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Biomedical subjects

G Severino

Publications and source records attributed to G Severino.

12 recordsLinked to original sources

Pharmacogenomics: state of the research and perspectives in clinical application.

The person-to-person variability of drug response is a major problem in clinical practice and in drug development. It can lead to therapeutic failure or adverse drug reactions (ADRs) in individuals or subpopulation of patients. In addition to the high occurence of ADRs and the associated morbidity and mortality, substantial costs are incurred. Potential risk factors for drug inefficacy or toxicity include drug-drug interactions, the patient's age, renal and liver functions or other disease factors, and lifestyle variables such as smoking and alcohol consumption. In addition, it has become clear in recent years that genetic factors may also significantly modify drug responses or increase the risk for ADRs. Genetic variations in genes (polymorphisms) for drug-metabolizing enzymes, drug receptors, and drug transporters have been associated with individual variability in the efficacy and toxicity of drugs. It is now widely accepted that migraine is a polygenic and multifactorial disorders, thus considered to be a genetic complex disease. Genetic studies on migraine suggested a role of CACNA1A and DRD2 genes as susceptibility genes in this disorder.

Acetylation↗

[Buruli ulcer. A case report].

The authors report a case of skin infection, Buruli ulcer, which is widespread in several parts of Africa: Ghana, Uganda, Ivory Coast, Senegal and most central African countries. This infection is caused by Mycobacterium ulcerans which belongs to the non-tubercular species Mycobacterium. It resembles Mycobacterium tuberculosis in colour and morphology, but differs in its speed of growth, its nutritional requirements, its capacity to produce pigments with enzymatic activities, its heat sensitivity and its resistance to anti-tubercular agents. Mycobacterium infection follows the percutaneous inoculation of the latter and appears as a painless, erythematous nodule that develops central necrosis and ulceration. Initially, the lesion appears as skin necrosis leading to the ulceration of the dermis and epidermis. The histological lesion shows a coagulative necrosis of the deep dermis and epidermis with destruction of the nerves and blood vessels; interstitial edema is also present. Healing is accompanied by a granulomatous response and the affected area is generally covered by a depressed scar. The authors initially treated the case in question using a conservative approach. A gel (Intrasite Gel) was used whose properties allowed the destruction of necrotic tissue present on the ulcer bed and the stimulation of granulation tissue formation. The layer of gel was in turn covered with a triple layer of polyurethane which enabled the humidity of the lesion to be maintained constant, thus promoting healing and acting as a barrier against external germs. This treatment enabled the skin lesion to be completely sterilised in about 30 days using new dressings every 3 days. Surgical treatment then led to complete healing after a further 20 days.

Child↗

No evidence of association between dopamine D3 receptor gene and bipolar affective disorder.

A recent study reported a possible association between allele 1 of the dopamine D3 receptor gene and bipolar affective disorder using the haplotype relative risk approach. In attempt to replicate these findings, we used similar family-based methods, such as the Haplotype-Based Haplotype Relative Risk method and the Transmission Disequilibrium Test, in a sample of 44 bipolar probands from Sardinia with both parents available. Using the Bal I restriction enzyme site polymorphism of Lannfelt et al. (1992), no differences were found between transmitted and non-transmitted alleles and no evidence of linkage disequilibrium was observed.

Alleles↗

Carbamazepine augmentation in lithium-refractory bipolar patients: a prospective study on long-term prophlyactic effectiveness.

Twenty-two patients affected by bipolar or schizoaffective disorder, in whom carbamazepine was added to lithium after recurrence when on maintenance with lithium alone, were followed up prospectively for 2 to 13 years. The number of episodes, hospitalizations, and cumulative affective morbidity was markedly reduced after carbamazepine augmentation. Seventeen patients presented a better course during combined treatment than during lithium alone, and of these 15 had no further recurrences. Four patients did not appear to improve after carbamazepine augmentation, whereas one featured reemergence of affective episodes after having derived satisfactory benefit from combination for 7 years (delayed tolerance). Carbamazepine augmentation was associated with a reduction of lithium doses in some patients, including a subgroup who had not tolerated lithium at usual therapeutic levels. Carbamazepine significantly reduced serum thyrotropin concentrations, which were abnormally high in approximately one half of patients when on lithium alone. Total serum thyroxine concentrations were also decreased after carbamazepine augmentation, but free thyroid hormone concentrations did not change. Other significant carbamazepine-induced changes in laboratory tests included increases in total cholesterol concentrations and decreases in white blood cell counts.

Adolescent↗

Pancreatic cholera syndrome: effect of a synthetic somatostatin analog on intestinal water and ion transport.

The effect of a synthetic somatostatin analog was studied in a patient with severe secretory diarrhea due to pancreatic cholera syndrome. Basal intestinal perfusion studies indicated an absence of water and sodium absorption, and active chloride secretion in the small bowel. Intravenous administration of the somatostatin analog (1 microgram/kg.h) changed zero net water movement to absorption (122 mL/30 cm of the jejunum per hour). Chloride secretion changed to absorption (5.0 to 7.9 meq/30 cm.h), and plasma vasoactive intestinal polypeptide concentration was reduced from 330 to 45 pmol/L (normal, less than 51). When the analog was given subcutaneously, 100 micrograms twice daily, stool weight decreased, and plasma vasoactive intestinal polypeptide concentration fell toward the normal range (67 pmol/L). Plasma concentration of pancreatic polypeptide was initially elevated and dropped during intravenous infusion of somatostatin analog but returned to baseline on maintenance therapy with the analog delivered subcutaneously. The patient has not had further diarrhea during 9 months of therapy.

Adenoma, Islet Cell↗

Synganglial and neurosecretory morphology of the chicken mite Dermanyssus gallinae (DeGeer) (Mesostigmata: Dermanyssidae).

Histological techniques and paraldehyde-fuchsin (PAF) staining were used to study the synganglion and to locate neurosecretory regions and neurosecretion within the synganglion of the chicken mite, Dermanyssus gallinae. The synganglion, which is formed internally by neuropilar ganglia, gives rise to a single esophageal and paired cheliceral, palpal, pedal (I-IV), and opisthosomal nerves. The neuropilar ganglia are interconnected by commissures and connectives within the synganglion. Twelve PAF-positive neurosecretory regions are present in unfed protonymphs, unfed deutonymphs, virgin males and females, and mated males. There are 11 PAF-positive neurosecretory regions in larvae, 24-72 hours post-fed deutonymphs and mated females. Neurosecretory regions in these developmental stadia are described in relation to their positions adjacent to individual neuropilar ganglia.

Animals↗