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Biomedical subjects

A Santoro

Publications and source records attributed to A Santoro.

At least 91 records · Page 5Linked to original sources

Frontotemporal orbitozygomatic craniotomy to exposure the cavernous sinus and its surrounding regions. Microsurgical anatomy.

BACKGROUND: The microsurgical anatomy of the cavernous sinus and its surrounding regions were examined via frontotemporal orbitozygomatic (FTOZ) craniotomy. Combined with other deep osteotomies, the possibility of exposing the petroclival region and basilar artery was also explored. METHODS: The study was made on 20 sides of 10 cadaveric specimens fixed with formalin, with the help of the surgical microscope (magnification 5-15). RESULTS: The FTOZ was performed with frontotemporal and orbitozygomatic flaps. Extradurally, V2, V3, the trigeminal ganglion, the posterior vertical segment of the intracavernous ICA and the VI nerve were exposed by FTOZ craniotomy. By further removal of the petrous apex (Kawase's triangle), exposure could be extended to the petroclival region; with anterior modification of the microscopic light, in 50% of the specimens, exposure reached as low as the convergence of the vertebral arteries. The anterior part of the cavernous sinus and the orbital apex were examined by removing the anterior clinoid process, orbital roof and unroofing the optic canal. Intradurally, the intrapeduncular fossa (upper 1/3 of the clivus) was examined. The intracavernous cranial nerves and vessels were studied via lateral and superior wall approaches. By removing both the anterior and posterior clinoid processes together, in 80% of the specimens, the exposure could be carried as far as the midpoint of the basilar artery. CONCLUSIONS: FTOZ craniotomy could be used to treat lesions involving the cavernous sinus and its surrounding regions. Incorporated with the petrous apectomy, it could be used to expose the petroclival region and, in selected cases, exposure could be extended to the convergence of the vertebral arteries. Combined with anterior and posterior clinoidectomies, it could also be used to treat midpoint regions of the basilar artery.

Basilar Artery↗

Cerebral hemodynamics on MR perfusion images before and after bypass surgery in patients with giant intracranial aneurysms.

BACKGROUND AND PURPOSE: Preoperative assessment of the anatomy and dynamics of cerebral circulation for patients with giant intracranial aneurysm can improve both outcome prediction and therapeutic approach. The aim of our study was to use perfusion MR imaging to evaluate cerebral hemodynamics in such patients before and after extraintracranial high-flow bypass surgery. METHODS: Five patients with a giant aneurysm of the intracranial internal carotid artery underwent MR studies before, 1 week after, and 1 month after high-flow bypass surgery. We performed MR and digital subtraction angiography, and conventional and functional MR sequences (diffusion and perfusion). Surgery consisted of middle cerebral artery (MCA)-internal carotid artery bypass with saphenous vein grafts (n = 4) or MCA-external carotid artery bypass (n = 1). RESULTS: In four patients, MR perfusion study showed impaired hemodynamics in the vascular territory supplied by the MCA of the aneurysm side, characterized by significantly reduced mean cerebral blood flow (CBF), whereas mean transit time (MTT) and regional cerebral blood volume (rCBV) were either preserved, reduced, or increased. After surgery, angiography showed good canalization of the bypass graft. MR perfusion data obtained after surgery showed improved cerebral hemodynamics in all cases, with a return of CBF index (CBFi), MTT, and rCBV to nearly normal values. CONCLUSION: Increased MTT with increased or preserved rCBV can be interpreted as a compensatory vasodilatory response to reduced perfusion pressure, presumably from compression and disturbed flow in the giant aneurysmal sac. When maximal vasodilation has occurred, however, the brain can no longer compensate for diminished perfusion by vasodilation, and rCBV and CBFi diminish. Bypass surgery improves hemodynamics, increasing perfusion pressure and, thus, CBFi. Perfusion MR imaging can be used to evaluate cerebral hemodynamics in patients with intracranial giant aneurysm.

Adult↗

Lymphomas.

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Humans↗

Nerve root compression by a gas-containing cyst associated with stenotic lateral recess. Case report and review of the literature.

The authors describe a case in which a gas-containing cyst was associated with a stenotic lateral recess at the same level in the absence of any disc material. A young man presented a one-month history of sciatica caused by compression of the left L5 nerve root. The neuroradiological investigations performed (CT, MRI) showed the presence of a gas-containing cyst associated with a stenotic lateral recess. The clinical, etiopathological characteristics and treatment of this condition are discussed and the pertinent literature is reviewed. Decompression of the nerve root was obtained by surgery. The herniated gas collected within a capsule (gas-containing cyst) can act as a mass and produce symptoms, much like a herniated nucleus pulposus. The antalgic stance adopted by the patient with marked flexion of the spine helps to distribute the pressure exerted by the cyst over a wider area (Pascal's law I). The appropriate procedure to relieve the radicular compression caused by gas-containing cyst seemed to be the surgical treatment.

Cysts↗

Spinal intradural endodermal cyst located anterior to the cervical spinal cord.

Spinal endodermic cysts are rare and may be associated with other congenital anomalies (mediastinal cysts, bony defects of the vertebral body), derive from defective displacement of the endoderm of the intestinal tract or, more rarely, the respiratory one. The authors describe a case of endodermic cyst of the cervical spine localized anteriorly to the spinal cord. In the case we treated the patient was a 17-year-old male who presented hypostenia of the lower limbs accompanied by hyperreflexia and spasticity; physical examination was negative. MRI, CT and CT-myelography documented a well-defined mass situated anteriorly to the spinal cord at C2-C4 level. A total-body CT-scan excluded the existence of other malformations. Surgery was performed via an anterior approach and the cyst completely removed. Histological examination confirmed the endodermal nature of the cyst. At long-term follow-up examination the patient was neurologically intact. Postoperative MRI showed a small residue of the cyst wall without spinal cord compression. Endodermic spinal cysts are very rare intradural lesions, predominantly with an anterior cervical localization, which derive from misplaced embryonic and endodermic cells. In the majority of cases, clinical onset is insidious and has a discontinuous progression. The best diagnostic tool is MRI. Treatment of choice is total surgical removal or emptying of the cyst followed by fenestration.

Adolescent↗

Human serine racemase: moleular cloning, genomic organization and functional analysis.

High levels of D-serine are found in mammalian brain, where it is an endogenous agonist of the strichinine-insensitive site of N-methyl D-aspartate type of glutamate receptors. D-serine is enriched in protoplasmic astrocytes that occur in gray matter areas of the brain and was shown to be synthesized from L-serine. We now report cloning and expression of human serine racemase, an enzyme that catalyses the synthesis of D-serine from L-serine. The enzyme displays a high homology to the murine serine racemase. It contains a pyridoxal 5'-phosphate attachment sequence similar to bacterial biosynthetic threonine dehydratase. Northern-blot analysis show high levels of human serine racemase in areas known to contain large amounts of endogenous D-serine, such as hippocampus and corpus callosum. Robust synthesis of D-serine was detected in cells transfected with human serine racemase, demonstrating the conservation of D-amino acid metabolism in humans. Serine racemase may be a therapeutic target in psychiatric diseases as supplementation of D-serine greatly improves schizophrenia symptoms. We identify the human serine racemase genomic structure and show that the gene encompasses seven exons and localizes to chromosome 17q13.3. Identification of the intron-exon boundaries of the human serine racemase gene will be useful to search for mutations in neuropsychiatric disorders.

Amino Acid Sequence↗

Ultrastructural and immunohistochemical study of basal lamina of the testis in adolescent varicocele.

OBJECTIVE: To evaluate a possible involvement of the extracellular matrix (ECM) in the testes of adolescents with varicocele. DESIGN: Cross-sectional study. SETTING: University-based medical center. PATIENT(S): Twenty-four adolescents aged between 13 and 18 years underwent surgical treatment for repair of left idiopathic varicocele. INTERVENTION: A testis biopsy was performed at time of surgery. MAIN OUTCOME MEASURE(S): Transmission electron microscopy study of basal lamina and immunofluorescence studies of collagen type IV and laminin, two major components of basal lamina. RESULT(S): Transmission electron microscopy observations showed an uneven profile of the basal lamina with a variable thickness. Immunofluorescence studies showed an irregular immunofluorescent line that appeared interrupted in some observations. Collagen type IV showed some areas of strong immunostaining with other areas with reduced immunoreactivity. CONCLUSION(S): Our ultrastructural and immunohistochemical observations highlight focal damage at the level of peritubular basal lamina, but this damage is not as severe as that described in adult varicocele. Initial involvement of basal lamina could represent one of the mechanisms responsible for varicocele-induced histologic alterations of the testes.

Adolescent↗

Chronic subdural haematomas in patients aged under 50.

The clinical findings in 31 patients with chronic subdural haematoma (CSH), aged between 20 and 50, are described. Aetiopathogenetic factors responsible for the formation of CSH match those of patients aged over 50 with CSH. A history of cranial trauma was present in 77% of the cases. In the remaining patients, a defect of haemostatic mechanisms was responsible for the subdural blood collection. On the computed tomography (CT) the haematoma generally appears as a thin subdural layer. The reliability of magnetic resonance imaging for detection of CSH makes it the most desirable investigation in such patients. Prognosis is influenced by preoperative clinical status and by the disease responsible for the formation of CSH.

Adult↗

Fludarabine and cladribine in relapsed/refractory low-grade non-Hodgkin's lymphoma: a phase II randomized study.

BACKGROUND: It is unclear whether the purine analogs fludarabine (Flu) and cladribine (CdA) are non-resistant. PATIENTS AND METHODS: Sixty patients with relapsed or refractory low-grade NHL were randomly allocated to initial treatment with either Flu 25 mg/m2, or CdA 0.14 mg/kg, each for five consecutive days every four weeks. Upon treatment failure, eligible patients were crossed over to the other study drug. RESULTS: Overall response and CR were 68% and 48% with Flu, and 72% and 38% with CdA, respectively. For responders, actuarial three-year progression-free survival was 58% with Flu and 52% with CdA. Treatment with both drugs was well tolerated, with toxic effects primarily hematological. Two patients (8%) in the Flu group and 15 patients (47%, P = 0.001) in the CdA group were taken off study because of persistent hematological toxicity. After cross over, none of seven refractory patients responded, while eight of nine previously responsive patients achieved second responses. CONCLUSIONS: Our study confirms that Flu and CdA have similar response rates and durations. However, further studies are required to optimize the CdA schedule and dosage in order to ameliorate its toxic profile while maintaining antitumor activity. The two drugs appear to be cross-resistant.

Adult↗

Confounding factors in the assessment of delivered hemodialysis dose.

A satisfactory dialysis patient's outcome results from an effective and personalized therapy. However, the higher the prescribed efficiency, the more likely it is that the prescribed dose is incorrectly administered. Avoiding discrepancies between the prescribed and delivered doses calls for a continuous surveillance, from urea kinetics to urea biosensors. An unexpectedly low efficiency result may affect several patients or may just be limited to the individual patient. An inadequate calibration of blood and dialysate pumps or manufacturing defects in blood tubings or needles may be responsible for a more diffuse phenomenon. The most frequently detected factors in the individual patient are poor vascular access, recirculation, decreases in dialyzer performance and insufficient anticoagulation. However, urea removal per se is not enough to satisfy all the assumptions underlying an adequate dialysis therapy. Indeed, dialysis adequacy is achieved by way of a complex combination of numerous elements transcending urea removal alone: acidosis correction, the achievement of dry body weight, fluid and electrolyte homeostasis, good blood pressure control, overall biocompatibility, anemia and malnutrition correction, and finally, a customized schedule together with treatment duration.

Dialysis Solutions↗

Efficacy and safety of oral betaine glucuronate in non-alcoholic steatohepatitis. A double-blind, randomized, parallel-group, placebo-controlled prospective clinical study.

In a prospective, randomized, double-blind therapeutic trial, 191 patients with non-alcoholic steatohepatitis were treated for 8 weeks daily b.i.d. orally either with betaine glucuronate combined with diethanolamine glucuronate and nicotinamide ascorbate (Ietepar) (96 patients) or with undistinguishable placebo capsules (95 patients). The verum treatment effectively reduced by 25% hepatic steatosis (p < 0.01) and by 6% hepatomegaly (p < 0.05), while placebo did not significantly reduce the disorders. Verum was also more effective than placebo on discomfort in abdominal upper right quadrant. The global efficacy of treatment was rated by the doctor "very good" or "good" in 48% of verum treated patients and only in 17% after placcbo (P of difference = 9 x 10(-6)). 52% of patients self-rated efficacy as "very good" or "good" after verum and only 34% after placebo (P of difference = 0.017). The verum treatment provoked a significant reduction of the increased liver transaminases (ALT, AST and gamma-GT) while placebo was ineffective. Adverse events were recorded in 10% of verum-treated patients and in 7% under placebo (no significant difference). In both groups the adverse events were mild and transient, did not require treatment discontinuation and were undistinguishable from common symptoms of liver disorders. In conclusion, the 8-week treatment with betaine glucuronate combined with diethanolamine glucuronate and nicotinamide ascorbate was found effective in non-alcoholic steatohepatitis, a disorder for which the hitherto pharmacological interventions were poorly and inconsistently effective.

Adult↗

Bioavailability and pharmacokinetic profile of glyceryl trinitrate and of glyceryl dinitrates during application of a new glyceryl trinitrate transdermal patch.

The pharmacokinetics and bioavailability of glyceryl trinitrate (GTN, CAS 55-63-0) and of its main metabolites, i.e. 1,2-glyceryl dinitrate (1,2-GDN, CAS 621-65-8) and 1,3-glyceryl dinitrate (1,3-GDN, CAS 623-87-0), were compared during a single 24-h application of a new GTN transdermal patch (Epinitril 10, hereinafter called EPI-10) or a reference patch (hereinafter called ND-10) releasing 10 mg GTN in 24 h. The study was an open, randomized balanced cross-over study on 24 healthy male volunteers to whom the patches were applied to the antero-lateral part of the thorax in two periods separated by a 3-day wash-out. Blood samples were collected before administration, during the 24-h patch application and at 0.5, 2 and 3 h after patch removal. Assayed in plasma were GTN, 1,2-GDN and 1,3-GDN using validated GC/MS methods with stable isotope-labeled internal standards (15N3-GTN, 15N2-1,2-GDN, and 15N2-1,3-GDN). The ratios of the AUCs of GTN, 1,2-GDN and 1,3-GDN measured during application of EPI-10 or of ND-10 were within the 0.85-1.25 limits required to assess equivalence of the extent of bioavailability. The ratios of the Cmax were within said limits for the signal metabolite 1,2-GDN and only slightly below (0.78-1.16) for the parent GTN. EPI-10 can therefore be considered equivalent to ND-10 also with regard to the rate of bioavailability. Under both patches GTN reached steady-state levels after 3-6 h of patch application and remained on sustained levels during the whole 24-h application. The plasma levels of 1,2-GDN were about 6 times higher than those of GTN. The plasma levels of 1,3-GDN were similar to those of GTN. Upon removal of the patches the concentrations of the three nitrates fell to negligible values within 3 h. Both patches were well tolerated at the application site. For its small size, thinness and transparency, EPI-10 is very patient friendly, a quality that improves compliance with the therapeutic regimen.

Adhesiveness↗

Plasma levels of glyceryl trinitrate and dinitrates during application of three strengths of a new glyceryl trinitrate transdermal patch.

The pharmacokinetic characteristics and the bioavailability of glyceryl trinitrate (GTN, CAS 55-63-0) and of its main metabolities 1,2-glyceryl dinitrate (1,2-GDN, CAS 621-65-8) and 1,3-glyceryl dinitrate (1,3-GDN, CAS 623-87-0) during a single 24-h application of three strengths of a newly developed GTN transdermal patch (Epinitril) were investigated. The three strengths coded in this paper EPI-5, EPI-10 and EPI-15 have a nominal release rate of GTN of 5, 10 and 15 mg, respectively, in 24 h. The study was an open, randomized balanced cross-over study on 18 healthy male volunteers, to whom the patches were applied for 24 h to the antero-lateral part of the thorax in three periods, separated by an at least 3-day wash-out. Blood samples were collected before administration, during the 24-h patch application and 1, 3 and 6 h after patch removal. Assayed in plasma were GTN, 1,2-GDN and 1,3-GDN using validated GC/MS methods with stable isotope labeled internal standards (15N3-GTN, 15N2-1,2-GDN, and 15N2-1,3-GDN). GTN and its two metabolites reached the plateau already 3 h after application of the patches and remained on extended and fairly constant levels during the whole 24-h application. The plasma levels of the three nitrates were proportional to the strengths of the patches. The plasma levels of 1,2-GDN were about 6 times higher than those of GTN. The plasma levels of 1,3-GDN were similar to those of GTN. Upon removal of the patches the concentrations of the three nitrates fell to negligible values within 3 h, an important property when an intermittent GTN therapy is needed in order to avoid tolerance to the drug. The patches were well tolerated at the application site. For their good tolerability, small size and transparency, the new GTN patches are very patient friendly, a quality that improves compliance with the therapeutic regimen.

Adhesiveness↗

Pharmaceutical development and characteristics of a new glyceryl trinitrate transdermal patch

The pharmaceutical development and characteristics of the new glyceryl trinitrate (GTN, CAS 55-63-0) transdermal patch Epinitril, hereinafter called EPI, are described. EPI is a thin (0.096 mm), transparent patch, with GTN uniformly dissolved in a monolayer pressure-sensitive acrylates vinyl acetate copolymer adhesive matrix. The patch provides an intense flux rate of GTN through the skin (33 micrograms/cm2/h). This is the result of the high concentration of GTN in the matrix (39.3% w/w) and of its thinness (0.033 mm), which elicit a high thermodynamic activity of GTN on the surface of the skin, promoting its absorption. EPI was developed in three strengths with release rates of 5, 10 and 15 mg GTN in 24 h, to allow the adaptation of the dose to the needs of the individual patient. During development, different tests were used to evaluate in vitro the release of GTN, i.e. a) the disk assembly dissolution test, b) the artificial membrane-controlled dissolution test and c) the diffusion test through the stratum corneum and epidermis of human skin. None was able to provide a reliable in vitro-in vivo correlation of the performance of the investigated patches. The tests, however, are useful to evaluate the effects of formulation changes during pharmaceutical development. For its small size, thinness, flexibility, transparency, easiness of application and of removal and for its good tolerability, EPI is very patient friendly, a quality that improves the compliance with the long-term therapeutic courses needed in angina pectoris.

Journal Article↗

The impact of haemofiltration on the systemic cardiovascular response.

Convective transport across the dialysis membrane has long been known to be a good alternative to diffusion. Among the advantages of haemofiltration over conventional haemodialysis is a better cardiovascular stability. Haemofiltration has a more physiological response to fluid removal than haemodialysis: (i) blood volume may be better preserved, especially in patients with a compromised cardiac function; (ii) arterial peripheral resistances and venous tone increase; and (iii) myocardial contractility is neither depressed nor altered. We discuss the role of the different pathophysiological mechanisms in the disparity in cardiovascular reactivity between haemofiltration and haemodialysis.

Blood Volume↗