The ATT strand of AAT.ATT trinucleotide repeats adopts stable hairpin structures induced by minor groove binding ligands.

AAT.ATT is the most abundant and also the most frequently polymorphic class of trinucleotide repeats in the human genome. To characterize its structural properties and conformational changes induced by minor groove ligands, (AAT)(6) and (ATT)(6) oligomers as well as their complexes with DAPI were investigated by electrophoretic mobility and UV thermal stability as well as fluorescence and NMR spectroscopy. The results show that individual (AAT)(6) and (ATT)(6) strands exist principally as monomeric non-hydrogen-bonded structures. Their individual interaction with DAPI induces the formation of base-paired structures with different thermal stabilities by quite spectroscopically distinct binding mechanisms. In the presence of DAPI, (ATT)(6) forms a monomeric hairpin structure stabilized by two ligands located in the minor groove with a strong apparent binding constant of 3.4 x 10(6) M(-)(1). The DAPI-induced (ATT)(6) hairpin is characterized by well-stacked A.T Watson-Crick and T.T wobble base pairs, a high electrophoretic mobility, and a melting temperature of 41 degrees C. Interaction of DAPI with the complementary (AAT)(6) strand favors less stable base-paired structures, and the results are consistent with electrostatic and hydrogen-bond interactions of the ligand with the phosphodiester backbone of (AAT)(6) by minor involvement of DNA bases.

[Primary hyperparathyroidism and acute pancreatitis. A rare clinical association]. / Iperparatiroidismo primitivo e pancreatite acuta. Una rara associazione clinica.

Hyperparathyroidism and hypercalcaemia are considered to be a rare cause of acute pancreatitis. The relationship between hyperparathyroidism and pancreatic inflammatory disease remains controversial, but it may be related to the translation from inactive to active trypsinogen by hypercalcaemia. Surgical correction of parathyroid disease and normalization of serum calcium levels may ameliorate the acute pancreatitis. Also the mechanism of pathologic zymogen activation during acute pancreatitis remain unknown; probably the pancreatic "autodigestion" is the result of anomalous intracellular transport of secretory proteins activated by lysosomal hydrolases. A case of acute pancreatitis and hyperparathyroidism due to solitary parathyroid adenoma occurred in a 66-years-old woman is reported. After the excision of parathyroid adenoma the serum calcium levels and the function of the pancreas returned to normal. This suggests a cause and effect relationship between hyperparathyroidism and acute pancreatitis.

[Malignant pheochromocytoma. A case report and comments on a rare pathology]. / Il feocromocitoma maligno. Case report e considerazioni sulla rara patologia.

Pheochromocytomas and functioning paragangliomas are rare tumors arising from the primitive neural crest, and found in the adrenal medulla or elsewhere within the sympathetic paraganglion axis. Clinical symptoms are related to catecholamine production or less frequently to dopamine or other neuropeptides secretion. Malignant pheochromocytomas are very rare tumors comprising between 5-35%, but this value is uncertain because the usual criteria for malignancy, such as mitotic activity, nuclear pleomorphism, are not suitable to discern benign from malignant pheochromocytomas. A specific diagnosis of malignancy requires evidence of invasion of the adjacent organs and the occurrence of metastases. Personal experience is presented with 92 patients affected by: adrenal pheochromocytomas (51 cases), cervical paragangliomas (32 cases), and extra-adrenal paragangliomas (9 cases). Malignant forms were observed in a 23-year-old young woman affected by malignant pheochromocytoma with lymphatic para-aortic metastases (1.9%), and in 2 patients affected by cervical paragangliomas (1 CBT, 1 VBT) with lymph nodal metastases. Careful follow-up of all patients with measurement of the urinary catecholamine is necessary to detect metachronous neoplasm and later metastases, identified with RMN and 131I-MIBG scintiscan.

[Primary retroperitoneal tumors. Treatment modality and prognostic factors]. / I tumori retroperitoneali primitivi. Modalità di trattamento e fattori prognostici.

BACKGROUND: Primary Retroperitoneal Tumors (PRT) form a heterogeneous group of malignant mesenchymal and neuroectodermal neoplasms making up only 1% of all solid neoplasms. METHODS: From 1965 to 1997, 27 patients (16 females and 9 males, age range 19-79 years) underwent operations at the General and Cardiovascular Institute of University of Milan for primary retroperitoneal tumors (22 malignant and 5 benign, sarcomas represented 68% of all malignant tumors). A retrospective analysis of these patients was performed to determine the prognostic parameters associated with a favourable prognosis. All patients were admitted with severe abdominal pain or a palpable mass, other symptoms included fewer and weight loss. The median duration of symptoms before presentation was 16 months (range 15 days-5 years). Before surgical treatment abdominal and pulmonary CT scanning and MRN were undertaken on all patients with PRT to define the size of the tumor and the involvement of other retroperitoneal structures. RESULTS: Complete resection was possible in 54% of malignant tumors (n = 12), incomplete resection was performed in 14% (n = 3) and in 31% (n = 7) only biopsy was possible. Recurrent tumor developed in 25% of patients with total resection (n = 3), (median time to recurrence 5 years). Independent treatment variables (size, signs and symptoms, histopathologic findings and grade) and treatment-dependent variables (type of surgical treatment and adjuvant chemotherapy) were analyzed. Patients with complete resection had a 12 month survival of 100% (n = 12) compared to 50% (n = 1) for those undergoing partial resection and 14.2% (n = 1) for those with simple biopsy. A 24-month survival of the patients undergoing complete resection was 25% (n = 3). Median survival for type of surgical treatment was 28 months for complete resection compared to 14 months for partial resection and only 8 months for biopsy. Twelve-months survival for tumor grade was 100% (n = 7) for low grade tumor (G1), compared to 66.6% (n = 4) for median differentiated tumors (G2), and 37.5% (n = 3) for high grade tumors (G3). Twenty-four-months survival was 28.5% (n = 2) for low grade tumors compared to 16.6% (n = 1) of median differentiated tumors. High grade tumors were associated with a 35-month median survival time compared to 17 months for median differentiated tumors and 10 months for low grade tumors. Other variables (histopathologic findings, size, symptoms) had not significant impact on survival. Operative mortality rate was 3.7% (n = 1). The overall 2 years survival rate in patients with totally resected tumors was 25% (n = 3), (2G1, 1G2), while the 5 year survival rate was 16.6% (n = 2), (2G1). CONCLUSIONS: Complete surgical excision and low grade of the tumor are the most important parameters of survival. Recurrent disease is a vexing problem; a careful and prolonged follow-up based on the use of CT and MRN is recommended.

Acute vascular abdomen. General outlook and algorithms.

Acute vascular abdomen is a severe and life-threatening pathology due to arterial degeneration, leading to hemorrhage or arterial occlusion leading to ischemia. Differential diagnosis of patients with severe abdominal pain and/or shock include several vascular and traumatic diseases, the most common being rupture of abdominal aortic aneurysm (AAA), or less frequently rupture of visceral artery aneurysm. Also acute aortic dissection, iatrogenic injury and acute mesenteric ischemia may lead to acute vascular abdomen. Clinical evaluation of the haemodynamic status of the patient may be very difficult, and may require airway maintenance and ventilation with a rapid treatment of hemorrhagic shock. In the stable patient with an uncertain diagnosis, CT scan, NMR and selective angiography may be helpful in diagnosis before vascular repair. On the contrary, the unstable patient, after hemodynamic resuscitation, must be operated on expeditiously. We present our vascular algorithms, to assess timing of diagnosis and treatment of this severe acute disease.

[Secondary aorto-enteric fistula]. / Le fistole vasculo-enteriche secondarie.

Aortic graft fistula is a rare and life-threatening complication after aortic reconstruction. The incidence ranges from 0.5 to 4%, and even if the diagnosis and treatment is appropriate, the results of surgery are poor: mortality rate ranges from 14 to 70%. The optimal method of treatment is still controversial; prosthetic removal and extra-anatomic bypass has been advocated as the standard method, but more recently, because the high mortality rate associated with this procedure, some have prompted to recommend in situ aortic graft replacement as a more successful treatment. Personal experience with incidence (0.7%) outcome and mortality (57%) in 7 patients treated over a period of 6 years (1990-1996) is reported. Results from this group are compared with another group (6 patients) previously treated (1975-1982) for the same pathology. Our results after 10 years, show the same incidence (0.7 vs 0.6%) and an elevated and unchanged mortality (57 vs 66%). Better results in the management of aorto-enteric fistulas could be achieved with the removal of infected infrarenal aortic prosthetic grafts and in situ homografts replacement.

[Intestinal anastomosis with a biofragmentable rind (BAR). Results in comparison with mechanical and manual anastomosis]. / Anastomosi intestinali con anello bioframmentabile (BAR). Risultati e confronto con le anastomosi meccaniche e manuali.

METHODS: The use of the biofragmentable anastomosis ring (Valtrac-BAR) was attempted in 25 selected patients (group I) undergoing elective colonic resection for primary colon cancer, at the General and Cardiovascular Institute of the University of Milan. The results were compared with those of 30 selected patients who underwent elective colonic resection for the same pathology during the same period, and had their bowel anastomosis stapled (group II) or hand-sutured (group III). RESULTS: In group I there were 2 complications requiring reoperation: a little tear of the bowel near the BAR, and a postoperative ileus, compared with none in group II, that developed only 3 cases of abdominal wall infections. In group III, 2 patients developed a leakage of the anastomosis, one of them required reoperation. In the perioperative course there were 2 deaths (3.6%), in group II and III due to cardiovascular diseases. The results obtained showed no significant difference in the clinical course of the patients, or time of return of bowel function, and hospital stay. CONCLUSIONS: The conclusions is drawn that Valtrac-BAR device is a safe and reliable alternative to conventional suture anastomosis in all areas of the intestinal tract, except the low rectum.

[Adrenal carcinoma. Clinical and anatomopathological prognostic factors]. / I carcinomi del surrene. Fattori prognostici clinici ed anatomopatologici.

We performed on 9 patients with adrenal cortical carcinoma a retrospective study during 1967-1995 to evaluate the most important prognostic factors. Four patients were males and five females (mean age: 40.3 years). Five patients had endocrine symptoms (55%) and four had "non-functioning" tumors (45%). The tumor involved the left adrenal gland in 5 cases and the right in 4. The mean diameter of the neoplasm was 9.5 cm, with a mean weight of 411 g. The average duration of symptoms before diagnosis was 7.3 months. One patient had invasion of the inferior vena cava with liver metastases. Eight patients underwent curative surgery, the median survival time was 13.7 months, only 1 patient is alive after 18 months from surgical resection. We concluded that adrenal carcinomas have poor prognosis; staging and grading of the neoplasm, and age of the patient at diagnosis are predictors of survival.

[Problems of differential diagnosis of lymphoma and celiac disease. A case report]. / Problemi di diagnostica differenziale fra linfoma e celiachia. Descrizione di un caso clinico.

An association between celiac disease and non-Hodgkin's lymphoma of the small intestine has been recognized for many years. Coeliac disease is characterized by an enteropathy sensitive to gluten, malabsorption of food and partial or total villous atrophy. Also malignant lymphoma may present with malabsorption and mucosal lesion similar to that found in coeliac patients. The diagnosis of lymphoma in coeliac patients can be extremely difficult because the presenting symptoms and histological lesion are similar, but the presence of a cluster of symptoms such as abdominal pain malabsorption, weight loss in patients older than 40 years with a history of poorly responsive coeliac disease should raise a suspicion of malignancy. We present a case of 55 year-old man with malignant lymphoma and coeliac disease surgically treated in our Institute for intestinal obstruction.

[Prognostic clinical and anatomopathological factors in surgery of carcinoma of the right colon]. / Fattori prognostici clinici ed anatomopatologici nella chirurgia del carcinoma del colon destro.

Between 1965 and 1990, 52 patients were treated for adenocarcinoma of the right colon at the General and Cardiovascular Institute of University of Milan. We have performed in all patients a curative right hemicolectomy. Five year survival rate was 57.7%. Among 12 clinical and pathological variables, the pathologic stage and the degree of cellular differentiation were the most important prognostic factors. Also other factors, like mucin production, tumor ulceration and duration of symptoms were important prognostic factors, because related to a poor prognosis. Our study emphasize the importance of an early diagnosis and a prompt curative surgical treatment to improve patient's survival rate.

[Traumatic lesion of the subclavian and axillary arteries]. / Le lesioni traumatiche delle arterie succlavia ed ascellare.

This study comprises 11 patients with traumatic vascular injuries of the subclavian and axillary vessels treated in the last 13 years at the Institute of General and Cardiovascular Surgery of Milan. Nine patients were male and two were female. In two patients the cause of injury was a penetrating trauma; blunt trauma occurred in nine patients. The majority of injuries were caused by motor vehicle accidents. Two patients suffered complete brachial plexus palsies with complete transection of the median nerve. Seven patients were affected by multiple bone injuries, while major venous injury was present in one case. Diagnosis was established by angiography performed in all stable patients. Vascular repair was performed in 10 patients; 4 patients were treated by primary repair, and 6 patients by interposition grafts. In one case we performed a transluminal percutaneous angioplasty (PTA) during angiographic examination, with a good result. There were no postoperative vascular complications and no patient died.

Detection of Chlamydia pneumoniae but not Helicobacter pylori in atherosclerotic plaques of aortic aneurysms.

Recent reports suggest an association between Chlamydia pneumoniae and Helicobacter pylori bacteria and atherosclerosis. We studied 51 patients (mean age, 68.3 years) who underwent abdominal aortic aneurysm surgery. For each patient we performed a microimmunofluorescence test for immunoglobulin G (IgG), IgA, and IgM antibodies to C. pneumoniae specific antigen (TW-183). Anti-H. pylori antibodies were determined by means of an EIA-G test. Each aortic aneurysm surgical specimen was sampled into multiple sections of 0.3 cm2 each and frozen at -20 degrees C. Two samples of each aneurysm were used for a nested PCR with two sets of C. pneumoniae and two sets of H. pylori specific primers. Specimens were treated with a solution containing 20 mM Tris-HCl, Tween 20-Nonidet P-40 (0.5% [vol/vol] each), and 100 micrograms of proteinase K per ml and incubated at 60 degrees C for 1 h and at 98 degrees C for 10 min. DNA was extracted twice with phenol-chloroform-isoamylic alcohol and precipitated with sodium acetate-ethanol by standard methods. Forty-one patients were seropositive for C. pneumoniae with past-infection patterns in 32 patients (16 < or = IgG < 512; 32 < or = IgA < 256) and high antibody titers in 9 patients (IgG > or = 512). In 26 of 51 patients, C. pneumoniae DNA was detected in aortic aneurysm plaque specimens. Of these patients, 23 had a serologic past-infection pattern, 2 had an acute reinfection pattern, and 1 was seronegative. Forty-seven of 51 patients were seropositive for H. pylori. In all cases PCR showed no evidence of H. pylori presence in plaque specimens. This study provides data on a possible C. pneumoniae involvement in the pathogenesis of aortic aneurysm and additional evidence for an association between this agent and atherosclerosis. Conversely, notwithstanding a high H. pylori seroprevalence observed, our results tend to rule out the possibility of a direct involvement of H. pylori in atherosclerosis.

[Association of rupture abdominal aneurysm and intestinal infarct]. / Associazione fra aneurisma addominale rotto e infarto intestinale.

The authors present one patient with ruptured abdominal aortic aneurysm (rAAA) who complicate with small bowel infarction and coproperitoneum; and two patients who suffered from rAAA and simultaneous colon infarction, successfully treated by one-stage operation. They comment upon this rare pathology and analyze hypothetical causes, considering the scanty literature about it.

[Intestinal infarction after ruptured aneurysm of the abdominal aorta. Clinical contribution]. / L'infarto intestinale dopo rottura di aneurisma dell'aorta addominale. Contributo clinico.

Acute mesenteric ischemia is a severe complication after aortic reconstructive surgery for AAA repair. This ischemic event, due to a poor intestinal perfusion especially in ruptured AAA in consequence of the hypotension and the hypovolemic shock, shows different clinical manifestations such as delayed canalization, ischemic colitis or more serious like intestinal infarction. Between 1989 and 1994, 965 cases of abdominal aortic aneurysms have been surgically treated in General and Cardiovascular Surgery Institute of University of Milan. Rupture had occurred in 150 patients, and intestinal infarction was observed in 6 cases (3.9%). Mortality rate of 33% was observed. Etiology and technical procedures to avoid this complication are discussed.

[Malignant neoplasms invading into the inferior vena cava. Surgical indications]. / Neoplasie maligne ed invasione della vena cava inferiore. Indicazioni chirurgiche.

Clinical conditions requiring resection and replacement of the inferior vena cava (IVC) are rare and have included tumors, traumatic or iatrogenic injuries. Intraluminal extension or direct mural involvement of the IVC is seen with a variety of tumors: renal cell carcinomas, adrenal cortical tumors, leiomyosarcomas and pheochromocytomas. Surgical treatment requires tumor resection with simultaneous en bloc resection of the involved IVC. Resection of the lower and middle segments of IVC is possible in nearly all cases and surgical reconstruction is generally made with a polytetrafluoroethylene (PTFE) tube graft. Resection at suprahepatic vein level is indicated only rarely: tumor invasion of the suprahepatic veins require liver transplantation. Venous bypasses have lower patency rates than prosthetic replacement because of the low pressure and lower-flow of the venous system.

[The physiopathology, clinical picture and therapy of chronic intestinal ischemia]. / Fisiopatologia, clinica e terapia dell'ischemia intestinale cronica.

Between January 1982 and April 1993, 8 patients suffering from a typical clinical picture of chronic intestinal ischemia, have been observed. All these patients were symptomatic and 7 cases presented stenosing or occlusive lesions of at least 2 of the 3 splanchnic trunks. 5 of these 7 patients underwent a corrective surgical procedure. 2 patients underwent percutaneous transluminal angioplasty. One patient affected by stenosis of the coeliac trunk due to external compression caused by the median arcuate ligament of the diaphragm was not operated because the symptomatology was atypical and the other 2 splanchnic trunks were perfectly patent. Three patients died following the therapeutic procedure: a woman in whom an aorto-mesenteric bypass graft was inserted, underwent, 4 months after, an intestinal infarction due to thrombosis of the graft; another woman, whose coeliac trunk and superior mesenteric artery were thrombosed and whose inferior mesenteric artery was reimplanted on the common iliac artery, died for acute hepatic failure, after 12 months of total parenteral nourishment; a third patient, successfully submitted to PTA of the superior mesenteric artery, died after 4 months due to the occurrence of acute renal insufficiency.

[Primary lymphoma of the gastrointestinal tract]. / I linfomi primitivi del canale alimentare.

Lymphomas of the gastrointestinal tract are rare tumors with unusual features and few characteristics. Clinical, radiological and endoscopic diagnosis is difficult, because they may be confused with inflammatory or neoplastic forms, especially in primary involvement of the gastrointestinal tract. From 1965 we observed 4 patients with primitive gastrointestinal tract lymphomas. Prognostically important features for GI lymphomas were: stage, site of the primary disease, histological type. Authors report on the clinical findings, diagnostic procedures, surgical treatment and results.

[Functioning paraganglioma]. / I paragangliomi funzionanti.

Pheochromocytomas and functioning paragangliomas are rare tumors arising from indifferent cells of the primitive neural crest. These tumors produce clinical symptoms (pheochromocytoma syndrome) related to catecholamine production. The pheochromocytoma syndrome, constituted by arterial hypertension, headache and sweating, is due in 80% of cases to adrenal pheochromocytomas and only in 20% of cases is due to extra-adrenal secreting paragangliomas. The diffused localization of the Paraganglion System and the common embryologic origin, can explain the occasional identification of multicentric tumors (10%), and the association with multiple endocrine neoplasms (MEN), especially in familial occurrence. Careful follow-up of patients, in order to detect the later development of multicentric or metachronous neoplasms is necessary. The Authors present their experience with 80 patients affected by neoplasms involving the adrenal medulla and the multicentric paraganglion system, surgically treated during the last 25 years. Eight patients (10%) were affected by functioning extra-adrenal paragangliomas: 7 patients (87.5%) had solitary extra-adrenal tumors (6 abdominal and 1 thoracic) with a classic pheochromocytoma syndrome, and 1 patient (12.5%) had a double asymptomatic abdominal paraganglioma.