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Biomedical subjects

A Macrì

Publications and source records attributed to A Macrì.

At least 19 recordsLinked to original sources

Endocrine effects in the hazard assessment of drugs used in animal production.

Criteria of toxicological assessment are currently reviewed to ensure an adequate protection to susceptible groups, such as infants and children; in particular, concern arises about altered endocrine homeostasis in the developing organism, eliciting possible persistent effects such as reproductive disturbances and increased risk of tumours in target organs. Such items are obviously relevant also for veterinary drugs, whose main safety issue is potential lifetime exposure to residues. Two groups of chemicals, nitroimidazoles and imidazole antifungals, are reviewed as examples of the relevance of endocrine toxicity to the hazard assessment of compounds used in animal production. Nitroimidazoles are metabolized into genotoxic intermediates; in rodents they induce testicular toxicity and carcinogenicity. In particular, mammary neoplasms, mostly fibroadenomas, are consistently induced in rats as the most important effect in chronic studies; this may hint to possible endocrine-related mechanisms. Accordingly, evidences on other chemicals (e.g., triazines) show mammary tumorigenicity in rodents associated to hormonal alterations. In fact, nitroimidazoles affect synthesis of both pituitary and steroid hormones in vitro and rise progesterone and FSH levels in rats; also, limited clinical data in humans indicate endocrine-related effects. Overall, nitroimidazoles appear to affect the endocrine balance; however, the actual importance of such alterations, especially in regards to rat mammary tumours, has yet to be clarified. Imidazole antimycotics are broad-spectrum inhibitors of steroid synthesis; accordingly, diverse reproductive and developmental alterations are observed, depending on age and sex of animals exposed. Effects include pregnancy loss, delayed pup growth as well as reduced weight of androgen-dependent tissue; however, it is still difficult to identify the most susceptible biological phase. Overall the potential for inducing endocrine-related alterations should be carefully evaluated also for drugs used in animal production. A screening battery should produce a distinct fingerprint for each major endocrine activity, thus targeting longer-term tests (such as the two-generation study) on the most relevant endpoints. Moreover, the validation of molecular approaches would contribute to a biologically-based evaluation, by providing insights on such items as early effects and species-specificity.

Animal Experimentation↗

Three-dimensional optic nerve head algorithm for the detection of glaucomatous damage.

PURPOSE: To determine whether a three-dimensional optic disc algorithm could be useful in differentiating optic nerve heads (ONH) with a normal visual field from those with an abnormal visual field also when using a simultaneous stereoscopic computerised ONH analyser. METHODS: One eye was randomly chosen from 45 normals and 55 patients with glaucoma (mean deviation -7.7 +/- 9.0 dB, corrected pattern standard deviation 3.1 +/- 2.3 dB). All the subjects were examined with the Humphrey Perimeter (program 30-2) and with the Topcon Image-net X Rev-3.51 b. Using the topographic map of the system, the algorithm of the third moment or cup shape measure was applied to the numbers (the number of points ranged from 623 to 1,883 depending on the size of the disc area) that identify the heights of all the points of the optic disc surface. Findings were analysed by means of the Mann-Whitney U test and receiver operator characteristic curves. RESULTS: The sensitivity and specificity of this three-dimensional ONH algorithm applied to Topcon Image-net was 90.6% and 85.1% respectively. No difference was found between the groups for age, disc area and number of the analysed points. CONCLUSIONS: The algorithm of cup shape measure or third moment is a useful parameter to separate eyes with normal from those with abnormal visual field also when using a simultaneous stereoscopic system such as Image-net.

Algorithms↗

The vesical granuloma: rare and late complication of laparoscopic cholecystectomy.

The spillage of gallstones into the peritoneal cavity from iatrogenic perforation of the gallbladder that occurs during laparoscopic cholecystectomy can result in late and serious complications. We report a case of vesical granuloma with symptoms of dysuria, pollakiuria, and vesical tenesmus that occurred 23 months after a laparoscopic cholecystectomy. Preoperative diagnostic evaluation showed a 3-cm vesical neoformation. A partial cystectomy was performed; macroscopic and histologic examination documented a central nidus of fragmented gallstones and a picture of chronic granulomatous inflammation. Although complications related to unretrieved gallstones that spill into the peritoneal cavity during laparoscopic cholecystectomy are rare, they are being reported with increasing frequency. Therefore, it is important to use tools and techniques that prevent lacerations of the gallbladder and involve retrieval of spilled gallstones.

Aged↗

Molecular fingerprinting of strains of Yersinia ruckeri serovar O1 and Photobacterium damsela subsp. piscicida isolated in Italy.

We studied the ribotypes, patterns of pulsed-field gel electrophoresis (PFGE) and interspersed repeated sequences (IRS)-PCR of 30 strains of Yersinia ruckeri O1 and 20 strains of Photobacterium damsela subsp. piscicida isolated from apparently unrelated epizootic outbreaks occurring on Italian fish farms between 1993 and 1999. All of the Y. ruckeri O1 strains had similar profiles, as demonstrated by all three typing methods, thus confirming the clonal structure of this species. The strains of P. damsela subsp. piscicida showed similar profiles when tested with ribotyping and PFGE; however, two slightly different profiles were distinguished by IRS-PCR using the primer ERIC2. The two profiles appeared to be related to the geographic origin of the strains, since each of them was specific to isolates from a certain area (i.e. northern or southern Italy). This result suggests that PCR fingerprinting may be a valuable tool in typing fish bacterial pathogens, which often present a great degree of genetic homogeneity.

Animals↗

Clinical and pharmacological profile in a clenbuterol epidemic poisoning of contaminated beef meat in Italy.

Long-acting beta adrenergic agonists, such as clenbuterol accumulate in the liver, but not meat of treated farm animals, and result in epidemic poisonings in consumers. We describe an outbreak of poisoning in 15 people, following the consumption of meat. Clinical symptoms (distal tremors, palpitations, headache, tachipnoea-dyspnoea, and also moderate hyperglycaemia, hypokalemia and leucocytosis) were seen in nine hospitalised patients, starting about 0.5-3 h after poisoning, and disappearing within 3-5 days later. Clenbuterol was found in the urine of all the symptomatic patients, at higher levels than pharmacokinetic computing (mean level 28 ng/ml, 36 h after ingestion), based on the levels found in the meat (1140-1480 ng/g edible tissue). Thus, epidemic poisoning can be produced following the consumption of contaminated meat. The need for a better definition of pharmaco- and toxico-kinetics, not only for drugs ingested as parent drug, but also when ingested as residues with animal tissues, is recommended.

Adrenergic beta-Agonists↗

Molecular analysis of the hydroxymethylbilane synthase (HMBS) gene in Italian patients with acute intermittent porphyria: report of four novel mutations.

Acute intermittent porphyria (AIP) is an autosomal disorder caused by molecular abnormalities in the hydroxymethylbilane synthase (HMBS) gene coding for the third enzyme in the heme biosynthetic pathway. So far, more than 160 different mutations responsible for AIP have been identified in this gene. We have now identified seven mutations in eight unrelated Italian patients with AIP: two splicing defects (IVS7+2T-->C, 612G-->T), three small deletions (308-309delTG, 730-731delCT, 182delA) and two missense mutations (134C-->A, 541C-->T). The splicing defects were responsible for activation of splicing cryptic sites respectively within intron 7 (15 bp insertion) and exon 10 (9 bp deletion). The small deletions resulted in frameshifts leading to the formation of premature stop codons. The 134C-->A and 541C-->T mutations caused the formation of stop codons likely to be responsible for drastic disruption of the HMBS structure (Ser45Ter, Gln181Ter). This is the first molecular study in AIP patients of Italian origin leading to the identification of four new mutations and three molecular defects that have already been described.

Adult↗

Echographic study of extraocular muscle thickness in children and adults.

BACKGROUND: Echobiometric evaluation of extraocular muscles in normal subjects has been performed previously, but only in adults. We determined extraocular muscle thickness in normal subjects in three age groups. METHODS: Extraocular muscle thickness was studied in 75 normal subjects divided into three age groups (5-10, 11-15 and 28-37 years) using a Biovision B-scan-S instrument in standardized A-mode (frequency, 10 MHz; biometry resolution, 0.15 mm; depth, 40-60 mm; points on X axis, 512; levels on Y axis, 256). All measurements were performed by the same operator and repeated five times. The reproducibility of the technique was determined using the coefficient of variation. The one-way ANOVA test was used to compare the three groups, and the two-tailed unpaired t-test was used to compare subjects aged 5-10 years and those aged 11-15 years, and subjects aged 11-15 years with those aged 28-37 years. RESULTS: The technique showed good reproducibility. In subjects 5-10 years old, the coefficient of variation was 8%; in subjects 11-15 years and 28-37 years old, it was 5%. Increased muscle thickness was observed with age (p < 0.001). A statistically significant difference between the medial and inferior recti muscles in subjects 11-15 years and 28-37 years old was found (p < 0.001). CONCLUSIONS: The increased thickness of all recti muscles may be influenced by growth (primarily during puberty), and the variations in thickness of the extraocular muscles may be attributable to near-vision stimulus of the inferior and medial recti muscles.

Adolescent↗

Optic disc surface smoothness and visual field indices.

BACKGROUND: In order to ascertain whether the optic disc surface smoothness (ODSS) could be used to predict the amount of visual field damage in glaucomatous eyes, the correlations between ODSS and visual field indices were evaluated. METHODS: One eye was randomly chosen from each of 40 normals and 50 patients with glaucoma. The morphology of the optic disc surface was analyzed using the Topcon IMAGEnet X Rev-3.51b. In order to define the level of "smoothness" of the optic disc surface, the differences of the relative position of each surface point was studied by measuring the standard deviation (SD) from the average height of the points (number of points ranged from 623 to 1883 depending on the size of the disc area) that identify the optic disc surface. All the subjects were also examined with the Humphrey perimeter (Program 30-2) and the results were analyzed by Mann-Whitney U-test and Spearman rank correlation coefficient. RESULTS: The difference in ODSS between the glaucomatous and the normal eyes was statistically significant. No significant correlation was found between age and ODSS. A significant correlation was found between ODSS and mean deviation (MD) and between ODSS and corrected pattern standard deviation (CPSD). In the glaucoma group there were significant correlations between ODSS and the perimetric indices MD and CPSD; no correlations were found in the normal group. CONCLUSION: The ability of ODSS to reflect the level of visual field change in glaucomatous eyes appears to be rather limited, even if statistically significant. This fact does not limit the clinical usefulness of ODSS as a diagnostic parameter in consequence of its strong correlations with the other morphometric parameters and its high sensitivity and specificity in separating normal from glaucomatous eyes.

Female↗

Effect of betaxolol on primary open-angle glaucoma and normal-tension glaucoma patients.

This study is aimed at establishing the efficacy of the therapeutic agent, betaxolol, in diurnal control of IOP (intraocular pressure). Therapy was performed on 32 eyes affected by POAG (primary open-angle glaucoma) and 16 eyes affected by NTG (normal-tension glaucoma). Two preparations of betaxolol were utilized: betaxolol hydrochloride 0.50% (Betoptic) was administered to 15 POAG and 7 NTG eyes; betaxolol hydrochloride 0.25% ophthalmic suspension (Betoptic S) was administered to 17 POAG and 9 NTG eyes. IOP measurements were taken every two hours from 8 a.m. to 8 p.m. IOP was measured before therapy and at 12 hours, 30 days, and 3 months of therapy. Betaxolol hydrochloride 0.50% was more effective at lowering IOP during the day. Diurnal pressure peaks, which are a risk factor concerning the maintenance of visual field in glaucoma patients, were also reduced using 0.50% betaxolol hydrochloride.

Adrenergic beta-Antagonists↗

Bacterial load and protein deposits on 15-day versus 1-day disposable hydrophilic contact lenses.

PURPOSE: This study quantified the bacterial load and protein deposits on 1- and 15-day disposable contact lenses after use in normal wearers. METHODS: Sixteen patients were randomly assigned to a 1-day contact lens (1-Day Acuvue) in one eye and to a 15-day contact lens (Acuvue) in the contralateral eye. Only one specified solution was allowed for the care of 15-day lenses. All patients were evaluated every month for 6 months (at times T1, T2, T3, T4, T5, T6). At times T1, T3, and T5, the lenses were removed in a sterile fashion and sent for laboratory quantification of Staphylococcus aureus and Pseudomonas aeruginosa. At T2, T4, and T6, quantification of protein deposits was determined, and at T0 and T6, impression cytology of the conjunctiva was performed. RESULTS: P. aeruginosa was not identified on any lens. At T1, T3, and T5, S. aureus was significantly greater on the 1-day versus 15-day lenses (p < 0.001). In contrast, protein deposits were significantly greater on the 15-day lenses at all time points (T2, T6: p < 0.01; T4: p < 0.05). Impression cytology of the 15-day lens eyes revealed a worsening trend compared to the 1-day lens; however, no statistically significant differences were found between the two groups (p = 0.29). CONCLUSION: Results of this study suggest that the use of cleaning and preservative solutions can alter the ocular surface bacterial environment of the contact lens wearer and that these changes are not a direct consequence of contact lens wear. The bactericidal activity of these solutions could, with time, also affect ocular surface cells, leading to contact lens intolerance and ocular surface disease.

Adult↗

RA/DA cumulative curve analysis of local and diffuse neuroretinal rim area damage in glaucoma patients.

AIM: To evaluate the validity of cumulative rim/disc area (RA/DA) curve analysis as a clinical tool for the identification of glaucoma induced optic disc pathology. METHODS: 71 normal and 83 glaucomatous eyes were evaluated from a series of 154 subjects recruited for this study. For each eye, the cumulative distribution of RA/DA was calculated from 36 equally spaced rim sectors of each optic disc obtained by the automatic evaluation of simultaneous videographics (Image-net X Rev.3/51b). To increase the sensitivity of this analysis in early glaucoma and in normal eyes, these cumulative curves were subsequently divided into two equal segments and the slopes of their respective regression lines compared. RESULTS: The median RA/DA value obtained from the 36 sectors was significantly different in glaucomatous eyes compared with normals (p < 0.001). Nevertheless, the curves (5th-95th percentile of the cumulative curves distribution) of early glaucomatous eyes fell within the normal range. When the cumulative curve of these marginal cases was then divided into two equal segments, the comparison of the slopes of the regression lines showed a significant difference (p < 0.05) in 100% of early glaucomatous eyes. Furthermore, normal eyes were shown to be true negatives in 93% of the cases in which no significant difference between the two slopes was observed. CONCLUSION: Analysis of the RA/DA cumulative curve from 36 sectors of the optic disc was a valid method for the identification of glaucomatous disc pathology; however, a further calculation of the slopes of the two RA/DA regression lines was needed to identify early glaucomatous damage.

Female↗