The future of aneurysm surgery.
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California↗
Biomedical subjects
G Guglielmi
Publications and source records attributed to G Guglielmi.
Interaction between Clostridium thermocellum endoglucanase CelD and polypeptides derived from the cellulosome-integrating protein CipA: stoichiometry and cellulolytic activity of the complexes.
Four mini-scaffoldins were constructed from modules derived from the Clostridium thermocellum cellulosome-integrating protein CipA. Cip7 and Cip6 contained one and two cohesin modules respectively. Cip14 and Cip16, also containing one and two cohesin modules respectively, were flanked by a cellulose-binding domain. Endoglucanase CelD formed stable complexes with all mini-scaffoldins. Analytical ultracentrifugation of the complexes showed that 1 mol of CelD bound per mol of Cip14, and 2 mol of CelD bound per mol of Cip16. Under the conditions used for assaying cellulase activity, 96% of CelD alone bound to Avicel. Association with Cip14 or Cip16 increased the cellulose binding of CelD to 99%, while association with Cip7 or Cip6 decreased binding to 79 and 75% respectively. The hydrolytic activity of CelD against Avicel was increased 3-fold in complexes with Cip14 and Cip16, but remained substantially the same in complexes with Cip6 and Cip7. Addition of whole CipA also enhanced the efficiency of Avicel hydrolysis by CelD. However, even at an optimal ratio of the components, CelD-CipA complexes were somewhat less active than complexes of CelD with Cip14 or Cip16. These results suggest that the synergism observed between CelD and Cip14 or Cip16 is mostly due to the presence of the cellulose-binding domain, which promotes productive binding of the enzyme.
Adsorption↗
Quantitative computed tomography at the axial and peripheral skeleton
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Journal Article↗
Ion implantation and protein coating of detachable coils for endovascular treatment of cerebral aneurysms: concepts and preliminary results in swine models.
OBJECTIVE: Complete anatomic obliteration remains difficult to achieve with endovascular treatment of wide-necked aneurysms using Guglielmi detachable platinum coils (GDCs). Ion implantation is a physicochemical surface modification process resulting from the impingement of a high-energy ion beam. Ion implantation and protein coating were used to alter the surface properties (thrombogenicity, endothelial cellular migration, and adhesion) of GDCs. These modified coils were compared with standard GDCs in the treatment of experimental swine aneurysms. METHODS: In an initial study, straight platinum coils were used to compare the acute thrombogenicity of standard and modified coils. Modified coils were coated with albumin, fibronectin, or collagen and underwent Ne+ ion implantation at a dose of 1 x 10(15) ions/cm2 and an energy of 150 keV. Coils were placed in common iliac arteries of 17 swine for 1 hour, to evaluate their acute interactions with circulating blood. In a second study, GDCs were used to treat 34 aneurysms in an additional 17 swine. GDCs were coated with fibronectin, albumin, collagen, laminin, fibrinogen, or vitronectin and then implanted with ions as described above. Bilateral experimental swine aneurysms were embolized with standard GDCs on one side and with ion-implanted, protein-coated GDCs on the other side. The necks of aneurysms were evaluated macroscopically at autopsy, by using post-treatment Day 14 specimens. The dimensions of the orifice and the white fibrous membrane that covered the orifice were measured as the fibrous membrane to orifice proportion. Histopathological evaluation of the neck region was performed by light microscopy and scanning electron microscopy. RESULTS: Fibronectin-coated, ion-implanted coils showed the greatest acute thrombogenicity (average thrombus weight for standard coils, 1.9 +/- 1.5 mg; weight for fibronectin-coated coils, 8.6 +/- 6.2 mg; P < 0.0001). By using scanning electron microscopy, an intensive blood cellular response was observed on ion-implanted coil surfaces, whereas this was rare with standard coils. At Day 14, greater fibrous coverage of the necks of aneurysms was observed in the ion-implanted coil group (mean fibrous membrane to orifice proportion of 69.8 +/- 6.2% for the ion-implanted coil group, compared with 46.8 +/- 15.9% for the standard coil group; P = 0.0143). CONCLUSION: The results of this preliminary experimental study indicate that ion implantation combined with protein coating of GDCs improved cellular adhesion and proliferation. Future application of this technology may provide early wound healing at the necks of embolized, wide-necked, cerebral aneurysms.
Animals↗
A pitfall in the surgery of a recurrent aneurysm after coil embolization and its histological observation: technical case report.
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Cerebral Angiography↗
Skeletal involvement in female acromegalic subjects: the effects of growth hormone excess in amenorrheal and menstruating patients.
Bone involvement is a common clinical feature in acromegalic patients, though previous studies gave divergent results possibly because of the different gonadal status of the patients studied. To study the influence of estrogen milieu in these patients, we evaluated 23 acromegalic patients with active disease, subdivided into two groups: menstruating and amenorrheal patients, comparable for duration and activity of disease. Forty-two matched women served as controls. Skeletal involvement was studied by measuring: (a) the main biomarkers of bone turnover: serum alkaline phosphatase total activity (AP), bone GLA protein (BGP), serum carboxy-terminal propeptide of type I collagen (PICP), serum type I cross-linked N-telopeptide (ICTP), and urinary pyridinoline and deoxypyridinoline corrected for creatinine (Pyr/Cr, D-Pyr/Cr) and urinary calcium/creatinine ratio (Ca/Cr); (b) bone mineral density (BMD), as measured by quantitative computed tomography both at lumbar spine and distal radius, and by dual X-ray absorptiometry both at lumbar spine and at three femoral sites (Ward's triangle, femoral neck, and great trochanter). AP, BGP, ICTP, Pyr/Cr, D-Pyr/Cr were significantly higher in patients than in controls, independent of the menstrual pattern. Higher PICP levels were found in the whole group and in menstruating acromegalics when compared with control women; no difference was found in amenorrheal patients, who in turn showed higher urinary Ca/Cr values. When patients were considered all together, BMD at spine, femoral neck, and trochanter was higher than in controls. In contrast, when the gonadal status was taking into account and, menstruating and amenorrheal subjects were considered separately, BMD at spine, but not in other sites, was significantly higher in menstruating patients than in controls. In contrast, no difference of BMD values at any site was observed between amenorrheal patients and controls. The mean BMD Z scores allowed us to detect an unequal involvement of different skeletal sites. Our results show that bone turnover is increased in acromegalic women and suggest that GH anabolic effect on bone is more evident in the presence of estrogens and that different skeletal sites may be affected differently by hormone excess.
Acromegaly↗
Intracranial aneurysms treated with the Guglielmi detachable coil: midterm clinical results in a consecutive series of 100 patients.
A prospective study was designed to evaluate clinical outcome in a series of 100 consecutively treated patients who underwent endovascular embolization of 104 intracranial aneurysms using Guglielmi detachable coils (GDCs). Midterm clinical outcome (2-6 years, average 3.5 years) was obtained for 94 patients and was classified according to a modified Glasgow Outcome Scale. Of nine patients treated in the acute phase of severe subarachnoid hemorrhage (Grade IV or V), seven died from the initial hemorrhage, one had a poor outcome, and one had a fair midterm outcome, with no post-GDC embolization hemorrhages. Twenty patients underwent subsequent surgical or endovascular procedures that did not include the use of GDCs. These included aneurysm clipping in nine patients and parent vessel sacrifice in 11 patients. None of these 20 patients experienced post-GDC embolization hemorrhage. The postoperative midterm clinical outcomes of these 20 patients did not significantly differ from the outcomes of patients who underwent GDC embolization as their definitive treatment. Six patients died of unrelated causes prior to reaching the 2-year survival point, with no post-GDC embolization hemorrhage. The midterm outcomes of the remaining 61 patients who underwent GDC embolization as their definitive treatment were classified as excellent (46 patients [75%]), good (seven patients [11%]), fair (three patients [5%]), poor (one patient [2%]), or dead (four patients [7%]). All four patients died from giant lesions. At midterm follow up, the surviving 57 patients' neurological statuses were unchanged or improved in 54 cases and worsened in three cases. The midterm post-GDC embolization hemorrhage rate was 0% for small aneurysms, 4% (one case) for large aneurysms, and 33% (five cases) for giant lesions. The GDC procedure is a safe, effective, and reliable means of preventing aneurysm hemorrhage in patients with small and large intracranial aneurysms. Results, however, are less satisfactory in cases involving giant lesions. Further follow-up review is necessary to establish durability in the longer term. Patients with Grade IV or V subarachnoid hemorrhage in this series generally had poor outcomes even if the GDC procedure was successful in occluding the aneurysm.
Adult↗
Incidence of cerebral vasospasm after endovascular treatment of acutely ruptured aneurysms: report on 69 cases.
Cerebral vasospasm is the most common cause of morbidity and mortality in patients admitted to the hospital after suffering aneurysmal subarachnoid hemorrhage (SAH). The early surgical removal of subarachnoid clots and irrigation of the basal cisterns have been reported to reduce the incidence of vasospasm. In contrast to surgery, the endovascular treatment of aneurysms does not allow removal of subarachnoid clots. In this study the authors measured the incidence of symptomatic vasospasm after early endovascular treatment of acutely ruptured aneurysms with Guglielmi detachable coils (GDCs). Sixty-nine patients classified as Hunt and Hess Grades I to III underwent occlusion of intracranial aneurysms via GDCs within 72 hours of rupture. The amount of blood on the initial computerized tomography (CT) scan was classified by means of Fisher's scale. Symptomatic vasospasm was defined as the onset of neurological deterioration verified with angiographic or transcranial Doppler studies. Hypertensive, hypervolemic, hemodilution therapy, with or without intracranial angioplasty, was used to treat vasospasm after GDC placement. Symptomatic vasospasm occurred in 16 (23%) of 69 patients. The clinical grade at admission and the amount of blood on the initial CT were both associated with the incidence of subsequent vasospasm. At 6-month clinical follow-up examination, 12 of these 16 patients experienced a good recovery, two were moderately disabled, and two patients had died of vasospasm. In conclusion, the 23% incidence of symptomatic vasospasm in this series compares favorably with that found in conventional surgical series of patients with acute aneurysmal SAH. These results indicate that endovascular therapy does not have an unfavorable impact on cerebral vasospasm.
Acute Disease↗
Quantitative computed tomography at the axial and peripheral skeleton.
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Animals↗
A simple method to reveal possible ras mutations in DNA of urinary sediment cells.
Occupational and environmental exposure to carcinogens is reported to be responsible for 25% of all bladder tumors. Among many genetic alterations found in tumor bladder cells, chromosome aberrations and mutations of some oncogenes, such as ras genes, are common. Studies conducted to determine the rate and type of ras mutations involved reported rather contrasting results. Researchers agree that among the three members of the ras family, only H-ras is subject to mutations, mostly at codon 12. The rate of these mutations is still under investigation, although it has been evaluated as being between 6 and 76%. Using various techniques, some studies have shown that when a ras mutation occurs in a bladder tumor, it is also present in urinary sediment cells of the same patient. We suggest a simple method to directly detect ras mutations at codon 12 in urinary sediment.
Carcinogens↗
Endovascular electrocoagulation: concept, technique, and experimental results.
PURPOSE: To evaluate the safety and efficacy of an embolotherapeutic technique that uses electrolytically detachable platinum coils and radio frequency (RF) energy to achieve rapid and distal occlusion of targeted vessels. METHODS: In swine, branches of the ascending cervical artery and the hepatic artery measuring 1.5 mm or less were subjected to endovascular electrocoagulation. RF energy was delivered through modified Guglielmi detachable platinum coils that were placed in the targeted arteries. Ohmic heating generated by RF caused vessel occlusion. After the vessel occlusions were confirmed angiographically, the platinum microcoils were electrolytically detached from the delivery wire and left in the vessels as implants. RESULTS: All vessels were rapidly and superselectively occluded by endovascular electrocoagulation. Following use of the appropriate methods derived from this research, we did not observe rupture of the artery, dissection of the artery, unintended occlusion, or migration of the platinum microcoil. Histologic examination of treated vessels at 6 and 12 weeks revealed obliteration of the vessel lumen by the platinum microcoil surrounded by granulation tissue. CONCLUSION: Endovascular electrocoagulation is a rapid method of achieving vessel occlusion. It may be a useful and controllable embolotherapeutic technique when expeditious occlusion of small vessels and distal superselectivity are desired.
Animals↗
[An experimental study of the treatment of aneurysms using an intravascular prosthesis].
Intracranial aneurysms occur frequently with the risk of major damage. Neurosurgery or endovascular techniques can be used for treatment. Current techniques are not well adapted for aneurysms with a wide implantation (or neck). The aim of this experimental work was to study a technique for treating aneurysms which can be used for wide neck aneurysms. A metal stent is implanted facing the neck of the aneurysm to allow occlusion. In the first part of the study, the stent was inserted alone. Ten aneurysms were created surgically in five dogs. The stents were positioned facing seven of the ten aneurysms. The stent led to immediate occlusion of the aneurysm in six of the cases. One aneurysm remained patent despite the correct position of the stent. One dog developed secondary thrombosis of the carotid. Three dogs have been followed for sixty days after insertion of the stent. Two aneurysms thrombosed and one was patent. Since these results were less than satisfactory, a second part of the study was undertaken to cover the stent with a fragment of the autologous vein. Results in five aneurysms, evaluated three and eight weeks after treatment, showed partial or total repermeabilization of the aneurysms. In the third part of the study, we associated stents and detachable coils. Twelve aneurysms of the carotid artery in pigs were thrombosed and two aneurysms were completely occluded after stent implantation. In the nine other cases, the aneurysms were completely occluded after stent implantation. In the nine other cases, the aneurysms remained patent despite the stent and treatment was then completed with a coil. Six of the animals have been followed for thirteen weeks. One carotid artery thrombosed. In the five other cases, the carotid arteries were patent and the aneurysms were occluded at the control angiogram. Histology results showed the presence of a fibromuscular endothelialized neointima at the neck of the aneurysm in four of the five cases. The technique described here could be proposed for the treatment of wide-neck aneurysms implanted low on the carotid artery in man. Improvements should render the system more flexible.
Aneurysm↗
Long-term in vitro precision of single slice peripheral Quantitative Computed Tomography (pQCT): multicenter comparison.
In a multicenter evaluation the precision and stability of single slice peripheral Quantitative Computed Tomography (pQCT) systems were assessed. Compared to central Europe the peripheral QCT device is also widely used in the Italian health care system. Phantoms were measured frequently on each machine in four pQCT scanners over a two-year period using an identical automated software program. Intrasite and intersite phantom mineral densities, expressed in units of mg/cm3, were analyzed and examined. The short and long term precision were estimated from the consistency of these measurements using the root mean square error and expressed as coefficient of variation in percent (% CV). Short term precision was good (mean intrasite coefficient of variation (CV) 0.21 +/- 0.056 standard deviation (SD)). Intersite measurements of a single phantom revealed differences between machines of the same type of not more than 2.9 mg/cm3. At four sites frequent phantom measurements revealed a mean CV of 0.18% (range 0.12-0.28). No significant changes in the regression slopes (drift of the machine versus time) were observed. We conclude that the in vitro precision and stability of the single slice pQCT systems are sufficiently high and unlikely to negatively affect the in vivo precision.
Absorptiometry, Photon↗
Magnetic resonance imaging of the calcaneus: preliminary assessment of trabecular bone-dependent regional variations in marrow relaxation time compared with dual X-ray absorptiometry.
RATIONALE AND OBJECTIVES: Marrow transverse relaxation time (T2*) in magnetic resonance (MR) imaging may be related to the density and structure of the surrounding trabecular network. We investigated regional variations of T2* in the human calcaneus and compared the findings with bone mineral density (BMD), as measured by dual X-ray absorpiometry (DXA). Short- and long-term precisions were evaluated first to determine whether MR imaging would be useful for the clinical assessment of disease status and progression in osteoporosis. METHODS: Gradient-recalled echo MR images of the calcaneus were acquired at 1.5 T from six volunteers. Measurements of T2* were compared with BMD and (for one volunteer) conventional radiography. RESULTS: T2* values showed significant regional variation; they typically were shortest in the superior region of the calcaneus. There was a linear correlation between MR and DXA measurements (r = .66 for 1/T2* versus BMD). Differences in T2* attributable to variations in analysis region-of-interest placement were not significant for five of the six volunteers. Sagittal MR images had short- and long-term precision errors of 4.2% and 3.3%, respectively. For DXA, the precision was 1.3% (coefficient of variation). CONCLUSION: MR imaging may be useful for trabecular bone assessment in the calcaneus. However, given the large regional variations in bone density and structure, the choice of an ROI is likely to play a major role in the accuracy, precision, and overall clinical efficacy of T2* measurements.
Absorptiometry, Photon↗
Endovascular embolization of superior hypophyseal artery aneurysms.
OBJECTIVE: Internal carotid artery aneurysms arising from the superior hypophyseal artery are frequently termed paraophthalmic or paraclinoid aneurysms, but they constitute a distinct anatomic entity. They are particularly amenable to endovascular treatment. METHODS: Between 1991 and 1995, we attempted treatment in 11 patients with superior hypophyseal artery aneurysms with Guglielmi detachable coil embolization and were successful in 10. Surgical exploration in seven of the patients was unsuccessful, three patients were considered to be at high risk for surgery or to have poor likelihood of surgical success by the referring neurosurgeon, and one patient refused operative clipping. Two aneurysms were giant (> 25 mm), three were large (10-25 mm), and six were small (< 10 mm). Of the six small aneurysms, two had wide necks (> 4 mm) and four had narrow necks (< or = 4 mm). RESULTS: There were no technical or clinical complications related to embolization. Immediate complete aneurysm obliteration was obtained in five aneurysms, all of which were small. Four of the remaining five aneurysms had obliteration of the dome and body, leaving only a small remnant neck. The remaining semifusiform aneurysm represented our single treatment failure. Recanalization occurred in only one patient; that patient had a giant aneurysm. Nine of the 10 patients for whom embolization was successful had good or excellent clinical outcomes; there were no clinical deteriorations attributable to embolization. CONCLUSION: We conclude that Guglielmi detachable coil embolization of superior hypophyseal artery aneurysms is an excellent treatment alternative, especially for smaller lesions.
Adult↗
Physical mapping of Mycobacterium bovis BCG pasteur reveals differences from the genome map of Mycobacterium tuberculosis H37Rv and from M. bovis.
A Dral restriction map of the approximately 4.35 Mb circular chromosome of the vaccine strain Mycobacterium bovis BCG Pasteur was constructed by linking all 21 Dral fragments, ranging in size from 6 to 820 kb, using specific clones that spanned the Dral recognition sites as hybridization probes. The positions of 20 known genes were also established. Comparison of the resultant genome map with that of the virulent tubercle bacillus Mycobacterium tuberculosis H37Rv revealed extensive global conservation of the genomes of these two members of the M. tuberculosis complex. Possible sites of evolutionary rearrangements were localized on the chromosome of M. bovis BCG Pasteur by comparing the Asnl restriction profile with that of M. tuberculosis H37Rv. When selected cosmids from the corresponding areas of the genome of M. tuberculosis H37Rv were used as hybridization probes to examine different BCG strains, wild-type M. bovis and M. tuberculosis H37Rv, a number of deletions up to 10 kb in size, insertions and other polymorphisms were detected. In addition to the known deletions covering the genes for the protein antigens ESAT-6 and mpt64, other genetic loci exhibiting polymorphisms or rearrangements were detected in M. bovis BCG Pasteur.
BCG Vaccine↗
Treatment of large and giant fusiform intracranial aneurysms with Guglielmi detachable coils.
Results in nine patients with large or giant fusiform intracranial aneurysms that were treated with Guglielmi detachable coils (GDCs) are reported. There were six males and three females between the ages of 12 and 63. Four patients presented with subarachnoid hemorrhage (SAH) and four with mass effect; in one patient the aneurysm was asymptomatic and located in an arterial feeder of an arteriovenous malformation. Five aneurysms were supratentorial and four were in the posterior fossa. Five were giant and four were large. Selective occlusion with preservation of the parent artery was attempted in three cases, and complete occlusion of the aneurysm and the parent artery was performed in six patients. The tolerance to parent artery occlusion was assessed by angiography, balloon test occlusion, and amytal testing. Six aneurysms were permanently occluded and two partially recanalized. In one case, GDC embolization was not possible. The four patients who presented with SAH made an excellent clinical recovery. Three of the four patients presenting with mass effect recovered completely and one remained unchanged. The patient with an incidental aneurysm remained asymptomatic. There were no permanent complications. In conclusion, GDCs were useful for the occlusion of large and giant intradural fusiform aneurysms. Occlusion of the aneurysm and the parent artery afforded the greatest opportunity for a complete cure. Advantages of GDCs compared to balloons include: occlusion of a shorter segment of normal artery, no traction on the parent vessel, and safer and easier catheterization techniques.
Adult↗
Endovascular treatment of multiple aneurysms involving the posterior intracranial circulation.
The results of surgery on multiple intracranial aneurysms tha involve the vertebrobasilar circulation are poor, and associated patient mortality remains high. We describe the endovascular treatment of four patients with mutiple aneurysms that involved the posterior intracrancial circulation. Satisfactory occlusion of all aneurysms was achieved by using electrolytically detachable coils, and all patients had a good clinical recovery. Our early experience suggests that endovascular coil occlusion may be a particularly suitable method for treating this high-risk condition.
Adult↗