Search PubMed⌕ Search

Biomedical subjects

D Testa

Publications and source records attributed to D Testa.

At least 19 recordsLinked to original sources
PubMed2000

Nitric oxide synthase induction in astroglial cell cultures: effect on heat shock protein 70 synthesis and oxidant/antioxidant balance.

Glial cells in the nervous system can produce nitric oxide in response to cytokines. This production is mediated by the inducible isoform of nitric oxide synthase. Radical oxygen species (ROS) and nitric oxide (NO) derivatives have been claimed to play a crucial role in many different processes, both physiological such as neuromodulation, synaptic plasticity, response to glutamate, and pathological such as ischemia and various neurodegenerative disorders. In the present study we investigated the effects of NO synthase (iNOS) induction in astrocyte cultures on the synthesis of heat shock proteins, the activity of respiratory chain complexes and the oxidant/antioxidant balance. Treatment of astrocyte cultures for 18 hr with LPS and INFgamma produced a dose dependent increase of iNOS associated with an increased synthesis of hsp70 stress proteins. This effect was abolished by the NO synthase inhibitor L-NMMA and significantly decreased by addition of SOD/CAT in the medium. Time course experiments showed that iNOS induced protein expression increased significantly by 2 hr after treatment with LPS and INFgamma and reached a plateau at 18 hr; hsp70 protein synthesis peaked around 18 and 36 hr after the same treatment. Addition to astrocytes of the NO donor sodium nitroprusside resulted in a dose dependent increase in hsp70 protein that was comparable to that found after a mild heat shock. Additionally, a decrease in cytochrome oxidase activity, a marked decrease in ATP and protein sulfhydryl contents, an increase in the activity of the antioxidant enzymes mt-SOD and catalase were found which were abolished by L-NMMA. These findings suggest the importance of mitochondrial energy impairment as a critical determinant of the susceptibility of astrocytes to neurotoxic processes and point to a possible pivotal role of hsp70 in the signalling pathways of stress tolerance.

Animals↗
PubMed2000

A randomized controlled trial of recombinant interferon beta-1a in ALS. Italian Amyotrophic Lateral Sclerosis Study Group.

OBJECTIVE: To evaluate the efficacy of recombinant interferon beta (IFNbeta)-1a in the treatment of ALS. BACKGROUND: It has been proposed that IFNs affect the progression of ALS by interfering with putative immune mechanisms involved in the pathogenesis of the disease. METHODS: Patients (n = 61) 40 to 70 years of age with a 6- to 24-month history of confirmed ALS with mild to moderate disability received IFNbeta-1a, 12 mIU (n = 31), or placebo (n = 30) subcutaneously three times a week for 6 months and were followed up for an additional 6 months. Patients were assessed after 4, 12, 24, 36, and 48 weeks. Medical Research Council scale, Norris scale, and bulbar scores as well as forced vital capacity were used to assess disability. Selected electrophysiologic measures (latency, amplitude, and duration of the compound muscle action potential) were also used. RESULTS: Twenty patients randomized to IFNbeta-1a and 17 patients given placebo completed the study. A total of 16 patients receiving IFNbeta-1a became non-self-supporting compared with 16 on placebo (52% versus 53%). There were no significant differences between the two treatment groups for any of the measures of disease progression and disability. Deaths were reported in six patients treated with IFNbeta-1a and four patients on placebo. Adverse events were reported more frequently with IFNbeta-1a (77% of patients) compared with placebo (57%), with flu-like symptoms and local erythema being the commonest complaints. CONCLUSIONS: This pilot study suggests that IFNbeta-1a is not effective in the treatment of ALS.

Aged↗
PubMed2000

Carbon dioxide laser turbinate surgery for chronic obstructive rhinitis.

BACKGROUND AND OBJECTIVE: The argon laser was first used to treat chronic obstructive rhinitis. Several other surgical lasers were later used to perform inferior turbinotomy. What is the ideal laser for turbinate surgery? STUDY DESIGN/MATERIALS AND METHODS: CO(2) laser with its longer wavelength (10.6 micrometer) scatters less on tissues, is less harmful than the other surgical lasers, minimizes local edema with very little damage to the nearby mucosa, and achieves excellent haemostasis. But CO(2) laser energy delivered through a fiberoptic cable is partially absorbed by the transmitting fiber. CO(2) laser delivered through surgical microscope obviates this problem, and a special self-retaining nasal speculum allows the surgeon to have both hands free to more easily perform inferior laser turbinotomy, creating a deep groove along the turbinate body. RESULTS: The laser vaporized tissues formed scar tissue, reduced turbinate bulk, restored nasal flow, and improved other symptoms: rhinorrhoea, sneezing, headache with a statistically significant reduction in total nasal airway resistance (NAR), P < 0.005, at 2 year follow-up. CONCLUSION: The CO(2) laser delivered through surgical microscope with the help of a self-retaining nasal speculum can be deemed a useful laser for turbinate surgery.

Adolescent↗
PubMed2000

Phenotypic manifestations associated with CAG-repeat expansion in the androgen receptor gene in male patients and heterozygous females: a clinical and molecular study of 30 families.

Spinal and bulbar muscular atrophy (Kennedy disease) is an adult form of X-linked motor neuron disease caused by the expansion of a polymorphic CAG-repeat sequence in the first exon of the androgen receptor gene. We studied clinical and molecular features of 36 patients and 19 heterozygous females. Phenotypic manifestations and disease severity broadly varied among our spinal and bulbar muscular atrophy patients. The size of CAG expansion significantly influences the age of disease onset, but neither clinical features nor disease severity. The majority of carrier women presented signs of chronic denervation at neurophysiological examination and, in three cases, low-amplitude sensory action potentials were recorded. Notably, a few women developed mild signs of bulbar motor neuron impairment later in life. The identification of a large number of patients by the use of the molecular test further supports the hypothesis that Kennedy disease had been previously underdiagnosed, probably because of the great variability of clinical presentation. Although an early diagnosis may not be crucial for treatment, given the lack of effective therapy, the molecular testing can be of great relevance for disease prognosis and genetic counseling.

Action Potentials↗
PubMed2000

Neuropsychological follow up in patients with Parkinson's disease, striatonigral degeneration-type multisystem atrophy, and progressive supranuclear palsy.

OBJECTIVES: Impairment of executive function is frequent in Parkinson's disease (PD), striatonigral degeneration-type multisystem atrophy (SND), and progressive supranuclear palsy (PSP); sometimes frank dementia is also present. However, the progression of cognitive decline has not been adequately studied. The objectives were to delineate the progression of cognitive impairment in these parkinsonisms and to elucidate interdisease differences. METHODS: Twenty three patients with SND and 21 with PSP, referred consecutively, and 18 patients with PD matched for severity of parkinsonism were compared on a comprehensive battery of cognitive tests and motor invalidity scales. A mean of 21 months later (range 18-24 months) the patients were called for retesting. RESULTS: Only 12 patients with PD (66.6%), 14 with SND (60.8%), and 11 with PSP (52.4%) were retested; those who dropped out refused, had died, or were too disabled. The patients with PSP performed worse than patients with PD or SND in the short tale, verbal fluency, visual search, and Benton tests at first evaluation. Overall cognitive performance was similar in the PD and SND groups except that the SND group did significantly worse on the verbal fluency test. Between group comparison of changes in scores from first to second evaluation showed that patients with PSP deteriorated significantly in the Nelson test compared with patients with PD or SND, and that patients with PSP or SND declined significantly on the visual search test compared with patients with PD. There was no difference between the groups for motor decline. Two patients with PSP were demented (DSM IV criteria) at first evaluation and six at second evaluation; no patients with PD or SND were demented at either evaluation. CONCLUSIONS: The greater decline of patients with PSP in attention, set shifting, and categorisation abilities is probably related to the conspicuous frontal deafferentation associated with direct premotor and prefrontal involvement, and to dysfunction of the midbrain ascending activating system, known to occur in PSP.

Aged↗
PubMed1999

Cognitive and magnetic resonance imaging aspects of corticobasal degeneration and progressive supranuclear palsy.

OBJECTIVE: To identify cognitive and MRI features important for the clinical diagnosis of corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP); these diseases share several clinical features and are often difficult to distinguish on clinical grounds. METHODS: Cognitive functions and MRI characteristics were examined in 16 patients with CBD and 28 patients with PSP, all diagnosed according to current clinical criteria (none was examined by autopsy). RESULTS: MRI findings differed significantly between the two groups: 87.5% of patients with CBD but none with PSP had asymmetric frontoparietal atrophy, whereas 89.3% of patients with PSP but only 6.3% of those with CBD had midbrain atrophy. Cognitive examination showed that ideomotor apraxia (De Renzi's test) was significantly more frequent in CBD, and executive functions (Nelson's test) were significantly more impaired in patients with PSP. CONCLUSIONS: MRI findings of asymmetric frontoparietal atrophy in CBD and midbrain atrophy in PSP are the most consistent and useful aids to careful clinical evaluation for differentiating between the two diseases.

Aged↗
PubMed1999

Affective symptoms in multiple system atrophy and Parkinson's disease: response to levodopa therapy.

The objective was to determine the extent to which psychiatric disturbances (especially mood disorders) generally considered poor prognostic factors, are present in patients with striatonigral (SND) type multiple system atrophy (MSA) compared with patients with idiopathic Parkinson's disease (IPD). The Hamilton depression scale (HAM-D), brief psychiatric rating scale (BPRS), and Unified Parkinson's disease rating scale (UPDRS) were administered to clinically probable non-demented patients with SND-type MSA and patients with IPD matched for age and motor disability, at baseline and after receiving levodopa. At baseline total HAM-D score was greater in patients with IPD. Overall, BPRS score did not differ between the two groups; however, patients with IPD scored higher on anxiety items of the BPRS, and patients with MSA had higher scores on the item indicating blunted affect. After levodopa, both groups improved significantly in UPDRS and HAM-D total scores (just significant for patients with MSA). Patients with IPD improved significantly in total BPRS score but patients with MSA did not. At baseline patients with IPD were more depressed and anxious than patients with MSA who, by contrast, showed blunted affect. After levodopa, depression and anxiety of patients with IPD improved significantly whereas the affective detachment of patients with MSA did not change. Major neuronal loss in the caudate and ventral striatum, which are part of the lateral orbitofrontal and limbic circuits, may be responsible for the blunted affect not responsive to levodopa therapy found in patients with MSA.

Antiparkinson Agents↗
PubMed1998

Cognitive dysfunction and impaired organization of complex motility in degenerative parkinsonian syndromes.

BACKGROUND: A frontostriatal pattern of cognitive decline, consisting of a frontal lobe-like syndrome without genuine cortical defects such as amnesia, apraxia, aphasia, or agnosia, is well established in basal ganglial diseases. Recent pathological investigations, however, have again noted cortical damage in progressive supranuclear palsy (PSP), suggesting that cortical defects could be present. OBJECTIVES: To delineate the pattern of cognitive impairment and to detect higher-order motor impairments (including ideomotor apraxia) in parkinsonian syndromes. PATIENTS AND METHODS: We assessed ideomotor apraxia, and simple and sequential tapping in patients with Parkinson disease, multiple system atrophy, and PSP with similar disease severity, age range, and education. We also administered a comprehensive battery of neuropsychological tests to examine general intelligence, memory, executive functions, attention, and visuospatial orientation. The results were compared between groups and with a matched normal control group. RESULTS: Sequential tapping and the imitation of sequences of gestures were impaired in all patient groups, with patients with PSP performing worse than the other groups. Based on ideomotor apraxia scores and a qualitative analysis of errors, 3 patients with PSP and 2 with multiple system atrophy were considered apraxic. General intelligence and executive functions were compromised in all patient groups. The impairment of patients with PSP was more pervasive than that of the other groups, and included compromise of visuospatial functions, attention, and memory. Discriminant analysis of all cognitive and motor tests showed that the tapping and ideomotor apraxia tests best identified the patients vs control subjects. CONCLUSIONS: The presence of cortical as well as subcortical damage in patients with PSP and those with multiple system atrophy is indicated by the presence of pervasive cognitive and motor disturbances in the former, substantial motor disorganization in the latter, and the finding of ideomotor apraxia in some patients with these diseases. Furthermore, the discovery that tests of motor and gesture best identified all patients vs control subjects is consistent with the existence of a common motor disorganization in these parkinsonian syndromes, in agreement with the known damage to the corticostriatal pathways in these conditions.

Aged↗
PubMed1998

[Anesthesiologic and surgical problems in adenotonsillectomy in pediatric patients. Our current trend].

AIM: To verify, in dissection adenotonsillectomy (AT) performed in Rose position under general anaesthesia with oro-tracheal intubation, the following: 1) the ability of tramadol to produce an effective intra- and postoperative analgesia without any considerable side effects or interferences with the normal post-surgical course of the operation; 2) the possibility of obtaining, thanks to mivacurium, a myoresolution closer both to surgical times of the operation and to the necessity of a fast recovering of the pharyngo-laryngeal reflexes. EXPERIMENTAL DESIGN: A perspective and retrospective clinical study. SETTING: University clinic department (operating room and facility). PATIENTS: 110 patients submitted to adenotonsillectomy, aged 4-10, belonging to the I-II ASA categories and not taking any drug for at least 30 days. INTERVENTIONS: Intravenous pre-medication with tramadol 2 mg/kg; myoresolution with mivacurium 0.2 mg/kg; postoperative analgesia with tramadol 2 mg/kg i.m. one hour after the first administration and, with an equivalent oral dose of tramadol, six hours later. MEASUREMENTS: During surgery: ECG, HR, Sat HbO2, non-invasive arterial blood pressure; after surgery: clinical evaluation of pain, through a three-point scale, and of the surgical course. RESULTS: Good analgesical level both during and after surgery; myoresolution especially suitable to adenotonsillectomy duration and characteristics; no considerable complications. CONCLUSIONS: Tramadol intra- and postoperative analgesia and mivacurium myoresolution represents, in personal opinion, an efficient approach to dissection adenotonsillectomy performed in children under general anaesthesia.

Adenoidectomy↗
PubMed1998

Increased cerebrospinal fluid and plasma levels of ultraweak chemiluminescence are associated with changes in the thiol pool and lipid-soluble fluorescence in multiple sclerosis: the pathogenic role of oxidative stress.

The pathogenesis of multiple sclerosis (MS), the major neurological disease of young adults in the western world, is still poorly understood and no effective therapy to block MS is yet available. It is generally accepted that reactive oxygen species have a major role in the mediation of cell damage and that free sulfhydryl groups are vital in cellular defense against endogenous or exogenous oxidants. Modification of the cellular oxidant/antioxidant balance has been involved in the neuropathogenesis of several diseases, e.g., stroke, Parkinson's disease, Alzheimer's disease and physiological aging. An increasingly important area of antioxidant defense is based on sulfhydryl chemistry, owing to the role of sulfhydryl groups in the function of macromolecular structures such as enzymes and cellular membranes. The chemical composition of human cerebrospinal fluid (CSF) is considered to reflect brain metabolism and in the present study we provided experimental evidence of a decrease in sulfhydryl groups and increased content of products of lipid peroxidation, such as ultraweak chemiluminescence and liposoluble fluorescence, which we found higher in the CSF and plasma of MS patients than in controls, pointing out the role of oxidative stress in the pathogenesis of MS.

Adult↗
PubMed1997

The renoprotective properties of angiotensin-converting enzyme inhibitors in a chronic model of membranous nephropathy are solely due to the inhibition of angiotensin II: evidence based on comparative studies with a receptor antagonist.

In several models of renal disease progression, angiotensin-converting enzyme (ACE) inhibitors reduced proteinuria and limited glomerulosclerosis, which suggested that reduction of renal angiotensin II (Ang II) activity is crucial for the preservation of glomerular structure and function. However, it cannot be ruled out that other hormonal systems, including inhibition of the bradykinin breakdown, also play a role. We compared the effects of chronic treatment with the ACE inhibitor lisinopril with those of a specific Ang II receptor antagonist, L-158,809, on proteinuria and renal injury in passive Heymann nephritis (PHN), a model of immune renal disease that closely resembles human membranous nephropathy, with long-lasting proteinuria followed by tubulointerstitial damage and glomerulosclerosis. Passive Heymann nephritis was induced with 0.5 mL/100 g of rabbit anti-Fx1A antibody in 24 male Sprague-Dawley rats. The animals were divided into three groups of eight rats each, and were given the following in the drinking water on a daily basis: lisinopril (40 mg/L), L-158,809 (50 mg/L), or no therapy. Treatment started at day 7 (proteinuria was already present) and lasted 12 months. Eight normal rats were used as controls. Untreated PHN rats developed hypertension, while rats with PHN given lisinopril or L-158,809 all had systolic blood pressure values even lower than those of normal rats. Urinary protein excretion progressively increased with time in untreated PHN rats, who developed tubulointerstitial damage and glomerulosclerosis. Both lisinopril and L-158,809 exhibited a potent antiproteinuric effect and preserved glomerular and tubular structural integrity at a similar extent. Renal gene expression of transforming growth factor-beta and extracellular matrix proteins was also effectively reduced by the two treatments. These results indicate that ACE inhibitors and Ang II receptor antagonists are equally effective in preventing renal injury in PHN and suggest that the renoprotective effects of ACE inhibitors in this model are solely due to inhibition of Ang II.

Angiotensin II↗
PubMed1997

Variations in axial, proximal, and distal motor response to L-dopa in multisystem atrophy and Parkinson's disease.

The purpose of this study was to quantitatively compare the motor response to L-dopa in Parkinson's disease (PD) and striatonigral-type multisystem atrophy (MSA) patients. Ten consecutive MSA patients were compared with nine PD patients selected to have similar overall motor compromise, age, and mental state. The performance of simple repetitive axial movements plus bilateral proximal and distal limb movements; overall motor response assessed by the Unified Parkinson Disease Rating Scale (UPDRS); as well as scores from the UPDRS items evaluating speech/facial expression, postural stability, and posture/gait were assessed 90 min and 12 h (baseline) after L-dopa administration. The total UPDRS score, all subcategory scores, and all body movements improved significantly in the PD group. Proximal and distal limb akinesias and speech/facial expression improved in some MSA patients. Lack of response of axial akinesia to L-dopa in MSA correlates with a presumed greater loss of postsynaptic dopaminergic receptors in the dorsolateral putamen, while improvement in distal and proximal limb muscle akinesias in MSA patients may be related to relative preservation of the ventral putamen.

Aged↗
PubMed1997

Renal expression of monocyte chemoattractant protein-1 in lupus autoimmune mice.

Mononuclear cell infiltration in glomeruli and renal interstitium is a prominent feature of some types of glomerulonephritis, including lupus nephritis. The mechanism(s) underlying monocyte influx into the kidney is not fully understood. Recently, monocyte chemoattractant protein-1 (MCP-1) has been identified as a chemotactic factor involved in the recruitment of monocytes/macrophages in the glomeruli of rats with mesangioproliferative as well as anti-glomerular basement membrane glomerulonephritis. In the study presented here, renal MCP-1 mRNA expression in New Zealand Black x New Zealand White (NZB/W) F1 mice, a model of genetically determined immune complex disease that mimics systemic lupus in humans, was investigated. Northern blot analysis revealed a single 0.7 kb MCP-1 transcript of very low intensity in kidneys from 2-month-old NZB/W mice that had not yet developed proteinuria nor renal damage. Message levels, which increased markedly with the progression of nephritis and in association with mononuclear cell infiltration, were 10- and 15- fold higher in 8-10-month-old mice than in 2-month-old mice. By in situ hybridization, increased expression of MCP-1 mRNA was demonstrated in glomeruli and, even more striking, in tubular epithelial cells. Western blot analysis demonstrated increased expression of MCP-1 protein in kidneys of 10-month-old NZB/W mice, consistent with MCP-1 mRNA data. When NZB/W mice were treated with cyclophosphamide up to 12 months of age, expression of MCP-1 in the renal tissue remained low, the influx of inflammatory cells did not appear, and glomerular and tubular structures remained well preserved. These data suggest that elevated MCP-1 might act as a signal for inflammatory cells to infiltrate the kidney in lupus nephritis.

Animals↗
PubMed1997

Comparison of a blocking vs. a flare-up protocol in poor responders with a normal and abnormal clomiphene citrate challenge test.

This study aimed to standardize the clomiphene citrate test (CC-t) in our laboratory while comparing two different protocols of controlled ovarian stimulation in poor responders. One hundred and forty-four patients scheduled for assisted reproductive techniques were submitted to the CC-t within 3 months before starting stimulation; 133 underwent controlled ovarian stimulation with a blocking protocol. Poor responders in the first cycle (n = 30) were subsequently treated with a flare-up protocol. Although it was not statistically significant, more patients reached oocyte retrieval with the flare-up protocol. In the completed cycles, more gonadotropin ampules (55 +/- 15 vs. 34 +/- 13; p < 0.001) and more stimulation days (12.6 +/- 1 vs. 11.6 +/- 1.2; p < 0.005) were needed in the blocking than in the flare-up protocol. No difference was observed in peak 17 beta-estradiol levels, preovulatory follicles, oocytes retrieved or pregnancy rate between the two protocols. According to the threshold values, established on CC-t of patients who obtained a clinical pregnancy (n = 44), the incidence of abnormal results was 10%. All but one patient with abnormal CC-t were poor responders during the first stimulation cycle. The flare-up protocol did not improve the ovarian response in these patients.

Adult↗
PubMed1996

Survival in multiple system atrophy: a study of prognostic factors in 59 cases.

The various clinical features of multiple system atrophy (MSA) make the diagnosis of the disease difficult, especially in its early stages, when signs of differentiated neuroanatomical system involvement have not yet appeared. Mortality studies may be affected by the variability of the diagnostic criteria and selection bias. We used strict clinical and MRI criteria to diagnose MSA in 59 patients. Patients with parkinsonian and cerebellar onset were compared. Median survival time from the onset of the first motor symptom was 7.5 years. Our results indicated a trend (P = 0.09) for the Northwestern University Disability Scale score to correlate with mortality, but we failed to find other characteristics identifying subgroups or predictors for survival.

Adult↗