Specific ultrarush desensitization in Hymenoptera venom-allergic patients.

BACKGROUND: Hymenoptera venom hypersensitivity is an epidemiologically important problem. The only effective treatment in the management of venom-allergic patients with a history of generalized reactions to insect sting is specific immunotherapy. OBJECTIVE: To demonstrate safety and effectiveness of a modified ultrarush desensitization protocol in venom-allergic patients. METHODS: Fifty-seven patients with Hymenoptera venom allergy underwent a specific 1-day ultrarush desensitization by the subcutaneous route, reaching the cumulative dose of 101.1 microg in 2.5 hours. The maintenance dose (100 microg) was administered after 15 days and thereafter once a month. Patients were followed up for a year. Antihistamines were withheld for 15 days before and during desensitization to not underestimate the incidence of adverse effects. RESULTS: All patients but I completed the ultrarush desensitization. (This patient discontinued the treatment because of a hypertensive crisis not related to the desensitization.) The treatment caused a rapid variation of immunological parameters (IgE, IgG4) since the 15th day. After the desensitization, skin prick test results became negative in 15 patients (27%, decrease of 3.5 log), whereas they decreased in 14 patients (25%, decrease of 1 log). Sixty-four percent showed no adverse effects. Only 7% had a mild systemic reaction. CONCLUSIONS: Ultrarush desensitization is an effective and safe therapy in the management of patients with Hymenoptera venom allergy. In fact, it provides a faster tolerance, without significant differences regarding incidence of severe adverse effects, compared with traditional and rush protocols. It can be adopted for all patients, even children and teenagers.     

Development and characterisation of neutralising monoclonal antibody to the SARS-coronavirus

There is a global need to elucidate protective antigens expressed by the SARS-coronavirus (SARS-CoV). Monoclonal antibody reagents that recognise specific antigens on SARS-CoV are needed urgently. In this report, the development and immunochemical characterisation of a panel of murine monoclonal antibodies (mAbs) against the SARS-CoV is presented, based upon their specificity, binding requirements, and biological activity. Initial screening by ELISA, using highly purified virus as the coating antigen, resulted in the selection of 103 mAbs to the SARS virus. Subsequent screening steps reduced this panel to seventeen IgG mAbs. A single mAb, F26G15, is specific for the nucleoprotein as seen in Western immunoblot while five other mAbs react with the Spike protein. Two of these Spike-specific mAbs demonstrate the ability to neutralise SARS-CoV in vitro while another four Western immunoblot-negative mAbs also neutralise the virus. The utility of these mAbs for diagnostic development is demonstrated. Antibody from convalescent SARS patients, but not normal human serum, is also shown to specifically compete off binding of mAbs to whole SARS-CoV. These studies highlight the importance of using standardised assays and reagents. These mAbs will be useful for the development of diagnostic tests, studies of SARS-CoV pathogenesis and vaccine development.     

Novel MC1R variants in Ligurian melanoma patients and controls

Several variant forms of the melanocortin-1 receptor gene (MC1R) have been associated with red hair, fair skin and an increased risk for melanoma. Their involvement in melanoma susceptibility is apparently linked both to skin sensitivity and to non-pigmentary pathways. We investigated the frequency of the MC1R variants in the Italian region of Liguria, where the occurrence and penetrance of melanoma are low and primary susceptibility is characterized by prevalence of the CDKN2A c.301G>T [p.G101W] founder mutation. Additionally, we attempted to establish the frequency of the red hair/fair skin phenotype in our region. As predicted by anecdotal evidence, the frequency of red hair/phototype I was very low (0.7%). Screening of 17 red-haired individuals and their red-haired relatives, 207 controls and 214 melanoma patients unselected for hair color but all of Ligurian descent, led to the detection of 8 novel substitutions (c.133T>C [p.F45L], c.248C>T [p.S83L], c.332C>T [p. A111V], c.479G>A [p.R160Q], c.637C>T [p.R213W], c.793G>A [p. V265I], c.923C>T [p. T308M], c.943T>C [p.C315R]), 1 novel deletion (c.520_523delGTC [p.V174del]) and 3 novel synonymous variants (c.366G>C [p. V122V], c.684G>A [p. Q228Q], c.726C>T [p.T241T]). Preliminary genotype/phenotype correlation seems to indicate that other genes involved in the regulation of human pigmentation may mask the recessive action of high-penetrance MC1R alleles, thus determining the low frequency of at-risk phototypes and of incidence and/or penetrance of melanoma in Liguria.     

Neutralizing and binding antibodies to IFN-beta: relative frequency in relapsing-remitting multiple sclerosis patients treated with different IFN-beta preparations.

The frequencies of anti-interferon-beta (IFN-beta) antibody development reported to date in patients treated with different IFN-beta preparations are not readily comparable mainly because of differences in underlying diseases and assay methods. Thus, the frequency of neutralizing antibody (NAb) and binding antibody (BAb) development was analyzed in a sample of sera derived from a homogeneous group of relapsing-remitting multiple sclerosis (RRMS) patients treated with different IFN-beta preparations. The frequency of developing NAb and BAb to IFN-beta varied according to the IFN-beta given. Specifically, the NAb seroconversion frequency was significantly higher in patients treated with Betaferon, Schering AG, Berlin, Germany (31.3%) than in patients treated with both preparations of recombinant IFN-beta 1a (Rebif, Serono, Geneva, Switzerland [7.4%] or Avonex, Biogen, Cambridge, MA [6.3%]). Analysis of BAb seroconversion frequency in the same patients revealed that different IFN-beta preparations may also have different capability to induce BAb development and that BAb are produced during IFN-beta therapy at a significantly higher rate than NAb. Our main conclusion is that different human IFN-beta preparations may possess different immunogenicities, leading to varying frequency of development of antibody to IFN-beta in RRMS.     

Localized lymphatic sporotrichosis after fish-induced injury (Tilapia sp.).

Localized lymphatic sporotrichosis generally develops after the fungus Sporothrix schenckii is traumatically introduced into skin or mucosa by contaminated plant material. An 18-year-old male fisherman was injured by spines of the dorsal fin of a fish on the left third finger. The lesion became ulcerated, edematous and suppurative and did not respond to tetracycline and cephalexin. Fifteen days after the accident, a nodular lymphangitic pattern of swelling was observed. Histopathological findings and an intradermal test were suggestive of sporotrichosis and mycological cultures confirmed the diagnosis. The lesions resolved after oral treatment with potassium iodide. Sporotrichosis is a common subcutaneous mycosis in Brazil, and there is a previous report in the literature of this disease being acquired via trauma involving fish spines.     

Ultrastructural analysis of pancreatic acinar cells from mice fed on genetically modified soybean

No direct evidence that genetically modified (GM) food may represent a possible danger for health has been reported so far; however, the scientific literature in this field is quite poor. Therefore, we investigated the possible effects of a diet containing GM soybean on mouse exocrine pancreas by means of ultrastructural, morphometrical and immunocytochemical analyses. Our observations demonstrate that, although no structural modification occurs in pancreatic acinar cells of mice fed on GM soybean, quantitative changes of some cellular constituents take place in comparison to control animals. In particular, a diet containing significant amount of GM food seems to influence the zymogen synthesis and processing.     

Expression of human CD81 in transgenic mice does not confer susceptibility to hepatitis C virus infection

We previously demonstrated that hepatitis C virus (HCV) binds to human CD81 through the E2 glycoprotein. Therefore, expression of the human CD81 molecule in transgenic mice was expected to provide a new tool to study HCV infection in vivo, as the chimpanzee is the only species currently available as a laboratory animal model that can be infected with HCV. We produced transgenic mice expressing the human CD81 protein in a wide variety of tissues. We confirmed binding of recombinant E2 glycoprotein to the liver tissue as well as to thymocytes and splenic lymphocytes in the transgenic mice. We inoculated chimpanzee plasma infected with HCV into these animals. None of these transgenic animals showed evidence of viral replication. Furthermore, human CD81 transgenic mice that lack expression of endogenous mouse CD81 were also resistant to HCV infection. We conclude that expression of human CD81 alone is insufficient to confer susceptibility to HCV infection in the mouse. The presence of additional possible factors for HCV infection is discussed.     

Pharyngotonsillitis caused by Streptococcus pyogenes: clinical and epidemiological aspects and resistance phenotypes towards macrolides

During 2001 we analyzed 1730 pharyngeal swabs for S. pyogenes (SGA): 1142 children (0-10 years old), 132 adolescent subjects (11-17 years old), and 456 adults (18 or more years old). 994 subjects (664 children, 85 adolescent ones, 245 adults) had acute pharyngotonsillitis. In this last group we observed 321 positivities (32.3 %) for SGA: 40.4 % among children, 24.7 % among adolescent people, 13.1 % among adults. The pharyngotonsillitis prevailed during winter and spring. The resistances (R) towards erythromycin were 27.7 % (89 cases), and among children 30.6 % (82 cases), towards clyndamicin 15.3 % (49 cases, and 17.2 %, 46 cases, among children), towards rokytamicin 11.8 % (38 cases, and 13.1 %, 35 cases, among children). These were the phenotypes of R to erythromycin: 25.8 % M-phenotype, 19.1 % inducible (iMLS), 55.1 % constitutive (cMLS); among children respectively 25.6 %, 18.3 % and 53.7 %. Increased resistances towards 16-C macrolides, increased resistances of cMLS to erythromycin, and the persistence of R to 14-C macrolides around 30 % are discussed.     

Isokinetic knee joint test in "gonalgia sine materia"

Fifty-four subjects, aged between 20 and 35 years, divided into two subgroups, respectively 30 healthy subjects (17 males and 13 females) and 24 subjects with "gonalgia sine materia" (13 males and 11 females) underwent isokinetic exercise test in order to compare their dominant limb with the not dominant one as regard as the strength of extensor and flexor muscles of the knee. No statistically significant difference was found in any of the studied parameters in the comparison between the dominant limb and the not dominant one, both within the subgroup of healthy subjects and within the subgroup of subjects with "gonalgia sine materia". Authors conclude that psychological features may play a preeminent role in the genesis, as well as in the maintenance of "gonalgia sine materia", thus confirming previous data available in medical literature.