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Biomedical subjects

M Guidotti

Publications and source records attributed to M Guidotti.

At least 19 recordsLinked to original sources
PubMed1995

Progress in the development of oxytocin antagonists for use in preterm labor.

From a targeted screening effort and medicinal chemistry program, L-368,899 was selected as the first orally-active oxytocin (OT) antagonist to enter clinical trials. In animal studies, L-368,899 was shown to be a potent and selective OT antagonist and was orally bioavailable in rats, dogs and chimpanzees. L-368,899 was further shown to be a potent OT antagonist in pregnant rhesus and to inhibit spontaneous nocturnal uterine contractions. In Phase I human studies, L-368,899 was generally well-tolerated given intravenously and showed significant plasma levels after oral administration. In addition, L-368,899 blocked OT-stimulated uterine activity in postpartum women with a potency similar to that in the pregnant rhesus monkey. More recently, another structural series has been pursued, represented by L-371,257 [1-(1-(4-(N-acetyl-4-piperidinyloxy)-2-methoxybenzoyl)pip eridin-4-yl)- 1,2-dihydro-4(H)-3,1-benzoxazin-2-one]. L-371,257 exhibits high affinity (Ki, 4.6 nM) for human uterine OT receptors with high selectivity vs. human vasopressin receptors. In rat tissues in vitro, L-371,257 is a potent and competitive OT antagonist (pA2, 8.4) and, in vivo, blocks OT-stimulated uterine activity given both i.v. and intraduodenally. L-371,257 highlights the promise of this novel structural class.

Animals↗
PubMed1993

Pathogenetic and prognostic features of lacunar transient ischaemic attack syndromes.

Lacunar ischaemic stroke syndromes are a well defined subgroup of ischaemic strokes. To determine whether a similar subgroup can be identified among patients with transient ischaemic attacks (TIAs) we studied prospectively 102 consecutive patients within 24 hours of their first TIA. Based on their history they were classified as lacunar TIA syndromes (LTIAS; n = 45) if isolated motor or sensory symptoms or their combination had involved at least two of three body parts (face, arm, leg), whereas all other subjects were grouped as non-lacunar TIA syndromes (NLTIAS; n = 57). All patients were investigated according to a standardised protocol and followed up for an average of 51.1 months. Cardiac and arterial sources of thromboembolism were more frequent among NLTIAS (p = 0.0001). Survival curve analysis demonstrated that LTIAS had a significantly lower long term mortality and incidence of major vascular events. In a multivariate regression analysis, the type of TIA (that is, NLTIAS) was an independent predictor of stroke or death. LTIAS share the same distinct pathogenetic and prognostic features of lacunar ischaemic stroke syndromes. These findings have implications for management of TIAs and for studies of their natural history and treatment.

Adult↗
PubMed1990

Silent cerebral ischemia in patients with chronic atrial fibrillation--a case-control study.

The cerebral CT-scan results of 72 patients with chronic atrial fibrillation (AF) were compared to those of an age- and sex-matched control group, affected by muscle-tensive headache. None of the patients in the study had any neurologic symptoms. All were normal on neurologic examination. Mean age was 68 years in both groups. Patients with atrial fibrillation had a higher prevalence of hypertension, diabetes and hyperlipidemia, although the differences were not significant. Thirty-two patients (44.4%) with AF showed hypodense lesions on cerebral CT-scan, suggestive of small infarcts, whereas this finding was present only in eight control subjects (11.1%) (p less than 0.05). These results confirm in part the observations reported in literature and suggest a more thorough examination of the problem regarding the prophylaxis of thrombo-embolic risk in patients affected by chronic AF.

Aged↗
PubMed1989

Reassessment of the role of splenic leukocyte oxidative activity and macrophage activation in expression of immunity to malaria.

The role of splenic leukocyte oxidative activity and macrophage activation in the development of protective immunity was examined during acute Plasmodium chabaudi adami malaria. Splenic leukocyte oxidative activity was compared in infected BALB/c and P/J mice; the latter are known to suffer from defects in macrophage function. Phorbol myristate acetate-stimulated chemiluminescence and superoxide anion production by splenic leukocytes from infected BALB/c mice were found to be increased dramatically, while the response of splenic leukocytes from infected P/J mice was elevated only minimally. Hydrogen peroxide release was slightly increased in splenic leukocytes from infected BALB/c mice but remained essentially unchanged in those from infected P/J mice. Macrophage function was assessed on the basis of measurements of tumoricidal activity. Splenic macrophages from uninfected BALB/c mice displayed significant tumoricidal activity against L929 target cells. As a result of splenomegaly during infection, tumoricidal activity, when calculated on a per-spleen basis, was increased further in infected BALB/c mice. In contrast, the tumoricidal activity of splenic macrophages from P/J mice was minimal, regardless of infection. Despite these differences, both strains of mice developed malarial infections that resolved within 16 days. Thus, while the production of reactive oxygen radicals by splenic leukocytes and the phenomenon of macrophage activation have traditionally been associated with the resolution of malarial infection, this study failed to establish a correlation between these parameters and the development of protective immunity to blood-stage infection with P. chabaudi adami.

Animals↗
PubMed1989

A case-control study of transient global amnesia.

To evaluate risk factors and prognosis of transient global amnesia (TGA), three groups of 30 subjects each affected respectively by: (1) first-ever TGA; (2) first-ever transient ischaemic attack (TIA); (3) depressive neurosis, were compared. Prevalence of cerebrovascular risk factors was similar in patients with TGA and TIA, but significantly lower in the third group. CT showed more hypodense lesions in TIA patients than in those with TGA. In a mean follow-up of 36 months, five TGA patients experienced a TIA and three others had recurrence of TGA, but none suffered stroke or myocardial infarction. In the TIA group, four had recurrence of TIA, two suffered a stroke and two others a myocardial infarction, whereas none had TGA attacks. None of the patients of the third group had any ischaemic event during follow-up. The similar prevalence of risk factors, but the different prognosis between TGA and TIA patients, suggest that TGA is an ischaemic event, probably not triggered by thromboembolism but by a different, possibly vasospastic, mechanism.

Adult↗
PubMed1989

Local murine recombinant gamma interferon enhances the acquisition of allergic contact dermatitis in the mouse.

Using the model of allergic contact dermatitis in mice, we have demonstrated that local administration of recombinant (r) murine gamma interferon (gamma-rIFN) to the sensitization site substantially enhances the acquisition of delayed-type hypersensitivity. Single doses of gamma-rIFN from 500 to 2,000 U immunopotentiate successfully, with a suggestion of a better response at the higher doses. The immunoadjuvant effect is lost when the injections of gamma-rIFN are at a site distant from the sensitization site. Kinetic studies imply that gamma-rIFN is most effective when given at the time of sensitization, but significant immunopotentiation can be seen when gamma-rIFN is given several days before or after sensitization.

Adjuvants, Immunologic↗
PubMed1985

Heroin myelopathy: a case report.

Acute transverse myelitis was observed as a complication of intravenous heroin addiction in a young man. Recovery within seven weeks was good, but not complete. The literature is reviewed and the possible pathogenetic mechanisms are discussed.

Adult↗
PubMed1985

Digital subtraction angiography in patients with cerebral ischaemic attacks and normal continuous wave Doppler studies.

The cervico-cranial arteries were studied using digital subtraction angiography in 50 patients with reversible cerebral ischaemic attacks and normal continuous wave Doppler examination. Digital subtraction angiography was able to visualise the arteries satisfactorily in 45 patients (90%), and revealed minor arterial abnormalities in 12 patients (24%). However, neither occlusions nor stenoses greater than 50% of the diameter of the vessel lumen were found. Although digital subtraction angiography is more accurate than continuous wave Doppler examination in detecting arterial lesions, it did not provide alternative therapeutic choices in any of these patients.

Adult↗
PubMed1985

Reversible ischemic attacks with normal angiogram: risk factors, clinical findings, and prognosis.

One hundred seventeen patients with reversible ischemic attacks were divided into two groups according to the presence of atheromatous lesions on angiography. Female sex, vertebrobasilar territory involvement, and younger age were related to normal angiograms. Among risk factors, only hypertension was associated with atheroma. However, the number of risk factors in each patient was related linearly to angiographic abnormality. Later stroke and myocardial infarction were significantly more common in patients with atheromatous lesions.

Adolescent↗
PubMed1983

Subcortical aphasia: two clinical-CT scan correlation studies.

Two clinical-CT scan studies were undertaken in order to investigate the frequency and the characteristics of aphasia following strictly subcortical left hemisphere lesions. In Study 1, all patients whose CT scan, carried out within a given period, showed subcortical lesions in both hemispheres, were evaluated for presence and type of aphasia; conversely, in Study 2 the records of all patients referred to our Aphasia Unit for language evaluation within a given period, were examined for presence of subcortical lesions on the CT scan. In Study 1 aphasia was found in two out of six patients. In Study 2 stabilized, strictly subcortical lesions of the left hemisphere were found in six out of 250 patients referred to the Aphasia Unit; 4 out of 6 were aphasics. Closer scrutiny of the type of language disorder in the aphasics from both studies (N = 6) suggests the possibility of differentiating two types of defect: an atypical non fluent aphasia, sometimes associated with anterior capsular-putaminal lesions, and a mild fluent aphasia, sometimes associated with posterior capsular-putaminal lesions.

Adult↗
PubMed1983

A case of aphasia following left thalamic hemorrhage.

In a patient without fluent speech, good comprehension, aphasia and frequent neologisms, computerized tomography (CT scan) demonstrated a left posterior thalamic hemorrhage sparing other language areas. We discuss the existence and the anatomical and pathogenetic mechanisms of thalamic aphasia.

Aged↗