Effect of cefodizime (HR 221) on immunological defects induced by surgical stress.

Cefodizime, a new aminothiazolylcephalosporin, has been shown to possess immunomodulating activity in many experimental models in vivo and in vitro. The in-vivo effect of the drug was evaluated in a model represented by the surgical patient, being surgical practices usually associated with an immunological impairment involving many aspects of the immune response. Two groups of ten subjects were treated respectively with cefodizime (2 g i.v. daily) and another cephalosporin (ceftriaxone) at the same dosage. Aspecific immunity (complement activity, neutrophil phagocytosis, chemiluminescence and superoxide anion production) and cell-mediated reactivity (lymphocyte subpopulations and E-rosette-forming cells) were evaluated before, and at predetermined intervals after, surgery and antibiotic treatment. In the control group an important immunological derangement is observed, involving both lymphocytes and neutrophil functions and complement system. The treatment with cefodizime displays a positive effect with a significant improvement of impaired functions. The effect of the drug particularly influences neutrophil phagocytosis, explored with both the NBT test and determinations of chemiluminescence, and the complement system, through both the classic and the alternative pathways. A slight effect is observed on lymphocyte functions.     

Clinical study on pharmacological interaction between nimesulide and warfarin.

This article describes the pharmacological interaction between nimesulide, a recently introduced non-steroidal anti-inflammatory drug, and warfarin, an indirect anticoagulant. The aim of the study was to demonstrate if nimesulide could potentiate the activity of this anticoagulant drug, as previously shown by some authors. Ten patients, who were taking 5 mg/day of warfarin, were treated with nimesulide 100 mg twice a day, for seven days: the association of the two drugs did not alter, in a statistical way, neither prothrombin time, nor partial thromboplastin time, nor fibrinogenemia, nor bleeding time. The findings showed that, in a short-term treatment, there was no bleeding risk in combining warfarin with nimesulide.     

Why do we take care of others? In clinical research

The practice of medicine is today, as in the past, influenced by clinical research, which represents the final conduit of preclinical and translational science in their application to the patient’s treatment. Since the patients and their diseases are the object of clinical investigation and the source of the derived knowledge, a method that favors this knowledge is required. Understanding the reality of the pathologic process in clinical practice and attempting to address it demands a fundamental openness to all the factors that constitute it, including both the patient and the physician experience, and their motivation for participating in clinical research. Ultimately, since we constantly learn from our patients and their disease, medical practice cannot be separated from clinical research.     

The long journey of salicylates in ulcerative colitis: The past and the future

The advent of salicylates in the treatment of ulcerative colitis started in 1938 with the discovery of Salazopyrin by Nanna Svartz. This drug offered for the first time a therapeutic chance to patients with ulcerative colitis. In this paper we describe the fascinating history of Salazopyrin and salicylates from the first serendipitous observations to the last randomized clinical trials. Attention was paid to the pharmacokinetics and the mechanism of action of 5-aminosalicylates and, in particular, to the issue of the mucosal concentrations of 5-aminosalicylates and its therapeutic efficacy. Moreover a look at the new oral mesalazine formulations that allow the homogenous distribution of 5-aminosalicylate through all the large bowel was taken. Lastly, the possible use of mesalazine in the prevention of colorectal cancer was reviewed.     

Familial Epilepsy with Unilateral and Bilateral Malformations of Cortical Development

Summary: Purpose: To describe a family in whom two sisters with epilepsy, mental retardation, and microcephaly had different malformations of cortical development detected by magnetic resonance imaging (MRI).
Methods: Clinical investigation of the patients and their family. High-resolution MRI, cognitive testing, and repeated EEG recording in both patients.
Results: In one patient, the malformation was bilateral and diffuse but much more pronounced in the parietal and occipital regions, with MRI characteristics indicating pachygyria-polymicrogyria. In the other patient, the abnormality involved the right hemisphere, predominating around the perisylvian region, with MRI more clearly indicative of polymicrogyria. A brother also had severe epilepsy, diffuse EEG abnormalities, mental retardation, and microcephaly, but could not be studied neuroradiologically.
Conclusions: Lack of MRI studies in the parents and brother does not allow a precise hypothesis on the mode of transmission. However, findings from this family indicate that unilateral malformations of cortical development detected during investigations after seizure onset may be genetically based, suggesting that a single genetic abnormality could be responsible for bilateral or unilateral malformations.     

Occupational risk of blood-borne viruses in healthcare workers: a 5-year surveillance program.

OBJECTIVE: This study presents the results of a 5-year surveillance program involving the prospective follow-up of healthcare workers (HCWs) in the Veneto region of Italy exposed to blood-borne viruses. DESIGN: All HCWs who reported an occupational exposure to blood-borne infection joined the surveillance program. Both HCWs and patients were tested for viral markers (hepatitis B surface antigen [HBsAg], antibody to hepatitis B surface antigen [anti-HBs], antibody to hepatitis B core antigen [anti-HBc], antibody to hepatitis C virus [anti-HCV], HCV RNA, and antibody to human immunodeficiency virus [HIV]) and had these markers plus transaminases assayed at 3, 6, and 12 months and then yearly thereafter. Moreover, a program of hepatitis B virus (HBV) prophylaxis was offered to those whose anti-HBs levels were less than 10 IU/mL. PARTICIPANTS: Two hundred forty-five HCWs (156 women and 89 men) with a mean age of 37 (+/- 10) years who reported occupational exposure during the 5-year period. RESULTS: At the time of exposure, 1 HCW was positive for HBsAg (0.4%) and 2 were positive for HCV RNA (0.8%). Among the patients involved, 28 (11.4%) were positive for HBsAg, 68 (27.8%) were positive for HCV RNA, 6 (2.4%) were positive for HIV, and 147 (60.0%) were negative for all viral markers (4 patients were positive for both HCV and HIV). During the follow-up period after exposure (mean, 2.7 [+/- 1.6] years), there was no increase in transaminases or seroconversions to any of the viral markers. CONCLUSION: Our accurate postexposure follow-up revealed a lack of transmission of HBV, HCV, and HIV.     

Protein phosphorylation at tyrosine residues in v-abl transformed mouse lymphocytes and fibroblasts

Phosphotyrosine antibodies were employed to immunodecorate and immunoprecipitate proteins phosphorylated at tyrosine residues in cells transformed by Abelson murine leukemia virus (A-MuLV). In pre-B and pre-T lymphoma cells transformed by A-MuLV, the major phosphotyrosine-containing protein has an MW of 160 kDa and shares immunologically detectable sequences with the v-abl oncogene product. Moreover, two different proteins of approximately 100 and 68 kDa, heavily phosphorylated at tyrosine, were identified. Lack of immunological cross-reactivity with viral products and phosphopeptide mapping showed that the 100 and 68 kDa proteins are coded by cellular genes. Phosphoproteins were undetectable in control resting lymphocytes. The 68 and the 100 kDa proteins were phosphorylated to different extents in proliferating lymphocytes, either stimulated by the growth factor IL-2, or transformed by M-MuLV (lacking the oncogene coded kinase). In fibroblasts transformed by A-MuLV, phosphotyrosine antibodies identified 2 proteins of 120 and 70 kDa. By immunological cross-reaction and by phosphopeptide mapping, the first was identified as a 120 kDa form of the v-abl coded kinase. The 70 kDa protein is coded by a cellular gene, is not structurally related to the 120 kDa v-abl kinase, and is different from any phosphotyrosine-containing protein detected in A-MuLV-transformed lymphocytes. These data show that, upon v-abl-induced transformation, phosphorylation at tyrosine takes place also on proteins other than the 160 or 120-kDa oncogene products. In lymphocytes and fibroblasts these proteins are different, suggesting that the cascade of events triggered by the v-abl gene in different cell types involves tyrosine phosphorylation of different specific proteins.