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Biomedical subjects

P Giovannini

Publications and source records attributed to P Giovannini.

At least 19 recordsLinked to original sources

Hysteroscopic findings in 344 women with recurrent spontaneous abortion.

STUDY OBJECTIVE: To evaluate the prevalence of different anatomic factors in women with recurrent spontaneous abortion (RSA). DESIGN: Retrospective analysis over 9 years (Canadian Task Force classification II-2). SETTING: University hospital-affiliated endoscopic unit. PATIENTS: Three hundred forty-four consecutive patients with RSA and 922 controls referred for abnormal uterine bleeding. INTERVENTION: Diagnostic hysteroscopy. MEASUREMENTS AND MAIN RESULTS: Major and minor uterine mullerian abnormalities (septate, unicornuate uteri) were found significantly more often in women with RSA than in controls (32% vs 6%, p <0.001). The frequency of acquired uterine anomalies (submucous myomas, polyps) was significantly higher in controls (32% vs 9%, p <0.001). No significant differences were observed between groups in frequency of adhesions (4% vs 2%). CONCLUSION: Major mullerian uterine abnormalities are associated with RSA, and minor uterine anomalies may be correlated with an increased risk of recurrent miscarriage.

Abortion, Habitual↗

Cabergoline in Parkinson's disease complicated by motor fluctuations.

Cabergoline is a long-acting D2 dopamine (DA) agonist. We conducted an open study to investigate the effectiveness and tolerability of cabergoline, administered once a day orally, in 50 consecutive patients with Parkinson's disease complicated by motor fluctuations and dyskinesias. In 15 patients cabergoline replaced another direct DA agonist. Evaluation after 6 months of treatment (also including patients who dropped out during this period), showed an improvement in off or on hours, or both, in excess of 50% in 27 patients, comprising 20 of the 35 patients (57%) previously untreated with DA agonists and seven of the 15 patients (47%) already on DA agonists when the study began. Of the 22 patients who received the treatment for 1 year, the improvement was maintained up to final evaluation in the patients not on DA agonists at admission (n = 16), whereas a slight deterioration in clinical condition was observed in the patients already on DA agonists at admission (n = 6). Only six patients showed a detectable increase in dyskinesias. The most common side effects were gastric upset (n = 12), orthostatic hypotension (n = 3), and ankle edema (n = 3), all mild; also observed were two cases of pleural effusion/pulmonary fibrosis. Twenty patients (40%) failed to complete the treatment; of these, five (10% of total) dropped out because of adverse effects. It is concluded that once-daily administrations of cabergoline are useful for treating patients with Parkinson's disease with motor fluctuations and may advantageously substitute other DA agonists. The side effects of the drug are generally mild, although two cases involving pleuropulmonary complications did emerge.

Aged↗

Intrathecal immune activation in three patients with progressive myoclonic ataxia.

Three patients displaying a clinical picture of progressively evolving multifocal action myoclonus and cerebellar ataxia showed a marked intrathecal immune activation, which was persistent over a 2- to 5-year time span in the two serially investigated patients. A thorough search for metabolic, toxic, infectious, or degenerative causes of myoclonus was unsuccessful. The presence of intrathecal immune activation in at least a subgroup of patients with the clinical features of progressive myoclonic ataxia suggests the possibility of immune-mediated damage within the central nervous system in this condition.

Adult↗

Clinical and magnetic resonance features of the classic and akinetic-rigid variants of Huntington's disease.

We studied 32 patients with confirmed Huntington's disease (HD); six (mean age, 31.7 years) had the akinetic-rigid form and 26 (mean age, 46.1 years) had the classic hyperkinetic form. Clinical examination included a count of abnormal involuntary movements, motor self-sufficiency evaluation by the Physical Disability Rating Scale, cognitive function assessment by the Mini-Mental State examination, and a verbal fluency test. Magnetic resonance imaging permitted measurement of bicaudate diameter, a sensitive indicator of caudate atrophy in HD. Patients with the akinetic-rigid form of HD were younger and had earlier disease onset than those with the classic form of HD. All patients with akinetic-rigid HD (group 1) had striatal hyperintensity on T2-weighted magnetic resonance images; seven patients with classic HD (group 2) had a similar abnormality. Groups 1 and 2 were in fact similar in all other respects, except that the number of abnormal involuntary movements was greater in group 2. Groups 1 and 2 together had significantly younger age at onset, lower Mini-Mental State Examination score, more severe motor disability, worse verbal fluency test result, and greater bicaudate diameter than the 19 patients with classic HD without magnetic resonance signal abnormality (group 3) and appear to be a uniform population, distinct from group 3. The abnormalities on magnetic resonance images indicated greater striatal damage in groups 1 and 2, which could be the neuroanatomic substrate of their greater motor and cognitive compromise.

Adult↗

Response to L-DOPA in multiple system atrophy.

A poor response to L-DOPA in addition to parkinsonian, cerebellar, and autonomic signs is commonly regarded as indicative of clinical multiple system atrophy (MSA). We compared the motor response to a single oral administration of 250 mg L-DOPA/25 mg carbidopa in eight MSA patients and eight Parkinson's disease (PD) patients with the "on-off" phenomenon, evaluating L-DOPA peripheral pharmacokinetics. Motor response was consistently good in all PD patients, but only four MSA patients had a (moderate) response. Pharmacokinetic parameters did not differ between the groups. The varying extent of putaminal damage could be responsible for the differing motor response to L-DOPA in MSA patients.

Adult↗

Respiratory chain and mitochondrial DNA in muscle and brain in Parkinson's disease patients.

There are several reports of a defect of complex I in the substantia nigra (SN) of Parkinson's disease (PD) patients. To evaluate whether this is specific to dopaminergic neurons or the phenotypically relevant consequence of a widespread failure of the mitochondrial oxidative phosphorylation (OXPHOS) system, we measured respiratory enzyme activities in muscle homogenates from 16 PD patients and eight age-matched controls, and in muscle isolated mitochondria of six PD patients and six age-matched controls. We found no difference between the PD and control groups. In addition, we detected, by polymerase chain reaction, the mitochondrial DNA (mtDNA) "common deletion" (CD) in muscle specimens of 14 of 17 PD patients, but we obtained similar results in age-matched controls. In both groups, the amount of CD-specific deleted (delta) mtDNA ranged from 0.0% to 0.1%. Our data suggest that PD cannot be attributed to a multisystem decline of mitochondrial OXPHOS, and that lesions of muscle mtDNA in PD are likely due to normal aging. However, there was a remarkable accumulation of delta mtDNA in the SN of a PD patient and an age-matched control, suggesting that the SN is exquisitely sensitive to age-dependent damage of the mitochondrial genome.

Adult↗

Early-onset Parkinson's disease.

The study was conducted on 120 patients (76 men and 44 women) affected by idiopathic Parkinson's disease (IPD) responsive to L-dopa and observed for many years. Sixty had clinical onset between the ages of 20-40, representing 10.2% of our PD population; in the others the symptoms began after the 40th birthday. The two groups were matched for sex and length of illness. In all patients a diagnosis of IPD depended on history and clinical and neuroradiological findings. Clinical, pharmacological, evolutive, and epidemiological data were collected on all patients. Thirty-six patients from each group performed motor dexterity tests (reaction time to expected and unexpected stimuli) and cognitive tests (Wechsler Adult Intelligence Scale. Benton, Short tale, and Zazzo's speed and accuracy test). To assess the prevalence of dementia and the severity of psychiatric side effects of L-dopa administration, the 60 patients with early-onset PD were compared with 134 consecutive unselected PD patients. Five percent of early-onset PD patients had a family history of the disorder. Our study showed that early-onset PD does not differ fundamentally from the late-onset form except that the former is characterized by a more rapid establishment of the full-blown parkinsonian clinical picture and deterioration of the therapeutic efficacy of L-dopa, with an earlier appearance of side effects. The results of our neuropsychological investigations suggest that early-onset PD may be a "pure" form of extrapyramidal compromise with exclusively motor manifestations.

Adult↗

Interobserver reliability between neurologists in training of Parkinson's disease rating scales. A multicenter study.

A multicenter study has been conducted to determine the interobserver reproducibility of four of the most frequently used rating scales for Parkinson's disease: the Columbia University Rating Scale (CURS) and the Webster Rating Scale (WRS), both for assessing clinical signs; the Northwestern University Disability Scale (NUDS); and the Hoehn and Yahr staging. Four resident neurologists, inexperienced in the use of the four scales, independently examined 48 parkinsonian patients. The extent to which their assessments agreed was determined by calculating the Cohen k index after the scores had been recodified. The physicians' scores agreed substantially for the CURS and the Hoehn and Yahr scale, while those for the NUDS and the WRS agreed only moderately. Analysis of individual item scores within the scales suggests improvements that would offer greater interobserver consistency.

Disability Evaluation↗

Terguride in the treatment of Parkinson disease: preliminary experience.

Terguride, a partial DA-agonist with both dopaminergic and antidopaminergic properties, was tested in 11 PD patients in the "decompensated" phase of the disease, characterized by the presence of dyskinesias and motor fluctuations. Combined treatment of these patients with 1 mg/day of terguride and stabilized doses of levodopa reduced the severity and frequency of dyskinesias and motor fluctuations along with a slight but significant improvement of parkinsonian clinical picture. The "modulatory" effect of terguride on DA receptors, in this experimental conditions, is discussed.

Dyskinesia, Drug-Induced↗

Variation of therapeutic response in Parkinson's disease: a retrospective study.

A retrospective study of variations of therapeutic response (dyskinesia and on-off phenomenon) in Parkinson's disease was conducted on 278 patients treated with levodopa for at least 6 months and hospitalized at National Neurological Institute "C. Besta" of Milan between 1974 and 1984. Variations of therapeutic response (TRV) were present in 105 of 278 patients; in this group, age at illness onset was significantly lower, while duration of levodopa treatment and also duration of illness were longer than in the group of patients without TRV. Multiple logistic regression analysis showed that the most important variables were age at illness onset and duration of treatment, but they were only modestly predictive. Other factors connected with progression of disease must also contribute to the TRV.

Age Factors↗

Mortality associated with early and late levodopa therapy initiation in Parkinson's disease.

We evaluated the possible influence of early levodopa treatment on the mortality of Parkinson's disease (PD). One hundred forty-five consecutive parkinsonian patients initiated treatment with levodopa between 1970 and 1983. Ninety-eight of those started levodopa therapy 2 or more years after symptom onset, while 47 received levodopa within the 1st 2 years of the disease. At the end of follow-up, in December 1985, 49 patients had died. Mortality was 2.5 times higher among patients who delayed initiation of levodopa therapy 2 or more years than among those who initiated the therapy earlier. Age and disease severity were the most significant predictors of survival after initiation of levodopa treatment. The risk of death was 10% higher every year of age increase and was 2 and 4 times higher, respectively, for patients at Hoehn and Yahr stages II and III than for patients at Hoehn and Yahr stage I. When we controlled for the effect of age and disease severity on mortality, the cumulative death probability was no longer significantly higher among patients who delayed levodopa treatment than among patients treated within 2 years from disease onset. As far as mortality is concerned, the results show that the time of levodopa treatment initiation during PD has no influence and the drug can be introduced as soon as indicated by the severity of the disease progression.

Female↗

Evidence by calorimetry for an activation of sodium-hydrogen exchange of young rat skeletal muscle in hypertonic media.

1. The rate of energy dissipation associated with Na(+)-H+ exchange in isolated, superfused soleus muscles from young rats was measured with an isothermal microcalorimeter during quasi-stationary states of oxidative metabolism. 2. Under normal physiological conditions, amiloride, an inhibitor of the Na(+)-H+ exchange across plasma membranes, had no measurable effect on the specific rate of muscle heat production (E); the ouabain-suppressible part of E was identical whether amiloride was absent or present. 3. E was increased under hyperosmotic conditions and the difference with respect to control (excess E) was proportional to the degree of hyperosmolarity of the superfusate. It was 48% of basal E during a +100 mosM stress (with no change of extracellular Na+ concentration, Na+o). Inhibition of Ca2+ release into the sarcoplasm with sodium dantrolene (10(-5) M) or tetracaine (5 x 10(-5) M) suppressed a substantial part (65 and 53%, respectively) of the steady-state excess E (1.2 mW (g wet weight)-1) induced by the +100 mosM stress. Practically 100% of excess E was suppressed in the nominal absence of extracellular sodium (Na+o = 0, Li+ substitution) or under 15 mM-Na+o, and excess E was enhanced when Na+o was increased (hyperosomolarity by addition of Na2SO4 instead of sucrose). 4. Under hyperosmotic conditions, amiloride at the 5 x 10(-7) M concentration had no effect on excess E whereas at 10(-4) M it induced a significant decrease of excess E. The absolute effect of 10(-4) M-amiloride was -0.34 mW (g wet weight)-1 (equal to 28% of the excess E due to a +100 mosM-sucrose stress and to 14% of the excess E due to a +100 mosM-Na2SO4 stress). It was left unaltered in the presence of dantrolene and was independent of the way the +100 mosM stress was obtained (i.e. 100 mM-sucrose or 50 mM-Na2SO4). It was suppressed at Na+o = 0-15 mM and could be mimicked by guanochlor, another potent inhibitor of Na(+)-H+ exchange. In the presence of 10(-4) M-amiloride, the ouabain-suppressible E was significantly reduced. In the presence of ouabain, amiloride had no effect. 5. Muscle tissue space available to [3H]inulin was measured in parallel experiments. It was 23.3% under control conditions and 30.6% after a 2 h exposure of the muscle to a +100 mosM-Na2SO4 stress.(ABSTRACT TRUNCATED AT 400 WORDS)

Amiloride↗

Evidence for a modulating effect of Na+/H+ exchange on the metabolic response of rat brown adipose tissue.

Membrane potential and intracellular pH (pHi) were simultaneously monitored in rat perifused brown adipose tissue fragments by means of double-barrelled microelectrodes. In parallel experiments, the respiratory rate was measured. The cytosolic pH of unstimulated brown adipocytes was about 0.5 units higher than the value expected for a passive transmembrane distribution of H ions. Isoproterenol (5.10(-10)M) had no effect on pHi and membrane potential while it induced a 3.1 +/- 0.5-fold increase of the respiratory rate. Clonidine (10(-7)M) alone was followed by a cytosolic alkalinization of 0.14 +/- 0.05 pH units with no concomitant increase in the respiratory rate. A mirror image of the intracellular alkalinization induced by clonidine, i.e. an acidification of 0.09 +/- 0.03, was noted by monitoring the extracellular pH. Addition of clonidine in the presence of isoproterenol induced an alkalinization of 0.17 +/- 0.03 pH units and a 7.7 +/- 1.0-fold increase of the respiratory rate. Thus the alkalinizing effect of clonidine developed despite a massive increase in CO2 production. Pretreatment of the preparation with amiloride (10(-3)M), an inhibitor of Na+/H+ exchange, completely prevented the alkalinization and markedly reduced the potentiating effect of clonidine on the isoproterenol-induced respiratory rate. The results obtained are compatible with the hypothesis of a modulating effect of Na+/H+ exchange on the brown adipocyte metabolic response to catecholamine stimulation.

Adipose Tissue, Brown↗

Lisuride in Parkinson's disease. 4-year follow-up.

Lisuride at a mean daily dose of 3 mg was given to 48 patients with idiopathic Parkinson's disease. Twenty received lisuride alone (Group A) and 36 received lisuride + L-Dopa + peripheral decarboxylase inhibitors (Group B). Dropouts were due primarily to lack of efficacy in Group A patients and to mental side effects in Group B patients. The patients who remained in the study for the full 4 years showed distinct improvement, which was maintained. Group A patients did not have the on-off phenomenon or abnormal involuntary movements.

Adult↗