Perugia urodynamic method of analysis (PUMA): a new advanced method of urodynamic analysis applied clinically and compared with other advanced methods.

AIMS: The aim of this study is to compare PUMA curves with different pathologic conditions causing bladder dysfunction in 158 men and 83 women. METHODS: PUMA results in terms of bladder outlet obstruction and detrusor contractility were compared in 92 men with benign prostatic hypertrophy (BPH) and p(ves) congruent with p(det) (i.e., p(abd) congruent with 0) with the results of the urodynamics operator's opinion, the provisional International Continence Society method, Abrams and Griffith's diagram, urethral resistence factor (URA), Sch?fer's diagram, and Watt factor. PUMA curves correlated reliably with different pathologic conditions such as obstructive BPH, orthotopic bladder, cystocele, the neurological bladder, and bladder diverticulum. Statistical analysis indicated excellent agreement between PUMA and URA; agreement with other methods was good in cases of obstruction and nonobstruction. In doubtful cases, as diagnosed by standard methods, PUMA agreed only with the Abrams and Griffith's diagram. PUMA and Wmax were in good agreement on detrusor con traction force. Agreement between PUMA and Sch?fer's diagram was excellent for patients with detrusor hypercontractility and good for patients with detrusor hypocontractility and normocontractility. PUMA is the only method applicable to women. It is easy to perform. When integrated with other diagnostic tests, it provides realistic data for diagnosis, medical or surgical therapy, and outcome.     

Nasal septal perforations: our surgical technique.

OBJECTIVE: The aim of this paper was to describe our surgical technique for the treatment of nasal septal perforations. STUDY AND DESIGN: We studied 31 patients with nasal septal perforation treated with an endoscope-assisted technique, based on a bilateral dissection of monopedicled mucosal flaps from the nasal fossa floor, sutured at the edge of the perforation previously unstuck, without any graft interposed between the two mucosal layers. RESULTS: In our experience with 31 patients, the use of this technique led to the persistent closing (with follow-up for at least one year) of 96.3% of the perforations smaller than 3 cm. CONCLUSIONS: Our technique has the advantage of an endonasal approach, without any external incision, and the use of monopedicled flaps from the nasal fossa floor without any graft interposition, avoiding any other surgical procedure and morbidity in the donor site of the graft. The use of nasal endoscopy permits superior precision in all surgical steps. SIGNIFICANCE: The high success rate in perforations smaller than 3 cm seems to confirm the effectiveness of this technique.     

Functioning human insulinomas

Sixty-seven insulinomas were investigated by immunohistochemistry using site-directed antibodies against insulin, proinsulin, chromogranin A, HISL-19, and four proteins directly or indirectly involved in the proteolytic processing of proinsulin: the prohormone convertases PC2 and PC3, carboxypeptidase H (CPH) and 7B2. Results were expressed in a six-grade score according to the frequency of immunoreactive tumour cells. Insulin was expressed by all tumours, appearing in either a diffuse or a polarized pattern and being detected in more than 30% of tumour cells in all cases but three. Proinsulin was also expressed in all tumours, with more than 50% of tumour cells immunoreactive in all cases but 5. It was consistently localized in the Golgi apparatus. In about half the cases, moreover, it also showed diffuse cytoplasmic staining, usually with a very sparse distribution. Trabecular and solid insulinomas did not present specific, homogeneous patterns of insulin immunostaining. However, insulin immunoreactivity was much more abundant in trabecular than in solid neoplasms, being present in virtually all tumour cells (score 6) in 50% and 8% of cases, respectively. Virtually all insulinomas expressed PC2, PC3, CPH and 7B2, usually in 30–100% of tumour cells, with a frequency significantly related to that of insulin. However, detection of PC2 and 7B2 was slightly less frequent than that of PC3 and CPH. In consecutive sections these proteins were found to be mostly co-localized with insulin and chromogranin A but not with proinsulin. They were heavily expressed in all 10 tumours with more than 10% of cells showing cytoplasmic proinsulin immunoreactivity, indicating that the leakage of proinsulin from the Golgi compartment is not associated with faulty expression of converting enzymes and possibly reflects a saturated processing capacity. HISL-19 immunoreactivity was found in both Golgi apparatus and insulin stores, indicating that the relevant antigen is different from all other proteins investigated. These results do not support a defect in expression or localization of proinsulin-processing enzymes in most insulinomas.     

Different patterns of 11q allelic losses in digestive endocrine tumors

Most foregut digestive endocrine neoplasms may be associated with the multiple endocrine type 1 (MEN-1) syndrome. In contrast, midgut/hindgut carcinoids never show such association. To investigate the pathogenetic involvement of the MEN-1 gene and of putative additional oncosuppressor gene(s) distal to it, a comparative analysis of loss of heterozygosity (LOH) at chromosome 11q13 to 11qter was performed in 27 foregut (pancreatic endocrine tumors [PETs]), 23 midgut (ileal and appendiceal), and 3 hindgut (rectal) endocrine tumors. LOH at the MEN-1 gene locus at 11q13 was observed in 52% of the 23 sporadic and in all 4 MEN-1-associated PETs and was found to consistently and continuously span to the most distal marker investigated at 11qter. In contrast, only occasional, discontinuous, and mostly interstitial LOH for 11q markers was observed in ileal (midgut) carcinoids, whereas no LOH was found in all appendiceal (midgut) and rectal (hindgut) carcinoids. The consistent extension of LOH from the MEN-1 region to 11qter in sporadic PETs suggests a mechanism of gene inactivation via chromosomal breakage and complete loss of chromosome 11q; furthermore, these results expand beyond the 11q13 region the search for additional oncosuppressor gene(s) potentially involved in the genesis of these neoplasms. The low frequency, limited extension, and discontinuous distribution of 11q deletions in midgut/hindgut carcinoids suggest that MEN-1 gene is not involved in the pathogenesis of these tumors.     

Conformational analysis of heparin binding peptides

A properly engineered biomaterial for dental/orthopaedic applications must induce specific responses from the osteoblasts at the implant site. A most desirable response is an efficient adhesion, as it represents the first phase in the cell/material interaction and the quality of this phase will influence the cell's capacity to organize into a new functional tissue. The four osteoblast-adhesive peptides discussed in this paper are mapped on the 339-364 sequence (339MAPRPSLAKKQRFRHRNRKGYRSQRG364) located in the primary heparin-binding site of human vitronectin (HVP). Adsorbed on a polystyrene scaffold, these peptides display different adhesive activities towards osteoblasts. In this paper we report on the structural analysis in solution of the peptides through NMR and computational techniques. We find that the peptides with the highest adhesive activities display a hydrophobic patch opposite to the charged surface candidate to interact with heparin. These findings suggest that the peptides might adsorb on the polystyrene support in a favourable orientation for their activity. Furthermore, molecular models obtained for the four peptides in solution were used in rigid docking simulations with a heparin model. Assuming that the peptide solution conformations are not very different from the polystyrene-adsorbed structures, the simulations reveal that peptide adhesive activity is also affected by the number of ionic interactions and spacing between charged residues.     

Well-being therapy of generalized anxiety disorder

BACKGROUND: There is increasing awareness that the goal of treatment in generalized anxiety disorder (GAD) should not simply be a response, but restoration of normal function. The aim of this study was to apply a novel psychotherapeutic approach for increasing the level of remission in GAD. METHODS: Twenty patients with DSM-IV GAD devoid of comorbid conditions were randomly assigned to 8 sessions of cognitive behavioral therapy (CBT) or the sequential administration of 4 sessions of CBT followed by other 4 sessions of well-being therapy (WBT). Assessment methods included the Anxiety and Depression Scales of Paykel's Clinical Interview for Depression, Ryff's Psychological Well-being Scales and Kellner's Symptom Questionnaire. A one-year follow-up was undertaken. RESULTS: Significant advantages of the CBT-WBT sequential combination over CBT only were observed with both observer and self-rated methods after treatment. Such gains were maintained at follow-up. CONCLUSIONS: These preliminary results suggest the feasibility and clinical advantages of adding WBT to the treatment of GAD. They lend support to a sequential use of treatment components for achieving a more sustained recovery.     

Malignancy-associated allelic losses on the X-chromosome in foregut but not in midgut endocrine tumours

Information on genetic changes involved in the progression of gastroenteropancreatic (GEP) endocrine tumours is scanty. On the other hand, the identification of molecular markers of malignancy could be crucial for the prognostic evaluation of these neoplasms, which is hardly predictable on the basis of conventional histological criteria. An association of X-chromosome deletions with malignancy has already been found in gastric endocrine tumours. To investigate this further, a comparative loss of heterozygosity (LOH) analysis was performed on 17 pancreatic endocrine tumours (PETs) and 17 intestinal (ten ileal, six appendiceal, and one rectal) carcinoids from female patients. The relationship of X-chromosome LOH with the ploidy status of the neoplasms was also investigated. LOH was found in six of eight malignant PETs (60% of the informative markers), but was infrequent in the nine benign ones (4.5%). In contrast, although retention of heterozygosity was consistently observed in benign midgut tumours, LOH was infrequent in malignant carcinoids (15%). No correlation was found between LOH and the ploidy status. These results indicate an association between X-chromosome LOH and malignancy in foregut endocrine tumours. The lack of such an association in midgut carcinoids suggests that different molecular mechanisms are involved in the progression of these two categories of endocrine neoplasms, which are otherwise considered to be closely related. These findings emphasize the need for further molecular studies on GEP endocrine tumours, carefully subdivided according to their anatomical site of origin.     

A Randomized Study of Epithelial Ovarian Cancer: Is Chemotherapy Useful after Complete Remission?

Objective. The aim of this study is to verify whether consolidation chemotherapy with Cisplatin improves disease-free survival and/or overall survival in patients affected by epithelial ovarian cancer.Methods. A multicenter study examined 122 randomized patients in complete remission as judged by laparoscopy or laparotomy following first-line chemotherapy consisting of ACy (Adriamycin + Cyclophosphamide), PCy (Cisplatin + Cyclophosphamide), or Mitoxantrone + Carboplatin. Sixty-one of these patients were treated with 3 cycles of 5-Fluorouracil (FU) 500 mg/m2 for 5 days followed by Cisplatin at 100 mg/m2 on the 6th or 7th day every 28 days; the other 61 received no further treatment (nihil group).Results. Sixty patients in the Cisplatin arm were evaluable. There were 36 relapses in the FU+Cisplatin arm and 30 in the nihil arm. Peritoneal relapses were 25% for Cisplatin treatment vs. 16.4 % for nihil. There were 29 deaths in the Cisplatin arm vs. 27 for nihil. Median overall survival time (95 months with Cisplatin vs. 96 months in the nihil group) and median disease-free survival (66 months with Cisplatin vs. 73 in the nihil group) were similar in both arms (p=0.66 and p=0.41, respectively). There were no significant differences in tumor stage and grade between the two arms. Seven patients presented a second neoplasm during follow-up: six in the nihil arm, but only one patient in the Cisplatin arm. Death in these patients was due to the second neoplasm and not to progression of ovarian cancer.Conclusion. Three courses of additional platinum+FU treatment after five cycles of first-line chemotherapy without FU produced no increase in overall survival or disease-free survival.