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Biomedical subjects

A Stocker

Publications and source records attributed to A Stocker.

30 records · Page 2Linked to original sources

Improving enzyme-electrode contacts by redox modification of cofactors.

Efficient electron transfer of redox proteins to and from their environment is essential for the use of such proteins in biotechnological applications such as amperometric biosensors and photosynthetic biocatalysts. But most redox enzymes lack pathways that can transport an electron from their embedded redox site to an electrode or a diffusing photoexcited species. Electrical communication between redox proteins and electrode surfaces has been improved by aligning proteins on chemically modified electrodes, by attaching electron-transporting groups and by immobilizing proteins in polymer matrices tethered by redox groups. Generally these methods involve contacting the enzymes at random with electron relay units. Here we report an approach that allows site-specific positioning of electron-mediating units in redox proteins. We strip glucose oxidase of its flavin adenine dinucleotide (FAD) cofactors, modify the latter with redox-active ferrocene-containing groups, and then reconstitute the apoprotein with these modified cofactors. In this way, electrical contact between an electrode and the resulting enzyme in solution is greatly enhanced in a controlled and reproducible way.

Apoproteins↗

High-flow, small-hole arteriovenous fistulas: treatment with electrodetachable coils.

We present one case of carotid-cavernous fistula caused by percutaneous treatment of trigeminal neuralgia and one case of vertebrovertebral fistula caused by percutaneous internal jugular vein cannulation. Each fistula had a small arteriovenous communication that prevented the use of detachable balloons. Endovascular transarterial treatment of these two iatrogenic fistulas with electrically detachable platinum coils was performed. Both fistulas were occluded with preservation of the parent artery, and the patients have fully recovered.

Aged↗

Active neurocysticercosis, parenchymal and extraparenchymal: a study of 38 patients.

In this retrospective study we have analysed a series of 38 patients seen from 1983 to 1992 (mean follow-up, 4.5 years) with active neurocysticercosis (NCC), 23 (60.5%) with parenchymal and 15 (39.5%) with extraparenchymal NCC. Classification into these two forms of NCC was based on computed tomography and magnetic resonance imaging criteria. The enzyme-linked immunosorbent assay performed in cerebrospinal fluid, for anti-Taenia solium antibodies, was positive in 18 of 23 (78%) cases. Epilepsy and/or intracranial hypertension were the most common clinical presentation (92%). Twenty-three (60.5%) of 38 patients were treated with praziquantel and/or albendazole. In parenchymal NCC, the efficacy of medical therapy was complete in 13 of 16 (81%) and partial in 3 of 16 (19%) patients. In contrast, in all cases of extraparenchymal NCC treated with cysticidal drugs the results were disappointing. A ventriculoperitoneal shunt was performed in 9 of 13 patients with extraparenchymal NCC and hydrocephalus. Severe complications, including two deaths, associated with the natural evolution of the disease or with surgery, occurred only in extraparenchymal NCC. Therefore, we confirm the existence of the two forms of active NCC, parenchymal and extraparenchymal, which are strikingly different in clinical presentation, medical therapy response, complications, morbidity and mortality.

Adolescent↗

Spontaneous thoracolumbar spinal cord infarction: report of six cases.

We present a retrospective study of 6 patients with spinal cord infarction in the territory of the Adamkiewicz artery. In all patients, the clinical picture was stereotyped: sudden onset of paraplegia and bilateral radicular pain, dissociated sensory loss below the level of infarction and sphincter dysfunction. Emergency neuroradiological investigation ruled out a compressive lesion in all cases. In one patient, spinal angiography was performed and identified an occlusion of the Adamkiewicz artery. Treatment was supportive and all patients had a substantial recovery over a period of weeks.

Aged↗

Quinazoline antifolates inhibiting thymidylate synthase: variation of the N10 substituent.

The synthesis of 12 new 5,8-dideazafolates with isopropyl, cyclopropylmethyl, 2-fluoroethyl, carbamoylmethyl, phenacyl, 3-fluorobenzyl, 5-uracilylmethyl, carboxymethyl, 2-carboxyethyl, 3-cyanopropyl, 3-hydroxypropyl, and cyanomethyl substituents at N10 is described. In general, the synthetic route involved monoalkylation of diethyl N-(4-amino-benzoyl)-L-glutamate, coupling of the resulting secondary amine with 2-amino-6-(bromomethyl)-4-hydroxyquinazoline hydrobromide in N,N-dimethylacetamide with calcium carbonate as the base, and deprotection using mild alkali. The cyanomethyl derivatives was found to be unexpectedly base labile and was therefore prepared by mild acid deprotection of a di-tert-butyl ester. The compounds were tested as inhibitors of purified L1210 thymidylate synthase (TS). Four members of the series were more potent that the N10-hydrogen compound, but none was superior to the previously described N10-propargyl-5,8-dideazafolic acid. Selected compounds were examined as inhibitors of purified L1210 dihydrofolate reductase (DHFR). As desired, N10 substitution in general reduced DHFR inhibitory activity; these results are discussed. As a measure of cytotoxicity, the compounds were examined for their inhibition of the growth of L1210 cells in culture. None of the new substituents conferred enhanced potency relative to N10-propargyl-5,8-dideazafolic acid (ID50 = 5 microM), which, as the best TS inhibitor and a relatively poor DHFR inhibitor, continues to lead this series.

Alkylation↗

Neurocysticercosis--a review of 231 cases.

Two hundred thirty-one cases of neurocysticercosis are reviewed. Diagnosis was established by cerebral computed tomography during a seven-year period (1983-1989). One hundred and fourty-four (62%) presented with symptom-related disease (symptomatic neurocysticercosis and in 87 the diagnosis was incidental (asymptomatic neurocysticercosis). In symptomatic neurocysticercosis the parasitosis was considered inactive in 115 cases and active in 29. Seizures occurred in 135 patients (96% of the symptomatic neurocysticercosis). In the active form we also found: meningitis (n = 15), intracranial hypertension (n = 12), hydrocephalus (n = 10) and arteritis (n = 2). Treatment included praziquantel (n = 21), albendazole (n = 4), dexamethasone (n = 18) and surgery (n = 10).

Albendazole↗

[Endovascular treatment of dissecting aneurysms of the posterior cerebral artery].

In the literature, there are few reports of posterior cerebral artery aneurysms resulting from isolated dissections. In these cases the treatment is still a matter of discussion and includes anticoagulation, surgical intervention, endovascular techniques and conservative management. We present five cases of Posterior Cerebral Artery (PCA) aneurysms, with angiographic criteria of dissection (double lumen, proximal narrowing), all being situated at the P2 segment, three being close to the P1/P2 junction. In one case, a large aneurysm ruptured during the attempted catheterization with subsequent death of the patient. In three patients occlusion of the parent vessel was performed with Guglielmi detachable coils located proximal to the aneurysm, with no new neurological deficits. In the other case there was spontaneous thrombosis of the aneurysm. Occlusion of the parent vessel by endovascular techniques in dissecting PCA aneurysms has a low probability of neurological deficits and seems to be an appropriate approach for these aneurysms.

Adult↗

[Dural fistulas of the anterior cranial fossa].

Dural arterio-venous shunts (DAVS) of the anterior cranial fossa are quite rare. There are only a few cases reported in the literature. The authors present 5 cases of dural arterio-venous shunts (DAVS) of the anterior cranial fossa, allowing more data for later reviews of this rare and aggressive localisation of DAVS. The clinical set, imaging findings (with emphasis in diagnostic angiography), treatment and outcome in these 5 patients are described. Haemorrhage was the presenting form in 4 patients; the other case presented was investigated for headache. There were bilateral symmetric feeders in two patients, unilateral feeders in another two and unilateral predominant feeders in one; contribution of the external carotid artery, when present, was always minimal. Venous drainage included one or combinations of these: superior sagittal sinus, sylvian veins and cavernous sinus. Three patients had venous aneurysms in anterior cranial fossa; of these, two presented with haemorrhage, but the third one of them has been asymptomatic for 7 years. Three patients were treated by surgical exclusion of the shunt and became clinical and angiographicaly normal. According to the literature, our cases confirm the highly aggressive behaviour of these DAVS. Surgical treatment is an efficacious method of therapy and should be done as soon as possible. Embolization can be attempted but is technically difficult and eventually too expensive.

Adult↗

Cysticercosis of the brain. The value of computed tomography.

Incidence and radiologic findings of neurocysticercosis were investigated in a series of 23,800 consecutive head examinations using computed tomography (CT). The condition was diagnosed in 168 cases (0.7%). The parenchymatous form was the most common presentation (96.3%), while the meningeal form corresponded to only 11.9 per cent of cases. These two forms coexisted in some cases. These findings reversed the knowledge on the condition based on conventional radiography. The different CT appearances in the brain are described and a new radiologic protocol for the CT evaluation of the condition is advocated, which includes a follow-up after a trial cure with Praziquantel in the presence of cysts not associated with suggestive brain calcifications. CT was more sensitive than conventional radiography in the differentiation between dead and living larvae, thus having an impact on the therapeutic management of the patients.

Adolescent↗