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Biomedical subjects

M Cossu

Publications and source records attributed to M Cossu.

At least 55 records · Page 3Linked to original sources

A randomized study comparing three cyclosporine-based regimens in cadaveric renal transplantation. Italian Multicentre Study Group for Renal Transplantation (SIMTRe).

Whether it is better to treat renal transplant patients with cyclosporine alone, combined with steroids, or combined with steroids and azathioprine is still unclear. After initial therapy with cyclosporine and steroids, 354 cadaver renal transplant recipients were randomly assigned at the post-transplant day 5 to cyclosporine alone (monotherapy), cyclosporine plus steroids (double therapy), or cyclosporine plus steroids plus azathioprine (triple therapy). Monotherapy patients, after a second acute rejection, were switched to either of the two alternative therapies. According to intention-to-treat (ITT) analysis, the 4-year patient survival was 97% in monotherapy, 91% in double therapy, and 96% in triple therapy; the graft survival including death was 84%, 77%, and 88%, respectively; and the pure graft survival was 87%, 85% and 91%, respectively (P = not significant). Acute rejections were diagnosed in 79 patients in monotherapy, 58 in double therapy, and 59 in triple therapy (P < 0.01). Of the patients on monotherapy, 52% were switched to double or triple therapy. In these patients, the 4-year graft survival including death was 68%, and the pure graft survival was 72%, in comparison with 93% and 94%, respectively, for patients who continued on cyclosporine alone. Patients with renal polycystic disease as a cause of renal failure and with low plasma creatinine at the time of randomization (5 days after transplant) had a higher probability of remaining on monotherapy, wherease those with glomerulonephritis or systemic lupus erythematosus (SLE) and with high plasma creatinine levels at randomization had a higher probability of being switched to double or triple therapy. According to ITT analysis, there were fewer ocular (P < 0.0001), osteomuscular (P < 0.002) and cardiovascular complications (P = 0.05) and fewer patients with hypercholesterolemia (P < 0.0028) in the monotherapy group, with no difference between double and triple therapy. Creatinine clearance at 3 years was lower in monotherapy, but no attrition of renal function was seen over the years in any of the groups. Cyclosporine, however used, provided good results in cadaveric renal transplantation. Triple therapy and monotherapy offered a nonsignificantly better patient and graft survival than double therapy. Patients on monotherapy had a higher risk of acute rejection but had fewer adverse events than those on double or triple therapy. Patients maintained on cyclosporine alone had the best graft survival, whereas those who were assigned to monotherapy and had to add steroids because of multiple rejections had the worst outcome. Therefore, it seems reasonable to limit the choice of monotherapy to patients without immune-mediated renal diseases and with good graft function in the early post-transplant period.

Adolescent↗

Ultrastructural localization of blood group antigens in human exocrine pancreas by immunogold labelling.

The cytochemical distribution of ABH and Lewis antigens was investigated in human pancreas by means of a post-embedding immunogold staining method which permitted antigens associated with secretory materials to be distinguished from those bound to cell surfaces. H and Le-b antigens were found in secretory granules of acinar and interlobular duct cells. In the form of surface-associated antigens, H and Le-b were found in acini and interlobular ducts, Le-a in intralobular ducts. In ductal cells, the same antigens detected in cell surfaces were also found in small cytoplasmic vesicles. It is suggested that by the emptying of these vesicles blood group antigens may be released both into the lumen and into the interstitial spaces.

ABO Blood-Group System↗

Ultrastructural localization of blood group antigens in human salivary glands.

The subcellular distribution of several blood group antigens was studied in human major and minor salivary glands by means of a postembedding immunogold staining method. In each gland, antigens were detected as secretory products and as cell surface components. A, B, H and Lewis (a,b,x,y) antigens were found in mucous cells depending on the ABO and secretor status; reactivities were confined to the secretory granules. In serous and ductal cells, both the secretory granules and cell membranes were reactive, but only for H, Le-b and Le-y irrespective of the ABO and secretor status.

ABO Blood-Group System↗

Low-dosage ibopamine treatment in progressive renal failure: a long-term multicentre trial.

A multicentre trial (11 nephrology centres) was carried out to test the effects of ibopamine, an orally active dopamine-like drug, on the progression of chronic renal failure. For a 2-year period 189 chronic renal failure patients (serum creatinine level 1.5-4.0 mg/dl) were observed. They were homogeneous for basic nephropathy, degree of residual renal function, blood pressure, and proteinuria. The patients were randomly divided into two groups: 96 took ibopamine at a dosage of 100 mg/day (group A) and 93 served as controls (group B). All were on a low-protein diet (mean 0.8 g/kg body weight). By the end of the observation period, the rate of decrease of the renal function indexes in time proved significantly slower (1.8 times) in group A than in group B. The survival curves for renal function (pre-established end points were creatinine level increases equal to or > 20% and equal to or > 40% of the basal values) proved significantly better (p < 0.02 and p < 0.002 respectively) in group A than in group B. The mean plasma creatinine values rose by 17% in group A and by 36% in group B. The creatinine clearance decreased by 5% in treated patients and by 14% in the controls. Statistical analysis ruled out any possible centre effect. The trial suggests that low-dosage ibopamine administration may be used as a valid and safe pharmacological adjunct for retarding the progression of renal failure in patients with mild or moderate chronic renal impairment.

Adolescent↗

Major COL4A5 gene rearrangements in patients with juvenile type Alport syndrome.

Mutations in the COL4A5 gene, which encodes the a5 chain of type IV collagen, are found in a large fraction of patients with X-linked Alport syndrome. The recently discovered COL4A6, tightly linked and highly homologous to COL4A5, represents a second candidate gene for Alport syndrome. We analyzed 177 Italian Alport syndrome families by Southern blotting using cDNA probes from both COL4A5 and COL4A6. Nine unrelated families, accounting for 5% of the cases, were found to have a rearrangement in COL4A5. No rearrangements were found in COL4A6, with the exception of a deletion encompassing the 5' ends of both COL4A5 and COL4A6 genes in a patient with Alport syndrome and leiomyomatosis. COL4A5 rearrangements were all intragenic and included 1 duplication and 7 deletions. Polymerase chain reaction (PCR) analysis was carried out to characterize deletion and duplication boundaries and to predict the resulting protein abnormality. The two smallest deletions involved a single exon (exons 17 and 40, respectively), while the largest ones spanned exons 1 to 36. The clinical phenotype of patients in whom a rearrangement in COL4A5 was detected was severe, with progression to end-stage renal failure in juvenile age and hypoacusis occurring in most cases. These data have some important implications in the diagnosis of patients with Alport syndrome.

Adolescent↗

Postero-lateral microsurgical approach to orbital tumors.

A modification of the lateral orbitotomy is reported for the microsurgical approach to tumors located in the posterior intraconal space. The orbital apex is entered through a small bone 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, and the lateral orbital rim being left intact. This surgical technique was employed in 8 cases of pure apical tumors, out of a consecutive series of 103 orbital growths. It proved to be reliable with regard to either adequate exposure and radical excision of the lesions or low rate of operative morbility.

Adult↗

The "VGF" protein in rat adenohypophysis: sex differences and changes during the estrous cycle and after gonadectomy.

Gene expression and cell localization of the neuroendocrine protein VGF were studied in the rat anterior pituitary. In females, four antisera against nonoverlapping regions of VGF immunostained a small number of lactotropes and many gonadotropes. In the latter cells, VGF immunoreactivity was localized to a subpopulation of secretory granules. Distinct changes were seen after estrus, with a significant increase in VGF messenger RNA (whole pituitary), whereas VGF immunostaining was strikingly reduced in gonadotropes and somewhat more abundant in lactotropes. In male rats, gene expression was low, and immunoreactivity was restricted to a few lactotropes. After castration or ovariectomy, VGF messenger RNA was high, and VGF immunoreactivity was abundant in gonadotropes. Selective localization and cyclic modulation suggest involvement of the VGF gene product(s) in pituitary gonadotrope and/or lactotrope function.

Animals↗

Cortical blood flow recorded during early or delayed surgery for ruptured intracranial aneurysms.

Forty-three patients were operated on for ruptured intracranial aneurysms during a 12-month-period. Intraoperative evaluation of cortical blood flow by means of a thermal diffusion probe was performed in 23 out of the 41 patients who were operated on for aneurysms of the anterior circulation. The autoregulation index was determined at the time of raising the systemic blood pressure after clipping of the aneurysm(s). No statistically significant difference was found between the averages of the autoregulation indexes calculated in the subgroups of patients submitted respectively to early or delayed surgery. There was no correlation of both cortical blood flow and autoregulation with either age of the patients, or preoperative neurological grade. On the contrary, the autoregulation index showed a statistically significant correlation with outcome.

Adult↗

Longitudinal study of cerebral blood flow following early or delayed surgery for ruptured intracranial aneurysms.

Out of a series of 43 cases operated on for ruptured intracranial aneurysms over a 12-month-period, 32 patients were followed up to 12 months postoperatively with repeated evaluations of cerebral blood flow, using the Xenon133 inhalation technique. No statistically significant differences in cerebral perfusion were detected between the subgroups of good-grade patients, who were submitted respectively to early, or delayed surgery. Depression of flow in the affected hemisphere of poor-grade patients was principally related to the preoperative occurrence of an intracerebral haematoma. The overall results were not consistent with the hypothesis that early surgical intervention results in long-lasting effects on the cerebral circulation.

Adult↗

Infratentorial ischaemia following experimental cerebellar haemorrhage in the rat.

Early changes of cerebellar and cerebral blood flow, as well as subsequent infratentorial ischaemia, were evaluated in an experimental model of cerebellar haemorrhage. Eight anaesthetized male adult Sprague-Dawley rats received an injection of autologous arterial blood (50 microliters) into the right cerebellar hemisphere. Eight animals were sham-operated and served as controls. Cerebellar blood flow, measured at regular time intervals in the hemispheric cortex ipsilateral to the lesion by the hydrogen clearance method, was significantly depressed in the experimental group as compared with the control animals. This drop in cerebellar blood flow was evident 5, 30, 60, 90, and 120 min postoperatively, with a return to pre-injection values recorded 180 min after surgery. No significant difference in supratentorial blood flow was detected over the entire period examined between the two groups of animals. Enzyme histochemistry demonstrated areas of ischaemia around the clot and within the brain stem in animals with an intracerebellar haemorrhage at the end of the experiment. These results provided evidence of ischaemic damage within the infratentorial compartment after the induction of experimental cerebellar haemorrhage.

Acetylcholinesterase↗

Immunocytochemical localization of blood group ABH antigens in the human parotid gland.

The aim of this study was to determine whether the parotid gland, like other salivary glands, produces blood group antigens. A post-embedding immunogold staining (IGS) method for ABH antigens was applied to osmicated and nonosmicated, routinely prepared specimens of normal human parotid glands. A and B antigens were not detected, whereas H antigen was found in acini and ducts of glands from A, B, and O subjects. In osmicated samples, the only sites of H labeling were secretory granules of a few acinar cells and those of most intercalated duct cells. In both cell types, only the pale matrix of the granules was stained. In non-osmicated samples, secretory granules showed the same distribution pattern of H, although gold particles were more abundant, and basolateral membranes of acinar and striated duct cells and the apical vesicles of striated duct cells were also labeled. Our results suggest that small amounts of H antigen are secreted by the parotid gland.

ABO Blood-Group System↗

Immunocytochemical localization of Lewis blood group antigens in human salivary glands.

We demonstrated the immunohistochemical distribution of Le-a and Le-b blood group antigens in human major and minor salivary glands at the ultrastructural level by applying a post-embedding immunogold staining method. In secretors' glands, a faint Le-a reactivity was found only in mucous droplets, whereas Le-b antigen was intensely stained in secretory granules of most mucous cells, in those of intercalated duct cells, in the pale granular matrix of some serous cells, and, when osmication was omitted, in cytoplasmatic vesicles and cell surfaces of striated ducts. In the submandibular gland of a non-secretor, Le-a antigen was considerably stained in mucous droplets, whereas Le-b reactivity was restricted to the striated duct cells. These results indicate that the secretor status affects the secretion of Lewis antigens by mucous, serous, and intercalated duct cells but not the presence of Le-b as a surface antigen in striated duct cells.

ABO Blood-Group System↗

Subsequent bleeding from ruptured intracranial aneurysms treated by wrapping or coating: a review of the long-term results in 47 cases.

Forty-seven patients, who underwent surgery over a 34-year period by the wrapping or coating of ruptured intracranial aneurysms, have been retrospectively evaluated. The following materials were used in the surgical procedures: muscle with gelatin sponge (7 cases), gauze (2 cases), oxidized cellulose with Biobond (28 cases), Histoacryl with gauze or fascia (10 cases). The patients were monitored for up to 37 years (mean, 13.7 +/- 8.2 yr). One or more subsequent bleedings occurred in eight patients (17%). Three patients had additional bleeding and died in the early postoperative phase (within 1 mo after surgery). In five patients, the subsequent bleeding occurred between 1 and 15 years postoperatively, with two fatalities. One patient experienced two recurrences. Therefore, the mortality rate for postoperative bleedings was 10.6% (five patients) in the whole series, and the incidence of early (within 1 mo after surgery) fatal bleedings was 6.4%. After the first month from the initial hemorrhage, the global risk of subsequent bleeding was 0.93%/yr. Among the nine patients whose aneurysms were wrapped with muscle, gelatin sponge, or gauze, four additional bleedings occurred, whereas four relapses were observed among the 38 cases treated by employing bioadhesive agents (P < 0.04; Fisher's exact test). The rate of further bleeding was higher (25%) in patients undergoing surgery in the premicrosurgical era compared with that (8.7%) recorded in patients treated by microsurgery (difference statistically not significant).

Adolescent↗

Pituitary adenoma associated with dural arteriovenous fistula. Case report.

The association of a pituitary adenoma with a dural arteriovenous fistula supplied by the posterior branches of the middle meningeal artery and draining into the transverse sinus is reported. Among the possible etiopathogenic explanations of such an unusual association, a progressive mechanical obstacle to the dural venous blood drainage to the left wing of the compressed cavernous sinus and subsequent opening of embryonic dural arterio-venous shunts with reversal of flow has been considered.

Adenoma↗

[Intra- and postoperative cerebral blood flow in patients with subarachnoid hemorrhage from a ruptured aneurysm].

The CBF of eight patients, who underwent surgery for ruptured aneurysm, was monitored using the termodiffusion technique (TDF). The device employed in this investigation allowed a continuous monitoring in "real time" of the cortical flow. The purpose of the study was to detect disorders of autoregulation, which were evaluated with the autoregulation index (AI). Autoregulation was correlated with the neurological preoperative grading, the postoperative changes of CBF (Xe133 clearance) and the outcome. The results of this preliminary study showed a correlation between these parameters and stressed the value of CBF monitoring during surgery.

Adult↗

The outcome from acute subdural and epidural intracranial haematomas in very elderly patients.

Out of a consecutive series of 1082 operations performed on head-injured patients over a 9-year period, 28 cases of acute subdural haematomas (SDHs) or epidural haematomas (EDHs) occurring in patients aged between 80 and 100 years were selected. Mortality rates in these patients (100% in 2 EDHs, 88% in 26 SDHs) were significantly higher (p less than 0.01) compared with patients under 80 years (12% in 308 EDHs, 57% in 215 SDHs). Pre-existing diseases, primary events precipitating falls, and multiple system failure complicating the postoperative course accounted for most of the deaths. None of the patients operated upon with a Glasgow Coma Scale score of 11 or less survived. A typical 'talk and die' course occurred in two cases. Three patients, all operated on for SDH, survived and returned to their pre-injury conditions. It was concluded that, whilst the question as to whether to submit very old comatose patients to life-prolonging measures remains unsettled, there is a case for the prompt evacuation of extra-axial clots in patients with minimal impairment of consciousness.

Aged↗