Gabexate mesilate vs gabexate mesilate combined with octreotide in the prevention of postoperative complications of pancreatic surgery: preliminary results

To date, gabexate mesilate, a synthetic protease inhibitor, has been used in the prophylaxis and treatment of acute pancreatitis, but has yet to be tested in preventing the postoperative complications of pancreatic surgery. For this purpose we planned a pilot study based on two treatment groups, each numbering 25 patients, submitted to high-risk pancreatic resection. In the first group, all patients received a continuous infusion of gabexate mesilate 1 g/day up to postoperative day 4; the second group of patients received the same treatment plus octreotide 0.1 mg every 8 hours for 5 days after surgery. All patients were followed until discharge with clinical and instrumental investigations to detect the onset of postoperative complications. The overall incidences of an uneventful course were 40% (10/25) and 32% (8/25), respectively. We found 12 complications closely related to pancreatic surgery in the former and 8 in the latter group. In the combined treatment group therefore we observe a 33% reduction in the incidence of related abdominal complications (12 vs 8). This favourable trend, however, needs to be confirmed in a larger multicentre trial.     

Simultaneous occurrence of ipsilateral cluster headache and chronic paroxysmal hemicrania: a case report

A 42-year-old man came to our headache unit in October 1995 complaining of recurrent attacks of headache, which had begun in February 1991. Chronic cluster headache was diagnosed, and he was given verapamil, 360 mg per day. The attacks ceased in the following months and verapamil was stopped in March 1996. In May 1997, a recurrence of the attacks required the readministration of verapamil, 360 mg per day. The attacks decreased (one to three per week), but after 2 months the patient reported a worsening in his condition due to the appearance of shorter attacks, which were diagnosed as chronic paroxysmal hemicrania. The administration of indomethacin, 225 mg per day, resulted in the disappearance of the short attacks. The concomitant occurrence of attacks of cluster headache and chronic paroxysmal hemicrania suggests the presence of shared factors in the pathophysiology of the two forms of headache. This hypothesis is supported by previous reports in the literature.     

The proprotein convertases furin and PACE4 play a significant role in tumor progression

Processing of latent precursor proteins by proprotein convertases (PCs) into their biologically active products is a common mechanism required for many important biologic functions. This process is tightly regulated, leading to the generation of active peptides and proteins including neuropeptides and polypeptide hormones, protein tyrosine phosphatases, growth factors and their receptors, and enzymes including matrix metalloproteases (MMPs). These processing reactions occurs at pairs of basic amino acids. Within the past several years, a novel family of Ca(2+)-dependent serine proteases has been identified, all of which possess homology to the endoproteases subtilisin (bacteria) and kexin (yeast). This family of PCs is currently comprised of fewer than a dozen members, known as furin/paired basic amino-acid-cleaving enzyme (PACE), PC1/PC3, PC2, PC4, PACE4, PC5/PC6, and PC7/PC8/lymphoma proprotein convertase. They share a high degree of amino-acid identity of 50-75% within their catalytic domains. Despite the relatively high degree of homology in the PC family, only PACE4 and furin localize to the same chromosome: mouse chromosome 7 and human chromosome 15. Recent reports have supported a possible functional role for PCs in tumorigenesis. For instance, convertases have been shown to be expressed in various tumor lines and human primary tumors. Furin and PACE4 process stromelysin 3 (MMP-11 or Str-3), an MMP involved in tumor invasion, into its mature, active form. Similarly, a growing family of MMPs, known as membrane-type metalloproteinases (MT-MMPs), and growth factors and adhesion molecules such as E-cadherin show similar amino-acid motifs and thus could be activated by furin and PACE4. These data, taken together with the high expression levels of PACE4 in 50% of murine chemically induced spindle cell tumors, confer to PACE4 and possibly other PCs a possible functional role in the activation of MMPs and consequently in tumor cell invasion and tumor progression. This was further supported by the remarkable enhancement in the invasive ability of the PACE4-transfected murine tumor cell lines. Mol. Carcinog. 28:63-69, 2000.     

The role of computerized tomography in the diagnosis of osteoid osteoma

Radiological diagnosis of osteoid-osteoma is based upon conventional radiographic techniques, i.e. plain film and tomography, scintigraphy and Computed Tomography (CT). The authors report on the use of CT in 13 patients affected by histologically verified osteoid-osteoma, in different locations, as related to their main clinical and epidemiological signs. A comparison is made of the diagnostic contribution of the different techniques, including scintigraphy and tomography, when available. CT results were evaluated referring to fundamental semiologic elements, such as the presence of the nidus--with or without calcifications--of perilesional sclerosis, hyperostosis and periosteosis. As a rule, we can affirm that CT allows a better spatial location in the metaphysodiaphyso-epiphyseal areas, the only exception being represented by location in the metacarpal and phalangeal bones, which are better evaluated in the axial plane due to their thinness. CT is otherwise indispensable for a correct evaluation of the posterior vertebral arch.     

Cellular and molecular gateways to urolithiasis: a new insight

Urolithiasis is a relevant clinical problem in everyday practice with a subsequent burden for the health system. Urolithiasis is classically explained as the derangement in the process of biomineralization involving the equilibrium between promoters and inhibitors of crystallization: a deficit of one or several inhibitors or an excess of one or several promoters plays a pivotal role in the stone formation. The revolutionary introduction of the molecular biology in medicine has given a new insight in urolithiasis too. Genetic factors have also been postulated to play an important role. A review of the current knowledge on urolithiasis based upon a molecular and genetic approach is reported.     

Neurological examination in healthy term infants aged 3-10 weeks

OBJECTIVES: The neurodevelopmental progress of newborn term infants is checked routinely at around 6 weeks of postnatal age. The maturation of neurological signs in this age range however has not been systematically studied and normative data are not available. The aim of this study was to document any changes in posture, tone, reflexes, behaviour and movements in low-risk full-term infants between 3 and 10 weeks of postnatal age. STUDY DESIGN: We performed a structured neurological examination previously standardised in full-term newborns in the first 48 h after birth. In the current study, a total of 76 examinations were performed between 3 and 10 weeks of age in low-risk full-term infants. RESULTS: The results of the examinations were divided according to postnatal age. In most items, the scores changed with time, with a definite shift in their distribution occurring around 6 weeks. At this age, a reduction in flexor tone of the limbs was observed, together with an increase in active neck tone. Visual orientation in contrast had already improved by 3 weeks when all infants were able to follow a target in a full circle compared to newborns that are often only able to follow a target in an arc. CONCLUSIONS: Our results suggest that 6 weeks post-term birth is an important milestone for changes in neurological signs, particularly those related to muscle tone and posture, probably reflecting maturation of the nervous system. These findings provide important guidelines for the interpretation of the neurological examination performed at this age.     

Endo/exo-proteolysis in neoplastic progression and metastasis

Biological control of individual cells, organs, and organisms is achieved through interplay of a host of specific interactions that involve various peptidic molecules as modulators or effectors. In tumor cells, these processes may result in uncontrolled growth as a consequence of autocrine and/or paracrine actions. In recent years, growing evidence has accumulated for the important role of proprotein convertases (PCs) and peptide -amidation enzymes in these processes. The widespread belief that these enzymes are involved in the major features of tumor progression, namely, invasiveness and metastasis, has taken place because of their capacity to process and activate many protein precursors involved in the neoplastic progression and metastasis. This includes degrading extracellular matrix proteases, growth promoting factors, and adhesion molecules. Usually, when the processing of these precursor proteins is achieved by one or more of the known PC family members within the general motif (K/R)-(X)_n-(K/R), where n=0, 2, 4, or 6, and X, any amino acid except Cys, the accomplishment of the maturation of these molecules is attained by various posttranslational modifications, including the carboxy-terminal -amidation. This review article summarizes recent findings on the role of these enzymatic systems in multiple cellular functions that impact on the invasive/metastatic potential of cancer cells and highlight the potential use of their inhibitors in the treatment of multiple cancers.