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Biomedical subjects

A Gruber

Publications and source records attributed to A Gruber.

At least 109 records · Page 6Linked to original sources
PubMed1998

Endovascular therapy of idiopathic cavernous aneurysms over 11 years.

PURPOSE: We report our experience with 42 patients with 48 cavernous carotid aneurysms, of whom 32 were treated with endovascular techniques and 10 were managed conservatively. METHODS: The 48 aneurysms were divided into two subgroups by location: 23 were at the C-3 portion of the carotid artery (small, saccular aneurysms with an epidural, partly intracavernous location) and 25 originated at the C4-5 segment (large or giant often fusiform aneurysms with a true intracavernous location). Morphologic features in both groups correlated well with differences in clinical presentation and also influenced therapy. Sixteen of the 25 C4-5 aneurysms (all large or giant) were treated by balloon occlusion of the parent artery, four (with narrow necks) were treated with Guglielmi detachable coils (GDCs), and five were not treated (asymptomatic or minimally symptomatic). Twelve of 13 C-3 aneurysms were treated with GDCs. Ten C-3 aneurysms were not treated. RESULTS: Ophthalmoplegia resolved or improved in nine of 12 patients treated with parent artery occlusion. All aneurysms treated by carotid occlusion thrombosed. Twelve of the 17 aneurysms treated with GDCs were 100% filled by the coils, four were 80% to 95% filled, and one was only 40% filled. Seven of the 100% filled aneurysms remained completely occluded, two showed slight coil compaction, and in three, follow-up angiography was not available. Among the incompletely filled aneurysms, two remained unchanged, one showed progressive thrombosis, a fourth revealed coil compaction, and in one, follow-up angiography was not available. One thromboembolic stroke and three transient ischemic attacks occurred perioperatively, for a permanent morbidity of 3.5% and a transient morbidity of 9%. There was no mortality. Mean clinical follow-up was 33 months; mean angiographic follow-up of patients treated with GDCs was 11 months. CONCLUSION: Surgically difficult cavernous aneurysms can be obliterated by embolization with excellent clinical results. Detachable coils have become an important endovascular tool, especially for narrow-necked cavernous aneurysms of the C-3 segment, which can be protected against rupture in the subarachnoid space in most cases.

Adult↗
PubMed1997

Anticoagulant synergism of heparin and activated protein C in vitro. Role of a novel anticoagulant mechanism of heparin, enhancement of inactivation of factor V by activated protein C.

Interactions between standard heparin and the physiological anticoagulant plasma protein, activated protein C (APC) were studied. The ability of heparin to prolong the activated partial thromboplastin time and the factor Xa- one-stage clotting time of normal plasma was markedly enhanced by addition of purified APC to the assays. Experiments using purified clotting factors showed that heparin enhanced by fourfold the phospholipid-dependent inactivation of factor V by APC. In contrast to factor V, there was no effect of heparin on inactivation of thrombin-activated factor Va by APC. Based on SDS-PAGE analysis, heparin enhanced the rate of proteolysis of factor V but not factor Va by APC. Coagulation assays using immunodepleted plasmas showed that the enhancement of heparin action by APC was independent of antithrombin III, heparin cofactor II, and protein S. Experiments using purified proteins showed that heparin did not inhibit factor V activation by thrombin. In summary, heparin and APC showed significant anticoagulant synergy in plasma due to three mechanisms that simultaneously decreased thrombin generation by the prothrombinase complex. These mechanisms include: first, heparin enhancement of antithrombin III-dependent inhibition of factor V activation by thrombin; second, the inactivation of membrane-bound FVa by APC; and third, the proteolytic inactivation of membrane-bound factor V by APC, which is enhanced by heparin.

Animals↗
PubMed1997

Activated protein C correlates inversely with thrombin levels in resting healthy individuals.

To study whether the circulating anticoagulant, activated protein C (APC), could be a regulator of thrombin activity in basal physiological conditions, fibrinopeptide A and activated protein C levels were determined in samples from 40 healthy individuals. There was a significant inverse correlation between the fibrinopeptide A and APC levels (Spearman rank correlation R = -0.487; P = 0.0023). Because of well-known mechanisms by which decreasing APC levels could cause increased thrombin formation, we suggest that APC may downregulate thrombin activity in subjects with normal protein C levels. Regulation of thrombin formation in health is likely significant for maintaining vascular patency but its molecular mechanisms are poorly understood. The current data suggest that a single physiological anticoagulant, namely APC, may be a significant regulator of procoagulant thrombin activity.

Adult↗
PubMed1997

False aneurysms of the intracavernous carotid artery--report of 7 cases.

We present 7 cases of false intracavernous carotid artery aneurysms. Four occurred after trauma and three were caused iatrogenically. Two of the latter occurred in patients with pituitary adenomas, one after transsphenoidal microsurgery and the other after yttrium [YI90] seed implantation into the sella. The third iatrogenic aneurysm was seen shortly after transcavernous tumour surgery. In five of our seven patients massive, delayed, life-threatening epistaxis was the leading symptom. All traumatic cases were associated with immediate unilateral blindness or blurred vision and with skull base fractures. One of these had a concomitant carotid cavernous fistula. Treatment of choice of our 5 recent cases was permanent balloon occlusion of the intracavernous carotid artery at the level of the lesion. Collateral circulation was evaluated prior to definitive carotid occlusion using a balloon test occlusion. During the balloon test adequate collateral circulation was defined as symmetric angiographic filling of both hemispheres. Awake patients were neurologically examined continuously. In unconscious patients transcranial Doppler sonography, electroencephalographic and somatosensory evoked potential monitoring was used in addition. Intra-operative heparin administration was not reversed with protamin. A postoperative continuous heparin infusion was not found necessary. In our two early cases this technique was not available: In the first case we accomplished aneurysm occlusion by a surgically introduced Fogarty balloon catheter. Our second patient needed surgical trapping of the involved carotid after early unsuccessful attempts of selective aneurysm occlusion. After treatment no further epistaxis occurred. Follow-up angiography showed persistent aneurysm occlusion. The results were excellent in 5 cases and good in 1 case. One patient with bilateral lesions suffered a stroke after occlusion of the second, remaining carotid artery, despite functioning bilateral extra-intracranial bypasses. Four years later there is a mild dysphasia still present in this patient. The mean follow-up time was 75.6 months.

Adult↗
PubMed1997

Treatment of post-traumatic carotico-cavernous fistulae using electrolytically detachable coils: technical aspects and preliminary experience.

We treated six patients with post-traumatic cavernous carotid fistulae by electrothrombosis using Guglielmi's new electrolytically detachable coils. The transarterial endovascular route was chosen in five and the transvenous in one case. Exophthalmos, chemosis and/or an audible bruit disappeared immediately after therapy or in the following month in all patients suffering from these symptoms. Third and sixth cranial nerve palsies resolved in three of four patients. Clinical results were excellent in three, good in two and fair in one. In this last patient massive thrombosis of an enormously dilatated superior ophthalmic vein occurred after treatment of a giant longstanding fistula, leading to unilateral visual impairment and increased sixth nerve palsy. In our first patient the intracavernous carotid artery was occluded by balloons after coil embolisation because of improper coil position and the fear of possible thromboembolic events. Angiographic cure was demonstrated in all cases by angiograms 1-6 months after therapy. The characteristics of these new coils are easy use, manoeuvreability and retrievability. They conform ideally to the shape of the vessel lumen to be obliterated and produce practically no trauma to the vessel walls. Furthermore, they can be positioned in the sinus close to the orifice of the fistula. In the last two cases partial occlusion of the fistula was sufficient to initiate the process of complete thrombosis, and delayed, complete occlusion was observed after 1 month. In our opinion this new device is not only a major contribution to treatment of intracranial aneurysms, but may also improve the results of treatment of carotico-cavernous fistulae.

Adult↗
PubMed1997

Increased plasma concentrations of LDL-unbound apo(a) in patients with end-stage renal disease.

Lipoprotein(a) [Lp(a)] and its characteristic glycoprotein apolipoprotein(a) [apo(a)] are risk factors for atherosclerosis in the general population. Patients with renal disease show an elevation of Lp(a). Recent studies have described an arteriovenous difference of Lp(a) in the renovascular bed as well as the plasma-derived fragmented LDL-unbound apo(a) in urine, suggesting that the kidney is involved in the metabolism of Lp(a). We therefore investigated whether patients with chronic renal failure have higher levels of LDL-unbound apo(a) and whether this could account for the increased Lp(a) concentrations in these patients. In addition, we studied the possible generation of apo(a) fragments in vitro by mimicking uremic plasma conditions and by investigating the assembly of Lp(a) in cell culture experiments. Patients treated by hemodialysis (N = 185) and by continuous ambulatory peritoneal dialysis (CAPD; N = 20) had markedly elevated absolute (1.22 +/- 1.55 mg/dl and 2.14 +/- 2.86 mg/dl) as well as relative (7.5% and 7.3%) amounts of LDL-unbound apo(a) in comparison to controls (0.46 +/- 0.48 mg/dl or 4.5%). Following renal transplantation the absolute amount decreased significantly. Lp(a) plasma concentration was the most important determining variable for the absolute amount of LDL-unbound apo(a) and showed a positive correlation in both hemodialysis patients (r = 0.85) and controls (r = 0.92). In vitro experiments demonstrated that "uremization" of plasma samples did not generate a higher amount of LDL-unbound apo(a). Although LDL of renal patients has different chemical and structural properties as compared to control LDL, the extracellular assembly of Lp(a) did not differ between patients and controls. Therefore, the higher amounts of LDL-unbound apo(a) found in renal disease are not caused by an impaired assembly of Lp(a), but rather indicate a catabolic role of the kidney for LDL-unbound apo(a) as was already shown for Lp(a). Despite a small contribution, these elevated levels cannot explain the higher Lp(a) values found in patients with end-stage renal disease.

Adult↗
PubMed1997

Isolated persistent fetal bradycardia in complete A-V block: a conservative approach is appropriate. A case report and a review of the literature.

Persistent fetal bradycardia is rarely encountered during pregnancy. When it is associated with a complete atrio-ventricular (A-V) block, it may prove dangerous to the fetus or newborn. The prenatal diagnosis is vital because it necessitates close follow-up during pregnancy to detect fetal compromise and proper preparation for delivery. We describe a woman who was found to be suffering from systemic lupus erythematosus during pregnancy. The fetus was diagnosed as having persistent fetal bradycardia due to complete A-V block at 28 weeks of gestation and was delivered at term with conservative management. The problems entailed in managing pregnancy and delivery of such fetuses are discussed.

Adult↗
PubMed1997

In vitro training model for endovascular embolization of cerebral aneurysms.

We present a new in vitro model for the training of endovascular embolizations of cerebral aneurysms. The technique and laboratory set-up described allow the embolization of thin-walled, transparent silicone aneurysm models under "semi-physiologic" conditions, i.e., in a closed circulation with pulsatile flow and pressure, simulating the hemodynamic conditions encountered in biologic systems.

Embolization, Therapeutic↗
PubMed1997

Recurrent aneurysmal subarachnoid haemorrhage: bleeding pattern and incidence of posthaemorrhagic ischaemic infarction.

This report is based on a consecutive series of 162 patients with aneurysmal subarachnoid haemorrhage (SAH), including 22 patients (14%) with recurrent SAH, who were treated within 72 h after the most recent bleed. Of the 22 patients with recurrent haemorrhage: 68% were in poor clinical condition (Hunt & Hess grade 4-5); 73% presented with intracerebral haemorrhage (ICH); 41% developed delayed ischaemic infarctions from chronic arterial spasm; 14% made a good recovery, while 41% died. Of the 140 patients with a single bleed: 34% were in poor clinical condition (Hunt & Hess grade 4-5); 33% presented with ICH; 22% developed delayed ischaemic infarctions; 53% made a good recovery, while 19% died. Our results suggest that a high incidence of intracerebral haemorrhage in conjunction with a more severe course of chronic arterial spasm substantially contributes to the high morbidity and mortality associated with recurrent SAH. In poor grade patients not suitable for acute open surgery, endovascular treatment should receive consideration for the prevention of early rebleeding.

Adolescent↗
PubMed1997

The long term effects of traumatic brain injury on the roles of caregivers.

This study was conducted to identify the long term effects of traumatic brain injury (TBI) on the roles of caregivers. The subjects consisted of 155 caregivers of survivors with TBI who were randomly selected from 15 midwestern state brain injury association databases. A questionnaire was developed by the researchers to determine factors affecting role changes of caregivers. The Role Checklist, by Barris, Oakley and Kielhofner, was also included with the questionnaire. Both were mailed to each selected caregiver and used for data gathering. The data obtained were analysed to determine existing trends in the data. Graphs were utilized to depict the trends that was identified. The following trends and conclusions established by this research include: (a) behavioural effects of the survivor with a TBI are associated with the number of role changes experienced by caregivers; (b) participation in support systems is associated with the number of role changes experienced by caregivers; and (c) caregivers who care for a person with a TBI in the home will show a larger number of role changes than those who do not provide direct care for a person with a TBI.

Adult↗
PubMed1997

Human immunodeficiency virus type 1 gp41 binds to Candida albicans via complement C3-like regions.

Oral candidiasis in human immunodeficiency virus type 1 (HIV-1)-infected persons is believed to be caused by the acquired T lymphocyte immunodeficiency. The direct interaction of C. albicans and HIV-1 in vitro was investigated. Twice as many yeasts adhered to cells transfected with the HIV-1 env gene as they did to controls. HIV-1 rsgp160 and rsgp41 but not rsgp120 were found to bind to Candida albicans via two C3-like regions within gp41. Normal human serum, but not C3-depleted serum, was able to inhibit rsgp41 binding to C. albicans. Vice versa, rsgp160 and rsgp41 were able to block rosetting of C. albicans with iC3b-coated sheep erythrocytes. Binding to C. albicans, and its inhibition by rsgp41 or rsgp160, was confirmed for the whole virus. Therefore, oral candidiasis in HIV-1-infected subjects may be augmented or may even be initiated by direct interaction between C. albicans and HIV-1 or HIV-1-infected cells.

Amino Acid Sequence↗
PubMed1997

Decreased feedback regulation of low density lipoprotein receptor activity by sterols in leukemic cells from patients with acute myelogenous leukemia.

Leukemic cells from patients with acute myelogenous leukemia (AML) have higher low density lipoprotein (LDL) receptor activity than normal white blood and bone marrow cells. The underlying mechanism behind this is unclear. We studied the inhibitory effect of sterols on induction of LDL-receptor activity in leukemic cells from 27 patients with AML and in white blood cells from 13 healthy individuals. The high affinity degradation rate of 125I-labeled LDL was determined in mononuclear blood cells directly after isolation from blood and after incubation for 2 days in medium with 10% lipoprotein-deficient serum with or without various concentrations of 25-hydroxycholesterol + cholesterol. The median sterol concentration for 50% inhibition (IC50) of induction was more than five times higher for leukemic cells than for normal mononuclear cells. At the highest sterol concentration (0.400 microg/mL 25-hydroxycholesterol + 8 microg/mL cholesterol), the LDL-receptor activity was abolished in cells from all healthy individuals while the induction of LDL-receptor activity in cells from three AML patients was unaffected. The LDL-receptor activity of leukemic cells, directly after isolation from blood, correlated with IC50 values (r = 0.53, P = 0.007) and WBC counts (r = 0.72, P = 0.0001) but not with cellular cholesterol levels. The results demonstrate decreased feedback regulation of LDL-receptor activity by sterols in AML cells and support the conclusion that elevated LDL-receptor activity is associated with sterol resistance and cell proliferation. The findings are of potential interest for diagnosis and specific treatment of leukemia.

Adult↗
PubMed1996

HIV type 1 glycoprotein 120 amplifies tumor necrosis factor-induced NF-kappa B activation in Jurkat cells.

This article demonstrates that human immunodeficiency virus type 1 (HIV-1) gp120 amplifies the activity of tumor necrosis factor alpha (TNF-alpha), a cytokine that stimulates HIV-1 replication through activation of NF-kappa B. In CD4-positive Jurkat cells, gp120 potentiates TNF-induced NF-kappa B activation. TNF-mediated activation of NF-kappa B is known to involve the intracellular formation of reactive oxygen intermediates (ROIs). Accordingly, we examined the influence of gp120 on the cellular redox state. We found that gp 120-modulated TNF-induced NK-kappa B activation was inhibited by the antioxidant butylated hydroxyanisole, indicating the involvement of redox-dependent mechanisms. In addition, we showed that gp120 induces intracellular formation of hydrogen peroxide, which is accompanied by a decrease in the ratio of glutathione to glutathione disulfide. In contrast, in the p56lck-deficient J.CaM1.6 T cell line, a derivative of the Jurkat cell line, gp120 was unable to stimulate hydrogen peroxide, to decrease the ratio of GSH to GSSG, and has no effect on TNF-induced NF-kappa B activation. This demonstrated that p56lck protein tyrosine kinase plays an active role in transmitting a signal that increases the oxidative state of the cell and as a consequence amplifies TNF-mediated NF-kappa B DNA binding. We have demonstrated that Tat protein decreased both the Mn-dependent superoxide dismutase (MnSOD) and the cellular glutathione content (GSH). Here we show that, in contrast to Tat, gp120 is unable to inhibit activity and expression of MnSOD and to decrease GSH content. Taken together, our data suggest that gp120 potentiates TNF-induced NF-kappa B activation by stimulating a signal pathway that involves p56lck and the increased formation of reactive oxygen intermediates such as H2O2. These findings may be relevant for the regulation of HIV-1 replication in T cells.

Antioxidants↗
PubMed1996

Higher in vivo protein binding of etoposide in children compared with adult cancer patients.

Etoposide is bound to plasma albumin (94%). Previous studies have revealed altered protein binding of etoposide in cancer patients. This has clinical implications since only the free fraction is considered pharmacologically active. We have studied the etoposide protein binding in 11 children (eight acute lymphocytic leukemia, two malignant histiocytosis, and one oligodendroglioma; age 1-17 years) and 46 adult patients (28 acute myelocytic leukemia, eight lymphoma, one multiple myeloma, and nine small cell lung cancer; age 38-81 years). All patients were treated with etoposide 50-200 mg/m2 i.v. or orally. Plasma from ten healthy volunteers, 26-50 years of age, was spiked with etoposide, 10 micrograms/ml, and the protein binding was compared with that in patient samples. The free etoposide concentration was determined by high performance liquid chromatography (HPLC) after ultrafiltration at room temperature. The free etoposide fraction was lower, 2.5 +/- 0.6% (mean +/- SD), in the children compared with 5.0 +/- 3.6% in adult cancer patients. In plasma from healthy adults it was 3.2 +/- 0.3%. It is concluded that children have significantly lower levels of free etoposide compared with adult patients (P = 0.03) as well as with healthy subjects (P = 0.001), which is likely to affect metabolism and renal clearance as well as cellular uptake of the drug.

Adolescent↗
PubMed1996

Expression of the low-density lipoprotein receptor, HMG-CoA reductase, and multidrug resistance (Mdr1) genes in colorectal carcinomas.

Some malignant cells have elevated uptake of plasma low-density lipoprotein (LDL). We determined the expressions in colorectal cancers of the LDL receptor gene, of the gene for the rate-limiting enzyme in cholesterol synthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and of the multidrug resistance gene (mdr1) by quantitative RNA-RNA solution hybridisation. LDL receptor RNA levels in tumor tissue exceeded those in normal mucosa in 20 of 23 patients (2-11-fold higher in 17 of 23 patients), with a mean +/- SD of 7.8 +/- 5.8 copies/cell in tumor tissue vs 3.5 +/- 2.5 in normal mucosa (P = 0.002). The HMG-CoA reductase gene was similarly expressed in tumor and normal tissue, with means and SD of 2.0 +/- 1.3 copies/cell versus 2.2 +/- 1.9 (pi = 21). Mdr1 RNA was undetectable ( < 0.15 copies/cell) in 5 of 20 tumors, with a mean +/- SD of 1.0 +/- 1.1 copies/cell vs 1.6 +/- 1.7 in normal mucosa. Expression of all three genes was, in most cases, higher in normal liver than in liver metastasis of colorectal carcinomas or normal colon mucosa. The results may form the basis for using LDL as a drug carrier for treatment of colorectal carcinomas, and may indicate that drug resistance in these tumors is not due to overexpression of the mdr1 gene.

Adolescent↗
PubMed1996

Evolution of different therapeutic strategies in the treatment of cranial dural arteriovenous fistulas--report of 30 cases.

30 cases of cranial dural arteriovenous fistuals, treated between 1983 and 1992, are reported. Twelve presented with an aggressive clinical course including intracranial haemorrhage, progredient neurological deficit, medically intractable seizures, and cerebellar symptoms. The other 18 patients had a more benign clinical presentation with audible bruit, exophthalmus, chemosis, and cranial nerve dysfunction. One of the latter had symptoms of pseudotumour cerebri due to sinus occlusion with contralateral sinus stenosis. The most common location was at the transverse sinus, followed by the cavemous sinus, the tentorial ring, and the orbita. Four vessel angiography verified the diagnosis and demonstrated all fistulas, mainly supplied by branches of the external carotid artery. 16 of 18 benign lesions were treated by endovascular therapy alone. Two recent patients received adjuvant stereotactic radiosurgery. Among these 18 patients 2 remained untreated, one because of spontaneous fistula thrombosis prior to therapy and one because of poor medical condition. 12 of 16 treated benign dural fistulas were partially occluded. In 6 of them spontaneous fistula thrombosis occurred during the following months. Total endovascular obliteration was achieved in the remaining 4 patients. 7 of 12 aggressive fistulas were embolized only, one of them having additional radiosurgery. Two of them were totally obliterated and five partially. Surgery was performed in the remaining 5 aggressive fistulas. Complete microsurgical excision was achieved in 2 and partial in further two, who presented initially with a life-threatening intracerebral clot. In one early case ligation of the external carotid artery was done, which is now obsolete. Over all 20 of 28 treated patients became asymptomatic or improved clinically. 3 of the remaining 8 patients were unchanged, two deteriorated despite therapy, and 3 worsened after therapy. All of the latter complications occurred early in our series due to thromboembolic events during the procedure. One surgical patient suffered from a new facial nerve palsy postoperatively. Follow up time in all treated patients was between 1 and 139 months with a mean of 48,3 months.

Adolescent↗
PubMed1996

The missing forgotten intrauterine contraceptive device.

Failure to locate the strings of an intrauterine contraceptive device may mean that the device is within the uterine cavity, was expelled or, worst of all, has perforated the uterine wall. We describe a 36-year-old woman complaining of infertility in whom two missing devices were found within the pelvis after having perforated the uterus. This report demonstrates the need to investigate every case of a missing intrauterine contraceptive device. An algorithm for the proper management of such cases is suggested.

Adult↗