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Biomedical subjects

A Romano

Publications and source records attributed to A Romano.

At least 163 records · Page 9Linked to original sources

Umbilical cord blood (UCB) transplant from unrelated mismatched donor in patients with high risk (HR) leukemia.

Ten consecutive children with high risk leukemia have been submitted to UCB transplant from unrelated HLA mismatched donors. All patients received an identical regimen for conditioning and GVHD prophylaxis. The median dose of viable nucleated cells infused was 2.6 x 10(6)/kg b.w. Among the nine patients evaluable for engraftment the hematopoiesis was of full donor origin in six patients and autologous in three. At a median follow-up of 9 months, six of nine (67%) patients are alive in CR.

Adolescent↗

New aspects in betalactam recognition.

The data presented in this review confirm that penicillin continues to be the most well defined model for studying drug allergy. The identification of new specificities has improved the understanding of allergy to penicillins, and different well defined subgroups now exist. The capacity of humans to respond to unique penicillin determinants has shown that although penicillin is a very small molecule it can be recognized in different ways by different IgE antibodies. These well defined models have left open the possibility that other betalactams can also induce specific reactions which implies that for diagnostic purposes, in addition to classical determinants, others are required for in vitro and/or in vivo evaluation. When the different subgroups now recognized are compared, not only are there differences in the manner of hapten recognition but also in the evolution of the natural sensitivity and in the capacity for recognizing other structures. The recognition of betalactams by T cells is also important and a number of studies have shown that subjects respond specifically to some aminopenicillins or cephalosporins with good tolerance to benzylpenicillin. The confirmation that these responses can be a T-cell-mediated reaction have been reported not only in vitro by the generation of T cell lines and T cell clones but also in vivo doing skin biopsies in subjects who have developed different types of delayed cutaneous reactions [44]. More studies are needed to determine the structure of T cell epitopes and this will help for a better understanding of both the IgE and IgG-mediated reactions.

Animals↗

[Clinico-functional respiratory assessment of the athlete with exercise-induced asthma or bronchospasm].

Asthmatic subjects can only be allowed to take part in sport activities after a careful functional evaluation of pulmonary function. For sport disciplines which require a mainly anaerobic metabolism it is enough to evaluate the respiratory function at rest, while for sport disciplines which require a mainly aerobic metabolism it is necessary to use an exercise tolerance test. The functional tests used must be able to demonstrate not only the suitability of the subjects to take up a sport, but also to recommend an appropriate sport discipline.

Algorithms↗

Upregulation of the angiogenic factors PlGF, VEGF and their receptors (Flt-1, Flk-1/KDR) by TSH in cultured thyrocytes and in the thyroid gland of thiouracil-fed rats suggest a TSH-dependent paracrine mechanism for goiter hypervascularization.

Placenta growth factor (PlGF) and vascular endothelial growth factor (VEGF) represent two closely related angiogenic growth factors active as homodimers or heterodimers. Since goiters of the thyroid gland are extremely hypervascular, we investigated the expression of PlGF, VEGF and their receptors, Flt-1 and Flk-1/KDR, in a small panel of human goiters from patients with Graves's disease, in an animal model of thyroid goitrogenesis and in in vitro cultured thyroid cells. Here we report that the mRNA expression of PlGF, VEGF and their receptors is markedly enhanced in biopsies of goiters resected from Graves's patients. In vivo studies demonstrated that in the thyroid gland of thiouracil-fed rats, increased mRNA and protein expression of PIGF, VEGF, Flt-1 and Flk-1/KDR occurred subsequent to the rise in the serum thyroid stimulating hormone (TSH) levels and in parallel with thyroid capillary proliferation. In vitro studies confirmed the existence of such TSH-dependent paracrine communication between thyroid epithelial cells and endothelium since the conditioned medium collected from TSH-stimulated thyrocytes acquired mitogenic activity for human umbilical vein endothelial (HUVE) cells. Altogether, these data suggest that PlGF and VEGF, released by thyrocytes in response to the chronic activation of the TSH receptor pathway, may act through a paracrine mechanism on thyroid endothelium.

Animals↗

Expression of teratocarcinoma-derived growth factor-1 (TDGF-1) in testis germ cell tumors and its effects on growth and differentiation of embryonal carcinoma cell line NTERA2/D1.

The teratocarcinoma-derived growth factor-1 (TDGF-1) gene codes for a 188-aminoacid glycoprotein that shares structural homology with the epidermal growth factor (EGF) family of growth factors. TDGF-1 is highly expressed in the undifferentiated embryonal carcinoma stem cell line NTERA2 clone D1 (NT2/D1) and its expression is downregulated in response to differentiating agents such as retinoic acid (RA) and hexamethylen-bisacetamide (HMBA). To assess the role of TDGF-1 in the onset and/or progression of human germ cell tumors, we analysed TDGF-1 expression by Northern blot and immunostaining in a panel of 59 human germ cell tumors of different histological origins. We show that TDGF-1 expression is markedly elevated in a subset of human testicular germ cell tumors as compared to normal testes. TDGF-1 overexpression occurs in about 100% of tumors with non-seminomatous phenotype, such as embryonal carcinomas and malignant undifferentiated teratocarcinomas. To address the questions of how TDGF-1 (previously called CRIPTO) may affect the growth and/or the differentiation of embryonal carcinoma cells, we have characterized the effects of exogenous recombinant TDGF-1 protein on the proliferation rate and differentiation 'potential of NT2/D1. Exogenous TDGF-1 protein stimulated DNA synthesis and cell proliferation in both undifferentiated and differentiated NT2/D1 cells. However, TDGF-1 protein treatment was unable to block differentiation induced by both RA and HMBA. These results suggest that TDGF-1 growth factor may represent an autocrine growth factor that may be involved in the process of development of testicular neoplasms.

Amino Acid Sequence↗

Angiotensin II (3-8) induces long-term memory improvement in the crab Chasmagnathus.

A shadow moving overhead acts as a danger stimulus and elicits an escape response in the crab Chasmagnathus that habituates after 15 trials and for a long period of time. Previous work showed that angiotensin II enhances this long-term memory. Present results indicate: (1) that the facilitatory effect of angiotensin II is not blocked by either losartan, DUP 753 or the Parke Davis compound PD 123177; (2) that the angiotensin II (3-8) fragment has an enhancing effect on crab's memory stronger than that reported for the integer octopeptide; (3) that the hypermnestic effect of angiotensin II (3-8) is dose-dependent and saralasin reversible. The possibility that the action of angiotensin II on crab's memory were not due to its own action but to that of the degradation fragment angiotensin II (3-8) is discussed.

Analysis of Variance↗

Determination of IgE antibodies to the benzylpenicilloyl determinant: a comparison of the sensitivity and specificity of three radio allergo sorbent test methods.

The quantitation of in vitro IgE antibodies to the benzylpenicilloyl determinant (BPO) is a useful tool for evaluating suspected penicillin allergic subjects. Although many different methods have been employed, few studies have compared their diagnostic specificity and sensitivity. In this study, the sensitivity and specificity of three different radio allergo sorbent test (RAST) methods for quantitating specific IgE antibodies to the BPO determinant were compared. Thirty positive control sera (serum samples from penicillin allergic subjects with a positive clinical history and a positive penicillin skin test) and 30 negative control sera (sera from subjects with no history of penicillin allergy and negative skin tests) were tested for BPO-specific IgE antibodies by RAST using three different conjugates coupled to the solid phase: benzylpenicillin conjugated to polylysine (BPO-PLL), benzylpenicillin conjugated to human serum albumin (BPO-HSA), and benzylpenicillin conjugated to an aminospacer (BPO-SP). Receiver operator control curves (ROC analysis) were carried out by determining different cut-off points between positive and negative values. Contingence tables were constructed and sensitivity, specificity, negative predictive values (PV-), and positive predictive values (PV+) were calculated. Pearson correlation coefficients (r) and intraclass correlation coefficients (ICC) were determined and the differences between methods were compared by chi 2 analysis. Analysis of the areas defined by the ROC curves showed statistical differences among the three methods. When cut-off points for optimal sensitivity and specificity were chosen, the BPO-HSA assay was less sensitive and less specific and had a lower PV- and PV+ than the BPO-PLL and BPO-SP assays. Assessment of r and ICC indicated that the correlation was very high, but the concordance between the PLL and SP methods was higher than between the PLL and HSA or SP and HSA methods. We conclude that for quantitating IgE antibodies by RAST to the BPO determinant, BPO-SP or BPO-PLL conjugates offer advantages in sensitivity and specificity compared with BPO-HSA. These results support and extend previous in vitro studies by our group and highlight the importance of the carrier for RAST assays.

Adult↗

Long-term tolerability of nimesulide and acetaminophen in nonsteroidal antiinflammatory drug-intolerant patients.

BACKGROUND: Oral challenges are used to identify alternative nonsteroidal antiinflammatory drugs (NSAIDs) for patients who react adversely to drugs of this class, but challenge conditions often differ from those in which the drug will actually be used. OBJECTIVE: To determine whether the results of oral challenges with nimesulide or acetaminophen, using cumulative administration of a single therapeutic dose while the patient is in good health, can predict the response to multiple doses of the drug during future illness. METHODS: Follow-up interviews were conducted with 248 NSAID-intolerant subjects who had tolerated oral challenges with nimesulide and/or acetaminophen 1 to 3 years earlier. We analyzed the adverse reaction rate in light of the febrile/non-febrile nature of the condition treated and the number of doses consumed. RESULTS: Nimesulide was tolerated by 115/122 (94.2%) of the patients who had tried it; acetaminophen by 71/75 (94.6%). A total of 8/159 (5%) patients had experienced reactions (seven urticarial and one asthmatic) to one or both drugs. Intolerance was unrelated to the nature of the condition treated or the number of doses administered, but all four patients who failed to tolerate acetaminophen and 3/7 of those who reacted to nimesulide had histories of chronic urticaria. CONCLUSIONS: Oral challenges can reliably predict long-term NSAID tolerability in patients with previous adverse reactions to other drugs of this class, except for patients with chronic urticaria.

Acetaminophen↗

Delayed hypersensitivity to flurbiprofen.

Immune-mediated reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are unusual, and true allergy to the drug flurbiprofen has never been documented. We observed a patient who developed a maculopapular rash 48 h after beginning oral therapy with this drug, and 2 days later, angioedema and hypotension. Patch tests with flurbiprofen were positive 48 and 72 h after application. The clinical and allergologic features of this case strongly suggest type IV hypersensitivity. Patch testing with NSAIDs is useful for confirming clinical diagnoses of delayed hypersensitivity to these drugs.

Adult↗

Chronic encapsulated intracerebral hematoma: contribution of thallium-201 single photon emission computed tomography in preoperative diagnosis: case report.

OBJECTIVE AND IMPORTANCE: Chronic encapsulated intracerebral hematoma is a fairly rare clinical entity. This unique lesion is peculiar for its clinical onset, formation of a capsule, and progressive enlargement. The mechanism for capsule formation and self-perpetuating expansion still remains uncertain, as well as the causal relationship with vascular malformations. Because of their pseudotumoral course and misleading neuroradiological features, these lesions can be misdiagnosed preoperatively as cerebral neoplasms. CLINICAL PRESENTATIONS: A 62-year-old man was referred with a 2-month history of generalized tonicoclonic seizures. There was no history of head injury or arterial hypertension. The results of a neurological examination were normal. Computed tomographic scans revealed a slightly hyperdense roundish area in the right parietotemporal region with ring-like enhancement after contrast medium injection, moderate mass effect, and perifocal low attenuation. With the provisional diagnosis of astrocytoma, the patient was admitted for a craniotomy. Before surgery, a thallium-201 single photon emission computed tomographic study was performed, which showed no abnormal uptake of the tracer, raising significant doubt regarding the presumptive diagnosis of a tumor. INTERVENTION: Intraoperative findings revealed a hematoma, with a well-demarcated, thick, fibrous-elastic capsule. There was evidence of repeated intracapsular hemorrhages. The lesion was totally removed, and the patient recovered fully. No other pathological findings, including vascular malformations, were noted. CONCLUSION: Chronic encapsulated intracerebral hematomas probably occur more frequently than the limited number of reported cases would indicate. This case represents a realistic clinical problem-solving setting in with thallium-201 single photon emission computed tomography was used because of its capacity for functional tumor detection and differential diagnosis.

Cerebral Hemorrhage↗

Immediate hypersensitivity to penicillins. Studies on Italian subjects.

The IgE response, the involvement of the different penicillins available for therapeutic use, and the specificity of the IgE antibodies found in a group of penicillin-allergic subjects from Italy were studied. Thirty subjects with a history of allergic reactions to penicillins were studied. In vivo and in vitro specific IgE antibodies were determined to different penicillin determinants. Fifteen subjects developed anaphylactic responses and the remainder urticaria and angioedema. The drug most frequently involved in the patients' allergic reactions was ampicillin (AMP). The benzylpenicilloyl (BPO) skin test was positive in 16 (53.3%) patients, whereas 23 (76.6%) patients were positive to minor determinant mixture (MDM), benzylpenicillin (PG), AMP, or amoxicillin (AX). When classified according to initial reaction type, most anaphylactic patients (93.3%) were associated with minor determinant reactivity, whereas most urticaria patients (80%) reacted to BPO. RAST results for the anaphylactic and urticaria subgroups were similar. RAST inhibition showed that most sera contained highly cross-reactive IgE antibodies. There was evidence of a specific response to AX and PG (one patient each). These data show that in a population of penicillin-allergic patients from Italy, AMP was the main drug inducing the allergic reaction. In skin tests and RAST, patients exhibited heterogeneous IgE responses with little indication of specific reactivity to AMP.

Adolescent↗

Aminopenicillin allergy.

Eight two children with histories of maculopapular or urticarial rashes during aminopenicillin treatment underwent skin tests, patch tests, radioallergosorbent assays and, in some cases, oral challenges. Hypersensitivity was diagnosed in eight (9.8%): immediate in four with urticarial reactions and delayed (that is cell mediated) in four with maculopapular rashes. In 49 children (38 with maculopapular eruptions, 11 with urticarial/angiooedematous reactions), negative allergologic findings were confirmed using oral challenges with the suspected drug. Maculopapular rashes may reflect delayed hypersensitivity to aminopenicillins, which can be diagnosed on the basis of late intradermal reactions and/or patch test positivity. The allergen panel must include the suspected aminopenicillin itself, as many cases are side chain specific. Most patients with urticarial reactions (more typical of immediate hypersensitivity) will also react to penicilloyl polylysine and minor determinant mixture. The time elapsed between the reaction and testing must be considered if negative results emerge, because IgE mediated sensitivity (unlike cell mediated forms) declines in the absence of antigen exposure.

Algorithms↗

Eosinophil-derived proteins in postprandial (food-dependent) exercise-induced anaphylaxis.

BACKGROUND: Postprandial exercise-induced anaphylaxis (PPEIAn) is a form of EIAn in which the ingestion of food before the exercise is associated with the onset of symptoms. Skin reactivity and the presence of specific serum IgE to several food allergens suggest the occurrence of food-dependent allergic mechanisms. METHODS: In order to study the involvement of eosinophils in the pathogenesis of PPEIAn we measured the changes in serum eosinophil cationic protein (ECP) and eosinophil protein X/eosinophil-derived neurotoxin (EPX/EDN) levels in 6 patients with PPEIAn, subjected to three separate challenges with either suspected foods only, exercise after a meal without or with suspected food ingestion. RESULTS: We found serum levels of both eosinophil-derived proteins increased only in challenges including both exercise and suspected food ingestion. Symptoms of anaphylaxis occurred in 3 of these patients. CONCLUSIONS: The increased release of eosinophil basic proteins in PPEIAn patients, caused by physical exercise following ingestion of suspected foods, is not obligatory for the definition of the syndrome.

Adolescent↗

Long-term habituation (LTH) in the crab Chasmagnathus: a model for behavioral and mechanistic studies of memory.

A decade of studies on long-term habituation (LTH) in the crab Chasmagnathus is reviewed. Upon sudden presentation of a passing object overhead, the crab reacts with an escape response that habituates promptly and for at least five days. LTH proved to be an instance of associative memory and showed context, stimulus frequency and circadian phase specificity. A strong training protocol (STP) (> or = 15 trials, intertrial interval (ITI) of 171 s) invariably yielded LTH, while a weak training protocol (WTP) (< or = 10 trials, ITI = 171 s) invariably failed. STP was used with a presumably amnestic agent and WTP with a presumably hypermnestic agent. Remarkably, systemic administration of low doses was effective, which is likely to be due to the lack of an endothelial blood-brain barrier. LTH was blocked by inhibitors of protein and RNA synthesis, enhanced by protein kinase A (PKA) activators and reduced by PKA inhibitors, facilitated by angiotensin II and IV and disrupted by saralasin. The presence of angiotensins and related compounds in the crab brain was demonstrated. Diverse results suggest that LTH includes two components: an initial memory produced by spaced training and mainly expressed at an initial phase of testing, and a retraining memory produced by massed training and expressed at a later phase of testing (retraining). The initial memory would be associative, context specific and sensitive to cycloheximide, while the retraining memory would be nonassociative, context independent and insensitive to cycloheximide.

Animals↗

[Circadian variation of sudden cardiac death in young people with and without coronary disease].

Sudden cardiac death is not well known and provoking factors are yet mainly unknown. To clarify whether sudden cardiac death has a circadian rhythm in young people we have studied 40 patients < 45 years who died in Brescia between 1984 and 1993 of sudden cardiac death showing at autopsy features of coronary artery disease (CAD) and 12 patients aged < 30 years who died of sudden cardiac death without autoptic features of CAD. We observed a circadian rhythm in the hours of the morning in the two groups, more evident in patients without CAD. In patients with autoptic features of CAD, we also observed a higher rate of events during the winter months. We would like to stress the importance of the adrenergic system as a trigger able to produce the event. We believe that the role of the sympathetic nervous system is more important than other risk factors (for example platelet aggregability and blood viscosity) to precipitate sudden cardiac death, mainly because the circadian rhythm was more evident in patients without CAD. An increase of the data-base and a more detailed analysis of subgroups is necessary if we concretely want to prevent sudden cardiac death fitting antiarrhythmic therapy with circadian distribution of major events. We underline the practical impact of "chronorisk" together with the other cardiovascular risk factors.

Adult↗