Next generation risk assessment for skin allergy: Decision making using new approach methodologies.

Our aim is to develop and apply next generation approaches to skin allergy risk assessment (SARA) that do not require new animal test data and better quantify uncertainties. Significant progress has been made in the development of New Approach Methodologies (NAMs), non-animal test methods, for assessment of skin sensitisation and there is now focus on their application to derive potency information for use in Next Generation Risk Assessment (NGRA). The SARA model utilises a Bayesian statistical approach to infer a human-relevant metric of sensitiser potency and a measure of risk associated with a given consumer exposure based upon any combination of human repeat insult patch test, local lymph node, direct peptide reactivity assay, KeratinoSens™, h-CLAT or U-SENS™ data. Here we have applied the SARA model within our weight of evidence NGRA framework for skin allergy to three case study materials in four consumer products. Highlighting how to structure the risk assessment, apply NAMs to derive a point of departure and conclude on consumer safety risk. NGRA based upon NAMs were, for these exposures, at least as protective as the historical risk assessment approaches. Through such case studies we are building our confidence in using NAMs for skin allergy risk assessment.

Fractal and stereological analyses of insulin-induced rat exocrine pancreas remodelling.

BACKGROUND: The effect of insulin on the endocrine pancreas has been the subject of extensive study, but quantitative morphometric investigations of the exocrine pancreas are scarce. This study was therefore undertaken to investigate the effect of acute and chronic insulin administration (two doses, 0.4 IU and 4 IU) on the morphology of rat pancreas acini. MATERIALS AND METHODS: Semi-fine sections stained with methylene blue and basic fuchsine or haematoxylin and eosin-stained 5-micrometer thick paraffin sections were used for fractal and stereological analysis of exocrine acini. Acute insulin treatment, independent of applied doses increased fractal dimension in line with decreased lacunarity of pancreas acini. Chronic low dose insulin decreased fractal dimension and increased lacunarity of pancreas acini, but a high dose had the opposite effect. The volume densities (Vv) of cytoplasm, granules and nucleus are affected differently: acute low dose and high chronic dose significantly decreased granules Vv, and in line increased cytoplasmic Vv, whereas other examined structures showed slight changes without statistical significance. RESULTS: The results obtained from this investigation indicate that insulin treatment induced structural remodelling of the exocrine pancreas suggesting a substantial role of insulin in its functioning. CONCLUSIONS: Additionally, we showed that fine architectural changes in acini could be detected by fractal analysis, suggesting this method as an alternative or addition to routine stereology.

Catecholaminergic signalling through thymic nerve fibres, thymocytes and stromal cells is dependent on both circulating and locally synthesized glucocorticoids.

Glucocorticoids have been shown to modulate the expression of noradrenaline metabolizing enzymes and ß(2)- and α(1B)-adrenoceptors in a tissue- and cell- specific manner. In the thymus, apart from extensive sympathetic innervation, a regulatory network has been identified that encompasses catecholamine-containing non-lymphoid and lymphoid cells. We examined a putative role of adrenal- and thymus-derived glucocorticoids in modulation of rat thymic noradrenaline levels and adrenoceptor expression. Seven days postadrenalectomy, the thymic levels of mRNAs encoding tyrosine hydroxylase, dopamine ß-hydroxylase, monoamine oxidase-A and, consequently, noradrenaline were decreased. Catecholamine content was diminished in autofluorescent nerve fibres (judging by the intensity of fluorescence) and thymocytes (considering HPLC measurements of noradrenaline and the frequency of tyrosine hydroxylase-positive cells), while it remained unaltered in non-lymphoid autofluorescent cells. In addition, adrenalectomy diminished the thymocyte expression of ß(2)- and α(1B)-adrenoceptors at both mRNA and protein levels. Administration of ketoconazole (an inhibitor of glucocorticoid synthesis/action; 25 mg kg(-1) day(-1), s.c.) to glucocorticoid-deprived rats increased the thymic levels of tyrosine hydroxylase, dopamine ß-hydroxylase and, consequently, noradrenaline. The increased intensity of the autofluorescent cell fluorescence in ketoconazole-treated rats indicated an increase in their catecholamine content, and suggested differential glucocorticoid-mediated regulation of catecholamines in thymic lymphoid and non-lymphoid cells. In addition, ketoconazole increased the thymocyte expression of α(1B)-adrenoceptors. Thus, this study indicates that in the thymus, as in some other tissues, glucocorticoids not only act in concert with cateholamines, but they may modulate catecholamine action by tuning thymic catecholamine metabolism and adrenoceptor expression in a cell-specific manner. Additionally, the study indicates a role of thymus-derived glucocorticoids in this modulation.

Signalling processes involved in C-peptide-induced chemotaxis of CD4-positive lymphocytes.

Previous data from our group demonstrated that C-peptide induces chemotaxis of CD4-positive lymphocytes in-vitro, mediated by activation of G-protein and PI 3-kinase gamma, but additional signalling pathways involved in this process remained unexplored. In the present study we further analyze intracellular signalling pathways which lead to C-peptide-induced CD4-positive lymphocyte migration. We provide evidence that C-peptide-induced chemotaxis of CD4-positive lymphocytes is critically dependent on activation of Src-kinase and RhoA, Rac-1 and Cdc42 GTPases. Furthermore, C-peptide stimulates phosphorylation of PAK, LIMK and cofilin downstream of Rac-1 and Cdc42, leading to cofilin inactivation and actin filament stabilization. In addition, C-peptide induces ROCK kinase activity and MLC phosphorylation downstream of RhoA, thereby stimulating myosin mediated cell contraction. In contrast, C-peptide does not activate ERK1/2, p38 or Akt in CD4-positive lymphocytes. Our data support an active role of C-peptide in CD4-positive lymphocyte chemotaxis and elucidate molecular mechanisms in C-peptide-induced cell migration.

Extracranial blood flow distribution during carotid surgery.

OBJECTIVE: The collateral function of the external carotid artery (ECA) for cerebral perfusion in cases of atherosclerotic occlusive disease of the internal carotid artery (ICA) is difficult to assess; for this reason, blood flow measurements were taken during carotid endarterectomy (CEA). METHODS: Blood flow was measured before and after CEA using a transit-time flow meter at the carotid artery in 1000 patients who underwent CEA for high-degree (>70%) ICA stenosis. The data were collected prospectively and analysed retrospectively. RESULTS: Median ICA blood flow increased significantly, up 46% from 160 ml min(-1) (IQR: 100-234 ml min(-1)) before CEA to 240 ml min(-1) (IQR: 187-309 ml min(1)) after CEA (P<0.001). Median ECA blood flow dropped by 4%, from 152 ml min(-1) (IQR: 108-220 ml min(-1)) to 150 ml min(-1) (IQR: 103-200 ml min(-1)) (P=0.001). Relative ICA blood flow volumes related to common carotid artery (CCA) flow increased from 58% before CEA to 73% after CEA, whereas relative ECA flow decreased from 54% to 44%. CONCLUSIONS: Increased blood flow in the ICA after CEA is accompanied by decreased ECA flow whereupon the absolute amount of this redistribution is relatively limited. A more profound evaluation of these haemodynamic conditions demands further study.

Outcome of carotid endarterectomy under local anaesthesia with respect to the patients' risk profile.

BACKGROUND: In the present study the perioperative complication rate is compared between high- and low-risk patients when carotid endarterectomy (CEA) is routinely performed under local anaesthesia (LA). PATIENTS AND METHODS: From January 2000 through June 2008 1220 consecutive patients underwent CEA under LA. High-risk patients fulfilled at least one of the following characteristics: ASA 4 classification, "hostile neck", recurrent ICA stenosis, contralateral ICA occlusion, age > or = 80 years. The combined complication rate comprised any new neurological deficit (TIA or stroke), myocardial infarction or death within 30 days after CEA, which was compared between patient groups. RESULTS: Overall 309 patients (25%) were attributed to the high-risk group, which differed significantly regarding sex distribution (more males: 70% vs. 63%, p = 0.011), neurological presentation (more asymptomatic: 72% vs. 62%, p = 0.001) and shunt necessity (33% vs. 14%, p < 0.001). In 32 patients 17 TIAs and 15 strokes were observed. In 3 patients a myocardial infarction occurred. Death occurred in one patient following a stroke and in another patient following myocardial infarction, leading to a combined complication rate of 2.9% (35/1220). In the multivariate analysis only previous neurological symptomatology (OR 2.85, 95% CI 1.38-5.91) and intraoperative shunting (OR 5.57, 95% CI 2.69-11.55) were identified as independent risk factors for an increased combined complication rate. CONCLUSIONS: With the routine use of LA, CEA was not associated with worse outcome in high-risk patients. Considering the data reported in the literature, it does not appear justified to refer high-risk patients principally to carotid angioplasty and stenting (CAS) when LA can be chosen to perform CEA.

Endovascular therapy of a symptomatic mobile thrombus of the thoracic aorta.

INTRODUCTION: The therapeutic strategies of a mobile luminal thrombus of the descending thoracic aorta with peripheral arterial embolization remain a matter of debate. REPORT: We report the case of recurrent peripheral arterial embolism caused by a mobile thrombus of the descending aorta, which was successfully treated by implanting an endovascular stent graft. DISCUSSION: Our case demonstrates, that endovascular stent graft placement is feasible and can be performed as an effective and minimally invasive treatment option for mobile thoracic aortic thrombi.

Balloon occlusion of the celiac artery: a test for evaluation of collateral circulation prior endovascular coverage.

INTRODUCTION: Visceral ischemia is a possible complication after endovascular coverage of the celiac artery (CA). A selective mesenteric angiography during simultaneous balloon occlusion of the CA imitates endovascular coverage and might therefore be suited for evaluation of collateral circulation. We report the feasibility of a balloon occlusion test (BOT) of the CA for this purpose. REPORT: We performed a BOT in 5 patients selected for endovascular surgery with intended coverage of the CA. The BOT could demonstrate sufficient collateral circulation in all cases, which was not evident without occlusion of the CA. The most important collateral vessels were the pancreaticoduodenal arcades and the dorsal pancreatic artery. All patients tolerated the BOT well without abdominal symptoms or pathological laboratory findings. DISCUSSION: Our report suggests that a BOT of the CA is a feasible and safe procedure. It can demonstrate collateral pathways before definite coverage is performed. This test might be useful for selection of patients prior intended coverage of the CA.

Evaluation of changes of systemic blood pressure and shunt incidence in CEA.

BACKGROUND: Induced hypertension is widely recommended as a protective measure in carotid endarterectomy (CEA) to prevent shunt insertion. In this study changes of systemic blood pressure were evaluated in relation to the shunt rate when CEA was performed under local anaesthesia. MATERIALS AND METHODS: In 930 CEAs performed for a high-grade (>70%) ICA stenosis under local anaesthesia the mean systemic blood pressure was measured preoperatively (RR1) and directly before carotid cross-clamping (RR2). A ratio was calculated from these values (RRR=RR2/RR1). A shunt was only inserted for clinical signs of cerebral ischemia. If that became necessary later after cross-clamping had been tolerated primarily, the blood pressure during this period was also recorded (RR3). Also the presence of a contralateral ICA occlusion and baseline blood pressure levels were considered as factors with potential impact on shunt necessity. RESULTS: Among the 638 male (69%) and 292 female (31%) patients with a median age of 70 years (ranging from 52 to 91 years) 82 (9%) had a contralateral ICA occlusion. A shunt was used in 177 operations (19%) and significantly more frequent in patients with a contralateral ICA occlusion (39/82=48% vs. 138/848=16%, p<0,001). RRR was significantly reduced in patients who needed a shunt (0.95 (0.41-1.53) vs. 1.0 (0.54-1.9), p=0.002) which was only true for patients with a patent contralateral ICA. The shunt rate did not differ when contrasting RRR thresholds (<0.7 vs. >1.3) or preoperative blood pressure levels (<100 mmHg vs. >120 mmHg) were compared. RRR did not differ between directly or delayed shunted patients. RR3 did not differ significantly from RR2. A regression analysis identified the presence of a contralateral ICA occlusion as the only independent parameter influencing shunt insertion. CONCLUSIONS: Changes in systemic blood pressure during CEA under local anaesthesia seem to influence shunting rather marginally. The value of induced hypertension to prevent cerebral ischemia should be newly discussed.

Endovascular treatment of a ruptured aneurysm of the inferior thyroid artery. Case report and literature review.

Aneurysms of the inferior thyroid artery are rare. The natural course of these aneurysms seems to be unfavourable, why aneurysm exclusion is recommended in the literature. Open surgical repair is complex why endovascular exclusion seems to be an appealing alternative. We present a patient who developed dysphagia and respiratory distress caused by a ruptured aneurysm of the right inferior thyroid artery. Successful coil embolization of the aneurysm is described along with a review of the literature. Despite the very rare data of these aneurysms, all reported cases of endovascular treatment (n=3) showed favourable results, therefore aneurysm embolization seems to be a feasible and safe alternative to open surgery, especially in emergency cases.

Primary extraanatomical revascularization for groin infections in drug addicts.

BACKGROUND: Arterial groin infections in drug addicts are associated with a risk of amputation and are potentially lethal. Primary revascularization with an obturator bypass represents a potential alternative to local revision and arterial ligation alone. We report our experience with this approach. PATIENTS AND METHODS: From January 1999 until December 2005 twelve drug addicts were treated due to arterial infections in the groin. In eight patients (seven men, one woman, 31 years old on average), the defect in the artery could not be repaired and ligation of the femoral vessels led to critical ischemia. Therefore, an iliaco-popliteal bypass via the foramen obturatorium was implanted either primarily or secondarily. In three patients a cryopreserved homologous vein was used, five patients received alloplastic grafts. RESULTS: Four of eight obturator bypasses were implanted primarily. In the other four patients the initial treatment was limited to local debridement and artery ligation and an obturator bypass was implanted at a later date. Two grafts occluded within the first 30 days. Thereof one was successful thrombectomized. The other patient had no critical ischemia and he refused further surgery. Three more grafts occluded at 74, 90 and 103 days after surgery. No patient demonstrated signs of graft infection and all groin incisions healed uneventfully. A lower limb amputation became necessary in one patient even though the reconstruction was patent due to embolisation of mycotic material. All patients remained drug dependent throughout the followup time which was 3 months on average and ranged from one to 40 months. CONCLUSIONS: The patency of obturator bypasses was 75% at one month. This appears low, especially if one considers the youthful age of the patients and the absence of arterial occlusive disease. Nevertheless, the amputation rate also remained low. Therefore, we feel that this technique may contribute to limb salvage in groin infections in drug addicts.

Immediate CEA for symptomatic carotid disease preferably performed under local anaesthesia is safe.

BACKGROUND: Previous general reservations against carotid endarterectomy (CEA) early after stroke, which were primarily based on concerns of postoperative intracerebral hemorrhage, are resolved. Moreover, a delay of surgery is proofed to be associated with a risk of recurrent cerebral ischemia. However, the complication rate of CEA seems to increase with less time interval to the onset of symptoms. The main purpose of this study was to assess the safety of very early CEA. PATIENTS AND METHODS: Patients having a symptomatic high-grade (> 70%) internal carotid artery (ICA) stenosis were referred by neurologists for CEA within different timeframes, so that they were later differentiated depending on whether surgery was performed within 2 days (immediate CEA = iCEA) or 2 weeks (urgent CEA = uCEA) after neurological deficits have occurred primarily. The perioperative complication rate in these groups was than evaluated and compared. RESULTS: From January 2000 until August 2006 130 consecutive patients (median age 68 years, range: 42-90; 66% male, 34%female)presenting with an ipsilateral TIA (n = 80), stroke (n = 50) underwent iCEA (n = 40) or uCEA (n = 90). Demographic and clinical characteristics were equally distributed between treatment groups. Mostly (121/130), CEA was performed under local anaesthesia with selective shunt use which became necessary in 26%. Besides postoperative hemorrhage (n = 4), cardiac complications (n = 2) and temporary cranial nerve lesions (n = 2), new perioperative neurological deficits occurred in total in 8 patients of which 6 were temporary. The other 2 patients developed strokes of which one patient died. Therefore, the combined stroke- and mortality rate was 1.5% (2/130) for the whole study population. With regard to the timing of surgery, a single incident was observed after iCEA (1/40) which also was the only intracerebral hemorrhage. CONCLUSIONS: It seems that patients with a symptomatic high-grade ICA stenosis can undergo CEA particularly under local anaesthesia as soon as possible without anticipating an increased complication rate.

Acidity constants of cefetamet, cefotaxime and ceftriaxone; the effect of the substituent at C3 position.

Ionization constants of three cephalosporin antibiotics, cefetamet (CEF), cefotaxime (CFX) and ceftriaxone (CFTR) are determined using pH-potentiometric titrations at I=0.1 M (NaCl) and t=25 degrees C. Cefetamet and cefotaxime have three ionization groups: carboxylic, amide and aminothiazole. Besides those three, ceftriaxone possesses an hydroxytriazinone group as new and additional ionization center. In acid medium two overlapping acid-base processes are occurring with acidity constants being: pK1 2.93 (COOH) and pK2 3.07 (aminothiazole) for cefetamet, and pK1 2.21 (COOH) and pK2 3.15 (aminothiazole) for cefotaxime. In the case of ceftriaxone the situation is even more complicated, three overlapping processes coexist with pK1 2.37 (COOH), pK2 3.03 (aminothiazole) and pK3 4.21 (hydroxytriazinone). Protolysis of amide group is happening in the alkaline medium as completely separated process from those in acid medium. The acidity constants which correspond to amide group are pK3 10.65 (CEF), pK3 10.87 (CFX) and pK4 10.74 (CFTR). The influence of the C3 substituent on the dissociation process of the neighboring ionization group, particularly carboxylic group, was considered. The differences in acidity of CEF, CFX and CFTR (pK1: 2.93, 2.21 and 2.37, respectively) are likely to be caused by the stereoelectronic properties of substituents in the beta-position to the carboxylic group due to the combined inductive, hyperconjugative and resonance effects.

Differentiated treatment of aneurysms of the extracranial carotid artery.

AIM: Aim of the study is to illustrate current therapeutic options for aneurysms of the extracranial carotid artery. METHODS: From 1987 until 2003 14 patients (average age: 60 years) with an aneurysm of the extracranial internal carotid artery were treated. The aneurysm diameter ranged from 5 mm to 60 mm. Thirteen patients underwent elective surgery. One patient was operated upon because of acute severe cervical bleeding. RESULTS: Most patients (10/14) presented with an asymptomatic pulsatile cervical mass. The aneurysm was diagnosed 3 times during carotid angiography. The underlying etiology was atherosclerosis in 10 patients. In 3 cases the aneurysm was considered mycotic. Ten aneurysms were localized at the carotid bifurcation whereas 2 each were found in the retrostyloideal region and at the base of the skull. Vascular continuity could be restored in 10 patients while in 3 the carotid artery had to be occluded (twice surgically and once radiologically). The final patient underwent stent insertion for post-traumatic distal aneurysm. In 5 patients perioperative neurological complications were noted which persisted in a single patient (dysphagia due to a lesion of the hypoglossus nerve). All hemispheric complications recovered completely. During follow-up (median 48 months ranging from 3 to 103 months), 1 patient died of unrelated cause. Another patient developed a contralateral ischemic insult. CONCLUSIONS: When adjusting treatment to the various etiological conditions and localizations, aneurysms of the extracranial carotid artery can be managed with a low complication rate and satisfying long-term results. However, success mainly depends on the timely diagnosis and availability of a range of surgical and radiological therapeutical options.

A comparison of cytology and cervicography in cervical screening.

The sensitivity and specificity of cervical cytology and of cervicography in the detection of CIN and invasive cancer of the cervix were determined in a screening programme of an asymptomatic population of 418 women. Because all of the subjects were examined colposcopically and biopsies were taken from any suspicious areas, the presence or absence of disease was determined by the histology of directed cervical biopsies independently of the screening methods being tested. Cervicography correctly identified 24 of the 27 women with CIN or invasive cancer, whereas cytology detected only 14 (sensitivity of 0.89 vs. 0.52; P < 0.01). Cervicography detected CIN in 11 women with negative smears, six having CIN III. Only one case of CIN I was detected by cytology when cervicography was negative. Two cases of CIN II were not detected by either method. Inclusion in the analysis of the results from 23 women with technically defective cervigrams reduced the size of the difference in sensitivity, but it remained significant (0.74 vs. 0.48; P < 0.05). Cervicography was only slightly less specific than cytology (0.92 vs. 0.94; NS). Cervicography appears to be more effective than cytology in screening for cervical premalignancy but may be more demanding of those who perform the test.

Study of heterogeneous equilibria in saturated solutions of some sparingly soluble 8-hydroxyquinolines.

Heterogeneous equilibria in saturated aqueous solutions of 8-hydroxyquinoline (A), 2-methyl-8-hydroxyquinoline (B) and 5-chloro-8-hydroxyquinoline (C) were investigated at constant ionic strength (1M sodium chloride), at 25.0 +/- 0.1 degrees , by the application of the following methods: the formation function method, the method of bound protons, the method of free proton sites and the solubility method. The following equilibrium constants were determined: K(s1)=[H(2)A(+)]/[H(3)O(+)], K(s2)=[HA] and K(s3)=[H(3)O(+)] [A(-)]. Their mean pK values are: -2.88, 2.42 and 12.09 for A, -3.27, 2.71 and 12.73 for B, and -0.34, 3.88 and 12.75 for C. In addition, the acidity constants of investigated 8-hydroxyquinolines were determined by pH-metric titrations. The values obtained for these constants were consistent with those calculated on the basis of corresponding equilibrium constants determined in heterogeneous systems.

Voltammetric methods for analytical determination of fleroxacin in quinodis tablets.

The direct current (dc) and differential pulse (dp) polarographic reduction of fleroxacin was done in a wide pH range from 2.48 to 13.00. The appropriate buffer choice was made for its dp polarographic determination in a range from 1.845 to 16.926 microg /ml, at pH 8.50. The adsorptive properties of fleroxacin were investigated in order to achieve an increase in sensitivity and a possibility of fleroxacin determination by applying the adsorptive stripping voltammetric method. The adsorptive processes at the hanging mercury drop electrode were investigated in Britton-Robinson and borate buffers. Adsorptive preconcentration followed by differential-pulse cathodic stripping showed one wave at approximately - 1.1 V being the most sensitive for analytical determination of fleroxacin. Two linear ranges were obtained, the first one from 18.465 to 258.51 ng/ml, and the second one from 3.693 to 18.465 ng/ml.

Quantitative analysis of analgoantipyretics in dosage form using planar chromatography.

In the therapy of pain of weaker genesis, frequently used drugs usually represent a mix of analgoantipyretics of different chemical structures, mostly derivatives of salicylic acid, pyrazolone and p-aminophenol as well as derivatives of propionic and acetylsalicylic acid. For the determination of these drugs, different chromatographic methods have been applied, mostly HPLC, due to the the lower polarity (pyrazolones derivatives) and thermolability, as well as nonvolatility of compounds investigated. TLC method, considering advantages which include simplicity, reasonable sensitivity, rapidity, excellent resolving power and low cost has been successfully explored for the determination of analgoantipyretic compounds. The aim of this work was to develop a simple and rapid HPTLC method for the determination of acetylsalicylic acid, paracetamol, caffeine and phenobarbitone in dosage form. The determination of analgoantipyretics were performed on pre-coated HPTLC silica gel plates (10 x 20 cm(2)) by development in the mobile phase dichlormethane-ethyl acetate-cyclohexane-isopropanol-0.1 M HCL-formic acid (9:8:3:1.5:0.2:0.2 v/v/v/v/v/v). Migration distances (68.6+0.2 mm, 54.1+0.1 mm, 36.4+0.14 mm and 85.9+0.11 mm for acetylsalicylic acid, paracetamol, caffeine and phenobarbitone, respectively) with low RSD values (0.13--0.39%) showed a satisfactory reproductivity of the chromatographic system. TLC scanner was used for direct evaluation of the chromatograms in the reflectance/absorbance mode. Established calibration curves (r>0.999), precision (0.3--1.02%) and detection limits, as well as recovery values (96.51--98.1%) were validated and found to be satisfactory. The method was found to be reproducible and convenient for the quantitative analysis of compounds investigated in their dosage forms.

Surgical approach to kinking and coiling of the internal carotid artery.

AIM: Whether kinking or coiling of the internal carotid artery (ICA) simply represents a morphological variation without clinical relevance still remains an object of debate. While most patients are incidentally diagnosed in an asymptomatic state due to the broad use of non-invasive investigations (like colour coded Doppler sonography), associated neurological deficits are often unspecific and might be related to coexisting proximal stenotic lesions. Its etiology is unclear. Beside artherosclerotic genesis, a persistent embryological condition or underlying fibromuscular dysplasia is discussed. Moreover, in contrast to precise recommendations concerning the indication for endarteriectomy in carotid artery stenosis, general guidelines for surgical intervention in case of kinking or coiling are not yet established. METHODS: The characteristics of 16 patients who underwent a total of 21 reconstructive operations for isolated kinking or coiling of the ICA during 5 years of observation were retrospectively analyzed. RESULTS: In 10 out of 14 kinkings and 5 out of 7 coilings central nervous symptoms were noted including unspecific vertigo, syncope, tinnitus synchronous to pulse, transient ischemic attacks and manifest cerebral infarction. All these individual complaints disappeared postoperatively. In 1 patient presenting with an ICA coiling histological examination revealed signs of fibromuscular dysplasia. The other specimens showed typical changes of artherosclerotic disease. CONCLUSION: By precluding significant proximal stenosis and effective elimination of symptoms after surgical correction, a causal connection between cerebral dysfunction and severe ICA kinking or coiling can be supposed. An actual abnormality of the arterial wall structure only exists in exceptional cases. Rather, a sequential development from kinking to coiling was noticed.

Electrochemical study of cefetamet-Na and its polarographic determination.

Polarographic behavior of cephalosporin cefetamet-Na (Cef-Na) in aqueous solutions of pH ranging from 1.7 to 12.5 was investigated by applying direct current (dc) polarography, differential pulse polarography (dpp), alternating current (ac) polarography, cyclic voltammetry and electrolysis at constant potential. The characteristics of the corresponding electrode reaction are presented and discussed. The electrode reaction was found to be affected by strong adsorption, strongly and slightly pronounced in acidic and alkaline media, respectively. The methoxyimino group electroreduction was carried out and the mechanistic scheme was suggested. In addition, a sensitive dpp method was proposed for analytical determination of a very low concentrations of Cef-Na.