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Biomedical subjects

A R Massaro

Publications and source records attributed to A R Massaro.

At least 19 recordsLinked to original sources

Transcranial Doppler ultrasonography in adults with sickle cell disease.

BACKGROUND: Transcranial Doppler (TCD) is used to select children with sickle cell disease (SCD) for primary stroke prevention using regular blood transfusion. Whether it can also identify high stroke risk in adults with SCD is not known. METHODS: The authors examined 112 adult patients from two convenience population samples with SCD and 53 healthy control subjects to compare velocities in adults to those reported in children with SCD and to evaluate the influence of age and hematocrit on TCD. RESULTS: Adults with SCD had a higher mean time-averaged maximum mean velocity (110.9 +/- 25.7 cm/s) compared with healthy controls (71.1 +/- 12.0 cm/s), and the difference is approximately proportional to their anemia. No cases with velocities >/=200 cm/s (the threshold used in children for prophylactic treatment) were found in this sample. CONCLUSIONS: Transcranial Doppler velocities in adults with sickle cell disease (SCD) are lower than those in children with SCD. Velocity criteria used in children cannot be used to stratify risk of stroke in adults.

Adult↗

Transcranial Doppler assessment of cerebral blood flow: effect of cardiac transplantation.

The authors prospectively studied transcranial Doppler changes in patients with refractory congestive heart failure before and after cardiac transplantation. They evaluated 22 patients preoperatively and 14 patients after transplantation. Mean postoperative flow velocity increased by 53.3% (p < 0.0001). Preoperative waveform changes became normal after transplantation.

Adult↗

Migraine-mimicking headache and sickle cell disease: a transcranial Doppler study.

Headache occurs in sickle cell disease (SCD), but its characteristics and frequency have not previously been studied. Our aim was to study patterns of headache in adults with SCD and to correlate its presence with blood flow velocities measured by transcranial Doppler (TCD) and with brain magnetic resonance imaging (MRI) abnormalities. We studied 56 adults with SCD. Twenty-eight patients (50%) had severe and frequent headaches. In 20 patients (35.7%) the headache met the International Headache Society criteria for migraine without aura. Patients with frequent and severe headache presented TCD velocities significantly higher than those without headache, or with milder headache. No correlation was found between headache and abnormalities in brain MRI. A migraine-mimicking headache occurs in SCD but we should not understand it as a primary headache because the blood flow abnormalities secondary to SCD detected by TCD seem to play an important role in these patients.

Adolescent↗

The role of NCAM in remyelination.

The neural cell adhesion molecule (NCAM) is expressed by myelinating precursor cells in neonatal mouse spinal cord and by remyelinating cells after chemically induced demyelination in adult mouse. It shows tempting suggestions about its possible involvement in the reparative mechanisms and the remyelination processes that take place in multiple sclerosis (MS). In fact, its levels progressively increase in the cerebrospinal fluid (CSF) of acute MS patients subjected to steroid treatment, paralleling the progressive clinical improvement after the attack. Such an increase is not found in acute MS patients not treated with steroids nor in non-acute patients subjected to the same steroid treatment.

Animals↗

Is the number of microembolic signals related to neurologic outcome in coronary bypass surgery?

Coronary artery bypass surgery (CABG) without cardiopulmonary bypass (CPB) may potentially reduce the number of microembolic signals (MES) associated with aortic manipulation or generated by the pump circuit, resulting in a better neurologic outcome after surgery. Our aim was to compare the frequency of MES and neurologic complications in CABG with and without CPB. Twenty patients eligible to routine CABG without CPB were randomized to surgery with CPB and without CPB and continuously monitored by transcranial Doppler. Neurologic examination was performed in all patients before and after surgery. The two groups were similar with respect to demographics, risk factors, grade of aortic atheromatous disease and number of grafts. The frequency of MES in the nonCPB group was considerably lower than in CPB patients, however, we did not observe any change in the neurologic examination during the early postoperative period. Neurologic complications after CABG may be related to the size and composition of MES rather than to their absolute numbers. A large prospective multicentric randomized trial may help to elucidate this complex issue.

Aortic Diseases↗

Interferon-beta (INF-beta) antibodies in interferon-beta1a- and interferon-beta1b-treated multiple sclerosis patients. Prevalence, kinetics, cross-reactivity, and factors enhancing interferon-beta immunogenicity in vivo.

We analysed the role of dosage, route and frequency of administration of clinical grade interferon-beta (IFN-beta) preparations in inducing anti-IFN-beta antibodies (IFN-beta-Abs) in 5 groups of relapsing-remitting multiple sclerosis (RRMS) patients who were respectively treated as follows: 1) weekly intramuscular (i.m.) injections of 30 mg of recombinant IFN-beta1a (Avonex), 2) subcutis (s.c.) injections of 250 mg IFN-beta1b (Betaferon) every other day, 3) weekly i.m. injections of 250 mg IFN-beta1b (Betaferon), 4) s.c. injections of 22 mg of IFN-beta1a (Rebif) three times a week, and 5) i.m. injections of 22 mg of IFN-beta1a (Rebif) twice a week. IFN-beta-Abs were determined by ELISA. IFN-beta1b was more immunogenic than IFN-beta1a not only when administered s.c. every other day, but also when administered i.m. at a lower weekly dose; i.m. injection, however, significantly delayed the appearance, and induced lower serum levels of IFN-beta-Abs. In patients treated with s.c. IFN-beta1b, Ab levels peaked 3 to 9 months after therapy initiation, and then slowly, but progressively, declined to pre-therapy levels that in some patients were reached after three years. Patients treated with i.m. or s.c. IFN-beta1a only rarely developed IFN-beta-Abs, and then at very low titers. Overall, the i.m. weekly administration of IFN-beta1a was the less immunogenic treatment. In IFN-beta1b-treated patients, a wash-out period of two/three months was sufficient to bring the IFN-beta-Ab levels below the cut-off. Our findings suggest that the immunogenicity of IFN-beta1a is low, regardless of the route of administration and the dosage, while that of IFN-beta1b is high, and is significantly, but not completely reduced by i.m. administration. As IFN-beta-Abs are cross-reactive, a wash-out period is suggested when the preparation is changed from IFN-beta1b to IFN-beta1a in order to maintain the clinical benefits of the therapy.

Antibodies↗

Cerebrospinal fluid markers in multiple sclerosis: an overview.

Cerebrospinal fluid (CSF), with its protein markers, is a formidable material for investigating the relationships among the various cell types involved during the initial phase of plaque formation, or, successively, in the remyelination process. Its analysis may give definite help in better focusing on therapeutic objectives and therapeutic tools. Therefore, the possible use of CSF MBP, S-100, GFAP, N-CAM, NGF, and CNTF in pathogenetic studies and in clinical follow-up is critically reviewed. The need for correct interpretation of the data, for uniformity and reliability of the analytical methods, and for easy access to them is stressed. CSF examination and MRI should not be considered as alternative tools, or in competition, but should be used together, to take the maximum advantage of their individual possibilities.

Biomarkers↗

Are there indicators of remyelination in blood or CSF of multiple sclerosis patients?

Knowing the mechanisms and the times of remyelination is not only an intriguing scientific challenge but it has also important consequences on the therapeutic approach to multiple sclerosis (MS). The neural-cell adhesion molecule (N-CAM) shows tempting suggestions about its possible involvement in reparative mechanisms, and, finally, in remyelination. In fact, its levels progressively increase in the cerebrospinal fluid (CSF) of acute MS patients, paralleling the progressive clinical improvement after the attack. Some information is also given about the ciliary neurotrophic factor (CNTF), whose CSF levels were found to be increased in MS patients who were recovering from an acute exacerbation.

Ciliary Neurotrophic Factor↗

Neurologic outcome after heart transplantation in Chagas' disease. Preliminary results.

OBJECTIVE: To evaluate the neurologic morbidity after orthotopic heart transplantation (OHT), we examined consecutive Chagas' (Ch) and non-Chagas' (NCh) patients, before and after surgery. MATERIAL AND METHODS: We undertook neurological and neuropsychological evaluations in Ch and NCh patients with end-stage cardiac failure, from September 1993 to September 1995. RESULTS: Of 10 Ch patients (mean age = 33.6 years; 7 male; mean follow-up = 10.8 months) and 13 NCh patients (mean age = 50.9 years; 12 male; mean follow-up = 15 months) 3 died (rejection and sepsis) without neurologic symptoms. Neurologic complications occurred in 4 Ch and 5 NCh patients. Two Ch patients had skin and myocardial Chagas' reactivation successfully treated, without CNS involvement. NPS performance and return to work rates were similar in both groups. CONCLUSION: Although Ch patients are potentially at a higher risk of Trypanosoma cruzi reactivation, in addition to all known neurologic complications of OHT, early neurologic complications detected in this sample were similar in Ch and NCh patients and could not be specifically related to Chagas' disease.

Adult↗

Cerebrospinal-fluid ciliary neurotrophic factor in neurological patients.

We developed a double sandwich immunoassay for the dosage of ciliary neurotrophic factor (CNTF) in cerebrospinal fluid (CSF). The detection limit was 100 pg/ml. This assay was applied to human CSF samples from 14 normal subjects, 26 patients with multiple sclerosis (MS), 17 with Guillain-Barré syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP), and 22 with tumours of the central nervous system (CNS) or leucaemic meningosis (LM). Samples from normal control subjects and from patients with tumours did not contain detectable CNTF. Only 2 patients with LM were positive, and all the patients with inflammatory diseases of the CNS and peripheral nervous system were positive. The MS group presented a mean value of 240 pg/ml CNTF and the GBS/CIDP group a value of 430 pg/ml.

Astrocytoma↗

Nerve growth factor (NGF) in cerebrospinal fluid (CSF) from patients with various neurological disorders.

It has been recently shown that NGF is not only involved in the survival and development of sympathetic and neural crest-derived sensory neurons, but also in some mechanisms of the immune system. For this reason, we studied the content of NGF in CSF samples from patients with diseases in which neuroimmunological mechanisms seem to be involved (multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer disease, chronic relapsing polyradiculoneuritis, Guillain-Barré syndrome, and tumors of the nervous system), as well as from a number of normal control subjects. We setup an ELISA aimed at the beta subunit of NGF, obtaining good validation tests and a detection limit of 28 pg beta NGF per ml. None of the samples was found to contain detectable levels of NGF and, when a concentration method for sample enrichment was used, only one patient was NGF-positive. This suggests that NGF is probably not involved in the neuroimmunological mechanisms underlying some inflammatory and degenerative diseases of the nervous system.

Antibody Specificity↗

[Orbital phlebography evaluation in 8 cases of Tolosa-Hunt syndrome].

Tolosa-Hunt syndrome (THS), or painful ophthalmoplegia is associated to a non-specific granulomatosis of unknown etiology, that involves the superior orbital fissure and its nervous and vascular structures. The clinical picture that responds to steroid therapy, is variable and is always associated with pain. Inflammatory conditions, tumors and aneurysms can produce similar symptoms. Computed tomography, cerebral angiography and orbital phlebography are the imaging methods of choice for making the diagnosis. We revised the results of these radiological examinations of eight patients seen at the Hospital São Paulo from 1989 to 1991, with the diagnosis of THS according to Hunt and Hannerz criteria. The analysis of orbital phlebographic changes based upon Hannerz et al. systematization showed non-specific features, but those were able to help the diagnosis.

Adult↗

Characterization of arteriovenous malformation feeding vessels by carbon dioxide reactivity.

PURPOSE: To characterize cerebral hemodynamics in patients immediately before microsurgical resection of moderate to large arteriovenous malformations during isoflurane anesthesia. METHODS: In angiographically defined arteriovenous malformation feeding and nonfeeding arteries, transcranial Doppler studies were performed in 25 surgeries on 22 patients. The mean blood flow velocity and pulsatility index were recorded in the middle, anterior, and posterior cerebral arteries. Transcranial Doppler velocities were measured at end-tidal carbon dioxide tensions (PetCO2) of about 25 and 35 mm Hg. Carbon dioxide reactivity was calculated as percentage mean blood flow velocity change per mm Hg PetCO2 change. RESULTS: Patient demographic and clinical data for the arteriovenous malformation group followed the expected strata of a large arteriovenous malformation population. All patients were neurologically stable before surgery. A total of 43 feeding arteries and 55 nonfeeding arteries were studied. Compared with nonfeeders, feeders exhibited higher mean blood flow velocity (68 +/- 5 vs 31 +/- 3 cm/sec, P < 0.0001) and lower pulsatility index (0.64 +/- 0.03 vs 0.88 +/- 0.04, P < 0.001); anterior and middle cerebral artery velocities at normo- and hypocapnia were significantly higher than posterior cerebral arteries for both feeders and nonfeeders (P < 0.001). Carbon dioxide reactivity was 0.2 +/- 0.2%/mm Hg in feeders and 2.1 +/- 0.2%/mm Hg in nonfeeders, with no significant difference between arteries. In four of eight patients with lesions fed by the anterior circulation (middle cerebral artery with or without anterior cerebral artery feeders), posterior cerebral artery nonfeeders exhibited low reactivity. In 2 of 5 patients with ipsilateral posterior cerebral artery feeders, contralateral posterior cerebral artery nonfeeders exhibited impaired reactivity. CONCLUSIONS: Quantitative transcranial Doppler studies are technically feasible in the operating room or interventional suite during anesthesia. Hemodynamic assessment using physiologic challenges of arteriovenous malformation feeders as well as angiographically uninvolved vessels may be useful as criteria in the assessment of malformations and arteriovenous malformation patients may exhibit abnormal vasoreactivity in distant uninvolved perfusion territories, suggesting a deranged neural control mechanism.

Adolescent↗

Transcranial Doppler changes during staged surgical resection of cerebral arteriovenous malformations: a report of three cases.

The removal of large arteriovenous malformations (AVMs) in stages has been advocated to reduce the risk of perioperative hyperemic complications. In three patients who had a two-stage surgical removal of their large (> 6 cm) frontal AVMs, transcranial Doppler (TCD) was performed 1 day before and 1 day after each surgery. Arteries still feeding the AVM after the first procedure had an increase in mean velocity (MV) and a decrease in the pulsatility index (PI) in the period between the two surgeries. MV reactivity to carbon dioxide before each stage was higher in feeding arteries at the second surgery, suggesting that the total magnitude of the shunt through the AVM was lower in spite of flow recruitment. TCD can be used to monitor the hemodynamic changes after embolization or partial surgery and may be of help in better defining the optimal time for final resection.

Adult↗

Notes on the therapy of multiple sclerosis (MS)

MRI, neuroimmunology and neurobiology have provided significant contributions to the rationale of the therapeutic approach in multiple sclerosis. It is clear that the ignorance of the etiologic factor has lead to a double treatment policy: the first is aimed to control the acute phase of the disease while the second strives to block the pathogenetic mechanisms underlying the disease itself and the relapses. The author reviews and discusses the latest issues on this topic based on his own clinical and laboratory experience.

Blood-Brain Barrier↗

Clinical discriminators of lobar and deep hemorrhages: the Stroke Data Bank.

Of the 1,805 patients with acute stroke enrolled in the Stroke Data Bank, 237 had parenchymatous hemorrhage. After excluding 34 secondary intracerebral and 31 infratentorial hemorrhage patients, a logistic regression analysis of the 172 patients with primary supratentorial intracerebral hemorrhage (ICH) elucidated clinical factors that distinguished the 65 patients with lobar hemorrhage (LH) from the 107 patients with deep hemorrhage (DH) located in the basal ganglia and thalamus. In LH, severe headache was more common than in DH, while hypertension and motor deficit were significantly less common. Patients with either LH or DH had a similar prognosis and mean Glasgow Coma Scale (GCS) scores, despite the hematoma volume measured on the initial CT being significantly greater for LH than DH. The presence of intraventricular extension (IVH) was more frequent in DH. The frequency of IVH increased with hematoma volume in LH, but remained constant for DH. Two CT variables (IVH and hematoma volume) that differed in these two hemorrhage groups were important predictors of coma (GCS less than or equal to 8) in a logistic regression model. Differences in the frequency of IVH may help explain why the degree of impairment in consciousness was similar in the two groups. Among patients with supratentorial ICH, location of the hematoma is related to both volume and IVH, which are important determinants of the level of consciousness.

Aged↗