Predictors of the early impairment of renal disease in human obesity.

OBJECTIVE: The mechanisms underlying the association of the increased albumin excretion rate (AER) with adiposity have yet to be clarified. We therefore investigated (1) the predictors of AER after 3 months of lifestyle intervention in a large cohort of nondiabetic obese women and (2) the relationships between AER and the adipose tissue gene expression of adipokines linked to inflammation and insulin resistance. SUBJECTS: A total of 269 obese nondiabetic women (age 49.9+/-13.1 years, body mass index (BMI) 36.8+/-4.6 kg m(-2)) participated in this program. Measurements used were anthropometrics parameters, blood pressure, oral glucose tolerance test, lipids, creatinine, AER, homeostasis model assessment of insulin resistance (HOMA-IR) and glomerular filtration rate at baseline and after 3 months of lifestyle intervention. At baseline, in a subgroup of 34 women, subcutaneous adipose tissue biopsy was carried out for the analysis of mRNA expression levels of adiponectin, suppressor of cytokine signaling 3 (SOCS-3), tumor necrosis factor alpha (TNF-alpha), pentraxine 3 (PTX-3), angiotensinogen and angiotensin-converting enzyme, and a blood sample was also taken from this group for the measurement of circulating adiponectin, interleukin-6, TNF-alpha and PTX-3. Microalbuminuria was defined as albumin/creatinine ratio >or=3.5 mg mmol(-1). Real-time PCR was used to quantify mRNA. RESULTS: Six percent of obese women had microalbuminuria. When dividing the whole cohort into three groups according to AER changes (decrease, stability and increase), we noted that 2 h glucose, insulin and HOMA-IR significantly decreased (P<0.05 for all) only in women who had a decrease in AER, whereas BMI and waist circumference significantly decreased in all the three groups (P<0.05). At baseline, higher AER was associated to significantly higher adipose tissue mRNA expression levels of SOCS-3 and PTX-3 (P<0.05) and to higher TNF-alpha and angiotensinogen expression. CONCLUSIONS: In obese women, weight loss alone is not sufficient to induce the AER decrease that occurs only with a concomitant improvement in glucose homeostasis. The adipose tissue gene expression profile seems to favor the early renal impairment often seen in obese subjects.

Inter-hospital extracorporeal life support.

A 60-year-old man with history of hypertension and unspecified left ventricular dysfunction had chest pain at home at 9 am. At 1 pm he was transported to a peripheal hospital and treated for acute myocardial infarction. At 4.30 pm, despite pharmacological and intra aortic balloon pump support , the extreme hemodynamic instability and the echocardiographic signs forced the doctors in charge to contact the "extracorporeal membrane oxygenation team" of our Intensive Care Unit. The team, that in our hospital is composed of an intensivist, a cardiac surgeon, a perfusionist and a nurse, reached the hospital at 5.15 pm and performed a percutaneous cannulation of right femoral artery and left femoral vein connecting the patient to the extracorporeal membrane oxygenation circuit. At 6.30 pm the patient on extracorporeal membrane oxygenation was transferred by ambulance to the Cardiac Surgery Intensive Care Unit of San Gerardo Hospital in Monza. On day 20 he was transferred back to the original hospital without neurological deficits, with normal renal function and normal blood gas analysis.

[Acute cardiotoxicity from 5-fluorouracil: un underestimated toxicity]. / Cardiotossicità acuta da 5-fluorouracile: una tossicità sottovalutata.

The most common toxicity in clinical trials with 5-FU, in mono or polychemotherapy, is stomatitis, diarrhea, hand-foot syndrome. In this case report, the 5-fluorouracil (5-FU) cardiotoxicity, an uncommon 5-FU-related toxicity, has been investigated. Cardiotoxicity reports are uncommon because the problem is not well known. This study is also a review of the recent literature and it recommend to take care in prescribing chemotherapy to patients with heart disease history.

Two distinct pathways of muscarinic current responses in rabbit sino-atrial node myocytes.

Acetycholine (ACh) slows the heart rate by acting on sino-atrial node currents. Low ACh concentrations act on muscarinic receptors to inhibit the hyperpolarization-activated current (if) by a adenosine 3',5'-cyclic monophosphate (cAMP)-dependent cytoplasmic pathway. ACh also activates a muscarinic potassium conductance (iK,ACh) via a pertussis toxin-sensitive guanine nucleotide-binding protein (G-protein) that gates the channel directly. This pathway has been called membrane-delimited or "fast" because cytoplasmic components are not required and hence activation is relatively rapid. Such a pathway has also been proposed for the muscarinic inhibition of if. Here we show that, under steady-state current conditions, 0.1-1 microM ACh activates iK,ACh with a time constant of 1 s or less that is inversely proportional to ACh concentration, consistent with a fast, membrane-delimited pathway. ACh also causes a significantly slower inhibition of if which is not proportional to ACh binding. The changes in if are consistent with muscarinic effects mediated exclusively through the cAMP pathway.

Differential control of the hyperpolarization-activated current (i(f)) by cAMP gating and phosphatase inhibition in rabbit sino-atrial node myocytes.

1. The actions of the phosphatase inhibitor calyculin A on the hyperpolarization-activated cardiac 'pacemaker' current (i(f)) were determined in single cells isolated from the sino-atrial (SA) node of the rabbit. 2. Cells were incubated for 8 min in Tyrode solution containing calyculin A (0.5 microM) and then superfused with normal Tyrode solution. The mean normalized i(f) measured in eight cells at mid-activation voltages during and after exposure to calyculin A increased maximally by 47% with a time constant of 466 s, a time much longer than that required for cAMP-mediated i(f) stimulation (about 8 s). 3. In two-pulse protocols, calyculin A treatment increased i(f) at full as well as at mid-activation voltages, indicating a higher i(f) conductance. 4. Measurement of the conductance-voltage (gf(V)) relation by voltage ramp protocols confirmed a conductance increase by calyculin A, with no significant change in the position of the activation curve on the voltage axis. Data pooled together from ramp and two-pulse protocols yielded a calyculin A-induced increase in fully activated i(f) conductance of 39.6 +/- 6.4% (n = 16 cells). 5. The positive and negative shift of i(f) voltage dependence in response to beta-adrenergic (1 microM isoprenaline) and muscarinic stimulation (1 microM acetylcholine), respectively, was preserved after the calyculin A-induced increase in conductance. The shift of the i(f) activation curve induced by 1 microM isoprenaline was significantly larger in calyculin A-treated cells (8.8 vs. 5.8 mV). 6. These data indicate that phosphatase inhibition increases i(f) in a manner distinct from the direct cAMP pathway and potentiates the beta-adrenergic-mediated i(f) modulation.

[Benign symmetrical lipomatosis: Madelung's disease]. / Lipomatosi simmetrica benigna: malattia di Madelung.

Multiple symmetrical lipomatosis, or Madelung's disease, is a rare disease of unknown etiology. It is characterized by the presence of loose adipose tissue deposits localized in the cervical region and in the upper body. The neoformations grow slowly and their initial consequence is purely esthetic. They can, however, lead to compression of the laryngeal-tracheal area and of the esophagus. This disease normally affects middle-aged males from the Mediterranean area with a history of alcohol abuse. Although most cases have been sporadic, a few authors have indicated that the disorder may be hereditary. It is thought that this pathology originates from an alteration in lipid metabolism. Surgical removal of the lipomatose mass is the treatment of choice even though there are frequently recurrences. A case is presented of a rare laryngeal localization of this disease and diagnosis and treatment are discussed.

[The "sump syndrome": a case treated by surgical endoscopy. A discussion about biliodigestive diversions and endoscopic sphincterotomies]. / "Sump syndrome": un caso trattato mediante endoscopia operativa. Spunto di discussione in merito a derivazioni biliodigestive e sfinterotomie endoscopiche.

A case of "sump syndrome", occurred in our department, suggested the discussion about the opportunity of endoscopic operative procedures in choledocholithiasis and in biliary tract surgery complications. Improvement of endoscopic operative procedures allow extensive indication of ERCP sphincterotomy instead of traditional choledochoduodenostomy or transduodenal papillosphincterotomy. Additionally, operative endoscopic procedures are good alternative to reoperation for traditional biliary tract surgery complications.

[The role of ERCP in the diagnosis and therapy of Mirizzi's syndrome. Apropos a clinical case]. / Ruolo della ERCP nella diagnosi e terapia della sindrome di Mirizzi. A proposito di un caso clinico.

Mirizzi syndrome is a rare variant of obstructive jaundice due to compression of the hepatic duct caused by a stone inserted in the cystic duct or in the Hartmann recess and it is referred with a prevalence of 0.05-1% of patients with cholelithiasis. These percentages are, nevertheless, unreliable because only an accurate preoperative cholangiography allow to detect a Mirizzi syndrome and so, very often, the real cause of the jaundice remains unacknowledged. Early diagnosis of the syndrome is particularly important because it suggests an accurate and prudential surgical approach considering the frequent fibrotic adherences caused by chronic inflammation. In this paper the authors present a clinical case quickly and successfully cured operative endoscopy, followed by traditional surgery. The authors believe that the study of obstructive jaundices must include an ERCP either for the diagnosis or because operative endoscopy could ameliorate clinical feature and hepatic performance in order to allow a safer surgical operation.

Activation of the hyperpolarization-activated current (if) in sino-atrial node myocytes of the rabbit by vasoactive intestinal peptide.

Vasoactive intestinal peptide (VIP) is a putative neurotransmitter found in extrinsic and intrinsic nerves of the heart. VIP can be released by vagal stimulation but, contrary to ACh, causes positive chronotropic effects as a result of binding to cardiac receptors which stimulate adenylate cyclase, and thus has been implicated in vagal tachycardias. Since the rate of diastolic depolarization of sinoatrial (SA) node myocytes depends on the hyperpolarization-activated current (if), which is directly activated by cytoplasmic cAMP, we studied the action of VIP on if in myocytes isolated from the SA node of the rabbit. VIP (0.65 microM) reversibly increased if at -65 mV but had no effect at -115 mV suggesting that its primary effect was to shift the activation curve to more positive voltages. Hyperpolarizing ramp and voltage compensation protocols indicated that VIP shifts the activation curve of if by approximately 5-6 mV in the positive direction with no change in maximal conductance. This shift may be the mechanism by which VIP produces its positive chronotropic effect and supports a negative feedback role for this peptide during elevated vagal activity.

Decisive role of immunocytochemistry in aspiration cytology of chordoma of the clivus: a case report with review of the literature.

Immunocytochemistry (ICC) proved to be an essential adjunct in the fine-needle aspiration (FNA) cytological diagnosis of chordoma of the clivus in a 62-year-old woman. The cytological picture in routinely stained smears was not entirely diagnostic for chordoma due to the paucity of typical 'physalipherous' cells. To exclude other primary or metastatic neoplasms of the skull base possibly sharing the same cytological picture, additional direct smears were immunostained with antibodies specific for cytokeratin (CK), vimentin (VIM), S100 protein (S100P), carcinoembrionic antigen (CEA), epithelial membrane antigen (EMA), glial fibrillary acidic protein (GFAP), CD68 antigen (KP1) and with the 'panepithelial' antibodies B72.3 and Ber-EP4. Chordoma cells showed the following immunoprofile: CK+/VIM+/S100P+/CEA-/EMA+/GFAP-/B72.3-/Ber-EP4-/CD68+. The pattern of immunoreactivity for CK, S100P and CEA confirms previously reported data, while the B72.3-/Ber-EP4-/CD68+ staining profile represents a novel observation. The detection of a CK+/S100+/CEA-/B72.3-/Ber-EP4- immunocytological profile of chordoma cells in aspirates is a basic requirement to exclude pertinent diagnostic differentials, such as metastatic carcinoma, ependymoma and sarcoma, and permits a reliable pre-operative diagnosis of the tumour by aspiration cytology.

[Abdominal aortic aneurysm ruptured into the inferior vena cava. Presentation of a clinical case. Review of the literature]. / Aneurisma dell'aorta addominale rotto in vena cava inferiore. Presentazione di un caso clinico. Revisione della letteratura.

Rupture of the major veins is a rare complication of abdominal aortic aneurysms and is generally followed by sudden haemodynamic changes, whose importance is strictly dependent on the size of the fistula and rapidity of onset. The final result is invariably hyperdynamic congestive heart failure, oligoanuria and hyperazotemia, expression of renal insufficiency. Early recognition and surgical operation, together with appropriate postoperative intensive care, are the key for successful treatment of aorto-caval fistulas. Despite the improvement of surgical and anaesthesiology techniques, operative mortality rate still remains elevated (36%), but not higher than in other abdominal aortic aneurysms ruptures. The aim of this paper is to review the literature and to report one case of a seventy-year-old patient affected by an aorto-caval fistula and successfully treated in our Surgery Division.

[Mechanical staplers in our surgical practice]. / Le suturatrici meccaniche nella nostra practica chirurgica.

On the basis of our experience from 1981 to 1989, advantages of staplers in digestive surgery are reported. Complications such as bleeding and stenosis are not clinically important, however, in most cases, they can be avoided if the instruments are properly used.