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Biomedical subjects

M Zaffaroni

Publications and source records attributed to M Zaffaroni.

At least 55 records · Page 3Linked to original sources

Erectile impotence in multiple sclerosis: a neurophysiological study.

Pudendal evoked potentials, motor evoked potentials of the bulbocavernosus muscle to magnetic stimulation and bulbocavernosus reflex were recorded in 34 patients with multiple sclerosis (MS). Responses were delayed in 26, 20 and 3 cases respectively. No relationship was found between neurophysiological abnormalities and the presence or severity of erectile dysfunction, showing that these tests have little diagnostic usefulness in MS patients with impotence. Nocturnal penile tumescence was assessed in 14 cases: the test result was normal in 10 patients, including 3 severely paraplegic subjects.

Adult↗

In vitro cytokine, sCD23 and IgG secretion in multiple sclerosis.

Synthesis of IgG by peripheral blood mononuclear cells from patients with multiple sclerosis (MS) and with other neurological diseases and from healthy controls was induced by Pokeweed mitogen (PWM) in short-term cultures. As expected, MS patients produced more immunoglobulin (Ig) G and had a higher percentage of 'high responders' to PWM stimulation as compared to controls. Interleukin (IL)-4 was undetectable in all samples. IL-6 and tumor necrosis factor (TNF)-alpha synthesis was induced by PWM stimulation in all groups, but MS patients showed the most significant increase of both cytokines. Interestingly, only MS patients showed a significant increase of the soluble form of CD23 receptor (sCD23). Moreover, only sCD23 levels correlated with in vitro IgG production in MS patients. The levels of IL-6, TNF-alpha, sCD23 were greater in high responders compared to low responders in all groups. The mean value of each molecule, however, did not differ significantly among overall groups. A highly significant difference was reported for sCD23 in MS patients. We suggest that sCD23, also known as B cell growth factor, may play a role in the well-documented phenomenon of in vitro IgG hypersynthesis in MS patients, adding support to the concept of B cell up-regulation in the peripheral blood of these patients.

Adjuvants, Immunologic↗

Evidence of linkage between susceptibility to multiple sclerosis and HLA-class II loci in Italian multiplex families.

To verify whether multiallelic polymorphisms belonging to HLA class II genes are linked to multiple sclerosis (MS) in the Italian population, we studied 28 multiplex MS families originating from different areas of Italy. Allelic characterization was carried out by analysis of RFLPs and oligonucleotide typing. Evidence supporting the existence of linkage between MS susceptibility and the HLA class II loci DRB1, DQA1 and DQB1 was provided using two non-parametric tests, affected sib-pair analysis, and affected-pedigree-member (APM) analysis. The APM analysis also suggested the existence of genetic heterogeneity for the HLA class II loci and MS susceptibility in our series. Linkage disequilibrium between MS susceptibility and the haplotype DRB1*1501,DQA1*0102,DQB1*0602 was demonstrated by applying the transmission linkage disequilibrium test to our families. Finally, lod score analysis suggests that in our Italian families, MS susceptibility is conferred by HLA class II alleles according to a low-penetrance autosomal recessive mode of inheritance.

Alleles↗

[Transient changes in thyroid function in the neonatal period].

Transient neonatal hypothyroidism (TH) is a state biochemically characterized by altered TSH and T4 values at screening and subsequently confirmed by serum analysis. TH can go or not go along with clinical manifestations of hypothyroidism and evolves to the normalization of the thyroid functional capacity independently of substitutive therapy. In addition to the complete TH the application of screening programs for congenital hypothyroidism has enable to acknowledge partial changes of the thyroid functional capacity in the neonatal age characterized by isolated anomalies of the individual hormonal parameters. Since the incidence of neonatal TH in Italy is remarkably high (the forms of complete TH being not less than 20% of the hypothyroidism cases diagnosed at the screening) we want to provide an overview of the latest acquisitions regarding TH. Finally the indications for treatment of the various forms of TH, a still controversial matter, are considered, in consideration of the primary role played by thyroid hormones on the development of central nervous system in the perinatal age.

Congenital Hypothyroidism↗

Growth hormone, insulin-like growth factor-I and somatostatin in human fetus, newborn, mother plasma and amniotic fluid.

During pregnancy, organism development and its differentiation are stimulated and modulated by fetal and placental hormones. However the exact role played by all the different growth factors has not been explained yet. This study summarizes knowledge about secretion, regulation and role of GH, IGF-1 and SRIF during perinatal age. It also reports the results of researches into GH, IGF-1 and SRIF in amniotic fluid, in mothers and in newborns at delivery and at four days of age. Amniotic fluid GH levels proved significantly higher during middle pregnancy that at delivery (p < 0.001); a significant difference was also found between mean GH concentrations observed in amniotic fluid collected at delivery in preterm and full-term pregnancies. In amniotic fluid, significant reductions of SRIF and IGF-1 concentrations correspond to a sudden decrease of GH concentration during the last months of pregnancy. Fetal serum GH levels resulted higher than venous cordonal GH concentration at birth (p < 0.001). High levels of IGF-1 were found in the amniotic fluid and in the maternal plasma. These values were higher than those observed in cord blood during pregnancy or at delivery. Preterm and full-term newborns showed similar serum GH levels at birth and at the age of 4 days. Mean GH values in newborns, both at birth and at the age of 4 days, proved to be significantly higher than the values of their mothers (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Amniotic Fluid↗

Interleukin-2 receptor expression on blood monocytes of patients with multiple sclerosis.

We studied the expression of class II MHC product (HLA DR) and IL-2 receptor on circulating monocytes (M phi) in MS patients, neurological and healthy controls, by double color flow cytometry. In all groups most M phi were DR+ without significant differences. More interesting, low percentages of IL-2+ M phi were detectable in healthy and neurological controls, whilst a few MS patients with active disease showed higher levels. This finding is in agreement with similar studies in other T-cell mediated diseases and with the report of rare IL-2+ macrophages in MS plaques. Although the actual role of IL-2+ M phi in the immune response still needs elucidation, our findings suggest their relevance to the pathological process of demyelinating disease.

Adult↗

Motor potentials of inferior orbicularis oculi muscle to transcranial magnetic stimulation. Comparison with responses to electrical peripheral stimulation of facial nerve.

Magnetic stimulation at the vertex evoked a motor potential (MP) in the inferior orbicularis oculi muscle of 10 healthy subjects with an onset latency of 8-13 msec. Its amplitude increased and its latency decreased when the muscle was contracted: the latency measured 9.5 +/- 1.3 msec with an intensity of stimulation 10-15% above threshold in the contracted muscle. This MP is secondary to excitation of the motor cortex. With the coil placed over the occipital scalp and the same stimulation intensity, an MP was recorded with an onset latency at 4.5 +/- 0.6 msec. This response reflects the activation of the facial nerve root. The peripheral electrical stimulation of the facial nerve at the mandible angle elicited an MP with an onset latency at 3.5 +/- 0.4 msec. Most records showed the presence of late components at about 30 msec for all types of stimulation.

Adolescent↗

Perineal motor potentials to magnetic stimulation, pudendal evoked potentials and perineal reflex in women.

Motor potentials to transcranial and lumbar magnetic stimulation were recorded from the perineum in 14 healthy women. The response to transcranial stimulation presented an onset at 20.2 +/- 1.3 ms and a negative peak at 25.1 +/- 1.9 ms. Lumbar responses presented an onset at 5.1 +/- 0.8 ms, and the motor central conduction time measured 14.4 +/- 1.5 ms. Perineal reflex, cortical and lumbar pudendal evoked potentials were recorded after electrical stimulation of the labia minora. These tests are of possible clinical use in the evaluation of sphincter disturbances as they investigate the afferent and efferent pathways concerning pudendal nerve function.

Adult↗

CD4+ lymphocyte subsets in the cerebrospinal fluid of multiple sclerosis and non-inflammatory neurological diseases.

We studied paired cerebrospinal fluid (CSF) and peripheral blood (PB) samples from 18 inactive multiple sclerosis (MS) patients and 10 with non-inflammatory neurological diseases. By means of a dual-colour cytofluorimetric micromethod we were able to count 1500 cells on average in each CSF sample. We found a significant reduction of CD45RA+ and CD4+CD45RA+ cells in the CSF of MS patients. Similarly, CD45RA+ and CD4+CD45RA+ CSF/PB ratios were lower compared with controls. The reduction of suppressor-inducer T-cells did not correlate with CD8+ cell levels in the CSF. The CD4+ subset ratio (CD4+CD45RA-/CD4+CD45RA+) was significantly increased in the CSF of MS patients. Our data suggest that the reduction of CD4+CD45RA+ cells in the PB is not due to a segregation of such cells in the CSF. Conversely, CSF changes reflect changes in the PB similar to these found for other T-cell subsets.

Adult↗

Study of central and peripheral motor conduction in normal subjects.

Motor potentials to transcranial and cervical magnetic stimulation and F-wave were recorded in 37 arms of 25 normal subjects. Clockwise and anticlockwise cervical stimulation were performed over C5, C7 and T2 spinous processes. A significant correlation was found between height and measurements of central and peripheral motor conduction. Peripheral motor conduction measured by F-wave derived techniques (Kimura formula) was 0.5 msec higher as compared with responses to cervical magnetic stimulation. The site and current flow direction of cervical magnetic stimulation influenced the amplitude of responses but not their latency: responses were larger in the right arm when the centre of the coil was placed over the C5 spinous process and clockwise stimuli were used. The same results were obtained in the left arm when the coil was reversed.

Adolescent↗

Motor potentials of bulbocavernosus muscle after transcranial and lumbar magnetic stimulation: comparative study with bulbocavernosus reflex and pudendal evoked potentials.

Motor potentials of the bulbocavernosus muscle were recorded in 17 healthy subjects after transcranial and lumbar magnetic stimulation. The latencies (SD) were respectively: 22.9 (1.8) and 5.9 (0.4) ms. The central conduction time was 17.0 (2.5) ms. The bulbocavernosus reflex presented an onset at 34.5 (3.3) ms and a negative peak at 43.1 (3.9) ms. The cortical pudendal evoked potential was W shaped: the first peak had a latency of 35.4 (2.8) ms. The concurrent recording of motor potentials, bulbocavernosus reflex, pudendal evoked potentials gives a measure of peripheral and central, afferent and efferent neurological pathways related to pudendal nerve function.

Brain↗

Decrease of CD4+CD45+ T-cells in chronic-progressive multiple sclerosis.

Circulating lymphocyte subpopulations defined by anti-CD45 and other more common T-cell-specific monoclonal antibodies were analysed in 77 patients with multiple sclerosis and 38 healthy controls. A selective decrease of CD4+CD45+ cell percentages and absolute numbers in chronic-progressive patients was found; in 13 out of 26 patients this subpopulation was less than 11% CD4+CD45+ cells. Similarly, the whole CD45+ cell subset, as well as CD45+ cells expressed as percentages of CD4+ cells, were significantly reduced in chronic-progressive multiple sclerosis. CD4+CD45+ cells, commonly termed "inducer of suppression" T-lymphocytes, did not correlate with percentages or numbers of CD8+ cells. It is concluded that suppressor inducer T-cells act on the CD8+ subset function rather than reducing CD8+ cell numbers. Since CD4+CD45+ cells represent an early stage of lymphocyte maturation (naive T-cells), an under-representation of this subpopulation in active multiple sclerosis might reflect an increased conversion of naive cells into memory cells. This concept may be relevant for a better understanding of the disease pathogenesis.

Adult↗

Epilepsy in multiple sclerosis.

In a series of 2,353 multiple sclerosis (MS) patients, 40 subjects presented seizures, with an overall prevalence of 1.70%. The prevalence was 2.33% (34/1,459) in definite MS cases, 0.58 in probable cases (3/518), 0.79 in possible cases (3/376). Twenty-six patients were females, 14 were males. In 13 cases, epilepsy had begun before MS onset; in 4 patients, the two diseases started contemporarily; in 23 patients, epilepsy followed MS onset. No relationship was found between frequency of seizures and course of MS nor between frequency of seizures and MS severity. In 12 patients, magnetic resonance imaging was performed: plaques adjacent to the cerebral cortex were found in 3 cases. The electroencephalogram showed paroxysmal discharges in 11 patients (focal in 2, diffuse in 9). Slow theta and/or delta activity was found in 15 patients (focal in 7, diffuse in 6, both focal and diffuse in 2). The EEG was normal in 14 patients. Possible etiological factors other than MS were recognized in 4 patients only: cranial trauma in 3, meningitis in 1. Our study on a large MS population confirms that MS is associated to a risk for epilepsy higher than that of the general population.

Adolescent↗

[Thyroid hormones and the development of the nervous system].

The growth and differentiation of the central nervous system are closely related to the presence of iodine and thyroid hormones. During the first trimester of human pregnancy the development of the nervous system depends entirely on the availability of iodine; after 12 week of pregnancy it depends on the initial secretion of iodothyronine by the fetal thyroid gland. During the early stages of the development of the nervous system a thyroid hormone deficit may provoke alterations in the maturation of both noble nervous cells (cortical pyramidal cells, Purkinje cells) and glial cells. Hypothyroidism may lead to cellular hypoplasia and reduced dendritic ramification, gemmules and interneuronal connections. Experimental studies in hypothyroid rats have also shown alterations in the content and organization of neuronal intracytoplasmatic microtubules, the biochemical maturation of synaptosomes and the maturation of nuclear and cytoplasmatic T3 receptors. Excess thyroid hormones during the early stages of development may also cause permanent damage to the central nervous system. Hyperthyroidism may initially induce an acceleration of the maturation processes, including the migration and differentiation of cells, the extension of the dendritic processes and synaptogenesis. An excess of thyroid hormones therefore causes neuronal proliferation to end precociously leading to a reduction of the total number of gemmules. Experimental research and clinical studies have partially clarified the correlation between the maturation of the nervous system and thyroid function during the early stages of development; both a deficit and excess of thyroid hormones may lead to permanent anatomo-functional damage to the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗

Two familial cases of Creutzfeldt-Jakob disease in Italy.

Two familial Italian cases of Creutzfeldt-Jakob disease are reported. Clinical picture and life history are presented and compared: 1) with the findings in familial cases reported in other countries, 2) with the findings (age at onset, disease duration) in sporadic Italian cases.

Adult↗