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Biomedical subjects

M Viola

Publications and source records attributed to M Viola.

At least 19 recordsLinked to original sources

A comparison of the performance of two penicillin reagent kits in the diagnosis of beta-lactam hypersensitivity.

BACKGROUND: Skin testing with penicilloyl polylysine (PPL) and minor determinant mixture (MDM) represents the first-line method for diagnosing beta-lactam hypersensitivity. However, in 2004, Allergopharma and Hollister-Stier announced their decision to stop the production of penicillin reagents (Allergopen and PrePen, respectively) within 1 year. Therefore, we decided to compare PPL and MDM from Allergopharma (Allergopen) with those from Diater (DAP). METHODS: We skin-tested 195 subjects with both Allergopen and DAP reagents, as well as with other beta-lactams; 74 (group A) had had immediate reactions to beta-lactams and 74 (group B) nonimmediate reactions, while 47 (group C) underwent prophylactic tests. RESULTS: One hundred two patients (52.3%) had positive skin tests; 29 (14.9%) were positive to PPL and/or MDM. Of the 102 skin-test-positive patients, 44 belonged to group A, 57 to B and 1 to C; the last was positive only to Allergopen PPL (PPL-A) and tolerated the benzylpenicillin challenge. Minor determinant mixture reagents produced identical results in the 148 patients of groups A and B, 22 (14.9%) of which were positive. Both PPL reagents produced negative results in 139 of these 148 patients and positive ones in 5; one subject was positive to DAP PPL (PPL-D) and negative to PPL-A, while three patients were positive to PPL-A and negative to PPL-D; two of the latter tolerated benzylpenicillin challenges. CONCLUSIONS: Minor determinant mixture reagents produced identical results in all 195 patients. Results of skin testing with PPL reagents were concordant in 190 (97.4%) of them. Therefore, DAP reagents are a reliable alternative to Allergopen ones.

Adolescent↗

Hypersensitivity reactions to ophthalmic products.

Adverse reactions after administration of ophthalmic products have frequently been observed. These reactions can be provoked by both active principles and excipients. Different pathogenic mechanisms have been suggested for such reactions, including immunologic ones. Basophils and mast cells participate in IgE-mediated reactions through the release of mediators like histamine and tryptase, whereas a T-cell-mediated pathogenic mechanism is involved in most delayed reactions, particularly conjunctival ones and eyelid dermatitis. Prick tests and immediate-reading intradermal tests are carried out to diagnose immediate hypersensitivity reactions, while patch tests are usually performed to evaluate delayed reactions. Other diagnostic tests, such as serum-specific IgE assays in immediate reactions, as well as delayed-reading intradermal tests and/or lymphocyte transformation tests in delayed ones, are rarely performed. In this review, particular attention is addressed to the clinical and practical aspects of both cell-mediated and IgE-mediated hypersensitivity reactions to ophthalmic products.

Administration, Topical↗

Diagnosing immediate reactions to cephalosporins.

BACKGROUND: After penicillins, cephalosporins are the betalactams that most often induce IgE-mediated reactions. The development of diagnostic tests has been delayed, however, because the cephalosporin allergenic determinants have not been properly identified. OBJECTIVE: To evaluate the usefulness of skin tests, serum specific IgE assays, and challenges in diagnosing immediate reactions to cephalosporins and to clarify the pathogenic mechanism of such reactions. METHODS: We studied 76 adults with immediate reactions to cephalosporins, mainly ceftriaxone, cefotaxime, and ceftazidime. Skin tests and serum specific IgE assays were performed for culprit cephalosporins and cefaclor, as well as for penicillin, amoxicillin, and ampicillin. Some subjects with negative results underwent challenges and re-evaluations. Responses to cephalosporins other than the culprit ones were also studied. RESULTS: In the first allergologic work-up, an IgE-mediated hypersensitivity to penicillins and/or cephalosporins was diagnosed in 63 (82.9%) of the 76 patients on the basis of skin-test and/or specific IgE assay positivity. Of the 13 negative patients, eight accepted challenges and underwent re-evaluations. Considering both first- and second-evaluation results, the skin-test-positivity rate increased from 76.3% to 85.5% and that of sepharose-radioimmunoassay positivity from 67.1% to 74.3%. Overall, an IgE-mediated hypersensitivity was diagnosed in 70 patients (in seven after retesting). On the basis of skin-test and CAP-FEIA results, we classified our 76 patients into five groups: group A (three patients), positive only to penicillin reagents; B (17), positive to both cephalosporin and penicillin reagents; C (24), positive to more than one cephalosporin; D (21), positive only to the responsible cephalosporin; E (11) negative to skin tests and CAP-FEIA, including five sepharose-radioimmunoassay positive. CONCLUSIONS: Most immediate reactions to cephalosporins appear to be IgE-mediated. Cephalosporin skin testing and sepharose-radioimmunoassay are useful tools for evaluating these reactions. Cephalosporin IgE-mediated hypersensitivity may be a transient condition; therefore, allergologic exams should be repeated in patients with negative initial allergologic work-ups, including challenges.

Administration, Oral↗

Allergic reactions to antibiotics, mainly betalactams: facts and controversies.

Allergic reactions to antibiotics are commonly reported. They can be classified as immediate or non-immediate according to the time interval between the last drug administration and their onset. Immediate reactions occur within the first hour and are manifested clinically by urticaria and/or angioedema, rhinitis, bronchospasm, and anaphylactic shock; they may be mediated by specific IgE-antibodies. The main non-immediate reactions (occurring more than one hour after drug administration) are maculopapular exanthems; specific T lymphocytes may be involved in this type of manifestation. The diagnostic evaluation of hypersensitivity reactions to antibiotics is usually complex. The patient's history is fundamental; the allergologic examination includes in vivo and in vitro tests selected on the basis of the clinical features. Prick and intradermal tests are sensitive in evaluating betalactam hypersensitivity. Together with delayed-reading intradermal testing, patch testing is useful in diagnosing maculopapular reactions to systemically administered aminopenicillins. Determination of serum specific IgE is the most common in vitro method for diagnosing immediate reactions, while the lymphocyte transformation test can be performed for evaluating both immediate and non-immediate ones. In selected cases, provocation tests should be performed.

Anti-Bacterial Agents↗

Transcobalamin and methionine synthase reductase mutated polymorphisms aggravate the risk of neural tube defects in humans.

The pathogenic mechanism of neural tube defects may involve genetic polymorphisms and nutritional factors related to homocysteine metabolism. We evaluated the association of polymorphisms of three genes affecting vitamin B12-dependent remethylation of homocysteine, transcobalamin (TC), methionine synthase (MTR) and MTR reductase (MTRR), combined or not with methylenetetrahydrofolate reductase (MTHFR), with the risk of having neural tube defect in 40 children with spina bifida and 58 matched controls from South Italy. MTR 2756 AG/GG, TC 777 CG/GG /MTHFR 677 CC and MTRR 66 GG /MTHFR 677 CC genotypes increased the risk with odds ratios of 2.6 (P=0.046), 2.4 (P=0.028) and 4.5 (P=0.023), respectively. In contrast, MTHFR 677 TT was protective (odds ratio=0.11, P=0.009). In conclusion, genetic determinants affecting the cellular availability or MTRR-dependent reduction of B12 may increase the risk of spina bifida.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

A multi-institutional phase II trial of a novel inpatient schedule of continuous interleukin-2 with interferon alpha-2b in advanced renal cell carcinoma: major durable responses in a less highly selected patient population.

BACKGROUND: A prospective multi-institutional phase II trial was undertaken to define the activity and toxicity of a unique decrescendo infusion of interleukin-2 (IL-2) in combination with interferon (IFN) in patients with metastatic renal cell carcinoma. The identical regimen has shown promise in advanced melanoma. PATIENTS AND METHODS: Between February 1997 and March 1999, 47 patients with metastatic renal cell carcinoma, from five institutions, were treated with outpatient s.c. IFN (10 mU/m2/day) on days 1-5, followed by inpatient IL-2 via continuous i.v. decrescendo infusion [18 million International Units (MIU) (I mg)/m2/6 h, followed by 18 MIU/m2/12 h, then 18 MIU/m2/24 h and 4.5 MIU/m2/24 h for the following 3 days] on days 8-12, in a hospital ward without intensive care unit (ICU)-type monitoring. Treatment was repeated every 4 weeks. In contrast to high dose IL-2 protocols, patient eligibility did not require pulmonary function tests and allowed serum creatinine up to 2 mg/dl. RESULTS: Among 44 eligible patients, 57% (25) had their primary in place, 57% (25) had bone or visceral involvement, and only 4% (2) had lung as their only site of disease. The overall response rate in 43 response-evaluable patients was 16.3% [95% confidence interval (CI) 5.3 to 27.3], with three complete responses and four partial responses observed. The median survival was 13 months; nine patients remain alive at >23 months. The median duration of response is 36 months (range 11.5 to 48+ months). Toxicity was modest, consisting of typical cytokine-induced systemic symptoms and rare organ dysfunction. Severe grade 4 toxicity occurred in only 13% of the 130 cycles. CONCLUSIONS: This unique, reasonably well tolerated IL-2/IFN combination induced a modest response rate with a number of durable remissions. While the optimal IL-2-based regimen for the treatment of advanced renal cell carcinoma remains elusive, the present regimen should attract considerable interest. This is based on tumor activity very similar to high dose IL-2 in a patient population not as carefully selected for optimal organ function.

Adult↗

Prevalence of sensitization to Cupressus sempervirens: a 4-year retrospective study.

In the last few years Cupressus sempervirens has been identified as the cause of an increasing number of cases of late winter-early spring pollinosis in Mediterranean countries. We conducted a 4-year retrospective study of a large group of subjects with documented allergic respiratory disease in order to determine the prevalence, clinical significance and annual rate of sensitization to C. sempervirens pollen. Anamnestic data and skin prick tests (SPT) with common aeroallergens and C. sempervirens extract were collected from 1397 subjects (712 male and 685 female) resident in Latium, a region in central Italy, with complaints related to upper- or lower-respiratory-tract disorders or conjunctival disease. Two hundred and forty-three subjects (17.4%) showed positive results to C. sempervirens extract: 47 (19.3%) of them were monosensitized. The annual sensitization rate of SPT positivity to C. sempervirens varied from 7.2% in 1995 to 22% in 1998. All the subjects monosensitized to cypress pollen had symptoms from January through April. Our study suggests that sensitivity to C. sempervirens is responsible for respiratory symptoms in an increasing percentage of subjects. Further studies are needed to determine its frequency at the national level.

Adolescent↗

Prevalence of celiac disease in Argentina: screening of an adult population in the La Plata area.

OBJECTIVES: Up to now, the epidemiological characteristic of celiac disease among adults in South America remains unknown. The present prospective screening was designed to determine the prevalence of celiac disease in adults from the general population in an urban area of Argentina. METHODS: Between January. 1998, and May, 2000, all couples attending a centralized laboratory for an obligatory prenuptial examination in the La Plata area were offered participation in a screening program for celiac disease. The study included 2000 subjects (996 women; median age 29 yr, range 16-79 yr). All individuals completed a clinical questionnaire at the time that serum samples were obtained. A three-step screening protocol was used, as follows: 1) all samples were tested for antigliadin antibodies (AGAs) (type IgA and IgG); 2) samples that were IgA AGA positive were tested for antiendomysial antibody (EmA type IgA); samples that were positive for AGA-G but negative for IgA AGAs were tested for total IgA serum levels and EmA type IgG; and 3) subjects who were EmA-positive were referred for intestinal biopsy. RESULTS: At the end of the screening we detected 10 subjects who were EmA-A positive and two others who were IgA-deficient (both were EmA-G positive). Up to now, 11 of the 12 subjects (including nine EmA-positive and two IgA-deficient subjects) had endoscopic intestinal biopsies showing the characteristic celiac histology. The remaining EmA-positive individual was considered to be affected by celiac disease. The overall prevalence assessed was 1:167 (6.0 x 1000 subjects; 95% CI = 3.1-10.5). Eight of the 12 (67%) subjects were female (1:124; 8.0 x 1000; 95% CI = 3.5-15.8) and four (33%) were male (1:251; 4.0 x 1000; 95% Cl = 1.1-10.2). Although eight new patients were considered to be asymptomatic, three presented with a subclinical course and one was classically symptomatic. Only one patient had been previously diagnosed with celiac disease. CONCLUSIONS: Our screening protocol showed a very high prevalence of celiac disease for an urban area of Argentina that is ethnically similar to 90% of the general population of the country. The prevalence among women was double that for men, and the heterogeneous clinical picture of new patients showed predominance of asymptomatic cases.

Adolescent↗

Food-dependent exercise-induced anaphylaxis: clinical and laboratory findings in 54 subjects.

BACKGROUND: In some subjects, specific foods trigger anaphylaxis when exercise follows ingestion (specific food-dependent exercise-induced anaphylaxis, FDEIAn). Skin test and/or RAST positivity to foods suggest an IgE-mediated pathogenic mechanism. Others suffer from anaphylaxis after all meals followed by exercise, regardless of the food eaten (nonspecific FDEIAn). We sought to identify the culprit foods with a diagnostic protocol. METHODS: We collected detailed histories and performed skin prick tests (SPT) with 26 commercial food allergens, prick plus prick tests (P+P) with 15 fresh foods (including 9 assessed with SPT), and RAST for 31 food allergens. Treadmill stress tests were administered after a meal without any positive food (food plus exercise challenge, FEC). RESULTS: Among the 54 patients, 6 could not recall any suspect food. The other 48 suspected a specific food in at least one episode. The most frequent were tomatoes, cereals and peanuts. Fifty-two subjects were positive to at least one food (22 to more than 20), whereas 2 showed no positive results. All suspect foods were positive. SPT, P+P and RAST displayed different degrees of sensitivity. Each test disclosed some positivities not discovered by others. Two subjects reacted to FEC. Overall, 48 patients probably had specific FDEIAn and the other 6 nonspecific FDEIAn. CONCLUSION: It is useful to test both in vivo and in vitro an extensive panel of foods. Avoidance of foods associated with skin test and/or RAST positivity for at least 4 h before exercise has prevented further episodes in all our patients with specific FDEIAn.

Allergens↗

[Idiopathic portal hypertension with splenic infarct. An unreported complication].

We present a case of Idiopathic Portal Hypertension (IPH) with Splenic infarct in a 23-year-old female. She was referred to the hospital because of enlargement of liver and spleen. A computed axial tomography revealed Splenic infarct. The spleen was surgically removed. At laparotomy the liver was found to be enlarged and a liver biopsy performed. The biopsy showed characteristic changes of IPH. After the splenic resection all hematologic manifestations disappeared, suggesting that they were due to hypersplenism. The IPH is very uncommon in western countries. We don't know of any case previously reported in Argentina and our patient is the first case of IPH with Splenic infarct.

Adult↗

[Subcutaneous emphysema caused by postoperative vomiting].

The authors present 3 cases of subcutaneous emphysema after postoperative vomiting treated during a 4-year period. All patients were female, they underwent positioning during general anaesthesia--rotation on their abdomen and they vomited postoperatively with subsequent development of subcutaneous emphysema. The course was benign in all cases after conservative treatment. The authors discuss the possible etiology, diagnosis and treatment.

Adult↗

Phase I chemotherapy study of biochemical modulation of folinic acid and fluorouracil by gemcitabine in patients with solid tumor malignancies.

PURPOSE: This phase I biochemical modulation study evaluated the maximum-tolerated dose (MTD), toxicity, and effectiveness of the combination of folinic acid (FA)/fluorouracil (5-FU) followed by escalated dose levels of gemcitabine (FFG) in patients with advanced solid tumors. PATIENTS AND METHODS: Patients were refractory to primary treatment and/or without effective treatment options. Twenty-eight patients received an intravenous (IV) infusion of FA 100 mg/m(2) over 1 hour and a 5-FU 450 mg/m(2) IV bolus in the middle of the FA infusion. After the FA infusion, gemcitabine was administered at a steady rate of infusion of 10 mg/m(2)/min over initially 30 minutes and with increases of an additional 15 minutes at each given level. One cycle consisted of six weekly treatments followed by a 2-week rest. RESULTS: The MTD of gemcitabine was established at 900 mg/m(2) given over 90 minutes. Eight patients of 21 with metastatic colorectal cancer achieved responses (one complete response; seven partial responses), for a response rate of 38%. Responses were seen across the gemcitabine doses of 300 to 900 mg/m(2). One patient had prior treatment with FA/5-FU for advanced disease. Patients with colorectal carcinoma had a median survival of 18 months, and the patient with lung carcinoma has been alive for 24+ months. CONCLUSION: The combination chemotherapy of FFG was well tolerated and may benefit patients with advanced colorectal carcinoma. A phase II evaluation in this patient population is in progress.

Adult↗