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Biomedical subjects

M Cossu

Publications and source records attributed to M Cossu.

At least 37 records · Page 2Linked to original sources
PubMed2002

Focal cortical dysplasia: neuropathological subtypes, EEG, neuroimaging and surgical outcome.

Since the original description by Taylor, the term focal cortical dysplasia has been used to refer to a wide range of alterations of the cortical mantle. More recently, these conditions have been described from neuroimaging, neuropathological and genetic standpoints, generating several classifications. It is widely recognized that these classifications are unsatisfactory. We propose a simplified classification of focal cortical dysplasias based on easily recognized neuropathological characteristics. We retrospectively re-examined histological sections of cortex from 52 of 224 (23%) patients operated on for drug-resistant partial epilepsy in which cortical dysplasia was present but not associated with other brain pathologies except hippocampal sclerosis. Three subgroups were identified: (i) architectural dysplasia (31 patients) characterized by abnormal cortical lamination and ectopic neurones in white matter; (ii) cytoarchitectural dysplasia (six patients) characterized by giant neurofilament-enriched neurones in addition to altered cortical lamination; and (iii) Taylor-type cortical dysplasia (15 patients) with giant dysmorphic neurones and balloon cells (all but two patients) associated with cortical laminar disruption. The patients with architectural dysplasia had lower seizure frequency than those with cytoarchitectural and Taylor-type dysplasia, and the epileptogenic zone was mainly in the temporal lobe. In patients with Taylor-type dysplasia, the epileptogenic zone was mainly extratemporal, and interictal stereo-EEG was distinctive. MRI was unrevealing in 34% of patients, but distinctive signal alterations characterized most patients with Taylor-type dysplasia, while focal hypoplasia with MRI abnormalities was found in architectural dysplasia. Patients with Taylor-type dysplasia had the best outcome, with 75% seizure-free (Engel class Ia) after at least a year of follow-up compared with 50% of cytoarchitectural dysplasia and 43% of architectural dysplasia patients seizure-free. This three-category classification is based on easily recognized histopathological characteristics and avoids complicated terminology, while the distinctive ensemble of other characteristics defines clinically homogeneous groups.

Adult↗
PubMed2001

Subcellular localization of epidermal growth factor in human parotid gland.

The intracellular distribution of epidermal growth factor was investigated in human parotid gland by immunogold cytochemistry at the electron-microscopy level. Epidermal growth factor immunoreactivity was demonstrated in both acini and ducts. In acinar cells, secretory granules appeared moderately stained, clearly indicating that parotid gland contributes to salivary epidermal growth factor through granule exocytosis. In ductal cells, gold particles were found to decorate numerous cytoplasmic vesicles, particularly abundant in striated duct cells. Since epidermal growth factor reactive vesicles were seen not only at the cellular apex, but nearby lateral plasma membranes as well, it leads to the hypothesis that epidermal growth factor may be discharged both apically into the saliva, and basally into the interstitium.

Adolescent↗
PubMed2001

Predilution haemofiltration--the Second Sardinian Multicentre Study: comparisons between haemofiltration and haemodialysis during identical Kt/V and session times in a long-term cross-over study.

BACKGROUND: The potential superiority of various renal replacement treatment modalities consisting largely of convective mass transfer as opposed to primarily diffusive mass transfer, is still a matter of debate. The objective of the present study was to evaluate acute and long-term clinical effects of varying degrees of convection and diffusion in a group of 24 clinically stable patients with end-stage renal disease. METHODS: The patients were prospectively assigned to three consecutive treatment schedules of 6 months each: phase I (HF1) (on-line predilution haemofiltration)-->phase II (HD) (high-flux haemodialysis)-->phase III (HF2; as phase I). We used the AK100/200 ULTRA monitor (Gambro), which prepares ultrapure dialysis fluid for HD and sterile, pyrogen-free substitution solution for HF. The membrane (polyamide), fluid composition, and treatment time were the same on HF and HD. The targeted equilibrated Kt/V was 1.2 for both treatment modes, creating a similar urea clearance. RESULTS: Fifteen patients, mean age 62.8+/-8.4 years, completed the study according to the above conditions. Urea kinetics, nutritional parameters, and dry weight were similar in the three periods. The frequency of intra-treatment episodes of hypotension/patient/month was significantly lower on HF1 (1.24) and HF2 (1.27) than on HD (1.80) (P<0.04). It decreased progressively on HF1, then increased on HD, and decreased again during HF2. Patients had fewer muscular cramps on HF than on HD (P<0.03) and required significantly less saline and plasma expander during HF than HD sessions. The prevalence of inter-treatment symptoms, including fatigue and hypotension, was lower on HF than on HD (score difference P=0.04). Quality of life, determined by the Laupacis method in all three periods, showed a tendency towards improvement during the study, reaching the best values during HF2. CONCLUSIONS: HF has a progressive stabilizing haemodynamic effect, producing a more physiological cardiovascular profile than HD. This long-term effect, observed in stable patients treated under strictly identical conditions, is probably due to the mechanism of convection, and is different from the acute effect observed mainly in unstable patients.

Blood Flow Velocity↗
PubMed2000

Sleep-EEG modulation of interictal epileptiform discharges in adult partial epilepsy: a spectral analysis study.

INTRODUCTION: In order to define accurately the relationship between EEG components (spindles, delta and theta frequencies) and the occurrence of interictal epileptiform discharges (IED) during sleep in partial epilepsy, a correlation study between spike overnight distribution and EEG spectral power time series was performed. METHODS: Eighteen patients (mean age: 24.7+/-5.5 years) affected by partial epilepsy underwent continuous EEG-polysomnography. The temporal series of Slow Wave Activity (SWA), Sigma Activity (SA) and Theta Band (TB), derived from spectral analysis, were obtained from a spike-free and pathologic alteration-free derivation, contralateral to the most active lead, where the IED count was performed. Relationships between SA, SWA and TB and time series of IED were tested by means of correlation techniques after data normalization. RESULTS: Our results revealed a significantly higher correlation between IED and SWA in 12 subjects; a significantly higher correlation between IED and SA in three subjects and a significant correlation with TB in three cases. CONCLUSIONS: Data suggest that in most adult patients with partial epilepsy IED production during sleep is facilitated by the action of synchronizing mechanisms which are active during NREM sleep and lead to the appearance of EEG delta waves. Nevertheless evidence is given of two smaller groups of patients. In one of them IED are more sensitive to the promoting action of the spindle generating mechanism, active during stage 2 of NREM sleep. In the other one the promoting action of TB, characterizing EEG during stage 1 and REM sleep, is evident.

Adult↗
PubMed2000

Subcellular localization of epidermal growth factor in human submandibular gland.

Epidermal growth factor in human submandibular gland was localized at the subcellular level by means of an immunogold staining method. Labelling was observed in serous acini and ducts. In the acini, gold particles were found within secretory granules, indicating that the growth factor is released into the saliva through granule exocytosis. In the ductal system, the most intense reactivity was revealed in the principal cells of striated ducts. In these cells, an abundant population of small cytoplasmic vesicles was specifically stained. Immunoreactive vesicles were found both apically and basally, suggesting that ductal cells can release their products not only into the saliva but also into the interstitium.

Adolescent↗
PubMed2000

Release of dopamine from human neocortex nerve terminals evoked by different stimuli involving extra- and intraterminal calcium.

The release of [(3)H]-dopamine ([(3)H]-DA) from human neocortex nerve terminals was studied in synaptosomes prepared from brain specimens removed in neurosurgery and exposed during superfusion to different releasing stimuli. Treatment with 15 mM KCl, 100 microM 4-aminopyridine, 1 microM ionomycin or 30 mM caffeine elicited almost identical overflows of tritium. Removal of external Ca(2+) ions abolished the overflow evoked by K(+) or ionomycin and largely prevented that caused by 4-aminopyridine; the overflow evoked by caffeine was completely independent of external Ca(2+). Exposure of synaptosomes to 25 microM of the broad spectrum calcium channel blocker CdCl(2) strongly inhibited the 4-aminopyridine-induced tritium overflow while that evoked by ionomycin remained unaffected. The Ca(2+) chelator, 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N' tetraacetic acid (BAPTA), reduced significantly the K(+)- and the caffeine-induced tritium overflow. The effect of caffeine was attenuated by exposure to the ryanodine receptor blocker dantrolene or when the membrane-impermeant inositol trisphosphate receptor antagonist, heparin, was entrapped into synaptosomes; the combined treatment with dantrolene and heparin abolished the release elicited by caffeine. Tetanus toxin, entrapped into human neocortex synaptosomes to avoid prolonged incubation, inhibited in a concentration-dependent manner the K(+)- or the 4-aminopyridine-evoked tritium overflow; in contrast, the release stimulated by ionomycin and by caffeine were both totally insensitive to the same concentrations of tetanus toxin. Western blot analysis showed about 50% reduction of the content of the vesicular protein, synaptobrevin, in synaptosomes poisoned with tetanus toxin. In conclusion, the release of dopamine from human neocortex nerve terminals can be triggered by Ca(2+) ions originating from various sources. It seems that stimuli not leading to activation of voltage-sensitive Ca(2+) channels elicit Ca(2+)-dependent, probably exocytotic, release that is insensitive to tetanus toxin.

Adult↗
PubMed1999

Native human neocortex release-regulating dopamine D2 type autoreceptors are dopamine D2 subtype.

Dopamine (DA) autoreceptors expressed at DA nerve terminals regulate DA release. Considerable evidence has indicated that, in rodents, these autoreceptors belong to the D2 type of the DA receptor family, which, in turn, comprises the D2, D3 and D4 subtypes. We investigated here, for the first time, the subclassification of native human DA autoreceptors by studying the release of [3H]DA evoked by electrical stimulation in fresh human neocortical slices. The results have been compared with those obtained in three animal systems: rat neocortical and striatal slices and rat mesencephalic neuronal cultures. In human neocortical slices, the D2/D3 receptor agonist quinpirole (1 nM-10 microM) inhibited tritium release with a calculated EC50 of 17 nM and a maximal inhibition of approximately 75% reached at 1 microM. In the presence of the D2/D3 receptor antagonist (-)-sulpiride (0.1 and 1 microM), the concentration-response curve of quinpirole was shifted to the right, and the apparent pA2 mean value was 8.5 (8.14-8.77); on the other hand, the inhibitory effects of quinpirole were not affected by the D3 receptor-selective antagonist [7-N,N-dipropylamino-5,6,7, 8-tetrahydro-naphtho(2,3b) dihydro,2,3-furane] (S 14297) and the D4 receptor-selective antagonist 3-(4-[4-chlorophenyl]piperazin-1-yl)-methyl-1H-pyrrolo [2,3-b]pyridine (L-745,870) (0.01-1 microM in each case). Superimposable results have been obtained when the release was elicited from rat striatal slices or dopamine mesencephalic neurons in culture, whereas quantitative differences emerged in the case of rat cortical slices. It is concluded that in human brain, as well as in rat brain, the release of DA in the terminal region of midbrain dopaminergic neurons is regulated through autoreceptors of the D2 subtype.

Adult↗
PubMed1999

Autoregulation of cortical blood flow during surgery for ruptured intracranial aneurysms.

BACKGROUND: Little information is available about the extent and the time course of possible impairment of cerebral circulation occurring after aneurysmal subarachnoid haemorrhage (SAH). The aim of this study was to correlate cerebral autoregulation, neurological impairment at surgery and timing of surgery in patients with ruptured intracerebral aneurysms. METHODS: Cortical blood flow (CoBF) was measured intraoperatively by a thermal diffusion probe in 77 patients during surgery for ruptured supratentorial aneurysms, who were operated on at different time intervals after bleeding. An autoregulation index (AI), expressed as the ratio between the change in CoBF and the change of mean arterial blood pressure at the time of rising the systemic blood pressure after occlusion of the aneurysm(s), was determined in each case. RESULTS: Among good-grade patients (WFNS grade I-II), those operated on days 0-2 after SAH had a significantly better autoregulatory response, compared either with patients who underwent surgery on days 3-7 after bleeding (p<0.01), or with those whose aneurysm was occluded more than 7 days after rupture (p<0.03). The mean AI of poor-grade patients (WFNS grade IV-V), who received surgery on days 0-2 after SAH, was significantly higher (p<0.01) compared with the corresponding value of good-grade patients. No significant difference was found between the mean AIs of patients who subsequently did, or did not, develop symptomatic vasospasm. CONCLUSIONS: It is concluded that good-grade patients operated on within 48 hours after bleeding take advantage of a preserved autoregulatory function during controlled hypotension.

Adult↗
PubMed1998

Removal of tumours of the orbital apex via a postero-lateral orbitotomy.

BACKGROUND: The surgical management of pure apical tumours of the orbit may be problematic with traditional approaches. A postero-lateral approach, specifically designed for apical growths, provides a more favourable angle of vision through a relatively small bone opening. METHODS: A series of 103 consecutive cases of intraorbital tumours, operated on in a community-based institution, was retrospectively reviewed. Out of this series, 8 patients, harbouring lesions located in the posterior intraconal space, underwent a postero-lateral orbitotomy. This approach, through a small opening on the orbital and temporal portions of the greater wing of the sphenoid, with the lesser sphenoidal wing, the orbital plate of the frontal bone, the lateral rim of the orbit being maintained intact, allowed adequate exposure of the orbital apex and successful extirpation of the tumours. In four patients the histological examination disclosed a cavernoma; the other patients had, respectively, a dermoid cyst, a lymphoma, a hemangiopericytoma and a metastatic melanoma. RESULTS: No recurrences were observed in a follow-up period ranging from 1 to 7 years postoperatively (the patient with melanoma died 16 months after operation for systemic complications of her illness). One patient showed transient weakness of lateral rectus muscle due to surgical manipulation, which subsided in few months. CONCLUSIONS: The postero-lateral orbitotomy represents a reliable alternative to other traditional surgical approaches when dealing with tumours of the orbital apex, providing excellent exposure of this region with a low rate of operative morbidity.

Adult↗
PubMed1998

Immunocytochemical investigation of the subcellular distribution of some secretory products in human salivary glands.

The subcellular distribution of epidermal growth factor (EGF) and of Lewis antigens was demonstrated by means of a post-embedding immunogold cytochemical method in human parotid and submandibular gland. Acinar secretory granules were reactive for EGF and difucosylated Lewis antigens, cell surfaces of acini and striated ducts reacted only for difucosylated antigens; a great number of cytoplasmic vesicles in acinar and ductal cells were reactive for all Lewis antigens and EGF. These results suggest that substances which enter saliva are released not only through granule exocytosis by acinar cells, but also via other routes: the vesicular system revealed in both acinar and ductal cells could play a fundamental role in driving some products both towards the lumen and towards basolateral cell surfaces and intercellular spaces.

Epidermal Growth Factor↗
PubMed1997

Prolactin decrease and shift to a normal-like isoform profile during treatment with quinagolide in a patient affected by an invasive prolactinoma.

Prolactin (PRL) circulates as multiple molecular weight variants: glycosylated phosphorylated, deamidated and sulphated forms. The profiles of the forms, as determined by isoelectrofocusing (IEF), differ in physiological and pathological conditions. The case of a 72-year-old woman affected by an invasive prolactinoma is described. The patient had undergone surgical treatment followed by radiotherapy at the age of 71 years. Bromocriptine therapy followed (up to 10 mg/die), but the PRL levels were still extremely high (over 13,000 micrograms/l as determined by IRMA, after dilution). We therefore treated the patient with quinagolide, at increasing dosages, from 150 micrograms/die on day 0 to 600 micrograms/die on day 220. This treatment progressively lowered PRL to 23.2 micrograms/l. In addition to a decrease in PRL levels, a progressive change in the IEF profile was also noted. Indeed, on day 0, the PRL isoforms were very acidic and during treatment they progressively shifted toward a more basic range. For purpose of comparison PRL profiles were also determined in 8 women with pathological hyperprolactinaemia (group A, aged 16-50 years, PRL levels: 25.1-170.4 micrograms/l), in 6 normal women (group B, aged 25-29 years, PRL levels: 3.4-7.9 micrograms/l) and in 5 normal women during a TRH test (group C, aged 17-52 years, PRL levels: 2.7-10.3 micrograms/l). The profiles observed in group A had a single major peak at isoelectric point (pI) 6.5, while the group B and C profiles were more heterogeneous displaying multiple minor peaks, the majority of the molecules being in a more basic range (pI 6.9 for group B and pI 7.5 for group C). During treatment, the profiles of our subject at first resembled those of group A; subsequently, when the PRL levels had normalised, the profile resembled those noted in group B. Altered (immature?, more glycosilated?, less bioactive?) PRL molecules could be secreted by the tumour. These data show that quinagolide successfully reduced PRL levels, while inducing secretion of forms more similar to those found in women affected by pathological hyperprolactinaemia or in normal women.

Adolescent↗
PubMed1997

Activation of brain nitric oxide synthase in depolarized human temporal cortex slices: differential role of voltage-sensitive calcium channels.

1. Nitric oxide (NO) synthase activity was studied in slices of human temporal cortex samples obtained in neurosurgery by measuring the conversion of L-[3H]-arginine to L-[3H]-citrulline. 2. Elevation of extracellular K+ to 20, 35 or 60 mM concentration-dependently augmented L-[3H]-citrulline production. The response to 35 mM KCl was abolished by N(G)-nitro-L-arginine (100 microM) demonstrating NO synthase specific conversion of L-arginine to L-citrulline. Increasing extracellular MgCl2 concentration up to 10 mM also prevented the K+ (35 mM)-induced NO synthase activation, suggesting the absolute requirement of external calcium ions for enzyme activity. 3. However, the effect of high K+ (35 mM) on citrulline synthesis was insensitive to the antagonists of ionotropic and metabotropic glutamate receptors dizocilpine (MK-801), 6-nitro-7-sulphamoylbenzo(f)-quinoxaline-2-3-dione (NBQX) or L-2-amino-3-phosphonopropionic acid (L-AP3) as well as to the nicotinic receptor antagonist, mecamylamine. 4. The 35 mM K+ response was insensitive to omega-conotoxin GVIA (1 microM) and nifedipine (100 microM), but could be prevented in part by omega-agatoxin IVA (0.1 and 1 microM). The inhibition caused by 0.1 microM omega-agatoxin IVA (approximately 30%) was enhanced by adding omega-conotoxin GVIA (1 microM) or nifedipine (100 microM). Further inhibition (up to above 70%) could be observed when the three Ca2+ channel blockers were added together. Similarly, synthetic FTX 3.3 arginine polyamine (sFTX) prevented (50% at 100 microM) the K+-evoked NO synthase activation. This effect of sFTX was further enhanced (up to 70%) by adding 1 microM omega-conotoxin GVIA plus 100 microM nifedipine. No further inhibition could be observed upon addition of MK-801 or/and NBQX. 5. It was concluded that elevation of extracellular [K+] causes NO synthase activation by external Ca2+ entering cells mainly through channels of the P/Q-type. Other Ca2+ channels (L- and N-type) appear to contribute when P/Q-channels are blocked.

Alanine↗
PubMed1997

On-line predilution hemofiltration versus ultrapure high-flux hemodialysis: a multicenter prospective study in 23 patients. Sardinian Collaborative Study Group of On-Line Hemofiltration.

The aims of the present prospective multicenter study were to assess the clinical tolerance and well being, the correlation between nPCr and Kt/V and the pretreatment beta 2-microglobulin level in patients sequentially treated with high-flux dialysis with ultrapure bicarbonate hemodialysis (HD; phase 1) and predilution hemofiltration (HF) with on-line prepared bicarbonate substitution fluid (phase II). The same monitor (Gambro AK 100 ULTRA) and membrane (polyamide) were used. Twenty-three patients, all in a stable clinical condition, entered the study. The treatment was targeted to an equilibrated Kt/V (eqKt/V) of 1.4 for HD and 1.0 for HF. No mortality or relevant morbidity were observed. The number of hypotensive episodes was 1.78 +/- 2.8 per patient and month during HD vs. 1.17 +/- 3.1 during HF (p = 0.003) and the number of the hypertensive episodes 1.28 +/- 2.8 during HD vs. 0.42 +/- 0.8 during HF (p = 0.04). Incidences of arrhythmia, muscular cramps and headache were significantly less frequent during HF. Interdialytic cramps, arthralgia and fatigue were also significantly less frequent during the HF period. The average beta 2-microglobulin level was 27.1 +/- 14.7 mg/dl at the start of the study, 22.9 +/- 4.9 mg/dl at the beginning of phase II and 22.4 +/- 4 mg/dl at the end of phase II (p = 0.01 compared to the start). A significant linear correlation between the normalized protein catabolic rate and eqKt/V was obtained faster during HD than during HF (45 vs. 120 days) indicating that HF affects the nutritional status with mechanisms different from HD. The present study is in agreement with the hypothesis that HF gives and adequate nutritional status with improved clinical stability and well being at a lower Kt/V compared to HD. Both therapies were efficient in controlling the pretreatment beta 2-microglobulin level.

Aged↗