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Biomedical subjects

L Bonati

Publications and source records attributed to L Bonati.

At least 19 recordsLinked to original sources

Conservation and specialization in PAS domain dynamics.

The PAS (Per-ARNT-Sim) superfamily is presented as a well-suited study case to demonstrate how comparison of functional motions among distant homologous proteins with conserved fold characteristics may give insight into their functional specialization. Based on the importance of structural flexibility of the receptive structures in anticipating the signal-induced conformational changes of these sensory systems, the dynamics of these structures were analysed. Molecular dynamics was proved to be an effective method to obtain a reliable picture of the dynamics of the crystal structures of HERG, phy3, PYP and FixL, provided that an extensive conformational space sampling is performed. Other reliable sources of dynamic information were the ensembles of NMR structures of hPASK, HIF-2alpha and PYP. Essential dynamics analysis was successfully employed to extract the relevant information from the sampled conformational spaces. Comparison of motion patterns in the essential subspaces, based on the structural alignment, allowed identification of the specialized region in each domain. This appears to be evolved in the superfamily by following a specific trend, that also suggests the presence of a limited number of general solutions adopted by the PAS domains to sense external signals. These findings may give insight into unknown mechanisms of PAS domains and guide further experimental studies.

Adiantum↗

Ultrasonography and cystic hyperplasia-pyometra complex in the bitch.

Cystic endometrial hyperplasia-pyometra complex is the most frequent and important endometrial disorder encountered in bitches. The pathogenesis of the disease is related to the activity of progesterone [Feldman and Nelson, Canine and Feline Endocrinology and Reproduction (1996) W.B. Saunders, Philadelphia]. Cystic endometrial hyperplasia (CEH) is an abnormal response of the bitch's uterus to ovarian hormones [De Bosschere et al. Theriogenology (2001) 55, 1509]. CEH is considered by many authors to be an exaggerated response of the uterus to chronic progestational stimulation during the luteal phase of the oestrous cycle, causing an abnormal accumulation of fluid within the endometrial glands and uterine lumen (De Bosschere et al. 2001). The resulting lesions of pyometra are due to the interaction between bacteria and hormones. The aim of this study was to evaluate if transabdominal uterine ultrasonography can be a useful and reliable diagnostic method to confirm Dow's [Veterinary Record (1958) 70, 1102] and De Bosschere's histopathological classification of CEH-pyometra complex. The study was carried out on 45 bitches with pyometra, 10 purebreds and 35 crossbreeds, 1-15 years old, 20% of which had whelped at least once. None of these animals had received exogenous oestrogen or progesterone treatment. On admission the 45 animals were in the luteal phase of the oestrus cycle. Clinical signs, blood parameters, uterine ultrasonography, bacterial swabs and uterine histopathological results were recorded. Results suggest that ultrasonographic examination is a useful and reliable tool for the diagnosis of cystic endometrial hyperplasia.

Animals↗

Heterotopic pancreas in the ampulla of Vater.

We report a patient in whom heterotopic pancreatic tissue was found within the ampulla and treated by ampullectomy. Only 16 cases of pancreatic tissue located at the ampulla of Vater have been reported in the literature and pancreaticoduodenectomy has been performed in more than half the cases because malignancy was suspected preoperatively, reflecting a rather aggressive surgical attitude. An accurate preoperative evaluation thus appears decisive to avoid unnecessary radical surgery. Endoscopic treatment of ampullary tumors is emerging as a viable alternative to surgical treatment. Local surgical excision is a reasonable option to endoscopic treatment. The possibility of heterotopic pancreatic tissue, though rare, should be included in the differential diagnosis of papillary tumors. Histologic confirmation (frozen or delayed) is mandatory before attempting such major surgery.

Aged↗

A model for recognition of polychlorinated dibenzo-p-dioxins by the aryl hydrocarbon receptor.

Ligand binding by the aryl hydrocarbon receptor (AhR), a member of the bHLH-PAS family of transcriptional regulatory proteins, has been mapped to a region within the second 'PAS' domain, a conserved sequence motif first discovered in the Per-ARNT-Sim family of proteins. In addition to the bacterial photoactive yellow protein (PYP), which had been proposed as a structural prototype for the three dimensional fold of PAS domains, two crystal structures of the PAS domain have recently been determined: the human potassium channel HERG and the heme binding domain of the bacterial O(2) sensing FixL protein. The three structures reveal a highly conserved structural framework in evolutionary rather distant PAS domains, provide a more general view of how these domains can recognize their ligands and suggest a structure-function relationship that we exploited to build a three-dimensional model of the ligand binding domain (LBD) of the mouse aryl hydrocarbon receptor (mAhR). The model allowed us to putatively identify the residues responsible for the recognition of polychlorinated dibenzo-p-dioxins (PCDDs) by AhR receptors and to formulate an hypothesis on the signal transduction mechanism.

Amino Acid Sequence↗

[Inflammatory abdominal aortic aneurysms].

The authors present a review of the literature on inflammatory abdominal aortic aneurysms. These aneurysms represent from 3 to 10% of all abdominal aortic aneurysms. Progress has occurred in the technical approach to these aneurysms, and operative morbidity and mortality have been remarkably reduced. However, the pathogenesis remains poorly understood. Early reports have considered the inflammatory aneurysm as a distinct clinical and pathological entity, whereas recent evidences suggest a common etiopathogenetic mechanism for both atherosclerotic and inflammatory aneurysms. Finally, genetic and environmental factors, such as tobacco use, may predispose certain persons to the development of non-inflammatory aneurysms and others to a wide spectrum of inflammatory reactions until inflammatory aneurysms development. The most common clinical features of these aneurysms are represented by symptoms, such as abdominal or back pain, obstructive uropathy and by an elevated erythrocyte sedimentation rate. Computed tomography (CT) allows a specific diagnosis by the typical image of soft tissue surrounding the aortic wall enhancing with contrast administration. Ultrasonography is less sensitive whereas nuclear magnetic resonance (RNM) is a promising technique. Excretory urography may suggest the diagnosis by demonstration of ureter entrapment. Surgical therapy, by a technique of limited dissection represents the definitive treatment. Evolution of fibrosis after surgery is still debated because some studies have reported complete regression of inflammation and other partial regression or persistence of fibrotic process. At present, endovascular treatment of these aneurysms is occasionally reported, although preliminary results appear satisfactory.

Aortic Aneurysm, Abdominal↗

[Prevalence of atherosclerosis in renal transplant recipients].

BACKGROUND: Cardiovascular diseases are a major cause of morbidity and mortality after kidney transplantation. Renal transplant recipients have in fact accelerated atherosclerosis because of prolonged hemodialysis, arterial hypertension, dyslipidemia and other vascular risk factors. Studies concerning carotid and lower limb atherosclerotic changes in renal transplanted patients are at present scant. METHODS: In the present study the prevalence of carotid and iliac-femoro-popliteal atherosclerosis was evaluated by color flow Doppler in 99 patients 64 +/- 41 DS months after renal transplantation. Statistical analysis was used to correlate the presence and grade of atherosclerotic lesions with vascular risk factors and other clinical-laboratoristic parameters of the patients. RESULTS: The overall incidence of atherosclerotic lesions in the population studied was 54.5%; 46.5% of patients presented atherosclerotic plaques at carotid district, 43.4% at lower limb arteries and 35.4% at both districts. Two of these patients were symptomatic; one patient affected by claudicatio intermittens was submitted to conservative therapy, whereas another patient with abdominal aortic aneurysm underwent to surgical treatment. Univariate analysis showed a significant difference between males and females for lower limb atherosclerotic lesions (p=0.0013), whereas no correlation was found between carotid lesions and sex, or between smoke and atherosclerosis. Significant correlations were found by multiple correlations analisys between: the grade of atherosclerotic lesions in both districts and the patient age (p<0.0001); the grade of carotid atherosclerotic plaques and duration of pretransplantation dialysis (p<0.01); the grade of lower limb atherosclerosis and respectively glicemic (p<0.01), hematocrit (p<0.01), potassium (p<0.002) values, systolic blood pressure (p<0.02). CONCLUSIONS: Relevant rates of renal transplant recipients have carotid and peripheral atherosclerotic lesions. The study of aorto-iliac and lower extremity vascular atherosclerosis have important implications for the transplanted kidney functionality. Color flow Doppler represents a sensitive method for the follow-up examination of these patients.

Adult↗

[Diagnosis and treatment of pheochromocytoma].

Early detection of a pheochromocytoma is necessary to avoid the cardiovascular complications of hypertension and to recognize the 10% of malignant neoplasms. Hypertensive changes, particularly hypertensive spikes and stable hypertension are the most common clinical features. A pheochromocytoma must be suspected in presence of various symptoms of which cephalea, tachycardia, diaphoresis are the most frequently encountered. Plasma catecholamines and 24-hours urine metabolites measurements have 60-100% and 72-99% sensitivity respectively. Radiologic procedures commonly used to locate a pheochromocytoma include CT and RM: they achieve 100% sensitivity for unilateral adrenal lesions and respectively 64% and 88% sensitivity for extra-adrenal lesions. Scintigraphic localization with MIBG provides functional informations and is recommended for follow-up of the recurrent or metastatic pheochromocytoma. Preoperative medical treatment using alpha and beta blocking agents or calcium channel blockers has contributed to reduce perioperative morbidity and mortality. Anterior transabdominal approach is advocated as the standard operative procedure; this approach allows ready access to any site where tumors are obviously present and permits thorough exploration of the abdominal cavity for additional contralateral adrenal or extra-adrenal lesions. An accurate preoperative localization of a sporadic, unilateral, of less than 7-10 cm, benign neoplasm constitutes the indication for the laparoscopic adrenalectomy. Pheochromocytoma-free survival were 92% and 80% at 5 and 10 years respectively; in living patients without recurrence, hypertension-free survival was 74% and 45% at 5 and 10 years respectively. Extra-adrenal pheochromocytomas are frequently malignant (36%) and are associated with a high incidence of persistent or recurrent disease (32%).

Adrenal Gland Neoplasms↗

Laparoscopic repair of a Morgagni hernia: report of a case and review of the literature.

A case is reported of an 85-year-old woman with subacute intestinal obstruction due to a large Morgagni hernia containing the transverse colon. The repair was carried out laparoscopically without a mesh. The procedure lasted 45 min, and the patient was discharged after 4 days. According to the literature, mini-invasive repair of a Morgagni hernia can be performed easily and without complications. In only few cases was a mesh necessary. The Morgagni hernia must be considered a clear indication for laparoscopic surgery, which should be offered as the first approach to this disease.

Aged↗

[Assessment and treatment of incidentally discovered adrenal tumors].

An incidentally discovered adrenal mass involves two main questions: the first is the evaluation of the hormonal activity of incidentalomas, that by definition are considered clinically silent. The second problem is to establish preoperatively the biologic behaviour of the masses, whether they are benign or malignant. An essential endocrinological screening of these masses includes the 24 hour urine VMA determination, serum potassium level, and a 1 mg overnight dexamethasone suppression test. Furthermore, the recent observation of a possible partial deficit of 21-hydroxylase suggests the advantage of 17-hydroxyprogesterone dosage after ACTH stimulation. At present no biochemical or radiologic markers can reliably distinguish benign from malignant masses. For this reason the association of imaging study with scintigraphy seems to be helpful, providing "concordant" or "discordant" patterns with CT images. As regard to therapeutic indications, the resection of all hypersecretive masses, proved malignant or increased in diameter tumors is suggested. As regards to biochemically silent lesions, the tumor size has been deemed to be the most helpful determinant of the nature although controversy remains over the size cutoff below which the masses can safely be presumed to be benign and therefore observed. The threshold to proceed surgically has been based on the perceived risk of cancer balanced against the operative risk. However it seems reasonable to recommend excision or surgical exploration for hormonally silent tumors greater than 3 cm, particularly in younger patients. According to personal opinion the laparoscopic approach might represent the gold standard in the treatment of incidentally discovered adrenal masses.

Adrenal Gland Neoplasms↗

[Uninodular bronchioalveolar carcinoma. Apropos of 10 operated cases].

BACKGROUND: This study reports 10 cases of uninodular bronchiolo-alveolar carcinoma (BAC) operated on in the General Surgery and Organ Transplantation Institute of the University of Parma between January 1st 1981 and December 31st 1995. METHODS: Seven patients were males and three females, mean age was 65 (DS 11, range 37-75) and globally accounted for 6.4% of all surgically treated lung malignant tumors. RESULTS: Hospital mortality was null; one patient was treated with assisted ventilation four days after surgery for respiratory insufficiency. Actuarial survival at 36 and 60 months was 48% and 36% respectively; survival rates were not significantly different at log-rank test from squamous carcinoma (46.2% at 36 months, 35% at 60 months) and adenocarcinoma (50.5% at 36 months, 34.3% at 60 months). The analysis of other series of literature shows significantly higher survival rates at 5 years for BAC than for adenocarcinoma (55.6% vs 40%). CONCLUSIONS: Broader series are needed for statistical confrontation with other histological types by stage and grade. There is no evidence of peculiar prognostic or clinical features in this histological type of pulmonary malignancy, prognosis so far is in fact conditioned by the same factors of other non small cell lung carcinomas.

Adenocarcinoma, Bronchiolo-Alveolar↗

[Carcinoid of the appendix. Observations on 4 cases].

Four cases of carcinoid tumors of the vermiform appendix are reported. Clinical presentation in 3 cases was suggestive of acute appendicitis and they were submitted to appendicectomy. The carcinoid tumor was discovered by the pathologist on specimen of appendix. The tumors's size, less than 2 cm, the absence of serosal involvement and lymphatics invasion suggested that simple appendicectomy was a satisfactory treatment for such patients. Occasionally clinical presentation of appendiceal carcinoid is characterized by symptoms of intestinal obstruction or intussusception, palpable mass, bleeding. In the fourth patient, that had symptoms consistent with ileal occlusion, we found at laparotomy a bulky tumor of the base of appendix infiltrating and obstructing the cecum and right colon, without liver metastases. A right hemicolectomy with end-to-end anastomosis was performed. Aggressive behaviour of this tumor was also revealed by the single pulmonary metastasis, finding very uncommon in carcinoid of appendix. This patient died postoperatively, at 25th day, of septic abdominal complications, secondary to anastomotic leak. The former patients at clinical and radiological (CT scan) follow-up performed at 3, 12, 36 months respectively, are still alive and disease free.

Adolescent↗

[Hemorrhagic pseudocyst of the adrenal gland: a case report].

A case of haemorrhagic cyst of the adrenal gland (pseudocyst) is reported. The interest is related to the histologic and pathogenetic aspects which are still controversial. In this case the cyst may be explained as a consequence of an hamartomatous vascular anomaly or as a traumatic consequence: the histopathological finding characterized by the presence of irregular vascular channels in the outer fibrous wall of the cyst may suggest that haemorrhage occurred in a preexisting blood vascular anomaly, whereas the anamnestic information of a trauma in the past suggests a traumatic origin of the mass. Clinical findings were characterized by lumbar tension and pain without palpable mass; the specific diagnosis was made preoperatively by ultrasonography and CT scan of the abdomen. Left adrenalectomy was performed through an anterior extraperitoneal approach following a supraumbilical incision.

Adrenal Gland Diseases↗

[Laparoscopic adrenalectomy. A critical review of the literature].

Open adrenalectomy needs surgical incisions often large and traumatic, with a not negligible morbidity. Laparoscopic adrenalectomy, according to the experiences reported in the literature, certainly initial, but nevertheless considerable, seems to offer a sound option and will probably become one of the strongest indications of the minimal-access surgery of the retroperitoneal space. Operative times are certainly longer initially than in open surgery but morbidity is very low and mortality almost nil. The authors make a review of the literature about laparoscopic adrenalectomy with about 400 operations collected, analyzing the results and the technical details. The collected data support the conclusion that the adrenal pathology, with the exception of the malignant tumors, will be treated in the future mainly laparoscopically. Even the size of the tumor, in case of a not malignant mass, can not be considered probably a true contraindication.

Adrenal Gland Neoplasms↗

[Clinical suspicion and instrumental diagnosis of ruptured aneurysm of the abdominal aorta. Analysis of our experience].

The authors report their experience in the management of 54 patients who underwent emergency surgery for rupture of an abdominal aortic aneurysm, correlating results to time of diagnosis. The overall mortality rate was 55.5%. The extent and the site of bleeding, free blood in peritoneal cavity or retroperitoneal hematoma alone, were critical factors influencing survival and were correlated to early of diagnosis. Patients with small hematomas had no mortality; cases with more extensive hematomas had a mortality rate of 53%; in case of intraperitoneal bleeding the mortality rose to 73% (p = 0.001). The median times between symptoms' onset and surgical intervention was correlated with a significant value to extent of retroperitoneal hematoma (p = 0.003). This time is also significantly different in dead patients compared to survivors (p < 0.001). In patients with incorrect admitting diagnosis the mean times between onset of symptoms and surgical treatment was significantly different from time of correctly diagnosed patients (p < 0.001). Our findings emphasize the need for rapid recognition of prodromal symptoms of rupture and the earlier referral of patients with known abdominal aneurysm; we suggest that in an unstable patient with a suspected ruptured aneurysm immediate surgery should be performed without delay for confirmatory tests or full resuscitation.

Aged↗

Evidence of pulmonary tropism of bamifylline and its main active metabolite.

The extent of the extraplasmatic tropism of bamifylline (Bamifix) was evaluated in the rat and in man by assaying concentrations of bamifylline and of its main active metabolite AC-119 in lung tissue and plasma. After a single oral and intravenous administration of bamifylline in the rat, the ratio between pulmonary and plasma concentrations was between 2.0 and 3.2 for bamifylline, and between 4 and 15 for AC-119 during the observation period considered. On the other hand, the same ratios, calculated after the oral and intravenous administration of theophylline, ranged between 0.20 and 0.39. In studies on man, samples of plasma and lung tissue were obtained during surgery in subjects affected by pulmonary neoplasia and previously subjected to therapy with bamifylline according to the usual dosage scheme. The ratios between tissue and plasma concentrations, at the steady-state and in conditions of equilibrium between the compartments, were 9.4 for bamifylline and 34.7 for its active metabolite. The particular tissue tropism of bamifylline, that appears to be due to its high lipophilic character, could partly explain its high therapeutic index.

Animals↗