Immuno-hemolytic anemia associated with lisinopril therapy. Report of a case]. / Anemia immunoemolitica associata a trattamento con lisinopril. Descrizione di un caso.

The Authors describe a case of immuno-hemolytic anemia in a 67-year-old woman with hypertension who had been treated irregularly with lisinopril for three months. The hemolytic crisis resolved promptly after withdrawal of lisinopril and did not recur under high-dose methylprednisolone therapy.

[An unusual case of regular menstrual cycles and endocrine pattern typical for the reproductive age in a patient of advanced age]. / Su un interessante caso di flussi mestruali regolari e pattern endocrino tipico dell'età riproduttiva in una paziente in età avanzata.

The Authors report the persistence of regular menses in a very old woman. Although in the absence of a pulsatile gonadotropin pattern the patient showed estradiol levels typical of the reproductive age.

Effect of estrogens and progesterone on gonadotropin and prolactin release in a patient with androgen insensitivity.

Response of serum levels of gonadotropins and prolactin to doses of estrogen and progesterone was measured in a patient with the complete form of androgen insensitivity, ie, testicular feminization. Before gonadectomy a single 2.5-mg dose of estradiol benzoate (E2B) produced a decrease in gonadotropin levels. Gonadectomy resulted in a rise of serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) but had no effect on levels of prolactin. The following results were obtained after gonadectomy: During low-dosage therapy with ethinyl estradiol (EE) a single 2.5-mg dose of E2B produced a decrease in FSH and LH levels, no LH surge, and a small rise in prolactin levels. With a tenfold higher EE priming, the same dose of E2B provoked an LH surge; progesterone administration produced FSH, LH, and prolactin release. However, progesterone priming blocked the positive feedback of estradiol and enhanced its negative feedback. Pituitary sensitivity ot nonandrogenic steroids appears to be normal in cases of testicular feminization. Under this condition, after gonadectomy, the dynamics of gonadotropins and prolactin in response to estrogens or progesterone administration are similar to those in normal women and suggest that aromatization products of testosterone do not produce any irreversible effects on neuroendocrine differentiation of androgen-insensitive patients

Progesterone positive feedback on gonadotropin release in estrogen-primed postmenopausal women: central nervous system and pituitary as possible sites of action.

To investigate the site and mode of action of progesterone in inducing gonadotropin release, the effects of catecholamine-depleting (methyldopa) or dopamine agonist (bromocriptine) drugs on progesterone positive feedback and the gonadotropin response to a centrally acting noradrenergic drug (clonidine) were evaluated in estrogen-primed postmenopausal women. Progesterone administration induced a significant rise in LH, FSH, and PRL serum levels in the control group. Bromocriptine administration was followed by a marked suppression of PRL release but did not modify the gonadotropin response to progesterone. Methyldopa pretreatment significantly reduced the progesterone-induced LH surge, while PRL release was unaffected. After estrogen priming, clonidine administration did not result in an increase in serum LH or FSH concentrations. The dissociated responses of LH and PRL in bromocriptine-pretreated subjects and the significant reduction of the LH rise after progesterone in methyldopa-pretreated women seem to invalidate the hypothesis that a fall in endogenous dopamine is responsible for progesterone positive feedback and suggest that neural noradrenergic mechanisms are involved in progesterone-induced gonadotropin release. The ineffectiveness of a centrally acting noradrenergic agonist in inducing gonadotropin rise provides indirect evidence that an increased pituitary responsiveness may also be involved in progesterone positive feedback.

[Adrenergic control of pancreatic glucagon secretion]. / Controllo adrenergico della secrezione del glucagone pancreatico.

In order to characterize the adrenergic control of pancreatic A cell, the effect on the glucagon secretion of three sympathomimetic substances (epinephrine, isoproterenol, phenylephrine) and two adrenergic blockers (propranolol and phentolamine) have been separately examined by the isolated perfused rat pancreas. The study was performed in basal state and during glucagon hypersecretion induced by arginine or glucopenia. Epinephrine and isoproterenol infusion determined a prompt an sustained glucagon release both in the basal state and during glucagon hypersecretion. The effect of phenylephrine infusion was slight. In the presence of propranolol, glucagon secretion induced by metabolic stimulus was significantly depressed. The glucagon secretion in the same experimental conditions was insignificantly enhanced by phentolamine. Finally propranolol infusion reverse the glucagon secretion induced by phenylephrine. In conclusion the pancreatic glucagon secretion in our model of study is clearly induced by B adrenergic receptor stimulation.

[Typing of the alpha adrenergic receptors of pancreatic B cells. In vitro studies with the isolated and perfused rat pancreas]. / Tipizzazione dei recettori alpha-adrenergici della cellula b insulare. Studio in vitro con il pancreas isolato e perfuso di ratto.

Two groups of receptors, one which develops a stimulating effect (alpha 1), the other an inhibitory effect hae recently been isolated in the alpha adrenergic group. In order to type the B cell adrenergic receptor of the endocrine pancreas, which mediates the inhibitory action exerted by the catecholamines on insulin secretion, the release of this hormone was evaluated in the presence of five alpha simpathomimetic substances that have a decreasing degree of efficiency on the adrenergic alpha 2 receptor of the presynaptic sympathic nerve terminal. The order of potency with which the alpha agonists tested depressed IRI secretion is superimposable on that of their potency on the sympathetic nerve and alpha 2 receptor. We concluded that adrenergic inhibition of insulin secretion is mediated by an alpha 2 receptor.

[A new model for the in vitro study of the entero-island of Langerhans axis]. / Un nuovo modello per lo studio in vitro dell'asse entro-insula re.

A new in vitro pancreas-intestine model which makes it possible to study the physiopathology of the intero-insular axis in greater depth, as it eliminates interference from other system, is proposed. The model, which is composed of the rat pancreas, duodenum and the first 25 cm of the small intestine, conserves both the circulation and the in vivo anatomical reltionship intact. Experiments were designed to evaluate the effect of a drug-induced disaccharidase-activity block on insulin secretion. The results obtained confirm the validity of the proposed model in investigating the entero-insular axis.